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   1. A Comparison ...
   2. The Role of F...
   3. Long-Term Cli...
   4. An Observatio...
   5. Melding Pharm...
   6. Furosemide St...
   7. Biomarker Eva...
   8. Correlation o...
   9. Anti-Inflamma...
   10. Depression i...
   11. Malignancy A...
   12. Risk Predict...
   13. Association ...
   14. Ketoanalog S...
   15. Endothelial ...
   16. Acute Kidney...
   17. Plasmapheres...
   18. Prevalence o...
   20. Prevalence o...
   21. Incidence, R...
   22. Peritoneal D...
   23. Effect of Lo...
   24. Clinico-Path...
   25. Retrospectiv...
   26. Genetic Pred...
   27. Prevalence a...
   28. Next-Generat...
   29. Obesity Modu...
   30. Nitrosodimet...
  Rekha Presentation
   1. A Study of In...
   2. Near-Death Ex...

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ABSTRAC
Year : 2019  |  Volume : 29  |  Issue : 7  |  Page : 22-38
 

Oral Presentation



Date of Web Publication13-Nov-2019

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How to cite this article:
. Oral Presentation. Indian J Nephrol 2019;29, Suppl S1:22-38

How to cite this URL:
. Oral Presentation. Indian J Nephrol [serial online] 2019 [cited 2022 Jun 29];29, Suppl S1:22-38. Available from: https://www.indianjnephrol.org/text.asp?2019/29/7/22/270894



  1. A Comparison of the Creatinine Clearance by Glomerular Filtration Rate Estimating Equations With Measured Glomerular Filtration Rate by Isotope Scan for Indian Population Top


Ruju Gala, Narayan Prasad, Amit Gupta, Anupma Kaul, D S Bhadauria, M R Patel, M R Behera, M Yachha, R S Kushwaha

Department of Nephrology; Sanjay Gandhi Post Graduate Institute of Medical Sciences; Lucknow; Uttar Pradesh; India

BACKGROUND: Glomerular filtration rate (GFR) is essential for renal function evaluation. While creatinine clearance can be measured by Tc-99m-DTPA isotope nuclear scan, equations such as Cockcroft–Gault formula (CGF), Modified Diet in Renal Disease (MDRD), and the Chronic Kidney Disease-Epidemiology Collaboration equation (CKD-EPI) are useful in estimating GFR. This study is to validate the different GFR estimating equations and their correlation with measured GFR by Isotope scan for healthy Indian population.

AIM OF THE STUDY: The aim of this study is to validate the different GFR estimating equations: Cockcroft–Gault, MDRD, and CKD-EPI and to determine their correlation with measured GFR by isotope scan for Indian population.

METHODS: In this study, we measured GFR with double-sample plasma clearance of 99mTc-DTPA (measured GFR [mGFR]) in 814 healthy Indian adult (≥18 years) individuals. Using mGFR as the gold standard, we evaluated the efficiency of three different GFR estimation equations (Cockcroft–Gault, MDRD, and CKD-EPI). We also calculated their correlation using linear regression analysis and their precision using Bland–Altmann analysis, using mGFR by nuclear isotope scan as a gold standard.

RESULTS: In our population, the mean age was 44 ± 11 years and there were 159 males and 655 females. The mean mGFR was 81.46 ± 14.35 mL/min/1.73 m2. In correlation analysis, the three equations Cockcroft–Gault, MDRD, and CKD-EPI had significant linear correlation with mGFR (P < 0.01, P < 0.01, P = 0.00, respectively) and the linear regression analysis demonstrated moderate explanatory capacity of eGFR produced by CKD-EPI (R2 = 0.22); CGF (R2 = 0.15), and MDRD (R2 = 0.12). The slopes in the Bland–Altman analysis of CGF, MDRD, and CKD-EPI were −0.68, −0.41, and −0.18, respectively. Intraclass coefficient was highest for CKD-EPI (0.63), followed by CGF (0.51) and MDRD (0.49). Thus, the CGF, MDRD, and CKD-EPI formula produced eGFR with strong correlation with mGFR, moderate explanation capacity of variance in mGFR, small bias, satisfactory performance in Bland–Altman analysis, and high intraclass correlation coefficients.

CONCLUSIONS: This study concludes a significant correlation between measured GFR by nuclear isotope scan and the GFR estimating equations: Cockcroft–Gault, MDRD, and CKD-EPI for the healthy Indian population. Of the three equations, CKD-EPI has the highest precision of GFR prediction, with respect to mGFR.


  2. The Role of Far-Infrared Therapy in the Unassisted Maturation of Arteriovenous Fistula in Patients With Chronic Kidney Disease: An Open-Labeled Randomized Control Trial Top


S Murugesh Anand, M Edwin Fernando, B Suhasini, K Elancheralathan, Valarmathi, N D Srinivasaprasad, S Sujith, K Thirumalvalavan, K Jeyashree

Department of Nephrology; Stanley Medical College and Hospital; Chennai; Tamil Nadu; India

BACKGROUND: The goal of arteriovenous fistula (AVF) creation is to achieve functioning dialysis access, which can be cannulated repetitively and to provide adequate flow for the dialysis.

AIM OF THE STUDY: The objective of this study is to assess the role of far-infrared (FIR) therapy in the unassisted maturation of newly created AVF in patients with chronic kidney disease.

METHODS: In this prospective open-labeled randomized control trial; 107 patients were randomized. All the participants were subjected to high-resolution ultrasonographic mapping of the vessels of upper limb to decide the site of AVF, and those who satisfied the inclusion and exclusion criteria were randomly assigned to either the test group or the control group. Participants in the control group received tablet clopidogrel 75 mg once daily for 30 days along with isometric hand exercise, whereas the participants in the test group received FIR therapy twice weekly, 40 min session each, for 4 weeks along with tablet clopidogrel and isometric hand exercise. Ultrasound and Doppler study of AVF and its arterial and venous limbs were done at the end of the 4th and 12th week to assess the maturation of the AVF. Vascular access guidelines proposed by NKF-KDOQI in 2006 were adapted to define the maturation of AVF.

RESULTS: Of 107 patients included, 51 were randomized to the test group and 56 were to the control group. (1) At the end of 3 months, Qa in radiocephalic (RCF) was 850.38 ± 316.07 and 649.77 ± 367.82 in the test and the control group, respectively (P = 0.003). Qa in brachiocephalic (BCF) at the end of 3rd month was 980.42 ± 403.29 and 922.12 ± 489.07 in the test and the control arm, respectively (P = NS). (2) The mean CVd was 6.35 ± 1.26 and 6.16 ± 1.71 in the test and the control arm, respectively, at the end of 3 months. (3) The number of AVF failures was 5 (10.2%) and 14 (28%) in the test and control groups, respectively, which is statistically significant (P = 0.025). However, when adjusted for patients with failure of AVF within 6 h of surgery (which may be related to the surgical technique), this difference in the AVF patency was statistically insignificant (P = 0.121). (4) The mean Qa is high in patients with arterial intimal medial thickness (IMT) <0.5 mm when compared with those with IMT ≥0.5 mm (P < 0.001).

CONCLUSIONS: FIR therapy is effective in increasing the AVF blood flow rate at the end of 3 months although the difference in the primary failure rate is statistically insignificant. We also found that the IMT of the anastomosed artery has impact on the primary failure rate of AVF.


  3. Long-Term Clinical Outcomes and Response to Immunosupression in Membranous Nephropathy: A Prospective, Interventional, Single-Center Study Top


Luvdeep Dogra, Manisha Sahay, Kiranmai Ismal, P S Vali, Vikram Kumar

Departments of Nephrology and1 Pathology; Osmania General Hospital; Hyderabad; Telangana; India

BACKGROUND: Membranous nephropathy (MN) is the most common etiology of primary nephrotic syndrome in adults. Usual causes of MN include autoimmune diseases, infections, and malignancies. When present, the disease is termed as “secondary MN” (sMN). Cases with no cause identified are classified as idiopathic MN (IMN). PLA2R (phospholipase A2 receptor) has been the area of interest for noninvasive diagnosis of MN. Cases of IMN have a variable prognosis, with up to 30% reaching end-stage renal disease on long-term follow-up. Various immunosuppressive (IS) regimens have been used to induce remission and halt progression.

AIM OF THE STUDY:





  • Primary: To study long-term outcomes of MN, prevalence of renal deposit of PLA2RAb in MN, and role of IS in IMN
  • Secondary: Subgroup analysis to compare tissue and serum PLA2R in the diagnosis of IMN.


METHODS: Sixty patients with MN studied. Inclusion criteria: MN confirmed on biopsy and no history of any prior IS use and if tissue PLA2R antibody staining done. Baseline serum biochemistry and urinary protein quantification were done. All patients underwent screening for secondary causes of MN, including a detailed history of medication use; physical examination; serology for systemic lupus erythematosus (SLE), hepatitis B, hepatitis C, and HIV; and age-appropriate evaluation of malignant diseases. A random subgroup of patients of IMN tested baseline serum PLA2R. Patients were managed as per the Kidney Disease Improving Global Outcomes guidelines for MN. All patients were started on angiotensin-converting-enzyme inhibitor (ACEi) unless they had a complicated MN when IS regimen was used. Modified Ponticelli regimen or tacrolimus (Tac) was used as first-line IS (primary IS). A randomly selected subgroup was administered rituximab as secondary IS. Progression to CKD was the primary end point. Institutional ethics committee clearance was obtained. Patients already exposed to IS therapy and patients with chronic kidney disease (CKD) at presentation were excluded.

RESULTS: At inclusion, there were 34 males and 26 females (1.3:1). The mean age 38.6 years (±12.7). The mean follow-up was 35 months (12–80). 100% Anasarca. The mean serum creatinine was 0.95 mg/dl (0.6–1.4); 80% had hypoalbuminemia with a mean of 2.6 g/dl; the mean 24-h urine protein was 5.6 g/day (3.5–12). PLA2R deposit was seen in 48 (80%) while absent in 12 (20%); among positives, 3 had SLE, 1 carcinoma ovary, and 1 pulmonary tuberculosis (PTB)-reclassify as sMN (5 cases; 10.4% false positive). Of 12 PLA2R negatives, 4 SLE (33.3%), 1 PTB, and 1 renal cell carcinoma while rest 6 cause unknown sMN (50%). Tissue PLA2R sensitivity: 87.7%; specificity: 54.5%; positive predictive value: 89% for IMN. A subgroup of 10 patients with IMN tested for serum PLA2R – 7 positive (sensitivity 70%) and 3 negative (false negative). Of 43 IMN patients, 37 (86.2%) were given ACEi and 9 remitted (24.3%). Primary IS therapy used for 34: 22 Modified Ponticelli-12 remitted (54.5%); 10 no response. Rest 12 Tac-7 remitted (58.3%); 5 no response. No difference was found between either IS (P > 0.05). Five patients who failed primary IS were given rituximab while 4 remitted (80%) and 14 IMN cases progressed to CKD: IFTA >30% significantly associated with progression, P < 0.05.

CONCLUSIONS: PLA2R staining is not sine qua non for IMN. Renal PLA2R deposits are more sensitive than serum PLA2R for IMN. Modified Ponticelli and Tac achieve remission in majority of patients. However, none is superior to other. Rituximab is useful in patients who fail primary IS. Baseline interstitial fibrosis (IF) and tubular atrophy (TA) predicts progression to Chronic kidney disease(CKD).


  4. An Observational Study on Hub and Spoke Model of Hemodialysis Network in Telangana State Top


Sarang Vijayan, G Swarnalatha, Uttara Das, Raja Karthik, T Gangadhar

Department of Nephrology; Nizams Institute of Medical Sciences; Hyderabad; Telangana; India

BACKGROUND: About 2.2 lakh new patients of end-stage renal disease get added in India every year and require dialysis and/or kidney transplantation to sustain their lives. The number of dialysis centers in India is less than 5000, most of which are run by private healthcare organizations. Patients and relatives frequently traveled long distances to the cities to avail the hemodialysis (HD) treatment in the tertiary care hospitals.

AIM OF THE STUDY: To assess the impact of hub and spoke model (H&S) of HD network implemented in Telangana state in terms of patient's convenience and quality of life and treatment outcomes.

METHODS: Patients undergoing HD in one hub, i.e., Nizams Institute of Medical Sciences, Hyderabad, and six spokes, i.e., peripheral centers, are studied to understand the improved quality of patient care. Patient demographics, duration of dialysis, distance required to travel to the dialysis center, etc., will be documented. Quality of life, vascular access, vaccination rate, hemoglobin levels, etc., will be noted. Patient quality of life will be analyzed using the Short Form (SF)-36 scoring system. All continuous variables summarized using mean and standard deviation, while all categorical variables summarized using frequency and percentage. Data were analyzed using EPI INFO version 7.

RESULTS: A total of 294 dialysis patients were included in the study, of which 141 members were included from the hub center and 153 members from six different spoke centers. The mean age of the study population was 45.65 years (standard deviation [SD] = 14.12). It was comparable in both H&S centers. Distance traveled before initiation of H&S model was significantly higher in spoke centers, with a mean difference of 30 km (P = 0.000001). After the initiation of H&S model, this distance was significantly reduced in spoke centers according to Wilcoxon signed-rank test (P = 0.0005). Regarding permanent access, spoke centers have more arteriovenous fistula patients (88.4% vs. 98%). Mean hemoglobin was comparable in both the centers at months 0, 1, and 6. Vaccinations against hepatitis B virus were almost comparable in H&S centers. Regarding quality of life assessment, both H&S centers have above average overall score with mean SF-36 score of 76.39 (SD = 13.8) in hub centers and 71.12 (SD = 16.94) in spoke centers.

CONCLUSIONS: Establishing the dialysis centers in remote locations in an H&S model in the government sector will provide similar quality dialysis compared to the urban tertiary dialysis centers. Patient treatment-related outcomes are comparable in both groups.


  5. Melding Pharmacogenomic Effect of Mdr-1 and Cyp3a5 Gene Polymorphism on Tacrolimus Dosing in Renal-Transplant Recipients Top


Akhilesh Jaiswal, Harshit Singh, Mantabya Singh, Kritika Singh1, Manas Ranjan Behera, Vikas Agarwal1, Amit Gupta, Narayan Prasad

Departments of Nephrology and1 Immunology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow; Uttar Pradesh; India

BACKGROUND: Tacrolimus (TAC) is the mainstay immunosuppressant for renal transplantation. Narrow therapeutic index, multiple drug interactions, and interindividual variability in pharmacokinetics enforce us for obligatory monitoring of therapeutic drug level. MDR-1 gene and CYP3A5 gene polymorphism may blend to achieve the optimum level. The optimum dose as per body weight is difficult to single out in the early posttransplant period.

AIM OF THE STUDY: We aimed to analyze the melding effect of both gene polymorphisms and elicit the dose depending on the combination of single nucleotide polymorphisms (SNPs) in Northern Indian transplant recipients, where data are limited.

METHODS: The daily TAC dose, weight-adjusted doses (mg/kg/day), TAC trough blood concentration (average of at least 3 levels), and dose normalized with corresponding dose using TAC co/weight-adjusted dose ratio (ng/ml/mg/kg/day) of 248 patients were recorded. All recipients were also genotyped for the SNPs of CYP3A5 at intron 3 A6986G (the *3 or *1 allele); MDR1 at exons 12 (C1236T), 21 (G2677A/T), and 26 (C3435T). We analyzed the blending effect of mutant SNPs of MDR-gene and CYP3A5 for optimized TAC level.

RESULTS: Among CYP3A5 genotypic variants, dose-adjusted TAC level was significantly lower, and the TAC dose required to achieve the target level was significantly higher in CYP3A5*1*1 (expressor) than that of CYP3A5*1*3 and CYP3A5*3*3. Of the MDR-1 gene SNPs, only G2677T/A homozygous mutant was significantly associated with TAC level, and it was strongly correlated with P-gp expression. The daily TAC dose requirement was highest with a combination of CYP3A5*1*1 and homozygous mutant TT + AA genotype of G2677T/A and lowest with CYP3A5* 3*3 and wild-type GG of G2677T/A genotype.

CONCLUSIONS: Both CYP and MDR-1 gene polymorphisms affect the TAC dose requirement, and there is a need to look for both in an individual to achieve the target trough concentration.


  6. Furosemide Stress Test to Predict the Severity of Acute Kidney Injury Top


R Vairakkani, P Arun Gokul, M Edwin Fernando, N D Srinivasa Prasad, S Sujit, K Thirumal Valavan, C Hariharan

Department of Nephrology; Government Stanley Medical College and Hospital; Chennai; Tamil Nadu; India

BACKGROUND: Various procedures have been tried to stress the glomerular and tubular reserve of kidneys, to bring out the “subclinical acute kidney injury (AKI).” Earlier protein loading tests were tried to ascertain the glomerular filtration reserve; now, antagonism of renin-angiotensin system is a promising alternative. The tubular function can be stressed by a test developed and standardized by Chawla et al. called the furosemide stress test (FST).

AIM OF THE STUDY: To determine the clinical significance of FST in predicting the severity of AKI.

METHODS: Patients >18 years of age who had Kidney Disease Improving Global Outcomes (KDIGO) Stage I or Stage II AKI in the absence of volume depletion, obstruction, baseline estimated glomerular filtration rate <30 mL/min/1.73 m2, pregnancy, postrenal transplant, or furosemide allergy between April 2018 and September 2018 were included. Urine output was measured for up to 2 h from the time of furosemide bolus administration (dose of 1 mg/kg for furosemide naive and 1.5 mg/kg for those who were previously exposed to furosemide in the past 7 days) and replaced mL per mL with normal saline unless contraindicated. The patients were followed up for 14 days or hospital discharge whichever occurred first. Progression to KDIGO Stage III within 14 days of FST was studied as the outcome measure. Appropriate statistical methods were employed.

RESULTS: A total of 80 AKI patients having Stage I (n = 44; 55%) or Stage II (n = 36; 45%) meeting the study criteria were assessed. Twenty-eight patients (35%) progressed to KDIGO Stage III during the study period, of which eight patients required renal replacement therapy. The mean creatinine at the time of administration of FST was 2.071 ± 0.09 mg/dl for progressors and 1.869 ± 0.05 mg/dl for nonprogressors (P = 0.051). The baseline characteristics of gender, diabetes mellitus, hypertension, cardiac failure, alcohol, and smoking status were not significantly different between the two groups, except for baseline CKD (n = 5 in progressors vs. n = 1 in nonprogressors; P = 0.018). The mean 2 h furosemide stress test output was 215.36 ± 56.13 ml for progressors and 546.54 ± 46.76 ml for nonprogressors (P = 0.0005). An optimal urine output cutoff of 325 ml at 2 h to distinguish between the two groups with a sensitivity of 82.14 and a specificity of 80.77 was determined using receiver operating characteristic curve analysis.

CONCLUSIONS: FST appears to be a promising bedside tool for predicting the progression of AKI and thus may help in identifying “at-risk” patients. The optimal urine output cutoff needs to be validated using large-scale studies.


  7. Biomarker Evaluation of The first South Asian Prospective Longitudinal Cohort Investigating the Clinical Course and Risk Profile of Iga Nephropathy: Glomerular Research and Clinical Experiments-Iga Nephropathy in Indians Cohort Top


Suceena Alexander, Santosh Varughese, Rajanbabu Franklin, Mandeep Singh Bindra, Theophilus Vijayakumar, Vinoi George David, Anna T Valson, Shibu Jacob, Elenjickal Elias John, Jeethu Joseph Eapen, Athul Thomas, Sabina Yusuf, L Jeyaseelan, Charles Pusey, Mohamed R Daha, Marc Seelen, John Feehally, Jonathan Barratt, George T John

Christian Medical College; Vellore; Tamil Nadu; India

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of end-stage kidney disease (ESKD). The 10-year renal survival in South Asia is approximately 35% as reported from retrospective registries. These observations cannot be entirely attributed to a lack of uniform screening protocols or late referral and attest to the probability that IgAN may not be the same disease in different parts of the world.

AIM OF THE STUDY: To measure exploratory biomarkers in an incident Indian population with IgAN and look for associations with clinical outcomes at 2 and 5 years of follow-up.

METHODS: We prospectively recruited renal biopsy-proven IgAN (Glomerular Research and Clinical Experiments-IgAN in Indians cohort). The recruitment period was from March 2015 to September 2017. 201 IgAN patients, 415 disease controls (non-IgAN GNs), and 103 healthy controls were enrolled prospectively. Absolute renal risk (ARR) score was used to categorize the risk groups at baseline. Rapid progression is defined as fall of estimated glomerular filtration rate (eGFR) by CKD-EPI >5 ml/min/m2 per year. The end of study composite outcome (EOS) is defined as at least 50% decline in eGFR and ESKD (eGFR <15 ml/min/1.73 m2), renal replacement therapy, or death. The cohort is registered with WHO: trial ID ISRCTN368341593. The protocol is published at https://doi.org/10.12688/wellcomeopenres. This study is funded by the Early Career Fellowship (Clinical) of the Wellcome DBT India Alliance.

RESULTS: A total of 201 IgAN patients at a median follow-up time of 23 (interquartile range 12–34) months. The median ARR score was 19 (103 patients in the low-risk [LR] and 98 patients in the high-risk [HR] cohort). The levels of serum KM55 (monoclonal antibody directed against the galactose-deficient hinge region of the IgA1 molecule) were not significantly different in IgAN patients versus HC as detected by sandwich ELISA (mean Optical density (OD) 6.249 vs. 5.88; P = NS). However, within the IgAN cohort, serum KM55 levels were significantly more in the HR than in the LR groups at baseline (P = 0.0002). Furthermore, serum KM55 levels were significantly more in the EOS group than the non-EOS group at follow-up (P = 0.010). The serum levels of secretory IgA (SIgA) as detected by sandwich ELISA was significantly more in IgAN patients than HC (mean OD 2.22 vs. 2.018; P = 0.039). Within the IgAN cohort, the serum levels of SIgA did not differ significantly between the risk groups at baseline or between the EOS outcome groups at follow-up.

CONCLUSIONS: The differences in biomarkers in the South Asian population may indicate differences in the underlying pathogenic pathways that need further elucidation. The relevant biomarkers may be incorporated into the renal risk score to delineate the subpopulation will benefit from immunosuppression.


  8. Correlation of Blood Heavy Metal Levels in Chronic Kidney Disease Patient With Estimated Glomerular Filtration Rate Top


Abhishek Kumar, K Sai Ram Reddy

Yashoda Hospital; Hyderabad; Telangana; India

BACKGROUND: Diabetes and hypertension are the leading causes of chronic kidney disease (CKD) worldwide. However, many cases of CKD have unknown etiology; the so-called “CKDu.” It cannot be denied that some of these could be due to heavy metal toxicity. Nephrotoxicity of heavy metals at high doses is well established, but chronic low exposure is more common. Many of these are preventable if identified early.

AIM OF THE STUDY: (1) To measure blood levels of heavy metals in CKD patients; (2) to find correlation between the blood level of heavy metal and the estimated glomerular filtration rate (e-GFR, based on creatinine).

METHODS: We measured the blood levels of nine different heavy metals: lead, mercury, cadmium, arsenic, barium, cobalt, chromium, selenium, and aluminum. Blood levels of heavy metals were measured using inductively coupled plasma-mass spectrometry technique. All samples were processed by Thyrocare™ Labs. Values were expressed in units of “μg/L.” GFR was calculated based on serum creatinine values using CKD-Epidemiology Collaboration creatinine formula. Creatinine was measured using enzymatic assay method.

RESULTS: The results of the correlation studies were as follows: (1) There was a significant correlation between e-GFR and blood levels of chromium, having a negative correlation (P = 0.000; correlation coefficient = −0.518). Hence, as e-GFR decreased, chromium value increased. (2) There was a significant correlation between e-GFR and blood levels of selenium, having a positive correlation (P = 0.001; correlation coefficient = 0.439). Hence, as e-GFR decreased, selenium value also decreased. (3) Apart from these heavy metals, e-GFR was also significantly associated with the hemoglobin levels, having a strong positive correlation (P = 0.000; correlation coefficient = 0.612). Hence, as e-GFR decreased, hemoglobin also decreased.

CONCLUSIONS: The blood levels of chromium progressively increased with advancing CKD (falling e-GFR), thus suggesting its nephrotoxicity. However, selenium, an antioxidant, was found to be lower in advanced CKD (and vice versa), thus suggesting its nephroprotective effect.


  9. Anti-Inflammatory Intervention: An Experimental Study for Russell's Viper Venom-Induced Nephrotoxic Model Top


Farhat Nasim, Raghwendra Mishra, Pinaki Mukhopadhyay, Roshnara Mishra

Department of Nephrology; NRS Medical College and Hospital; Kolkata; West Bengal; India

BACKGROUND: Viper envenomation can jeopardize renal physiology either directly through its nephrotoxic component or via inflammatory mediators or both. Snake venom-induced renal complication is associated with high morbidity and mortality (≈30%) despite the alternative c-terminal splicing variants (ASVs) administration. Hence, targeting inflammation soon after the envenomation with some potent anti-inflammatory pharmaceutical agent in snake bite cases can prevent or reduce nephrotoxicity.

AIM OF THE STUDY: To check the potential of anti-inflammatory agents in reducing or preventing the pathophysiological consequences of renal injury in experimental murine model of venom-induced nephrotoxicity.

METHODS: To accomplish our aim, the effect of intraperitoneal administration of prednisolone as an anti-inflammatory agent was evaluated in murine model of viper venom-induced nephrotoxicity. Renal, inflammatory, oxidative, and carbonyl stress markers and renal histopathological alterations were assessed in the studied group. Data were represented as mean ± standard error. One-way ANOVA followed by Bonferroni post hoc analysis was performed to evaluate any significant variation among the different groups; P < 0.05 was considered statistically significant.

RESULTS: Renal compromise in venom group was confirmed from oliguria, elevated urinary microprotein, and decreased urinary creatinine and creatinine clearance. Kidney damage was reaffirmed by signs of tubular injury and glomerular damage with mesangial proliferation in renal histopathological studies (H and E, picrosirius red, and periodic acid-Schiff staining). The renal changes are associated with significant inflammation and oxidative damages accompanied with elevation in neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), Nitric Oxide (NO), Inducible Nitric Oxide (iNOS), Inerleukin-6 (IL-6), Interferon Gama (IFN-γ), TNF-α, thoracic outlet syndrome (TOS), and thiobarbituric acid reactive substances (TBARS) and methylglyoxal associated with reduced platelet-to-lymphocyte ratio, glyoxal 1(GLO-1), and total antioxidant status (TAS) in animals of venom-induced nephrotoxic group, which favors a state of acute inflammation and oxidative stress. Administration of prednisolone was found to significantly prevent the above changes in treatment group.

CONCLUSIONS: Findings of the present study suggest that administration of anti-inflammatory agents can improve/prevent snake venom-induced nephrotoxicity and associated inflammatory and redox changes and therefore can be considered for therapeutic purpose.


  10. Depression in Patients With Chronic Kidney Disease on Hemodialysis at a Tertiary Care Center in Nepal Research Top


Krishna K Agrawaal, Pramod K Chhetri, Pradip Man Singh, Dhiraj N Manandhar, Prakash Poudel

Nepal Medical College; Kathmandu; Nepal

BACKGROUND: Psychiatric disorders are common among patients with chronic kidney disease (CKD), depression being the most common. Comorbid depression impacts negatively on the quality of life. It is unclear if self-reported depression rating scales can be used accurately for screening. This study used PHQ-9, Hamilton Depression Rating Scale, and ICD-10 to screen for depression in CKD and compared with a gold standard. This study is first of its kind where it identified tools which can be used by patients, primary care physicians, or specialists.

AIM OF THE STUDY: (1) To study the prevalence of depression in patients on maintenance hemodialysis (HD) using PHQ-9. (2) To compare accuracy of PHQ-9, Hamilton Depression Rating Scale, and ICD-10 for diagnosis of depression.

METHODS: Study design: A hospital-based prospective observational study. Site: Nepal Medical College Teaching Hospital, Jorpati, Kathmandu. Duration: November 2017 till June 2018. Ethics approval: Ethical Review Committee, NHRC. Sample size: 100. Consent: Informed and written taken. Inclusion criteria: (1) Patients above the age of 18 years and (2) HD at Nepal Medical College and Teaching Hospital >3 months duration. Exclusion criteria: (1) Refusal to give the consent. Patients on HD were asked to fill previously validated Nepali translated version of PHQ-9. Psychiatrist administered Max Hamilton Rating Scale for diagnosis and categorization of depression and also confirmed depression diagnosis with personal interview and labeled them based on ICD-10. SPSS v 17 was used for statistical analysis. Data were presented as mean (standard deviation) or median (interquartile range) and percentage. Sensitivity and specificity of the test were compared with the gold standard. P < 0.05 was considered statistically significant.

RESULTS: A total of 100 patients completed the study. The median age was 47.5 (33.0–60.75) years and median duration since HD was 24.0 (9.25–36.00) months. The prevalence of depression was 78% using PHQ-9 and 65% using Max Hamilton (HAD-17) score. 16% of patients had severe depression using PHQ-9 and 25% using HAD-17. Mean PHQ-9 score was 8.86 ± 5.48 and Max Hamilton score was 12.33 ± 7.01. The male-to-female ratio was 1.17:1. The most common symptom was fatigue (82%). Mean depression in males using PHQ-9 was 7 ± 4.33 and in females was 11.04 ± 5.90 with P < 0.001 (confidence interval [CI]: 2.00–6.08). Similarly, the mean depression in males using Max Hamilton score was 11.76 ± 6.75 and in females was 13.00 ± 7.32, with P = 0.38 (CI: 1.55–4.03). Age was not statistically significant for level of depression using any scales (P = 0.27). Comparing PHQ-9 with Max Hamilton score, the sensitivity of PHQ-9 was 84.62% (95% CI: 73.52–92.3) and specificity was 34.3% (95% CI: 19.13–52.21) with P = 0.04. On comparing with ICD-10, the sensitivity was 84.3% and specificity was 28.6%, with P = 0.15.

CONCLUSIONS: There is high prevalence of depression in patients on HD. PHQ-9 is good screening tool for the detection of depression in patients on HD. PHQ-9 is self-administered with nominal cost taking 1 min to complete. HAD-17 can be administered by in-house physician, especially in PHQ-9 score >9 for confirmation.


  11. Malignancy After Kidney Transplantation in India: A Single-Center Retrospective Cohort Study Spanning 42 Years Top


Anna T Valson, Sabina Yusuf, Jeethu Joseph Eapen, Elenjickal Elias John, Athul Thomas, Suceena Alexander, Anjali Mohapatra, Vinoi George David, Santosh Varughese

Christian Medical College; Vellore; Tamil Nadu; India

BACKGROUND: There have been no reports regarding the epidemiology of posttransplant malignancy (PTM) in Indian kidney-transplant recipients (KTRs) barring case series limited to posttransplant lymphoproliferative disease (PTLD) from various centers. We report here, for the first time, the incidence, risk factors, and outcome of PTMs at a single center spanning the years 1971–2013.

AIM OF THE STUDY: To determine the incidence rate of PTMs, age-adjusted rate ratio of PTM in relation to the general population, risk factors, and outcome of PTM in KTRs.

METHODS: In this retrospective cohort study, adult and pediatric KTRs who underwent renal transplantation at our center between 1971 and 2013 were included. Data pertaining to baseline characteristics, type of malignancy, details of treatment, and outcome were retrieved from transplant records and the hospital information system. The incidence rate of PTMs was calculated per 100,000 person-years of follow-up, and the age-adjusted incidence rate of various PTMs (per 100,000 person-years) was compared to the age-adjusted incidence rate of malignancies (per 100,000 population) reported in the National Cancer Registry for the years 1997–1998 to obtain the rate ratio of PTMs compared to the general Indian population. Cox proportional hazard analysis with time to malignancy as outcome was carried out to determine the independent predictors of PTMs. Data were censored at diagnosis of malignancy, death, or last follow-up visit.

RESULTS: Of 3136 patients who underwent kidney transplant during this period, 80 malignancies occurred in 78 patients over a median follow-up of 5.2 years. The median age at diagnosis of PTM was 45 years; 83% were male; and the median time to PTM was 8 years. The cumulative incidence of PTM was 2.5% with an incidence rate of 391.6 per 100,000 person-years. PTLD was the most common malignancy (n = 31; 38%); followed by nonmelanoma skin cancer (NMSC; n = 19; 23%); head and neck cancer (HNC; n = 11; 13.7%); and genitourinary cancer (GUC; n = 7; 8.7%). The risk of PTM was found to be 50-fold for PTLD; 5–10-fold for GUC; 3–5-fold for HNC; 2-fold for gut and hepatopancreatobiliary cancer; while NMSC population rates were not available. The risk for lung and breast cancer was similar to the general population. Cyclosporine-based immunosuppression, new-onset diabetes after transplant, and age >40 years at transplant were the independent predictors of PTM. Death and graft loss occurred in 31.2% and 8.7%, respectively.

CONCLUSIONS: PTLD, NMSC, HNC, and GUC have an incidence of 3–50 times that of the general population, reduction in immunosuppression is integral to their management and tailored cancer prevention programs are indicated. A diagnosis of lung or breast cancer may not require a reduction in immunosuppression.


  12. Risk Prediction of Acute Kidney Injury After Cardiac Surgery in a High-Risk South Asian Population: Data from a Single Center Top


Ankita Gharge, Shobhana Nayak1, Pradeep Shenoy1

Departments of General Medicine and1 Nephrology; K. S. Hegde Medical Academy; Nitte University; Mangalore; Karnataka; India

BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is a frequent postoperative complication associated with an increased risk of mortality, morbidity, and hospital costs. Preoperative risk scores such as the Cleveland Clinic Scoring Tool (CCST) have been validated in Western population group to identify patients at higher risk of AKI and may facilitate preventive strategies. However, the scoring tool has not been validated systematically in a South Asian cohort.

AIM OF THE STUDY: To evaluate the applicability of the CCST in prediction of AKI after open cardiac surgery in a South Indian tertiary care center.

METHODS: This was a retrospective study on all patients who underwent elective open cardiac surgery over 7 years from January 2012 to December 2018 at a single center, and relevant details were extracted from a comprehensive chart review. The primary outcome was AKI as defined by the Kidney Disease Improving Global Outcomes criteria. Patients were risk stratified as per the CCST to assess for prediction of AKI into low-risk (0–2); intermediate-risk (3–5); and high-risk (>6) groups.

RESULTS: A total of 490 patients underwent open cardiac surgery, with a mean age of 52.27 ± 12.03 years. Overall incidence of AKI was 11.6%. Mean age, sex, body mass index, preoperative serum creatinine, diabetes mellitus, chronic obstructive pulmonary disease, and cardiopulmonary bypass time were not statistically different in patients who developed AKI versus those who did not have AKI postoperatively. The mean CCST scores were 1.6 in those without AKI; 1.8 in Stage 1 AKI; 3.0 in Stage 2 AKI; and 4.3 in Stage 3 AKI. Higher risk scores predicted greater risk of AKI. A total of 108 patients (22%) were on angiotensinconverting enzyme (ACE)/angiotensin-receptor blockers (ARBs); 135 patients (27.5%) received beta-blockers; 119 (24.2%) received diuretics; while 193 (39.3%) had received preoperative statins. Comparison of drug use between the two groups revealed that preoperative use of ACEI/ARB was associated with highest risk of AKI (P = 0.006). Mortality rate was also high at 26.3% in those with AKI compared to 1.8% in non-AKI group (P = 0.04).

CONCLUSIONS: The modified CCST was valid in risk identification of patients with severe stage of AKI but did not have strong discrimination for early AKI stages. Preoperative statin use did not protect against AKI; however, preoperative ARB/ACEI use was significantly associated with occurrence of postoperative AKI.


  13. Association of Cyp3a5 Polymorphism With Trough Levels of Tacrolimus and Graft Outcomes in Indian Renal-Transplant Recipients Top


N Saxena, M Maurya, N J Gogtay, U M Thatte, T Jamale, D Bajpai, N K Hase

Seth G. S. Medical College and KEM Hospital; Parel; Mumbai; Maharashtra; India

BACKGROUND: Tacrolimus has narrow therapeutic index, and its dosing is associated with polymorphisms of liver enzyme CYP3A5.

AIM OF THE STUDY: Association of CYP3A5 genotype with renal graft outcome and tacrolimus trough levels; assess prevalence of CYP3A5 polymorphisms.

METHODS: Informed consent was obtained from renal-transplant recipients (4–80 years) on tacrolimus therapy for ≥3 months (N = 100). Genotyping was done for CYP3A5*1/*1 [expressors]; *1/*3 [intermediate expressors]; and *3/*3 [nonexpressors]. The association of dose-adjusted tacrolimus levels and acute and chronic rejection episodes was correlated with genotyping.

RESULTS: Chronic rejections were higher (P < 0.05) in CYP3A5*1/*1 group. There were higher tacrolimus trough levels in CYP3A5*3/*3 group (9.51 ± 4.13 ng/ml) on day 30; dose-adjusted tacrolimus levels were higher in the CYP3A5* 3/*3 group on day 30 (107.30 ± 63.15); day 180 (140.55 ± 91.35); and day 360 (142.56 ± 102.26) expressed in ng/ml(mg/kg)-1 compared with CYP3A5*1/*1 and *1/*3 groups. CYP3A5 genotype prevalence for *3/*3 genotype was 44%; for genotype *1/*3 was 36%; and for *1/*1 genotype was 20%.

CONCLUSIONS: Increase in number of chronic graft rejections and raised tacrolimus trough levels and dose-adjusted trough levels in CYP3A5*3/*3 group compared with CYP3A5*1/*1 and CYP3A5*1/*3 groups was found. Preprescription genotyping for CYP3A5 alleles may help optimize calcineurin inhibitor (CNI) levels and graft outcomes.


  14. Ketoanalog Supplementation Preserves Renal Function, but Decline in Renal Function Is Observed After Withdrawing Supplementation: A Follow-Up Study of Randomized Clinical Trial Top


Anita Saxena, Amit Gupta, Trisha Sachan, Anup Kumar

Departments of Nephrology and Biostatistics and Health Informatics; Sanjay Gandhi Post Graduate Institute of Medical Sciences; Lucknow; Uttar Pradesh; India

BACKGROUND: Preventing progression of chronic kidney disease (CKD) to end-stage renal disease is a concern for nephrologists. In CKD, postprandial hyperfiltration is associated with subsequent histological lesions and decreased glomerular filtration. Although low-protein diet alleviates uremic symptoms, it results in essential amino acid deficiency, thus deteriorating patient's nutritional status. Progression of renal failure can be retarded if patients are prescribed ketoanalogs-supplemented low protein diet.

AIM OF THE STUDY: (1) To evaluate effect of combined therapy of very low protein diet (vLPD) and ketoanalogs on renal function of patients in CKD Stage 2 and above and (2) to study compliance to vLPD.

METHODS: This was a prospective randomized controlled study approved by the ethics committee. Patients were divided into two groups of 20 each (15 males and 5 females) with glomerular filtration rate (GFR) <90 but >15 ml/min. Ketoanalog-supplemented group was advised vLPD 0.4 g/kg/day and supplemented with ketoanalogs 6 tablets/day (1 tablet/10 kg bw), and controls were kept on standard diet of 0.6 g/kg/day of protein. GFR was measured with 99mTc-DTPA nuclear scan and Cockcroft–Gault (CCG) formula. Intervention was for 10 months, and the patients were followed for 58 months after stopping ketoanalog supplementation. Biochemical profile included hemoglobin, serum creatinine, albumin, and random blood glucose. Nutritional status was assessed using Subjective Global Assessment (SGA) and 3 days of dietary intake. There was no significant difference in body weight and serum creatinine (supplemented 1.66 ± 0.484 and control 1.61 ± 0.48), protein (supplemented 35.11 ± 7.8 and control 31.30 ± 7.0 g/kg), and energy (supplemented 1104 ± 212.283.28 and control 1006 ± 261.25 kcal) intake between groups.

RESULTS: GFR was preserved in supplemented group till 22 months (46.71 ± 13.45; 45.12 ± 14.38; and 42.98 ± 13.35) after which it declined (37.86 ± 16.91; 39.60 ± 20.46; and 36.34 ± 18.96). In controls, decline was observed from baseline till 58 months (49.51 ± 15.19; 47.17 ± 16.47; 45.04 ± 16.35; and 30.68 ± 17.67; 31.55 ± 16.36; 34.14 ± 21.71). The rate of change in supplemented group was 1.59, −2.34, −12.08, −11.57, and −19.30 GFR/year and in controls was −2.53, −6.39, −32.24, −39.50, −44.02 ml/min/year. Kaplan–Meier survival analysis showed a faster decline in renal function in controls compared to treatment group (P = 0.031). None of the patients in treatment group reached Stage 5. In supplemented group, there was maintained serum albumin at baseline (4.28 ± 0.44 g/dL) and at 22 months (4.18 ± 1.95 g/dL). Significant decline was observed at 34 months (3.96 ± 0.49 g/dL). In controls, there was decline in serum albumin from baseline (3.81 ± 0.93 g/dL) to 36 months (3.69 ± 0.94 g/dL). Ketoanalog group was noncompliant to vLPD (protein 0.62/kg/day).

CONCLUSIONS: Effect of intervention was seen as slower decline in renal function compared to controls even without adherence to vLPD. In treatment group, probability of patient's transition into higher CKD stage was low. Patients can benefit from diet supplemented with ketoanalogs.


  15. Endothelial Injury in Iga Nephropathy Top


Niharika Bharti, Mohit Kumar Rai, Vinita Agrawal, Vikas Agarwal, Narayan Prasad, Rakesh Pandey

Departments of Pathology; Immunology and Nephrology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow; Uttar Pradesh; India

BACKGROUND: Microparticles (MPs) are 0.1–1.0 μm membrane vesicles shed from the damaged or activated cell surface following injury. MPs play an important role in promoting endothelial dysfunction and may prove to be true biomarkers of progression. Plasma concentration of von Willebrand factor (VWF) has been also used as an index of endothelial dysfunction. Because MPs can affect endothelial cells, this study investigated the relationship between circulating MPs and endothelial injury in IgA nephropathy (IgAN) patients.

AIM OF THE STUDY: To compare the presence of endothelial injury in patients with IgAN and healthy controls and to study the association between various histological parameters related to MEST-C score.

METHODS: Twenty-five biopsy-proven IgAN (mean age = 32.8 ± 8.2 years) and 25 healthy control (mean age = 30 ± 7.6 years) were recruited in this study. Platelet-poor plasma from citrated blood was isolated and centrifuged at 20,000 g (90 min) at 4°C. Endothelial MPs (EMPs) were analyzed by flow cytometry using EMPs specific antibodies for antiCD31-FITC and antiCD146-PE. All quantification related to size and number was done using cell count beads of known concentration. Detection of serum vWF was done by enzyme-linked immunosorbent assay with known standard concentration.

RESULTS: There is a significant increase in EMPs in patients with IgAN compared to healthy control (P < 0.05) and also EMPs strongly correlated with mesangial (P < 0.05) and endothelial hypercellularity (P < 0.05) in IgAN patients. There is a significantly elevated level of vWF in patients serum with IgAN compared to healthy controls (0.80 ± 0.17 pg/ml vs. 1.28 ± 0.22 pg/ml, respectively; P < 0.05). vWF, when compared to histopathological parameters, shows highly significant correlation with endothelial hypercellularity compared to without endothelial hypercellularity (with vs. without 1.16 ± 0.30 pg/ml vs. 0.89 ± 0.32 pg/ml; P < 0.05). vWF is also found elevated in IgAN patients with severe proteinuria (mild 0.76 ± 0.32 pg/ml; moderate 1.04 ± 0.24 pg/ml; severe 1.37 ± 0.10 pg/ml; P < 0.05) and hypertension (with vs. without 1.32 ± 0.17 pg/ml vs. 0.87 ± 0.24 pg/ml; P < 0.05).

CONCLUSIONS: Thus, this may be the simple and highly reproducible method useful for monitoring endothelial injury/dysfunction in IgAN.


  16. Acute Kidney Injury in Acute Myocardial Infarction and Its Outcome at 3 Months Top


Jaspreet Saini, Sanjay D'Cruz, Srinivas Reddy

Government Medical College and Hospital; Chandigarh; India

BACKGROUND: Studies on acute kidney injury (AKI) in acute coronary syndrome (ACS) have used different criteria to define AKI, leading to lack of heterogeneity and difficulty in interpretation of studies. Epidemiological data on the prevalence of AKI in ACS are sparse. Most of the studies are retrospective. Various risk factors for AKI have been identified. This study aims to prospectively analyze the incidence of AKI in patients of ACS and to identify the risk factors for AKI and their renal and cardiovascular outcomes at 3 months.

AIM OF THE STUDY: (1) To study the incidence and risk factors of acute kidney injury in acute myocardial infarction (AMI). (2) To study the 3-month renal and cardiovascular outcome of patients with AMI and AKI.

METHODS: This was a prospective, observational study carried over 18 months. A total of 80 patients were included. Inclusion cohort was adults presenting with the first episode of AMI. Patients were excluded if they denied consent, were on dialysis, had some other known cause of AKI, readmitted cases of ACS, or were renal allograft recipients. Demographic data, history, physical examination, and the type of management were noted and the data were entered. Standard criteria were used to diagnose AMI. Kidney Disease Improving Global Outcomes was used to diagnose AKI. Electrocardiography, urine analysis, renal function test (RFT), blood glucose levels, HbA1c, uric acid levels, and cardiac markers were done in all patients. All patients received nonionic contrast agents. RFT was done at the time of admission, at 48 h during hospital, or at the time of discharge. Follow-up along with RFT was done at 3 months.

RESULTS: Eighty patients with AMI were included. The mean age was 55.8 years; the male-to-female ratio was 7:3. 25% were diabetic; 33% were hypertensive; and 23.8% were smokers. The average serum creatinine at admission was 1.16 mg/dl. At presentation, 77.5% were Killip Class 1 and 11.3% were in Killip Class 2 and Killip Class 4. Eight patients died at 3 months; six of them had AKI at discharge. Conservative therapy was given to 27.5%, thrombolytic therapy was given to 32.5%, and 40% received percutaneous coronary artery intervention (PCI). At discharge, 7/80 patients had AKI. There was no significant difference seen between the incidence of AKI among three groups. At 3 months of follow-up, 5/72 had renal dysfunction. There was no significant difference seen between the incidence of AKI among three groups. Logistic regression analysis was performed to look at the predictors of AKI. Diabetic had increased incidence of AKI at discharge and at 3 months. Killip Class 4 at admission was associated with increased incidence of AKI at 3 months. The performance of PCI leads to no significant difference in the incidence of AKI.

CONCLUSIONS: In this study, determinants of AKI in ACS patients were Killip Class at admission and presence diabetes mellitus. Previous renal dysfunction, decreased ejection fraction, and risk factors such as smoking, hypertension, and coronary intervention did not have a bearing on the development of AKI.


  17. Plasmapheresis in Acute Severe Pancreatitis Top


Prawash Kumar Chowdhary, S A Kale Sandeep Pandey, Lalit Nihal, Vishal Singh, Rakesh Agrawal, Imran Prashant, Madhusudan

Ramkrishna Care Hospital; Raipur; Chhattisgarh; India

BACKGROUND: Severe hypertriglyceridemia is a well-known etiology of acute pancreatitis and is currently the third leading cause of acute pancreatitis after alcohol abuse and gall stone disease. Although various modalities exist for the management of such patients, apheresis is one such lesser-known therapeutic option.

AIM OF THE STUDY: To analyze the role of plasmapheresis in triglycerides (TGs)-induced pancreatitis.

METHODS: A retrospective chart review of patients who underwent plasmapheresis at Ramkrishna Care Hospital from March 2018 to April 2019 was done. A total of 18 patients underwent plasmapheresis. Fourteen patients were excluded for various other indications of plasmapheresis. Four patients fulfilled the criterion for severe hyper-TGs-induced acute pancreatitis with treatment modalities of plasmapheresis being used to lower TG level. The demographic profile, clinical presentation, and biochemical and radiological investigation with their clinical course were noted. Severity of the acute pancreatitis was done by Modified Atlanta Classification. Severe hyper-TGs were defined by serum TGs levels more than 1000 mg/dl.

RESULTS: The mean age of patients was 41.75 years, with an age range of 30–55 years. Mean TGs level on admission was 1416.75 mg/dl (range 1265–1718 mg/dl). All patients showed a significant improvement in TG level after plasmapheresis, but one died due to sepsis. The mean number of sessions of plasmapheresis was 1.25 (range 1–2). The mean TG after first session apheresis was 379.5 mg/dl (range 310–521 mg/dl). After the first session, the mean decrease in TG level was 73.45% (69.6%–76.6%). At the time of discharge, the mean TG of patients was 217 mg/dl (range 168–242 mg/dl). None of patients developed complications related to plasmapheresis. No evidence of gallstones on imaging was noted, and patients did not have any endoscopic intervention before admission to the hospital for acute pancreatitis.

CONCLUSIONS: Plasmapheresis is an effective and rapid treatment in patients with severe TG-induced acute pancreatitis. Plasmapheresis should be performed as early as possible to lower serum TG level below 350 mg/dl.


  18. Prevalence of Nonalcoholic Fatty Liver Disease in Chronic Kidney Disease: A Prospective Single-Center Study Top


Harish Saini, Shivendra Singh, Shiv Shankar Sharma, Prem Shankar Patel, Partha Pratim Mandal

Department of Nephrology; Institute of Medical Sciences; Banaras Hindu University; Varanasi; Uttar Pradesh; India

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome. Interestingly, NAFLD and chronic kidney disease (CKD) may share common pathogenic mechanisms such as obesity, abdominal obesity, insulin resistance, hyperlipidemia, hypertension, and inflammation. Accumulating clinical evidence indicates that the presence and severity of NAFLD are associated significantly with CKD, and it predicts the development and progression of CKD, independently of traditional cardiorenal risk factors.

AIM OF THE STUDY: (1) To study the prevalence of NAFLD in CKD. (2) To asses severity and risk factors of NAFLD in relation to CKD.

METHODS: This was an observational, cross-sectional study. A total of 200 cases of CKD above 18 years of age attending in the hospital over a 2-year period were included. Exclusion criteria were patients with chronic hepatitis B and/or C virus infection, cirrhosis of liver, high liver stiffness measurement (LSM) ≥13 kPa by FibroScan; those with alternative etiology of liver disease; history of alcohol intake ≥20 g/day for women and 30 g/day for men; pregnant females; and renal-transplant patients. Detail history, anthropometric examination, and investigation were done. CKD defined by estimated glomerular filtration rate (Modified Diet in Renal Disease formula) ≤60 ml/min/1.73 m2 for >3 months. NAFLD was diagnosed by lack of secondary causes of hepatic fat accumulation such as significant alcohol consumption, long-term use of a steatogenic medication, and detection of steatosis by abdominal ultrasonography (USG). Severity of NAFLD was assessed by grading of steatosis on USG and presence and degree of hepatic fibrosis as measured by FibroScan.

RESULTS: Of 200 CKD patients, 132 were male and 68 were female with an average age of 64.9 ± 8.6 years. Among them, 41% had diabetic etiology while 59% had nondiabetic etiology. 32.5% of patients had CKD Stage III, 43% CKD Stage IV, and 24.5% CKD Stage V. Prevalence of NAFLD was 58.5% (n = 117) by USG abdomen, which revealed 32 (27.3%) Grade I (mild) steatosis, 58 (49.57%) Grade II (moderate) steatosis, and 27 (23.07%) Grade III (severe) steatosis. Hepatic fibrosis was measured by FibroScan revealed that 58 (49.57%) patients had no fibrosis (LSM ≤5.7 kPa); 38 (32.47%) had significant fibrosis (LSM >7 kPa; ≥F2); 21 (17.9%) had advance fibrosis (LSM >8.7 kPa ≥F3). The number of NAFLD-positive patients was not significantly different between CKD stages. Severity of liver steatosis was negatively correlated with kidney function (P < 0.01). CKD with NAFLD has high fasting blood sugar, body mass index, and triglycerides as compared to non-NAFLD patients.

CONCLUSIONS: The study suggests a high prevalence of NAFLD in CKD. Screening and early preventive measures may go long way in reducing morbidity.

[TAG:2]19. Expression and Function of P-Glycoprotein and Multidrug Resistance-Associated Protein-1 and Presence of Homozygous Mutant of Multidrug Resistance-Associated Protein-1 Single Nucleotide Polymorphism G2677t/a Identify Steroid Resistance Phenotype in Childhood Idiopathic Nephrotic Syndrome[/TAG:2]

Harshit Singh, Narayan Prasad, Akhilesh Kumar Jaiswal, Vikas Agarwal1, Mantabya Kumar Singh, Ranjeet Chauhan

Departments of Nephrology and1 Clinical Immunology; SGPGIMS; Lucknow; Uttar Pradesh; India

BACKGROUND: Steroids remain the mainstay of therapy for idiopathic nephrotic syndrome (INS). Other than histological changes, pharmacogenomic factors may also affect steroid response. Overexpression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1) modulate the pharmacokinetics of steroids and may contribute to steroid resistance.

AIM OF THE STUDY: To study expression and function of P-gp and MRP-1 also to correlate MDR-1 polymorphism with P-gp expression and whether expression of P-gp and MRP-1 can predict steroid resistance in NS patients.

METHODS: Flow cytometric evaluation of P-gp, MRP-1 expression on whole blood, and functional activity on peripheral blood mononuclear cells were carried out in steroid-sensitive NS (SSNS) (n = 170; male 103; mean age = 8.54 ± 4.3 years) and steroid-resistant NS (SRNS) (n = 81; male 43; mean age = 7.43 ± 4.6) patients. The genetic variants of MDR-1 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism technique.

RESULTS: Expression of P-gp (9.80 ± 3.44 and 4.36 ± 2.05; P < 0.001) and MRP-1 (13.46 ± 4.80 and 7.75 ± 3.22; P < 0.001) on lymphocyte were significantly higher in SRNS than SSNS. Functional activity of P-gp and MRP-1 was significantly increased in SRNS as compared to SSNS (66.26 ± 15.77 and 30.82 ± 9.87, P < 0.001 and 67.62 ± 14.67 and 32.97 ± 11.36, P < 0.001, respectively). Receiver operating characteristic curve analysis of 81 steroid-resistant patient's predictive cutoff values for P-gp and MRP-1 was found to be 7.13% and 9.62%, respectively, with sensitivity of 90% and 80.7% and specificity of 90% and 80%, respectively. Moreover, MDR-1 homozygous-mutant allele TT + AA for G2677T/A was significantly associated with SRNS (P = 0.025, odds ratio = 2.86, confidence interval = 1.14–7.14). However, heterozygous (GT + GA) and mutant alleles (T + A) were not significantly associated with SRNS patients as compared to SSNS patients. Moreover, expression of P-gp (9.68 ± 4.99 vs. 5.88 ± 3.38, P = 0.002) was significantly higher in the patients of homozygous-mutant alleles compared to wild-type GG.

CONCLUSIONS: Overexpression and increased functionality of P-gp and MRP-1 may contribute to steroid resistance, and polymorphism of MDR-1 variants G2677T/A may promote steroid resistance by inducing P-gp expression in INS in children.


  20. Prevalence of Incomplete Distal Renal Tubular Acidosis in Patients With Recurrent Renal Stone Disease Top


Rohit Raj, M Sreelatha, T P Noushad, E K Jayakumar

Department of Nephrology; Government Medical College; Kozhikode; Kerala; India

BACKGROUND: Renal stones are a common problem in primary clinical practice and its incidence is on the rise. Distal renal tubular acidosis (dRTA) is a probable cause for recurrent renal stone disease. Incomplete dRTA, a relatively underdiagnosed entity, is characterized by defective urinary acidification ability in the absence of systemic metabolic acidosis and contributes to recurrent stone formation. It is often asymptomatic and goes unnoticed unless the patient is subjected to acid loading test.

AIM OF THE STUDY: To study the prevalence of incomplete dRTA among patients with recurrent renal stone disease in our population and to study the biochemical profile and risk factor in incomplete distal RTA patients.

METHODS: This is a cross-sectional study done in patients with recurrent renal stone disease, carried out in the outpatient clinics and wards of the Department of Nephrology and Urology, Government Medical College. Relevant clinical data and a detailed stone history were collected. Laboratory investigations including routine biochemistry, 24-h urine study, and metabolic workup were done. All patients were subjected to acid load test. A baseline urine pH and arterial blood gas (ABG) analysis were done at 0 h. Patient was then asked to take 100 mg/kg of ammonium chloride orally, and their urine pH was measured along with a corresponding ABG analysis after 3 h.

RESULTS: Thirteen patients could not complete the study as they had developed gastrointestinal intolerability to oral ammonium chloride and hence were withdrawn. Results of remaining 105 patients were analyzed. Majority of the patients were in the age group of 41–50 years. 41% had bilateral renal calculi. Nephrocalcinosis was seen in eight patients out of the total 105. Sixty-six patients had multiple stones and 25 had staghorn calculi. Majority of them had calcium oxalate stones on stone analysis. 33.3% of the patients had a urine pH ≥5.5 at 3 h after acid loading, indicating an acidification defect in distal tubules. Hence, the prevalence of incomplete dRTA in our study population is 33.3%. The mean 24-h urine citrate excretion in patients with incomplete dRTA was significantly low (P = 0.000) as compared to those without incomplete dRTA. The mean 24-h urine phosphorus excretion in individuals with incomplete dRTA was significantly high (P = 0.003).

CONCLUSIONS: The prevalence of incomplete dRTA is 33.3% among patients with recurrent renal stone disease in our population. The 24-h urine citrate levels are significantly low in patients with incomplete dRTA and are the most likely cause for stone formation in them.


  21. Incidence, Risk Factors, and Patient Outcomes of Acute Kidney Injury in Patients Undergoing Living Donor Liver Transplant Top


Abhyudaysingh Rana, Shyam B Bansal, Arvinder S Soin, Amit Mahapatra, Ashwini Gadde, Neeraj Saraf, Vijay Kher

Department of Nephrology; Medanta Medicity; Gurgaon; Haryana; India

BACKGROUND: Acute kidney injury (AKI) is a common postoperative complication after liver transplant (LT). Early posttransplant AKI has been associated with increased rates of acute rejection and infectious complications, longer intensive care unit (ICU) stays, higher mortality rates, and poor long-term survival independent of pretransplant renal function. There is dearth of data on AKI in patients' post-living donor LT (LDLT) from India; hence, the study to assess incidence rate, risk factor, and outcome in AKI in post-LDLT at our center was chosen.

AIM OF THE STUDY: The aim of this study is to assess the incidence, risk factor, and outcomes of patient developing AKI in patients undergoing LDLT (postoperative 1-month period).

METHODS: Patients over age of 18 years undergoing LDLT at our center were selected consecutively from January 2019 to April 2019, prospectively followed for 1 month postoperative to assess incidence of AKI (early ≤7; late >7 to <30) and reassessed at 3 months for persistence of renal dysfunction. Patients with fulminant liver failure, those undergoing combined liver kidney transplant, and patients who died within the first 72 h post-LT were excluded. AKI was defined by Kidney Disease Improving Global Outcomes criteria. Preoperative, intraoperative, and postoperative variables were analyzed for risk factor and patient outcomes by regression analysis.

RESULTS: Sixty-two patients underwent LDLT between January 2019 and April 2019. 22 (35%) patients developed AKI. 15 (68%) had Stage 1 AKI; 5 (23%) Stage 2; and 2 (9%) had Stage 3 AKI requiring continuous renal replacement therapy (CRRT). 14 (64%) patients had early AKI while 8 (36%) had late AKI. Acute Calcineurin Inhibitor (CNI) toxicity (3; 14%) was the most common cause of early AKI. Most common cause of late AKI was sepsis (7; 11%). Use of vasopressors intraoperative and the history of AKI hepatorenal syndrome (HRS) were the only statistically significant (P < 0.001) risk factors for AKI. The mean ICU stay among patients with AKI was 7.2 ± 4.2 versus 4.5 ± 1.2 days in patients without AKI. Median days to normalization of liver enzymes in non-AKI group were 10 versus 20 days in AKI group. Two (3.2%) patients had persistence of renal dysfunction at 3 months. Seven (11.2%) patients died during the analysis period; 2 (3%) of them from AKI group.

CONCLUSIONS: Incidence of AKI (35%) was higher as compared to other cohort but lead to CKD in only two patients. History of AKI was a significant risk factor. Although AKI was transient and lead to increase ICU stay and prolonged normalization of graft function in patients undergoing LDLT.


  22. Peritoneal Dialysis Technique Failure: Results from a Large Tertiary Care Center in Southern India Top


V C Annamalai, Santosh Varughese

Department of Nephrology; Christian Medical College; Vellore; Tamil Nadu; India

BACKGROUND: Peritoneal dialysis (PD) is an established form of renal replacement therapy (RRT) for patients with end-stage kidney disease (ESKD). Patients on PD experience significantly shorter technique survival compared with patients on hemodialysis (HD). PD-related infections, catheter complications, inadequate peritoneal ultrafiltration, inadequate small solute clearance, and psychosocial barriers are the important causes of technique failure.

AIM OF THE STUDY: (1) To determine the reasons for PD technique failure. (2) To determine if undergoing HD before initiation of PD is associated with technique failure.

METHODS: Data were obtained from patient records for obtaining demographic data, laboratory parameters, etiology of ESKD, concomitant comorbidities, date of RRT initiation, initial RRT modality, duration of HD before PD initiation, catheter-related complications, and causal factor for technique failure. PD technique failure was defined as switch of RRT modality from PD to HD for 3 months or more, excluding death, renal transplantation, or recovery of renal function sufficiently as to stop RRT.

RESULTS: During the study period, 294 patients underwent PD catheter insertion at our center. Twenty-six patients (8.8%) had technique failure, the most common cause being PD catheter-related infective complications (65.4%). Eleven of 26 patients who had technique failure (42.3%), compared to 4 of 55 patients continuing on PD (7.3%), had received HD for more than 8 weeks before PD initiation (P = 0.001). Poor PD fluid outflow in the initial period was associated with technique failure – 9 patients (34.6%) versus 4 patients (7.3%, P = 0.002). Peritonitis after 4 weeks of PD catheter insertion occurred in 21 patients (80.8%) with technique failure, compared to 17 patients (30.9%) continuing on PD (P < 0.0001).

CONCLUSIONS: Similar to available worldwide data, the most common cause of technique failure was PD-related infection. HD for more than 8 weeks before PD initiation, poor PD fluid outflow in the initial period, and occurrence of late peritonitis were significantly associated with technique failure.


  23. Effect of Low-Intensity Intradialytic Exercises on Urea-Creatinine Clearance and Fatigue Level in Patients Undergoing Hemodialysis Top


Anubha Devagourou, Kamlesh K Sharma, Raj Kanwar Yadav, V P Gupta

Department of Nephrology; AIIMS; Delhi; India

BACKGROUND: In chronic kidney disease (CKD) patients, toxins accumulate in the muscles and cause fatigue, mental impairment, and muscle dysfunction (cramps). Exercises result in opening of capillaries and increased blood flow, thereby greater movement of urea and creatinine from the tissues to the vascular compartment and subsequent removal through dialysis.

AIM OF THE STUDY: To evaluate the effect of low-intensity intradialytic exercises (IDEs) on urea-creatinine clearance and fatigue level in patients undergoing hemodialysis (HD).

METHODS: This is a quasi-experimental study conducted at HD unit of AIIMS, New Delhi. Sixty-four CKD Stage 5 patients were enrolled using total enumeration and divided into experimental and control groups (32 each). Pre- and post-HD serum urea, creatinine, and fatigue levels were assessed at baseline, 2, 4, and 6 weeks. A set of six low-intensity IDEs were implemented for experimental group patients 90 min after the start of HD. Exercises were repeated thrice at an interval of 10 min. Blood samples for serum urea creatinine were sent to the Renal Laboratory, AIIMS, and FACIT fatigue scale was used to assess fatigue levels of the patients.

RESULTS: Data were analyzed using descriptive and inferential statistics. Statistically significant difference was found between the control and experimental groups in terms of serum urea, creatinine, and fatigue levels (P = 0.007, 0.001, and 0.001, respectively) at 6 weeks post-HD. Within the experimental group, there was significant decrease in serum creatinine levels from baseline to 6 weeks (P = 0.04). It was found that 97% of experimental group patients were compliant to low-intensity IDEs with 99.3% in the upper limb and 86% in lower limb exercises. Patients in the experimental group also reported that they felt better and comfortable with the use of IDE with decrease in felt fatigue levels. There was no significant association between duration of illness, duration of maintenance HD, and comorbidities with serum urea, serum creatinine, serum, and fatigue levels.

CONCLUSIONS: The present study shows that low-intensity IDEs performed regularly were effective in decreasing serum urea, creatinine, and fatigue levels of CKD patients undergoing HD with vital signs remaining within the normal range. No overt complications were reported; hence, the exercises were also safe.


  24. Clinico-Pathological Spectrum of Primary Iga Nephropathy among Adults in North India Top


Mudit Khurana, Narayan Prasad, Amit Gupta, Anupama Kaul, D S Bhadauria, M R Patel, M R Behra, M Yachha

Department of Nephrology, Sanjay Gandhi Postgraduate Institute; Lucknow; Uttar Pradesh; India

BACKGROUND: Primary IgA nephropathy is the most common glomerular disease in the world and a major contributor to the worldwide burden of end-stage renal failure. There is wide geographic variation in the incidence as well as clinico-pathological spectrum of IgA nephropathy and limited data are available from the developing world.

AIM OF THE STUDY: To determine the clinical profile and histological pattern of IgA nephropathy in our institute.

METHODS: We retrospectively reviewed all patients who had biopsy-proven primary IgA nephropathy between 2007 and 2018. Diagnosis of IgA recurrence was made on the basis of immunofluorescence finding of dominant or codominant IgA deposition. Their clinical presentation and histopathological data were analyzed.

RESULTS: A total of 560 patients of primary IgA nephropathy were reviewed; 406 (72.5%) were males; and the mean age of presentation was 31.97 years. Most common presentation was chronic kidney disease (CKD), with 307 (54.8%) patients presenting as CKD. Macroscopic hematuria was the least common presentation, seen in only 26 (4.6%) patients, while nephrotic syndrome occurred in 18.6% of patients, and 15% of patients were diagnosed because of asymptomatic urinary abnormality. Hypertension occurred in majority of the patients; 391 (69.8%) patients had hypertension at the time of presentation and 13 (2.3%) patients presented with hypertensive emergencies. Microhematuria occurred in majority of the patients (63.2%); and mean proteinuria at the time of presentation was 4.21 g/day with 262 (46.8%) patients having nephrotic range proteinuria. Renal biopsy showed diffuse global glomerulosclerosis (HAAS-V) in 205 patients (36.6%) and crescents occurred in 177 (31.6%) biopsies.

CONCLUSIONS: Our study like previous studies from India revealed severe clinical presentation of IgA nephropathy, characterized by hypertension, renal insufficiency, and nephrotic range proteinuria with advanced histological stages.


  25. Retrospective Cohort Study of Demography, Clinical, and Histopathological Profile of Infection-Related Glomerulonephritis in Adult Patients and Predictors of Outcome (Grace Irgn Trial) Top


Elenjickal Elias John, Jeethu Joseph, Anjali Mohapatra, Anna T Valson, Shibhu Jacob, Athul Thomas, Vinoi George, Succena Alexander, Santosh Varughese

???; Christian Medical College; Vellore; Tamil Nadu; India

BACKGROUND: Infection-related glomerulonephritis (IRGN) is primarily a disease that occurs after an upper respiratory tract infection (URTI) or impetigo; its occurrence in adult patients is undergoing changes in clinical presentations, histopathological findings, and outcomes. Here, we report the largest series of biopsy-proven IRGN in 710 adult patients who underwent renal biopsy at Christian Medical College, Vellore, between January 2005 and December 2017.

AIM OF THE STUDY: (1) To analyze the demography and clinical profile of patients with IRGN. (2) To study various histopathological parameters of patients with IRGN. (3) To analyze various predictors of renal outcome.

METHODS: The male-to-female ratio was 2.6:1. An immunocompromised background was present in 48%, the most common being diabetes mellitus. The most common site of infection was skin, followed by lower respiratory tract infection, urinary tract infection, and URTI. No underlying infection could be detected in 22% of patients. The most common causative agent was Staphylococcus (35%) followed by Streptococcus (22%) and Gram-negative organisms. Hypocomplementemia was present in 76%. The mean peak serum creatinine was 2.6 mg/dl and 32% of patients required hemodialysis. Nephrotic range proteinuria was present in 26% of patients. The most common light microscopic patterns were diffuse (68%), mesangial (18%), membranoproliferative (12%), and focal (2%) proliferative GN. IgA-dominant IRGN occurred in 14% and crescentric GN in 9% cases.

RESULTS: Of the 506 patients with ≥3 months of follow-up (mean 17 months), 46% achieved renal remission, 21% had renal stabilization, 18% developed renal worsening, and 15% progressed to end-stage renal disease (ESRD). The presence of diabetes, higher creatinine at diagnosis, dialysis at presentation, the presence of diabetic glomerulosclerosis, and greater tubular atrophy and interstitial fibrosis, presence of fibrous crescents, and IgA-dominant deposits predicted ESRD. Age below 50 years and use of steroid predicted renal remission and faster time to remission. IRGN patients diagnosed between 2012 and 2017 as compared to before 2012 had higher creatinine at presentation, predominant C3 deposits, and lower renal remission rates.

CONCLUSIONS: The epidemiology of IRGN is shifting with time. There is need for prospective studies to evaluate role of steroids in adults with IRGN.


  26. Genetic Predisposition With Regard to the Role of Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases in Allograft Rejections Following Renal Transplantation Top


Mansi Bhatt, Aneesh Srivastava, Narayan Prasad1

Departments of Urology and1 Nephrology; SGPGIMS; Lucknow; Uttar Pradesh; India

BACKGROUND: Allograft rejection remains to be one of the crucial impediments in successful renal transplantation. Matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases [TIMPs]) play an important role in immune-mediated tissue destruction of the allograft by allowing influx of leucocytes and mononuclear cells into the graft. The study of MMPs and TIMPs in transplant rejection may also lead to novel approaches in the therapy of rejection processes.

AIM OF THE STUDY: To investigate the association of functional polymorphisms in MMP-1, MMP-3, MMP-9, TIMP1, and TIMP3 gene with risk of allograft rejection in renal-transplant recipients of North India.

METHODS: A total of 200 live-related renal-transplant donors and recipients pairs' blood sample were collected and were genotyped for MMP-1 (-1607 1G/2G); (-519 A/G); MMP-3 (5356 A/G); (1161 A/G); MMP-9 (1721G/C); (Q279R A/G); (R668Q G/A); TIMP1 (+536 C/T) and TIMP3 (-1298 C/T) gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism methodology. All 200 renal-transplant recipients were categorized into 162 nonrejecters and 32 rejecters and were analyzed further. All the statistical analysis was done using SPSS software.

RESULTS: The genotype frequencies of MMP-1 (-1607 1G/2G, 2G/2G; odds ratio [OR] =2.97; 95% confidence interval [95% CI] = 1.69–5.20; P ≤ 0.05); MMP-9 (Q279R, RQ; OR = 0.47; 95% CI = 0.25–0.99; P = 0.02 and QQ; OR = 0.49; 95% CI = 0.25–0.94; P = 0.03); MMP-9 (P574R, PR; OR = 2.70; 95% CI =1.77–4.13; P ≤ 0.05 and RR; OR = 2.70; 95% CI = 1.09–6.71; P = 0.03); TIMP-1 (+536 C/T, CT; OR = 15.41; 95% CI = 9.12–26.05; P ≤ 0.05 and TT; OR = 7.01; 95% CI = 3.39–14.49; P ≤ 0.05); and TIMP-3 (-1298 C/T, CT; OR = 0.31; 95% CI = 0.19–0.50; P ≤ 0.05) were significantly associated with allograft rejection. On comparison of genotypic frequencies of nonrejecters with donors, a significant association was observed in MMP-1 (-1607 1G/2G) (P ≤ 0.05); MMP-9 (Q279R) (P = 0.02); MMP-9 (P574R) (P ≤ 0.05); TIMP-1 (P ≤ 0.05), and TIMP-3 (P ≤ 0.05). MMP-1 (-1607 1G/2G) (P ≤ 0.02); MMP-9 (P574R) (P ≤ 0.05); TIMP-1 (P ≤ 0.05), and TIMP3 (P = 0.01) were also found significantly associated on comparison between rejecters and donors.

CONCLUSIONS: Mutant genotypes/alleles for MMP-1 (-1607 1G/2G), MMP-9 (Q279R), MMP-9 (P574R), TIMP-1, and TIMP-3 are associated with reduced risk for allograft rejection and improved allograft survival in North Indian transplant recipients and could serve as an ideal marker to predict pretransplant allograft outcome.


  27. Prevalence and Risk Factors for Impaired Kidney Function at Uddanam Region, India: A Cross-Sectional Population-Representative Survey in Those at Risk of Chronic Kidney Disease of Unknown Etiology Top


Balaji Gummidi, Oommen John, Arpita Ghosh, Vivekanand Jha; on Behalf of the CKDu-Andhra Pradesh Steering Committee

???; George Institute for Global Health; New Delhi; India

BACKGROUND: High prevalence of chronic kidney disease (CKD) not associated with known risk factors, dubbed Uddanam nephropathy, has been reported from coastal districts of Andhra Pradesh, India. Despite the reported high burden of CKD, systematic estimation of the prevalence of CKD or its causes in this region has not been undertaken.

AIM OF THE STUDY: To estimate the proportion of individuals with CKD including those without any known cause in the Uddanam region of Andhra Pradesh and to determine association with known and novel risk factors.

METHODS: We conducted a cross-sectional study of the representative population of the Uddanam region through multistage cluster random sampling methodology. A total of 2419 participants were recruited between May and December 2018 from 167 villages divided into 60 clusters. All abnormal estimated glomerular filtration rate (eGFR, estimated using CKD-EPI equation) and proteinuria values were reconfirmed after 3 months. A detailed risk factor analysis is being undertaken. CKDu was defined as eGFR <60 ml/min/1.73 m2 and/or uPCR >0.15 at two time points 3 months apart in individuals who do not have diabetes, long-standing (>5 years' duration) hypertension, or uPCR >3. We describe the prevalence of CKD and CKDu in this population and their clinico-demographic correlates.

RESULTS: The mean age of participants was 45.7 (±13.3) years; 51% were females. The eGFR distribution in the study subjects was ≥60 ml/min/1.73 m2 in 2098 (86.7%); 30–60 in 208 (8.6%); 15–29.9 ml/min in 81 (3.3%); and <15 ml/min in 32 (1.3%) subjects. The uPCR distribution was as follows: ≤15 in 2004 (82.8%); 0.15–0.29 in 174 (7.2%); 0.3–2.99 in 240 (9.9%); and ≥3 in 1. A total of 508 (21%) had CKD, with the mean age being 51.82 (±13.11) years; 154 (6.4%) were known to have CKD and 384 (74.6%) were newly diagnosed during the present evaluation. A total of 363 (15%) participants met the criteria of CKDu. Modified Poisson regressions analysis showed that males (aRR = 1.42 [1.16–1.76]), landless/unskilled manual laborer (aRR = 1.45 [1.13–1.83]), tobacco use (aRR = 1.75 [1.42–1.73]), alcohol intake (1.6 [1.29–1.98]), family history of hypertension (1.10 [0.96–1.23]), and diabetes (1.15 [1.01–1.27]) were risk factors associated with CKDu. Prevalence of CKD and CKDu varied across the clusters, ranging from 47% to 2%.

CONCLUSIONS: This study, conducted using standardized methodology, demonstrates a high prevalence of CKD and CKDu in Uddanam. CKDu is associated with unskilled labor, tobacco use, and alcohol use. The ongoing longitudinal study will help to clarify understanding of etiology, risk factor, and natural history of CKDu.


  28. Next-Generation Sequencing of Micrornas Revealed Involvement of Mitogen-Activated Protein Kinase Pathway in Patients With Chronic Antibody-Mediated Rejection of Renal Transplant Top


Sushma Singh, Mantabya Singh, Harshit Singh1, Vikas Agrawal1, Narayan Prasad

Departments of Nephrology and1 Clinical Immunology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow; Uttar Pradesh; India

BACKGROUND: MicroRNAs (miRNAs) are noncoding RNA that play a pivotal role in modulating expression of multiple target genes at posttranscriptional level and have potential to modulate physiological and pathological processes, thus can be used as potential therapeutic targets. The impact of miRNA regulations have been shown in various kidney disorders, but its involvement in allograft function and immunity has not been investigated thoroughly; thus, we studied the miRNAs expression involved in chronic antibody-mediated rejection (CABMR).

AIM OF THE STUDY: The impact of miRNA regulation involved in allograft function and immunity has not been investigated thoroughly; thus, we studied the miRNAs expression involved in CABMR.

METHODS: Patients with CABMR (Banff's Classification-2017) were included. 25 blood donors (male = 18) with a mean age of 52.4 years were served as controls. Samples were processed for RNA isolation. Massive parallel sequencing was performed by HiSeq 3000 sequencing system (Illumina Inc.; USA). The data were processed and filtered using the miRNA analysis app (Illumina Inc.; USA) and analysis was performed using the BaseSpace Sequence Hub genomics computing environment (Illumina Inc; USA). Dysregulated miRNAs were detected by quantitative miRNA stem-loop RT-PCR technology (TaqMan MicroRNA Assays, Applied Biosystems, CA) as per the manufacturers' protocol. Expression was measured by calculating fold change. Targets of dysregulated miRNAs were predicted by computational analysis using bioinformatics tools as well as using databases. Pathway analysis of predicted targets was performed using DIANA-mirPath online analysis tool and KEGG database. Evaluation of MAPK signaling pathway was done by immunohistochemistry.

RESULTS: A total of 46 patients (male = 40 with a mean age of 46.82 years) were enrolled for the study with posttransplant duration of 33.72 months. The demographic details with mean values were serum creatinine = 1.68 mg/dl; BUN = 28.26 mg/dl; tacrolimus (Tac) level = 5.98 ng/ml; serum uric acid = 6.95 mg/dl; serum albumin = 3.46 g/dl; and Na+/K+ = 128.9/4.16 mmol/L. Induction regimen (basiliximab = 40; ATG = 6) baseline immunosuppression MMF + Pred (Tac/cyclosporine) = 43/3. C4d were positive in 23 and DSA were positive in 3 patients. The expression of highly dysregulated miR-9 (P ≤ 0.0001), miR-21 (P = 0.0024), miR-29a (P = 0.0001), miR-126 (P = 0.0076), miR-210 (P = 0.0001), and miR-223 (P = 0.0006) was significantly upregulated in CABMR patients compared to healthy controls. Pathway analysis shows involvement of MAPK signaling pathways, TGF-β superfamily signaling pathways, Wnt signaling pathways, and ErbB signaling pathways. Immuno Histochemistry (IHC) of MAPK signaling shows significantly positive cytoplasmic tubular intensity as well as inflammatory cells intensity.

CONCLUSIONS: Altered miRNA expression profiling was found in CABMR compared to healthy controls. MAPK signaling pathways are involved in the pathogenesis of CABMR. miRNAs are crucial regulators of cell function. They are easy to detect and represent potentially good targets for novel therapies.


  29. Obesity Modulates Effect of Vitamin D Supplementation on Inflammatory Markers in Chronic Kidney Disease Top


Prabhjot Kaur, Ashok Kumar Yadav1, Vivek Kumar, Kajal Kamboj, Vivekanand Jha2

Departments of Nephrology and1 Experimental Medicine and Biotechnology; Post Graduate Institute of Medical Education and Research; Chandigarh;2 George Institute for Global Health-India; New Delhi; India

BACKGROUND: Circulating interleukin (IL)-6 and high sensitivity C-reactive protein (hsCRP) levels are biomarkers of inflammation in chronic kidney disease (CKD). We had observed favorable effect of cholecalciferol supplementation on IL-6 but not hsCRP in Stage G3–4 nondiabetic CKD in our placebo-controlled randomized controlled trail. As obesity is considered to modulate coupling of IL-6 and hsCRP, we sought to see if this observed uncoupling in our previous study could be explained by status of obesity in the study population.

AIM OF THE STUDY: To compare change in IL-6 and hsCRP levels in cholecalciferol and placebo arms of our previous trial when stratified by groups based on body mass index (BMI).

METHODS: This is a secondary analysis of our previously published clinical trial (https://jasn.asnjournals.org/content/28/10/3100). Briefly, adult patients with nondiabetic CKD Stage G3–4 and Vitamin D deficiency (≤20 ng/ml) were randomized to receive two doses of either 300,000 IU of cholecalciferol or placebo at baseline and after 8 weeks. The primary outcome was change in Fibromuscular Dysplasia (FMD) at 16 weeks. IL-6 and hsCRP were measured at baseline and 16 weeks. For this analysis, the study population was further subdivided into two subgroups based on BMI (≤25 and >25 kg/m2). Differences in change in IL-6 and hs-CRP in either arm, when stratified by groups based on BMI, were compared by Student's t-test and paired t-test.

RESULTS: A total of 120 subjects were enrolled. Cholecalciferol supplementation led to significant favorable change in FMD. Baseline IL-6 and hsCRP levels were comparable in both arms even in subgroups defined by BMI. Overall, IL-6 levels decreased significantly in cholecalciferol arm, but hsCRP did not change between treatment arms at 16 weeks. When stratified by BMI category, IL-6 and hsCRP levels did not change significantly at 16 weeks in the placebo arm. In the cholecalciferol arm, significant decrease in levels of IL-6 was seen in both groups stratified by BMI (P = 0.018 for BMI ≤25 and P = 0.007 for BMI >25). However, hsCRP levels decreased significantly only in group with higher BMI (P = 0.784 for BMI ≤25 and P = 0.028 for BMI >25).

CONCLUSIONS: The coupling of change in IL-6 and hs-CRP levels in cholecalciferol arm only in obese subjects suggests that underlying obesity modulates changes in these inflammatory markers. These observations require further study to enable meaningful interpretation of changes in these biomarkers in CKD.


  30. Nitrosodimethylamine and Methylamine, Novel Metabolites in Systemic Sclerosis, May Drive Dual Pathogenic Processes of Endothelial Cell Apoptosis and Fibrosis Top


Mohit Kumar Rai, Durga P Misra, Sakir Ahmed, Durgesh Dubey, Atul Rawat, Dinesh Kumar, Vikas Agarwal

Department of Immunology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow; Uttar Pradesh; India

BACKGROUND: Proton-based nuclear magnetic resonance (1HNMR) serves as an open-ended approach to quantify small molecules in body fluids. We analyzed metabolic perturbations in sera of patients with systemic sclerosis (SSc) to identify potential biomarkers of the disease.

AIM OF THE STUDY: To find the novel metabolite present in the serum SSc patients and their role in their pathogenesis.

METHODS: Sera from 87 patients meeting the ACR 1980 criteria for SSc and 40 age and sex similar controls were analyzed using 1HNMR spectroscopy coupled with multivariate statistical analysis.

RESULTS: There was clear distinction between SSc and healthy controls on partial least square-discriminate analysis (R2 = 0.98). Several metabolites of discriminatory relevance were identified and further evaluated using analysis of variance and receiver operating characteristic curve analysis. N-Nitrosodimethylamine (NDMA), citrate, malonate, and a derivative of methylamine were four metabolites that had maximum area under curve (>0.95) in distinguishing patients with SSc from controls. Both NDMA and a derivative of methylamine were uniformly elevated almost exclusively in SSc patients. In addition, in vitro, methylamine could induce apoptosis in endothelial and fibroblast cells in a dose-dependent manner. Methylamine significantly potentiated fibroblasts isolated from SSc patients to express profibrotic genes (COL1A1, COL1A2, ACTA2, CTGF, FN1, and TIMP1) (P < 0.05) in a dose-dependent manner.

CONCLUSIONS: NDMA and methylamine may be potential biomarkers in SSc, which induced endothelial cell apoptosis as well as drove a profibrotic phenotype in fibroblasts from SSc patients, which are the key pathogenic processes in SSc.


  Rekha Presentation Top



  1. A Study of Insulin Resistance in Nondiabetic Chronic Kidney Disease Patients Top


Praveen Nallamothu, B Sangeeta Lakshmi, Rapur Ram, Vishnubotla Siva Kumar

Department of Nephrology; Sri Venkateswara Institute of Medical Sciences; Tirupati; Andhra Pradesh; India

AIM OF THE STUDY: To assess the insulin resistance (IR) patterns in nondiabetics with chronic kidney disease (CKD) and correlate IR patterns with different CKD stages.

MATERIALS AND METHODS: Study design: This was a cross-sectional, prospective, and observational study. Sample size: 25 in each group and 25 controls, with a total sample size of 175. CKD patients in different stages as per the NKF-KDOQI CKD staging including dialysis and renal-transplant recipients attending the Nephrology outpatient department at Sri Venkateswara Institute of Medical Sciences, with healthy controls, were included after written informed consent. Those with diabetes mellitus 1 or 2 were excluded from the study. Diabetes mellitus and impaired fasting glycemia were defined as per the ADA criteria. The estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modified Diet in Renal Disease formula. Height, weight, body mass index (BMI), and resting blood pressure were recorded. Venous blood was collected for the estimation of serum fasting insulin and glucose levels. IR was assessed by homeostasis model assessment for insulin resistance (HOMA-IR) (mmol/l × μU/ml) = fasting glucose mmol/l × fasting insulin (mU/l) 22.5.

RESULTS: The mean ± standard deviation age of controls is 42.56 ± 10.08 and of CKD patients is 45.8 ± 13.4 years. Renal-transplant recipients were the youngest and dialysis group were older. Predialysis, peritoneal dialysis (PD) group had more BMI and waist circumference (WC) than transplant groups. Serum 25(OH) Vitamin D3 levels were highest in hemodialysis (HD) group and lowest in PD icodextrin group.

DISCUSSION: Metabolic syndrome increases risk for developing CKD. Hyperinsulinemia induces glomerular hyperfiltration and increases vascular permeability. IR is determined by BMI and WC in this study. BMI and WC predict IR (HOMA-IR); similar results were reported among Americans. Defronzo et al. studied IR in patients with ESRD undergoing dialysis, using euglycemic insulin clamp techniques. HOMA-IR was studied as parameter to assess IR in nondiabetic CKD Indians. In our study, the mean HOMA-IR reported is 2.3 in patients and 1.3 in controls, with fasting insulin level being 6.5 in cases and 5.5 in controls. In a study by Stanisław et al., 33 HD patients compared with 33 healthy controls. Mean fasting plasma glucose concentrations were lower in HD patients than healthy persons (P = 0.001). Fasting serum insulin concentrations were similar in both groups (P = 0.698). HOMA1-IR values were not significant (P = 0.189). This is contrast to our study with reported higher IR in Maintenance Haemodilysis (MHD) patients. The PD dextrose group had lower BMI, WC, eGFR than healthy controls but FBS, insulin, HbA1c, total cholesterol, serum triglycerides, and HOMA-IR were higher than healthy controls. Our study results were supported by those reported earlier. Our study findings were supporting the positive metabolic effects of icodextrin in reducing the atherogenic lipids which can be translated toward reducing IR and the incidence of metabolic syndrome among continuous ambulatory PD patients.

CONCLUSIONS: Periodic monitoring of IR by HOMA-IR may be prudent in end-stage renal disease patients on chronic PD and also in postrenal-transplant patients to prevent appearance of diabetic state.


  2. Near-Death Experience in Chronic Kidney Disease and Dialysis Patients Top


N Sai Sameera

Department of Nephrology; Sri Venkateswara Institute of Medical Sciences; Tirupati; Andhra Pradesh; India

INTRODUCTION: Dialysis patients form a distinctive group. During the past decade, with the opening of the state-sponsored free dialysis programs, more patients have sought dialysis therapy. Consequently, the numbers of complications have raised. Many times, dialysis patients suffered life-threatening conditions and would have been rescued. However, to our knowledge, near-death experience (NDE) in dialysis patients in our country was not studied. The objective of this study is to investigate the characteristics of NDEs in patients on dialysis therapy.

MATERIALS AND METHODS: We performed a prospective study of the adult patients of chronic kidney disease Stage 5 and chronic kidney disease Stage 5 on dialysis who survived cardiac arrest by cardiopulmonary resuscitation (CPR) as per Advanced Cardiac Life Support guidelines and who sustained pulseless ventricular tachycardia/ventricular fibrillation and received CPR and/or direct cardioversion. We used two scales to study NDE. Greyson's NDE scale and Ring's weighted core experience index (WCEI) with 10 questions are used to quantify the depth of the NDE.

RESULTS: Between 2016 and 2018, the study was performed. We approached the patients who satisfied the inclusion criteria on a day they were comfortable to answer questions after the NDE. A total of 21 patients of chronic kidney disease Stage 5 on dialysis and three patients of chronic kidney disease stage 5 were included. The scores for the Greyson's scale and the Ring's WCEI were calculated.

DISCUSSION: More number of patients felt separated from their bodies (question 12, Greyson's scale) but fewer than that felt the sense of “return” to life (question 15, Greyson's scale). The experiences of two patients (question 12, Greyson's scale) who reported that they have “left their bodies” and viewed their own resuscitation procedures cannot be verified as veridical or are hallucinations. The depth NDE as given by Ring's WCEI showed that tunnel experience and meeting with deceased persons were less common in the present study than other studies.




 

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Indian Journal of Nephrology
Published by Wolters Kluwer - Medknow
Online since 20th Sept '07