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January-February 2017
Volume 27 | Issue 1
Page Nos. 1-83

Online since Monday, January 02, 2017

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COMMENTARY  

Deceased donor transplantation in India: How the challenges are being met? p. 1
R Parthasarathy, G Abraham, M Mathew
DOI:10.4103/0971-4065.183601  
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ORIGINAL ARTICLES Top

Deceased donor renal transplantation: A single center experience p. 4
N Gopalakrishnan, T Dineshkumar, J Dhanapriya, R Sakthirajan, T Balasubramaniyan, ND Srinivasa Prasad, K Thirumalvalavan, S Murugananth, K Kawaskar
DOI:10.4103/0971-4065.179206  
Deceased donor renal transplantation (DDRT) constitutes less than 5% of all kidney transplantats in India. A retrospective analysis of 173 deceased donor renal transplants performed in a public funded government hospital was done. Mean age of the recipients was 36 years (male:female ratio 2.4:1), and that of the donors was 32.3 years (male:female ratio 6:1). The cold ischemic time was 340 ± 170 minutes. Mean follow-up period was 36 months. Forty one patients died, 75% of them in the first post – transplant year. Sepsis and cardiovascular disease were the most common causes of death. Twenty two percent had acute rejection. There was no significant difference in the incidence in the rate of acute rejection, bacterial, fungal infections and death rate between the cohorts of induction and non induction immunosuppression. The patient and death censored graft survival at 1 year were 80 and 82.6% and at 5 years were 76 and 80% respectively.
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Fibroblast growth factor-23 levels in maintenance hemodialysis patients in India p. 9
U Anandh, P Mandavkar, B Das, S Rao
DOI:10.4103/0971-4065.177137  
Fibroblast growth factor-23 (FGF-23) levels start rising early in patients with chronic kidney disease and is implicated in cardiovascular and overall mortality of hemodialysis patients. We conducted a prospective observational cohort study in stable dialysis patients looking into the levels of FGF-23 in hemodialysis patients and its association with various demographic and biochemical variables and mortality. A total of 91 patients were enrolled in the study. The mean FGF-23 levels were very high (1152.7 pg/ml). FGF-23 levels were significantly associated with serum phosphorus and parathyroid hormone (PTH) levels in univariate and multivariate analysis. No significant association between FGF-23 and cardiovascular comorbidities and overall mortality was seen. FGF-23 levels rise exponentially in maintenance hemodialysis patients. There is a strong association between FGF-23 and phosphorus and PTH levels. No association between FGF-23 and mortality was noted in our patients.
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Acute kidney injury and mortality in hematopoietic stem cell transplantation: A single-center experience p. 13
B Sehgal, P George, MJ John, C Samuel
DOI:10.4103/0971-4065.177138  
Hematopoietic stem cell transplant (HSCT) is a life-saving procedure for patients with several malignant and nonmalignant hematological disorders. Acute kidney injury (AKI) is a common complication after HSCT. The aim of the study was to identify the incidence and outcomes of AKI associated with HSCT in our center. Sixty-six HSCT recipients from October 2008 to March 2014 at Christian Medical College, Ludhiana, were followed up till July 31, 2014. RIFLE criteria utilizing serum creatinine was used to diagnose and stage AKI. Mortality and AKI were the primary outcomes studied. The risk of AKI in relation to conditioning regimen, type of HSCT (allogeneic and autologous), co-morbidities, graft versus host disease, drug toxicity, and veno-occlusive disease were analyzed. Sixty-five patients were included in the study. Male: Female ratio was 3.6:1 with a median age of 17 years (1.5–62). Forty-nine (75.4%) patients had AKI over 3 months, R 17 (26.2%), I 19 (29.2%), and F 13 (20%). AKI occurred at a mean of 19.4 ± 29.2 days after the HSCT. AKI was more commonly observed in patients undergoing allogeneic versus autologous HSCT (85.2% in allogeneic vs. 27.8% in autologous, P = 0.005). Mortality was seen in 20 patients (30.8%) in 3 months. AKI in the first 2 weeks (P < 0.016) was a significant risk factor for mortality. Incidence of AKI in HSCT is high and accounts for significant mortality and morbidity. RIFLE classification of AKI has prognostic significance among HSCT patients with an incremental trend in mortality.
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Biomarker response to contrast administration in diabetic and nondiabetic patients following coronary angiography p. 20
VL Ashalatha, AR Bitla, VS Kumar, D Rajasekhar, MM Suchitra, AY Lakshmi, PVLNS Rao
DOI:10.4103/0971-4065.179335  
Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C represent early renal injury markers for contrast-induced nephropathy (CIN). Baseline parameters such as type and quantity of contrast, patient preparation, renal function status, and diabetes mellitus (DM) are known to affect the response of the kidney to contrast-induced injury. This study was taken up to know the biomarker response to contrast administration in 58 diabetic and 59 nondiabetic male patients with same baseline parameters and baseline serum creatinine <1.2 mg/dl undergoing coronary angiography and their role in predicting the development of CIN. Serum creatinine, serum cystatin C, and urinary-NGAL (u-NGAL) were analyzed at baseline (0 h), 4 h, and 24 h after the administration of contrast medium. CIN was defined as a 25% increase in serum creatinine concentration from the baseline value or an absolute increase of at least 0.5 mg/dl within 48 h after the administration of contrast media. Serum creatinine rose 24 h after contrast administration in the diabetic group compared to 48 h in the nondiabetic group. Serum cystatin C levels rose 24 h after contrast administration in both the groups. The earliest marker to rise in both the groups was u-NGAL at 4 h. Diabetic patients had significantly higher u-NGAL (P = 0.005), and serum creatinine levels (P = 0.008) 4 h, and 24 h after contrast administration, respectively. Serum creatinine and u-NGAL/creatinine at 4 h were found to be the best predictors of CIN in the DM and non-DM patients, respectively. Biomarker response to contrast administration is different in diabetic and nondiabetic patients following contrast administration. Diabetic patients exhibit early and greater degree of renal impairment compared to the nondiabetic patients irrespective of the outcome. We propose the use of serum creatinine in patients with DM and u-NGAL/creatinine in non-DM patients to identify CIN as early as 4 h after contrast administration.
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Efficacy and safety of early tacrolimus conversion to sirolimus after kidney transplantation: Long-term results of a prospective randomized study p. 28
AE El-Agroudy, SM Alarrayed, SM Al-Ghareeb, E Farid, H Alhelow, S Abdulla
DOI:10.4103/0971-4065.176146  
We report a prospective, open-label, randomized study to evaluate the safety and efficacy of converting patients with a stable renal function from tacrolimus (Tac)-based regimen to a sirolimus (SRL)-based regimen after kidney transplantation. Fifty-eight low-risk renal allograft recipients who receiving Tac 6 months posttransplant, were randomly assigned to continue Tac (n = 29) or convert to SRL (n = 29). We evaluated the 3-year outcomes including patient and graft survival, graft function, and safety profile. Three-year patient and graft survival in SRL and Tac groups were 93.1% versus 100% (P = 0.32), and 89.7% versus 100% (P = 0.11), respectively. However, the SRL group had a significantly better renal function, from the 2nd year posttransplant until the last follow-up. Four (13.8%) patients in the SRL group and 3 (10.3%) in the Tac group (P = 0.5) developed biopsy-proven acute rejection. Mean urinary protein excretion increased significantly after SRL conversion. Diastolic blood pressure was significantly lower at the end of the study in patients who eliminated Tac (80.4 vs. 75.6 mmHg in Tac and SRL group, respectively) (P = 0.03). Mean hemoglobin concentrations decreased after SRL conversion and remained significantly lower from 12 months to 36 months (P = 0.01). The mean serum cholesterol (540 ± 44 mg/dl) and triglyceride (177 ± 27 mg/dl) increased significantly in the SRL group, compared to Tac group (487 ± 62 mg/dl) (P = 0.03) and (141 ± 26 mg/dl) (P = 0.04). Our experience demonstrates that conversion to SRL from calcineurin inhibitors-based therapy may result in better renal function and blood pressure control in renal transplant recipients without an increased risk of acute rejection. However, these benefits have not resulted in a growing advantage in graft or patient survival.
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Assessment of health-related quality of life and its determinants in patients with chronic kidney disease p. 37
M Manavalan, A Majumdar, KT Harichandra Kumar, PS Priyamvada
DOI:10.4103/0971-4065.179205  
Health-related quality of life is an important, yet neglected aspect of chronic kidney disease (CKD) care. We evaluated the quality of life and its determinants across CKD 3 to 5D using a kidney disease specific tool (Kidney Disease Quality of Life-SF™) in an underprivileged, predominantly rural population with high rates of illiteracy and unemployment. The scores of individual domains were summarized to three composite scores – physical composite summary (PCS), mental composite summary (MCS), and kidney disease component summary score (KDCS). A total number of 204 participants were recruited from nephrology outpatient clinics. About 68.1% of participants were males. The mean age of the study population was 49.14 ± 13.63 years. There was a high proportion of illiteracy (36.3%) and unemployment (80.9%). KDCS showed a significant decline (P = 0.01) from CKD 3 to CKD 5D whereas MCS and PCS showed a nonsignificant decrease. There was no difference in KDCS, PCS, or MCS scores between patients treated by hemodialysis and CAPD. Illiteracy and unemployment were associated with significantly lower KDCS, PCS, and MCS scores. Age ≥50 years was associated with poor PCS (29.49 ± 8.20 vs. 34.17 ± 9.99 ; P< 0.001). Hemoglobin <10 g/dL was associated with poor KDCS (58.93 ± 13.09 vs. 65.55 ± 13.38 ; P< 0.001) and PCS (29.56 ± 8.13 vs. 33.37 ± 9.82; P< 0.001). The presence of comorbidities such as diabetes and hypertension had no impact on the composite scores. KDCS, MCS, or PCS scores did not vary among patients having high serum phosphorus (≥4.5 mg/dL), low albumin (<3.5 g/dL), and elevated parathyroid hormone (≥150 pg/ml). On multiple linear regression analysis, the predictors of KDCS were unemployment (P < 0.001) and illiteracy (P = 0.03). Unemployment (P < 0.001) and age (P < 0.001) were predictors of PCS whereas literacy level (P < 0.001) was predictive of MCS.
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Study of anemia in nondialysis dependent chronic kidney disease with special reference to serum hepcidin p. 44
H Goyal, S Mohanty, M Sharma, A Rani
DOI:10.4103/0971-4065.179301  
We studied the role of serum hepcidin in anemia of chronic kidney disease (CKD) in a hospital-based cross-sectional study. Serum hepcidin, ferritin, and high-sensitivity C-reactive protein (hsCRP) levels were evaluated in patients of CKD. Hepcidin levels were increased in patients as compared to healthy adults. Hepcidin levels increased as CKD progressed through stage 3–5 (P trend = 0.015) but did not correlate with estimated glomerular filtration rate. Hepcidin correlated positively with ferritin (P < 0.0001) and transferrin saturation (TSAT) (P = 0.0217) and negatively with erythropoietin (EPO) levels (P = 0.0258) but did not correlate with either hsCRP or estimated glomerular filtration rate. Iron status influenced hepcidin levels of patients. Patients were divided according to iron status on the basis of TSAT and serum ferritin levels. We observed that while absolute iron deficiency (transferrin saturation <20%, ferritin <40 ng/ml) is associated with downregulation of hepcidin, hepcidin is elevated in other two categories of CKD patients (P = 0.0039). Iron status of patients also influenced interaction between hepcidin and hemoglobin (Hb). Hepcidin correlated negatively with Hb in patients with sufficient iron status (r = −0.7452, P< 0.0001) but nearly correlated positively with Hb in patients with absolute iron deficiency (r = 0.9428, P = 0.0572). Almost similar association persisted when cutoff value for serum ferritin was raised to 100 ng/ml as per NKF/KDOQI 2006 clinical practice guidelines except that no association was observed in absolute iron deficiency category. Cutoff value for hepcidin for differentiating absolute iron deficiency from other categories in our study population is ≤ 34 ng/ml (area under curve = 0.836, P< 0.0001). In conclusion, serum hepcidin level is increased in nondialysis CKD patients as compared to healthy adults possibly due to associated inflammation and decreased renal clearance. Furthermore, iron status modifies hepcidin level and its association with Hb. Raised hepcidin can predict the need for parenteral iron therapy and need for higher dose of recombinant human EPO to overcome iron-restricted erythropoiesis.
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Hemodialysis outcomes and practice patterns in end-stage renal disease: Experience from a Tertiary Care Hospital in Kerala p. 51
GR Lakshminarayana, LG Sheetal, A Mathew, R Rajesh, G Kurian, VN Unni
DOI:10.4103/0971-4065.177210  
This study was planned to analyze the hemodialysis practice patterns from a tertiary care referral centre as there is very limited data from India. All patients of ESRD on maintenance hemodialysis (MHD) in dialysis unit at AIMS, Kochi, Kerala for a minimum period of 3 months were included. A total of 134 patients (M: F 2:1) with age of 20 to 84 years (Mean: 59.83; SD: 11.98) were studied. The most common causes of ESRD in study population were diabetic nephropathy (DN) (59.7%) followed by unclassified group (19.4%), chronic glomerulonephritis (CGN) (11.9%). Majority (81%) were initiated on MHD through temporary vascular access on emergency basis. Majority (79%) of the patients were on twice weekly MHD. The range of eGFR (ml/min/1.73 m2) at the time of initiation of MHD was 1.26-11.78 by CG formula and 2.18-16.4 by MDRD equation. The mean duration on hemodialysis was 37.16 months and 50.7% patients had died during the follow-up period (3-108 months). The mean survival time on hemodialysis was 40.31 months (SD = 26.69). The mean survival time was lower in diabetic nephropathy (35.93 months) than in non-diabetic renal disease (47.46 months). The most common causes of deaths were cardiovascular events (51.5%), and infections (26.5%). In conclusion, males outnumbered females, among those on hemodialysis. There was no significant difference in eGFR at initiation of MHD based on etiologies. Initiation of MHD via temporary access, presence of LVH, acute coronary syndrome, use of acetate dialysate, need for parenteral iron therapy had impact on mortality. Survival rates while on hemodialysis at end 1st, 3rd, 5th and 7th years were 87.31, 45.52, 21.64 and 7.46 percentages respectively.
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CASE REPORTS Top

Eculizumab for atypical hemolytic-uremic syndrome in India: First report from India and the challenges faced p. 58
SK Sethi, S Rohatgi, MA Dragon-Durey, V Raghunathan, M Dhaliwal, A Rawat, P Jha, SB Bansal, R Raina, V Kher
DOI:10.4103/0971-4065.179369  
Much progress has been made in understanding the pathophysiology and treatment of atypical hemolytic uremic syndrome (aHUS). Plasma therapy is the mainstay of treatment for aHUS. The availability of the first effective anti-complement therapeutic agent, eculizumab, has dramatically changed the outlook of this disease. However, its use in clinical practice raises important questions, such as who should receive the drug, when to start such therapy, and is it safe to stop treatment once the disease is controlled. We describe here for the 1st time in India, use of eculizumab in a 12-year-old boy with aHUS. We also describe in this report challenges faced in procuring the drug, and an ideal, evidence-based method of treating aHUS in children.
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Unusual cause of glomerular deposition disease: Collagenofibrotic glomerulopathy p. 62
S Nimmagadda, K Mukku, SR Devaraju, MS Uppin
DOI:10.4103/0971-4065.179300  
Collagenofibrotic glomerulopathy is a rare condition characterized by deposition of Type III collagen fibers in the subendothelial space and mesangium of the glomerulus. Only 17 cases have been reported from India. A definite diagnosis can only be established when typical histological findings are supported by electron microscopy. It is characterized by indolent progression and has no definitive therapy.
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Tumor-induced hypophosphatemia p. 66
M Mulani, K Somani, S Bichu, V Billa
DOI:10.4103/0971-4065.179302  
Significant hypophosphatemia is commonly due to Vitamin D deficiency. Any sporadic onset of hypophosphatemia in adults warrants workup to identify alternate causes. Hypophosphatemia may also be the only manifestation of an occult malignancy. A high index of clinical suspicion can help diagnose such conditions in early stages. Prompt treatment of the cause can correct this biochemical abnormality. We describe a case report of a woman presenting with severe hypophosphatemia and osteomalacia, leading eventually to the diagnosis of a phosphaturic mesenchymal tumor of the temporo-occipital bone. Surgical resection of tumor led to normalization of the biochemical parameters as well as a complete clinical recovery.
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A patient with serum creatinine of 61 mg/dl p. 69
S Sriram, S Srinivas, PSR Naveen
DOI:10.4103/0971-4065.179202  
Spurious elevation of serum creatinine by Jaffe assay is known to occur due to a variety of substances. This results in subjecting the patient to invasive and complicated procedures such as dialysis. We report a rare case of false elevation of this renal parameter following exposure to an organic solvent.
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Idiopathic erythrocytosis in IgA nephropathy p. 72
E Mahesh, PR Madhyastha, M Kalashetty, KC Gurudev, S Bande, MM John
DOI:10.4103/0971-4065.194390  
We report a case of idiopathic erythrocytosis in a 31-year-old male who was incidentally detected to have hypertension during his preemployment checkup. Urine routine showed proteinuria and hematuria. Biochemical parameters revealed raised serum creatinine, and histological findings of the renal biopsy showed IgAN.
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Hyponatremia - A rare complication of Gitelman's syndrome p. 74
A Ganguli, JH Veis
DOI:10.4103/0971-4065.177208  
Gitelman's syndrome (GS) is a rare autosomal recessive disorder caused by mutations in thiazide-sensitive NaCl cotransporter. We report a 49-year-old, normotensive lady with prolonged hypokalemia since her 20s who was diagnosed with GS at our renal clinic. During follow-up, she was found to have mild, asymptomatic, euvolemic hyponatremia with low serum uric acid, inappropriately high urine osmolality and sodium consistent with syndrome of inappropriate antidiuretic hormone-like presentation. Despite life-long urinary sodium losses, hyponatremia has rarely been reported in GS to be due to the primary disease process. We present relevant clinical data and hypothesize on why this disease per se may be a risk factor for dilutional hyponatremia.
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Warfarin related acute kidney injury: A case report p. 78
S Mendonca, D Gupta, A Valsan, R Tewari
DOI:10.4103/0971-4065.177142  
Warfarin is an oral anticoagulant used extensively in clinical practice; However, its side-effect of causing renal damage has been recently detected. The mechanism leading to renal damage is glomerular hemorrhage and red blood cell tubular casts prothrombin time. Recently, it was found that warfarin causes renal damage in patients with chronic kidney disease and is also associated with progression of renal disease. Warfarin causing acute kidney injury in patients with normal renal function is a rare manifestation. It is important to be aware of this condition as its innocuous presence can lead to chronic kidney disease if not corrected in time. Further studies have also found that novel oral anticoagulants such as dabigatran also cause a similar syndrome and hence a new term called anticoagulant-related nephropathy is now in vogue.
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Thrombotic microangiopathy: An unusual cause of renal failure in rheumatoid arthritis p. 81
R Sakthirajan, J Dhanapriya, T Dineshkumar, N Gopalakrishnan, S Murugan, T Balasubramaniyan
DOI:10.4103/0971-4065.179207  
Rheumatoid arthritis (RA) is one of the commonest rheumatological diseases. Renal involvement is not common but can occur as a result of chronic inflammation as part of disease process or drug toxicity. Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ failure of variable severity. Only a few cases of TMA in patients with RA were reported to date. We describe a 45-year-old female patient with RA who presented with oliguria and edema. Renal biopsy showed TMA with patchy cortical necrosis. She improved with hemodialysis and plasmapheresis.
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Indian Journal of Nephrology
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