The number of patients needing renal replacement therapy (RRT) is increasing rapidly with an increase in lifestyle diseases such as diabetes, hypertension, and metabolic syndrome. Kidney transplantation, whenever feasible, is the most preferred mode of RRT. However, there is a growing shortage of donor kidneys for transplantation. While dialysis is partially able to perform the filtration and excretion function of the kidneys, it is still not able to perform the other renal tubular and endocrine functions of a normal kidney and has quality-of-life issues with significant long-term morbidity. The need of the hour is to develop an ideal artificial kidney that would be wearable or implantable and would be able to perform the complete excretory, filtration, tubular, endocrine, and metabolic functions of the kidney while preserving the quality of life and minimizing complications. In this review, we discuss the characteristics of an ideal artificial kidney, the challenges of developing such a device, a brief description of the past and current work on this topic, and what the artificial kidney of the future should look like.

Urea is an organic compound that has been reported to be effective against many pathological conditions. However, many other studies have reported the toxic effects of urea. These controversies on the biological roles of urea remain unresolved. This review aims to evaluate the biological roles of urea in experimental animals from data published in peer-reviewed journals. A PubMed search was conducted using the phrase, “urea application in experimental animals.” A total of 13 publications that met the inclusion criteria were evaluated. The test substance, animal model, number of animals, doses, duration of treatment, and effects were recorded. Regarding the toxic effect, urea caused decreased excretion of other nitrogenous compounds, increased oxidative stress, decreased insulin, and impairment of beta-cell glycolysis. Furthermore, it caused endothelial dysfunction, loss of synapsis, and decreased olfaction. Regarding the therapeutic effects, urea caused increased growth, increased digestion, and decreased hepatic dysfunction. It also induced apoptosis of tumor cells and exerted neuroprotective properties. Products containing urea should be used with caution, especially in individuals with symptoms of chronic kidney disease. However, more studies are needed to elucidate the mechanisms of its therapeutic effects.

Background: Infection-related glomerulonephritis (IRGN) is an important source of renal morbidity with adverse outcomes in adults. Data from large centers in India is lacking on this common, yet poorly understood entity. Materials and Methods: We performed a prospective observational study of all patients diagnosed with IRGN at our center over a 3-year period between 2017 and 2019. “Typical IRGN” patients were diagnosed based on clinical and laboratory assessment; others underwent renal biopsy. Renal and patient survival outcomes were assessed in addition to factors that help predict outcomes. Results: One hundred and twenty-five patients with a diagnosis of IRGN were included in the study, including 86 patients who underwent renal biopsy. This represented 24% of all biopsies during this time period, and IRGN was the most common nondiabetic kidney disease identified in diabetic biopsies at our center. Female preponderance and a seasonal variation were striking. Atypical sources of infection like otomycosis, tooth abscess, and dengue virus infection were noted. Male gender and diabetes were important risk factors for severe disease. Rapidly progressive glomerulonephritis (RPGN), atypical serum complement profiles, and comorbid illnesses were common in adults. Though children had more benign disease and outcomes, life-threatening complications were also noted. C3 dominance was the most striking immunofluorescence (IF) finding and was associated with poorer outcomes. Crescentic IRGN was rare, and four cases of IgA-dominant IRGN were noted. Also, 24% of the cohort required renal replacement therapy. RPGN presentation of IRGN portended worst prognosis with end-stage renal disease (ESRD) in 31% and death in 22% of patients. Conclusion: IRGN is a common clinical entity in adults with the potential for adverse renal and survival outcomes. We have identified clinical and biopsy characteristics that are associated with ESRD and death.

Background: Iron status assessment is crucial in end-stage renal disease hemodialysis (ESRD-HD) patients because iron deficiency may cause unresponsiveness to erythropoiesis-stimulating agent. Soluble transferrin receptor (sTfR) is a potential iron marker that is not influenced by inflammation, and the results among studies are still conflicting. This study evaluated the role of sTfR in determining iron deficiency in ESRD-HD patients. Methods: This cross-sectional study was conducted at the Hemodialysis Unit in Cipto Mangunkusumo Hospital, Indonesia, from August to September 2018 and included 127 ESRD-HD patients. The sTfR level, sTfR index (sTfR/log ferritin), iron status, ferritin level, and complete blood count were assessed. Transferrin saturation (TSAT) was used as a reference. The role of sTfR was analyzed using the Chi-square test and receiver operating characteristic curve analysis. Results: The median sTfR was 3.0 (range, 1.0–8.5) mg/l, and the median TSAT was 23% (4.0%–100%). The sTfR level in ESRD-HD patients with absolute iron deficiency was 3.9 (1.9–8.5) mg/l, in those with functional iron deficiency was 3.5 (1.9–5.4) mg/l, and in those with no iron deficiency was 2.6 (1.0–6.4) mg/l. The previous sTfR cut-off value of 2.5 mg/l had a sensitivity of 83.3%, specificity of 48.2%, positive predictive value (PPV) of 44.3%, and negative predictive value (NPV) of 85.4%, whereas the new sTfR cut-off value of 2.71 mg/l had a sensitivity of 83.3%, specificity of 56.5%, PPV of 48.6%, and NPV of 87.3%. TSAT and index TSAT were not influenced by inflammation. Conclusion: The cut-off sTfR value of 2.71 mg/l is better than 2.5 mg/l to determine the iron status in ESRD-HD patients.

Introduction: Fibroblast growth factor 23 (FGF-23) is a phosphate metabolism regulator in patients with chronic kidney disease (CKD). The present study is aimed to examine the FGF-23 level in pre-dialysis patients with CKD and its correlation with carotid artery calcification (CAAC). Methods: This cross-sectional study included patients with CKD and controls. The patients were compared with controls having similar distribution of age and sex to determine serum FGF-23 level in Indian healthy adult population. Detailed medical history, physical examination, and investigations were done for each patient. Atherosclerotic risk factors, cardiovascular comorbidities, and drug history were recorded. Carotid calcification was observed using carotid ultrasound. Results: In total, 62 patients with a mean age of 50.0 years were enrolled. Majority of the patients had hypertension (66.1%), followed by diabetes (27.4%) and dyslipidemia (3.2%). Mean serum corrected calcium levels were significantly higher in patients with CAAC compared to the patients without CAAC (9.21 ± 1.34 vs. 8.53 ± 0.93 mg/dL; P = 0.014). The FGF-23 levels were significantly higher in patients with CAAC compared to those without CAAC (396.0 vs. 254.0 pg/mL; P = 0.008). CAAC was found to be present in both early and late stages of CKD. Multivariate analysis showed that log FGF-23 and serum corrected calcium remained as independent determinants of CAAC. The prevalence of CAAC increased with the ascending quartiles of FGF23. Conclusion: In conclusion, FGF-23 was found to be independently associated with CAAC in CKD.

Introduction: Peripheral neuropathy is one of the most common complications in chronic kidney disease (CKD). The neuroprotective role of ghrelin is being explored recently. Here we aim to determine the burden of neuropathy in nondiabetic CKD and to find the association of peripheral nerve function with plasma ghrelin levels in these patients. Methods: This was a cross-sectional study conducted in nondiabetic CKD patients on conservative management to determine the magnitude of neuropathy. The association of ghrelin isoforms with nerve functions was assessed between three groups, namely CKD with neuropathy, CKD without neuropathy, and healthy volunteers, with 20 participants in each group. Results: The proportion of neuropathy in nondiabetic CKD was 78% (n = 78), of which 51% (n = 40) were asymptomatic. Des acyl ghrelin (DAG) and total ghrelin (TG) levels were 1545.5 ± 487.4 and 1567.4 ± 485.3 pg/mL, respectively, in CKD patients with neuropathy and were found to be elevated compared to those without neuropathy, who had 1000.4 ± 264.2 and 1019.7 ± 264.3 pg/mL of DAG and TG, respectively (P < 0.001). Assessment of correlation between nerve conduction parameters and DAG levels showed positive correlation between DAG levels and common peroneal latency (r = 0.69; P < 0.01), median sensory latency (r = 0.45; P < 0.05), and sural latency (r = 0.51; P < 0.05). We found negative correlation between median velocity (r =−0.56; P < 0.05), common peroneal velocity (r = −0.64; P < 0.01), median sensory velocity (r =−0.49; P < 0.05), and sural velocity (r = −0.54; P < 0.05). There was no statistically significant difference in acyl ghrelin levels among the groups. Conclusion: The prevalence of peripheral neuropathy in CKD is significantly higher with almost half of them being asymptomatic. Impaired renal clearance in CKD leads to the accumulation of DAG, which subsequently inhibits the neuroprotective functions of AG leading to neuropathy in CKD.

Background: There is paucity of clinical evidence on target serum phosphorus levels in early chronic kidney disease (CKD). Present longitudinal study was done to find target phosphorus level and its association with fibroblast growth factor (FGF23) in three different hyperphosphatemia management groups. Methods: This 1-year, prospective, randomized controlled, open-labelled study was conducted among three equally allocated treatment groups that consisted of 120 screened early CKD patients totally. Group 1 patients were given dietary phosphorus modification (n = 40), group 2 patients were administered calcium-based phosphate binders (n = 40), and group 3 patients were given non–calcium-based phosphate binders (n = 40). Three-monthly dietary assessment, MDRD estimated glomerular filtration rate (eGFR), phosphorus, calcium, iPTH, alkaline phosphatase, and six-monthly FGF23, 2D echocardiography, and X-ray of chest and abdomen were performed. Association of three categories of phosphorus level up to 3.9, 4–5, and >5mg/dl, rate of progression of all parameters, and correlation with FGF23 were studied among all three groups. Results: At baseline, all clinical and biochemical parameters were equally distributed with a controlled nutritional phosphate among all groups. There was no significant difference of FGF23 levels from all the three categories of phosphorus level among all groups. Serum phosphorus at the level of 5 mg/dl was associated with iPTH and eGFR at 1 year. Over 1 year, there was a significant decline in serum phosphorus levels in group 1 (P 0.02), group 2 (P 0.00), and group 3 (P 0.05). FGF23 declined significantly only in group 3 (P 0.00).There was no correlation of FGF23 with serum phosphorus levels (P 0.13). However, FGF23 correlated positively with iPTH (P 0.03, r = 0.19) Conclusion: Serum phosphorus levels upto 5mg/dl had no effect on FGF23 at early CKD stages. Although different treatment groups showed significant phosphorus reduction, non-calcium phosphate binder had a major impact on FGF23 reduction.

Background: Hyperphosphatemia is linked to increased mortality and morbidity in patients on hemodialysis. Currently, the phosphate intake and dialytic removal in predominantly vegetarian patients on twice-weekly dialysis is not well studied. Materials and methods: This prospective, study recruited patients on twice-weekly dialysis of at least 3 months duration. Baseline clinical variables were measured. Dietary protein and phosphorus intake was assessed using a validated food frequency questionnaire. Phosphate binder use was assessed, hourly blood was collected for serum phosphorus during dialysis, and spent dialysate was collected to estimate cumulative phosphorus removal during the session. Results: Forty (67%) of the 60 patients studied were vegetarians. Twenty-eight (48%) were hyperphosphatemic, and 15 (25%) had serum parathormone (PTH) >500 pg/ml. The mean phosphorus intake was 1247 (±312) mg/day, the mean serum phosphorus was 5.49 (±2.01) mg/dl, and the mean dialytic phosphorus removal was 910 (±383) mg/session. Up to 67% of the study population took calcium-based phosphate binders, 25% took sevelamer carbonate, and 40% took activated vitamin D preparation. The lowest tertiles of phosphorus intake correlated with low energy-adjusted protein intake and hypoalbuminemia. Hyperphosphatemic subjects had better nutritional indices (mid-upper arm circumference and body mass index). Dietary intake and serum phosphorus levels were not mutually associated, but both were strongly correlated with total phosphorus removal in the spent dialysate. Serum phosphorus levels fell by 32% by the first hour of hemodialysis. Conclusion: Twice-weekly dialysis is often practised in resource-limited Asian countries. However, due to a predominantly vegetarian diet, hyperphosphatemia was noted only in up to half of the patients, despite twice-weekly hemodialysis schedules. This reinforces the fact that plant-based dietary phosphate is less well absorbed.

Introduction: There may be a role of reducing the total steroid doses for the treatment of relapses of nephrotic syndrome in children with milder and more stable disease. The primary objective of this study was to compare the effectiveness of a low-dose prednisolone regimen with standard therapy for the treatment of relapses in steroid-sensitive nephrotic syndrome (SSNS) at the end of treatment, the secondary objectives being time to remission and sustained remission after 3 months. Methods: This randomized controlled trial included a total of 40 children (20 in each group) with SSNS (presently infrequently relapsing course) and with a relapse. Both groups received prednisolone at a dose of 2 mg/kg/day until remission; subsequently, the patients in the study group received 1 mg/kg, and the control group participants received 1.5 mg/kg prednisolone on alternate days for 4 weeks. The patients were followed up till 3 months after stopping the therapy. Results: The median (IQR) age of children enrolled was 7.5 (range: 5–9.65) years, and the age at onset of nephrotic syndrome was 4 (range: 2.3–5.5) years. The median time to achieve remission was 9 days (comparable in low dose vs. standard therapy group; P = 0.14). All patients were in remission at the end of therapy; 85% of patients were in the low-dose group and 90% in the standard therapy group after 1 month (P = 0.32). At the end of 3 months, 60% continued to be in remission in the low-dose group and 65% with standard therapy (P = 0.37). Hazard ratios for relapse at the end of 1, 2, and 3 months were 1.05, 1.08, and 1.13, respectively. Patients who were infrequently relapsing (79%) from the onset of nephrotic syndrome had higher remission rates at the end of 3 months (80% in the low-dose group vs. 76.9% in the standard therapy group). Hazard ratios for relapse in these patients at the end of 1, 2, and 3 months were 1.01, 1.03, and 1.08, respectively. Conclusions: Lower doses of prednisolone can be used for the treatment of relapse of steroid sensitive nephrotic syndrome, with an infrequently relapsing course.

Introduction: Lupus nephritis (LN) is an immune complex glomerulonephritis, which is a very serious complication of systemic lupus erythematosus (SLE) as it can progress to end-stage kidney disease (ESKD). Methods: In this study of 92 renal biopsy-proven LN, the patients were followed up for a minimum period of 2 years with a mean follow-up period of 5.4 ± 3.4 years. Results: The mean serum creatinine of our study population was 1.4 ± 1.53. Our study population included 2 patients with class I lesions, 5 with class II, 22 with Class III, 53 with Class IV, and 10 with Class V lesions. Our therapeutic approach included only oral steroids for class I and class II lesions; for class III, IV, and V lesions, our approach included pulse steroids followed by oral steroids with either intravenous (IV) monthly cyclophosphamide (CYC) or mycophenolate mofetil (MMF). For maintenance, azathioprine or MMF were used along with low-dose oral steroids after 6 months of CYC or MMF. In CYC induction group containing 78 patients (84.7%), 66 patients (84.6%) attained remission (CR + PR), relapse in five patients (6.4%), ESRD on HD in five patients (6.4%), and death in two patients (2.6%). Conclusion: At the end of the study, in all groups, 79 patients (85.86%) were in remission (CR + PR), six patients (6.5%) were in relapse, five patients (5.4%) had reached the ESKD stage on HD, and two patients (2.2%) died.

Introduction: Creatinine kinetics denotes that under steady-state conditions, creatinine production (G) will equal creatinine excretion rate (E). The glomerular filtration (GFR) is impaired when excretion is less than production. The kinetic estimate of GFR (keGFR) and E/G ratio were proposed as a more accurate estimate of GFR in acute settings with rapidly changing kidney function. We evaluated keGFR and E/G to diagnose AKI, predict recovery, death or dialysis. Methods: This is a prospective observational study of critically ill patients. Inclusion criteria were patients >18 years old with sepsis, defined as clinical infection with an increase in SOFA score >2, and plasma procalcitonin >0.5 ng/mL. Plasma creatinine and Cystatin C were measured on ICU admission and 4 h later, and their keGFR was calculated. Urine creatinine and urine output were measured over 4 h to calculate the E/G ratio. Results: A total of 70 patients were recruited, of which 49 (70%) had AKI. Of these, 33 recovered within 3 days, and 15 had a composite outcome of death or dialysis. Day 1 keGFR_Cr and keGFR_CysC discriminated AKI from non-AKI with AUCs of 0.85 (95% Confidence interval: 0.74–0.96), and 0.86 (0.76–0.97), respectively. The E/G ratio predicted AKI recovery (AUC: 0.81 (0.69–0.97)). The keGFRs were not predictive of death or dialysis, whereas E/G was predictive (AUC: 0.76 (0.63–0.89). Conclusion: keGFR was strongly diagnostic of AKI. The E/G ratio predicted AKI recovery and a composite outcome of death and dialysis.

Background: Cardiovascular disease is the major cause of mortality in patients undergoing chronic hemodialysis treatment. The oxidative modification of low-density lipoprotein is a crucial step in the pathogenesis of atherosclerosis. Paraoxonase 1 (PON1) is the protein responsible for most of the antioxidant activity of high-density lipoprotein, and its reduced levels are associated with more cardiovascular events in several populations. In hemodialysis patients, reduced PON1 activity has been shown to be associated with increased cardiovascular mortality. Studies have shown that after the hemodialysis session, the activity of PON1 increases. The influence of dialyzer reuse on the activity of PON1 is unknown. We aimed to evaluate the effect of the reuse of two types of dialyzers (polynephron and polyethersulfone) on the PON1 activity of hemodialysis patients. Subjects and Methods: A total of 30 patients on hemodialysis were included. Pre- and post-dialysis blood samples were collected to analyze the activity of PON1 in the first use of the dialyzer and in the hemodialysis session of its sixth reuse. This process was carried out with polynephron (bisphenol-free) and polyethersulfone dialyzers. Results: We found that post-dialysis PON1 activity was significantly higher than pre-dialysis activity in both the first use and sixth reuse (P < 0.001). Conclusion: The practice of reusing the dialyzer did not interfere with the improvement of PON1 activity after the hemodialysis session.

Renal involvement in non-Hodgkin lymphoma (NHL) has myriad of morphological features. We discuss an unusual case who presented as acute pyelonephritis (leucocytosis and acute kidney injury), ovarian mass and compressive myelopathy finally diagnosed as Non Hodgkins Lymphoma.

Human immunodeficiency virus (HIV)-associated renal disease is a pan-nephropathy, causing glomerular, tubular, and interstitial changes. The common lesion is the collapsing variant of focal segmental glomerulosclerosis. Multiple myeloma presenting as light chain cast nephropathy in an HIV-positive patient is very rare. A 45-year-old female retropositive patient presented with one episode of hematuria. Kidney biopsy was performed with a clinical diagnosis of acute interstitial nephritis (AIN). Biopsy showed unremarkable glomeruli. Tubules were dilated and showed a few periodic acid–Schiff (PAS) positive and many PAS-negative fractured casts surrounded by histiocytic reaction. Immunofluorescence and immunohistochemistry (IHC) showed lambda restriction by the casts. Bone marrow aspirate showed an increase in plasma cells, and the biopsy showed nodular aggregates of atypical plasma cells, which showed lambda restriction by IHC. PAS-negative fractured tubular casts are known to be associated with HIV-related nephropathy and need detailed hematological workup to rule out an associated plasma cell dyscrasia.

Atherosclerosis and fibromuscular dysplasia are the commonest types of diseases associated with renovascular hypertension, with atherosclerosis accounting for 70%–80% of all cases and the latter accounting for 10% of cases. We report a case of a 65-year-old asian male with stenosis of the right renal artery with early bifurcation treated by percutaneous balloon dilation and simultaneous kissing balloon stenting technique.

Multiple myeloma (MM) is usually a disease of the elderly and only less than 1% are young individuals below 35 years of age. Central nervous system (CNS) manifestations of MM are even rarer, the most common being leptomeningeal involvement. We report a case of a 35-year-old male who presented with a fever of 3 weeks duration associated with slurring of speech, nasal regurgitation, hearing loss, and decreased urine output. CNS examination showed IX, X, and XII cranial nerve palsies with right otitis media and bilateral mastoiditis with conductive hearing loss. Renal biopsy showed cast nephropathy. The kappa–lambda ratio was 18, with β2 microglobulin measuring 12 mg/L. Bone marrow showed 90% plasma cells, and skeletal survey had bony lytic lesions. He responded well to dexamethasone, bortezomib, and thalidomide. His renal functions returned to normal, and palsies have improved completely. This report shows that MM should be suspected even in young patients with classical features of myeloma and CNS involvement is very rare in MM.

Fabry disease (FD) is a rare, lysosomal storage disorder characterized by multiorgan accumulation of predominantly globotriaosylceramide (GL3) and its metabolite. Resulting renal, cardiac, and cerebrovascular complications are crucial causes of morbidity and mortality in FD. Enzyme replacement therapy (ERT) shows promising outcomes for these patients, provided that therapy is initiated early. Thus, precise and early diagnosis of the disease is a pivotal factor determining the corollary of the disease. We report two cases of young adult males who presented to the nephrology department with proteinuria. A kidney biopsy was performed in both cases, which was suggestive of FD. The final conclusive diagnosis of FD was provided by electron microscopy.

Multisystem inflammatory syndrome is a rarely reported post-COVID (coronavirus disease) phenomenon in adults. Our understanding of the multisystem inflammatory syndrome–adult (MIS-A) is based on multiple case reports that have demonstrated heterogeneous clinical presentations and treatment options. Rhabdomyolysis is an unusual presentation of MIS-A. We report the case of a 61-year-old man who presented with rhabdomyolysis with acute kidney injury (AKI), acute inflammatory demyelinating polyneuropathy (AIDP), myocarditis, disseminated intravascular coagulation, and minimal respiratory symptoms. The patient was found to have post-COVID inflammatory syndrome and recovered with supportive treatment and intravenous immunoglobulin (2 g/kg over 5 days). COVID-19 (coronavirus disease 2019) antibody positivity played a significant role in making the diagnosis of MIS-A and in providing prompt treatment.

Bardet–Biedl syndrome (BBS) is a rare disorder with a frequency of 1:1,60,000. The disease is inherited in an autosomal recessive manner. Less than 15 cases have been reported from India. We present a case of Bardet–Biedl syndrome presenting to the medical emergency with acute breathlessness because of de-compensated renal failure and salient features such as marked polydactyly, central obesity, retinitis pigmentosa, end-stage renal diseases, and mental retardation. Genetic study showed that the patient had BBS genetic variant 9 (MIM#615896), VUS variant. The patient was primarily treated for end-stage chronic renal failure with hemodialysis. We are reporting this case for its rarity and the presence of a novel genetic variant of an unidentified significance as per genome mapping. BBS is often not diagnosed at all or diagnosed late until end-stage renal failure sets in. Timely diagnosis might not help treat the condition but surely improve the quality of life for the patient.

Polyomavirus nephropathy (PVN) is a known complication of renal transplantation due to the reactivation of latent BK virus (BKV) infection. Viral replication is usually confined to tubules. However, in severe viremia and late stages of PVN, it can involve glomerular parietal epithelial cells. Glomerular involvement by BKV can cause crescent formation and may lead to graft failure. We describe a relatively rare case of PVN with glomerular involvement and crescent formation in a 52-year-old male who had undergone a transplant 16 months ago. Despite the stoppage of immunosuppression, graft failure occurred eventually. Interestingly, we observed the intense positivity for IgG and c4d in the Bowman capsule on immunofluorescence. Observation of such positivity along Bowman capsule in renal biopsies with a limited number of glomeruli should alert pathologists to do a vigilant search of BKV inclusion and perform immunohistochemistry for SV 40 large T antigen.