Kl Gupta

The Utility of 1‐ and 3‐Month Protocol Biopsies on Renal Allograft Function: A Randomized Controlled Study

Identification of pathological events in the renal allograft using protocol biopsies at predetermined time intervals may yield useful information and improve outcomes. We examined the influence of decisions taken on the basis of 1‐ and 3‐month protocol biopsies findings on 1‐year renal allograft function in a prospective randomized study. Out of 102 living‐donor allograft recipients, 52 were randomized to undergo protocol biopsies and 50 controls had only indicated biopsies. All acute rejection (AR) episodes (clinical and subclinical) were treated. Calcineurin inhibitor (CNI) dose adjustments were made on clinical judgment. Baseline recipient and donor characteristics, immunosuppressive drug usage, HLA matches and 2‐h cyclosporine levels were similar in both groups. At 1 and 3 months, protocol biopsies revealed borderline (BL) changes in 11.5% and 14% patients, AR in 17.3% and 12% and chronic allograft nephropathy (CAN) in 3.8% and 10%. The incidence of clinically evident AR episodes was similar in the two groups, but biopsy group had lower serum creatinine at 6 months (p = 0.0003) and 1 year (p < 0.0001). The renal functions were similar in those with normal histology and BL changes. Protocol biopsies are helpful in detecting subclinical histological changes in the graft and improving short‐term renal allograft function.

The Comparative Safety of Various Intravenous Iron Preparations in Chronic Kidney Disease Patients

The relative safety of parenteral iron preparations is a controversial issue in the management of anemia in chronic kidney disease (CKD), as direct head-to-head comparative trials are lacking. In this study, patients of CKD were randomized to receive intravenous low molecular weight iron dextran (ID), sodium ferrigluconate complex (SFGC), and iron sucrose (IS) at doses and infusion rates recommended by the product manufacturer. One time test dose was used only for ID and SFGC. A total of 2,980 injections (n = 339) of i.v. iron was given, and 49 patients (14.45% per patient) and a total of 56 adverse events (1.88% per infusion) were noted. Odds ratios (OR) of serious adverse drug events (ADE; i.e., death, anaphylaxis, or suspected immuno-allergic events) per patient was not significant between ID vs. SFGC (3.566) and SFGC vs. IS (2.129), whereas that between ID vs. IS (7.594) was highly significant (p = 0.034). OR of serious ADE exposure was significantly higher in ID vs. SFGC (OR = 5.670, p = 0.0147) and ID vs. IS (OR = 7.799, p < 0.001). No significant difference was seen between the three groups in terms of non-serious ADEs. Drug discontinuation occurred significantly more often with ID. One patient who developed anaphylactoid reaction with SFGC and ID tolerated iron sucrose well.

Iron status, inflammation and hepcidin in ESRD patients: The confounding role of intravenous iron therapy

Uremia is a state of heightened inflammatory activation. This might have an impact on several parameters including anemia management. Inflammation interferes with iron utilization in chronic kidney disease through hepcidin. We studied the body iron stores, degree of inflammatory activation, and pro-hepcidin levels in newly diagnosed patients with end-stage renal disease (ESRD), and compared them with normal population. In addition to clinical examination and anthropometry, the levels of iron, ferritin, C-reactive protein, tumor necrosis factor alfa, interleukin-6, and prohepcidin were estimated. A total of 74 ESRD patients and 52 healthy controls were studied. The ESRD patients had a significantly lower estimated body fat percentage, muscle mass, and albumin; and higher transferrin saturation (TSAT) and raised serum ferritin. Inflammatory activation was evident in the ESRD group as shown by the significantly higher CRP, IL-6, and TNF-α levels. The pro-hepcidin levels were also increased in this group. Half of the ESRD patients had received parenteral iron before referral. Patients who had received intravenous iron showed higher iron, ferritin, and TSAT levels. These patients also showed more marked inflammatory activation, as shown by the significantly higher CRP, TNF-α, and IL-6 levels. We conclude that our ESRD patients showed marked inflammatory activation, which was more pronounced in patients who had received IV iron. High hepcidin levels could explain the functional iron deficiency. The cause of the relatively greater degree of inflammatory activation as well as the relationship with IV iron administration needs further studies.

PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians

BACKGROUND Antibodies to M-type phospholipase A2 receptor (PLA2R) correlate with clinical activity of primary membranous nephropathy (PMN). Risk alleles in PLA2R1 and HLA-DQA1 genes are associated with PMN. Whether these alleles are associated with the development of anti-PLA2R is unknown. In this prospective study we evaluated anti-PLA2R, enhanced glomerular staining for PLA2R and variations in PLA2R1 and HLA-DQA1 genes in Indian patients with PMN and examined their association with response to treatment. METHODS A total of 114 adult PMN patients were studied. Anti-PLA2R was estimated before treatment and after 6 and 12 months of therapy. Enhanced glomerular staining for PLA2R was assessed on fresh frozen tissue. Genotype analysis was done on recruited patients and 95 healthy controls by TaqMan assays for six single-nucleotide polymorphisms (SNPs; rs4664308, rs3749119, rs3749117, rs4664308, rs3828323 and rs2187668). Patients were followed up monthly for a period of 12 months. RESULTS Of 114 patients, 66.7% showed elevated serum anti-PLA2R by ELISA and 64.9% by indirect immunofluorescence. About 75% had enhanced glomerular staining for PLA2R. A total of 82% of patients had PLA2R-related disease. Reduction in serum anti-PLA2R titer had a significant association with remission of nephrotic syndrome (P = 0.0003) at 6 and 12 months. More than 85% of patients showing >90% reduction in the anti-PLA2R titer achieved remission of the nephrotic state, whereas of those showing <50% reduction in titers, 87.5% had persistent nephrotic state. The SNPs rs3749119, rs3749117, rs4664308 in PLA2R1 and rs2187668 in HLA-DQA1 were significantly associated with PMN. The SNP rs2187668 was associated with anti-PLA2R positivity. Patients with a high-risk genotype had higher anti-PLA2R levels. CONCLUSION To conclude, anti-PLA2R and enhanced glomerular PLA2R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA2R titer correlated with response to therapy.

Presentation and outcome of emphysematous renal tract disease in patients with diabetes mellitus.

Background: Emphysematous renal tract disease (ERTD) is a rare necrotizing infection of the renal parenchyma and urinary tract caused by gas-producing organisms. ERTD deserves special attention because of its life-threatening potential. Objectives: To study the clinical features, radiological classification and prognostic factors of ERTD; and to compare the modalities of management and the outcome among the various radiological classes of ERTD. Patients and Methods: Twenty consecutive patients with diabetes and ERTD, seen over last 3 years in a tertiary care institute of north India, were included in the study. All patients were subjected to computerized tomography (CT) after initial diagnosis by ultrasonography. They were classified into 5 classes as previously described. All patients included in the study were conservatively managed with appropriate antibiotics and/or percutaneous drainage or surgery if required. Result: Mean age (± SD) of these subjects was 54.4 ± 20.6 years; duration of diabetes mellitus 8.6 ± 5.8 years, and duration of symptoms related with ERTD ranged from 3 days to 3 months. Two patients had isolated emphysematous cystitis, 13 patients had emphysematous pyelonephritis (EPN), 3 had both EPN and cystitis, and 1 patient had EPN with cholecystitis, and 1 patient had EPN with pyomyositis. Only 7 (35%) patients had a history of pneumaturia. Escherichia coli was the commonest microorganism. The radiological distribution in 18 (2 had isolated cystitis) patients with EPN was: 2 patients had class 1; 1 had class 2; 2 had class 3A; 11 had class 3B, and 2 had class 4. Of 20 patients 11 (55%) survived. However, those patients who died had severe EPN based on radiological class (6 had class 3B and 1 had class 4). There was no significant difference between the survivor and non-survivor groups with respect to age, gender, duration of diabetes mellitus, duration of symptoms, serum creatinine level, total leukocyte count, hemoglobin, platelet count and culture positivity. Conclusion: Computerized tomographic class 3B or 4 is the most reliable predictor of outcome in patients with ERTD.

Bardet-Biedl syndrome with end-stage kidney disease: A case report and review of literature

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive condition characterized by retinitis pigmentosa, postaxial polydactyly, central obesity, and renal involvement. Renal failure is the commonest cause of death. We report the first case of BBS with documented end-stage kidney disease from India. The diagnosis had been missed until the patient presented at our hospital. The relevant literature has also been reviewed.

Central nervous system complications in renal transplant recipients in a tropical environment.

Renal transplant recipients are at risk of developing various infectious and non-infectious complications affecting the central nervous system (CNS). There is paucity of data regarding the spectrum of CNS complications and the epidemiology of infective agents varies according to geographical location. We retrospectively studied the spectrum of CNS complications seen in 792 renal allograft recipients followed up at this tertiary care centre in north India over a 19-year period. Autopsy findings of 78 allograft recipients who died in the hospital were also reviewed and included. The brain was examined in 22 of these patients. Overall, 79 (10%) patients developed some form of CNS dysfunction with a mortality rate of 60.8%. CNS infections occurred in 31 renal allograft recipients (3.9% of total) and accounted for the largest group (39.2%). Fungi were the commonest etiological agents (21 patients) and were associated with a 70% mortality, with cryptococcal meningitis occurring in 12, mucormycosis in six, aspergillosis in one, and other unusual fungal infections in the remaining two patients. All patients with mucormycosis had a fatal outcome. The second largest group comprised of patients with non-uremic encephalopathies (23 patients, 29.1%) with metabolic encephalopathy occurring in 13, toxic encephalopathy in nine and hypertensive encephalopathy in one patient) and was associated with an overall mortality rate of 60.9%. Cerebrovascular accidents occurred in 12 patients (15.2%) and were associated with a mortality of 91.7%. Other CNS complications included treatment related complications in four (5.1%), primary CNS lymphomas in three (3.8%), and miscellaneous complications in six patients (7.6%). Patients with non-cryptococcal fungal infections of the CNS, hepatic and toxic encephalopathy and those with cerebrovascular accidents had the worst outcome. There was no relationship between the development of infection or stroke and the type of maintenance immunosuppression used. We conclude that complications involving the CNS occur in 10% of all renal transplant recipients and are associated a with high mortality, warranting early diagnosis and aggressive treatment.

Antibodies to m-type phospholipase A2 receptor in children with idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN), the commonest cause of adult nephrotic syndrome (NS), accounts for only a minority of paediatric NS. Antibodies to m‐type phospholipase A2 receptor (PLA2R) are seen in two‐thirds of adult IMN cases. PLA2R staining in glomerular deposits is observed in 74% and 45% of adult and paediatric IMN cases, respectively. However, there are no reports of anti‐PLA2R in paediatric IMN. We evaluated anti‐PLA2R levels and PLA2R in gloemrular deposits in paediatric IMN seen at our center. Five cases were enrolled, all the cases stained for PLA2R in glomeruli and three (60%) had antibodies to PLA2R antigen. There was a parellel reduction in proteinuria and anti‐PLA2R titer. The present report suggests that PLA2R has a contributory role in the pathogenesis of paediatric IMN.

Corticotropin-Dependent Cushing's Syndrome in a Patient with Chronic Renal Failure—A Rare Association

Corticotropin-dependent Cushings syndrome was detected in a 32-year-old male suffering from membranous nephropathy and chronic renal failure. Cortisol dynamics revealed high basal cortisol, loss of circadian rhythm, and nonsuppressibility with low-dose dexamethasone. However, the latter was suppressible with high-dose dexamethasone. Treatment with ketoconazole led to a remarkable response both clinically and biochemically. The occurrence of Cushings syndrome in a patient with chronic renal failure is extremely rare and poses significant diagnostic and therapeutic problems.

Allograft and prostatic involvement in a renal transplant recipient with disseminated tuberculosis

Tuberculosis is a serious opportunistic infection in renal transplant recipients and is disseminated in nature in one-third of patients. Genito urinary tuberculosis is rare in renal transplant recipients. We report a patient presenting 5 years after renal transplantation with disseminated tuberculosis and allograft and prostatic involvement.