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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.

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.

Multiplex PCR for rapid diagnosis of gastrointestinal tuberculosis.

Background: Rapid and specific diagnosis of gastrointestinal tuberculosis (GITB) is of utmost importance. Aim: To evaluate Multiplex PCR (MPCR) using MPB64 and IS6110 primers specific for M. tuberculosis for rapid diagnosis of GITB. Materials and Methods: MPCR was performed on colonoscopy biopsy specimens on 11 GITB confirmed (culture/AFB/histopathology was positive), 29 GITB suspected and 30 Non GITB (control group) patients. Results: MPB64 PCR had sensitivity and specificity of 90% and 100% for confirmed GITB cases. In 29 clinically diagnosed but unconfirmed GITB cases, MPCR was positive in 72.41%. MPCR was negative in all control group patients. The overall sensitivity and specificity of microscopy, culture, histopathology and MPCR was 5%, 2% 20% and 77.5% and 100%, 100%, 100% and 100% respectively. Conclusion: MPCR has good sensitivity and specificity in diagnosing gastrointestinal tuberculosis.

Ulcerative colitis after renal transplantation: A case report and review of literature

Diarrhea is common after kidney transplantation and is usually related to immunosuppressive medication or is infective in etiology. Inflammatory bowel disease (IBD) is rare after kidney transplantation and is unexpected because the patient is already immunosuppressed. Specific immunomodulatory actions of calcineurin inhibitors have been hypothesized to play a role in the development of IBD in such patients. We report a case of IBD developing de novo after kidney transplantation. Our case is unique in that the patient was not on calcineurin inhibitors for 8 years prior to the development of IBD.

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.

Childhood lupus nephritis in a developing country—24 years' single-center experience from North India

Objective Data on outcome of childhood lupus nephritis from developing countries are sparse. This study looks at outcome in children with lupus nephritis from a federal government-funded teaching hospital in North India. Methods This study included children less than 14 years of age with lupus nephritis who presented to a single center during a period of 24 years (1991 to 2013). Data on clinical characteristics and outcome were extracted from medical records. The primary outcome was actuarial survival (time-to-death) and secondary outcome was actuarial renal survival using Kaplan-Meier analysis. A worst-case scenario that assumed children who were lost to follow-up as having either died or gone into end-stage renal disease was also calculated. Log-rank test and Cox-regression were used to assess difference in survival by histological class and predictors of poor outcome, respectively. Results This study included 72 children, with a female:male ratio of 3:1, mean (±SD) age at onset of lupus 9.3 (±2.4) years and mean (±SD) time from onset-to-nephritis being 9.4 (±12.6) months. Renal biopsy was conducted in 53 children. The most common histological class was class IV (35 children). Mortality occurred in 22 children (30%), with half of these occurring at presentation. The two important causes of death were infection and end-stage renal disease. Actuarial survival was 81%, 67% and 59% at one, five and 10 years, respectively. In the worst-case scenario, actuarial survival was 72%, 53% and 38%, respectively. Renal survival was 96%, 89% and 78% (worst-case scenario 86%, 73% and 52%) at one, five and 10 years, respectively. There was no difference in survival by histological class. On univariate analysis, serum creatinine at presentation (hazard ratio = 2.2 (95% CI 1.3–3.9)) and serious infection (hazard ratio 7.9 (95% CI 2.6–23.5)) were statistically significant predictors of time-to-death. Conclusion Outcome of children with lupus nephritis from India is worse than developed countries. Nearly one-third of the children died, half at presentation, with common causes being infection and end-stage renal disease.

Should ultrasound guided percutaneous renal biopsy in children be done in a day care setting

Percutaneous renal biopsy (PRB) is an important diagnostic tool in pediatric nephrology units. But controversy exists whether the procedure can be done in the day care setting. This study was done to document complications of PRB done with automated gun under continuous ultrasonographic guidance and to find whether the procedure can be undertaken as a day care procedure. Retrospective analysis of 67 PRBs is presented. A total of 44% (n = 30) minor and 12% (n = 8) major complications such as gross hematuria, perinephric hematoma, and hemodynamic instability were observed through the study period. All major and 90% of minor complications were detected within four hours in the current study. The procedure may be undertaken in the day care setting with strict pre and postprocedure monitoring up to eight hours in children with normal blood pressures, renal functions, hemoglobin concentrations, and coagulation parameters.

Cytomegalovirus disease among renal transplant recipients in India

SUMMARY: There is a paucity of data on cytomegalovirus (CMV) disease in renal transplant recipients from India. We have encountered this problem with increasing frequency at our centre, and document our experience in this paper. Case records of 514 recipients of renal transplants performed between 1980 and 1997, including 96 autopsies, were reviewed. Diagnosis was made by demonstration of classic cytomegaly and intranuclear inclusions on histology, and/or detection of CMV pp‐65 antigen in the peripheral blood leucocytes. Cytomegalovirus disease was documented in 21 cases (11 at autopsy, six by antigen detection, and four by a combination of histological demonstration and antigenemia detection). the incidence of this infection rose from 0.6% in 1980–1991 (pre‐cyclosporin era) to 5.5% (4.4% lethal) during 1992–1997 (postcyclosporin era). At autopsy, the lung was the most frequently involved organ followed by the gastrointestinal tract. Ninety‐five per cent of patients had co‐infection with other organisms, and fungi were isolated in 80% of all patients with co‐infection. Graft dysfunction was present in 17 cases (81%). We conclude that there has been a four fold increase in the incidence of lethal CMV disease in renal transplant recipients after the introduction of cyclosporin immunosuppression. There is a high incidence of co‐infection with other organisms, with fungi being the commonest offenders in tropical environment. This, along with allograft dysfunction, could account for the high mortality seen with CMV disease.

Pauci-immune glomerulonephritis: does negativity of anti-neutrophilic cytoplasmic antibodies matters?

A significant proportion of pauci‐immune glomerulonephritis (PIGN) patients are reported to have absence of anti‐neutrophilic cytoplasmic antibodies (ANCA). However, studies are controversial regarding their significance and there is limited data after the new prognostic classification of PIGN.

Drug-induced acute interstitial nephritis: A clinicopathological study and comparative trial of steroid regimens.

Steroids are used in the management of drug-induced acute interstitial nephritis (AIN). The present study was undertaken to compare the efficacy of pulse methyl prednisolone with oral prednisolone in the treatment of drug-induced AIN. Patients with biopsy-proven AIN with a history of drug intake were randomized to oral prednisolone (Group 1) 1 mg/kg for 3 weeks or a pulse methyl prednisolone (Group II) 30 mg/kg for 3 days followed by oral prednisolone 1 mg/kg for 2 weeks, tapered over 3 weeks. Kidney biopsy scoring was done for interstitial edema, infiltration and tubular damage. The response was reported as complete remission (CR) (improvement in estimated glomerular filtration rate [eGFR] to ≥60 ml/min/1.73 m2), partial remission (PR) (improvement but eGFR <60 ml/min/1.73 m2) or resistance (no CR/PR). A total of 29 patients, Group I: 16 and Group II: 13 were studied. Offending drugs included nonsteroidal anti-inflammatory drugs, herbal drugs, antibiotics, diuretic, rifampicin and omeprazole. There was no difference in the baseline parameters between the two groups. The biopsy score in Groups I and II was 5.9 ± 1.1 and 5.1 ± 1.2, respectively. At 3 months in Group I, eight patients each (50%) achieved CR and PR. In Group II, 8 (61%) achieved CR and 5 (39%) PR. This was not significantly different. Percentage fall in serum creatinine at 1 week (56%) was higher in CR as compared to (42%) those with PR. (P = 0.14). Patients with neutrophil infiltration had higher CR compared to patients with no neutrophil infiltration (P = 0.01). Early steroid therapy, both oral and pulse steroid, is equally effective in achieving remission in drug-induced AIN.