Post-transplant complications, patient, and graft survival in pediatric and adolescent kidney transplant recipients at a tropical tertiary care center across two immunosuppression eras.

BACKGROUND: We report pediatric PAKT patient and graft outcomes at a large tropical tertiary center spanning two transplant eras. METHODS: In this retrospective cohort study, all children ≤18 years who underwent kidney transplantation at our center between 1991 and 2016 were included. Data pertaining to their baseline characteristics, post-transplant events, and outcome were retrieved from transplant records and compared between transplant eras (1991-2005 and 2006-2016). RESULTS: A total of 139 children (mean age 15.2 ± 2.9 years) underwent PAKT during this period. The incidence of UTIs, CMV disease, BKVN, invasive fungal infections, new-onset diabetes after transplant, leucopenia, and recurrent NKD was higher in the 2006-2016 era (P < .001 for all), while 1-year cumulative BPAR was comparable (P = .100). Five-year graft and patient survival in the two eras were 89.9% and 94.2% (P = .365) and 92.1% and 95.3% (P = .739), respectively. Incidence of CMV disease, BKVN, graft loss, and death was lower in the calcineurin withdrawal group. Non-adherence accounted for 36% of graft loss; infections caused 43.7% of deaths. On multivariate Cox proportional hazards analysis, independent predictors for graft loss were UTIs and blood transfusion naïve status and for death were serious infections and glomerular NKD. CONCLUSIONS: PAKT in India has excellent long-term graft outcomes, though patient outcomes remain suboptimal owing to a high burden of infections. Current immunosuppression protocols need to be re-examined to balance infection risk, graft, and patient survival.

Safety and utility of kidney biopsy in patients with estimated glomerular filtration rate < 30 ml/min/1.73 m2.

AIM: Kidney biopsy (KBx) is the gold standard for evaluation of kidney disease, but is associated with a higher risk of complications in patients with reduced glomerular filtration rate (GFR). We studied the safety and utility of KBx in patients with eGFR <30 ml/min/1.73 m2 . METHODS: Consecutive adult patients with eGFR <30 ml/min/1.73 m2 , who were planned for a KBx and consented to participate were prospectively enrolled. Patients with solitary/transplant kidney or acute kidney injury were excluded. Haemoglobin was checked on the day of KBx and repeated 18-24 h later along with a screening ultrasound. Post-KBx complications were noted and their risk-factors analysed. The utility of the KBx was graded as effecting significant, some, or no change to subsequent management. RESULTS: Of the 126 patients included, 75% were male, 27.7% were diabetic, and the median eGFR was 13.5 ml/min/1.73m2 . Major complications occurred in 5.6%. Peri-renal haematomas were detected in 37.3%, and haematomas ≥2 cm were significantly more frequent in those with eGFR <15 ml/min/1.73 m2 (29.2% vs. 13%, p = .032). Dialysis was a risk factor, while pre KBx blood transfusion, diabetes and higher serum albumin were protective against any complication. KBx was more likely to make a significant difference in management in those with eGFR 15-29 ml/min/1.73m2 (44.1% vs. 11.1%, p < .001). Increasing age, lower serum creatinine and albumin were independently associated with KBx utility. CONCLUSION: KBx is relatively safe in severe kidney disease but its risk to benefit balance needs to be carefully considered when eGFR is <15 ml/min/1.73m2 .

Podocyte Infolding Glomerulopathy (PIG) in a Patient With Undifferentiated Connective Tissue Disease: A Case Report.

Podocyte infolding glomerulopathy (PIG) is a recently described pathologic entity characterized by diffuse podocyte infolding into the glomerular basement membrane (GBM) associated with ultrastructurally demonstrable microspherular aggregates. The clinical features, significance, and pathogenesis of this condition are still not well delineated because only a few cases have been documented to date, all from Japan. We report a case of PIG associated with undifferentiated connective tissue disease in an Indian woman who presented with nephrotic syndrome while undergoing treatment for an autoimmune disorder. Ultrastructural analysis of the kidney biopsy specimen revealed unusual subepithelial aggregates of microspherules admixed with few microtubules alongside extensive infolding of podocyte foot processes into the underlying GBMs. Characteristic clustering of these microparticles near the invaginated tips of podocyte foot processes in the GBM was observed on transmission electron microscopy. The patient's clinical condition responded favorably to immunosuppressive therapy. The clinical, light microscopic, and diagnostic electron microscopic features of this condition are highlighted in this report in an attempt to contribute some insights into the possible pathogenetic mechanisms of this obscure entity.

Spectrum of biopsy proven renal disease in South Asian children: Two decades at a tropical tertiary care centre.

AIM: We report findings from a large single centre paediatric renal biopsy cohort in South Asia. METHODS: We analyzed all renal biopsies performed on children aged ≤18 years between 1996 and 2015 at our centre. The clinical characteristics and histological diagnosis pertaining to each case, distribution of renal diseases in children with various clinical presentations, and changes in the pattern of kidney disease during the study period were analyzed. RESULTS: A total of 1740 paediatric kidney biopsies were performed during the study period. The mean age was 12.8 ± 4.9 years (8 months to 18 years) and the male: female ratio was 1.5:1. The most common indication for renal biopsy was nephrotic syndrome (63.2%) followed by acute nephritic syndrome (13%). Minimal change disease was the most common cause of nephrotic syndrome while endocapillary proliferative glomerulonephritis (65.7% infection related), remained the commonest cause of acute nephritic syndrome. IgA nephropathy was the commonest cause of chronic kidney disease. Contrary to trends in European paediatric cohorts, the frequency of lupus nephritis increased over the two decades of the study, while that of endocapillary proliferative glomerulonephritis did not show any appreciable decline. CONCLUSION: This study provides the largest data on biopsy proven renal disease in children from South Asia published till date and highlights important differences in the spectrum and trends of kidney disease compared to data from other regions.

Pharmacokinetics of concentration-controlled mycophenolate mofetil in proliferative lupus nephritis: an observational cohort study.

BACKGROUND: Mycophenolate mofetil (MMF) has variable pharmacokinetics. This study examines the pharmacokinetic and clinical correlations in proliferative lupus nephritis. METHODS: Thirty-four patients were started on MMF, and the area under the concentration-time curve (AUC) was measured by limited sampling strategies, and dosing was adjusted to achieve an AUC of 30-60 mg·h·L. Twenty-seven patients had at least 2 measurements, and renal response was assessed within 1 year. RESULTS: About 61.8% of patients had mycophenolic acid (MPA) AUC <30 mg·h·L with an empiric starting dose of 30 mg/kg. About 79.4% of patients achieved renal response by 1 year, and the median time to renal response was 111 days. MMF dose per body weight had a weak correlation with the AUC and did not correlate with trough concentrations. The median dose was 1.5 g/d at entry and 2 g/d after dose modification during the induction phase. Trough concentrations had a weak correlation with AUC. Patients with serum albumin ≥35 g/L had a greater chance of having an AUC ≥30 mg·h·L. The between-patient coefficient of variability for dose-normalized AUC was 37.9% at entry and 31% within 1 year, whereas repeated measurements over time in an individual had a good intraclass correlation of 0.78. Infections occurred in 11.8% and toxicities in 5.9%. MPA exposure was not significantly associated with adverse events. Patients with an AUC ≥30 mg·h·L had greater renal response at 1 year. CONCLUSIONS: Lupus nephritis patients induced with concentration-controlled MMF had excellent renal response and fewer adverse events with lower than usual dosing. MPA exposure had high interpatient variability, requiring measurements for personalized dosing, and fewer adverse events. Long-term cost reduction is achievable with lower doses and good renal response in the majority of patients.

"Why I Chose Hemodialysis Over Peritoneal Dialysis": An Opinion Survey Among In-Center Hemodialysis Patients.

Peritoneal dialysis (PD) penetration in India remains low despite the huge chronic kidney disease burden and unmet need for renal replacement therapy (RRT). In order to understand the socioeconomic reasons that govern patients' preference for hemodialysis (HD), we carried out an opinion survey among prevalent in-center HD patients at our institution using a multiple response questionnaire that was verbally administered to them at the dialysis facility by the investigators. Close to 80% were self-financed and 49.5% were on twice weekly HD. Despite the majority (95%) receiving RRT education from a nephrologist, 43.4% were not aware of PD as an RRT modality. The treating nephrologist's recommendation was the most important reason given for choosing HD (77.8%) and not choosing PD (69.7%). Other reasons for not choosing PD included lack of a dedicated caregiver or "clean area" at home (15.1%), fear of infection (15.1%), disruption of work (14.1%), and the high cost of PD (7%). The perceived advantages of HD over PD were greater convenience because of need for only twice or thrice weekly sessions (61%), supervised care received in a hospital setting (28.8%), and less disruption of the patient's and family's routine (22%). We discuss the implications of these findings and what policy makers and nephrologists in India and other developing countries can do to improve PD penetration and utilization.

Comparison of Early Mechanical and Infective Complications in First Time Blind, Bedside, Midline Percutaneous Tenckhoff Catheter Insertion with Ultra-Short Break-In Period in Diabetics and Non-Diabetics: Setting New Standards.

♦ BACKGROUND: There are no large studies that have examined ultra-short break-in period with a blind, bedside, midline approach to Tenckhoff catheter insertion. ♦ METHODS: Observational cohort study of 245 consecutive adult patients who underwent percutaneous catheter insertion for chronic peritoneal dialysis (PD) at our center from January 2009 to December 2013. There were 132 (53.9%) diabetics and 113 (46.1%) non-diabetics in the cohort. ♦ RESULTS: The mean break-in period for the percutaneous group was 2.68 ± 2.6 days. There were significantly more males among the diabetics (103 [78%] vs 66 [58.4%], p = 0.001). Diabetics had a significantly higher body mass index (BMI) (23.9 ± 3.7 kg/m2 vs 22.2 ± 4 kg/m2, p < 0.001) and lower serum albumin (33.1 ± 6.3 g/L vs 37 ± 6 g/L, p < 0.001) compared with non-diabetics. Poor catheter outflow was present in 6 (4.5%) diabetics and 16 (14.2%) non-diabetics (p = 0.009). Catheter migration was also significantly more common in the non-diabetic group (11 [9.7%] vs 2 [1.5%], p = 0.004). Primary catheter non-function was present in 17(15%) of the non-diabetics and in 7(5.3%) of the diabetics (p = 0.01). There were no mortality or major non-procedural complications during the catheter insertions. Among patients with 1 year of follow-up data, catheter survival (93/102 [91.2%] vs 71/82 [86.6%], p = 0.32) and technique survival (93/102 [91.2%] vs 70/82 [85.4%], p = 0.22) at 1 year was comparable between diabetics and non-diabetics, respectively. ♦ CONCLUSIONS: Percutaneous catheter insertion by practicing nephrologists provides a short break-in period with very low mechanical and infective complications. Non-diabetic status emerged as a significant risk factor for primary catheter non-function presumed to be due to more patients with lower BMI and thus smaller abdominal cavities. This is the first report that systematically compares diabetic and non-diabetic patients.

Percutaneous continuous ambulatory peritoneal dialysis (CAPD) catheter insertion--a preferred option for developing countries.

Continuous ambulatory peritoneal dialysis (CAPD) as a modality of renal replacement therapy in patients with chronic kidney disease stage 5 (CKD 5) has the advantage of being a home-based therapy and is a preferred option in patients with inadequate access to haemodialysis and transplantation facilities and in those infected with HIV and other blood-borne viruses. While open surgical CAPD catheter placement has been the conventional mainstay of access placement, percutaneous techniques are being increasingly used with similar success rates. We report our experience over the past two years with blind insertion of the swan neck percutaneous double-cuffed Tenckhoff CAPD catheter using a trocar. There was considerable decrease in hospital stay and surgical costs. There was only one major complication of injury to the jejunal mesenteric artery requiring emergency laparotomy in one patient. In three patients, drain of peritoneal fluid was inadequate, presumably due to omental wrapping around the in-dwelling catheter, and required surgical removal of the omentum.