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.

Bone broth ingestion and acute kidney injury following kidney transplant: a role for cystatin C.

Measurement of graft dysfunction following kidney transplant through creatinine is well known to be impacted by many different factors. We report here a clinical scenario demonstrating the importance of dual measurement of glomerular filtration rate (GFR) based on creatinine and cystatin C while also examining within-subject variability of both tests.

Parkinsonism and prolonged cognitive decline as a manifestation of cryptococcal meningitis in a renal transplant patient.

We report a case of a 67-year-old male recipient of a second renal allograft, presenting with a 9-month history of progressive cognitive and physical decline with features of Parkinsonism. He was HIV-negative. Serum and cerebrospinal fluid (CSF) cryptococcal antigen was positive though CSF culture was sterile. He had progressive deterioration despite induction and consolidation antifungal treatment. Postmortem brain examination confirmed a large burden of yeast forms in the substantia nigra with widespread chronic meningitis. The significant delay in presentation and diagnosis owing to the atypical, subacute neurocognitive features serves as a timely reminder of the variety of neurological presentations that may be associated with cryptococcal infection in solid organ transplant recipients.

Analytical and clinical validation of dried blood spot and volumetric absorptive microsampling for measurement of tacrolimus and creatinine after renal transplantation.

BACKGROUND: Serial monitoring of tacrolimus and serum creatinine after renal transplantation is of vital importance. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the estimation of tacrolimus and creatinine, obtained from dried blood spots (DBS) or by volumetric absorptive microsampling (VAMS) was validated and the two sampling strategies were compared with traditional venous sampling. METHODS: The LC-MS/MS assay was validated using a shared extract for the estimation of tacrolimus and creatinine from DBS and VAMS independently. The relationship between the concentrations in DBS/VAMS specimens and in venous samples was assessed using Passing-Bablok (PB) analysis and the bias between the two methods was determined by the Bland Altman (BA) analysis. RESULTS: The imprecision and bias of tacrolimus and creatinine estimated from DBS and VAMS samples was <12% and was independent of the hematocrit (Hct). Samples were stable for five days at ambient temperature. From the PB regression analysis, correction equations were generated for the prediction of tacrolimus and creatinine values from DBS and VAMS samples. In a separate cohort of patients for validation, the corrected DBS and VAMS concentrations had a mean (95% CI) bias for tacrolimus of -0.64 (-2.98 to 1.70)% and -0.92 (-3.69 to 1.85)% respectively and for creatinine of 1.00 (-2.73 to 4.72)% and -0.71 (-3.74 to 2.32)% respectively. Using DBS and VAMS respectively, for tacrolimus, 91.8 and 89.8% of patient values and for creatinine, 69.4 and 81.6% of patient values were within the limits of clinical acceptance (within 15% agreement against the venous samples). CONCLUSION: We conclude that VAMS is the preferred single sampling option for estimating tacrolimus and creatinine in renal transplant patients.

Leflunomide with low-dose everolimus for treatment of Kaposi's sarcoma in a renal allograft recipient.

Current treatment of Kaposi's sarcoma is reduction of immunosuppression with or without addition of mammalian target of rapamycin inhibitors (mTORi). Akt signalling plays a central role in oncogenesis of Kaposi's sarcoma. We describe a case of multifocal Kaposi's sarcoma in a renal allograft recipient, which showed unsatisfactory early response to immunosuppression reduction along with everolimus therapy but completely resolved after adding leflunomide. mTORi impair Kaposi's sarcoma oncogenesis by inhibiting mTOR downstream from the Akt signalling. Leflunomide inhibits Akt phosphorylation. This synergistic effect may be beneficial in treatment of Kaposi sarcoma and needs to be explored in trials.

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.