Clinical indicators of slow graft function and outcome after pediatric kidney transplantation.

BACKGROUND: Lesser degrees of perioperative ischemia-reperfusion injury that does not require dialysis may nonetheless influence allograft outcomes, necessitating evaluation of suitable surrogate indicators of perioperative allograft injury. METHODS: This retrospective analysis of pediatric kidney transplants evaluated two indicators representing pace and completeness of recovery, for association with 12-month estimated glomerular filtration rate (eGFR) and first-year rate of eGFR decline: time to creatinine nadir (TTN) and ratio of recipient/donor unadjusted GFR (uGFRR/D ) at 1-month post-transplant. Donor, recipient, and perioperative risk factors were tested further for association with these 2 indicators. RESULTS: 179 patients (190 transplants) aged 13 (IQR 7-17) years and 56% male were included. Twelve-month eGFR was strongly associated with unadjusted GFR at 1 month (uGFR1M , p < .001) and uGFRR/D (p = .003), but not with TTN. None of the indicators was associated with the rate of subsequent eGFR decline after 1-month post-transplant. As a potential surrogate indicator, uGFR1M is effectively modeled by TTN and uGFRR/D (adjusted R2  = 0.57) and is associated with 12-month eGFR (ß = 0.81 ± 0.08; p < .001). Clinical factors associated with uGFRR/D included donor uGFR (p < .001), BSA (p = .026), age (p = .074), and recipient BSA (p < .001). Factors associated with pace of recovery (TTN) included donor uGFR (p = .018), type (p = .019), and recipient BSA (p = .022). CONCLUSIONS: The uGFRR/D ratio, but not TTN, is a useful indicator of perioperative allograft damage that is associated with one-year functional outcome; and uGFR1M is a potential early surrogate outcome. Donor, recipient, and perioperative factors that are associated with slow allograft function are identified.

Early surveillance biopsy utilization and management of pediatric renal allograft acute T cell-mediated rejection in Canadian centers: Observations from the PROBE multicenter cohort study.

BACKGROUND: Early TCMR surveillance with protocol kidney biopsy is used differentially among pediatric kidney transplant centers. Little has been reported about actual center-based differences, and this variability may influence TCMR ascertainment, treatment, and monitoring more broadly. METHODS: Data from the PROBE multicenter study were used to identify patients from centers conducting ESB or LSIB. ESB was defined as >50% of patients having at least 1 surveillance biopsy in the first 9 months. Patients were compared for number of biopsies, rejection episodes, treatment, and follow-up monitoring. RESULTS: A total of 261 biopsies were performed on 97 patients over 1-2 years of follow-up. A total of 228 (87%) of biopsies were performed in ESB centers. Compared to LSIB centers, ESB centers had 7-fold more episodes of TCMR diagnosed on any biopsy [0.8 ± 1.2 vs 0.1 ± 0.4; P < .001] and a 3-fold higher rate from indication biopsies [0.3 ± 0.9 vs 0.1 ± 0.3; P = .04]. The proportion of rejection treatment varied based on severity: Banff borderline i1t1 (40%);>i1t1 and < Banff 1A (86%); and ≥ Banff 1A (100%). Biopsies for follow-up were performed after treatment in 80% of cases (n = 28) of rejection almost exclusively at ESB centers, with 17 (61%) showing persistence of TCMR (≥i1t1). CONCLUSIONS: Practice variation exists across Canadian pediatric renal transplant centers with ESB centers identifying more episodes of rejection. Additionally, treatment of Banff borderline is not universal and varies with severity regardless of center type. Lastly, follow-up biopsies are performed inconsistently and invariably show persistence of rejection.

Risk factors associated with allograft failure in pediatric kidney transplant recipients with focal segmental glomerulosclerosis.

BACKGROUND: With improved outcomes for children transplanted with FSGS since previous NAPRTCS registry reports, this study re-evaluates the association of living donation, immunosuppression, and DGF on graft survival. SETTING: Patients transplanted between 2002 and 2016, comparing FSGS diagnosis vs other glomerular diseases. METHODS: Primary outcomes were allograft survival and FSGS recurrent-free graft survival. Potential risk factors were obtained at the time of transplant and up to 30 days post-transplantation. Analysis considered a priori that DGF may be a proxy for severe FSGS recurrence. Multivariable survival models for outcome were tested for sensitivity without/with DGF to determine features independent of recurrence. RESULTS: From the larger cohort of 3010 patients, 5-year graft survival in children with FSGS (n = 455) was worse (74.3%) compared with other glomerular diseases (87.1%, n = 690) (HR 1.45, P = 0.033). Modeling all glomerular diseases, survival risk was associated with deceased donor (HR 1.83, P = 0.002), re-transplantation (HR 1.58, P = 0.013), and recipient age (HR 1.06/y, P = 0.002). The living donor advantage was not confirmed in a FSGS model (HR 1.51 for deceased, P = 0.12). DGF was highly associated with graft failure (HR 4.39, P < 0.001) and independent of re-transplant history but not FSGS diagnosis. Induction agents or primary immunosuppression choices were not associated with survival. CONCLUSION: Graft survival rates have improved since the previous report. Living donor did not predict graft failure, but there remains no survival advantage. DGF was the primary independent predictor for graft loss secondary to FSGS recurrence, consistent with DGF being a proxy for severe recurrent disease.

The concurrent presentation of minimal change nephrotic syndrome and aplastic anemia.

Minimal change nephrotic syndrome (MCNS) has been associated with primary immunological disorders, such as lymphoma and thymoma. While several different explanations have been proposed, much of the literature has implicated activated T-lymphocytes in the pathogenesis. We report a patient with minimal change nephrotic syndrome presenting concurrently with thrombocytopenia and anemia, with a subsequent diagnosis of aplastic anemia. To our knowledge, this is the first such case described in the literature.

Biopsy-proven acute tubular necrosis in a child attributed to vancomycin intoxication.

Acute renal failure in children treated with vancomycin typically presents with interstitial nephritis. There is debate as to the extent of direct tubular toxicity attributable to vancomycin, especially in the absence of aminoglycoside treatment. We report a case of acute tubular necrosis (ATN) associated with vancomycin toxicity in an 8-year-old boy where there is no likely alternate explanation for toxic or ischemic injury. Treatment with hemodialysis resulted in the elimination of vancomycin from the circulation and subsequent improvement in renal function.