Pioglitazone enhances proteinuria reduction in complicated pediatric nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) is a common pediatric kidney disease, yet current treatments for complicated NS are only partially effective and have significant toxicity. There is no Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-approved safe and effective treatment for NS. Thiazolidinediones (TZDs) have been shown to reduce proteinuria in both diabetic and non-diabetic kidney disease and in preclinical studies to directly protect podocytes from injury and reduce proteinuria. Here, we report on the potential utility of the addition of the TZD pioglitazone (PIO) to enhance proteinuria reduction in 8 children and young adults with steroid dependent NS and steroid resistant NS. METHODS: Clinical data were analyzed in comparable time periods before and after the addition of PIO to their medical regimens. Eight NS patients with minimal change NS (n = 2), focal segmental glomerulosclerosis (FSGS) (n = 4), or collapsing FSGS (n = 2) were evaluated. RESULTS: Prior to PIO initiation, all children and young adults had already received multiple immunosuppressive medications (mean = 3.75). Five of eight patients (63%; "Responders") had notable proteinuria reduction within 1 month of PIO initiation (62% reduction; P = 0.04) and normalization within 6 months (97% reduction; P = 0.04). PIO-related benefits among the responders included notable increases in serum albumin (2.5 to 3.7 g/dl; P = 0.08), dramatic reductions in hospitalizations for IV albumin infusions and diuresis (11 to 0; P < 0.01), and considerable reduction in total immunosuppression (43% reduction; P > 0.1). Importantly, no patients experienced any adverse events attributable to PIO during a total of 136 patient-months of treatment. CONCLUSIONS: While confirmatory safety and efficacy studies are needed, these findings suggest pioglitazone (a non-immunosuppressive drug) may be useful to enhance proteinuria reduction in some children and young adults with complicated NS. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Relationship Between Change in Employment Status, Insurance Coverage, and Graft Failure or Death After Kidney Transplant.

Introduction: Early change of insurance coverage after kidney transplantation may be associated with worse graft outcomes. We examine how return to employment moderates the hazard of graft failure associated with exit from Medicare within 36 months after transplantation. Design: Patients undergoing kidney transplantation covered by Medicare between January 2005 and December 2016 were identified in the United Network for Organ Sharing (UNOS) database. A composite outcome of graft failure or death was analyzed across four groups: (1) no change in coverage within the first 3 years post-transplant, and no return to work (2) no change in coverage, return to work (3) change in coverage, no return to work (4) change in coverage, return to work. Results: The sample included 46 120 patients; 28% changed insurance coverage from Medicare posttransplant. Among patients who returned to work (36%), change in coverage from Medicare to other insurance was associated with lower hazard of death or graft failure (hazard ratio: 0.93; 95% confidence interval: 0.87, 0.99; P = 0.030). Conclusions: Exit from Medicare was associated with patient and graft survival greater than 3 years after transplant, depending on return to work. Among patients returning to work, changes in insurance from Medicare to private coverage were associated with favorable outcomes.

Factors associated with follow-up outside a transplant center among pediatric kidney transplant recipients.

BACKGROUND: Transfer of follow-up care after pediatric kidney transplantation (KTx) may jeopardize quality of care and patient outcomes. We sought to determine if minority status and socioeconomic factors were associated with increased likelihood of follow-up outside a transplant center, and whether this transition of care was associated with worse long-term graft and patient survival. METHODS: We performed an analysis of the United Network for Organ Sharing database, including children age < 18 years who received a kidney transplant between 2003 and 2018. Survival analysis (conditional on survival with functioning graft to 1 year) was performed using a Cox proportional hazards model where transfer of care (place of follow-up recorded as any setting other than a transplant center) was entered as a time-varying covariate. RESULTS: The study included 10,293, of whom 2083 received care outside of a transplant center during follow-up. Medicare coverage, but not minority race/ethnicity or socioeconomic status, was associated with increased likelihood of follow-up outside a transplant center. Follow-up outside a transplant center was associated with a 10% increased hazard of death or graft failure (hazard ratio: 1.10; 95% confidence interval: 1.004, 1.21; p = 0.041). CONCLUSION: Follow-up outside of a transplant center increased risk of poor outcomes, though the likelihood of receiving care outside a transplant center did not vary by race/ethnicity or socioeconomic status. Our results highlight the need to improve continuity of care after KTx and to further understand the mechanisms leading to poor survival rates among minority populations. A higher resolution version of the Graphical abstract is available as Supplementary information.

HIV-Associated CKDs in Children and Adolescents.

INTRODUCTION: Limited information is available describing the current prevalence of proteinuria and HIV-associated CKDs (HIV-CKDs) in children and adolescents living with HIV and receiving antiretroviral therapy in the United States. METHODS: To address this issue, we performed a retrospective study of children and adolescents living with HIV who received medical care at Children's National Hospital in Washington, DC, between January 2012 and July 2019. Demographic data, clinical parameters (mode of HIV transmission, viral loads, CD4 cell counts, serum creatinine, glomerular filtration rate [GFR], plasma lipid levels, proteinuria, blood pressure, renal biopsies), and medical treatments, all done as a standard of clinical care, were collected and analyzed. RESULTS: The majority of the 192 patients enrolled were of African descent (88%) and acquired HIV through vertical transmission (97%). The prevalence of all HIV-CKDs was 6%. Of these patients, 39% had intermittent or persistent proteinuria, and 7% percent had proteinuria with a mild decline in GFR (60-80 ml/min per 1.73 m2), and 6% had a mild decline in GFR without proteinuria. Documented hypertension was present in 6% of the patients, mainly in association with HIV-CKD. Patients with persistent proteinuria (3%) and biopsy-proven HIV-CKD had a slow but constant progression of their renal diseases. CONCLUSIONS: The prevalence of persistent proteinuria and HIV-CKD was lower than that reported in previous studies conducted in the United States. However, intermittent proteinuria, mild reductions in GFR, and progression of established HIV-CKD were common findings in this group of patients with predominantly vertically acquired HIV who were receiving antiretroviral therapy.