Practice patterns and influence of allograft nephrectomy in pediatric kidney re-transplantation: A pediatric nephrology research consortium study.

INTRODUCTION: There are no guidelines regarding management of failed pediatric renal transplants. MATERIALS & METHODS: We performed a first of its kind multicenter study assessing prevalence of transplant nephrectomy, patient characteristics, and outcomes in pediatric renal transplant recipients with graft failure from January 1, 2006, to December 31, 2016. RESULTS: Fourteen centers contributed data on 186 pediatric recipients with failed transplants. The 76 recipients that underwent transplant nephrectomy were not significantly different from the 110 without nephrectomy in donor or recipient demographics. Fifty-three percent of graft nephrectomies were within a year of transplant. Graft tenderness prompted transplant nephrectomy in 91% (P < .001). Patients that underwent nephrectomy were more likely to have a prior diagnosis of rejection within 3 months (43% vs 29%; P = .04). Nephrectomy of allografts did not affect time to re-listing, donor source at re-transplant but significantly decreased time to (P = .009) and incidence (P = .0002) of complete cessation of immunosuppression post-graft failure. Following transplant nephrectomy, recipients were significantly more likely to have rejection after re-transplant (18% vs 7%; P = .03) and multiple rejections in first year after re-transplant (7% vs 1%; P = .03). CONCLUSIONS: Practices pertaining to failed renal allografts are inconsistent-40% of failed pediatric renal allografts underwent nephrectomy. Graft tenderness frequently prompted transplant nephrectomy. There is no apparent benefit to graft nephrectomy related to sensitization; but timing / frequency of immunosuppression withdrawal is significantly different with slightly increased risk for rejection following re-transplant.

Diagnosis, Treatment, and Outcomes in Children With Congenital Nephrogenic Diabetes Insipidus: A Pediatric Nephrology Research Consortium Study.

Background and Objectives: Congenital or primary nephrogenic diabetes insipidus (NDI) is a rare genetic disorder that severely impairs renal concentrating ability, resulting in massive polyuria. There is limited information about prognosis or evidence guiding the management of these patients, either in the high-risk period after diagnosis, or long-term. We describe the clinical presentation, genetic etiology, treatment and renal outcomes in a large group of children <21 years with NDI. Design: A multi-center retrospective chart review. Results: We report on 66 subjects from 16 centers. They were mainly male (89%) and white (67%). Median age at diagnosis was 4.2 months interquartile range (IQR 1.1, 9.8). A desmopressin acetate loading test was administered to 46% of children at a median age of 4.8 months (IQR 2.8, 7.6); only 15% had a water restriction test. Genetic testing or a known family history was present in 70% of the patients; out of those genetically tested, 89 and 11% had mutations in AVPR2 and AQP2, respectively. No positive family history or genetic testing was available for 30%. The most common treatments were thiazide diuretics (74%), potassium-sparing diuretics (67%) and non-steroidal anti-inflammatory drugs (42%). At the time of first treatment, 70 and 71% of children were below -2 standard deviations (SD) for weight and height, respectively. At last follow-up, median age was 72.3 months (IQR 40.9, 137.2) and the percentage below -2 SD improved to 29% and 38% for weight and height, respectively. Adverse outcomes included inpatient hospitalizations (61%), urologic complications (37%), and chronic kidney disease (CKD) stage 2 or higher in 23%. Conclusion: We found the majority of patients were treated with thiazides with either a potassium sparing diuretic and/or NSAIDs. Hospitalizations, urologic complications, short stature, and CKD were common. Prospective trials to evaluate different treatment strategies are needed to attempt to improve outcomes.

Correction to: Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings : A Midwest Pediatric Nephrology Consortium (MWPNC) study.

The original version of this article unfortunately contained a mistake. The subtitle "A Midwest Pediatric Nephrology Consortium (MWPNC) study" was missing. The correct title including subtitle is given above.

Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings.

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence. METHODS: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence. RESULTS: We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI 5.6; 1.3-23.7) compared to FSGS predicted disease recurrence. CONCLUSIONS: Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.

De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease.

BACKGROUND: Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naïve patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy. METHODS: One-hundred sixteen pediatric ESA-naïve subjects (aged 1-18 years) with CKD stages 3-5D and hemoglobin (Hb) <10 g/dl from 43 centers in the US, Europe, and Mexico were randomized by age (three groups) and dialysis status (yes vs. no) to receive darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) subcutaneously (not on dialysis and peritoneal dialysis subjects) and intravenously (hemodialysis subjects). The drug was titrated to achieve Hb levels of 10.0-12.0 g/dl over 25 weeks. Patient- and parent-reported health-related outcomes were measured by the Pediatric Quality of Life Inventory (PedsQL™) in children ≥2 years. RESULTS: In both groups, mean Hb concentrations increased to ≥11.0 g/dl over the first 3 months of treatment and remained stable within the 10.0-12.0 g/dl target range. The median time to achieve hemoglobin ≥10 g/dl was slightly longer for subjects <12 years (QW and Q2W, both 28 days) vs. those ≥12 years (23 and 22 days, respectively). Adverse event profiles were similar between groups, with QW, four (7%) and Q2W, five (9%). PedsQL™ scores showed modest increases. CONCLUSIONS: Darbepoetin alfa can be safely administered either QW or Q2W to ESA-naïve pediatric patients with CKD-related anemia to achieve Hb targets of 10.0-12.0 g/dl.

Post-Transfer Predictors of Poor Outcomes in Pediatric Renal Transplant Recipients.

The aims of this study were twofold: 1) to describe the post-transfer (defined as from pediatric to adult providers) incidence of predictors (medication nonadherence, acute rejection, and change in kidney function), as well as outcomes (graft loss) for adolescent and young adult kidney transplant recipients during a three-year post-transfer follow-up period; and 2) to identify variables to monitor these predictors, in the form of a clinical profile, so providers can promote early intervention for these medically at-risk adolescents. National data were used to describe predictors and outcomes for 250 youth (16 to 25 years old) three years after transfer of care. These predictors were combined with previous literature to develop a preliminary clinical profile. Using an evidence-based clinical profile with predictors for graft loss by a dedicated healthcare professional as a transition coordinator will assist in identifying those at risk for poor outcomes after transfer.

Veno-Venous Extracorporeal Membrane Oxygenation for Continuous Renal Replacement in a Neonate with Propionic Acidemia.

The usual indications for extra corporeal membrane oxygenation (ECMO) are for respiratory or cardiac failure. Although continuous renal replacement therapy (CRRT) is frequently used when patients are on ECMO, the need for CRRT as the primary indication for ECMO is rare. A case of a neonate placed onto veno-venous ECMO for the use of CRRT to treat hyperammonemia from propionic acidemia is presented.

Longitudinal analysis of living donor kidney transplant rates in pediatric candidates in the United States.

Among adults, living donor kidney transplant rates began declining in the United States after 2004 but whether a similar decline is occurring in the pediatric candidates has not been well studied. Share 35, a change in allocation rules implemented in October of 2005, may also have influenced rates of living donation. We sought to determine whether a decline in rates was occurring in pediatric candidates and whether the Share 35 program was the cause of the decline. All children listed for a kidney transplant or transplanted with a living donor without listing between 1996 and 2011 were identified in the United States (N=14 911) of which 6046 had received a living donor transplant during follow-up. Kaplan-Meier analysis showed a decline in living donor rates in candidates listed after 2001. Logistic regression analysis for living donor kidney transplantation confirmed the timing of the drop but also showed that changes in candidate demographics and center listing practices were impacting rates. A large drop in parental donation was the main cause for the drop. The rate of living donor transplant among pediatric candidates declined after 2001 predating by 4 years the implementation of Share 35, suggesting that factors other than changes in allocation rules are responsible for the decline.

Renin Angiotensin System Blocker Fetopathy: A Midwest Pediatric Nephrology Consortium Report.

OBJECTIVES: Fetuses continue to be exposed to renin angiotensin system (RAS) blockers despite their known teratogenicity and a black box warning. We hypothesized that fetopathy from in utero exposure to RAS blockers has a broader spectrum of clinical manifestations than described previously and that there are a variety of clinical scenarios leading to such exposures. STUDY DESIGN: This was a retrospective study performed through the Midwest Pediatric Nephrology Consortium. Cases of RAS blocker fetopathy were identified, with determination of renal and extrarenal manifestations, timing of exposure, and the explanation for the fetal exposure. RESULTS: Twenty-four cases were identified. RAS blocker exposure after the first trimester was associated with more severe renal manifestations. Chronic dialysis or kidney transplantation was required in 8 of 17 (47%) patients with RAS blocker exposure after the first trimester and 0 of 7 patients with exposure restricted to the first trimester (P = .05). Extrarenal manifestations, some not previously noted in the literature, included central nervous system anomalies (cystic encephalomalacia, cortical blindness, sensorineural hearing loss, arachnoid cysts) and pulmonary complications (pneumothorax, pneumomediastinum). RAS blocker exposure usually was secondary to absent or poor prenatal care or undiagnosed pregnancy. CONCLUSION: RAS blocker fetopathy continues to be a cause of considerable morbidity, with more severe renal manifestations associated with exposure after the first trimester. A variety of significant extrarenal manifestations occur in these patients. Clinicians should emphasize the risk of fetopathy when prescribing RAS blockers to women of childbearing age.

Surgical outcomes analysis of pediatric peritoneal dialysis catheter function in a rural region.

PURPOSE: The purpose of this study was to analyze the experience with peritoneal dialysis (PD) at a high-volume, single center institution that supports a rural population. METHODS: From 2000 to 2010, 88 children (median age: 1.98 years, [range: 2 days-20.2 years]) received 134 PD catheters for the management of acute and chronic renal failure. The primary outcome of interest was the incidence of primary PD catheter failure (replacement or revision within 60 days). Operative technique, longitudinal outcomes, and time intervals to transplantation were analyzed. RESULTS: Median time to transplant from the institution of dialysis was 1.4 years [range: 0.3-6.4 years]. Primary catheter failure occurred in 24.6% of cases. Infants less than 6 months of age demonstrated an increased incidence of primary catheter failure (p = 0.02). The operative technique for catheter placement was not associated with the incidence of primary failure. Postoperative complications included peritonitis (22.7%), omental plugging (11.9%), pericatheter drainage (9.0%), and exit site infection (3.0%). CONCLUSION: Peritoneal dialysis provides a safe and effective renal replacement therapy for regional pediatric centers that serve a rural population. However, primary catheter failure rates remain high at 24.6%. The surgical technique for placement had no effect on this failure rate in our patient population. Infants less than 6 months of age are at increased risk for primary catheter failure and warrant intensive surveillance.