Acute kidney injury in infants with hypoxic-ischemic encephalopathy.

BACKGROUND: This study aimed to investigate the prevalence of acute kidney injury (AKI) in infants with varying degrees of hypoxic-ischemic encephalopathy (HIE) and its associated outcomes, including mortality and length of stay (LOS). METHODS: The study used the National Inpatient Sample (NIS) dataset from 2010 to 2018. Regression analysis was used to control confounding variables. RESULTS: Of 31,220,784 infants included in the study, 30,130 (0.1%) had HIE. The prevalence of AKI was significantly higher in infants with HIE (9.0%) compared to those without (0.04%), with an adjusted odds ratio (aOR) of 77.6 (CI:70.1-85.7, p < 0.001), with the highest prevalence of AKI in infants with severe HIE (19.7%), aOR:130 (CI: 107-159), p < 0.001). Infants with AKI had a higher mortality rate compared to those without AKI in those diagnosed with any degree of HIE (28.9% vs. 8.8%), aOR 3.5 (CI: 3.2-3.9, p < 0.001), particularly among those with severe HIE, aOR:1.4 (1.2-1.6, p < 0.001). CONCLUSIONS: HIE is associated with an increased prevalence of AKI. Infants with severe HIE had the highest prevalence of AKI and associated mortality. The study highlights the need for close monitoring and early detection of AKI in infants with HIE, particularly those with severe HIE, to ameliorate the associated adverse outcomes.

Kidney replacement therapy in neonates: utilization trends and outcomes.

BACKGROUND: We aimed to assess prevalence and clinical characteristics of newborns receiving kidney replacement therapy (KRT). METHODS: We used the National Inpatient Sample (NIS) dataset for the years 2000-2017. Newborns treated with peritoneal dialysis (PD), hemodialysis (HD), and continuous KRT (CKRT) were included. Trend analysis using the Cochran-Armitage test was used to assess prevalence over the years. RESULTS: A total of 64,532,552 hospitalized newborns were included. Among the 4281 infants treated with KRT, 2501 (58.4%) were treated with PD, 997 (23.3%) had HD, and 783 (18.3%) used CKRT. Associated diagnoses included congenital kidney anomalies (37.4% vs. 15% vs. 9.5%), urinary tract anomalies (35% vs. 12.5% vs. 6.3%), and congenital heart disease (68% vs. 25.7% vs. 72.3%). Median length of stay was longest in PD patients (39 days vs. 18 days vs. 26 days), respectively. However, cost of hospitalization was greatest in CKRT patients (US $490,916 vs. US $218,514 vs. US $621,554), respectively. In the entire cohort, 54,424 newborns had acute kidney injury (AKI); of them 16,999 (31%) died. KRT was used in 2,688 (4.9%) of infants with AKI. Over the study period, trends for utilization of PD (from 0.042 to 0.06%) and CKRT (from 0.03 to 0.21%) increased whereas the hemodialysis trend decreased (from 0.021 to 0.013%). CONCLUSIONS: Congenital heart disease (CHD) and congenital anomalies of the kidneys and urinary tract (CAKUT) are the major diagnoses in newborns receiving KRT. Utilization of PD was greater than HD and CKRT. Trends of PD and CKRT utilization increased over time. Less than 5% of infants diagnosed with AKI received KRT.

APOL1 genotype-associated morphologic changes among patients with focal segmental glomerulosclerosis.

BACKGROUND: The G1 and G2 alleles of apolipoprotein L1 (APOL1) are common in the Black population and associated with increased risk of focal segmental glomerulosclerosis (FSGS). The molecular mechanisms linking APOL1 risk variants with FSGS are not clearly understood, and APOL1's natural absence in laboratory animals makes studying its pathobiology challenging. METHODS: In a cohort of 90 Black patients with either FSGS or minimal change disease (MCD) enrolled in the Nephrotic Syndrome Study Network (58% pediatric onset), we used kidney biopsy traits as an intermediate outcome to help illuminate tissue-based consequences of APOL1 risk variants and expression. We tested associations between APOL1 risk alleles or glomerular APOL1 mRNA expression and 83 light- or electron-microscopy traits measuring structural and cellular kidney changes. RESULTS: Under both recessive and dominant models in the FSGS patient subgroup (61%), APOL1 risk variants were significantly correlated (defined as FDR <0.1) with decreased global mesangial hypercellularity, decreased condensation of cytoskeleton, and increased tubular microcysts. No significant correlations were detected in MCD cohort. Independent of risk alleles, glomerular APOL1 expression in FSGS patients was not correlated with morphologic features. CONCLUSIONS: While APOL1-associated FSGS is associated with two risk alleles, both one and two risk alleles are associated with cellular/tissue changes in this study of FSGS patients. Our lack of discovery of a large group of tissue differences in FSGS and no significant difference in MCD may be due to the lack of power but also supports investigating whether machine learning methods may more sensitively detect APOL1-associated changes.

Trends and racial disparities for acute kidney injury in premature infants: the US national database.

BACKGROUND: To assess prevalence and outcomes of acute kidney injury (AKI) in very-low-birth-weight infants. METHODS: This cross-sectional study utilized the National Inpatient Sample (NIS) dataset for years 2000-2017. All premature infants with birth weight (BW) <1500g and/or gestational age (GA) ≤32 weeks were included. Analyses were conducted for overall population and two BW categories: <1000g and 1000-1499g. Adjusted odds ratios were calculated after controlling for confounding variables in logistic regression analysis. Cochrane-Armitage test was used to assess for statistically significant trends in AKI frequency over the years. RESULTS: In total, 1,311,681 hospitalized premature infants were included; 19,603 (1.5%) were diagnosed with AKI. The majority (74.3%) were BW <1000g and 63.9% ≤28 weeks gestation. Prevalence of AKI differed by ethnicity; White had significantly less AKI than Black (OR=0.79, p<0.001) and Hispanic (OR=0.83, p<0.001). AKI was significantly associated with higher mortality compared to controls (35.1 vs. 3.0%, p<0.001). AKI was associated with comorbidities such as necrotizing enterocolitis, patent ductus arteriosus, bronchopulmonary dysplasia, intraventricular hemorrhage, and septicemia. In a regression model, AKI was associated with higher mortality after controlling confounding factors (aOR=7.79, p<0.001). AKI was associated with significant increase in length of stay (p<0.001) and cost of hospitalization in survivors (p<0.001). There is a significant trend for increased AKI frequency over the years (Z score=4.33, p<0.001). CONCLUSION: AKI is associated with increased mortality and comorbidities in preterm infants, especially in infants with BW <1000g. Further studies are needed to understand precipitating factors and assess preventative measures for this serious complication.

Treatment Patterns Among Adults and Children With Membranous Nephropathy in the Cure Glomerulonephropathy Network (CureGN).

INTRODUCTION: The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Glomerulonephritis recommend that patients with membranous nephropathy (MN) at risk for progression receive immunosuppressive therapy (IST), usually after 6 months of observation. A cyclophosphamide (CYC) or calcineurin inhibitor (CNI)-based regimen is recommended as first-line IST. However, the extent to which KDIGO recommendations are adopted in practice remains largely unknown. METHODS: We evaluated prescribing practice among patients with primary MN (diagnosed 2010-2018) enrolled in the Cure Glomerulonephropathy Network (CureGN) cohort study. We also evaluated the availability of testing for phospholipase A2 receptor (PLA2R) in the contemporary era. RESULTS: Among 361 patients (324 adults and 37 children) with MN who were IST-naïve at biopsy and had at least 6 months of follow-up, 55% of adults and 58% of children initiated IST <6 months after biopsy. Of these, 1 in 5 had no indication for (i.e., urine protein-to-creatinine ratio [uPCR] <4 g/g) or an apparent contraindication to (i.e., an estimated glomerular filtration rate [eGFR] <30 ml/min per 1.73 m2) IST. As first-line IST, half of treated patients received either CYC (16% of adults; 0% of children) or a CNI (40% and 46%, respectively), whereas 1 in 5 received corticosteroid monotherapy (20% and 27%, respectively) and 1 in 6 rituximab (15% and 15%, respectively). More than 80% of surveyed centers had access to PLA2R testing. CONCLUSION: These findings suggest that providers are not aware of, or lack confidence in, current KDIGO guidelines for MN. Treatment patterns observed in this cohort might critically inform the drafting of planned updates to KDIGO guidelines.

Use of complement monoclonal antibody eculizumab in Shiga toxin producing Escherichia coli associated hemolytic uremic syndrome: A review of current evidence.

Complement activation plays an important role in the pathogenesis of atypical hemolytic uremic syndrome. Eculizumab is a monoclonal antibody that blocks complement activity and has been approved for use in the treatment of atypical hemolytic uremic syndrome (HUS). Less well appreciated is the role of complement in Shiga toxin-induced HUS (Shiga toxin producing Escherichia coli [STEC]-HUS). To a limited extent, eculizumab has been used off label in patients with severe STEC-HUS with neurological involvement. Through a systematic search of available databases, we identified 16 reports describing the use of eculizumab in STEC-HUS (eight case reports/series, seven retrospective studies, and one prospective cohort study). All studies described its use in severe STEC-HUS with neurological or multiorgan dysfunction; none were randomized or blinded. Four studies used the control groups. Although the overall quality of evidence is low, some published studies showed positive clinical improvement after treatment with eculizumab in severe STEC-HUS with progressive neurological involvement.

Kidney biopsy findings in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND: Renal damage is a progressive complication of sickle cell disease (SCD). Microalbuminuria is common in children with SCD, while a smaller number of children have more severe renal manifestations necessitating kidney biopsy. There is limited information on renal biopsy findings in children with SCD and subsequent management and outcome. METHODS: This is a multicenter retrospective analysis of renal biopsy findings and clinical outcomes in children and adolescents with SCD. We included children and adolescents (age ≤ 20 years) with SCD who had a kidney biopsy performed at a pediatric nephrology unit. The clinical indication for biopsy, biopsy findings, subsequent treatments, and outcomes were analyzed. RESULTS: Thirty-six SCD patients (ages 4-19 years) were identified from 14 centers with a median follow-up of 2.6 years (0.4-10.4 years). The indications for biopsy were proteinuria (92%) and elevated creatinine (30%). All biopsies had abnormal findings, including mesangial hypercellularity (75%), focal segmental glomerulosclerosis (30%), membranoproliferative glomerulonephritis (16%), and thrombotic microangiopathy (2%). There was increased use of hydroxyurea, angiotensin-converting-enzyme inhibitors, and angiotensin receptor blockers following renal biopsy. At last follow-up, 3 patients were deceased, 2 developed insulin-dependent diabetes mellitus, 6 initiated chronic hemodialysis, 1 received a bone marrow transplant, and 1 received a kidney transplant. CONCLUSIONS: Renal biopsies, while not commonly performed in children with SCD, were universally abnormal. Outcomes were poor in this cohort of patients despite a variety of post-biopsy interventions. Effective early intervention to prevent chronic kidney disease (CKD) is needed to reduce morbidity and mortality in children with SCD.

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study.

INTRODUCTION: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. METHODS: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. RESULTS: A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). CONCLUSION: This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.

Bortezomib in the treatment of antibody-mediated rejection in pediatric kidney transplant recipients: A multicenter Midwest Pediatric Nephrology Consortium study.

Antibody-mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody-mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven antibody-mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients. Thirty-three patients received bortezomib for antibody-mediated rejection at nine pediatric kidney transplant centers. Ninety percent of patients received intravenous immunoglobulin, 78% received plasmapheresis, and 78% received rituximab. After a median follow-up of 15 months, 65% of patients had a functioning graft. The estimated glomerular filtration rate improved or stabilized in 61% and 36% of patients at 3 and 12 months post-bortezomib, respectively. The estimated glomerular filtration rate at diagnosis significantly predicted estimated glomerular filtration rate at 12 months after adjusting for chronic histologic changes (P .001). Fifty-six percent of patients showed an at least 25% reduction in the mean fluorescence intensity of the immune-dominant donor-specific antibody, 1-3 months after the first dose of bortezomib. Non-life-threatening side effects were documented in 21 of 33 patients. Pediatric kidney transplant recipients tolerated bortezomib without life-threatening side effects. Bortezomib may stabilize estimated glomerular filtration rate for 3-6 months in pediatric kidney transplant recipients with antibody-mediated rejection.