Persistent Increase in Serum Ferritin Levels despite Converting to Permanent Vascular Access in Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study.

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (p = 0.035), being from a center that enrolled >10 cases (p = 0.049) and baseline serum ferritin level (p = 0.017). Increasing serum ferritin after conversion to PVA is concerning. This increase is not associated with serum hematocrit trends. Future studies should investigate the correlation of serum transferrin saturation and ferritin levels in pediatric HD patients.

Simultaneous kidney and pancreas transplantation in a patient with nail-patella syndrome and insulin-dependent diabetes.

BACKGROUND: Nail-patella syndrome (NPS) is a rare autosomal dominant disorder caused by a mutation in LIM-homeodomain transcription factor 1-beta (LMX1B) and characterized by nail dystrophy, skeletal changes, glaucoma, and kidney disease with up to 30% of patients progressing to kidney failure. Autoimmune diseases, including thyroid disease, have been reported previously in patients with NPS. CASE-DIAGNOSIS/TREATMENT: We report the case of a pediatric patient with NPS with kidney failure, hypothyroidism, and type 1 diabetes mellitus. The patient's pedigree and identification of a kidney specific mutation in LMX1B was a result of whole exome sequencing. Clinical data was obtained from retrospective chart review and included the 1-year post-transplant follow-up period. At 15 years of age, our patient received a simultaneous kidney-pancreas transplantation, from a 3 HLA antigen mismatched deceased donor. The donor was CMV + , EBV - and our patient was CMV - , EBV - at time of transplant. Our patient maintained normal kidney function and euglycemia without insulin therapy at 1 year post-transplant. CONCLUSIONS: The patient's hypothyroidism, diabetes mellitus, and kidney failure may all be related to LMX1B mutation. Further study is needed to clarify the genetic link between these processes. Simultaneous kidney-pancreas transplantation can be used to successfully treat diabetes mellitus and kidney failure in a pediatric patient.

Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis.

The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic profile-based clustering identified three patient subgroups with shared molecular signatures across independent, North American, European, and African cohorts. One subgroup had significantly greater disease progression (Hazard Ratio 5.2) which persisted after adjusting for diagnosis and clinical measures (Hazard Ratio 3.8). Inclusion in this subgroup was retained even when clustering was limited to those with less than 25% interstitial fibrosis. The molecular profile of this subgroup was largely consistent with tumor necrosis factor (TNF) pathway activation. Two TNF pathway urine markers were identified, tissue inhibitor of metalloproteinases-1 (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1), that could be used to predict an individual's TNF pathway activation score. Kidney organoids and single-nucleus RNA-sequencing of participant kidney biopsies, validated TNF-dependent increases in pathway activation score, transcript and protein levels of TIMP-1 and MCP-1, in resident kidney cells. Thus, molecular profiling identified a subgroup of patients with either MCD or FSGS who shared kidney TNF pathway activation and poor outcomes. A clinical trial testing targeted therapies in patients selected using urinary markers of TNF pathway activation is ongoing.

Focal segmental glomerulosclerosis and proteinuria associated with Myo1E mutations: novel variants and histological phenotype analysis.

BACKGROUND: Pathogenic mutations in the non-muscle single-headed myosin, myosin 1E (Myo1e), are a rare cause of pediatric focal segmental glomerulosclerosis (FSGS). These mutations are biallelic, to date only reported as homozygous variants in consanguineous families. Myo1e regulates the actin cytoskeleton dynamics and cell adhesion, which are especially important for podocyte functions. METHODS: DNA and RNA sequencing were used to identify novel MYO1E variants associated with FSGS. We studied the effects of these variants on the localization of Myo1e in kidney sections. We then analyzed the clinical and histological observations of all known pathogenic MYO1E variants. RESULTS: We identified a patient compound heterozygote for two novel variants in MYO1E and a patient homozygous for a deletion of exon 19. Computer modeling predicted these variants to be disruptive. In both patients, Myo1e was mislocalized. As a rule, pathogenic MYO1E variants map to the Myo1e motor and neck domain and are most often associated with steroid-resistant nephrotic syndrome in children 1-11 years of age, leading to kidney failure in 4-10 years in a subset of patients. The ultrastructural features are the podocyte damage and striking diffuse and global Alport-like glomerular basement membrane (GBM) abnormalities. CONCLUSIONS: We hypothesize that MYO1E mutations lead to disruption of the function of podocyte contractile actin cables resulting in abnormalities of the podocytes and the GBM and dysfunction of the glomerular filtration barrier. The characteristic clinicopathological data can help to tentatively differentiate this condition from other genetic podocytopathies and Alport syndrome until genetic testing is done. A higher resolution version of the Graphical abstract is available as Supplementary information.

Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic mice.

Calcium-calmodulin-dependent protein kinase II (CaMKII) is upregulated in diabetes mellitus (DM), leading to the overproduction of collagen in the myocardium. We hypothesized that CaMKII plays a role in the development of diabetic nephropathy (DN). Streptozotocin (STZ) injection into FVB wild-type mice led to mild mesangial matrix expansion, reproducing an essential feature of early human DN. Mesangial matrix measurements were performed on trichrome-stained paraffin sections using a trainable segmentation method based on WEKA (Waikato Environment for Knowledge Analysis) Image J-Fiji plugin (TWS plugin), and the electron micrographs of the whole glomeruli stitched from individual 4800x partial glomerular images. Both methods demonstrated that the statistically significant mesangial matrix expansion seen in the diabetic mice was prevented by chronic pretreatment with KN-93, a small molecule CaMKII inhibitor. This study indicates a role for CaMKII in the development of mesangial alterations in diabetes and suggests a possible new therapeutic target.

Determinants of medication adherence in childhood nephrotic syndrome and associations of adherence with clinical outcomes.

BACKGROUND: Pediatric patients with nephrotic syndrome take medications long-term with significant toxicity and complex regimens, yet data on medication adherence are limited. METHODS: In a multicenter observational study of patients with nephrotic syndrome, NEPTUNE (NCT01209000), we surveyed caregivers of patients <19 years old and adolescent patients on medication adherence during longitudinal follow-up beginning in June 2015. Data extraction was in October 2020. We described the proportion of nonadherent patients at first survey. Participant social and economic factors, condition-related factors, therapy-related factors, and patient-related factors were examined for relationships with nonadherence by generalized linear mixed models using the longitudinal data. In exploratory fashion, we assessed the relationship between adherence and subsequent steroid response classification by binary logistic regression and adherence with healthcare utilization by Poisson regression. RESULTS: A total of 225 participants completed a median of 3 surveys during follow-up (IQR, 2-5), with a total of 743 surveys. Overall, 80 (36%) reported nonadherence with medications. In adjusted analysis, older age (per 1 year; OR 1.08; 95% CI, 1.03 1.12), lower maternal educational level (≥ high school vs. < high school; OR 0.47; 95% CI 0.25 to 0.89), and increased parent and self-identification of medications barriers (per 1 point; OR 1.57; 95% CI, 1.15-2.15) were significantly associated with nonadherence. No relationship between nonadherence and subsequent frequency of healthcare utilization was observed. A trend toward increased subsequent steroid resistance classification was seen with nonadherence, though not statistically significant. CONCLUSIONS: Medication nonadherence is common in pediatric nephrotic syndrome. Investigations into the use of surveys in the clinic setting to identify at-risk patients and ways to support families over time are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

Conversion to permanent vascular access is associated with improved markers of hemodialysis efficacy in children: Pediatric nephrology research consortium study.

BACKGROUND AND OBJECTIVES: Arteriovenous fistulae (AVF) and grafts (AVG) are preferred permanent vascular access (PVA) for chronic hemodialysis (HD) patients. Our objective was to examine the change in markers of HD efficacy after successful establishment of a PVA among children who started HD with a tunneled cuffed catheter (TCC). MATERIALS AND METHODS: Retrospective chart reviews were completed on patients from 20 pediatric dialysis centers. All patients used TCC prior to AVF/AVG, and each patient acted as his/her own control. Data on markers of HD efficacy (single-pool Kt/V, urea reduction ratio (URR), serum albumin and hematocrit (Hct)) were collected at the creation of AVF/AVG and for 2 years thereafter. Statistical methods included hypothesis testing and statistical modeling after adjusting for relevant demographic variables. RESULTS: First PVA was created in 98 individual children: 87 (89%) were AVF and 11 (11%) were AVG. The mean TCC vintage prior to AVF/AVG was 10.4 ± 17.3 months. At 1-year follow-up, Kt/V improved by 0.15 ± 0.06 (p = 0.02) and URR improved by 4.54 ± 1.17% (p < 0.0001). Furthermore, PVA was associated with improved serum albumin by 0.31 ± 0.07 g/dL (p < 0.0001) and Hct by 2.80 ± 0.65% (p < 0.0001) at 1 year. These HD efficacy markers remained statistically significant at 2nd-year follow-up. These observations were further supported by the adjusted models. Conversion to AVF was associated with statistically significant improvement in all four markers of HD efficacy at 1-year follow-up. This trend was not demonstrated for subjects who were converted to AVG. CONCLUSION: Switching to PVA was associated with improved markers of HD efficacy, single-pool Kt/V, URR, serum albumin, and Hct. This improvement was mostly demonstrated at 1 year and maintained for the 2nd year. The potential differential impact of the type of PVA on the trajectory of markers of HD efficacy should be further investigated.

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.

The longitudinal relationship between patient-reported outcomes and clinical characteristics among patients with focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network.

BACKGROUND: Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS). METHODS: FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied. RESULTS: There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (-7.6 points, P = 0.02) and mobility (-4.2, P = 0.02), the number of reported symptoms was associated with worse depression (-2.7 per symptom, P = 0.009) and anxiety (-2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (-2.8 per visit, P < 0.001) and fatigue (-2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P = 0.03). CONCLUSIONS: PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes.

Urinary Epidermal Growth Factor as a Marker of Disease Progression in Children With Nephrotic Syndrome.

INTRODUCTION: Childhood-onset nephrotic syndrome has a variable clinical course. Improved predictive markers of long-term outcomes in children with nephrotic syndrome are needed. This study tests the association between baseline urinary epidermal growth factor (uEGF) excretion and longitudinal kidney function in children with nephrotic syndrome. METHODS: The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. uEGF was measured at baseline for all participants and normalized by the urine creatinine (Cr) concentration. Renal epidermal growth factor (EGF) mRNA was measured in the tubular compartment microdissected from kidney biopsy cores from a subset of patients. Linear mixed models were used to test if baseline uEGF/Cr and EGF mRNA expression were associated with change in estimated glomerular filtration rate (eGFR) over time. RESULTS: Higher uEGF/Cr at baseline was associated with slower eGFR decline during follow-up (median follow-up = 30 months). Halving of uEGF/Cr was associated with a decrease in eGFR slope of 2.0 ml/min per 1.73 m2 per year (P < 0.001) adjusted for age, race, diagnosis, baseline eGFR and proteinuria, and APOL1 genotype. In the biopsied subgroup, uEGF/Cr was correlated with EGF mRNA expression (r = 0.74; P < 0.001), but uEGF/Cr was retained over mRNA expression as the stronger predictor of eGFR slope after multivariable adjustment (decrease in eGFR slope of 1.7 ml/min per 1.73 m2 per year per log2 decrease in uEGF/Cr; P < 0.001). CONCLUSION: uEGF/Cr may be a useful noninvasive biomarker that can assist in predicting the long-term course of kidney function in children with incident nephrotic syndrome.

Predictors of time to first cannulation for arteriovenous fistula in pediatric hemodialysis patients: Midwest Pediatric Nephrology Consortium study.

BACKGROUND: Permanent vascular access (PVA) is preferred for long-term hemodialysis. Arteriovenous fistulae (AVF) have the best patency and the lowest complication rates compared to arteriovenous grafts (AVG) and tunneled cuffed catheters (TCC). However, AVF need time to mature. This study aimed to investigate predictors of time to first cannulation for AVF in pediatric hemodialysis patients. METHODS: Data on first AVF and AVG of patients at 20 pediatric dialysis centers were collected retrospectively, including demographics, clinical information, dialysis markers, and surgical data. Statistical modeling was used to investigate predictors of outcome. RESULTS: First PVA was created in 117 children: 103 (88%) AVF and 14 (12%) AVG. Mean age at AVF creation was 15.0 ± 3.3 years. AVF successfully matured in 89 children (86.4%), and mean time to first cannulation was 3.6 ± 2.5 months. In a multivariable regression model, study center, age, duration of non-permanent vascular access (NPVA), and Kt/V at AVF creation predicted time to first cannulation, with study center as the strongest predictor (p < 0.01). Time to first cannulation decreased with increasing age (p = 0.03) and with increasing Kt/V (p = 0.01), and increased with duration of NPVA (p = 0.03). Secondary failure occurred in 10 AVF (11.8%). Time to first cannulation did not predict secondary failure (p = 0.29), but longer time to first cannulation tended towards longer secondary patency (p = 0.06). CONCLUSIONS: Study center is the strongest predictor of time to first cannulation for AVF and deserves further investigation. Time to first cannulation is significantly shorter in older children, with more efficient dialysis treatments, and increases with longer NPVA duration.

Text Messaging for Disease Monitoring in Childhood Nephrotic Syndrome.

INTRODUCTION: There is limited information on effective disease monitoring for prompt interventions in childhood nephrotic syndrome. We examined the feasibility and effectiveness of a novel text messaging system (SMS) for disease monitoring in a multicenter, prospective study. METHODS: A total of 127 patients <19 years with incident nephrotic syndrome were enrolled in the ongoing Nephrotic Syndrome Study Network between June 2015 and March 2018. Text messages soliciting home urine protein results, symptoms, and medication adherence were sent to a designated caregiver (n = 116) or adolescent patient (n = 3). Participants responded by texting. Feasibility of SMS was assessed by SMS adoption, retention, and engagement, and concordance between participant-reported results and laboratory/clinician assessments. The number of disease relapses and time-to-remission data captured by SMS were compared with data collected by conventional visits. RESULTS: A total of 119 of 127 (94%) patients agreed to SMS monitoring. Retention rate was 94%, with a median follow-up of 360 days (interquartile range [IQR] 353-362). Overall engagement was high, with a median response rate of 87% (IQR, 68-97). Concordance between SMS-captured home urine protein results and edema status with same-day in-person study visit was excellent (kappa values 0.88 and 0.92, respectively). SMS detected a total of 108 relapse events compared with 41 events captured by scheduled visits. Median time to remission after enrollment was 22 days as captured by SMS versus 50 days as captured by scheduled visits. CONCLUSION: SMS was well accepted by caregivers and adolescent patients and reliably captured nephrotic syndrome disease activity between clinic visits. Additional studies are needed to explore the impact of SMS on disease outcomes.

Does MEST-C score predict outcomes in pediatric Henoch-Schönlein purpura nephritis?

BACKGROUND: Children with Henoch-Schönlein purpura nephritis (HSPN) have an increased risk of chronic kidney disease (CKD). Renal biopsy diagnostic of HSPN is graded using the International Study of Kidney Disease in Children criteria, which do not predict outcomes. The 2016 Oxford Classification's MEST-C scoring system predicts outcomes in adults with histologically identical IgA nephropathy, but evidence of its utility in pediatric HSPN is lacking. Our hypothesis was that MEST-C scores predict outcomes in children with HSPN. METHODS: A retrospective cohort analysis of data from 32 children with HSPN who underwent renal biopsy was performed. We used logistic regression and receiver operator characteristic curves to analyze the ability of MEST-C to predict the composite outcome of hypertension (blood pressure ≥ 95% for age/sex/height), CKD (estimated glomerular filtration rate < 90 mL/min/1.73 m2), or proteinuria (urine protein-to-creatinine ratio > 0.2 mg/mg). RESULTS: The median age at diagnosis was 7.9 years (IQR 5.8, 11.7); 56% were male, 19% were Hispanic, and 9% were Black. After a median follow-up of 2.7 years, 38% of patients (n = 12) reached the outcome. S1 score was significantly associated with the outcome (OR 7.9, 95% CI 1.5-42.6). S1 accurately predicted the outcome (area under the curve 0.72, 95% CI 0.55-0.88) with 58.3% sensitivity and 85.0% specificity, indicating a positive predictive value of 70.0% and a negative predictive value of 77.3%. CONCLUSIONS: S1 accurately predicted our composite outcome of hypertension, CKD, and proteinuria in a diverse cohort of U.S. children with HSPN. Further investigation is warranted to validate these findings.

Correction to: Predictors of patency for arteriovenous fistulae and grafts in pediatric hemodialysis patients.

The original version of this article unfortunately contained a mistake. The name of Vimal Chadha was presented incorrectly. The corrected author list is given above.

Predictors of patency for arteriovenous fistulae and grafts in pediatric hemodialysis patients.

BACKGROUND: Hemodialysis (HD) guidelines recommend permanent vascular access (PVA) in children unlikely to receive kidney transplant within 1 year of starting HD. We aimed to determine predictors of primary and secondary patency of PVA in pediatric HD patients. METHODS: Retrospective chart reviews were performed for first PVAs in 20 participating centers. Variables collected included patient demographics, complications, interventions, and final outcome. RESULTS: There were 103 arterio-venous fistulae (AVF) and 14 AV grafts (AVG). AVF demonstrated superior primary (p = 0.0391) and secondary patency (p = 0.0227) compared to AVG. Primary failure occurred in 16 PVA (13.6%) and secondary failure in 14 PVA (12.2%). AVF were more likely to have primary failure (odds ratio (OR) = 2.10) and AVG had more secondary failure (OR = 3.33). No demographic, clinical, or laboratory variable predicted primary failure of PVA. Anatomical location of PVA was predictive of secondary failure, with radial having the lowest risk compared to brachial (OR = 12.425) or femoral PVA (OR = 118.618). Intervention-free survival was predictive of secondary patency for all PVA (p = 0.0252) and directly correlated with overall survival of AVF (p = 0.0197) but not AVG. Study center demonstrated statistically significant effect only on intervention-free AVF survival (p = 0.0082), but not number of complications or interventions, or outcomes. CONCLUSIONS: In this multi-center pediatric HD cohort, AVF demonstrated primary and secondary patency advantages over AVG. Radial PVA was least likely to develop secondary failure. Intervention-free survival was the only predictor of secondary patency for AVF and directly correlated with overall access survival. The study center effect on intervention-free survival of AVF deserves further investigation.

Genetic Testing for Steroid-Resistant-Nephrotic Syndrome in an Outbred Population.

Background: Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children and young adults. Despite advances in genomic science that have led to the discovery of >50 monogenic causes of SRNS, there are no clear guidelines for genetic testing in clinical practice. Methods: Using high throughput sequencing, we evaluated 492 individuals from 181 families for mutations in 40 known SRNS genes. Causative mutations were defined as missense, truncating, and obligatory splice site variants with a minor allele frequency <1% in controls. Non-synonymous variants were considered pathogenic if determined to be deleterious by at least two in silico models. We further evaluated for differences in age at disease onset, family history of SRNS or chronic kidney disease, race, sex, renal biopsy findings, and extra-renal manifestations in subgroups with and without disease causing variants. Results: We identified causative variants in 40 of 181 families (22.1%) with SRNS. Variants in INF2, COL4A3, and WT1 were the most common, accounting for over half of all causative variants. Causative variants were identified in 34 of 86 families (39.5%) with familial disease and 6 of 95 individuals (6.3%) with sporadic disease (χ2 p < 0.00001). Family history was the only significant clinical predictor of genetic SRNS. Conclusion: We identified causative mutations in almost 40% of all families with hereditary SRNS and 6% of individuals with sporadic disease, making family history the single most important clinical predictors of monogenic SRNS. We recommend genetic testing in all patients with SRNS and a positive family history, but only selective testing in those with sporadic disease.

Severe intellectual disability is not a contraindication to kidney transplantation in children.

Renal transplantation in children with ID is controversial. Acceptability of these children as candidates varies between programs. Limited outcome data in pediatric renal TXP recipients with cognitive impairment diminish their access to TXP. A retrospective chart review was performed of all children who underwent renal transplantation between January 1, 2002 and June 30, 2012 (N=72). Patients were divided into two groups, those with ID prior to transplantation (n=10) and those without (non-ID; n=62). Graft survival and BPAR episodes were compared between the two groups using Kaplan-Meier estimates. Graft survival rates at 3 years post-TXP were 100% in the ID group and 80% in the non-ID group (P=.13). Rates of BPAR at 3 years post-TXP were 10% in the ID group and 27% in the non-ID group (P=.29). Graft survival and acute rejection-free survival rates are similar between children with ID and those without. Based on midterm outcomes, there is no apparent contraindication to renal transplantation in pediatric patients with ID. Children with ID should be considered as TXP candidates provided that they have an adequate social support network.

Dysregulation of WTI (-KTS) is Associated with the Kidney-Specific Effects of the LMX1B R246Q Mutation.

Mutations in the LIM homeobox transcription factor 1-beta (LMX1B) are a cause of nail patellar syndrome, a condition characterized by skeletal changes, glaucoma and focal segmental glomerulosclerosis. Recently, a missense mutation (R246Q) in LMX1B was reported as a cause of glomerular pathologies without extra-renal manifestations, otherwise known as nail patella-like renal disease (NPLRD). We have identified two additional NPLRD families with the R246Q mutation, though the mechanisms by which LMX1BR246Q causes a renal-specific phenotype is unknown. In this study, using human podocyte cell lines overexpressing either myc-LMX1BWT or myc-LMX1BR246Q, we observed dominant negative and haploinsufficiency effects of the mutation on the expression of podocyte genes such as NPHS1, GLEPP1, and WT1. Specifically, we observed a novel LMX1BR246Q-mediated downregulation of WT1(-KTS) isoforms in podocytes. In conclusion, we have shown that the renal-specific phenotype associated with the LMX1BR246Q mutation may be due to a dominant negative effect on WT1(-KTS) isoforms that may cause a disruption of the WT1 (-KTS):(+KTS) isoform ratio and a decrease in the expression of podocyte genes. Full delineation of the LMX1B gene regulon is needed to define its role in maintenance of glomerular filtration barrier integrity.

Renal Abscess Due to Community-acquired Extended-spectrum ß-Lactamase-producing Escherichia coli in a 15-Year-old Girl.

Infections caused by community-acquired (CA) extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae are an increasing public health concern. We report a 15-year-old girl with a history of recurrent urinary tract infections who developed a right renal abscess. Percutaneous abscess drainage and subsequent microbiological culture revealed CA-ESBL Escherichia coli. To our knowledge, this is the first reported pediatric case of CA-ESBL E coli renal abscess complicating urinary tract infection. Establishing a definitive diagnosis of ESBL E coli renal abscess may necessitate obtaining a microbiological culture via surgical specimen, especially in children with apparent risk factors for the selection of ESBL-producing organisms.