Carter CE, Kula AJ, Bauer A
… +9 more, Weidemann DK, Soranno DE, Carlson J, Hains DS, George RP, Gattineni J, Atkinson MA, Drake KA, American Society for Pediatric Nephrology
BACKGROUND: Renal tubular disease causes loss of electrolytes and other molecules. One of these electrolytes is inorganic sulfate, which is reabsorbed by dedicated transporters, including NaS1, encoded by the SLC13A1 gen...BACKGROUND: Renal tubular disease causes loss of electrolytes and other molecules. One of these electrolytes is inorganic sulfate, which is reabsorbed by dedicated transporters, including NaS1, encoded by the SLC13A1 gene. Still, inorganic sulfate is rarely measured in clinical practice, although it is essential for the development and functioning of several organ systems. The importance of adequate sulfate stores is emphasized by genetic disorders impairing sulfate metabolism in the brain, bone, and the endocrine system, causing severe neurodevelopmental disorders, skeletal dysplasia, and hormonal imbalance. Low availability due to renal loss of inorganic sulfate has also been linked to these disorders. We aimed to assess the prevalence of renal inorganic sulfate wasting in renal tubular diseases in a small cohort as an exploratory study. METHODS: Inorganic sulfate was measured in serum and urine of patients with proximal renal tubular disorders using remnant material obtained during routine check-ups. Fractional excretion of inorganic sulfate was calculated alongside plasma inorganic sulfate concentrations and cystatin C-based eGFR. RESULTS: Fourteen patients were included, in whom 1 to 4 paired measurements of urine and plasma inorganic sulfate were available. Five patients had decreased plasma sulfate on at least one occasion; 13 patients had increased fractional excretion in at least one measurement. In patients with cystinosis, during cysteamine treatment plasma inorganic sulfate levels were often normal despite increased fractional excretion. CONCLUSIONS: Increased inorganic sulfate loss is prevalent in children with proximal tubular defects and sulfate stores can be repleted by oral drugs like cysteamine.
BACKGROUND: We evaluated the prevalence and phenotype of hypertension in untreated children with autosomal dominant polycystic kidney disease (ADPKD) and examined associations with blood pressure (BP), cyst burden, and l...BACKGROUND: We evaluated the prevalence and phenotype of hypertension in untreated children with autosomal dominant polycystic kidney disease (ADPKD) and examined associations with blood pressure (BP), cyst burden, and left ventricular (LV) structure and function. METHODS: Single-centre, cross-sectional study included children and young people (< 18 years) with ADPKD. Data regarding demographics, office BP, 24-h ambulatory BP monitoring if > 5-years, biochemistry and echocardiography were collated. Cyst burden was assessed by kidney ultrasound and classified as 'low burden' or 'high burden'. Participants with hypertension (BP ≥ 95th percentile) or 'high-normal' BP (BP ≥ 90th and < 95th percentile) were grouped as 'High BP' (BP ≥ 90th percentile), and the remaining as normotensive (BP < 90th percentile). RESULTS: Amongst 116 children (mean age 9.99 ± 5.2 years; 57.8% female), hypertension prevalence was 12% (n = 14), 8 with masked hypertension. Those with High BP (26% (n = 30)) had a higher cyst burden (56% vs. 34%, P = 0.036), LV hypertrophy (LVH) (16.6% vs. 4.6%, P = 0.034) and relative LV wall thickness (0.34 ± 0.08 vs. 0.29 ± 0.05, P < 0.001) but similar indexed LV mass (LVMI) and LV function when compared with normotensives. In multivariable analysis, cyst burden independently predicted LVMI (standardised β = 0.23, P = 0.02), whereas systolic BP did not (standardised β = 0.19, P = 0.14). CONCLUSIONS: Hypertension affected 12% of untreated children with ADPKD and preserved kidney function. High BP was associated with increased prevalence of LVH and relative wall thickness when compared to those who were normotensive. Cyst burden correlated with adverse cardiac remodelling, suggesting a BP-independent mechanism.
Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury, most commonly acute kidney injury (AKI). It may occur as a primary complement‑mediated disorder...Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury, most commonly acute kidney injury (AKI). It may occur as a primary complement‑mediated disorder or secondary to other diseases. Germline mutations in GATA1 cause X‑linked thrombocytopenia with or without dyserythropoietic anemia. We report an 8‑year‑old boy with long‑standing steroid‑dependent cytopenias and congenital anomalies who presented with severe infection, hemolysis, thrombocytopenia, and AKI requiring hemodialysis. Although the presentation fulfilled criteria for suspected TMA, ADAMTS13 activity, complement factor H levels, and anti-factor H antibodies were normal, excluding primary TMA. Whole‑exome sequencing identified a hemizygous pathogenic GATA1 variant (c.646C>T; p.Arg216Trp), establishing GATA1‑related dyserythropoietic anemia with thrombocytopenia. Renal function fully recovered following supportive therapy, immunomodulation, and dialysis discontinuation. This case underscores the importance of considering secondary TMA‑like syndromes in inherited marrow disorders and highlights the diagnostic value of genomic testing in atypical TMA presentations.
BACKGROUND: Neonates with congenital kidney failure or acute kidney injury often require continuous kidney replacement therapy (CKRT). Historically, venous access for CKRT in this population has relied on non-approved ad...BACKGROUND: Neonates with congenital kidney failure or acute kidney injury often require continuous kidney replacement therapy (CKRT). Historically, venous access for CKRT in this population has relied on non-approved adult catheters, commonly via the internal jugular (IJ) vein. Limited international reports describe using the umbilical vein for CKRT, but this practice is not widespread in the USA. The Nuwellis® dual lumen extended length catheter (dELC), originally created for adult ultrafiltration, may support alternative access for neonatal CKRT. METHODS: This case series describes the clinical course of four neonates requiring CKRT using a 6 French Nuwellis® dELC placed in the umbilical vein at University of Iowa Stead Family Children's Hospital and Children's of Alabama. Patient demographics, CKRT prescriptions, access characteristics, and complications were reviewed. RESULTS: All four neonates underwent successful umbilical vein placement of the 6 Fr dELC. Weight at initiation ranged from 2.23 to 4.1 kg, with blood flow rates 20-40 mL/min. Epoprostenol anticoagulation was used in three patients. Half of the cohort later transitioned to a tunneled catheter, and one transitioned to an IJ catheter following fluid removal. One catheter developed hub cracks likely related to lumen caps, and one patient experienced flow limitations attributed to positioning rather than catheter function. Two patients had no catheter-related complications. CONCLUSIONS: Umbilical venous access using the 6Fr dELC may represent a viable alternative for neonatal CKRT. Coil reinforcement within the catheter may support patency and better functionality. Additional studies are needed to assess safety and broader applicability.
BACKGROUND: Renal imaging suggests that congenital anomalies of the kidney and urinary tract (CAKUT) affect one in 200 of the population, and 20% have a monogenic cause. This study determined the population frequency of...BACKGROUND: Renal imaging suggests that congenital anomalies of the kidney and urinary tract (CAKUT) affect one in 200 of the population, and 20% have a monogenic cause. This study determined the population frequency of predicted pathogenic variants in six commonly affected CAKUT genes. METHODS: HNF1B, SALL1, EYA1, PBX1, GATA3, and PAX2 variants were downloaded from gnomAD v.2.1.1 (n = 141,456) and the population frequency of predicted disease-causing variants calculated from the sum of structural, null, and predicted pathogenic missense changes in the overall cohort or from variants shared with ClinVar, HGMD, or LOVD. Population frequencies were also determined in constituent ancestries and, using our method and ClinVar assessments, in a replication cohort (gnomAD v.4.1, n = 807,162). RESULTS: The population frequency of disease-causing variants in these six genes in CAKUT lies between one in 249 (our strategy) and one in 1263 (ClinVar assessments) in the gnomAD v.2.1.1 database. More than half these variants were missense changes. Predicted pathogenic variants were commonest in African-Americans (one in 149) and least common in Ashkenazim (one in 864). The population frequency estimated from gnomAD v.4.1 lies between one in 372 (our strategy) and one in 1,762 (with ClinVar). CONCLUSIONS: These calculations suggest that monogenic causes of CAKUT due to variants in these six genes are likely more common than the previously calculated one in 1,000. The ClinVar results are underestimates since assessments were not available for structural, copy number and many missense changes. However, some disease-causing variants identified here will not result in clinical disease because of incomplete penetrance and variable expressivity.
BACKGROUND: Many individuals with sickle cell disease (SCD) survive into adulthood, posing a challenge in managing and preventing damage to vital organs such as the heart and kidneys. Studies on hypertension in this popu...BACKGROUND: Many individuals with sickle cell disease (SCD) survive into adulthood, posing a challenge in managing and preventing damage to vital organs such as the heart and kidneys. Studies on hypertension in this population have shown conflicting results, and limited studies on polysomnography highlight a gap in research. This study aims to investigate the prevalence of ambulatory blood pressure abnormalities, obstructive sleep apnea (OSA), and end-organ damage in these children and examine the relationship between these factors. METHODS: Fifty-nine children aged 5-18 years with SCD (homozygous and compound heterozygous) were evaluated through history, laboratory tests, ambulatory blood pressure monitoring (ABPM), and polysomnography; estimated glomerular filtration rate (eGFR) by creatinine and cystatin C, echocardiography including left ventricular mass index (LVMI), carotid intimal medial thickness (CIMT), and flow-mediated dilation (FMD) were also assessed. RESULTS: Ambulatory hypertension, masked hypertension, and non-dipping pattern were observed in 13.6%, 11.9%, and 66.1% of participants, respectively. End-organ damage was noted in 71% and was associated with higher frequency of vaso-occlusive crisis (p = 0.003). OSA was identified in 66.1% of participants, and they had lower hemoglobin (p = 0.004). Higher CIMT and LVMI Z-scores were observed in children with OSA (p = 0.004 and p = 0.016, respectively). A negative correlation was observed between FMD and apnea-hypopnea index (AHI) (p = 0.009). Proteinuria was reported in 32.2% and AHI correlated significantly with urine protein-creatinine ratio (r = 0.3; p = 0.02). Although eGFR by both methods showed poor correlation, agreement improved at lower eGFR. CONCLUSIONS: Children with SCD show a high prevalence of ABPM abnormalities, OSA, and early vascular dysfunction.
BACKGROUND: Childhood idiopathic nephrotic syndrome (INS) responds to corticosteroids (CS), but tends to relapse, often requiring steroid sparing agents (SSA). Long standing treatment free remission (LTFR) evolves in mos...BACKGROUND: Childhood idiopathic nephrotic syndrome (INS) responds to corticosteroids (CS), but tends to relapse, often requiring steroid sparing agents (SSA). Long standing treatment free remission (LTFR) evolves in most cases, but whether this is related to puberty or disease length is unknown. METHODS: We retrospectively analyzed the computerized database of Israel's largest health maintenance organization. Children with a new INS diagnosis between 2000-2010 were divided into 2 groups according to INS presentation age. Disease length was determined based on CS or SSA use. Children with disease shorter than 1 year or those not reaching LTFR, defined as more than 3 years from last purchase, were excluded. RESULTS: Out of 1,669,977 eligible children, 608 were diagnosed with INS, 524 relapsed, 174 were excluded, leaving 350 for analysis: 272 (77.7%) and 78 (22.2%) presented between 2-6.9 and 7-9.9 years, respectively. There was no difference in the need for SSA, time to SSA initiation and drug purchase count between the groups. After 15.5 ± 5.1 years of follow up, time until LTFR was longer in the older group (5.4 ± 4 vs. 7.1 ± 5.1 years, p = 0.002), without correlation between INS onset age and disease length. Many patients, especially in the older group, still relapsed beyond Tanner stage 3's 97th percentile age (age 14 years) (14.7% vs. 51.3%, p < 0.001), irrelevant of sex. CONCLUSIONS: In this population-based study LTFR occurred in many cases well beyond puberty, in both groups, favoring the role for disease length on LTFR, probably due to maturational immune system changes.
BACKGROUND: Adverse social determinants are known contributors to poorer long-term allograft outcomes. Yet optimal measures of social determinants are lacking. We sought to evaluate the association between socioeconomic...BACKGROUND: Adverse social determinants are known contributors to poorer long-term allograft outcomes. Yet optimal measures of social determinants are lacking. We sought to evaluate the association between socioeconomic status (SES) and graft loss in children using several different metrics of social determinants of health (SDOH). METHODS: Our study included 137 pediatric kidney transplant recipients (< 18 years at kidney failure onset) transplanted between 2010 and 2020. The association between SES measures (individual- and area-level) and graft survival was examined using Cox regression models. Measures were dichotomized: HOUSES Index [low SES(Q1) vs. high (Q2-Q4)], Area Deprivation Index (ADI) [high deprivation (76-100 percentile) vs. low (1-75 percentile)], and Childhood Opportunity Index (COI) [low opportunity (1s-25 percentile) vs. high (26-100)]. All models were adjusted for transplant age, sex, donor type, pretransplant dialysis, insurance, kidney failure cause, and body mass index z-score. RESULTS: After adjusting for covariates, we observed a significantly increased risk of graft loss in HOUSES Q1 vs. Q2-4 recipients (adjusted hazard ratio [aHR]: 3.25; 95% CI: 1.38, 7.64; p = 0.007) and nationally standardized low-opportunity COI vs. high-opportunity COI recipients (aHR: 5.01; 95% CI: 2.01, 12.5; p = 0.001). In contrast, we observed no significant association between ADI and graft loss. CONCLUSIONS: Using the HOUSES Index and COI, we identified a 3-fold to fivefold higher risk of pediatric graft loss among recipients with lower SDOH. These tools provide robust non-biological predictors for transplant outcomes; however, larger studies are required to compare their relative impact.
Abukasm K, Widger K, Rapoport A
… +13 more, Chanchlani R, Dionne JM, Samuel S, Hamiwka L, Davison SN, Lai V, Carter SA, Bei KF, Loverock K, Oketola B, Dufault B, Matsuda-Abedini M, Dart AB
BACKGROUND: Life participation is a priority outcome for children and families living with chronic kidney disease (CKD). This study aimed to assess the construct validity of the PRO-Kid-LP, a novel three-item tool measur...BACKGROUND: Life participation is a priority outcome for children and families living with chronic kidney disease (CKD). This study aimed to assess the construct validity of the PRO-Kid-LP, a novel three-item tool measuring CKD's impact on children's life participation. METHODS: Participants were children aged 8-18 years from Canada, with stages 3-5 CKD, who were part of the PRO-Kid validation cohort. Using 5-point adjectival scales, the PRO-Kid-LP tool measures CKD's impact on three domains over 1 week: (1) school participation, (2) meaningful time with family and friends, (3) participation in hobbies/recreational activities. Higher scores reflected more impact of CKD on life participation. The PedsQL™ and PRO-Kid symptom assessment tool were also completed. Construct validity was evaluated with Spearman correlations and internal consistency, with Cronbach's alpha (C). RESULTS: Ninety-seven children were included, with a mean age of 14.4 years (IQR 11, 16.6), and 62.9% (61/97) were male. Impact on life participation increased by CKD stage (p = 0.003). There was an inverse relationship between PRO-Kid-LP and PedsQL™ scores (r = - 0.65, p < 0.001), and a positive relationship between PRO-Kid-LP scores and CKD symptoms (PRO-Kid frequency [r = 0.51, p < 0.001] and impact [r = 0.49, p < 0.001] scores). PRO-Kid-LP scores were associated with the PRO-Kid "Feeling left out" item (p < 0.001). Internal consistency was high (C = 0.81), which supports reliability. CONCLUSIONS: This study supports the validity of the PRO-Kid-LP to quantify the impact of CKD on life participation in children with stages 3-5 CKD. The tool shows internal consistency, a positive correlation with symptom burden, and a negative correlation with quality of life.
Phillips M, Kallash M, Tang C
… +10 more, Rust S, Jubert-Bacon K, Wenderfer S, Mohan S, Blatt N, Batisky D, Quiroga A, Vasylyeva TL, DeJesus N, Lane JC
BACKGROUND: There are few prospective studies of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) for pediatric lupus nephritis (pLN) and none evaluating rituximab (RTX). METHODS: The Prospective Pediatric Lupus...BACKGROUND: There are few prospective studies of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) for pediatric lupus nephritis (pLN) and none evaluating rituximab (RTX). METHODS: The Prospective Pediatric Lupus Nephritis Registry (ProPeL-R) enrolled patients < 21 years within 4 weeks of an initial kidney biopsy diagnostic of pLN. Demographic, clinical, and laboratory data were collected prospectively at enrollment, 3 months, 6 months, and then every 6 months thereafter for up to 5 years of follow-up. For this study, we compared patients receiving initial therapy with corticosteroids (CS) and either MMF (n = 33) vs. CYC (n = 18), and those treated with CS, either MMF or CYC, with RTX (n = 20) vs. without RTX (n = 51). RESULTS: Histology consisted of 18% class III; 35% class IV; 25% mixed class; and 22% pure class V. Eighty-two percent were female. No significant differences in response or infection rates were identified between those receiving MMF or CYC. There was a significant increase in combined complete (CR) and partial response (PR) at 24 months with RTX use. Overall CR rates at 6 and 24 months were 35% and 58%, respectively. At 24 months, 51% of patients continued on CS, and 56% of patients experienced at least one CS side effect. CONCLUSIONS: MMF and CYC had similar efficacy as initial therapies for pLN. RTX may augment long-term response. However, response rates were suboptimal. Large variations in initial therapy were observed. Given the paucity of prospective data in pLN, our study further illustrates the need for data-driven, pediatric-specific protocols to standardize care and improve outcomes.
BACKGROUND: Children with chronic kidney disease (CKD) often have a reduced functional capacity. The study aimed to evaluate the functional capacity of children with CKD by using three field tests: 6 min walk (6MWT), 2 m...BACKGROUND: Children with chronic kidney disease (CKD) often have a reduced functional capacity. The study aimed to evaluate the functional capacity of children with CKD by using three field tests: 6 min walk (6MWT), 2 min walk (2MWT), and 3 min step test (3MST), and investigate relationships between these tests and to determine which tests patients prefer. METHODS: This study evaluated 51 children with CKD (19 female, 32 male). The 6MWT, 2MWT, and 3MST were used to measure functional capacity. After performing the tests, participants reported their preferred one. Quadriceps muscle strength (QMS) and hand grip strength (HGS) were assessed using dynamometers. RESULTS: The mean age of the patients was 13.7 ± 3.2 years. A total of 22 patients (43.1%) were in stage 2 CKD, 13 patients (25.5%) in stage 3, six patients (11.8%) in stage 4, two patients (3.9%) in stage 5 non-dialysis (3.9%) and eight patients (15.7%) in stage 5 on dialysis. No statistically significant differences were observed between the early and advanced CKD groups for any of the field tests (p > 0.05). However, the early CKD group had a significantly higher dominant QMS than the advanced CKD group (p = 0.023). Most children preferred walking tests (6MWT: 43.1%; 2MWT: 43.1%), while 13.8% preferred the 3MST. Moderate positive correlations were found between 6 and 2MWT (r = 0.669, p < 0.001) and between 6MWT and 3MST (r = 0.422, p = 0.002). CONCLUSIONS: Peripheral muscle strength was deteriorated in advanced CKD. The 2MWT is a practical and time-efficient alternative to the 6MWT. The 3MST remains a viable option when walking tests are not feasible. TRIAL REGISTRATION: NCT06683339.
Two male siblings, aged 15 and 13 years, born to consanguineous parents, presented with hereditary anemia and thrombocytopenia associated with unexplained hepatosplenomegaly. Both were initially diagnosed with hereditary...Two male siblings, aged 15 and 13 years, born to consanguineous parents, presented with hereditary anemia and thrombocytopenia associated with unexplained hepatosplenomegaly. Both were initially diagnosed with hereditary cytopenia and maintained on transfusion therapy since childhood. At age 15, the elder sibling developed acute thrombotic microangiopathy (TMA) with hypertensive encephalopathy, hemolytic anemia, severe thrombocytopenia, and acute kidney injury requiring hemodialysis and plasma exchange. The younger sibling exhibited predominantly hematological manifestations with severe anemia and thrombocytopenia but preserved kidney function, responding favorably to plasma transfusion. Whole-exome sequencing identified two distinct pathogenic variants: a homozygous mutation in ADAMTS13 associated with hereditary thrombotic thrombocytopenic purpura (TTP; OMIM 274150), and a homozygous 57.1 Kb deletion at 1q31.3 involving CFHR1 and CFHR3, associated with atypical hemolytic uremic syndrome (aHUS; OMIM 235400). This case series highlights the phenotypic variability of TMA syndromes and underscores the importance of comprehensive genetic testing in hereditary cytopenia.
BACKGROUND: Microalbuminuria indices may miss early diabetic kidney disease (DKD) and can regress. Urinary podocyte and tubular injury biomarkers may detect subclinical kidney injury before albuminuria. We evaluated urin...BACKGROUND: Microalbuminuria indices may miss early diabetic kidney disease (DKD) and can regress. Urinary podocyte and tubular injury biomarkers may detect subclinical kidney injury before albuminuria. We evaluated urinary podocyte- and tubule-derived biomarkers in adolescents/young adults with type 1 diabetes mellitus (T1DM) and compared 12-year prognostic performance with albuminuria. METHODS: A total of 130 participants with T1DM were screened; 109 were eligible and included in the baseline analysis, and 30 age-matched healthy controls were enrolled. Baseline urinary podocalyxin (u-PCX), nephrin (u-nephrin), and liver-type fatty acid-binding protein (u-LFABP) were measured by ELISA and indexed to creatinine; albuminuria was assessed by 24-h albumin excretion rate (u-AER) and spot albumin-to-creatinine ratio (u-ACR). Fifty-one participants were reassessed after 12 years; measurements were obtained at baseline and at the 12-year follow-up visit. Incident DKD (micro-/macroalbuminuria) was the primary outcome. Discrimination was assessed by ROC curves and Youden thresholds. RESULTS: At baseline, 90% had normoalbuminuria. Participants with normoalbuminuria had higher u-PCX/Cr, u-nephrin/Cr, and u-LFABP/Cr vs. controls (all p ≤ 0.001). Over 12 years, 7/51 developed DKD. Baseline u-PCX/Cr discriminated incident DKD (AUC 0.96; 95% CI 0.91-1.00): <78 ng/mgCr (NPV 100%) and ≥193 ng/mgCr had specificity 95.5%; DKD incidence across <78, 78-193 and ≥193 ng/mgCr strata was 0%, 20% and 75%, respectively (p-trend < 0.001). Baseline spot u-ACR also performed well (AUC 0.87; 95% CI 0.74-1.00). CONCLUSIONS: Baseline u-PCX/Cr and u-LFABP/Cr were elevated in those who developed micro-/macroalbuminuria at 12 years. Spot u-ACR remains a practical prognostic tool, while u-PCX/Cr provides complementary, actionable long-term risk cut-points requiring external validation.
Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI) characterized by defective NADPH oxidase activity, leading to severe infections, hyperinflammation, and immune dysregulation. Autoimmune manifestat...Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI) characterized by defective NADPH oxidase activity, leading to severe infections, hyperinflammation, and immune dysregulation. Autoimmune manifestations are increasingly recognized, whereas systemic lupus erythematosus (SLE) with renal involvement is exceedingly rare. We report an 11-year-old boy with X-linked CGD who developed SLE complicated by class IV/V lupus nephritis (LN), presenting with progressive cutaneous lesions, nephrotic-range proteinuria, hypocomplementemia, and high-titer anti-double-stranded DNA antibodies. Renal biopsy confirmed active proliferative and membranous LN. Unlike previously reported cases, the patient was treated with a full induction and maintenance immunosuppressive regimen, including high-dose corticosteroids and MMF, together with careful antimicrobial prophylaxis. The patient achieved complete clinical, renal, and immunological remission without infectious complications. This case highlights the diagnostic and therapeutic challenges of managing LN in CGD and suggests that a full immunosuppressive regimen may lead to favorable outcomes even in this highly vulnerable population.
BACKGROUND: The North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry has tracked outcomes of children receiving maintenance dialysis since 1992. METHODS: We analyzed 8923 incident pediatric...BACKGROUND: The North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry has tracked outcomes of children receiving maintenance dialysis since 1992. METHODS: We analyzed 8923 incident pediatric dialysis patients enrolled from 1992 to 2020, grouped into three eras (1992-2000, 2001-2010, 2011-2020). Demographics, primary diagnoses, dialysis modality, survival, causes of death, and time to kidney transplant were assessed. RESULTS: The cohort was 56% male and 49% White. The most common causes of kidney failure were hypoplasia/dysplasia (15%), focal segmental glomerulosclerosis (14%), and obstructive uropathy (12%). Dialysis practices changed over time, with peritoneal dialysis (PD) declining as the initial modality from 66% in the 1990s to 40% in 2011-2020, while hemodialysis (HD) increased correspondingly. Infants represented an increasing proportion of patients initiating dialysis, rising from 15% in the 1990s to 25% in the most recent era. Three-year survival improved between the first and second eras to 90% but has remained stable in the past decade (91%). Infants had the lowest survival (77%). Among 734 deaths, cardiopulmonary causes remained stable across eras (22%), whereas infection-related mortality declined from 22 to 15% and occurred more frequently in PD than HD (23% vs. 12%, p < 0.05). 90% of children listed received a kidney transplant, and this was the most common cause of dialysis discontinuation. CONCLUSIONS: Over time survival on dialysis has improved, though survival rates have recently been relatively static. Cardiopulmonary causes of death have not shown a decrease in prevalence across dialysis eras.
BACKGROUND: Antibodies to factor H (anti-FH) are a leading cause of atypical hemolytic uremic syndrome (aHUS) in school-going children. While terminal complement blockade with eculizumab (ECZ) is standard of care for all...BACKGROUND: Antibodies to factor H (anti-FH) are a leading cause of atypical hemolytic uremic syndrome (aHUS) in school-going children. While terminal complement blockade with eculizumab (ECZ) is standard of care for all forms of aHUS, anti-FH associated aHUS is uniquely amenable to combination therapy with plasma exchange (PEX) and immunosuppression. There are no controlled comparisons on the relative short- or medium-term efficacy of the two strategies of management. OBJECTIVES: The primary objectives were to compare the time from initiation of therapy to hematological remission and renal recovery between patients managed with PEX versus ECZ, with or without immunosuppression, for anti-FH associated aHUS in native kidneys. We also compared the proportions of patients attaining hematological remission or renal recovery by 7, 14 and 28 days of therapy, and proportion of patients with chronic kidney disease G1-5, dialysis-dependence, or death. DATA SOURCES: PubMed and Embase were searched from January 2004 to April 2025. STUDY ELIGIBILITY CRITERIA: Studies, in English language, were eligible if they reported the time to hematological remission and renal recovery in individual patients with anti-FH antibody-associated aHUS in native kidneys and treated with either PEX or ECZ with or without additional immunosuppression. PARTICIPANTS AND INTERVENTIONS: Within studies, individual patients were included if they had received either, and not both, PEX or ECZ, and information regarding time to hematological remission and renal recovery was available. STUDY APPRAISAL AND SYNTHESIS METHODS: The risk of bias for retrospective cohort studies and case reports or series was assessed using the Newcastle-Ottawa Quality Assessment Scale and Joanna Briggs Institute (JBI) tool for systematic reviews, respectively. Individual patient data were combined by therapy group to report time-to-event outcomes as hazard ratios (95% confidence intervals, CI), compared using the log rank test. Other continuous measures were compared between groups using the rank sum test. RESULTS: Fourteen of 57 studies shortlisted from among 403 search results met eligibility criteria, within which 99 patients, including 81 managed with PEX and 18 with ECZ, with/without immunosuppression, were eligible. Patients receiving PEX presented later with more severe anemia and lower eGFR, and more often required dialysis. Median time to hematologic remission was significantly shorter with PEX (9 vs. 20 days; P = 0.0007) while time to renal recovery was similar (16 vs. 20 days; P = 0.36). The proportion with CKD G3-5 and mortality was insignificantly higher with PEX than ECZ (respective P 0.077 and 0.36). LIMITATIONS: Our findings are limited by small numbers of participants and studies, lack of comparative studies, heterogeneity in disease severity, and variations in definitions of outcomes. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Patients managed with PEX achieved hematological remission faster than those on ECZ; the time to renal recovery was similar. Given the precautions and vigilance necessary with complement blockade, PEX appears to be a satisfactory initial choice for managing anti-FH associated HUS, particularly in low-resource settings. Prospective trials should compare the efficacy, safety and healthcare costs of these strategies in managing patients with anti-FH associated HUS. SYSTEMATIC REVIEW REGISTRATION NUMBER:PROSPERO ID: CRD420251033150.