BACKGROUND: Dent disease is a hereditary kidney tubular disorder caused by pathogenic variants in either the CLCN5 (Dent disease 1) or OCRL1 (Dent disease 2) genes. As a rare genetic disorder, Dent disease often presents...BACKGROUND: Dent disease is a hereditary kidney tubular disorder caused by pathogenic variants in either the CLCN5 (Dent disease 1) or OCRL1 (Dent disease 2) genes. As a rare genetic disorder, Dent disease often presents with variable clinical manifestations, leading to frequent misdiagnosis or underdiagnosis, especially in milder cases. Consequently, limited research has addressed the long-term clinical outcomes of Dent disease. METHODS: This retrospective multicenter cohort study was conducted at 9 hospitals in Korea. A total of 48 male patients from 44 unrelated families with genetically confirmed Dent disease were enrolled, and their clinical phenotypes, and genetic backgrounds were assessed. RESULT: The median age at diagnosis for Dent disease was 6.8 years, and 42 patients were diagnosed with Dent disease 1. At diagnosis, 17 patients (37.0%) demonstrated the classic triad of Dent disease features, whereas 12 patients (26.1%) presented solely with isolated low-molecular-weight proteinuria. During follow-up, whereas all patients maintained low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, and nephrolithiasis occurred in 82.6%, 56.5%, and 8.3% of patients, respectively. The cases with Dent disease 2 had a higher rate of hypophosphatemia and significant proteinuria compared to Dent disease 1. A negative correlation was identified between hypercalciuria and age in the overall Dent disease cohort. The decline rate of annual estimated glomerular filtration rate was 0.6 mL/min/1.73 m, without the case of kidney failure. At last follow-up, kidney dysfunction was present in 39.5% of cases. CONCLUSIONS: Due to its rarity and phenotype variability, Dent disease is frequently under-recognized by clinicians. As over one-third of patients progress to chronic kidney disease by early adulthood, a high index of clinical suspicion and early genetic testing are essential, alongside rigorous monitoring of kidney function.
BACKGROUND: Chronic kidney disease (CKD) in children is associated with substantial morbidity and risk of progression to kidney failure in some cases. Identifying clinical predictors of kidney function decline is essenti...BACKGROUND: Chronic kidney disease (CKD) in children is associated with substantial morbidity and risk of progression to kidney failure in some cases. Identifying clinical predictors of kidney function decline is essential for early intervention. This study evaluated demographic, clinical, and biochemical determinants of CKD progression in a pediatric cohort. METHODS: This retrospective study included 70 children with CKD stages 2-4 followed for at least two years at a tertiary pediatric nephrology center. CKD progression was defined as a ≥ 25% decline in estimated glomerular filtration rate (eGFR) over 24 months. Demographic, anthropometric, biochemical, and clinical parameters were assessed at baseline and during follow-up. Univariate and multivariate logistic regression analyses were performed to identify predictors of progression. RESULTS: CKD progression occurred in 41 of 70 patients (58.6%), and 17 (24.2%) developed kidney failure within two years. In univariate analyses, older age at follow-up was associated with increased progression risk (OR 1.008; p = 0.044), while longer CKD follow-up showed a borderline protective trend. Lower baseline calcium levels and first-year metabolic acidosis demonstrated clinically relevant but non-significant associations with progression. Baseline height Z-score remained the only independent predictor of CKD progression in multivariate analysis (OR 1.54; 95% CI 1.03-2.30; p = 0.034). CONCLUSION: Baseline linear growth impairment represents an important anthropometric marker associated with accelerated CKD progression in children. Early growth assessment may aid risk stratification and support timely implementation of preventive strategies.
Hemolytic uremic syndrome (HUS) in infancy may be difficult to classify because infection-associated HUS and genetic thrombotic microangiopathies (TMAs) can present with similar findings. We report a 7-month-old boy admi...Hemolytic uremic syndrome (HUS) in infancy may be difficult to classify because infection-associated HUS and genetic thrombotic microangiopathies (TMAs) can present with similar findings. We report a 7-month-old boy admitted with pneumonia, anemia, thrombocytopenia, and acute kidney injury. Radiologically confirmed pneumonia, elevated CRP levels, positive nasopharyngeal pneumococcal PCR testing initially suggested pneumococcal-associated HUS; however, microangiopathic hemolysis and anuria persisted despite infection control, dialysis, plasma exchange, and complement inhibition therapy. Genetic analysis subsequently revealed a homozygous DGKE mutation, establishing the diagnosis of complement-independent TMA. During follow-up, the course was further complicated by secondary hemophagocytic lymphohistiocytosis (HLH) triggered by severe inflammation and catheter-related sepsis. This case demonstrates that an apparent infectious trigger does not exclude an underlying genetic etiology in infants with TMA and highlights the importance of early genetic evaluation and awareness of hyperinflammatory complications such as HLH in patients with persistent disease activity.
BACKGROUND: Temporary discontinuation of mycophenolate mofetil (MMF) is frequently required in pediatric kidney transplant recipients, most often in response to viral complications. However, data regarding the long-term...BACKGROUND: Temporary discontinuation of mycophenolate mofetil (MMF) is frequently required in pediatric kidney transplant recipients, most often in response to viral complications. However, data regarding the long-term safety of MMF discontinuation, feasibility of reintroduction, and predictors of the need for MMF withdrawal in children remain limited. METHODS: We conducted a retrospective, single-center cohort study of pediatric kidney transplant recipients with longitudinal follow-up. Clinical, virologic, immunologic, and transplant-related data were collected. Outcomes included longitudinal estimated glomerular filtration rate (eGFR), biopsy-proven acute rejection, graft loss, de novo donor-specific antibody (dnDSA) development, unplanned hospitalization, and MMF reintroduction. Factors associated with MMF discontinuation were evaluated using multivariable regression analysis. RESULTS: Among 65 pediatric kidney transplant recipients, 22 (33.8%) required temporary MMF discontinuation, most commonly within the first post-transplant year. Opportunistic viral infections accounted for the majority of MMF withdrawal events, with BK virus as the predominant indication. MMF reintroduction was feasible in most patients (15/22). Longitudinal eGFR trajectories, rates of rejection, graft loss, dnDSA development, and unplanned hospitalization did not differ between patients who discontinued MMF and those who maintained full therapy. Younger age at transplantation emerged as the sole independent predictor of the need for MMF discontinuation. CONCLUSIONS: In this real-world pediatric cohort, temporary MMF discontinuation, when clinically indicated, closely monitored, and followed by cautious reintroduction, was not associated with adverse long-term graft outcomes. Younger age at transplantation was associated with a higher likelihood of MMF discontinuation, supporting individualized immunosuppression strategies and proactive efforts to identify children at risk for viral-driven immunosuppression intolerance.
BACKGROUND: The shortage of pediatric kidney donors has increased interest in donation after circulatory death (DCD) as an alternative for transplantation. METHODS: This multicenter, retrospective study analyzed all pedi...BACKGROUND: The shortage of pediatric kidney donors has increased interest in donation after circulatory death (DCD) as an alternative for transplantation. METHODS: This multicenter, retrospective study analyzed all pediatric kidney transplants (KT) from DCD donors performed in Spain between 2013 and 2024 in recipients under 18 years and compared them with 490 KTs from donation after brain death (DBD) donors during the same period. RESULTS: Sixty-four DCD KTs were included. Delayed graft function (DGF) occurred in 12% of cases. DGF risk was higher with donor age > 40 years (p > 0.05) and in grafts retrieved using the rapid recovery (RR) extraction technique (p < 0.05). The median functional warm ischemia time was 13 min (IQR:9-18) and was not associated with an increased risk of DGF. The median cold ischemia time (CIT) was 12.8 h (IQR:9.4-17), and longer CIT was associated with a nonsignificant increase in DGF risk. No DGF occurred when CIT was < 14 h and no additional risk factors were present. Recipients with DGF had a lower estimated glomerular filtration rate one month post-transplant (p < 0.05), but no significant difference at one year. Five-year graft survival rates were not significantly lower in DCD compared to DBD KTs (89.7% vs. 88.5%). CONCLUSIONS: Although DGF risk was associated with older donor age, RR technique, and longer ischemia times, it did not affect one-year graft function. Graft survival with DCD donors did not appear inferior to that with DBD. DCD KT appears feasible in pediatric recipients and may help expand donor availability under carefully selected conditions.
Hematuria has traditionally been considered a benign sign of glomerular injury, as reported in autosomal dominant type IV collagen-related nephropathy. However, growing clinical and experimental evidence suggests that it...Hematuria has traditionally been considered a benign sign of glomerular injury, as reported in autosomal dominant type IV collagen-related nephropathy. However, growing clinical and experimental evidence suggests that it may be an active driver of kidney dysfunction. Persistent microscopic hematuria is associated with an increased risk of progression to kidney failure. Likewise, episodes of macroscopic hematuria, particularly in Immunoglobulin A nephropathy, can precipitate acute kidney injury and contribute to chronic impairment of kidney function. Glomerular bleeding may be associated with alterations in the glomerular filtration barrier, allowing erythrocyte leakage into the urinary space. At the molecular level, erythrocyte breakdown products, such as free hemoglobin and heme, induce oxidative stress and inflammation, exerting direct cytotoxic effects on kidney parenchymal cells. In this comprehensive review, we describe the prevalence of hematuria in pediatric patients, elucidate the cellular and molecular mechanisms by which hemoglobin and its heme derivatives promote kidney injury, evaluate the impact of hematuria on long-term kidney outcomes, and discuss emerging therapies against hematuria-induced nephrotoxicity.
Children after kidney transplantation (KTx) are prone to mineral and bone disease (MBD) including growth restriction, bone pain, skeletal deformities, fractures, and vascular calcifications. We present a position paper o...Children after kidney transplantation (KTx) are prone to mineral and bone disease (MBD) including growth restriction, bone pain, skeletal deformities, fractures, and vascular calcifications. We present a position paper on the diagnosis and management of post-transplant MBD in this population based on the available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD, Dialysis and Transplantation Working Groups. PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and structured literature searches were conducted for a population of children under 18 years of age who were kidney transplant recipients with a functioning allograft. Patients with a failing allograft (i.e., with an eGFR less than 30 mL/min per 1.73 m) are not discussed here. Clinical practice points (CPPs) were developed and graded using the American Academy of Pediatrics grading matrix. A Delphi consensus method was followed. We present 46 CPPs for the diagnosis and management of MBD in paediatric KTx, including assessment and management before and after KTx, highlighting the specifics of monitoring post-transplant MBD between 0 and 3 months after KTx, and including the impact of steroid minimization and withdrawal. As there are few high-quality studies in this field, the strength of most statements is weak to moderate and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested.
Przygodda S, Brieger LC, Bohlen AV
… +43 more, Rehberg M, Konrad M, Schlingmann KP, Hiort O, Schmidt D, John-Kroegel U, Wühl E, Kemper MJ, Derichs U, Patzer L, Albers N, Dunstheimer D, Heger S, Grohmann-Held K, Schroeder C, Jorch N, Schmid E, Staude H, Weitz M, Lecher L, Freiberg C, Huebner A, Heitmeyer-Pyper A, Sparta G, Evers K, Ostendorf AJ, Partsch CJ, Marx M, Land C, Baus I, Wilkening F, Moeller K, Simic-Schleicher G, Empting S, Müller D, Metzing O, Wagner V, Holder M, Žebec MS, Schnabel D, Haffner D, Živičnjak M, German Society for Pediatric Nephrology (GPN), the German Society for Pediatric, Adolescent Endocrinology, Diabetology (DGPAED)
BACKGROUND: X-linked hypophosphatemia (XLH) is the most common form of inherited rickets, resulting in short stature despite treatment with oral phosphate and active vitamin D. Detailed data of anthropometric parameters...BACKGROUND: X-linked hypophosphatemia (XLH) is the most common form of inherited rickets, resulting in short stature despite treatment with oral phosphate and active vitamin D. Detailed data of anthropometric parameters at birth, during infancy, and on the influence of an affected parent on outcome are lacking. METHODS: In this prospective multicenter observational study, conducted from 1998 to 2023 in Germany, Austria, and Switzerland, body length, body weight, and head circumference were investigated in 198 children with XLH from birth until the age of 18 years, all being only on supplementation therapy. RESULTS: XLH newborns presented with disproportionate body shape characterized by decreased birth length relative to weight and head circumference with a 2.4-fold increased risk to be born small for gestational age (SGA). A positive family history for XLH was associated with lower anthropometric characteristics at birth. Body disproportion increased during 0-2 years old, resulting in significantly increased head circumference (+ 0.82 SD) and reduced body length (-2.00 SD) compared to healthy 2-year-old patients. Supplementation therapy failed to prevent progressive growth failure and reduced final height, regardless of whether treatment was started early due to an affected family member, which was associated with overall poor control of metabolic bone disease indicated by persistent hypophosphatemia and rising alkaline phosphatase z-score. CONCLUSIONS: XLH is associated with an increased risk for SGA and progressive disproportional body growth during infancy. Routine medical check-ups may soon use this unique growth pattern to identify children with XLH. Supplemental therapy fails to prevent progressive growth failure.
BACKGROUND: Discovery of autoantibodies in steroid-sensitive nephrotic syndrome (SSNS) has transformed our understanding of SSNS as an immune-mediated disease; however, mechanisms underlying autoantibody production are u...BACKGROUND: Discovery of autoantibodies in steroid-sensitive nephrotic syndrome (SSNS) has transformed our understanding of SSNS as an immune-mediated disease; however, mechanisms underlying autoantibody production are unknown. Current treatments for SSNS are non-targeted and cause serious adverse effects. We sought to identify circulating proteins with a causal relationship to SSNS, which likely reflect underlying immune derangements, using an unbiased two-sample Mendelian randomization (MR) and colocalization approach to inform novel drug targets for disease. METHODS: Summary-level data from eight large independent proteome-wide association studies were used to estimate the causal effect of 1540 proteins on SSNS risk by Mendelian randomization (MR) using cis genetic determinants (protein quantitative trait loci, pQTL). Genetic colocalization, gene expression, and affinity binding analyses were performed to further investigate loci identified by MR. RESULTS: Two proteins, apolipoprotein M (APOM) and Tenascin XB (TNXB), were causally linked to SSNS by MR and colocalization analysis. Increases in APOM and TNXB levels were associated with decreased risk of SSNS (p = 1.37 × 10;[OR] = 0.40;95%[CI] = 0.27-0.61 for APOM, and p = 2.95 × 10;[OR] = 0.49;95%[CI] = 0.33-0.72 for TNXB). Colocalization with SSNS occurred at HLA-DRB1 (98%) and HLA-DQA1 (80%) for APOM and TNXB, respectively. Binding affinity and gene expression analysis showed that APOM peptides have strong affinity for HLA-DRB1, that APOM has a biologically plausible causal relationship with SSNS, and that there are approved drugs targeting the APOM pathway. CONCLUSIONS: We identified APOM and TNXB as novel blood proteins associated with SSNS in children. These proteins are promising targets for the development or repurposing of drugs as novel treatments for SSNS.
BACKGROUND: Extremely low gestational age neonates (ELGANs) remain at high risk for morbidity and mortality. Acute kidney injury (AKI) is increasingly recognized, but data in the most immature neonates, especially those...BACKGROUND: Extremely low gestational age neonates (ELGANs) remain at high risk for morbidity and mortality. Acute kidney injury (AKI) is increasingly recognized, but data in the most immature neonates, especially those born at 22-23 weeks, are limited. METHODS: We conducted a retrospective cohort study of inborn neonates at the University of Alabama at Birmingham between 2015 and 2021, born at 22-27 + 6 weeks gestation and ≥ 400 g without major anomalies. Early AKI was defined using KDIGO serum creatinine criteria based on postnatal days 3-7 measurements. The primary outcome was death within 7 postnatal days, and we evaluated AKI with logistic regression models to adjust for gestational age (GA), birth weight z-score, antenatal steroids, 5-min Apgar, and study year. RESULTS: Of 813 neonates, 487 (59.9%) had sufficient creatinine data for AKI assessment. Median GA was 25.5 weeks, and birth weight was 717 g. Overall, 60 neonates (12.3%) developed AKI. Incidence decreased with advancing gestation, from 27% in 22-week GA neonates to 5% in 27-week GA neonates. Early mortality occurred in 39 of 487 (8.0%). After adjustment, AKI was associated with higher odds of early mortality (aOR 2.48, 95% CI 0.88-7.02), though this did not reach statistical significance. Severe AKI showed a stronger association (aOR 3.99, 95% CI 0.94-16.9). CONCLUSIONS: AKI incidence was inversely associated with GA in this large cohort enriched with 22-23-week neonates. Severe AKI may increase early mortality risk, underscoring the need for systematic kidney monitoring in the most immature neonates.
BACKGROUND: Systemic lupus erythematosus (SLE) is a rare but severe autoimmune disease in children, with neurological involvement reported in 22-95% of cases and contributing significantly to morbidity and mortality. Thi...BACKGROUND: Systemic lupus erythematosus (SLE) is a rare but severe autoimmune disease in children, with neurological involvement reported in 22-95% of cases and contributing significantly to morbidity and mortality. This study aimed to assess the prevalence and characteristics of neuropsychiatric manifestations in pediatric patients with lupus nephritis. METHODS: A retrospective multicenter study was conducted in four university hospitals in France, including pediatric patients with biopsy-confirmed lupus nephritis between 2020 and 2024. Clinical, biological, radiological, and treatment data were analyzed. RESULTS: Among the 23 included patients (74% female, median age 11 years), six presented neurological manifestations. All had significant proteinuria (median 2.12 g/g) and most had acute kidney injury (AKI). Lupus nephritis was predominantly class IV. Neurological symptoms varied widely, from headaches and attention deficits to catatonia and stroke. MRI findings included hyperintensities and atrophy in 50% of cases. No significant differences were observed between groups in univariate analyses. Given the limited number of neurological events, multivariable analyses were considered exploratory; in this context, AKI was associated with neurological involvement. CONCLUSION: Neurological involvement affects at least one-quarter of children with lupus nephritis and may be underdiagnosed. Systematic, standardized screening is essential for early detection and tailored treatment.
Aksoy GK, Akman S, Kacıroğlu F
… +34 more, Aksu B, Bulut İK, Erfidan G, Karadoğan E, Nalçacıoğlu H, Pınarbaşı AS, Selçuk ŞZ, Tülpar S, Yel S, Zorlu BP, Alpay H, Balat A, Baskın E, Bayazıt AK, Bayrakçı US, Bülbül M, Candan C, Canpolat N, Çakıcı EK, Çomak E, Delibaş A, Demir BK, Düzova A, Dönmez O, Erdoğan H, Ertan P, Bakkaloğlu SA, Koyun M, Noyan ZA, Özçakar ZB, Özkayın EN, Yavuz S, Yılmaz D, Yüksel S
BACKGROUND: Dialysis is a life-saving treatment for children with stage 5 chronic kidney disease (CKD), but it is associated with a high long-term mortality that varies between countries. The aim of this study was to com...BACKGROUND: Dialysis is a life-saving treatment for children with stage 5 chronic kidney disease (CKD), but it is associated with a high long-term mortality that varies between countries. The aim of this study was to compare 3-year survival rates of children and adolescents on peritoneal dialysis (PD) and hemodialysis (HD) based on national data from Türkiye. METHODS: We analyzed the national registry data to assess survival rates among pediatric patients on dialysis in Türkiye. Kaplan-Meier and Cox proportional hazards models compared PD and HD survival outcomes, adjusting for age, period of initial dialysis commencement, and primary diagnosis. RESULTS: The study included 1,002 children with a mean age of 12.71 ± 4.80 years. The overall mortality rate among pediatric dialysis patients was 25.8 deaths per 1000 patient-years, with adjusted analyses showing a 5-year survival advantage for PD over HD (adjusted p = 0.000001). The median adjusted survival probability was 0.89 (IQR 0.26) for PD and 0.83 (IQR 0.08) for HD, and PD demonstrated superior outcomes particularly in non-CAKUT children aged 6-12 and > 12 years (p = 0.004 and 0.013, respectively). Multivariate Cox regression analysis revealed that haemodialysis, initiation of dialysis between 2006 and 2018, and younger age (< 12 years) were independently associated with an increased risk of mortality in paediatric dialysis patients. CONCLUSION: In Türkiye, peritoneal dialysis has been shown to be associated with better survival rates than haemodialysis in children with stage 5 CKD, particularly among younger patients.
Promoting physical activity is a global initiative. However, published systematic syntheses regarding physical activity among children and young people with chronic kidney disease (CKD) are limited. The aim of this revie...Promoting physical activity is a global initiative. However, published systematic syntheses regarding physical activity among children and young people with chronic kidney disease (CKD) are limited. The aim of this review was to determine the evidence relating to physical activity among children and young people with CKD and identify research gaps. A comprehensive search across seven databases was conducted, and two reviewers screened and synthesised the data. Fifty-seven primary studies were included. Most studies were observational, conducted in Europe and North America, and focused on kidney transplant recipients. Physical activity levels measured by various parameters, tools, and reporting methods showed children with CKD had a lower or similar percentage of physical activity participation, intensity, frequency, duration, and overall activeness compared with healthy controls. Associations between physical activity and sex, age, CKD stages, and outcomes varied in size, direction, and strength among studies. No prospective longitudinal studies have examined the associations between physical activity and CKD progression. Nor did any explicitly describe children's/carer's experience of engaging in physical activity, although five qualitative studies reported impacts and adaptations in children with different CKD stages. Most interventions described were short-term (<6 months) home-based exercise training programmes incorporating endurance, resistance, or flexibility elements. In conclusion, evidence on physical activity in children with CKD is predominantly quantitative, cross-sectional, relying on self-reported data, and focusing primarily on adolescents and kidney transplant recipients. Further research should establish more precise physical activity estimates using validated, standardised measures across CKD stages and diverse populations.
Ku E, Copeland T, McCulloch CE
… +11 more, Savant JD, Warady BA, Furth SL, Kizilbash S, Feig DI, George RP, Flynn JT, Jerry-Fluker J, Matheson MB, Amaral S, CKiD investigators
Pediatr Nephrol
· 2026 Apr · PMID 41940939
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BACKGROUND: Slower chronic kidney disease (CKD) progression allows more time for transplant preparation. Whether differences in CKD progression by race/ethnicity associate with preemptive or living donor transplantation...BACKGROUND: Slower chronic kidney disease (CKD) progression allows more time for transplant preparation. Whether differences in CKD progression by race/ethnicity associate with preemptive or living donor transplantation in youth has not been well studied. METHODS: We examined the association between time spent with low eGFR (between 10-30 mL/min/1.73 m) and odds of preemptive or living donor transplantation among youth with CKD. eGFR was estimated using the bedside Schwartz (if < 18 years) and CKD-EPI 2021 equations (if ≥ 18 years) and the CKiD U25 equation in sensitivity analysis. Time spent with low eGFR was compared by race/ethnicity. RESULTS: Among 333 youth with CKD (median age 11 years [IQR 7,14]), median time spent with low eGFR was 28.8 months. 77% were preemptively waitlisted, and 45% received preemptive transplantation (56% of White and 24% of Black youth). Black (vs. White) youth had shorter time with low eGFR (-6.5 months; 95% CI -11.5, -1.4). Time with low eGFR did not differ across other groups. Findings were similar using the U25 equation. Every additional year spent with low eGFR was associated with higher odds of preemptive (OR 1.45; 95% CI 1.24-1.70) and living donor transplantation (OR 1.42; 95% CI 1.21-1.67), but not preemptive waitlisting (OR 0.96; 95% CI 0.83-1.11) in unadjusted analyses. CONCLUSIONS: Longer time spent with low eGFR is associated with greater odds of preemptive and living donor transplantation. Earlier transplant referral for all children, especially Black youth, may help improve access to preemptive and living donor transplantation.
BACKGROUND: Sickle cell nephropathy (SCN) is a common and under-recognized complication of sickle cell disease (SCD) in children. While albuminuria is widely used as an early marker of renal disease in SCD, emerging evid...BACKGROUND: Sickle cell nephropathy (SCN) is a common and under-recognized complication of sickle cell disease (SCD) in children. While albuminuria is widely used as an early marker of renal disease in SCD, emerging evidence suggests that tubular dysfunction may play a critical role in SCN pathogenesis. Megalin -a renal tubular receptor- is essential for albumin reabsorption and may serve as a biomarker of tubular injury. There is a paucity of human studies assessing the relationship between megalin and albuminuria. This study aimed to evaluate the association between urinary level of megalin and spot urine albumin-creatinine ratio (UACR) in children with sickle cell anemia (SCA) compared with those of age- and sex-matched hemoglobin A (HbAA) controls. METHODS: This hospital-based comparative cross-sectional study included 120 steady-state SCA children and 120 HbAA controls. Early morning urine was assayed for megalin and albumin, using enzyme-linked immunosorbent assay (ELISA) and UACR respectively. RESULTS: Children with SCA had higher UACR and greater prevalence of SCN (UACR ≥ 3 mg/mmol) than healthy controls (3.6 ± 2.8 vs. 2.0 ± 1.7 mg/mmol, p = 0.001, and 30.8% vs. 14.2%, p = 0.003, respectively). Urinary megalin levels were similar in SCA (1459.3 ± 483.1 ng/L) and controls (1552.3 ± 662.4 ng/L), p = 0.215. However, urine megalin was significantly lower in children with SCN (1063.3 ± 388.4 ng/L) compared to children with SCA without nephropathy (1635.8 ± 683.6 ng/L, p = 0.002) and compared to albuminuric controls (1592.4 ± 530.8 ng/L, p = 0.001). There was a significant negative correlation between urinary megalin and UACR in SCA subjects (r = -0.4, p = 0.001) as well as in the SCN subgroup (r = -0.5, p = 0.000). No such correlation was found in controls. CONCLUSION: In children with SCN, urine megalin concentration, reflecting renal tubule megalin expression, is decreased in comparison to children with SCA without nephropathy and inversely associated with UACR. Further experimental and clinical studies are needed to understand megalin regulation in SCN and whether downregulation is protective or not for tubular damage.
BACKGROUND: Acute kidney injury (AKI) is a common cause of morbidity and mortality in critically ill children, yet data on its prevalence and associated factors in low-resource settings remain limited. METHODS: A hospita...BACKGROUND: Acute kidney injury (AKI) is a common cause of morbidity and mortality in critically ill children, yet data on its prevalence and associated factors in low-resource settings remain limited. METHODS: A hospital-based cross-sectional study was conducted from March to June 2020 at Benjamin Mkapa Hospital and Dodoma Regional Referral Hospital. Critically ill children aged 1 month to 15 years were enrolled. AKI was defined using KDIGO criteria based on serum creatinine and urine output assessed with repeat measurements within the first seven days to ensure accurate classification. Multivariable Poisson regression identified factors associated with AKI, while Firth penalized logistic regression assessed predictors of in-hospital mortality. RESULTS: Ninety-two children were enrolled; 53 (57.6%) met KDIGO criteria for AKI. Most cases (84.9%) were identified at admission. AKI severity was stage 1 in 53%, stage 2 in 17%, and stage 3 in 30%. Respiratory distress was associated with AKI (aPR 1.83; 95%CI 1.02-3.33; p = 0.045), though it likely reflected overall illness severity. In-hospital mortality was significantly higher among children with AKI (35.8%) compared to those without (7.7%). Severe dehydration independently predicted mortality (adjusted OR 4.29; 95%CI 1.0-18.4; p = 0.049). Children aged 13-59 months had lower odds of death compared with infants. CONCLUSIONS: AKI is highly prevalent among critically ill children in Dodoma and is associated with increased mortality. Dehydration and younger age are key predictors of death. Early recognition, prompt fluid management, and improved access to dialysis are essential to improve outcomes in resource-limited settings.