In pediatric nephrotic syndrome (NS), conventionally, spot urinary protein-creatinine ratio (PCR) is used for diagnosis and to define relapse and remission. This study evaluates whether urine albumin-creatinine ratio (ACR) can reliably predict proteinuria status to manage NS according to existing guidelines, when PCR values are unavailable. Children between 1 to 18 years of age with steroid sensitive NS (SSNS) were included. Blood samples for albumin, creatinine, and first or second morning urine samples for albumin, total protein, and creatinine were collected; PCR and ACR were calculated in mg/mg. Correlation between ACR and PCR was assessed using Spearman’s rank correlation coefficient and agreement by Bland–Altman analysis. ACR thresholds corresponding to PCR-defined remission and relapse were derived using fivefold internal cross-validation with bootstrap resampling and linear regression modelling. Diagnostic performance was evaluated by sensitivity and specificity using PCR thresholds as the reference standard. In 202 patients (median age 7.4 years, 63
C-reactive protein (CRP) is an acute-phase protein elevated in inflammatory and infection processes. Acute post-streptococcal glomerulonephritis (APSGN) is an infectious and inflammatory process characterized by the formation of immune complexes and renal injury. Although increased CRP levels have been reported in APSGN, whether CRP acts only a systemic biomarker or also contributes to disease mechanisms remain unclear. Therefore, the objective of this review is to highlight data that could reveal a role for CRP in the pathogenesis of APSGN. PubMed/Medline, Embase, Cochrane, and Google Scholar databases were searched from 1970 to 2026 addressing CRP biology, APSGN pathogenesis, and renal inflammatory mechanisms. Current evidence indirectly supports the idea that CRP, particularly through complement-, coagulation- and IgγFc receptors-dependent pathways, could amplify the inflammatory process during APSGN. In this regard, CRP could activate the complement and coagulation systems, interact with streptococcal neuraminidase, induce angiotensin II, immune complexes, and IgγFc receptors, events that could lead to increased inflammation, pro-inflammatory cytokines production, apoptosis, opsonization, phagocytosis, and renal injury in APSGN. Further research is needed to define the expression of CRP in renal tissues and its contribution to glomerular inflammation and define whether the use of CRP blockers can reduce the inflammatory events in APSGN.
Cystinosis-associated metabolic bone disease (CMBD) is a severe complication in patients with infantile nephropathic cystinosis, which is a rare inherited lysosomal storage disease due to pathogenic variants in the CTNS gene that results in an accumulation of cystine in all organs. The kidneys are the organs primarily affected, resulting in renal Fanconi syndrome at around the age of 6–12 months. Without adequate treatment with the cystine-depleting agent cysteamine, this is followed by progressive chronic kidney disease (CKD) and kidney failure in the second decade of life. Patients usually present with progressive disproportionate short stature, rickets, and bone pain in the first 2 years of life. This may be followed by muscle weakness in childhood, and scoliosis and fractures in adulthood, especially if treatment is inadequate. Early diagnosis and treatment are crucial, and this is facilitated by a positive family history, screening programs and care at specialized centers. Therapeutic measures include physical activity, physiotherapy, adequate calcium and phosphate intake, vitamin D supplements, a combination of phosphate supplements and active vitamin D, correction of metabolic acidosis, and, if necessary, growth hormone therapy and surgical correction of persisting leg deformities. Unfortunately, current treatments cannot always prevent progressive bone loss and related skeletal comorbidity. There is increasing evidence for an underlying intrinsic osteoblast and osteoclast defect in cystinosis. Cystine crystal accumulation in macrophages (e.g., in bone and muscle) may result in an inflammatory state promoting increased osteoclast activity and other alterations in myokines and osteokines. Future interventions may target these factors to improve outcomes in patients with cystinosis.
C3 glomerulopathy and acquired partial lipodystrophy (APL) are rare disorders associated with dysregulation of the alternative complement pathway and occasionally coexist. We report a 14-year-old girl who developed nephritic–nephrotic syndrome due to C3 glomerulonephritis concomitant with APL. Despite treatment with mycophenolate mofetil and tacrolimus, kidney function deteriorated, proteinuria increased, and she developed marked faciotruncal lipoatrophy with a 10-kg weight loss. Pegcetacoplan, a C3/C3b inhibitor, was initiated. Five weeks later, serum C3 levels were normal. Creatinine clearance subsequently improved from 25 to 133 mL/min, while proteinuria progressively declined from 3.2 to 0.15 g/g. Within 40 weeks, the patient recovered her usual body weight with marked clinical improvement in subcutaneous fat distribution. This observation suggests that pegcetacoplan may represent a novel therapeutic option for APL.
Pediatric and young adult patients with kidney failure on dialysis are at increased risk of developing thrombotic events (TE). Antithrombotic therapy in this population is challenging due to a concomitant elevated risk of bleeding and the lack of pediatric and young adult–specific data. We conducted a 10-year single-center retrospective cohort study of patients < 23 years of age with kidney failure on dialysis to describe antithrombotic therapy use and evaluate associated safety and clinical outcomes. Among 77 patients with kidney failure on dialysis, 33 (42.9
While successful kidney transplantation has been reported in pediatric patients with primary mitochondrial diseases, immunosuppression regimen and its effect on systemic disease were not described. We present four pediatric patients with genetically confirmed RMND1 disease in a quaternary nephrology center. They presented at a very young age and progressed rapidly to stage 5 chronic kidney disease. All underwent successful kidney transplantation. Their allograft function remained stable throughout the follow-up period, and they did not manifest any major systemic deterioration.
Kidney transplantation requires the anastomosis of the graft’s kidney vein to the recipient's iliac vein or inferior vena cava (IVC). The venous reconstruction can be challenging in case of extended ilio-caval thrombosis. We report the case of a child with Denis Drash syndrome, with right Wilms tumor and intra-caval tumoral extension, left nodules of nephroblastomatosis on a horseshoe kidney, proteinuria, and progressive kidney failure, resulting in bilateral nephrectomy and iliac veins and vena cava thrombosis extended to the retro-hepatic IVC. At the age of 7 years, 32 months after the end of the oncological treatment, she underwent kidney transplantation. Venous reconstruction was achieved by using the donor IVC as a venous conduit anastomosed to the recipient's retro-hepatic IVC at the level of the hepatic veins. Postoperative course was uneventful, and the child is alive and well, free of tumor and with normal kidney function, 5 years after the end of oncological treatment, and 32 months after transplantation. This technique appears as a safe and physiological alternative to previously described venous anastomoses to the portal system or pelvic varices, preventing chronic venous hypertension of the graft.
Effective healthcare transitions and transfers of care are crucial for improving long-term health outcomes among adolescents and young adults (AYA) with chronic kidney disease (CKD). Patient-reported outcomes are an important tool to understand patient experience and are underused in CKD transfer evaluation. This study sought to preliminarily identify differences in the transfer experience among AYAs with CKD and identify contributing factors. Participants enrolled in the Chronic Kidney Disease in Children (CKiD) study who had transferred to adult care between 2017 and 2024 were included in this analysis (N = 110). Participants rated their transfer experience on a 1 to 5 Likert scale. Ratings of 4–5 were categorized as “satisfactory” and ratings of 1–3 were categorized as “unsatisfactory.” Factors assessed because of their potential influence on transfer included maternal education, eGFR, dialysis/transplant status, intelligence quotient (IQ), and executive functioning (EF). Logistic regression using a curated set of a priori predictors was used to estimate odds of unsatisfactory transfer. The median age of participants at the time of transfer rating was 22.2 years [IQR 20.2–24.4]. The transfer experience was rated as satisfactory by 79 participants (72
Peritoneal dialysis (PD) is the preferred home dialysis treatment for children awaiting kidney transplant worldwide. There is significant variance in clinical outcomes across centers, which may be related to PD training for caregivers. This scoping review provides an overview of existing research regarding characteristics of training provided to caregivers of children receiving home PD. Searches were conducted via PubMed, Embase, CENTRAL, PsycINFO, CINHAL and ProQuest electronic databases (2005–2025). Studies in children under 21 years of age were included. Characteristics of training programs were summarized and compared against the International Society of Peritoneal Dialysis (ISPD) pediatric guidelines. Implementation, clinical and service outcomes were reported. Relationships between training program characteristics and the child and family were also reviewed. Twelve articles met inclusion criteria. Overall, there was poor alignment with existing guidelines. Training programs were reported in most articles (n = 9; 75
X-linked hypophosphatemia (XLH) is the most prevalent form of hereditary rickets due to pathogenic variants in the PHEX gene. Since 2018, a treatment with burosumab, which inhibits the activity of fibroblast growth factor 23 (FGF23), has been approved for XLH patients. In contrast, hereditary hypophosphatemic rickets with hypercalciuria (HHRH), caused by pathogenic variants in the SLC34A3 gene, exhibits a similar increase in urinary phosphate excretion due to abnormal function of the renal phosphate transporter; however, FGF23 levels are elevated in XLH but low in HHRH, whereas the levels of biologically active 1,25(OH)₂ vitamin D show the opposite pattern. We present a case of a female patient with XLH due to PHEX deletion, who is also a carrier of two pathogenic variants in the SLC34A3 gene in cis- verified through long-read sequencing. Given these distinct pathophysiological mechanisms and the potential influence of even heterozygous SLC34A3 variants on the clinical phenotype, this case underscores the need to screen WES/WGS data in patients with XLH not only for PHEX variants, but also for variants in other phosphate-regulating genes before initiating burosumab therapy, particularly when biochemical parameters are inconsistent with "classical" XLH.
Distal renal tubular acidosis (dRTA) is a heterogeneous group of disorders of impaired distal acid secretion, leading to normal anion gap metabolic acidosis, growth failure and nephrocalcinosis. Although a genetic basis is well established, the genetic aetiology may differ in Asian populations; however, large multicenter studies from Asia are limited. This multicenter observational study, conducted under Indian Council of Medical Research Task Force on Rare Diseases, included incident and prevalent cases of dRTA between 2020 and 2024. Detailed clinical, biochemical, genetic, and outcome data were analysed. Of 96 children initially suspected to have dRTA, five were reclassified following next-generation sequencing. The remaining 91 cases were diagnosed as dRTA. Genetic testing identified pathogenic/likely pathogenic variants in 56 (61.5
Monoclonal gammopathy, paraprotein secreted by a clonal B-lymphoproliferative or plasma cell disorder, is quite rare in children and adolescents and may be transient. Kidney injury related to monoclonal proteins, or monoclonal gammopathy of renal significance (MGRS), is correspondingly rare and may be relatively unfamiliar to pediatric nephrologists when encountering such diagnoses on kidney biopsy (e.g., amyloid, light chain tubulopathy, light chain cast nephropathy). Several recently described glomerulonephritides with monotypic deposits, characterized by deposits of a single heavy chain and a light chain, without a matching clone in serum or bone marrow, are emerging as more common in this age group than true MGRS, such as proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID), IgA nephropathy with light chain restriction, monotypic membranous nephropathy, and membranous-like nephropathy with masked IgG-kappa (MGMID). PGNMID may arise after infection or other triggers and, in children, is often associated with hypocomplementemia. A recent adult study employing sensitive bone marrow immunoglobulin repertoire sequencing has failed to identify a true clone in many cases, particularly those with IgG3 glomerular deposits. Unfortunately, PGNMID has a propensity for post-transplant recurrence. The pathophysiology, etiology, and treatment for PGNMID and other monotypic entities remain yet to be elucidated in children and adults. Nevertheless, a screening immunofluorescence microscopy panel that includes kappa and lambda light chains is essential for biopsy diagnosis, with confirmation sometimes requiring additional studies such as IgG subclasses and/or antigen retrieval immunofluorescence. This review aims to comprehensively cover monoclonal and monotypic immunoglobulin-related kidney disease in young people.
Children with type 1 diabetes mellitus (T1DM) are at increased risk of early cardiovascular alterations, including hypertension and arterial stiffness. This study aimed to evaluate ambulatory blood pressure monitoring (ABPM) patterns, arterial stiffness parameters, and factors associated with ambulatory hypertension and arterial stiffness in children with T1DM. In this cross-sectional study, 60 children with T1DM (mean age 13.36 ± 3.38 years) and 32 healthy controls underwent 24-h ABPM and pulse wave analysis. Blood pressure variability (BPV) was quantified using average real variability. Clinical, laboratory, and metabolic parameters were recorded. Children with T1DM had significantly higher 24-h peripheral systolic and diastolic blood pressure standard deviation score (SDS), mean arterial pressure SDS, 24-h central diastolic blood pressure, and higher 24-h and daytime diastolic BPV compared with controls (all p ≤ 0.002). Pulse wave velocity (PWV)-related measures were also higher, including 24-h pulse wave velocity (PWV) (4.60 vs. 4.40 m/s, p = 0.011) and 24-h PWV SDS (− 0.32 vs. − 0.95, p = 0.001). Compared with healthy controls, normotensive children with T1DM showed only higher nighttime PWV SDS (p = 0.004), accompanied by a trend toward higher nighttime blood pressure parameters, whereas 24-h and daytime PWV and PWV SDS were similar between the groups (p > 0.05). Compared with normotensive children with T1DM, those with ambulatory hypertension had significantly higher central blood pressure, PWV, and PWV SDS across all time periods (all p < 0.05). Ambulatory hypertension was detected in 38.3
Arteriovenous fistula (AVF) dysfunction is a common complication in pediatric patients on hemodialysis (HD). Early detection using clinical, radiological, and biochemical markers is essential to preserve vascular access. This study evaluated the diagnostic value of physical examination, duplex ultrasonography (DUS), intradialytic hemodynamic parameters, and inflammatory biomarkers in detecting AVF dysfunction. This prospective cohort study included 59 pediatric patients (< 18 years) with chronic kidney disease (CKD) stage 5 on maintenance HD via functioning AVF, followed for 12 months. Patients underwent serial clinical assessment, laboratory testing (hs-CRP, IL-10, TNF-α), and DUS evaluation. Intradialytic venous pressure (VP) and transmembrane pressure (TMP) were recorded, and AVF complications were analyzed. AVF complications occurred in 55.9
A 12-year-old girl presented with steroid-resistant nephrotic syndrome and was found on kidney biopsy to have membranous nephropathy with a full-house immunofluorescence pattern. At presentation, she had marked hypercholesterolemia, with an LDL-C level of 589 mg/dL, and a family history suggestive of familial hypercholesterolemia. Multiple immunosuppressive therapies resulted in only transient or insufficient improvement in proteinuria, while conventional lipid-lowering agents failed to control hypercholesterolemia. On hospital day 98, evolocumab was initiated for refractory hypercholesterolemia. LDL-C levels declined rapidly, and proteinuria subsequently improved during the clinical course. Corticosteroids were tapered and discontinued. Evolocumab was administered for three doses, and nephrotic remission was achieved during the subsequent clinical course and maintained for nearly 1 year. This case illustrates that evolocumab may be an effective lipid-lowering option for selected pediatric patients with nephrotic syndrome complicated by severe refractory hypercholesterolemia. The subsequent improvement in proteinuria should be interpreted cautiously as a temporal association.
