Pediatric Nephrology最新文献

Background: Exocrine pancreatic insufficiency (EPI) is an extremely rare complication of hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) and, to our knowledge, only one patient has been reported to have received pancreatic enzyme replacement therapy (PERT). Furthermore, STEC-HUS is not usually included among EPI causes.

Case diagnosis/treatment: We report a 4-year-old girl with STEC-HUS who required dialysis and 4 days after admission developed acute pancreatitis (ACPAN) and diabetes mellitus (DM). Amylase and lipase normalized 15 days later but on the 73rd day of admission, she presented abdominal discomfort, bloating, and bulky and malodorous stools with a low fecal elastase-1 level (FE-1) of 15.74 µg/g confirming EPI diagnosis. She received 3 months of PERT until normalization of FE-1 levels.

Conclusions: In children with STEC-HUS with ACPAN or DM, a high index of suspicion for EPI is required, since its symptoms are often mild, nonspecific, or delayed. In addition, STEC-HUS should be further recognized as a cause of secondary EPI.

Background: Autosomal dominant polycystic kidney disease (ADPKD) demonstrates broad genetic and phenotypic variability, with kidney failure (KF) occurring across a wide age spectrum. Despite several predictor tools, there remains a need to identify factors associated with rapid disease progression. This study describes the phenotypic characteristics of a multicentric cohort experiencing early-onset KF by age 40.

Methods: This retrospective, multicenter cohort study analyzed longitudinal data of rapidly progressive ADPKD patients (n = 199). The prevalence of established risk factors was compared to nine existing ADPKD cohorts (n^total = 6782) with KF after 40 years of age. We examined the longitudinal impact of early hypertension and urological events on the risk of developing KF.

Results: The median age at ADPKD diagnosis was 22.3 years (IQR, 16.5-28.6) and median age of KF was 35.6 years (31.7-38.0). Hypertension was observed in 68.1% of cases, with early-onset hypertension being more common among those with accelerated progression towards KF. Urological events were present in 60.1% of cases, with a high burden of gross hematuria (30.4%). Existing ADPKD cohorts had a mean age of 45.5 years, with weighted prevalences of hypertension (71.1%), kidney stones (22.4%), hematuria (22.9%), and urinary tract infections (22.8%). Extrarenal manifestations were less prevalent compared to other ADPKD cohorts.

Conclusion: This study outlines a cohort of ADPKD patients with accelerated disease progression, reaching KF before age 40. Hypertension and urological events were highly prevalent at a young age, emphasizing the importance of early and regular blood pressure monitoring.

We report on a 14-year-old girl who developed post-transplantation smooth muscle tumours (PTSMT) located in the spleen, lungs, liver, and central nervous system (CNS), 4 years after kidney transplantation. She was asymptomatic, and the disease was detected during the work-up for a urinary tract infection. Diagnosis was performed by the analysis of a tissue specimen, through the biopsy of a lung tumour, which revealed a proliferation of spindle-shaped cells which were positive for actin and vimentin. In situ hybridization studies were positive for Epstein-Barr virus, and her serologic status was negative prior to transplantation. We reduced immunosuppression by stopping mycophenolate and switching tacrolimus for sirolimus. After 18 months of follow-up, she remains asymptomatic, and the CNS tumour reduced its diameter from 24 × 21 mm to 14 × 13 mm. PTSMT should be considered in the differential diagnosis of transplanted patients who develop neoplastic complications associated with immunosuppression.

Background: Limited data exists on clinical predictors of kidney outcomes in children with lupus nephritis (LN).

Methods: Children aged below 18 years with biopsy-proven LN followed from January 2010 to February 2024 in a tertiary-care center were enrolled in order to characterize their clinical presentations, flares, infections, histology and determine Major Adverse Kidney Events (MAKE) (defined as eGFR < 60 mL/min/1.73 m² and/or death). Data was analysed to identify predictive factors of adverse outcomes.

Results: Seventy-five children (20% boys) with median (IQR) age at diagnosis 11.2 (9,13) years, were studied. Clinical presentations were nephritic syndrome, mixed nephritic-nephrotic features, rapidly progressive glomerulonephritis (RPGN), and nephrotic syndrome in 24 (32%), 15 (20%), 11 (14.7%) and 5 (6.7%) patients, respectively. Proliferative LN was the major (70.6%) histological subtype. In total, 75 kidney flares (21.3% nephritic) with incidence rate (IR) of 0.48 flares per person-year were noted in 31 (41.3%) children. Infections occurred in 32 (42.6%), with IR of 0.58 episodes per person-year. Bacterial pneumonia 14 (22.9%), sepsis 10 (16.3%) and tropical infections 6 (9.8%) were most common. At median last follow-up of 2.3 (1.3, 5.6) years with 85.4% kidney-survival rate, 41 (54.6%), and 21 (28%) were in complete-response (CR), and partial-response (PR), respectively. Proliferative LN and those in PR or NR were at significantly higher risk of kidney flares and infections, regardless of initial induction therapy. RPGN at presentation, non-responders at 6 months and severe kidney flare ever predicted MAKE in 11 (14.6%) children.

Conclusions: Multiple kidney flares and infections constitute a significant morbidity in LN. RPGN, non-responders and severe kidney flare predict adverse kidney outcomes.

We report a child with biallelic COQ6 variants presenting with familial thrombotic microangiopathy (TMA). A Chinese boy presented with steroid-resistant nephrotic syndrome at 8 months old and went into kidney failure requiring peritoneal dialysis at 15 months old. He presented with hypertensive encephalopathy with the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute on chronic kidney injury at 25 months old following a viral illness. Kidney biopsy showed features of chronic TMA. He was managed with supportive therapy and plasma exchanges and maintained on eculizumab. However, he had another TMA relapse despite complement inhibition a year later. Eculizumab was withdrawn, and supportive therapies, including ubiquinol (50 mg/kg/day) and vitamins, were optimized. He remained relapse-free since then for 4 years. Of note, his elder sister succumbed to multiple organ failure with histological evidence of chronic TMA at the age of 4. Retrospective genetic analysis revealed the same compound heterozygous variants in the COQ6 gene.

Background: Elevated cefepime blood concentrations can cause neurotoxicity in adults. The consequences of elevated cefepime concentrations among pediatric patients are unknown. Future exploration of such effects requires first identifying patients at risk for elevated cefepime exposure. We investigated the role of acute kidney injury as a risk factor for increased cefepime concentrations in critically ill children.

Methods: This was a retrospective analysis at a single pediatric intensive care unit. Analyzed patients received at least 24 h of cefepime and had at least two opportunistic samples collected for total cefepime concentration measurement. Individual pharmacokinetic (PK) profiles during treatment courses were reconstructed using Bayesian estimation with an established population PK model. Elevated trough concentration (C_min) was defined as ≥ 30 mg/L based on adult toxicity studies. The effect of kidney dysfunction on cefepime PK profiles was interrogated using a mixed-effect model.

Results: Eighty-seven patients were included, of which 13 (14.9%) had at least one estimated C_min ≥ 30 mg/L. Patients with elevated C_min were more likely to have acute kidney injury (AKI) during their critical illness (92% vs. 57%, p = 0.015 for any AKI; 62% vs. 26%, p = 0.019 for severe AKI). Patients who had AKI during critical illness had significantly higher cefepime exposure, as quantified by the area under the concentration-time curve over 24 h (AUC_24h) and C_min.

Conclusions: Among critically ill children, AKI is associated with elevated cefepime concentrations. Identifying these high-risk patients is the first step toward evaluating the clinical consequences of such exposures.

Background: Limited data, primarily from small case series, exist regarding the clinical profile, genetic variants, and outcomes of WDR72-associated distal renal tubular acidosis (WDR72-dRTA).

Methods: Our study enrolled children diagnosed with WDR72-dRTA below 18 years of age from 9 Indian centers and analyzed their clinical characteristics, genetic profiles, and outcomes. Potential genotype-phenotype correlations were explored.

Results: We report 22 patients (59% female) with WDR72-dRTA who were diagnosed at a median age of 5.3 (3, 8) years with polyuria (n = 17; 77.3%), poor growth (16; 72.7%), and rickets (9; 40.9%). Amelogenesis imperfecta was present in 21 (95.5%) cases. At presentation, all patients had normal anion gap metabolic acidosis; hypokalemia and nephrocalcinosis were seen in 17 (77.3%) patients each. Seven (31.8%) patients had concomitant proximal tubular dysfunction. Genetic analysis identified biallelic nonsense variants in 18 (81.8%) patients, including novel variants in 6 cases. A previously reported variant, c.88C > T, and a novel variant, c.655C > T, were the most frequent variants, accounting for 10 (45.5%) cases. Over a median follow-up of 1.3 (1, 8) years, the height velocity improved by 0.74 (0.2, 1.2) standard deviation scores, while 3 children (13.6%) progressed to chronic kidney disease (CKD) stage 2, with eGFR ranging from 67 to 76 mL/min/1.73 m², respectively, after 11.3-16 years of follow-up. No specific genotype-phenotype correlation could be established.

Conclusions: WDR72-dRTA should be considered in children with typical features of amelogenesis imperfecta and dRTA. Biallelic nonsense variants are common in Asians. While most patients respond well to treatment with improved growth and preserved eGFR, on long-term follow-up, a decline in eGFR may occur.