Pediatric Nephrology最新文献

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.

IgA nephropathy and IgA vasculitis with nephritis, albeit rare, represent two relatively frequent glomerular conditions in childhood. Compared to adults, pediatric IgA nephropathy has a more acute presentation, most frequently with synpharyngitic macrohematuria and histologically with more intense inflammation and less intense chronic damage. Management of these conditions is controversial and supported by little high-quality evidence. The paucity of evidence is due to the disease heterogeneity, its inter-ethnic variability, and the difficulty of extrapolating data from adult studies due to the peculiarities of the condition in children. IgA vasculitis with nephritis is a kidney manifestation of a systemic disorder, typical of the pediatric age, in which both the diagnosis of kidney involvement and its management are poorly defined, and an interdisciplinary approach is crucial. Both conditions can have a profound and long-lasting impact on kidney function and the global health of affected children. The International Pediatric Nephrology Association has therefore convened a diverse international group of experts from different disciplines to provide guidance on the recommended management of these conditions in children and to establish common definitions and define priorities for future high-quality, evidence-based collaborative studies for the benefit of children.

Background: Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis. It can be classified as either typical, primarily caused by Shiga toxin-producing Escherichia coli (STEC) infection, or as atypical HUS (aHUS), which results from uncontrolled complement activation.

Methods: We report the case of a 9-year-old boy with aHUS due to compound heterozygous complement factor H-related genes (CFHR) 1/3 and CFHR1-CFHR4 deletions, leading to the development of anti-complement factor H (CFH) autoantibodies. The patient presented nephrological and neurological thrombotic microangiopathy with STEC positivity. Additionally, we provide an extensive literature review of aHUS cases initially classified as typical.

Results: A total of 11 patients were included, 73% of whom were pediatric. Kidney replacement therapy was required in 73% of patients. The recurrence rate was 55%. All cases were found positive for pathological variants of the complement system genes. The most commonly implicated gene was CFH, while the CFHR genes were involved in 36% of cases, although none exhibited anti-CFH autoantibodies. Anti-complement therapy was administered in 54% of cases, and none of the patients who received it early progressed to kidney failure.

Conclusions: STEC infection does not exclude aHUS diagnosis, and early use of anti-complement therapy might be reasonable in life-threatening conditions. Genetic testing can be helpful in patients with atypical presentations and can confirm the necessity of prolonged anti-complement therapy.

Background: The aim of this study was to evaluate associations between pre-pregnancy maternal obesity and adolescent blood pressures (BPs) among children born extremely preterm.

Methods: This longitudinal observational cohort study included participants in the multicenter Extremely Low Gestational Age Newborn (ELGAN) study, born before 28 weeks of gestation, recruited at birth between 2002 and 2004, and followed prospectively through late adolescence. Between 2015 and 2022, three oscillometric BPs were obtained from participants (mean age 17.8 years). We used linear regression modeling to evaluate the association between maternal self-reported pre-pregnancy body mass index (BMI) and offspring adolescent systolic BP (SBP). In secondary analyses, we evaluated the association between maternal pre-pregnancy and offspring preadolescent (10-year-old) BMI and between offspring preadolescent BMI and adolescent SBP.

Results: The 100 (24%) participants born to a mother with a history of pre-pregnancy obesity (BMI ≥ 30) had a greater mean SBP of 120.5 (± 14.3) mmHg compared to the 324 (76%) of adolescents born to mothers without pre-pregnancy obesity (SBP 115.6 (± 12.0) mmHg). Pre-pregnancy obesity was associated with higher offspring BMI (aβ 10.8, 95% CI 2.3, 19.2), and higher offspring BMI was associated with higher adolescent SBP (aβ 0.12, 95% CI 0.09,0.16).

Conclusions: For ELGANs, higher maternal pre-pregnancy BMI was associated with higher adolescent SBP. Findings from secondary analyses suggest potential mediation through preadolescent BMI. Future research directions include multi-level interventions to reduce maternal pre-pregnancy obesity, followed by offspring obesity prevention interventions as a way of reducing intergenerational cardiovascular disease in high-risk infants born extremely preterm.

Background: Information on the clinical characteristics and outcomes of children undergoing continuous kidney replacement therapy (CKRT) from lower-middle-income countries (LMIC) is limited.

Methods: Records of consecutive children 1 month to 18 years of age who underwent CKRT from Jan 2016 to Jan 2024 in a tertiary care pediatric intensive care unit (PICU) were retrospectively reviewed and analyzed for clinical and machine-related characteristics, and outcomes.

Results: Over the 8-year period, 102 patients (61.8% boys) with median age 4 (1.5-9) years underwent CKRT. Among these, 52 (51%) weighed < 15 kg, 37 (36.3%) were underweight, and 27 (26.5%) were stunted. Mean (SD) PRISM III score at admission was 17 (6.8), with 94.1% of patients ventilated and 90.2% on two or more inotropes at CKRT initiation. Septic shock (28.4%) and inborn errors of metabolism with acute decompensation (23.5%) were the most common diagnoses at PICU admission. Indications for CKRT were fluid overload, hyperammonemia or inborn errors of metabolism with acute decompensation, dyselectrolytemia, or their combination in 33.3%, 32.4%, 5.9%, and 19.6% patients, respectively. Continuous veno-venous hemodiafiltration (CVVHDF) was the most common (60.8%) modality employed, with an effluent dose of 32.8 ± 7.3 ml/kg/h. Despite heparin anticoagulation in 87.2% patients, circuit clot occurred in 28 patients, 18 (17.6%) of which led to termination of CKRT session. Overall mortality was 75%.

Conclusions: CKRT can be safely performed in critically ill children from LMIC despite the presence of significant undernutrition and multi-organ dysfunction. Further studies from similar settings are required to evolve strategies to identify modifiable risk factors for the observed high mortality.

Predicting the risks of progression to chronic kidney disease (CKD) stage 5 in idiopathic nephrotic syndrome (NS) and recurrence of the disease (rNS) following kidney transplantation (KT) is a key assessment to provide essential management information. NS has been categorized etiologically as genetic and immune-based. A genetic cause can be identified in ~ 30% of children with steroid-resistant NS (SRNS), a finding associated with a very low risk of rNS following KT. In immune-based NS, clinical overlap is observed among steroid-sensitive NS, secondary-resistant NS, and SRNS not associated with disease-causing genetic variants (non-monogenic SRNS). While ~ 50% of SRNS patients with no identified monogenic disease respond to intensified immunosuppressive treatments, the ones that do not respond to this therapy have a high risk of progression to CKD stage 5 and post-KT rNS. Secondary-resistant patients who progress to CKD stage 5 display the highest risk of post-KT rNS. The proposed shared underlying mechanism of the immune-based NS associated with post-KT rNS is based on a systemic circulating factor (CF) that affects glomerular permeability by inducing foot process effacement and focal segmental glomerulosclerosis. However, identifying patients without a detected genetic form who will recur post-KT is a major challenge. Extensive efforts, therefore, have been made to identify CFs and biomarkers potentially capable of predicting the risk of progression to CKD stage 5 and post-KT rNS. This review discusses the in vitro and in vivo approaches employed to date to identify and characterize potential CFs and CF-induced biomarkers of recurrent NS and offers an assessment of their potential to improve outcomes of KT in this patient population.

Patients with kidney failure require dialysis or kidney transplantation. Kidney transplantation offers great benefits, including reduced mortality; however, many patients who wish to undergo kidney transplantation are unable to do so due to a shortage of donor organs. This shortage is a global issue, and xenotransplantation has emerged as a potential solution. The history of xenotransplantation is characterized by overcoming the immunological challenge of hyperacute rejection. Recently, breakthroughs such as gene-edited pigs and novel immunosuppressants have successfully lowered rejection rates. Recent clinical studies have reported transplants in patients diagnosed with brain death, and in March 2024, a gene-edited pig kidney was transplanted into a patient with kidney failure at Massachusetts General Hospital, marking the first instance of a gene-edited xenotransplantation into a living patient. Our research focuses on applying xenotransplantation in pediatric and obstetric fields, specifically exploring fetal therapy using pig fetal kidneys. We have long been researching the development of a novel kidney replacement therapy involving the transplantation of fetal pig kidneys. Fetal pig kidneys have the advantage of not requiring vascular anastomosis and are less likely to be rejected compared to adult pig kidneys. Currently, we are advancing nonhuman primate studies aimed at clinical trials of pig fetal kidney transplant therapy for fetuses diagnosed with Potter syndrome, characterized by bilateral kidney agenesis. We sincerely hope that xenotransplantation will soon become a viable treatment option for adult, pediatric, and fetal patients with kidney failure.

Background: The 2023 IPNA guidelines recommended a 12-h mycophenolic acid (MPA) area under the curve (AUC) estimation for managing pediatric nephrotic syndrome and MPA AUC > 50 mg * h/L for an optimal therapeutic response to mycophenolate mofetil (MMF). The IPNA guidelines endorsed two limited AUC formulae based on three-point MPA measurements to predict 12-h MPA AUC. The relative performance of these two limited AUC formulae has not been tested.

Methods: We analyzed 156 MPA AUCs from 122 stable kidney transplant recipients to predict the 12-h AUC (10 MPA measurements analyzed with trapezoid rule) using the IPNA-recommended three-point Formula 1 and Formula 2.

Results: Three-point Formula 1 and Formula 2 classified 69% and 60% limited MPA AUCs as > 50 mg * h/L (difference 8.90%, p = 0.10). Three-point Formula 1 and Formula 2 demonstrated a similar association with 12-h AUC (R² 0.72 vs. 0.71) and exhibited identical areas under ROC (AUROC) for predicting 12-h AUC > 50 mg * h/L (AUROC 0.82, 95% CI 0.75, 0.88 vs. 0.80, 95% CI 0.73, 0.86; p = 0.53). Fixed MMF dose and MPA C0 level showed a relatively weaker association (R² 0.16 and 0.43) with 12-h AUC. Four-point MPA formulae improved the prediction of 12-h AUC compared to the three-point formulae. Among all C0 thresholds, C0 > 3.5 mg/L demonstrated the best prediction of 12-h AUC > 50 mg * h/L (AUROC 0.74, 95% CI 0.66, 0.80).

Conclusions: IPNA recommended limited AUC formulae perform equivalently and improve upon MMF dose and C0 level to predict 12-h MPA AUC.

This case report presents a newborn with pyruvate dehydrogenase complex deficiency who developed significant lactic acidosis and acute kidney injury after birth. Peritoneal dialysis with glucose-based peritoneal dialysis fluid was initially started, but the patient had worsening hyperglycemia and lactic acidosis, likely related to excess glucose reabsorption with shunting to lactate due to the underlying metabolic disorder. As amino acid-based dialysis solution was not available in our formulary, a dialysis fluid was manually created with Vaminolact, which was commonly used in neonatal parenteral nutrition. Switching to the new dialysis fluid led to significant biochemical improvement.

Acute kidney injury (AKI) in paediatric kidney transplant recipients is common. Infection including urinary tract infection (UTI) and rejection are the most common causes in children. Surgical complications often cause AKI early post-transplant, whereas BK polyomavirus nephropathy rarely occurs in the first month post-transplant. Understanding kidney physiology helps to appreciate the sensitivity of the allograft to AKI, more so than native kidneys. Although the cause of AKI is often multi-factorial, there may be an underlying process that is treatable. Eliciting the aetiology, in this regard, is of paramount importance. Pre-renal and post-renal causes of allograft dysfunction are important to distinguish from intrinsic kidney disease. Clinical information and examination of fluid balance, urine dipstick testing, blood tests, bladder and kidney transplant ultrasound, and kidney transplant biopsy remain vital assessment tools in narrowing the differential diagnosis. A careful prescribed and recreational drug history is always warranted as many drugs including supplements are nephrotoxic. Additional causes such as allograft rejection, recurrent disease, and calcineurin inhibitor toxicity need to be considered in cases of allograft dysfunction, which would not affect the native kidneys. Early detection and assessment of AKI is crucial in promoting recovery. Significant progress has been made in specific pathologies over the last 20 years, which has improved kidney allograft survival rates considerably. Research into identifying AKI biomarkers to assist early diagnosis, before the serum creatinine rises, is ongoing.