Pediatric Nephrology最新文献

Herein, we review the devastating consequences of the worldwide obesity epidemic on kidney health and outcomes. We submit that the obesity epidemic is the most pressing public health crisis facing the nephrology community today. A historical approach has been undertaken, wherein major breakthroughs in the recognition and understanding of obesity-related kidney disease (ORKD) are highlighted. We begin with a description of the worldwide obesity epidemic followed by an account of the discovery and characterization of ORKD. A detailed summary of the pathophysiology of ORKD disease is presented, wherein we set forth the following two propositions: first, ORKD is due to a maladaptive response to caloric surplus; and second, this maladaptive response causes kidney damage via hemodynamic (hyperfiltration), hormonal (adipokine dysregulation), and lipotoxic pathways. Each of these pathways is described, with particular emphasis on the relatively recent discovery that the final stage of cellular injury in ORKD is mitochondrial oxidative damage. The prevention and treatment of ORKD are then discussed, including environmental, behavioral, pharmacologic, and surgical options. Finally, we conclude with suggestions for future research to improve early recognition and treatment of ORKD.

PDSS1 mutations hamper Coenzyme Q10 biosynthesis and cause a rare multisystem mitochondrial disease characterized by diverse clinical features and limited treatment options. To date, renal involvement has been reported in only one patient. We report a new female patient with compound heterozygous PDSS1 mutations and the clinical outcome following a trial of Coenzyme Q10 therapy. Our patient presented with developmental delay and regression at age three, which progressed to steroid-resistant nephrotic syndrome at age six, leading to stage 5 chronic kidney disease. Whole exome sequencing identified two pathogenic variants in the PDSS1 gene. High doses of Coenzyme Q10 therapy had no effect at this advanced stage of disease. Coenzyme Q10 treatment did not appear to improve the clinical outcome in this patient. Further data is needed to better understand the phenotypic spectrum of PDSS1-associated disruption, and the potential benefit of early Coenzyme Q10 therapy.

Milky white urine is most commonly due to chyluria secondary to filariasis, though other causes of milky white urine and other etiologies of chyluria must be considered. Evaluation of a 3-year-old girl with milky white urine demonstrated chyluria, but testing for filariasis was negative despite a history of travel to an endemic region. Magnetic resonance lymphangiography demonstrated a congenital lymphatic malformation, which was repaired following this minimally invasive imaging technique.

Background: Anthropogenic vanadium (V) emissions and exposure in the general population have recently increased. Experimental studies have shown that V is a nephrotoxic agent, but little is known about its effects on human kidney health. This work evaluated the association between urinary V concentrations with early kidney damage biomarkers and function in a pediatric population without any disease diagnosed.

Methods: A cross-sectional study was carried out and included 914 healthy subjects and determined urinary V concentrations, glomerular filtration rate (eGFR), albumin-creatinine ratio (ACR), and the presence of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in urine. We evaluated the V effect using linear and logistic regression models adjusted by confounders.

Results: Subjects found in the second and third tertiles of V showed an increase in urinary log-NGAL levels (βT2 vs. T1 = 0.39; 95% CI 0.14, 0.64, and βT3 vs. T1 = 1.04; 95% CI 0.75, 1.34) and log-KIM-1(βT2 vs. T1 = 0.25; 95% CI 0.04, 0.45 and βT3 vs. T1 = 0.39; 95% CI 0.15, 0.63); in addition, subjects in the third tertile had a positive and significant association with ACR (ORT3 vs. T1 = 1.96; 95% CI 1.29, 2.97) and increased in eGFR (βT3 vs. T1 = 3.98, 95% CI 0.39, 7.58), compared with subjects in the first tertile.

Conclusions: Our study reports the effect of V on kidney markers in a healthy pediatric population. It could be related to tubulointerstitial lesions and function abnormalities.

Three-weekly 4-h hemodialysis/hemodiafiltration (HD/HDF) per week has become the "standard HD/HDF" regimen in children across the globe, although increasingly criticized, since crucial determinants such as residual kidney function and patient preferences are not considered. As a consequence, several children fail to achieve adequate dialysis while on a "standard HD/HDF." In these circumstances, an extended dialysis prescription such as short daily (2-3 h/session, 5-7 days a week) or nocturnal HD/HDF (6-9 h/session, 3-5 days a week), either at home or in a dialysis center, may be considered. The purpose of this educational review is to summarize the impact of dialysis duration and frequency on uremic toxin and fluid removal. Moreover, we aim to summarize the existing literature on HD/HDF strategies with extended dialysis duration and/or increased frequency (> 12 h dialysis time per week) in pediatrics. Dialysis duration and frequency plays a crucial role in uremic toxin removal, in particular for uremic toxins with retarded transport in patients, such as phosphate, β₂-microglobulin (β₂m), and protein-bound uremic toxins. Also, increasing dialysis duration and/or frequency decreases the gap between plasma refilling and ultrafiltration volume), thereby decreasing the need for a high ultrafiltration rate. Observational studies in children demonstrate a beneficial effect of extended dialysis regimens (i.e., more frequent or longer duration) on blood pressure control, left ventricular hypertrophy, growth, and quality of life. PTH levels tend to decrease in the majority of studies, while hypocalcemia or suppressed PTH levels were also reported. Dietary restrictions were decreased or stopped, along with tapering of phosphate binders and potassium chelators. Extended HD/HDF regimens are beneficial in a particular group of children. Pediatric-specific international guidelines are needed to support pediatric nephrologists in determining for which children extended HD regimens are beneficial, along with increasing efforts to decrease the financial, organizational, and psychosocial barriers that are present in extended HD/HDF.

Chyloperitoneum is an uncommon diagnosis in peritoneal dialysis (PD) patients. While admitted for emesis and feeding intolerance, a 16-month-old male on PD developed milky-colored dialysate with increased triglycerides, indicating chyloperitoneum. In adult PD patients, chyloperitoneum can indicate potentially life-threatening pathologies including malignancies and liver or heart disease. By contrast, pediatric patients on PD with chyloperitoneum had recently undergone PD catheter or gastrostomy tube placement with presumed disruption of abdominal lymphatics. Slowing lymph flow through dietary manipulation and rarely, temporary withholding of PD, resolved chyloperitoneum. We report a toddler on PD with chyloperitoneum in whom abdominal investigation showed multifocal hepatoblastoma. Chemotherapy and a medium chain triglycerides (MCTs)-based diet led to prompt resolution of chyloperitoneum. Intrabdominal malignancy in this patient illustrates the importance of a prompt, thorough evaluation of chyloperitoneum to allow definitive therapy if required.

A 3-month-old girl presented with symptoms indicative of dysuria, gross hematuria, chronic diarrhea, and nephrocalcinosis. She was born to fourth-degree consanguineous parents. The infant exhibited hypercalciuria and hyperoxaluria, and her stool tested positive for reducing sugars. She responded positively to dietary lactose restriction, and her hyperoxaluria improved over the course of 3 months. This suggests an enteric hyperoxaluria phenotype, although her hypercalciuria persisted. Whole exome sequencing identified a homozygous variant in the LCT gene, which is associated with congenital lactase deficiency, as well as a heterozygous variant in the ADCY10 gene, which is linked to absorptive hypercalciuria.

Background: Aripiprazole-associated hypertension is a previously described side effect, but its mechanism has not been clearly elucidated. Here we present a 16-year-old male patient who developed aripiprazole-associated hypertension, and we discuss the mechanisms that may cause hypertension.

Case diagnosis: Antipsychotic drugs are beneficial for the control of mental health conditions. In this report, we present a case of a patient who developed hypertension after using aripiprazole. A 16-year-old male patient was admitted with headache and high blood pressure. In the examinations conducted for etiology, the aldosterone/plasma renin activity (PRA) was found to be high, but in follow-up, hypertension regressed and aldosterone/PRA were detected normal. The patient was questioned again in terms of medical history. It was learned that the patient was initiated on aripiprazole, and hypertension developed after the drug. The aldosterone/PRA was studied 15 days after he stopped the drug. In this patient, hypertension and hyperaldosteronism were associated with aripiprazole.

Background: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy. Genetic defects in the alternative complement (AP) pathway have been identified in 60-70% of individuals. Eculizumab is recommended as a first-line therapy.

Methods: We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed.

Results: A 15-year-old Chinese girl was diagnosed with aHUS at 3.7 years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8 months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8 ml/min/1.73 m². A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant.

Conclusions: Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure.