A broad clinical spectrum of PLCε1-related kidney disease and intrafamilial variability.

BACKGROUND: The phenotypic and genotypic spectrum and kidney outcome of PLCε1-related kidney disease are not well known. We attempted to study 25 genetically confirmed cases of PLCε1-related kidney disease from 11 centers to expand the clinical spectrum and to determine the relationship between phenotypic and genotypic features, kidney outcome, and the impact of treatment on outcome. METHODS: Data regarding demographics, clinical and laboratory characteristics, histopathological and genetic test results, and treatments were evaluated retrospectively. RESULTS: Of 25 patients, 36% presented with isolated proteinuria, 28% with nephrotic syndrome, and 36% with chronic kidney disease stage 5. Twenty patients underwent kidney biopsy, 13 (65%) showed focal segmental glomerulosclerosis (FSGS), and 7 (35%) showed diffuse mesangial sclerosis (DMS). Of the mutations identified, 80% had non-missense, and 20% had missense; ten were novel. No clear genotype-phenotype correlation was observed; however, significant intrafamilial variations were observed in three families. Patients with isolated proteinuria had significantly better kidney survival than patients with nephrotic syndrome at onset (p = 0.0004). Patients with FSGS had significantly better kidney survival than patients with DMS (p = 0.007). Patients who presented with nephrotic syndrome did not respond to any immunosuppressive therapy; however, 4/9 children who presented with isolated proteinuria showed a decrease in proteinuria with steroids and/or calcineurin inhibitors. CONCLUSION: PLCε1-related kidney disease may occur in a wide clinical spectrum, and genetic variations are not associated with clinical presentation or disease course. However, clinical presentation and histopathology appear to be important determinants for prognosis. Immunosuppressive medications in addition to angiotensin-converting enzyme inhibitors may be beneficial for selected patients. "A higher resolution version of the Graphical abstract is available as Supplementary information".

Renal tubular function and urinary N-acetyl-ß-d-glucosaminidase and kidney injury molecule-1 levels in asthmatic children.

BACKGROUND: Asthma is a chronic inflammatory disorder of the airways which results in chronic hypoxia. Chronic hypoxia and inflammation can affect renal tubular function. OBJECTIVES: The aim of this study was to investigate renal tubular function and early kidney injury molecules such as urinary N-acetyl-betaglucosaminidase (NAG) and kidney injury molecule-1 (KIM-1) excretion in children with asthma. METHODS: Enrolled in the study were 73 children diagnosed with asthma and 65 healthy age- and gender-matched control subjects. Urine pH, sodium, phosphorus, potassium, microalbumin, creatinine, NAG, KIM-1, and serum creatinine, sodium, phosphorus were evaluated. The diagnosis of asthma and classification of mild or moderate were done according to the Global Initiative for Asthma guidelines. RESULTS: Serum sodium, phosphorus, creatinine, and urinary microalbumin were within normal levels in the both groups. Urinary pH, sodium, potassium, phosphorus, microalbumin, and KIM-1 excretions were similar between the control and study groups. Tubular phosphorus reabsorption was within normal limits in two groups. Urine NAG was elevated in the study group (P = 0.001). Urinary KIM-1 and NAG levels were positively correlated (r = 0.837; P = 0.001). When children with mild and moderate asthma were compared, all of the parameters were similar (P >0.05). CONCLUSIONS: This study showed that chronic asthma can lead to subtle renal impacts. We suggest that in children with asthma, urinary NAG level is a more valuable parameter to show degree of renal tubular injury than markers such as microalbumin and KIM-1. Chronic hypoxy and inflammation probably contributes to these subclinical renal effects.