Targeted Audiological Surveillance Program in Campania, Italy

To identify children with postnatal hearing loss, a structured monitoring system is needed. The goal of this study was to describe a targeted surveillance program in Italy to identify children with postnatal hearing loss

Occurrence of ischemic nephropathy in patients with atherosclerotic lesions. Retrospective Study

NTRODUCTION AND AIMS Ischemic renal disease (IRD) is caused by hemodynamically significant mono or bilateral renal artery stenosis. IRD is responsible for reduction of glomerular filtration rate (GFR) and/or loss of renal parenchyma. Clinical features can be renovascular hypertension and ischemic nephropathy. The exact prevalence of IRD is not well known since it is often asymptomatic. Therefore few patients are screened for IRD unless they become symptomatic. Ischemic nephropathy prevalence are based on autopsies and angiographic studies in patients with renovascular hypertension or atherosclerotic disease. This study aimed at assessing the prevalence of IRD, defining its clinic characteristics, evaluating useful imaging procedures in a cohort of patients with chronic kidney disease not in dialysis (CKD) and atherosclerotic lesions. METHODS 1607 CKD patients were retrospectively evaluated during the period 2008-2013 referred to the “Federico II” Department of Nephrology, Naples. Inclusion criteria were: CKD ( I - V KDOQI stages), presence of atherosclerotic lesions anywhere in arterial tree. Kidney transplant recipients and patients with chronic kidney disease requiring dialysis were excluded. Clinical characteristics ( age, sex, blood pressure, body weight, BMI, height), medical history ( previous cardiovascular events, history of familiar cardiovascular events,diabetes mellitus, hypertension ),data of imaging procedures ( angio-TC, angio- RM, color doppler ultrasound (US), renal scintigraphy, angiography, coronarography ) were collected. RESULTS 1 284 patients fulfilled inclusion criteria. Clinical characteristics are reported in Fig 1. Causes of CKD in the study cohort were: hypertension (16,9%), diabetes mellitus (13%), glomerulonephritis (10.9%), interstitial nephritis (3.2%), kidney stones (2.5%), polycystic kidney disease (1.8%),unknown (40%) . IRD prevalence was 11,3 %. The main imaging procedure used to detect renal artery stenosis was color-doppler US (71,9%) in IRD. Other imaging procedures were: angio TC (32%), renal scintigraphy (31%), renal angiography (15%), angio RM (12%). Compared to others, patients with IRD had higher prevalence of history of cardiovascular events in family (46.9% Vs 33.7%) (NS), dyslipidemia (84.4% vs 69%) (NS) and previous cardiovascular events (53.1% vs 32.1%) (NS) . CONCLUSIONS The present study shows that the IRD is frequently misdiagnosed. More careful evaluation should be performed among patients with not well defined cause of CKD and concomitant presence of atherosclerotic lesions on arterial tree. Color-doppler US is the most useful imaging procedure to identify IRD

Clinical and Genetic Characterization of Patients with Bartter and Gitelman Syndrome

Bartter (BS) and Gitelman (GS) syndrome are autosomal recessive inherited tubulopathies, whose clinical diagnosis can be challenging, due to rarity and phenotypic overlap. Genotype–phenotype correlations have important implications in defining kidney and global outcomes. The aim of our study was to assess the diagnostic rate of whole-exome sequencing (WES) coupled with a bioinformatic analysis of copy number variations in a population of 63 patients with BS and GS from a single institution, and to explore genotype-phenotype correlations. We obtained a diagnostic yield of 86% (54/63 patients), allowing disease reclassification in about 14% of patients. Although some clinical and laboratory features were more commonly reported in patients with BS or GS, a significant overlap does exist, and age at onset, preterm birth, gestational age and nephro-calcinosis are frequently misleading. Finally, chronic kidney disease (CKD) occurs in about 30% of patients with BS or GS, suggesting that the long-term prognosis can be unfavorable. In our cohort the features associated with CKD were lower gestational age at birth and a molecular diagnosis of BS, especially BS type 1. The results of our study demonstrate that WES is useful in dealing with the phenotypic heterogeneity of these disorders, improving differential diagnosis and genotype-phenotype correlation

Pediatr Nephrol

BACKGROUND: Associations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT. METHODS: We included patients  1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates. RESULTS: We included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78-0.86), tall (aHR: 0.65, 95% CI: 0.56-0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71-0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92-2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38-2.23) and obese (aHR: 1.49, 95% CI: 1.11-1.99) patients showed higher all-cause mortality risk than normal weight subjects. CONCLUSIONS: Short and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients. A higher resolution version of the Graphical abstract is available as Supplementary information

Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria

The recent Chandos House meeting of the Alport Variant Collaborative extended the indications for screening for pathogenic variants in the COL4A5, COL4A3 and COL4A4 genes beyond the classical Alport phenotype (haematuria, renal failure; family history of haematuria or renal failure) to include persistent proteinuria, steroid-resistant nephrotic syndrome, focal and segmental glomerulosclerosis (FSGS), familial IgA glomerulonephritis and end-stage kidney failure without an obvious cause. The meeting refined the ACMG criteria for variant assessment for the Alport genes (COL4A3-5). It identified 'mutational hotspots' (PM1) in the collagen IV α5, α3 and α4 chains including position 1 Glycine residues in the Gly-X-Y repeats in the intermediate collagenous domains; and Cysteine residues in the carboxy non-collagenous domain (PP3). It considered that 'well-established' functional assays (PS3, BS3) were still mainly research tools but sequencing and minigene assays were commonly used to confirm splicing variants. It was not possible to define the Minor Allele Frequency (MAF) threshold above which variants were considered Benign (BA1, BS1), because of the different modes of inheritances of Alport syndrome, and the occurrence of hypomorphic variants (often Glycine adjacent to a non-collagenous interruption) and local founder effects. Heterozygous COL4A3 and COL4A4 variants were common 'incidental' findings also present in normal reference databases. The recognition and interpretation of hypomorphic variants in the COL4A3-COL4A5 genes remains a challenge

Guidelines for Genetic Testing and Management of Alport Syndrome

Genetic testing for pathogenic COL4A3–5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic COL4A3 or COL4A4 is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that COL4A3 or COL4A4 heterozygotes do not act as kidney donors. Testing for variants in the COL4A3–COL4A5 genes should also be performed for persistent proteinuria and steroid-resistant nephrotic syndrome due to suspected inherited FSGS and for familial IgA glomerulonephritis and kidney failure of unknown cause