Peritoneal ultrafiltration in refractory heart failure: a cohort study.

INTRODUCTION: Acutely decompensated heart failure (HF) in patients with diuretic resistance is often treated with extracorporeal ultrafiltration. Peritoneal ultrafiltration (PUF) has been proposed for the long-term management of severe HF after resolution of the acute episode. The aim of the present study was to evaluate the use of PUF in the treatment of chronic refractory HF in patients without end-stage renal disease. ♢ METHODS: This multicenter (10 nephrology departments throughout Italy) retrospective observational study included patients with severe HF refractory to maximized drug treatment. The patients were proposed for PUF because they had experienced at least 3 hospital admissions in the preceding year for acutely decompensated HF requiring extracorporeal ultrafiltration. ♢ RESULTS: Of the 48 study patients (39 men, 9 women; mean age 74 ± 9 years), 30 received 1 nocturnal icodextrin exchange, 5 required 2 daily exchanges, and 13 received 2 - 4 sessions per week of automated peritoneal dialysis. During the first year, renal function remained stable (initial: 20.8 ± 10.0 mL/min/1.73 m(2); end: 22.0 ± 13.6 mL/min/1.73 m(2)), while pulmonary artery systolic pressure declined to 40 ± 6.09 mmHg from 45.5 ± 9.18 mmHg (p = 0.03), with a significant concomitant improvement in New York Heart Association functional status. Hospitalizations decreased to 11 ± 17 days/patient-year from 43 ± 33 days/patient-year before the start of PUF (p < 0.001). The incidence of peritonitis was 1 episode in 45 patient-months. Patient survival was 85% at 1 year and 56% at 2 years. ♢ CONCLUSIONS: This study confirms the satisfactory results of using PUF for chronic HF in elderly patients.

COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome.

UNLABELLED: COL4A3/COL4A4 mutations: From familial hematuria to autosomal-dominant or recessive Alport syndrome. BACKGROUND: Mutations of the type IV collagen COL4A5 gene cause X-linked Alport syndrome (ATS). Mutations of COL4A3 and COL4A4 have been reported both in autosomal-recessive and autosomal-dominant ATS, as well as in benign familial hematuria (BFH). In the latter conditions, however, clinical features are less defined, few mutations have been reported, and other genes and non-genetic factors may be involved. METHODS: We analyzed 36 ATS patients for COL4A3 and COL4A4 mutations by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing. Sporadic patients who had tested negative for COL4A5 mutations were included with typical cases of autosomal recessive ATS to secure a better definition of the phenotype spectrum. RESULTS: We identified seven previously undescribed COL4A3 mutations: in two genetic compounds and three heterozygotes, and one in COL4A4. In agreement with the literature, some of the mutations of compound heterozygotes were associated with microhematuria in healthy heterozygous relatives. The mutations of heterozygous patients are likely dominant, since no change was identified in the second allele even by sequencing, and they are predicted to result in shortened or abnormal chains with a possible dominant-negative effect. In addition, both genes showed rare variants of unclear pathogenicity, and common polymorphisms that are shared in part with other populations. CONCLUSIONS: This study extends the mutation spectrum of COL4A3 and COL4A4 genes, and suggests a possible relationship between production of abnormal COL IV chains and dominant expression of a continuous spectrum of phenotypes, from ATS to BFH.