Novel mutations in NPHP4 in a consanguineous family with histological findings of focal segmental glomerulosclerosis.

Nephronophthisis is a form of autosomal recessive hereditary cystic kidney disease that typically progresses to end-stage renal disease by early adulthood. Conversely, focal segmental glomerulosclerosis is a histological glomerular phenotype that can be familial, primary (idiopathic), or secondary to a multitude of pathological processes affecting the kidney, including such tubulointerstitial diseases as nephronophthisis. Mutations in 6 distinct nephronophthisis genes have been described to date. We describe a consanguineous Filipino family with 2 novel sequence variants in the NPHP4 gene. Affected individuals presented with end-stage renal disease and histological features of focal segmental glomerulosclerosis on biopsy. They also had atypical radiological findings, making the clinical diagnosis of the genetic syndrome difficult. Furthermore, although ocular abnormalities and hearing loss were described previously, this is the first report of hepatic disease in patients with mutations in NPHP4. The diagnosis of nephronophthisis was made by means of mutational analysis of the NPHP4 gene after isolation of a region of homozygosity in affected individuals by using whole-genome single-nucleotide polymorphism analysis. Because establishment of the correct diagnosis has implications for therapeutic interventions, prognosis, and, in the case of heritable diseases, appropriate genetic counseling for affected individuals and their families, this report emphasizes the importance of obtaining meticulous clinical information, considering alternative diagnoses, and, when possible, performing genetic evaluation to confirm the diagnosis. We outline an approach to patients with hereditary kidney disease, focusing specifically on the molecular genetic techniques available to evaluate such families and determine a chromosomal region of interest and, subsequently, the diagnosis.

Infective Endocarditis in Patients with Kidney Failure: Chronic Dialysis and Kidney Transplant.

Physicians who treat patients with infective endocarditis (IE) are encountering a growing number of dialysis and kidney transplant patients. Both groups have 30 to 100 times higher risk of IE, with 1-year mortalities of 40% to 60%. The predominant organisms causing IE are gram positive, with 60% to 80% of cases due to Staphylococcus aureus, and another 10% to 20% of cases due to coagulase-negative staphylococci. Renal transplant patients may develop fungal IE, but this risk is primarily in the first 3 months after transplant. In addition to blood cultures, transesophageal echocardiogram is the most useful diagnostic examination for IE in these patients. Initial antibiotic therapy, pending final culture and antibiotic susceptibility results, should provide coverage against the most common organisms and allow for the potential of either methicillin or vancomycin-resistant species. Removal of infected hemodialysis access devices and at least 4 to 6 weeks of intravenous antibiotics are recommended. Antibiotic prophylaxis against IE has been recommended for all dialysis and renal transplant patients, but this strategy is controversial and unproven.