Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease.

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.

Hepatic lymphangiomatosis mimicking polycystic liver disease.

Hepatic lymphangiomatosis is a rare disorder characterized by cystic dilatation of the lymphatic vessels in the hepatic parenchyma. It can occur in the liver alone, in the liver and spleen, or in multiple organs. Clinically, diagnosis can be difficult because of the rarity and protean manifestations of this disorder. We describe a 53-year-old woman with hepatic lymphangiomatosis in whom polycystic liver disease had been previously diagnosed. In addition, we review 12 cases of hepatic, splenic, and hepatosplenic lymphangiomatosis with or without systemic lymphangiomatosis and discuss the differential diagnosis.

Improved biochemical variables, nutrient intake, and hormonal factors in slow nocturnal hemodialysis: a pilot study.

OBJECTIVE: To determine whether slow nocturnal hemodialysis (SNHD) can be safely performed in patients with end-stage renal disease to improve the biochemical and clinical outcome. MATERIAL AND METHODS: We conducted an 8-week pilot study in nondiabetic adult patients, who underwent dialysis 6 nights per week for 8 hours each night. A dialysate flow rate of 300 mL/min and a blood flow rate of 250 mL/min, through an internal jugular dual-lumen venous catheter, were used. The equipment used was a COBE Centry System 3 dialysis machine and Fresenius F-80 (1.8 m2) or Baxter CT 190 (1.9 m2) dialyzers. Five patients were enrolled in the study. RESULTS: Two patients did not complete the study because of catheter-related infections--one at day 7 and one after 4 weeks of SNHD. All patients had improved blood pressure control, and no intradialytic adverse events occurred. Dietary intake improved, urea and creatinine levels significantly decreased, and weekly delivery of dialysate increased on SNHD. Potassium, chloride, beta 2-microglobulin, phosphorus, calcium, and high-density lipoprotein cholesterol all improved on SNHD. Serum testosterone increased in the three men on SNHD, but parathyroid hormone, luteinizing hormone, and follicle-stimulating hormone remained unchanged. Erythropoietin levels increased on SNHD, despite no change in exogenous erythropoietin doses in three patients and discontinuation of administration of erythropoietin in one. The following biochemical factors did not change significantly: serum sodium, bicarbonate, vitamin B12, folate, alkaline phosphatase, total cholesterol, triglycerides, and albumin. CONCLUSION: Higher doses of hemodialysis benefit nutrition, improve biochemical variables, and may improve many hormonal systems.

Biochemical recovery and purification of gene therapy vectors.

Rapid progress has been made with the molecular design of novel viral and non-viral gene therapy vectors. Exploiting upstream processes of producer cell-culture and downstream operations adapted from protein recovery, vectors have been accumulated in quantities and purities appropriate for the initiation of clinical trials. It is not clear, however, if such methodologies will be appropriate for efficient operation at the manufacturing scales required for clinically successful vectors. Technologies suited to the fractionation of nanoparticles may bypass practical bottlenecks experienced by current processes. The behaviour in such fractionation systems of natural and synthetic particles, which variously mimic the size, density and surface chemistry of vector products, could benefit the improved design of efficient manufacture for gene therapy vectors.

Expression of polycystin in mouse metanephros and extra-metanephric tissues.

The presence of messenger RNA for the mouse homologue of the polycystic kidney disease 1 gene (PKD1) was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) methods in mouse embryo messenger RNA. A single locus for the PKD1 gene was detected on mouse chromosome 17 by fluorescent in situ hybridization. Immunoprecipitation of proteins from [35S] methionine-labeled mouse metanephric explants with an anti-polycystin antibody (Pc1) revealed high molecular weight bands, the highest being > 400 kDa. Immunoperoxidase staining of mouse embryos with Pc1 revealed expression of polycystin as early as day 8 gestation. The expression was seen in epithelial cells of the ureteric bud, in condensing blastemal cells of the developing metanephros and, subsequently, in cells of the nascent tubules. In addition, Pc1 immunoreactivity was seen in hepatocytes and biliary epithelium, cardiac and skeletal muscle, neural tissue, gut, and bronchial epithelium. In post-natal and adult mouse kidney and liver persistent slight to moderate immunoreactivity was observed. Immunofluorescent studies of cultured 13-day mouse metanephroi revealed polycystin expression in ureteric bud epithelium, early glomerular structures (that is, condensates, S-shaped and comma-shaped bodies) and in proximal and distal tubular epithelia. These data indicate that the mouse has a single gene homologous to human PKD1 on chromosome 17, and polycystin is expressed in a variety of tissues during embryonic development.