Familial collapsing focal segmental glomerulosclerosis.

The majority of patients with non-HIV-related collapsing focal segmental glomerular sclerosis (FSGS) have idiopathic disease. Only a few genetic forms associated with rare syndromes have been described in families. Here we report two families with multiple members who have collapsing FSGS with no clear associated secondary etiology. Genetic analysis revealed a defect in the TRPC6 gene in one family, but excluded all known common inherited podocyte defects in the other family. The course and response to treatment differed dramatically among members of the same family.

Induction of creatininase activity in chronic renal failure: timing of creatinine degradation and effect of antibiotics.

Creatinine degradation was prospectively studied in four healthy subjects and 35 patients with varying degrees of chronic renal failure by measuring creatininase activity in stool isolates. Patients were subdivided into those with serum creatinine above and below 6 mg/dL. Creatinine degradation in the former group of patients who had not taken antibiotics in the previous 3 months was significantly greater than the latter (64% v 26%; P < 0.001), which was similar to healthy controls. This degradation was abolished when antibiotics were added directly to the patient's stool during incubation (P < 0.002). In a subset of five patients, duodenal intubation demonstrated small bowel bacterial overgrowth associated with high concentrations of toxic methylamines generated there from and increased stool creatinine consumption. We conclude that retained creatinine in advanced chronic renal failure induces bacterial creatininase activity throughout the bowel, causing creatinine degradation and subsequent potential loss of creatinine to the creatinine pool. The modifying effects of antibiotics on creatinine degradation has important clinical implications for the interpretation of serum creatinine measurements in renal failure.

Disseminated histoplasmosis presenting as urinary tract obstruction in a renal transplant recipient.

Disseminated histoplasmosis occasionally involves the kidney, but the infection usually does not cause either urinary symptoms or a decrease in renal function. We present a case of disseminated histoplasmosis in a renal transplant recipient who presented with urinary obstruction in the allograft from a sloughed renal papilla infected with the fungus. At the same time the patient had chronic meningitis from Histoplasma capsulatum. The literature on renal involvement with histoplasmosis is reviewed.

ATP-inhibitable Cl- channel in apical membranes of cultured rabbit cortical collecting duct cells.

Excised patches of apical membranes from immunodissected rabbit cortical collecting duct cells in primary culture were studied by the patch-clamp technique. Barium (1 mM) and tetraethylammonium chloride (5 mM) were added to all solutions to block potassium channel activity. A unique channel was observed that exhibited inward rectification under symmetrical ionic conditions with a measured chord conductance of 54.0 +/- 2.5 pS at -80 mV (n = 11) and 22.1 +/- 1.7 pS at +80 mV (n = 5). This channel was chloride selective, with a PNa:PCl of 0.16 (n = 3). Kinetic analysis revealed a voltage-independent open-time probability of 0.80 +/- 0.07 (n = 6). Open-time probability within bursts was 0.96 +/- 0.01. Addition of ATP to the cytosolic surface of the channel resulted in a dose-dependent decrease in open probability, with a threshold effect at 10(-4) M, due to a reduction in burst open time. The effect of ATP was immediate, rapidly reversible at room temperature, and mimicked by GTP, adenosine 5'-O-(3-thiotriphosphate), and guanosine 5'-O-(3-thiotriphosphate). This channel may link epithelial chloride permeability to cellular ATP content in the rabbit cortical collecting duct.

Immunosuppressive drugs and their effects.

The growing success of organ transplantation for the treatment of diabetes mellitus and end-stage renal, heart, lung, and liver disease is attributable, in part, to improvements in immunosuppressive regimens. This article reviews the immune response and the mechanism by which many immunosuppressants exert their effects. Immunosuppressants discussed include azathioprine, glucocorticoids, cyclosporine A, cyclosporine G, FK506, rapamycin, mycophenolic acid, mycophenolate mofetil (RS-61443), mizoribine (bredinin), brequinar sodium, and deoxyspergualine. The efficacy and nonspecificity of these agents has led to significant side effects from their use, which can be predicted based on their mechanisms of action. The development and use of more specific immunosuppressants or the design of protocols, which would induce organ tolerance, may result in long-term organ survival without infectious or malignant complications.

Severe arteriosclerosis in the kidney of a cocaine addict.

Cocaine abuse has been associated with sudden cardiac death with coronary artery thrombosis with or without underlying vessel disease. Additional vascular beds thus far implicated in cocaine-associated arteriopathy include thoracic and abdominal aorta, and pulmonary, cerebral, and placental vessels; abnormalities include vasospasm, thrombosis, and accelerated atherosclerosis. We report the case of an adult male cocaine user with severe arteriosclerosis of renal vessels, and suggest that cocaine may also affect the renal vasculature.