Detection of human herpesvirus-8 DNA in kidney allografts prior to the development of Kaposi's sarcoma.

Human herpesvirus-8 (HHV-8) DNA was identified in kidney allografts in 2 of 3 transplant recipients prior to the development of Kaposi's sarcoma, and increase in viral antibody titer was found in the third. Combined genotypic and serologic analyses could be used to identify patients at risk and suggest that the kidney may be a site of HHV-8 latency.

Amyloidosis induced, end stage renal disease in patients with familial Mediterranean fever is highly associated with point mutations in the MEFV gene.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of fever and serositis. Amyloidosis is the most significant complication of FMF, leading to end stage renal disease (ESRD). Recently the gene (MEFV) causing this disease was cloned and more than 18 mutations have been identified. The hypothesis that the development of amyloidosis is associated with one of these mutations was tested. METHODS: 23 patients with FMF and ESRD were analysed for their MEFV mutations and correlated with their corresponding rectal and renal biopsies. As case controls 23 patients with FMF free of renal disease, but with similar origin, sex, age, and age at onset of FMF, were chosen. RESULTS: All the patients with ESRD induced by amyloidosis were homozygous for the M694V or M694I mutations. This finding was significantly different from that seen in the control group. CONCLUSIONS: Amyloidosis is highly associated with the 694 substitution in the MEFV gene causing FMF. It seems that genetic predisposition plays a part in the development of this complication of FMF.

Outbreak of bloodstream infections associated with dialysis machine waste ports in a hemodialysis facility.

Eight cases of gram-negative bloodstream infection without a clinically evident source occurred at a hemodialysis unit in Jerusalem between February and September 1997. All infections could be traced to three of the 13 dialysis machines in use. Epidemiological investigation, including pulsed-field gel electrophoretic characterization of organisms isolated from the patients and dialysis machines, implicated the Waste Handling Option system of the machines as the source of the infections. Discontinuation of the Waste Handling Option system use was associated with prompt cessation of the outbreak.

Evidence for interference of vitamin D with PTH/PTHrP receptor expression in opossum kidney cells.

Vitamin D counters the phosphaturic action of parathyroid hormone (PTH) in rats in vivo. The present study was undertaken to examine this interaction using monolayers of Opossum kidney (OK) cells. 32P uptake, cAMP generation, PTH/PTHrP receptor mRNA expression and intracellular Ca2+ [Ca2+]i were measured in (1) control cells, (2) cells exposed to PTH, (3) cells pretreated with 1, 25-dihydroxyvitamin D3 [1,25(OH)2D3], and (4) 1,25(OH)2D3-pretreated cells exposed to PTH. 32P uptakes were in (1) 5.00+/-0.20 (mean +/-SE), in (2) 2.30+/-0.14 (P<0.001 versus group 1), in (3) 4.80+/-0. 24 (P NS versus group 1) and in (4) 3.70+/-0.20 (P<0.001 versus group 2) nmol Pi/(mg.prot 10 mm). cAMP levels were in (1) 10+/-3, in (2) 210+/-8, in (3) 12+/-4, and in (4) 122+/-12 pmol cAMP/mg protein (P<0.001 versus group 2). PTH/PTHrP receptor mRNA expression was in relative units: (1) 100+/-0, (2) 99.5+/-6.2, (3) 68.7+/-2.6 (P<0.001 versus group 1), and (4) 34.8+/-3.3 (P<0.001 versus group 1). In groups 2 and 4 PTH induced equal transient increments in [Ca2+]i. These experiments demonstrate that the effect of vitamin D on phosphate transport is associated with a commensurate diminution in PTH/PTHrP receptor gene expression and PTH-induced cAMP formation but not with Ca2+ transients. Vitamin D per se does not affect 32P uptake or cAMP generation while it slightly decreased PTH/PTHrP receptor gene expression. These observations demonstrate that: (1) 1. 25(OH)2D3 directly antagonizes the effects of PTH on 32P uptake in OK cells, (2) this effect is mediated via inhibition of PTH-induced activation of AC/cAMP system, (3) the diminution in PTH-induced cAMP formation may stem at least in part from a decrease in the expression of PTH/PTHrP receptor mRNA.

Glycerol-induced acute renal failure attenuates subsequent HgCl2-associated nephrotoxicity: correlation of renal function and morphology.

Glycerol induced acute renal failure (ARF) is known to attenuate subsequent mercuric chloride nephrotoxicity. This protection was evaluated in rats. Glycerol induced varying degrees of renal insufficiency. After 14 days, when serum creatinine (SCr) creatinine clearance (CCr) and fractional excretion of sodium (FENa) had returned to baseline, injection of mercuric chloride caused significantly milder renal insufficiency in recovered rats than in controls (SCr 356 +/- 46 vs. 475 +/- 19 mumol/L; CCr 0.12 +/- 0.02 vs. 0.02 +/- 0.02 mL/min, p < .05; and mortality 0 vs. 45%, respectively, p < .01). A striking finding was that the degree of renal insufficiency induced by mercuric chloride correlated inversely with the degree of renal insufficiency previously induced by glycerol (r = -0.496, p < .05 for SCr and CCr), but there was no correlation with other measures of previous renal function such as urine volume, sodium excretion, or FENa. Glycerol induced ARF also attenuated the renal toxicity of mercuric chloride injected 4 days after glycerol, before full recovery of renal function. The decrements in renal function after the two insults were also inversely related (r = -0.76, p < .01). A third renal insult with a second mercuric chloride injection after three weeks was still attenuated. However, after the third insult, there was no longer an inverse or any statistical relationship with previous measurements of renal function. Histopathology revealed a good correlation between peak Scr after glycerol, and percentage of tubules undergoing re-generation 14 days later (r = 0.97, p < .01). There was an inverse correlation between Scr after mercuric chloride (administered 14 days after glycerol) and percentage of tubular regeneration seen two days later (r = -0.79, p < .05). The correlations of SCr and CCr with regeneration was greater than the correlations with tubular necrosis, suggesting that the regenerative process is involved in the protection from repeated renal insults. In conclusion, glycerol-induced ARF attenuates subsequent mercuric chloride renal insult. The attenuation correlates directly with the initial glycerol-induced damage, so that the more severe the initial renal insufficiency, the milder the renal insufficiency following subsequent mercuric chloride. This protection can be seen as early as 4 days and also 14 days after previous renal insult. The degree of renal tubular regeneration correlates well with the protection seen, and probably plays a role in acquired renal resistance to repeated insults.

Comparison of eosinophilia in patients undergoing peritoneal dialysis and hemodialysis.

Eosinophilia (E) has been noted in hemodialysis (HD) patients, but its etiology is not clear. In an effort to clarify this phenomenon, we prospectively studied patients initiating dialysis in our outpatient HD and peritoneal dialysis programs. Rate of E was greatest for a small group of four continuous cycling peritoneal dialysis patients (75%), less for 63 HD patients (41%), and least for 66 continuous ambulatory peritoneal dialysis (CAPD) patients (21%, P less than .05, HD v CAPD). Increasing E rates among the groups paralleled increased frequency of tubing changes. There were no differences in etiology of renal disease, medications, types of dialyzers, types of access, or transfusion frequency that could account for the E. IgE levels did not correlate with E. The data suggest that the dialysis procedure or the tubing changes may be causing the E, but the possibility that uremia, itself, is important in the pathogenesis of dialysis E is also discussed.

Effect of converting enzyme inhibitors on prostaglandin synthesis by isolated glomeruli and aortic strips from rats.

In addition to their effect on angiotensin and bradykinin metabolism, converting enzyme inhibitors (CEI) may also alter prostaglandin (PG) synthesis. We therefore examined two CEI, SQ 14,225 (captopril) and SQ 20,881, for their in vitro effect on PG synthesis by glomeruli and aortic strips from rats. Glomeruli incubated in test tubes produced predominantly PGE2 and PGF2 alpha. Both CEI selectively stimulated PGE2 synthesis with maximal effects at 25 microM. During superfusion of glomeruli with captopril (25 microM) synthesis of PGE2 increased 5- to 10-fold and that of 6-keto-PGF1 alpha doubled. No significant change in PGF2 alpha or thromboxane B2 occurred. This effect of CEI was independent of angiotensin or bradykinin. In contrast captopril had no effect on PG synthesis by aortic strips, which produced predominantly prostacyclin assayed as 6-keto-PGR1 alpha and little PGE2 and PGF2 alpha. These results demonstrate that CEI can directly stimulate PG synthesis in glomeruli. This additional mechanism of action of CEI may require reinterpretation of the role of angiotensin based on results obtained with CEI.