Factors associated with poor outcomes in patients with lupus nephritis.

The objective of this study was to identify the factors associated with important clinical outcomes in a case-control study of 213 patients with lupus nephritis. Included were 47% Hispanics, 44% African Americans and 9% Caucasians with a mean age of 28 years. Fifty-four (25%) patients reached the primary composite outcome of doubling serum creatinine, end-stage renal disease or death during a mean follow-up of 37 months. Thirty-four percent African Americans, 20% Hispanics and 10% Caucasians reached the primary composite outcome (P < 0.05). Patients reaching the composite outcome had predominantly proliferative lupus nephritis (WHO classes: 30% III, 32% IV, 18% V and 5% II, P < 0.025) with higher activity index score (7 +/- 6 versus 5 +/- 5, P < 0.05), chronicity index (CI) score (4 +/- 3 versus 2 +/- 2 unit, P < 0.025), higher baseline mean arterial pressure (MAP) (111 +/- 21 versus 102 +/- 14 mmHg, P < 0.025) and serum creatinine (1.9 +/- 1.3 versus 1.3 +/- 1.0 mg/dL, P < 0.025), but lower baseline hematocrit (29 +/- 6 versus 31 + 5%, P < 0.025) and complement C3 (54 +/- 26 versus 65 + 33 mg/dL, P < 0.025) compared to controls. More patients reaching the composite outcome had nephrotic range proteinuria compared to controls (74% versus 56%, P < 0.025). By multivariate analysis, CI (hazard ratio [95% CI] 1.18 [1.07-1.30] per point), MAP (HR 1.02 [1.00-1.03] per mmHg), and baseline serum creatinine (HR 1.26 [1.04-1.54] per mg/dL) were independently associated with the composite outcome. We concluded that hypertension and elevated serum creatinine at the time of the kidney biopsy as well as a high CI are associated with an increased the risk for chronic renal failure or death in patients with lupus nephritis.

Detection of anti-hepatitis C virus antibodies in patients undergoing dialysis by utilizing a hepatitis C virus 3.0 assay: correlation with hepatitis C virus RNA.

Hepatitis C virus (HCV) infection is endemic in long-term dialysis units. We assessed the performance of a recently developed HCV 3.0 assay for the detection of HCV antibodies in patients undergoing dialysis. The study evaluated 128 patients undergoing long-term maintenance hemodialysis. Anti-HCV was detected by 2.0 and 3.0 enzyme immunoassay (EIA). Results were confirmed with recombinant immunoblot assays (RIBA 2.0 and RIBA 3.0). HCV RNA was detected by using reverse transcriptase-polymerase chain reaction (RT-PCR). Thirty-two patients (25%) were HCV EIA 2.0 positive. Of these, 1 was RIBA 2.0 negative (PCR positive), 3 were indeterminate (3 PCR positive), and 28 were positive (23 PCR positive). Thirty-five (27%) were HCV EIA 3.0 positive. One was RIBA 3.0 negative (PCR positive), 1 was indeterminate (c33c, PCR positive), and 33 were positive (27 PCR positive) by RIBA 3.0. Thus only 1 PCR-positive patient was negative with RIBA 2.0 and 3.0 assays. Two of the 3 RIBA 2.0 indeterminate samples were positive with RIBA 3.0. One remained indeterminate but was HCV RNA positive. In summary, HCV 3.0 EIA detected 4 additional viremic patients but was positive in 6 PCR-negative subjects. A high correlation of the presence of antibody to c33c with HCV RNA (28 of 34, 82%) was found, and it was found in all anti-HCV positive samples and in 1 indeterminate sample. We conclude that the HCV EIA 3.0 test with the supplemental confirmatory RIBA 3.0 test may improve the sensitivity for the detection of anti-HCV. Nevertheless, in potentially immunocompromised patients undergoing dialysis, PCR continues to be the only reliable test for detecting viremia.

Prevalence of hepatitis C and G virus infection in chronic hemodialysis patients.

An RNA virus designated hepatitis G virus (HGV) has been recently identified in patients with acute and chronic liver disease. HGV is transfusion transmissible, it has global distribution, and it is present in the volunteer blood donor population in the United States. One hundred sixty patients undergoing maintenance hemodialysis at the University of Miami-affiliated unit were evaluated. There were 99 men and 61 women ranging in age from 22 to 80 years. Sixty percent had a history of blood transfusion, 6% had a history of drug abuse, and 9% were infected with the human immunodeficiency virus. HGV-RNA was detected by reverse-transcriptase polymerase chain reaction with amplification of two independent regions (5'-nontranslated region and NS5a coding region). Detection of digoxigenin-labeled amplification products with specific capture probes to the coding and noncoding regions was performed with the Enzymun-test DNA on an ES-300 Immunoassay System (Boehringer-Mannheim, Mannheim, Germany). Hepatitis C antibodies were measured with anti-hepatitis C virus enzyme-linked immunosorbent third-generation assays and hepatitis C virus RNA by reverse-transcriptase polymerase chain reaction. There were 32 (20%) patients with detectable HGV RNA with both primer pairs. Because of possible mutations, the HGV virus may be detectable only with one primer pair. We considered the latter as indeterminate: 12 had detectable levels to the NS5a region only, seven to the 5'-nontranslated region, and six had borderline results. Detectable and indeterminate samples were confirmed by repeat measurements in a new blood sample. Seven of 24 (29%) patients with detectable hepatitis C virus RNA had coexisting HGV with one or both HGV primer pairs (four with both and three with one). Five patients were hepatitis B surface antigen positive and HGV negative. We conclude that HGV infection is prevalent in our dialysis patients. The clinical significance of HGV infection remains to be established.

Use of beta-lactamase-producing anaerobes to prevent ceftriaxone from degrading intestinal resistance to colonization.

Six adult volunteers were given 1 g/d of intravenous ceftriaxone for 5 d (consecutive). Ceftriaxone and beta-lactamase activities were assayed in fecal samples obtained before and during drug administration, and anaerobic bacteria, Enterobacteriaceae, and fungi were counted. In two volunteers, no fecal beta-lactamase activity was detected, but ceftriaxone was present during treatment at concentrations of 1.8-2.0 mg/g of feces. Concomitantly, fecal counts of anaerobes in these volunteers dropped from 10.5 to less than 8 log10 colony-forming units (cfu)/g of feces, and those of Candida species increased more than 100-fold. However, in the feces of the four other volunteers, beta-lactamase activity was high during ceftriaxone administration, but no ceftriaxone was detected. In these volunteers, ceftriaxone administration was not followed by any significant change in counts of anaerobes or Candida species. This appeared to be due to the intraintestinal hydrolysis of ceftriaxone by resident beta-lactamase-producing anaerobes. In gnotobiotic mice associated with a human fecal flora containing no beta-lactamase-producing anaerobes, it was possible to prevent the deleterious effects of ceftriaxone on intestinal microbial composition and on colonization resistance (against a strain of Candida albicans and one of ceftriaxone-resistant Enterobacter cloacae) by feeding the animals with an association of four beta-lactamase-producing anaerobic strains.

Ifosfamide/mesna related encephalopathy: a case report with a possible role of phenobarbital in enhancing neurotoxicity.

A case of reversible encephalopathy after one dose of ifosfamide/mesna in an epileptic 15-year-old girl is reported. No other pathology could be responsible for the symptoms. An epilepsy or a toxicity induced by vincristine were discussed. Nevertheless, the possible role of phenobarbital, known to induce hepatic microsomal activity, seems the more probable mechanism.