The interleukin-10 promoter genotype determines clinical immune function in hemodialysis patients.

BACKGROUND: Immune dysfunction and the impaired hepatitis B vaccination response are complications of chronic renal failure that are tightly associated with inflammation induced by uremia and blood-membrane contacts. Proinflammatory cytokines, such as interleukin (IL)-6, are counter-regulated by IL-10 with a large interindividual variability. Part of the variability of cytokine production is genetically determined since polymorphisms in the cytokine gene promoters lead to high or low production. The aim of this study was to detect the genetic influence of the IL-10 promoter on immune function of chronic hemodialysis patients. METHODS: The IL-10 genotype (polymorphic bases at positions -1082 and -819) was determined in 272 chronic hemodialysis patients using highly specific PCR and related to the patients' response to a triple vaccination against hepatitis B. Secretion of IL-10 and IL-6 by peripheral blood leucocytes in vitro was determined by ELISA. RESULTS: The prevalence of the IL-10 genotypes in dialysis patients with well-preserved immune function (vaccination responders) was similar to the general population. In contrast, prevalence of the -1082G* allele (associated with high production of IL-10) was low in the nonresponders. The relative risk of vaccination nonresponse in patients homozygous for the -1082A* allele was 1.394 (95% CI, 1.091 to 1.781, P < 0.05) compared to those homozygous for -1082G*. There was no relationship between the IL-10 genotype and the type of renal disease. CONCLUSIONS: The IL-10 genotype determines IL-10 production in dialysis patients, which down-regulates uremia- and dialysis-induced chronic inflammation and helps to preserve immune defense functions.

Randomized, double-blind trial of Lithostat (acetohydroxamic acid) in the palliative treatment of infection-induced urinary calculi.

In a prospective, double-blind, placebo-controlled study, the efficacy and safety of acetohydroxamic acid (AHA) in preventing urinary calculogenesis was evaluated in 94 patients with chronic urinary infection. Stone growth occurred in 17% of the AHA group and in 46% of the placebo group (p less than 0.005). Completely reversible side effects consisting predominantly of psychoneurologic and musculo-integumentary symptoms were more prevalent in the AHA group (p less than 0.01). Side effects which were judged 'intolerable' were experienced by 10 (22.2%) of patients in the AHA group and 2 (4.1%) in the placebo group. It is concluded that AHA treatment is effective, relatively safe, and clinically useful in preventing infection-induced urinary calculogenesis.