Gd Nuyts

New occupational risk factors for chronic renal failure

Occupational pollutants may have a role in development of chronic renal failure (CRF). Most epidemiological studies have been cross-sectional, limited to certain renal diagnoses, or concentrated on early transient renal effects. In a case-control study, we examined the association between CRF and occupational exposure. Occupational histories of 272 men and women with CRF (of all types) were compared with those of 272 controls matched for age, sex, and region of residence. Exposures were assessed and degree and frequency were scored independently by three industrial hygienists unaware of case/control status. Significantly increased risks of CRF were found for exposure to lead (odds ratio 2.11 [95% CI 1.23-4.36]), copper (2.54 [1.16-5.53]), chromium (2.77 [1.21-6.33]), tin (3.72 [1.22-11.3]), mercury (5.13 [1.02-25.7]), welding fumes (2.06 [1.05-4.04]), silicon-containing compounds (2.51 [1.37-4.60]), grain dust (2.96 [1.24-7.04]), and oxygenated hydrocarbons (5.45 [1.84-16.2]). The frequencies of various occupational exposures were high among patients with diabetic nephropathy. This epidemiological study confirms previously identified risk factors and suggests that additional occupational exposures, for which there is some other experimental evidence, may be important in the development of CRF. The role of grain dust and the association between occupational exposure and diabetic nephropathy merit further investigation.

Nephropathies and exposure to perchloroethylene in dry-cleaners

Even in specific risk groups, the relation between exposure to organic solvents and chronic renal diseases remains controversial. Thus, in a collaborative European study, we assessed the renal effects of occupational exposure to perchloroethylene (PCE) in dry-cleaners compared with matched controls who were simultaneously examined. Single high and low molecular weight proteins, kidney-derived antigens and enzymes, and prostanoids were measured in urine. beta 2-microglobulin, creatinine, laminin fragments, and anti-glomerular basement membrane antibodies were also measured in serum. A canonical function based on 23 such variables correctly classified 93% of individuals as either PCE-exposed or controls; with 13 markers, group membership was identified in 87% of subjects. Increased high molecular weight protein in urine was frequently (17/50 vs 1/50, p less than 0.0001) associated with tubular alterations. Changes were consistent with diffuse abnormalities along the nephron in workers exposed to low levels of PCE (median 15 parts per million). Generalised membrane disturbances might account for the increased release of laminin fragments, fibronectin, and glycosaminoglycans, for high molecular weight proteinuria, and for the increased shedding of epithelial membrane components from tubular cells with different location along the nephron (brush-border antigens and Tamm-Horsfall glycoprotein). These findings of early renal changes indicate that solvent-exposed subjects, especially dry-cleaners, need to be monitored for the possible development of chronic renal diseases.

Significance of elevated urinary human intestinal alkaline phosphatase in Japanese people exposed to environmental cadmium

Urinary human intestinal alkaline phosphatase (IAP), beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) were analyzed in 40 Japanese environmental-cadmium (Cd)-exposed and 40 non-exposed subjects to evaluate early biological markers for Cd-induced renal damage. All urinary indicators were significantly higher in the Cd-exposed subjects than non-exposed subjects. A fourth-order function was fitted for the relationship between beta 2-MG and IAP or NAG. The beta 2-MG concentration corresponding to the inflexion point for IAP was smaller than that for NAG. This result may support the contention that the cells containing IAP are damaged earlier than those containing NAG, and that IAP is a useful marker for detecting renal tubular dysfunction in people moderately exposed to Cd. However, in the stage of severe renal damage, the combination of IAP and beta 2-MG is considered to be more useful.

Health impact of renal disease due to nephrotoxicity

Both acute and chronic renal failure are reported in the context of nephrotoxicity. This overview of some major nephrotoxins reflects both the magnitude and the cost of this preventable health problem. Aminoglycosides and other antibiotics, contrast media and nonsteroidal anti-inflammatory drugs are the best documented nephrotoxins related to acute renal failure. Analgesic nephropathy is the best known drug-induced chronic renal disease. The cost of renal failure due to nephrotoxicity is not easy to compute. Drug-induced acute renal failure costs more than 2750 ECU per patient, depending on whether dialysis is required or not, and chronic renal failure costs at least 128,000,000 ECU annually in the European Communities. Recent epidemiological evidence, however, indicates that the cost may be even higher.

Bone lead and renal failure.

M.E. De Broe, MD, PhD, Head of the Department of Nephrology-Hypertension, University of Antwerp, p/a University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem-Antwerp (Belgium) Dear Sir, Winterberg et al. [1] recently reported on higher bone lead levels (μg/g wet weight) in a small group of hemodi-alysis patients as compared to two small groups of patients with chronic renal failure or after renal transplantation. These results were reported as a reply to the observations of Martegani et al. [2], who found increased erythrocyte zinc protoporphyrin IX levels in hemodialy-sis patients as compared to chronic renal failure patients. These authors also found important amounts of chelat-able lead in the ultrafiltrate by treatment with EDTA during hemofiltration in patients normally under dialysis. They concluded that lead body burden depends on renal function and is increased in hemodialysis patients as compared to chronic renal failure or healthy subjects [1,2]. These findings are not in agreement with our findings published in 1988. Indeed we could not find any correlation between the degree of renal failure and bone lead by measuring bone lead/gram wet weight and lead/calcium ratio in transiliac bone biopsies of 35 patients with moderate degree of renal failure and 153 dialysis patients [3]. Levels in dialysis patients with well-documented analgesic nephropathy (n = 10) and no occupational lead exposure were in the same range as those from deceased subjects (cadavers) with past normal renal function and without clearly documented lead exposure (table 1). Winterberg et al. [1] give no information on the occupational or environmental lead exposure in their hemodialysis group. Indeed, we found [3] high levels of bone lead Table 1. Mean transiliac bone lead and bone lead/calcium ratio (mean ± SD)