The aim of this study was to assess the effects of chronic exposure to cadmium (Cd) on the structure and function of kidneys, as well as to establish the body burden of Cd at which the changes occur. For this purpose we have created an experimental model using rats intoxicated with Cd administered in drinking water at the concentration of 5 or 50 mg Cd/l for 6, 12 and 24 weeks. The degree of kidney damage was evaluated biochemically and histopathologically. Sensitive biomarkers of Cd-induced proximal tubular injury such as urinary total N-acetyl-β-d-glucosaminidase (NAG-T) and its isoenzyme B (NAG-B), and alkaline phosphatase (ALP) were used. Cd content in the kidney increased with the level and duration of exposure leading to dose- and time-dependent structural and functional renal failure. In rats exposed to 5 mg Cd/l, first symptoms of injury of the main tubules of long and short nephrons (structural damage to epithelial cells, increased urinary activities of NAG-T and NAG-B) were noted after 12 weeks of the experiment. The damage occurred at a low kidney Cd concentration amounting to 4.08±0.33 µg/g wet weight (mean ±SE) and a urinary concentration of 4.31±0.28 µg/g creatinine. On exposure to 50 mg Cd/l, damage to the main tubules (blurred structure of tubular epithelium, atrophy of brush border, partial fragmentation of cells with release of nuclei into tubular lumen as well as increased urinary activities of NAG-T, NAG-B and ALP) was already evident after 6 weeks with the kidney Cd concentration of 24.09±1.72 µg/g wet weight. In rats exposed to 50 mg Cd/l, a lack of regular contour of glomeruli was noted after 12 weeks, whereas after 24 weeks thickening of capillary vessels and widening of filtering space were evident. After 24 weeks of exposure to Cd, increased urea concentration in the serum with simultaneous decrease in its level in the urine, indicating decreased clearance of urea, and increased excretion of total protein were observed, but endogenous creatinine clearance remained unaffected. At the lower exposure, symptoms of structural, but not functional, damage to the glomeruli were also evident after 24 weeks of the experiment. Our results provide evidence that chronic exposure to Cd dose-dependently damages (structurally and functionally) the whole kidney. The injury affects the main resorptive part (proximal convoluted tubules and straight tubules) and the filtering part (glomeruli) of the nephron. But the target site for Cd action is the main tubule. We hypothesize that the threshold for Cd effects on the kidney is less than 4.08±0.33 µg/g wet kidney weight and greater than 2.40±0.15 µg/g (at this Cd concentration no symptoms of kidney damage were noted), and it may be close to the latter value. A very important finding of this study is that Cd acts on the whole kidney, especially on the main tubules, even at relatively low accumulation in this organ. It confirms the hypothesis that humans environmentally exposed to Cd, especially smokers, are at risk of tubular dysfunction.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Aughey E, Fell GS, Scott R, Black M (1984) Histopathology of early effects of oral cadmium in the rat kidney. Environ Health Perspect 54:153–161
Bem EM, Piotrowski JK, Turzyńska E (1993) Cadmium, zinc, and copper levels in the kidneys and liver of the inhabitants of north-eastern Poland. Pol J Occup Med Environ Health 6:133–141
Bernard A, Thielmans N, Roels H, Lauwerys R (1995) Association between NAG-B and cadmium in urine with no evidence of a threshold. Occup Environ Med 52:177–180
Chalkley SR, Richmond J, Barltrop D (1998) Measurement of vitamin D3 metabolites in smelter workers exposed to lead and cadmium. Occup Environ Med 55:446–452
dell'Omo M, Muzi G, Piccinini R, Gambelunghe A, Morucci P, Fiordi T, Ambrogi M, Abbritti G (1999) Blood cadmium concentrations in the general population of Umbria, central Italy. Sci Total Environ 226:57–64
Giles AR (1987) Guidelines for the use of animals in biomedical research. Thromb Haemost 58:1078–1984
Hac E, Krzyzanowski M, Krechniak J (1998) Cadmium content in human kidney and hair in the Gdansk region. Sci Total Environ 224:81–85
Järup L, Hellstrom L, Alfven T, Carlsson MD, Grubb A, Persson B, Pettersson C, Spang G, Schutz A, Elinder CG (2000) Low level exposure to cadmium and early kidney damage: the OSCAR study. Occup Environ Med 57:668–672
Jin T, Nordberg G, Wu X, Ye T, Kong Q, Wang Z, Zhuang F, Cai S (1999) Urinary N-acetyl-β-d-glucosaminidase isoenzymes as biomarkers of renal dysfunction caused by cadmium in a general population. Environ Res 81:167–173
Kahan E, Derazne E, Rosenboim J, Ashkenazi R, Ribak J (1992) Adverse health effects in workers exposed to cadmium. Am J Ind Med 21:527–537
Khassouani CE, Soulaymani R, Mauras Y, Allain P (2000) Blood cadmium concentration in the population of the Rabat area, Morocco. Clin Chim Acta 302:155–160
Kjellström T (1986) Renal effects. In: Friberg L, Elinder CG, Kjellström T, Nordberg GF (eds) Cadmium and health: a toxicological and epidemiological appraisal, vol 2. CRC Press, Boca Raton Florida, pp 21–109
Koyama H, Satoh H, Suzuki S, Tohyama C (1992) Increased urinary cadmium excretion and its relationship to urinary N-acetyl-β-d-glucosaminidase activity in smokers. Arch Toxicol 66:598–601
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Mitsumori K, Shibutani M, Sato S, Onodera H, Nakagawa J, Hayashi Y, Ando M (1998) Relationship between the development of hepato-renal toxicity and cadmium accumulation in rats given minimum to large amounts of cadmium chloride in the long-term: preliminary study. Arch Toxicol 72:545–552
Mueller PW, Price R, Finn W (1998) New approaches for detecting thresholds of human nephrotoxicity using cadmium as an example. Environ Health Perspect 106:227–230
Noonan CW, Sarasua SM, Campagna D, Kathman SJ, Lyberger JA, Mueller PW (2002) Effects of exposure to low levels of environmental cadmium on renal biomarkers. Environ Health Perspect 110:151–155
Nordberg GF, Jin T, Nordberg M (1994) Subcellular targets of cadmium nephrotoxicity: cadmium binding to renal membrane proteins in animals with or without protective metallothionein synthesis. Environ Health Perspect 102 [Suppl 3]:191–194
Ohta H, Yamauchi Y, Nakakita M, Tanaka H, Asami S, Seki Y, Yoshikawa H (2000) Relationship between renal dysfunction and bone metabolism disorder in male rats after long-term oral quantitative cadmium administration. Ind Health 38:339–355
Pearse AGE (1972) Histochemistry: theoretical and applied. JA Churchill, London, p 2
Price RC, Patel S, Chivers I, Milligan P, Taylor SA (1999) Early markers of nephrotoxicity: detection of children at risk from environmental pollution. Ren Fail 21:303–308
Roels HA, Hoet P, Lison D (1999) Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risk of nephrotoxicity. Ren Fail 21:251–262
Rydzewski B, Sułkowski W, Miarzyńska M (1998) Olfactory disorders induced by cadmium exposure: a clinical study. Int J Occup Med Environ Health 11:235–245
Uriu K, Kaizu K, Qie YL, Ito A, Takagi I, Suzuka K, Inada Y, Hashimoto O, Eto S (2000) Long-term oral intake of low-dose cadmium exacerbates age-related impairment of renal function reserve in rats. Toxicol Appl Pharmacol 169:151–158
WHO (World Health Organisation) (1992) Environmental health criteria 134. Cadmium. International Programme on Chemical Safety (IPCS), WHO, Geneva
Zwierz K, Gindzieński A, Głowacka D, Porowski T (1981) The degradation of glycoconjugates in the human gastric mucous membrane. Acta Med Acad Sci Hung 38:145–152
The present study was supported by the Grant (No. 4PO5D 012 19) from the Committee for Scientific Research (KBN, Poland).
About this article
Cite this article
Brzóska, M.M., Kamiński, M., Supernak-Bobko, D. et al. Changes in the structure and function of the kidney of rats chronically exposed to cadmium. I. Biochemical and histopathological studies. Arch Toxicol 77, 344–352 (2003). https://doi.org/10.1007/s00204-003-0451-1