Hormones – Cytokines – Signalling

Kidney International (2004) 66, 2155–2166; doi:10.1111/j.1523-1755.2004.66006.x

High calcium diet down-regulates kidney angiotensin-converting enzyme in experimental renal failure

ILKKA PÖRSTI, MENG FAN, PEETER KÖÖBI, PASI JOLMA, JARKKO KALLIOVALKAMA, TUIJA I VEHMAS, HEIKKI HELIN, HARRY HOLTHÖFER, EERO MERVAALA, TUULIKKI NYMAN and ILKKA TIKKANEN

Department of Internal Medicine, University of Tampere, Tampere, Finland; Department of Pharmacological Sciences, University of Tampere, Tampere, Finland; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; Department of Anaesthesia and Intensive Care, University of Tampere, Tampere, Finland; Department of Pathology, Tampere University Hospital, Tampere, Finland; Programme of Molecular Medicine, Helsinki, Finland; Institute of Biomedicine, Biomedicum Helsinki, Helsinki, Finland; and Minerva Institute for Medical Research, Helsinki, Finland

Correspondence: Ilkka Pörsti, M.D., Medical School, Department of Internal Medicine, FIN-33014 University of Tampere, Finland. E-mail:ilkka.porsti@uta.fi

Received 21 March 2004; Revised 3 June 2004; Accepted 18 June 2004.

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Abstract

High calcium diet down-regulates kidney angiotensin-converting enzyme in experimental renal failure.

Background

 

Calcium salts are used as phosphate binders in renal failure, while high calcium diet also improves vasorelaxation and enhances natriuresis. The influences of calcium intake on renal renin-angiotensin system (RAS) are largely unknown.

Methods

 

Four weeks after NTX, rats were put on 3.0% or 0.3% calcium diet for 8 weeks (12-week study). In additional experiments, 15 weeks after NTX, rats were put on similar diets for 12 weeks (27-week study). Appropriate blood, urine, and kidney samples were taken. Renal angiotensin-converting enzyme (ACE) and angiotensin II receptors (AT1, AT2) were examined using autoradiography, ACE also using Western blotting, and connective tissue growth factor (CTGF) using immunohistochemistry.

Results

 

In the 12-week study, albuminuria increased 5-fold in NTX rats, but only 2-fold in calcium NTX rats on 3.0% calcium. In the 27-week study, high calcium intake decreased blood pressure, retarded progression of renal failure, reduced glomerulosclerosis, interstitial damage, and aortic calcifications, and improved survival from 50% to 92% in NTX rats. In both experiments plasma parathyroid hormone and phosphate were elevated after NTX, and suppressed by high calcium diet, while kidney ACE was down-regulated by 40% or more after increased calcium intake. In the 27-week study renal CTGF was decreased and cortical AT1 receptor density reduced after high calcium diet.

Conclusion

 

High calcium diet down-regulated kidney ACE, reduced albuminuria and blood pressure, and favorably influenced kidney morphology in experimental renal failure. These findings suggest a link between calcium metabolism and kidney ACE expression, which may play a role in the progression of renal damage.

Keywords:

angiotensin-converting enzyme, calcium diet, phosphate, parathyroid hormone, renal failure

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