Dietary potassium and magnesium supplementation in cyclosporine-induced hypertension and nephrotoxicity

Background Cyclosporine A (CsA)-induced hypertension and nephrotoxicity are aggravated by high sodium intake. Accumulating evidence suggests that pota ssium and magnesium supplementation could protect against the detrimental e ffects of dietary salt. In the present study, we tested the hypothesis of w hether concurrent supplementation with potassium and magnesium could protec t against the development of CsA-induced hypertension and nephrotoxicity mo re effectively than supplementation with one mineral alone. Methods. Eight-week-old spontaneously hypertensive rats (SHRs) were divided into four groups (N = 10 in each group): (I) CsA group (5 mg/kg subcutaneo usly) receiving high-sodium diet (Na 2.6%, K 0.8%, Mg 0.2% wt/wt); (2) CsA group receiving a high-sodium, high-potassium diet (Na 2.6%, K 2.4%, Mg 0.2 %); (3) CsA group receiving high-sodium, high-magnesium diet (Na 2.6%, K 0. 8%, Mg 0.6%); and (4) CsA group receiving high-sodium, high-potassium, high -magnesium diet (Na 2.6%, K 2.4%, Mg 0.6%). Results. CsA induced severe hypertension and deteriorated renal functions i n SHRs on high-sodium diet. Histologically, the kidneys showed severe thick ening of the media of the afferent artery with fibrinoid necrosis. Potassiu m supplementation lowered blood pressure (198 +/- 5 vs. 212 +/- 2 mm Hg, P < 0.05) and partially prevented the development of proteinuria (-25%, P < 0 .05). Magnesium supplementation decreased blood pressure to the same extent but improved renal functions more effectively than potassium. The greatest protection against CsA toxicity was achieved when dietary potassium and ma gnesium supplementations were combined. Urinary N-acetyl-beta -D-glucosamin idase (NAG) excretion, a marker for renal proximal tubular damage, increase d progressively in CsA-treated SHRs on the high-sodium diet, Neither potass ium nor magnesium influenced urinary NAG excretion. We also estimated the a ctivity of the renal dopaminergic system by measuring 24-hour urinary dopam ine excretion rates. CsA suppressed the renal dopaminergic system during hi gh-sodium diet. Magnesium supplementation, done and in combination with pot assium, protected against the development of renal dopaminergic deficiency in CsA-treated SHRs on high-sodium diet. Magnesium supplementation increase d plasma-free ionized magnesium (iMg) and bone magnesium by 50 and 16%, res pectively. Conclusions. Our findings indicate that both potassium and magnesium supple mentations showed beneficial effects against CsA-induced hypertension and n ephrotoxicity. The protective effect of magnesium clearly exceeded that of potassium. The greatest protection against CsA toxicity was achieved when p otassium and magnesium were combined. We also provide evidence that the dev elopment of CsA-induced glomerular, tubular, and vascular lesions are assoc iated with renal dopaminergic deficiency.