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Mechanisms of cyclosporine-induced hypertension
D Cusi1, C Barlassina, E Niutta
1Nephrology, Dialysis and Hypertension Unit, Ospedale S. Raffaele, Milano, Italy.
Insights
Cyclosporine A (Cs A) increases blood pressure and proximal tubule resorption in kidney transplant patients, even with normal kidney function. This may explain Cs A-associated hypertension and early interstitial damage.
Area of Science:
- Nephrology
- Pharmacology
- Hypertension Research
Background:
- Cyclosporine A (Cs A) nephrotoxicity mechanisms remain unclear, potentially linked to hypertension and hyperuricemia.
- Erythrocyte cation transport systems are implicated in essential hypertension.
Purpose of the Study:
- To evaluate proximal tubular resorption and its relation to erythrocyte cation transport in kidney transplant recipients on Cs A versus azathioprine.
- To investigate the impact of Cs A on blood pressure and kidney function markers.
Main Methods:
- Compared fractional excretion of uric acid (FE Ur%) and lithium (FE Li%) in Cs A and azathioprine groups with normal kidney function.
- Assessed erythrocyte sodium concentration, Na-K pump, Na-K cotransport, and Li-Na countertransport.
- Matched patients for demographics and monitored antihypertensive treatment.
Main Results:
- The Cs A group exhibited higher blood pressure (108.6 vs 98.3 mmHg) despite increased antihypertensive treatment.
- Cs A treatment was associated with increased proximal tubular resorption (FE Li%: 20.5% vs 12.8%) and global proximal tubular resorption (FE Ur%: 7.09% vs 5.2%).
- Erythrocyte sodium transport systems were similar between groups.
Conclusions:
- Elevated proximal tubular resorption and higher blood pressure in the Cs A group may explain the increased prevalence of hypertension.
- Increased urate resorption could contribute to early interstitial abnormalities, a hallmark of Cs A toxicity.
- Cs A does not appear to alter erythrocyte ion transport systems in this context.
Abstract:
The mechanisms of cyclosporine A (Cs A) nephrotoxicity are not clear, but may be associated with high blood pressure and high serum uric acid levels even when kidney function is still normal. To evaluate proximal tubular resorption and its relationship with erythrocyte cation transport systems that are known to be abnormal in essential hypertension, we measured fractional excretion of endogenous uric acid (FE Ur%) and exogenous lithium (FE Li%), erythrocyte sodium concentration, Na-K pump, Na-K cotransport and Li-Na countertransport in two groups of kidney transplant recipients with normal kidney function (creatinine less than 1.6 mg/dL), one treated with Cs A and steroid (Cs A group) and the other with azathioprine and steroid (Aza group). Patients were matched for sex, body mass index, and age. Antihypertensive treatment was measured using arbitrary scores. Erythrocyte sodium transport systems were similar in the two groups. Despite normal kidney function, the Cs A group had higher blood pressure (mean blood pressure 108.6 +/- 3.1 mmHg vs 98.3 +/- 2.4, p less than 0.01), although taking more antihypertensive treatment, and increased proximal tubular resorption (FE Li%: 12.8 +/- 1.5 vs 20.5 +/- 1.7, p less than 0.001) and global proximal tubular resorption (FE Ur%: 5.2 +/- 0.48 vs 7.09 +/- 0.41, p less than 0.05). These findings may explain the greater prevalence of hypertension in the Cs A group. Increased urate resorption may be involved in interstitial abnormalities, which are the earliest signs of Cs A toxicity. Cs A did not modify erythrocyte ion transport systems.