Mechanisms of cyclosporine-induced hypertension.
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.
Cusi
D
D
Nephrology, Dialysis and Hypertension Unit, Ospedale S. Raffaele, Milano, Italy.
Barlassina
C
C
Niutta
E
E
Elli
A
A
Quarto di Palo
F
F
Bianchi
G
G
D000042:Absorption; D017920:Antiporters; D002352:Carrier Proteins / Q000378:metabolism; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation; D007687:Kidney Tubules, Proximal / Q000503:physiopathology; D008094:Lithium / Q000652:urine; D012964:Sodium / Q000097:blood; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D014527:Uric Acid / Q000652:urine
D017920:Antiporters; D002352:Carrier Proteins; D028021:Sodium-Potassium-Chloride Symporters; C045885:sodium-lithium countertransporter; D014527:Uric Acid; D016572:Cyclosporine; D008094:Lithium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase