Red blood cell Li+/Na+ exchange in patients with diabetic nephropathy and essential hypertension: therapeutic implications.
Patients who develop diabetic nephropathy, one of the leading causes of end-stage renal diseases in Western communities, have an increased red cell Li+/Na+ countertransport (CT). Li+/Na+ CT is a membrane function which exchanges intracellular Li for extracellular Na in vitro. High Li+/Na+ CT reflects abnormal kinetic properties of red cell membrane Na/H exchange. A widespread abnormality of Na/H exchange could play a major role in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases since Na/H exchange is involved in the regulation of cell pH and cell volume; in the cellular response to hormones, mitogens, and growth factors; and in the renal reabsorption of Na and bicarbonate. Li+/Na+ CT is under genetic control and raised in a subgroup of patients with essential hypertension. Among these patients, high Li+/Na+ CT is associated with increased glomerular filtration rate, filtration fraction, proximal fractional Na reabsorption, microalbuminuria, plasma renin activity, and kidney and cardiac volume. Increased Li+/Na+ CT is often associated with hyperlipidemia, hyperuricemia, reduced insulin sensitivity, and obesity. The whole of these observations may explain why patients with diabetes or essential hypertension and increased Li/Na CT are at risk of early renal and cardiac impairment.
Semplicini
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A
Institute of Clinical Medicine, University of Padova, Italy.
Marzola
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M
Mozzato
G
G
Ceolotto
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G
Pessina
A C
AC
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D017920:Antiporters; D002352:Carrier Proteins / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003928:Diabetic Nephropathies / Q000097:blood* / Q000453:epidemiology; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D017379:Hypertrophy, Left Ventricular / Q000097:blood; D007676:Kidney Failure, Chronic / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D000959:Antihypertensive Agents; D017920:Antiporters; D002352:Carrier Proteins; C045885:sodium-lithium countertransporter