Amiloride-sensitive Na+/H+ exchange in erythrocytes of patients with NIDDM: a prospective study.
Intensive treatment of non-insulin-dependent diabetes mellitus (NIDDM) decreases the rate of microvascular complications, but is associated with increased incidence of cardiovascular morbidity. Enhanced permeability of plasma membranes for sodium (e.g. sodium-hydrogen exchange, NHE) may predict the subset of diabetic patients for whom intensive modalities of treatment are indicated despite their potential risk. However, the accuracy of NHE as a marker of microangiopathy has not been assessed. In this study NHE as initial velocity of amiloride-inhibited H+ efflux from erythrocytes (pHi 6.35-6.45) into an Na(+)-containing medium (pHo 7.95-8.05), was estimated during 8 years of follow-up in 138 non-microalbuminuric diabetic patients (74 women, 64 men, age 52 +/- 4 years) treated with antihyperglycaemic drugs for 14 +/- 2 years. Appearance of microalbuminuria, overt proteinuria, azotaemia and retinopathy was assessed annually. Enhanced erythrocyte NHE predicted diabetic nephropathy alone and in association with a family history of hypertension and/or nephropathy with a sensitivity of 86 and 93%, respectively. No association was found between NHE and retinopathy in NIDDM. It is concluded that assessment of erythrocyte NHE can identify a subset of patients likely to develop renal damage, for whom an aggressive treatment approach might be considered.
Koren
W
W
Hypertension Unit, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Koldanov
R
R
Pronin
V S
VS
Postnov
I Y
IY
Peleg
E
E
Rosenthal
T
T
Berezin
M
M
Postnov
Y V
YV
D000419:Albuminuria; D000584:Amiloride / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D003928:Diabetic Nephropathies / Q000097:blood / Q000453:epidemiology* / Q000652:urine; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000235:genetics; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012680:Sensitivity and Specificity; D012964:Sodium / Q000097:blood*; D017923:Sodium-Hydrogen Exchangers / Q000097:blood*; D013997:Time Factors; D015430:Weight Gain
D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D012964:Sodium