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.