Sodium/hydrogen exchange activity in Type 1 diabetes mellitus: The never-ending story

The amiloride-sensitive Na+/H+ exchanger (NHE) mediates uphill H+ extrusion and thus causes intracellular alkalinization. The NHE plays a major role i n pH homeostasis, Na+ absorption, cell volume regulation, and cell prolifer ation; it is activated by growth factors, mitogens, neurotransmitters, tumo r promoters, and others. At intracellular pH (pHi)>7.2-7.4, the system is q uiescent; when pHi falls, the rate of H+ -efflux increases in an allosteric manner to reach a maximum around pHi=6.0. The kinetics for external Na+ fo llows the Michaelis-Menten model with a single, binding site. The effect of intracellular H+ best fits an allosteric model with at least two binding s ites. According to the postulate that erythrocyte sodium-lithium countertra nsport (NLCT) might be one mode of operation of the ubiquitous NHE, and fol lowing the trail of previous investigations of NLCT association with hypert ension and diabetic nephropathy, several studies have confirmed elevated NH E activity in different cell types in patients with essential hypertension. However, the relation between NHE and either NLCT or hypertension remains unclear and the usefulness of NLCT activity as a risk marker for the develo pment of essential hypertension has been now excluded. On the contrary, few publications have dealt with the physiologic NHE in diabetic nephropathy, and contrasting results have been reported. We have observed an accelerated NHE in essential hypertension and in Type I diabetes, however without any relationship with urinary albumin excretion rate. Furthermore, NHE activity increased in non-diabetic first-degree relatives of Type 1 diabetic patien ts, yet no difference could be observed between relatives of probands. with diabetic nephropathy and relatives of probands with normoalbuminuria. Unli ke erythrocyte NHE activity, abnormal albumin excretion was a distinctive f eature of non-diabetic first-degree relatives of Type I diabetic patients w ith nephropathy. The lack of agreement among Authors, even using both the s ame cell and the same method, testifies to the difficulty in performing a c orrect patient selection and uniformly reproducible NHE measurement. We com pare individual clinical characteristics among different study populations confirming previous conclusions regarding NLCT in essential hypertension: m ain determinant for the flux values of NHE seems to be patient selection ra ther than methodology. A common effort is advisable to collaborate, standar dise, compare methodologies, and unify criteria of subject recruitment. (C) 2001, Editrice Kurds.