ELEVATED SODIUM-LITHIUM COUNTERTRANSPORT ACTIVITY IN ERYTHROCYTES IS PREDICTIVE OF THE DEVELOPMENT OF MICROALBUMINURIA IN IDDM

Pathogenetic mechanisms other than the quality of metabolic control ma y play a role in the development of diabetic nephropathy. Some cross-s ectional studies have shown that elevated erythrocyte sodium-lithium c ountertransport (Na+/Li+ CT) activity may be linked to incipient or ov ert nephropathy in insulin-dependent diabetic (IDDM) patients. The aim of the present work was to ascertain if high erythrocyte Na+/Li+ CT a ctivity anticipates the development of microalbuminuria in IDDM patien ts. Evaluation of this cation transport system was carried out in 159 normotensive, normoalbuminuric IDDM patients, who were divided into tw o groups: these with values above (Group A) and those with values belo w (Group B) the median level in the overall population (300 mu mol/ery throcytes x h). A total of 79 patients in Group A and 80 in Group B un derwent periodic examinations over a similar time period (5.2 years, r ange 3.3-7.4 years and 5.4 years, range 3.4-7.5 years, respectively). Median sodium-lithium countertransport activity was stable when evalua ted after 2 and 4 years of follow-up. Only seven patients were exclude d from the protocol because changes in their sodium-lithium countertra nsport activity placed them on the other side of the median value with respect to their baseline measurement. Thus, 152 patients completed t he study (76 in Group A and 76 in Group B). Of the 76 patients in Grou p A, 17 developed persistent microalbuminuria (22.3%). The number of p atients in Group B showing persistent microalbuminuria was significant ly lower (4 of 76; 5.2%; p < 0.01). The sensitivity of erythrocyte Na/Li+ CT in predicting the development of microalbuminuria was 85 % and its specificity was 55 %. Seven patients of Group A and five of Group B developed arterial hypertension. Subjects in Group A had significan tly higher mean HbA(1c) values of twice yearly measurements than those in Group B (9.6+/-1.7 vs 8.3+/-1.7%, p < 0.002, mean+/-SD) despite si milar daily insulin requirements. Systolic and diastolic blood pressur e levels were also evaluated every 6 months and were significantly hig her in the Group A than in the Group B patients, although on average w ithin the normal range. The odds ratio for developing persistent micro albuminuria in IDDM with elevated baseline erythrocyte Na+/Li+ CT acti vity after adjustment for gender and baseline albumin excretion rate, and mean 6 monthly plasma creatinine, HbA(1c) and systolic and diastol ic blood pressure levels was 4.2 (95 % confidence intervals 2.0-11.1). It was also found that the percentage of offspring having both parent s with Na+/Li+ CT activity above the median value was significantly hi gher in Group A than in Group B (Group A vs Group B: 35 vs 19%; p < 0. 01). On the contrary the percentage of offspring whose erythrocyte Na/Li+ CT was lower in both parents was lower in Group A than in Group B : 10 vs 38 %, p < 0.01). Parents of Group A offspring had arterial hyp ertension more frequently than those of Group B. These results indicat e that erythrocyte Na+/Li+ CT activity is a useful diagnostic tool in identifying normotensive, normoalbuminuric patients who may be predisp osed to develop persistent microalbuminuria. This disorder in the cati on transport system is associated with poor metabolic control, higher blood pressure, and male sex; it also appears to be, at least partly g enetically transmitted.