Increased Na+/Li+ countertransport activity may help to identify type 1 diabetic adolescents and young adults at risk for developing persistent microalbuminuria.
OBJECTIVE
To evaluate whether erythrocyte sodium-lithium countertransport (Na+/Li+ CT) activity may identify adolescents and young adults with childhood-onset of type 1 diabetes to be at greater risk to develop persistent microalbuminuria and incipient diabetic nephropathy.


METHODS
In January 1989, Na+/Li+ CT was measured in 170 normoalbuminuric diabetic adolescents and young adults (age 12-23 years; onset of diabetes before age 18 years; duration of diabetes longer than 7 years). Participants were clinically examined at baseline and biennially thereafter. Na+/Li+ CT activity was measured every 2 years during the 8-year follow-up period. Na+/Li+ CT activity was measured also in parents of diabetic offspring.


RESULTS
Over 8 years, 18 (10 male, 8 female) out of 170 patients (10.5%) developed persistent microalbuminuria; no patient developed overt nephropathy. The risk of developing microalbuminuria was higher in children with increased Na+/Li+ CT (using 300 mumol.1 erythrocytes-1.h-1 as the arbitrary cutoff point) (group 1) compared with those with normal Na+/Li+ CT at the beginning of the study (group 2) (18.98 vs. 3.29%, P < 0.01; sensitivity 96.7%; specificity 57.9%). Sex did not influence predictive value, sensitivity, or specificity. Na+/Li+ CT was not significantly correlated with HbA1c or duration of type 1 diabetes. The percentage of offspring with both parents having Na+/Li+ CT activity above the median values was significantly higher in patients in group 1 than in group 2. The odds ratio for the occurrence of microalbuminuria after adjustment for confounding variables (albumin excretion rate [AER], sex, HbA1c, mean blood pressure, cholesterol, triglycerides) in type 1 diabetic adolescents with elevated baseline erythrocyte Na+/Li+ CT was 4.5 (95% CI of 2.1-11.4).


CONCLUSIONS
These results confirm those of previous studies and suggest that Na+/Li+ CT may be one of the predictors and risk factors for incipient diabetic nephropathy in adolescents and young adults with onset of diabetes during childhood. Persistently increased Na+/Li+ CT activity may help to identify normotensive, normoalbuminuric patients with type 1 diabetes who are predisposed to develop microalbuminuria and incipient diabetic nephropathy.
Chiarelli
F
F
Department of Medicine, University of Chieti, Italy. chiarelli@unich.it
Catino
M
M
Tumini
S
S
de Martino
M
M
Mezzetti
A
A
Verrotti
A
A
Vanelli
M
M
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000419:Albuminuria / Q000453:epidemiology*; D017920:Antiporters / Q000097:blood*; D001794:Blood Pressure; D002648:Child; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D003928:Diabetic Nephropathies / Q000453:epidemiology* / Q000517:prevention & control; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008094:Lithium / Q000097:blood; D008297:Male; D010290:Parents; D012307:Risk Factors; D012964:Sodium / Q000097:blood; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D017920:Antiporters; D007328:Insulin; D014280:Triglycerides; C045885:sodium-lithium countertransporter; D002784:Cholesterol; D008094:Lithium; D012964:Sodium; D003404:Creatinine