Renal Hyperfiltration Is Associated With Glucose-Dependent Changes in Fractional Excretion of Sodium in Patients With Uncomplicated Type 1 Diabetes

Gary K. Yang, Ronnie L.H. Har, Yuliya Lytvyn, Paul Yip, David Z.I. Cherney
2014 Diabetes Care  
OBJECTIVE Renal hyperfiltration is a common abnormality associated with diabetic nephropathy in patients with type 1 diabetes (T1D). In animal models, increased proximal tubular sodium reabsorption results in decreased distal sodium delivery, tubuloglomerular feedback activation, afferent vasodilatation, and hyperfiltration. The role of tubular factors is less well understood in humans. The aim of the current study was therefore to compare the fractional sodium excretion (FE Na ) in
more » ... Na ) in hyperfiltering (T1D-H) versus normofiltering (T1D-N) patients and healthy control (HC) subjects, as well as the role of ambient hyperglycemia on FE Na . RESEARCH DESIGN AND METHODS Blood pressure, renal function (inulin for glomerular filtration rate [GFR], and paraaminohippurate for effective renal plasma flow), FE Na , and circulating neurohormones were measured in T1D-H (n = 28, GFR ‡135 mL/min/1.73 m 2 ), T1D-N (n = 30), and HC (n = 35) subjects during clamped euglycemia. Studies were repeated in a subset of patients during clamped hyperglycemia. RESULTS During clamped euglycemia, T1D-H exhibited lower FE Na than T1D-N and HC subjects (0.64 6 0.06% vs. 0.91 6 0.12% and 0.90 6 0.10%, P < 0.05). During clamped hyperglycemia, FE Na increased (D + 0.88 6 0.22% vs. D + 0.02 6 0.21%; betweengroup effect, P = 0.01) significantly in T1D-H, whereas FE Na did not change in T1D-N. When treated as continuous variables, elevated GFR values were associated with hyperglycemia-induced increases in FE Na (R 2 = 0.20, P = 0.007). CONCLUSIONS Patients with uncomplicated T1D-H exhibit lower FE Na under euglycemic conditions, which may help to identify patients with hyperfiltration outside of a controlled laboratory setting. Increased FE Na in T1D-H but not T1D-N under clamped hyperglycemic conditions suggests that the mechanisms responsible for increased sodium reabsorption leading to hyperfiltration can be saturated.
doi:10.2337/dc14-0798 pmid:25011944 fatcat:dcnkhbnhfbfkjj6rj2c7t3m5z4