Abnormal Na-li Countertransport Kinetics in Type 1 Diabetic Patients with Nephropathy and in Their Parents

Zerbini, Gianpaolo; Maestroni, Anna; Maestroni, Silvia; Gabellini, Daniela; Luzi, Livio
June 2007
Diabetes;Jun2007 Supplement 1, Vol. 56, pA91
Academic Journal
An inherited predisposition to essential hypertension is presently considered the most important cause of susceptibility to nephropathy in diabetic patients. This hypothesis is confirmed by the evidence that diabetic nephropathy is characterized by an increased activity of erythrocyte Na-Li counter-transport (SLC), the most consistent intermediate phenotype of essential hypertension. Although family studies and genetic epidemiology have suggested that variability of SLC measured at 150 mM external Na (standard assay) is under genetic control, it is unknown whether family members share similar SLC kinetic parameters. To clarify this issue we have therefore evaluated Vmax and Km for external Na of SLC in 21 type 1 diabetic patients with increased albumin excretion rate, in 25 normoalbuminuric patients matched for age, gender and duration of diabetes, and in their parents. As a result, SLC activity (standard assay) was confirmed to be increased in patients with diabetic nephropathy (547.9±51 µmol⋅lcell-1⋅h-1 mean±SEM) when compared to normoalbuminuric patients (381.0±30, p=0.02). Both Vmax (668.3±69 vs 428.4±37 µmol⋅1cell-1⋅h-1, p=0.004) and Km for external Na (61.1±5 vs 34.9±3 mM Na, p=0.0001) were also increased in patients with nephropathy. In parents of patients with nephropathy SLC activity (standard assay) was higher, though not significantly, that in parents of normoalbuminurics (423.8±127 vs 354.3±29 µmol⋅1cell-1⋅h-1, p=0.09). Both Vmax (518.7±35 vs 386.7±18 µmol⋅1cell-1⋅h-1, p=0.0007) and Km for external Na (57.5±4 vs 34.2±4 mM Na, p=0.0001) were instead significantly increased in parents of patients with nephropathy Finally, Vmax and Km of patients were respectively correlated to the mean of the Vmaxs (r2=0.42, p=0.0001) and Kms (r2=0.46, p=0.0001) of parents. In conclusion, this results demonstrate that a dysfunction of both Vmax and Km for external Na of SLC characterizes type 1 diabetic patients with nephropathy and their parents. This finding suggests that the SLC carrier is possibly affected by a major structural damage in nephropatic patients and that this dysfunction is probably extended also to relatives.


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