Relative contributions of diabetes and chronic kidney disease to neuropathy development in diabetic nephropathy patients.

OBJECTIVE

Chronic kidney disease (CKD) caused by diabetes is known as diabetic kidney disease (DKD). The present study aimed to examine the underlying mechanisms of axonal dysfunction and features of neuropathy in DKD compared to CKD and type 2 diabetes (T2DM) alone.

METHODS

Patients with DKD (n = 30), CKD (n = 28) or T2DM (n = 40) and healthy controls (n = 41) underwent nerve excitability assessments to examine axonal function. Neuropathy was assessed using the Total Neuropathy Score. A validated mathematical model of human axons was utilised to provide an indication of the underlying causes of nerve pathophysiology.

RESULTS

Total neuropathy score was significantly higher in patients with DKD compared to those with either CKD or T2DM (p < 0.05). In DKD, nerve excitability measures (S2 accommodation and superexcitability, p < 0.05) were more severely affected compared to both CKD and T2DM and worsened with increasing serum K (p < 0.01). Mathematical modelling indicated the basis for nerve dysfunction in DKD was an elevation of extracellular K and reductions in Na permeability and the hyperpolarisation-activated cation current, which was similar to CKD.

CONCLUSIONS

Patients with DKD manifested a more severe neuropathy phenotype and shared features of nerve dysfunction to that of CKD.

SIGNIFICANCE

The CKD, and not diabetes component, appears to underlie axonal pathophysiology in DKD.