Renal hemodynamic dysfunction and neuropathy in longstanding type 1 diabetes: Results from the Canadian study of longevity in type 1 diabetes.

Aims: To determine the relationship between renal hemodynamic function and neuropathy in adults with ≥50-years of type 1 diabetes (T1D) compared to nondiabetic controls.
Methods: Glomerular filtration rate (GFR, inulin), effective renal plasma flow (ERPF, p-aminohippurate), modified Toronto Clinical Neuropathy Score (mTCNS), corneal confocal microscopy, nerve conduction, and heart rate variability (autonomic function) were measured; afferent (R _A ) and efferent (R _E ) arteriolar resistances were estimated using the Gomez equations in 74 participants with T1D and in 75 controls. Diabetic kidney disease (DKD) non-resistors were defined by eGFR _MDRD  < 60 ml/min/1.73 m ² or 24-h urine albumin excretion >30 mg/day. Linear regression was applied to examine the relationships between renal function (dependent variable) and neuropathy measures (independent variable), adjusted for age, sex, HbA1c, systolic blood pressure, low density lipoprotein cholesterol, and 24-h urine albumin to creatinine ratio.
Results: Higher mTCNS associated with lower renal blood flow (β ± SE:-9.29 ± 4.20, p = 0.03) and greater R _E (β ± SE:32.97 ± 15.43, p = 0.04) in participants with T1D, but not in controls. DKD non-resistors had a higher mTCNS and worse measures of corneal nerve morphology compared to those without DKD. Renal hemodynamic parameters did not associate with autonomic nerve function.
Conclusions: Although neurological dysfunction in the presence of diabetes may contribute to impaired renal blood flow resulting in ischemic injury in patients with T1D, early autonomic dysfunction does not appear to be associated with kidney function changes.
Competing Interests: Declaration of competing interest J.A.L. has received either consulting fees or speaking honorarium or both from Novo Nordisk, Eli Lilly & Co, Merck Sharp & Dohme, and AstraZeneca. G.B. has received speaker honoraria from Johnson & Johnson. H.A.K. has received support from Sanofi. P.B. has acted as a consultant for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli-Lilly, LG Chemistry, Sanofi, Novo Nordisk, and Horizon Pharma. P.B. serves on the advisory boards for AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk and XORTX. LEL receives support from a CIHR Canada Graduate Scholarship Doctoral Award. B.A.P. has received speaker honoraria from Medtronic, Johnson & Johnson, Roche, GlaxoSmithKline Canada, Novo Nordisk, and Sanofi; has received research grant support from Medtronic and Boehringer Ingelheim; and serves as a consultant for NeuroMetrix. D.Z.I.C. has received consulting fees or speaking honorarium or both from Janssen, Boehringer Ingelheim-Eli, Lilly, AstraZeneca, Merck, and Sanofi, and has received operating funds from Janssen, Boehringer Ingelheim-Eli, Lilly, AstraZeneca and Merck.
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