Advanced Diabetic Nephropathy with "Clean" Eyes: An Extreme Phenotype

It is generally accepted that renal and eye changes in diabetes are concordant. There are however a fair number of patients with diabetes who have end-stage renal disease (ESRD) without any of the typical eye changes. The present study highlights the discordance between retinopathy and nephropathy and describes a series of patients of long-standing diabetes undergoing renal transplant who had little or no evidence of retinopathy.

All patients with ESRD undergoing renal transplants underwent comprehensive fundus evaluation including dilated indirect ophthalmoscopy, slit lamp biomicroscopy, and fundus photography. The patients' age, gender, physical parameters (body mass index and blood pressure), duration of diabetes, glycosylated hemoglobin (HbA1c), albumin creatinine ratio, and presence of diabetic peripheral neuropathy (DPN) were determined. Renal histopathology was reviewed, if available.

Five patients with diabetic nephropathy (DN) underwent renal transplant and had no evidence of diabetic retinopathy (DR) or up to two microaneurysms per fundus. All the patients were between 50 and 65 (mean ± standard deviation - 58.6 ± 4.67) years of age. The mean duration of diabetes was 16 ± 2.91 years. All had poor glycemic control with a mean HbA1c of 9.2 ± 0.837%. All had hypertension, macroalbuminuria, and DPN.

There is a well-recognized association between retinopathy and nephropathy, in which nephropathy without retinopathy is rare but retinopathy without nephropathy is common. We have identified a subset of patients with kidney disease of sufficient severity to warrant renal transplant but who are protected from retinopathy. It is possible that there is an extreme phenotype of DN patients with unaffected eyes who carry genes protecting against DR.