Diabetic retinopathy is a prognostic factor for progression of chronic kidney disease in the patients with type 2 diabetes mellitus

Abstract

Since both retinopathy and nephropathy are major diabetic microvascular complications, we investigated whether severity of diabetic retinopathy (DR) has adverse effects on renal function and albuminuria in the patients with type 2 diabetes mellitus (DM). We screened 2,197 adult patients with type 2 DM who had undergone fundus exam between August 2006 and February 2014. Among them, 1,592 subjects with available serial renal function and albuminuria measurement were included in the analysis. DR status was classified as no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). The risk of CKD progression was assessed according to DR severity. A total of 384 (24.1%) had NPDR and 202 (12.7%) had PDR at either eye. The mean follow-up period was 5.6±2.1 years. DR was associated with lower body mass index, lower plasma hemoglobin, lower serum albumin level, longer duration of DM, poorer control of blood sugar, lower estimated glomerular filtration rate (eGFR), and greater amount of albuminuria. Interestingly, baseline DR severity was associated with faster renal function decline and greater albuminuria progression. In multivariate analysis, NPDR had 2.9 times and PDR had 16.6 times higher risk for CKD progression. Our findings showed that baseline DR severity is a prognostic factor for future CKD progression in type 2 DM patients. Therefore, clinicians must evaluate DR severity at the first visit and closely monitor renal function and albuminuria in the subjects with severe DR.

Fig 1. Description of study participants.

A total of 2,197 adult DM patients who visited ophthalmologic clinic at Kangnam Sacred Heart Hospital was screened. Among them, 17 patients were type 1 DM, 49 did not received retinal exam, 8 was diagnosed as hypertensive retinopathy, 6 already was blind, 6 had artificial eyes, and 1 had retinal vein occlusion. Another 400 patients were not available for serial renal function data over 1 year and 118 subjects were already in the advanced stage of chronic kidney disease (stage 4 and 5). Therefore, after excluding 605 patients, a total of 1,592 subjects were included in the final analysis for renal outcome.

Fig 2. Annual renal function decline rate according to initial diabetic retinopathy status.

To exclude the effect of baseline renal function upon future renal function decline rate, we performed subgroup analysis according to baseline CKD stages based on eGFR. In CKD stage 1 (n = 517), patients with NPDR and PDR at baseline showed faster decline of renal function compared to those without DR (-3.2±6.44 and -4.16±5.43 vs. -0.83±3.48 mL/min/1.73m²/year, p<0.001). The patients with NPDR and PDR with baseline CKD stages 2 (n = 797), 3a (n = 188), and 3b (n = 90) showed decline in renal function during follow up (-1.91±5.71, -0.53±4.25 and -2.3±3.34 mL/min/1.73m² per year for NPDR and -3.97±6.08, -2.58±5.71 and -2.89±9.19 mL/min/1.73m² per year for PDR) while those without DR showed preserved renal function during follow-up (0.47±3.22, 1.24±3.91 and 0.5±4.34 mL/min/1.73m² per year, p<0.001). eGFR, estimated glomerular filtration rate; CKD, chronic kidney disease; DR, diabetic retinopathy; NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy.

Fig 3. Proportion of the subjects with CKD progression according to initial diabetic retinopathy status.

CKD progression was defined by one or more of the following: 1) decline in GFR category (≥90 [G1], 60–89 [G2], 45–59 [G3a], 30–44 [G3b], 15–29 [G4], <15 [G5] mL/min/1.73m²) accompanied by a 25% or greater drop in eGFR from baseline, 2) sustained decline in eGFR of more than 5 mL/min/1.73m²/year. The proportion of the subjects with CKD progression increased as DR severity increased (9.5 vs. 29.9 vs. 49.5%, p<0.001). GFR, glomerular filtration rate; DR, diabetic retinopathy; NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy.

Fig 4. Proportion of the subjects with albuminuria progression according to initial diabetic retinopathy status.

Albuminuria progression was defined by one or more step progression in albuminuria (normo-albuminuria (UACR < 30mg/g) to micro-albuminuria (30mg/g ≤ UACR < 300 mg/g) or macro-albuminuria (UACR ≥ 300 mg/g), micro-albuminuria to macro-albuminuria) during follow-up. The proportion of the subjects with albuminuria progression increased as DR severity increased (14.4% vs. 27.1% vs. 43.5%, p<0.001). DR, diabetic retinopathy; NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy.