Rate and Determinants of Association Between Advanced Retinopathy and Chronic Kidney Disease in Patients With Type 2 Diabetes

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Abstract

OBJECTIVE

To evaluate the rate and determinants of concordance between advanced diabetic retinopathy (DR) and chronic kidney disease (CKD), as assessed by both albuminuria and estimated glomerular filtration rate (eGFR), in the large cohort of the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study.

RESEARCH DESIGN AND METHODS

Patients with type 2 diabetes ( n = 15,773) visiting consecutively 19 hospital–based diabetes clinics in years 2007 and 2008 were examined. DR was assessed by dilated fundoscopy. CKD was defined based on albuminuria and eGFR.

RESULTS

CKD was present in 58.64% of subjects with advanced DR, whereas advanced DR was detectable only in 15.28% of individuals with any CKD and correlated with the albuminuric CKD phenotypes more than with the nonalbuminuric phenotype. Age, male sex, diabetes duration, hemoglobin A _1c, hypertension, triglycerides, previous cardiovascular disease, and, inversely, HDL-cholesterol correlated independently with the presence of any CKD in individuals with advanced DR; correlates differed according to the presence of albuminuria, reduced eGFR, or both. Conversely, factors associated with the presence of advanced DR in subjects with any CKD were diabetes treatment, previous cardiovascular disease, albuminuria, and, inversely, smoking, eGFR, and age at diagnosis.

CONCLUSIONS

Concordance of CKD with advanced DR is low in subjects with type 2 diabetes, and CKD without advanced DR is more frequent than isolated advanced DR, at variance with type 1 diabetes. Factors independently associated with the presence of any CKD in individuals with advanced DR differ, at least in part, from those correlating with the presence of advanced DR in subjects with any CKD and by CKD phenotype.

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Most cited references 21

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Important causes of visual impairment in the world today.

Nathan G Congdon, David Friedman, Thomas Lietman (2003)

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Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL.

Dick de Zeeuw, Giuseppe Remuzzi, Hans-Henrik Parving … (2004)

Proteinuria or albuminuria is an established risk marker for progressive renal function loss. Albuminuria can be effectively lowered with antihypertensive drugs that interrupt the renin-angiotensin system (RAS). We investigated whether albuminuria could not only serve as a marker of renal disease, but also function as a monitor of the renoprotective efficacy of RAS intervention by the angiotensin II (Ang II) antagonist, losartan, in patients with diabetic nephropathy. The data from the RENAAL (Reduction in End Points in Noninsulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan) study, a double-blind, randomized trial, were used to examine the effects of losartan on the renal outcome [i.e., the primary composite end point of doubling of serum creatinine, end-stage renal disease (ESRD) or death] in 1513 type 2 diabetic patients with nephropathy. We examined the effect of the degree of albuminuria at baseline, initial antiproteinuric response to therapy, and the degree of remaining (residual) albuminuria on renal outcome (either the primary composite end point of RENAAL or ESRD). We also evaluated the contribution to renal protection of the antiproteinuric effect of losartan independently of changes in blood pressure. Baseline albuminuria is almost linearly related to renal outcome, and is the strongest predictor among all measured well-known baseline risk parameters. After adjusting for baseline risk markers of age, gender, race, weight, smoking, sitting diastolic blood pressure, sitting systolic blood pressure, total cholesterol, serum creatinine, albuminuria, hemoglobin, and hemoglobin A(1c) (HbA(1c)) patients with high baseline albuminuria (> or =3.0 g/g creatinine) showed a 5.2-fold (95% CI 4.3-6.3) increased risk for reaching a renal end point, and a 8.1-fold (95% CI 6.1-10.8) increased risk for progressing to ESRD, compared to the low albuminuria group (<1.5 g/g). The changes in albuminuria in the first 6 months of therapy are roughly linearly related to the degree of long-term renal protection: every 50% reduction in albuminuria in the first 6 months was associated with a reduction in risk of 36% for renal end point and 45% for ESRD during later follow-up. Albuminuria at month 6, designated residual albuminuria, showed a linear relationship with renal outcome, almost identical to the relationship between baseline albuminuria and renal risk. Losartan reduced albuminuria by 28% (95% CI -25% to -36%), while placebo increased albuminuria by 4% (95% CI +8% to -1%) in the first 6 months of therapy. The specific (beyond blood pressure lowering) renoprotective effect of the Ang II antagonist, losartan, in this study is for the major part explained by its antialbuminuric effect (approximately 100% for the renal end point, and 50% for ESRD end point). Albuminuria is the predominant renal risk marker in patients with type 2 diabetic nephropathy on conventional treatment; the higher the albuminuria, the greater the renal risk. Reduction in albuminuria is associated with a proportional effect on renal protection, the greater the reduction the greater the renal protection. The residual albuminuria on therapy (month 6) is as strong a marker of renal outcome as is baseline albuminuria. The antiproteinuric effect of losartan explains a major component of its specific renoprotective effect. In conclusion, albuminuria should be considered a risk marker for progressive loss of renal function in type 2 diabetes with nephropathy, as well as a target for therapy. Reduction of residual albuminuria to the lowest achievable level should be viewed as a goal for future renoprotective treatments.

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Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus.

Holly Kramer, Quan Nguyen, Gary Curhan … (2003)

Kidney disease in type 2 diabetes mellitus (DM) is more heterogeneous than in type 1 DM. Reduced glomerular filtration rate (GFR) among individuals with type 2 DM may not always be due to classic diabetic glomerulosclerosis, which is associated with albuminuria and retinopathy. To determine the prevalence of chronic renal insufficiency (CRI), defined as a GFR less than 60 mL/min per 1.73 m2 body surface area (BSA) in the absence of microalbuminuria or macroalbuminuria and diabetic retinopathy among adults with type 2 DM. Cross-sectional analysis of adults aged 40 years or older with type 2 DM in the Third National Health and Nutrition Examination Survey, a probability sample of the total civilian US noninstitutionalized population conducted from 1988-1994. The GFR per 1.73 m2 BSA, calculated with serum creatinine, urea nitrogen, and serum albumin levels using the Modification of Diet in Renal Disease Study prediction equation; albuminuria, assessed using spot urine albumin/creatinine ratio; and presence of retinopathy, determined with fundus photography. Overall, 13% (sampled n = 171) of adults with type 2 DM (n = 1197) had CRI with a population estimate of 1.1 million. Among these adults with CRI, diabetic retinopathy was noted in 28% (n = 58), while the frequencies of microalbuminuria and macroalbuminuria were 45% (n = 64) and 19% (n = 47), respectively. Retinopathy and albuminuria (microalbuminuria or macroalbuminuria) were both absent in 30% (n = 51) of adults with type 2 DM and CRI. The population estimate of adults with type 2 DM and CRI in the absence of diabetic retinopathy or albuminuria was approximately 0.3 million. A substantial burden of CRI among persons with type 2 DM in the United States is likely due to renal parenchymal disease other than classic diabetic glomerulosclerosis. Approaches to screening renal disease in the type 2 DM population should incorporate assessment of GFR in addition to monitoring urine albumin excretion and funduscopic changes to ensure that individuals with type 2 DM and CRI not due to diabetic glomerulosclerosis will receive appropriate intervention.

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Author and article information

Journal

Journal ID (nlm-ta): Diabetes Care

Journal ID (iso-abbrev): Diabetes Care

Journal ID (hwp): diacare

Journal ID (pmc): dcare

Journal ID (publisher-id): Diabetes Care

Title: Diabetes Care

Publisher: American Diabetes Association

ISSN (Print): 0149-5992

ISSN (Electronic): 1935-5548

Publication date (Print): November 2012

Publication date (Electronic): 13 October 2012

Volume: 35

Issue: 11

Pages: 2317-2323

Affiliations

[1] ¹Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy; the

[2] ²Department of Internal Medicine, University of Pisa, Pisa, Italy

[3] ³Division of Endocrinology and Metabolic Diseases, University of Verona, Verona, Italy the

[4] ⁴Department of Medical Sciences, the Endocrinology and Diabetes Unit, Fondazione IRCCS, Cà Granda – Ospedale Maggiore Policlinico, Milan, Italy the

[5] ⁵Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan, Italy the

[6] ⁶Diabetes Unit, Hospital of Bergamo, Bergamo, Italy the

[7] ⁷Department of Internal Medicine, University of Turin, Turin, Italy the

[8] ⁸Department of Clinical and Biological Sciences, the Unit of Internal Medicine, University of Turin, Turin, Italy

[9] ⁹Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy the

[10] ¹⁰Department of Internal Medicine and Medical Specialties, La Sapienza University, Rome, Italy the

[11] ¹¹Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro, Chieti, Italy the

[12] ¹²Department of Clinical and Molecular Medicine, La Sapienza University, Rome, Italy

Author notes

Corresponding author: Giuseppe Pugliese, giuseppe.pugliese@ 123456uniroma1.it .

Article

Publisher ID: 0628

DOI: 10.2337/dc12-0628

PMC ID: 3476898

PubMed ID: 23093684

SO-VID: 8dd6a3ef-7065-4367-b942-4e973a340e88

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Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

Rate and Determinants of Association Between Advanced Retinopathy and Chronic Kidney Disease in Patients With Type 2 Diabetes : The Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study

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Abstract

OBJECTIVE

RESEARCH DESIGN AND METHODS

RESULTS

CONCLUSIONS

Related collections

Journal of the ASEAN Federation of Endocrine Societies

Most cited references 21

Important causes of visual impairment in the world today.

Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL.

Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus.

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