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      Non-diabetic renal disease in type 2 diabetes mellitus: Study of renal - retinal relationship

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          Abstract

          Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease worldwide. Non-diabetic renal disease (NDRD), is known to occur in diabetic patients. The renal and retinal relationship in type 2 diabetes mellitus (T2DM) with nephropathy is not uniform. This study was carried to study the histological spectrum of nephropathy in type 2 diabetic patients with proteinuria and its relationship with diabetic retinopathy (DR). Total 31 (males - 26; females - 5) proteinuric type 2 diabetic patients were studied. Average age of patients was 50.7 years. Nephrotic syndrome was noted in 21 (67.7%) patients. Overall, isolated DN, NDRD and NDRD superimposed on DN (mixed lesion) were observed in 12 (38.7%), 13 (41.9%) and 6 (19.4%) cases, respectively. DR was absent in 21/31 (67.7%) cases. The spectrum of nephropathy in patients without DR included: DN in 6 (28.57%), NDRD in 12 (57.14%) and mixed lesion in 3 (14.29%). Kidney histology in patients with DR ( n-10) revealed DN in 6 (60%), NDRD in 1 (10%) and mixed lesion in 3 (30%) patients. Thus, absence of DR favors NDRD but does not exclude DN because isolated DN was noted in 28.57% cases in absence of DR. Similarly biopsy proven NDRD (pure NDRD; 10% and mixed lesion; 30%) was noted in 40% of cases in presence of DR. In summary, patients with T2DM had higher incidence of NDRD. DR is less frequent (32.3%) in type 2 diabetes and is a poor predictor of type of nephropathy. Hence, renal biopsy is essential for precise diagnosis of nephropathy in patients with T2DM.

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          Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus: prospective, observational study.

          To evaluate putative risk factors for the development of incipient diabetic nephropathy (persistent microalbuminuria) and overt diabetic nephropathy (persistent macroalbuminuria) in patients with non-insulin dependent diabetes. Prospective, observational study of a cohort of white, non-insulin dependent diabetic patients followed for a median period of 5.8 years. Outpatient clinic in tertiary referral centre. 191 patients aged under 66 years with non-insulin dependent diabetes and normoalbuminuria (urinary albumin excretion rate or = mg/24 h in two out of three consecutive collections) during follow up. The five year cumulative incidence of incipient diabetic nephropathy was 23% (95% confidence interval 17% to 30%). Cox's multiple stepwise regression analysis revealed the following risk factors for the development of incipient or overt diabetic nephropathy: increased baseline log urinary albumin excretion rate (relative risk 11.1 (3.4 to 35.9); P < 0.0001); male sex (2.6 (1.2 to 5.4); P < 0.02); presence of retinopathy (2.4 (1.3 to 4.7); P < 0.01); increased serum cholesterol concentration (1.4 (1.1 to 1.7); P < 0.01); haemoglobin A1c concentration (1.2 (1.0 to 1.4); P < 0.05); and age (1.07 (1.02 to 1.12); P < 0.01). Known duration of diabetes, body mass index, arterial blood pressure, serum creatinine concentration, pre-existing coronary heart disease, and history of smoking were not risk factors. Several potentially modifiable risk factors predict the development of incipient and overt diabetic nephropathy in normoalbuminuric patients with non-insulin dependent diabetes.
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            The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus.

            Despite the numerous studies on the relation of albuminuria with increased risk of all-cause mortality in type 2 diabetes mellitus, it remains uncertain whether microalbuminuria and/or gross proteinuria are independent risk factors for cardiovascular mortality. Moreover, the association of albuminuria with cardiovascular mortality in people with type 2 diabetes mellitus has not been well described in US populations. To estimate the relative risks (RRs) for the associations of microalbuminuria and gross proteinuria with cardiovascular disease mortality among persons with older-onset diabetes mellitus. We conducted a prospective cohort study of 840 people with older-onset diabetes mellitus who provided urine samples in the 1984-1986 examination of a population-based study of diabetic persons. The presence of microalbuminuria was determined by an agglutination inhibition assay and gross proteinuria by a reagent strip. The main outcome was time to mortality from cardiovascular disease, as determined from death certificates. Of the 840 older-onset diabetic persons, 54.8% had normoalbuminuria, while 24.8% had microalbuminuria and 20.5% had gross proteinuria. During the 12-year follow-up (6127 person-years), we identified 364 deaths from cardiovascular disease. Compared with persons with normoalbuminuria, those with microalbuminuria and gross proteinuria had significantly higher risks of cardiovascular mortality. The RR as controlled for age, sex, glycemic control, insulin use, alcohol intake, physical activity, cardiovascular disease history, antihypertensive use, and retinopathy severity, was 1.84 (95% confidence interval [CI], 1.42-2.40) for those with microalbuminuria and 2.61 (95% CI, 1.99-3.43) for those with gross proteinuria. Further adjustment for other factors did not change the relations we found. When the end point used was mortality from coronary heart disease, stroke, or all causes, the increased risks were significant for both microalbuminuria (adjusted RRs [95% CIs], 1.96 [1.42-2.72], 2.20 [1.29-3.75], and 1.68 [1.35-2.09], respectively) and gross proteinuria (adjusted RRs [95% CIs], 2.73 [1.95-3.81], 2.33 [1.28-4.24], and 2.47 [1.97-3.10], respectively). Results from our population-based study strongly suggest that both microalbuminuria and gross proteinuria were significantly associated with subsequent mortality from all causes and from cardiovascular, cerebrovascular, and coronary heart diseases. These associations were independent of known cardiovascular risk factors and diabetes-related variables.
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              Diabetic retinopathy in predicting diabetic nephropathy in patients with type 2 diabetes and renal disease: a meta-analysis.

              The aim of this meta-analysis is to determine the predictive value of diabetic retinopathy in differentiating diabetic nephropathy from non-diabetic renal diseases in patients with type 2 diabetes and renal disease. Medline and Embase databases were searched from inception to February 2012. Renal biopsy studies of participants with type 2 diabetes were included if they contained data with measurements of diabetic retinopathy. Pooled sensitivity, specificity, positive predictive value, negative predictive value and other diagnostic indices were evaluated using a random-effects model. The meta-analysis investigated 26 papers with 2012 patients. The pooled sensitivity and specificity of diabetic retinopathy to predict diabetic nephropathy were 0.65 (95% CI 0.62, 0.68) and 0.75 (95% CI 0.73, 0.78), respectively. The pooled positive and negative predictive value of diabetic retinopathy to predict diabetic nephropathy were 0.72 (95% CI 0.68, 0.75) and 0.69 (95% CI 0.67, 0.72), respectively. The area under the summary receiver operating characteristic curve was 0.75, and the diagnostic odds ratio was 5.67 (95% CI 3.45, 9.34). For proliferative diabetic retinopathy, the pooled sensitivity was 0.25 (95% CI 0.16, 0.35), while the specificity was 0.98 (95% CI 0.92, 1.00). There was heterogeneity among studies (p < 0.001), and no publishing bias was identified. Diabetic retinopathy is useful in diagnosing or screening for diabetic nephropathy in patients with type 2 diabetes and renal disease. Proliferative diabetic retinopathy may be a highly specific indicator for diabetic nephropathy.
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                Author and article information

                Journal
                Indian J Nephrol
                Indian J Nephrol
                IJN
                Indian Journal of Nephrology
                Medknow Publications & Media Pvt Ltd (India )
                0971-4065
                1998-3662
                Jul-Aug 2015
                : 25
                : 4
                : 222-228
                Affiliations
                [1]Department of Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
                [1 ]Department of Medicine, TNMC, Mumbai, Maharashtra, India
                [2 ]Department of Ophthalmology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
                [3 ]Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
                [4 ]Department of Community Medicine, IMS, BHU, Varanasi, Uttar Pradesh, India
                Author notes
                Address for correspondence: Dr. Jai Prakash, Department of Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh, India. E-mail: jpojha555@ 123456hotmail.com
                Article
                IJN-25-222
                10.4103/0971-4065.144420
                4495476
                3e8b4e17-6109-432f-9899-13b9935746b1
                Copyright: © Indian Journal of Nephrology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Original Article

                Nephrology
                diabetic retinopathy,nephrotic syndrome,non-diabetic renal disease,type 2 diabetes mellitus

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