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      Clinical predictive factors in diabetic kidney disease progression

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          Abstract

          Diabetic kidney disease ( DKD) represents a major component of the health burden associated with type 1 and type 2 diabetes. Recent advances have produced an explosion of ‘novel’ assay‐based risk markers for DKD, though clinical use remains restricted. Although many patients with progressive DKD follow a classical albuminuria‐based pathway, non‐albuminuric DKD progression is now well recognized. In general, the following clinical and biochemical characteristics have been associated with progressive DKD in both type 1 and type 2 diabetes: increased hemoglobin A1c, systolic blood pressure, albuminuria grade, early glomerular filtration rate decline, duration of diabetes, age (including pubertal onset) and serum uric acid; the presence of concomitant microvascular complications; and positive family history. The same is true in type 2 diabetes for male sex category, in patients following an albuminuric pathway to DKD, and also true for the presence of increased pulse wave velocity. The following baseline clinical characteristics have been proposed as risk factors for DKD progression, but with further research required to assess the nature of any relationship: dyslipidemia (including low‐density lipoprotein, total and high‐density lipoprotein cholesterol); elevated body mass index; smoking status; hyperfiltration; decreases in vitamin D, hemoglobin and uric acid excretion (all known consequences of advanced DKD); and patient test result visit‐to‐visit variability (hemoglobin A1c, blood pressure and high‐density lipoprotein cholesterol). The development of multifactorial ‘renal risk equations’ for type 2 diabetes has the potential to simplify the task of DKD prognostication; however, there are currently none for type 1 diabetes‐specific populations. Significant progress has been made in the prediction of DKD progression using readily available clinical data, though further work is required to elicit the role of several variables, and to consolidate data to facilitate clinical implementation.

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          Obesity-related glomerulopathy: an emerging epidemic.

          We report the first large renal biopsy-based clinicopathologic study on obesity-related glomerulopathy. Obesity was defined as body mass index (BMI)> 30 kg/m2. Obesity-related glomerulopathy (ORG) was defined morphologically as focal segmental glomerulosclerosis and glomerulomegaly (O-FSGS; N = 57) or glomerulomegaly alone (O-GM; N = 14). Review of 6818 native renal biopsies received from 1986 to 2000 revealed a progressive increase in biopsy incidence of ORG from 0.2% in 1986-1990 to 2.0% in 1996-2000 (P = 0.0001). Mean BMI in ORG was 41.7 (range 30.9 to 62.7). Indications for renal biopsy included proteinuria (N = 40) or proteinuria and renal insufficiency (N = 31). Seventy-one patients with ORG were compared to 50 patients with idiopathic FSGS (I-FSGS). Patients with ORG were older (mean 42.9 vs. 32.6 years, P < 0.001) and more often Caucasian (75% vs. 52%; P = 0.003). ORG patients had a lower incidence of nephrotic range proteinuria (48% vs. 66%; P = 0.007) and nephrotic syndrome (5.6% vs. 54%; P < 0.001), with higher serum albumin (3.9 vs. 2.9 g/dL; P < 0.001), lower serum cholesterol (229 vs. 335 mg/dL; P < 0.001), and less edema (35% vs. 68%; P = 0.003). On renal biopsy, patients with ORG had fewer lesions of segmental sclerosis (10 vs. 39%; P < 0.001), more glomerulomegaly (100% vs. 10%; P < 0.001), and less extensive foot process effacement (40 vs. 75%; P < 0.001). Glomerular diameter in ORG (mean 226 mu) was significantly larger than age- and sex-matched normal controls (mean 168 mu; P < 0.001). Follow-up was available in 56 ORG patients (mean 27 months) and 50 idiopathic FSGS controls (mean 38 months). A total of 75% of ORG patients received angiotensin-converting enzyme (ACE) inhibition or A2 blockade while 78% of the I-FSGS patients received immunosuppressive therapy. ORG patients had less frequent doubling of serum creatinine (14.3% vs. 50%; P < 0.001) and progression to ESRD (3.6% vs. 42%; P < 0.001). On multivariate analysis, presenting serum creatinine and severity of proteinuria were the only predictors of poor outcome in ORG. ORG is distinct from idiopathic FSGS, with a lower incidence of nephrotic syndrome, more indolent course, consistent presence of glomerulomegaly, and milder foot process fusion. The ten-fold increase in incidence over 15 years suggests a newly emerging epidemic. Heightened physician awareness of this entity is needed to ensure accurate diagnosis and appropriate therapy.
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            Nephropathy in diabetes.

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              The hyperfiltration theory: a paradigm shift in nephrology.

              Experimental studies incriminate glomerular hypertension in mediating progressive renal damage after any of a variety of initiating injuries. Prevention of glomerular hypertension by dietary protein restriction or antihypertensive therapy lessens progressive glomerular damage in several experimental models of chronic renal disease. Glomerular hypertension and hyperfiltration also occur in humans with diabetes mellitus, solitary or remnant kidneys, and various forms of acquired renal disease. Clinical studies indicate that dietary protein restriction and antihypertensive therapy also slow progression in many of these disorders. Large multicenter trials confirm the beneficial effects of these therapeutic maneuvers on the rate of progression of chronic renal disease.
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                Author and article information

                Contributors
                elif.ekinci@unimelb.edu.au
                Journal
                J Diabetes Investig
                J Diabetes Investig
                10.1111/(ISSN)2040-1124
                JDI
                Journal of Diabetes Investigation
                John Wiley and Sons Inc. (Hoboken )
                2040-1116
                2040-1124
                08 June 2016
                January 2017
                : 8
                : 1 ( doiID: 10.1111/jdi.2017.8.issue-1 )
                : 6-18
                Affiliations
                [ 1 ]Austin Clinical School Melbourne VictoriaAustralia
                [ 2 ]The University of Melbourne Melbourne VictoriaAustralia
                [ 3 ]Austin Health Endocrine Center Melbourne VictoriaAustralia
                [ 4 ] Department of Endocrinology & DiabetesSt Vincent's Hospital Melbourne VictoriaAustralia
                [ 5 ]Menzies School of Health Darwin Northern TerritoryAustralia
                Author notes
                [*] [* ] Correspondence

                Elif I Ekinci

                Tel.: +61‐3‐9496‐5489

                Fax: +61‐3‐9497‐4554

                E‐mail address: elif.ekinci@ 123456unimelb.edu.au

                Article
                JDI12533
                10.1111/jdi.12533
                5217935
                27181363
                790fb806-5cf0-416a-a584-fcccbd7e60fc
                © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 19 November 2015
                : 10 March 2016
                : 14 March 2016
                Page count
                Figures: 2, Tables: 0, Pages: 13, Words: 10960
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                jdi12533
                January 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.0 mode:remove_FC converted:05.01.2017

                diabetic kidney disease,diabetic nephropathy,risk factors

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