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      Preservation of renal function by intensive glycemic control

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          Summary

          We report the case of a 67-year-old Japanese woman with type 1 diabetes mellitus. At 47 years of age, her hemoglobin A1c (HbA1c) was 10.0%, and she had overt nephropathy. The first renal biopsy yielded a diagnosis of diabetic nephropathy. Intensive glycemic control was initiated and her HbA1c improved to 6.0%. Renal dysfunction showed no progression for 15 years. At 62 years of age, a second renal biopsy was performed. Glomerular lesions did not show progression but tubulointerstitial fibrosis and vascular lesions showed progression compared with the first biopsy. Intensive glycemic control can prevent the progression of glomerular lesions, but might not be effective for interstitial and vascular lesions.

          Learning points:
          • Intensive control of blood glucose can prevent the progression of glomerular lesions.

          • Intensive control of blood glucose may not be able to prevent progression of interstitial and vascular lesions.

          • CSII reduces HbA1c without increasing the risk of hypoglycemia.

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          Most cited references8

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          Pathologic classification of diabetic nephropathy.

          Although pathologic classifications exist for several renal diseases, including IgA nephropathy, focal segmental glomerulosclerosis, and lupus nephritis, a uniform classification for diabetic nephropathy is lacking. Our aim, commissioned by the Research Committee of the Renal Pathology Society, was to develop a consensus classification combining type1 and type 2 diabetic nephropathies. Such a classification should discriminate lesions by various degrees of severity that would be easy to use internationally in clinical practice. We divide diabetic nephropathy into four hierarchical glomerular lesions with a separate evaluation for degrees of interstitial and vascular involvement. Biopsies diagnosed as diabetic nephropathy are classified as follows: Class I, glomerular basement membrane thickening: isolated glomerular basement membrane thickening and only mild, nonspecific changes by light microscopy that do not meet the criteria of classes II through IV. Class II, mesangial expansion, mild (IIa) or severe (IIb): glomeruli classified as mild or severe mesangial expansion but without nodular sclerosis (Kimmelstiel-Wilson lesions) or global glomerulosclerosis in more than 50% of glomeruli. Class III, nodular sclerosis (Kimmelstiel-Wilson lesions): at least one glomerulus with nodular increase in mesangial matrix (Kimmelstiel-Wilson) without changes described in class IV. Class IV, advanced diabetic glomerulosclerosis: more than 50% global glomerulosclerosis with other clinical or pathologic evidence that sclerosis is attributable to diabetic nephropathy. A good interobserver reproducibility for the four classes of DN was shown (intraclass correlation coefficient = 0.84) in a test of this classification.
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            Reversal of lesions of diabetic nephropathy after pancreas transplantation.

            In patients with type I diabetes mellitus who do not have uremia and have not received a kidney transplant, pancreas transplantation does not ameliorate established lesions of diabetic nephropathy within five years after transplantation, but the effects of longer periods of normoglycemia are unknown. We studied kidney function and performed renal biopsies before pancreas transplantation and 5 and 10 years thereafter in eight patients with type I diabetes but without uremia who had mild to advanced lesions of diabetic nephropathy at the time of transplantation. The biopsy samples were analyzed morphometrically. All patients had persistently normal glycosylated hemoglobin values after transplantation. The median urinary albumin excretion rate was 103 mg per day before transplantation, 30 mg per day 5 years after transplantation, and 20 mg per day 10 years after transplantation (P=0.07 for the comparison of values at base line and at 5 years; P=0.11 for the comparison between base line and 10 years). The mean (+/-SD) creatinine clearance rate declined from 108+/-20 ml per minute per 1.73 m2 of body-surface area at base line to 74+/-16 ml per minute per 1.73 m2 at 5 years (P<0.001) and 74+/-14 ml per minute per 1.73 m2 at 10 years (P<0.001). The thickness of the glomerular and tubular basement membranes was similar at 5 years (570+/-64 and 928+/-173 nm, respectively) and at base line (594+/-81 and 911+/-133 nm, respectively) but had decreased by 10 years (to 404+/-38 and 690+/-111 nm, respectively; P<0.001 and P=0.004 for the comparisons with the base-line values). The mesangial fractional volume (the proportion of the glomerulus occupied by the mesangium) increased from base line (0.33+/-0.07) to 5 years (0.39+/-0.10, P=0.02) but had decreased at 10 years (0.27+/-0.02, P=0.05 for the comparison with the baseline value and P=0.006 for the comparison with the value at 5 years), mostly because of a reduction in mesangial matrix. Pancreas transplantation can reverse the lesions of diabetic nephropathy, but reversal requires more than five years of normoglycemia.
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              A new Classification of Diabetic Nephropathy 2014: a report from Joint Committee on Diabetic Nephropathy

              The Joint Committee on Diabetic Nephropathy has revised its Classification of Diabetic Nephropathy (Classification of Diabetic Nephropathy 2014) in line with the widespread use of key concepts, such as the estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). In revising the Classification, the Committee carefully evaluated, as relevant to current revision, the report of a study conducted by the Research Group of Diabetic Nephropathy, Ministry of Health, Labor and Welfare of Japan. Major revisions to the Classification are summarized as follows: (i) eGFR is substituted for GFR in the Classification; (ii) the subdivisions A and B in stage 3 (overt nephropathy) have been reintegrated; (iii) stage 4 (kidney failure) has been redefined as a GFR <30 mL/min/1.73 m2, regardless of the extent of albuminuria; and (iv) stress has been placed on the differential diagnosis of diabetic nephropathy versus non-diabetic kidney disease as being crucial in all stages of diabetic nephropathy.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                8 January 2018
                2018
                : 2018
                : 17-0136
                Affiliations
                [1 ]Nephrology Center and Department of Rheumatology , Toranomon Hospital, Tokyo, Japan
                [2 ]Department of Pathology , Toranomon Hospital, Tokyo, Japan
                [3 ]Okinaka Memorial Institute for Medical Research , Tokyo, Japan
                [4 ]Department of Pathology , Yokohama City University, Graduate School of Medicine, Yokohama, Japan
                [5 ]Department of Nephrology , Kyoto University Graduate School of Medicine, Japan
                Author notes
                Correspondence should be addressed to N Toriu or Y Ubara; Email: torippy.naoya@ 123456gmail.com or ubara@ 123456toranomon.gr.jp
                Article
                EDM-17-0136
                10.1530/EDM-17-0136
                5763276
                0ab93eba-d54a-4927-af07-ac2d40ecc951
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

                History
                : 20 November 2017
                : 6 December 2017
                Categories
                Insight into Disease Pathogenesis or Mechanism of Therapy

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