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High Risk of ESRD in Type 1 Diabetes: New Strategies Are Needed to Retard Progressive Renal Function Decline

      Summary

      Care of patients with type 1 diabetes (T1D) has changed during the past 30 years. Tools to control hyperglycemia have improved and it was shown that improvement in glycemic control diminished the risk of late diabetic complications, including nephropathy. Moreover, in patients with impaired renal function, aggressive treatment of hypertension and renoprotective blockade of the renin-angiotensin system were shown to postpone end-stage renal disease (ESRD), albeit for a short while. Despite these achievements, the incidence of ESRD caused by T1D in the US population has not decreased but rather has increased over the past 20 years, although it now occurs at slightly older ages. This state of affairs is a call to action. This should begin with adopting a new model of diabetic nephropathy in human beings. In that model, instead of microalbuminuria or proteinuria, the focus should be on diagnosis and treatment of progressive renal function decline that leads to ESRD. Such a model has received significant support in clinical and epidemiologic studies. Investigation of mechanisms of such progressive renal function decline should help in the identification of new therapeutic targets and the development of new interventions. To evaluate these interventions, accurate diagnostic algorithms are needed so T1D patients will be stratified according to time to onset to ESRD. Consistent with concepts of personalized medicine, the new interventions should be tailored to and evaluated in patients predicted to have rapid, moderate, or even slow progression to ESRD.

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      References

        • Nawroth P.P.
        • Isermann B.
        Mechanisms of diabetic nephropathy–old buddies and newcomers part 1.
        Exp Clin Endocrinol Diabetes. 2010; 118: 571-576
        • Nawroth P.P.
        • Isermann B.
        Mechanisms of diabetic nephropathy–old buddies and newcomers part 2.
        Exp Clin Endocrinol Diabetes. 2010; 118: 667-672
        • Thomas M.C.
        Pathogenesis and progression of proteinuria.
        Contrib Nephrol. 2011; 170: 48-56
        • The Diabetes Control and Complications Trial Research Group
        The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.
        N Engl J Med. 1993; 329: 977-986
        • de Boer I.H.
        • Sun W.
        • Cleary P.A.
        • et al.
        Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes.
        N Engl J Med. 2011; 365: 2366-2376
        • American Diabetes Association
        Standards of medical care in diabetes–2009.
        Diabetes Care. 2009; 32: S13-S61
        • Saaddine J.B.
        • Cadwell B.
        • Gregg E.W.
        • Engelgau M.M.
        • Vinicor F.
        • Imperatore G.
        • et al.
        Improvements in diabets processes of care and intermediaye outcomes: United States, 1988-2002.
        Ann Inter Med. 2006; 144: 465-474
        • Paris C.A.
        • Imperatore G.
        • Klingensmith G.
        • Petitti D.
        • Rodriguez B.
        • Anderrason A.M.
        • et al.
        Predictors of insulin regimens and impact on outcomes in youth with type 1 diabetes: the SEARCH for diabetes in youth study.
        J Pediatr. 2009; 155: 183-189
        • Krolewski A.S.
        • Laffel L.M.
        • Krolewski M.
        • Quinn M.
        • Warram J.H.
        Glycosylated hemoglobin and the risk of microalbuminuria in patients with insulin-dependent diabetes mellitus.
        N Engl J Med. 1995; 332: 1251-1255
        • Mogensen C.E.
        Long-term antihypertensive treatment inhibiting progression of DN.
        BMJ. 1982; 285: 685-688
        • Parving H.H.
        • Andersen A.R.
        • Smidt U.M.
        • Svendsen P.A.
        Early aggressive antihypertensive treatment reduces rate of decline in kidney function in DN.
        Lancet. 1982; 1: 1175-1179
        • Trocha A.K.
        • Schmidtke C.
        • Didjurgeit U.
        • Muhlhauser I.
        • Bender R.
        • Berger M.
        • et al.
        Effect of intensified antihypertensive treatment in diabetic nephropathy: mortality and morbidity results of a prospective controlled 10-year study.
        J Hypertens. 1999; 17: 1497-1503
        • UK Prospective Study Group
        Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38.
        BMJ. 1998; 317: 703-713
        • Carter B.L.
        Implementing the new guidelines for hypertension: JNC 7, ADA, WHO-ISH.
        J Manag Care Pharm. 2004; 10: S18-S25
        • Zatz R.
        • Meyer T.W.
        • Rennke H.G.
        • Brenner B.M.
        Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy.
        Proc Natl Acad Sci U S A. 1985; 82: 5963-5967
        • Hollenberg N.K.
        • Raij L.
        Angiotensin-converting enzyme inhibition and renal protection.
        Arch Intern Med. 1993; 153: 2426-2435
        • Lewis E.J.
        • Hunsicker L.G.
        • Bain R.P.
        • Rohde R.D.
        The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy.
        N Engl J Med. 1993; 329: 1456-1462
        • Mauer M.
        • Zinman B.
        • Gardiner R.
        • Suissa S.
        • Sinaiko A.
        • Strand T.
        • et al.
        Renal and retinal effects of enalapril and losartan in type 1 diabetes.
        N Engl J Med. 2009; 361: 40-51
        • Viberti G.
        • Mogensen C.E.
        • Groop L.C.
        • Pauls J.F.
        Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria.
        JAMA. 1994; 272: 275-279
        • Laffel L.M.
        • McGill J.B.
        • Gans D.J.
        The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria.
        Am J Med. 1995; 99: 497-504
        • Parving H.H.
        • Mauer M.
        • Ritz E.
        Diabetic nephropathy.
        in: Brenner B.M. Brenner and Rector's the kidney. 7th ed. Elsevier, Inc, Philadelphia2004: 1777-1818
        • Perkins B.A.
        • Ficociello L.H.
        • Roshan B.
        • Warram J.H.
        • Krolewski A.S.
        In patients with type 1 diabetes and new onset micro-albuminuria the development of advanced chronic kidney disease may not require progression to proteinuria.
        Kidney Int. 2010; 77: 57-64
        • Macisaac R.J.
        • Jerums G.
        Diabetic kidney disease with and without albuminuria.
        Curr Opin Nephrol Hypertension. 2011; 20: 246-257
        • Rosolowsky E.T.
        • Skupien J.
        • Smiles A.M.
        • Niewczas M.A.
        • Roshan B.
        • Stanton R.
        • et al.
        Risk of ESRD in type 1 diabetes remains high in spite of renoprotection.
        J Am Soc Nephrol. 2011; 22: 545-553
        • Forsblom C.
        • Harjutsalo V.
        • Thorn L.
        • Wadén J.
        • Tolonen N.
        • Saraheimo M.
        • et al.
        Competing-risk analysis of ESRD and death among patients with type 1 diabetes and macroalbuminuria.
        J Am Soc Nephrol. 2011; 22: 537-544
        • Perkins B.A.
        • Ficociello L.H.
        • Silva K.H.
        • Finkelstein D.M.
        • Warram J.H.
        • Krolewski A.S.
        Regression of microalbuminuria in type 1 diabetes.
        N Engl J Med. 2003; 348: 2285-2293
        • Perkins B.A.
        • Ficociello L.H.
        • Ostrander B.E.
        • Silva K.H.
        • Weinberg J.
        • Warram J.H.
        • et al.
        Microalbuminuria and risk of early progressive renal function decline in type 1 diabetes.
        J Am Soc Nephrol. 2007; 18: 1353-1361
        • Merchant M.L.
        • Perkins B.A.
        • Boratyn G.M.
        • Ficociello L.H.
        • Wilkey D.W.
        • Barati M.T.
        • et al.
        Urinary peptidome may predict renal function decline in type 1 diabetes and microalbuminuria.
        J Am Soc Nephrol. 2009; 20: 2065-2074
        • Skupien J.
        • Warram J.H.
        • Smiles A.M.
        • Niewczas M.A.
        • Gohda T.
        • Pezzolesi M.G.
        • et al.
        The early decline in renal function in patients with type 1 diabetes and proteinuria predicts the risk of end-stage renal disease.
        Kidney Int. 2012 May 23; ([Epub ahead of print])
        • Krolewski M.
        • Eggers P.W.
        • Warram J.H.
        Magnitude of end-stage renal disease in IDDM: a 35 year follow-up study.
        Kidney Int. 1996; 50: 2041-2046
        • Zahran A.
        • El Husseini A.
        • Shoker A.
        Can cystatin C replace creatinine to estimate glomerular filtration rate?.
        Am J Nephrol. 2007; 27: 197-205
        • Eriksen B.O.
        • Mathisen U.D.
        • Melsom T.
        • Ingebretsen O.C.
        • Jenssen T.G.
        • Njølstad I.
        • et al.
        Cystatin C is not a better estimator of GFR than plasma creatinine in the general population.
        Kidney Int. 2010; 78: 1305-1311
        • Krolewski A.S.
        • Warram J.H.
        • Forsblom C.
        • Smiles A.M.
        • Thorn L.
        • Skupien J.
        • et al.
        Serum Concentration of Cystatin C and Risk of End-Stage Renal Disease in Diabetes.
        Diabetes Care. 2012 Jul 30; ([Epub ahead of print])
        • Gohda T.
        • Niewczas M.A.
        • Ficociello L.H.
        • Walker W.H.
        • Skupien J.
        • Rosetti F.
        • et al.
        Circulating TNF receptors 1 and 2 predict stage 3 of CKD in type 1 diabetes.
        J Am Soc Nephrol. 2012; 23: 516-524
        • Niewczas M.A.
        • Gohda T.
        • Skupien J.
        • Smiles A.M.
        • Walker W.H.
        • Rosetti F.
        • et al.
        Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes.
        J Am Soc Nephrol. 2012; 23: 507-515
        • Thomas M.C.
        • Groop P.H.
        New approaches to the treatment of nephropathy in diabetes.
        Expert Opin Investig Drugs. 2011; 20: 1057-1071
        • Stanton R.C.
        Oxidative stress and diabetic kidney disease.
        Curr Diab Rep. 2011; 11: 330-336
        • Ruggenenti P.
        • Cravedi P.
        • Remuzzi G.
        The RAAS in the pathogenesis and treatment of diabetic nephropathy.
        Nat Rev Nephrol. 2010; 6: 319-330
        • Mathew A.
        • Cunard R.
        • Sharma K.
        Antifibrotic treatment and other new strategies for improving renal outcomes.
        Contrib Nephrol. 2011; 170: 217-227
        • Goel G.
        • Perkins B.A.
        Can improved glycemic control slow renal function decline at all stages of diabetic nephropathy?.
        Semin Nephrol. 2012; 32: 423-431
        • Doria A.
        • Niewczas M.A.
        • Fiorina P.
        Can existing drugs approved for other indications retard renal function decline in patients with type 1 diabetes and nephropathy?.
        Semin Nephrol. 2012; 32: 437-444
        • Bonventre J.V.
        Can we target tubular damage to prevent renal function decline in diabetes?.
        Semin Nephrol. 2012; 32: 452-462
        • Humphreys B.D.
        Targeting pericyte differentiation as a strategy to modulate kidney fibrosis in diabetic nephropathy.
        Semin Nephrol. 2012; 32: 463-470
        • Mima A.
        • Qi W.
        • King G.L.
        Implications of treatment that target protective mechanisms against diabetic nephropathy.
        Semin Nephrol. 2012; 32: 471-478
        • Osafune K.
        iPS cell technology-based research for the treatment of diabetic nephropathy.
        Semin Nephrol. 2012; 32: 479-485
        • Gilbert R.E.
        • Zhang Y.
        • Yuen D.A.
        Cell therapy for diabetic nephropathy: is the future, now?.
        Semin Nephrol. 2012; 32: 486-493
        • Chokrungvaranon N.
        • Deer J.
        • Reaven P.D.
        Intensive glycemic control and cardiovascular disease; are there patients who may benefit?.
        Postgrad Med. 2011; 123: 114-123
        • Degome E.M.
        • Rivera G.
        • Lilly S.M.
        • Usman M.H.
        • Mohler E.R.
        Personalized vascular medicine; individualizing drug therapy.
        Vasc Med. 2011; 16: 391-404
        • Higgins M.J.
        • Baselga J.
        Targeted therapies for brest cancer.
        J Clin Invest. 2011; 121: 3797-3803
        • Cantarovich D.
        • Perrone V.
        Pancreas transplant as treatment to arrest renal function decline in patients with type 1 diabetes and proteinuria.
        Semin Nephrol. 2012; 32: 432-436
        • Pavlakis M.
        • Kher A.
        Pre-emptive kidney transplantation to improve survival in patients with type 1 diabetes and imminent risk of ESRD.
        Semin Nephrol. 2012; 32: 505-511