CoChat
Sign Up
Cited by 156Chronic Kidney Disease and DiabetesDiabetes Treatment and ManagementDiabetes Management and Research

Diabetic kidney disease: New clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on “The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function”

Open access
Pugliese, Giuseppe, Penno, Giuseppe, Natali, Andrea, Barutta, Federica, Di Paolo, Salvatore, Reboldi, Gianpaolo, Gesualdo, Loreto, De Nicola, Luca·2019·Nutrition, Metabolism and Cardiovascular Diseases
DOI 10.1016/j.numecd.2019.07.017
Open this paper in CoChat — free accountOpen PDF

Abstract

AIMS: This joint document of the Italian Diabetes Society and the Italian Society of Nephrology reviews the natural history of diabetic kidney disease (DKD) in the light of the recent epidemiological literature and provides updated recommendations on anti-hyperglycemic treatment with non-insulin agents. DATA SYNTHESIS: Recent epidemiological studies have disclosed a wide heterogeneity of DKD. In addition to the classical albuminuric phenotype, two new albuminuria-independent phenotypes have emerged, i.e., "nonalbuminuric renal impairment" and "progressive renal decline", suggesting that DKD progression toward end-stage kidney disease (ESKD) may occur through two distinct pathways, albuminuric and nonalbuminuric. Several biomarkers have been associated with decline of estimated glomerular filtration rate (eGFR) independent of albuminuria and other clinical variables, thus possibly improving ESKD prediction. However, the pathogenesis and anatomical correlates of these phenotypes are still unclear. Also the management of hyperglycemia in patients with type 2 diabetes and impaired renal function has profoundly changed during the last two decades. New anti-hyperglycemic drugs, which do not cause hypoglycemia and weight gain and, in some cases, seem to provide cardiorenal protection, have become available for treatment of these individuals. In addition, the lowest eGFR safety thresholds for some of the old agents, particularly metformin and insulin secretagogues, have been reconsidered. CONCLUSIONS: The heterogeneity in the clinical presentation and course of DKD has important implications for the diagnosis, prognosis, and possibly treatment of this complication. The therapeutic options for patients with type 2 diabetes and impaired renal function have substantially increased, thus allowing a better management of these individuals.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.numecd.2019.07.017

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 249 · Cited by 156

Research works printed but not linked: 210

  1. Ritz E, Zeng XX, Rychlík I. Clinical manifestation and natural history of diabetic nephropathy. Contrib Nephrol 2011;170:19e27.
  2. Doshi SM, Friedman AN. Diagnosis and management of type 2 diabetic kidney disease. Clin J Am Soc Nephrol 2017;12:1366e73.
  3. Pugliese G. Updating the natural history of diabetic nephropathy. Acta Diabetol 2014;51:905e15.
  4. Parving HH, Oxenbøll B, Svendsen PA, Christiansen JS, Andersen AR. Early detection of patients at risk of developing diabetic nephrop- athy: a longitudinal study of urinary albumin excretion. Acta Endocrinol (Copenh) 1982;100:550e5.
  5. Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin- dependent diabetes mellitus. Lancet 1982;1:1430e2.
  6. Ruggenenti P, Cravedi P, Remuzzi G. The RAAS in the pathogenesis and treatment of diabetic nephropathy. Nat Rev Nephrol 2010;6: 319e30.
  7. de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, et al. Albuminuria, a therapeutic target for cardio- vascular protection in type 2 diabetic patients with nephropathy. Circulation 2004;110:921e7.
  8. Afkarian M, Zelnick LR, Hall YN, Heagerty PJ, Tuttle K, Weiss NS, et al. Clinical manifestations of kidney disease among US Adults with diabetes, 1988e2014. J Am Med Assoc 2016;316:602e10.
  9. Kume S, Araki SI, Ugi S, Morino K, Koya D, Nishio Y, et al. Secular changes in clinical manifestations of kidney disease among Japa- nese adults with type 2 diabetes from 1996 to 2014. J Diabetes Investig 2018 Nov 19. https://doi.org/10.1111/jdi.12977. · DOI
  10. Gregg EW, Li Y, Wang J, Burrows NR, Ali MK, Rolka D, et al. Changes in diabetes-related complications in the United States, 1990e2010. N Engl J Med 2014;370:1514e23.
  11. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS. Regression of microalbuminuria in type 1 diabetes. N Engl J Med 2003;348:2285e93.
  12. Giorgino F, Laviola L, Cavallo Perin P, Solnica B, Fuller J, Chaturvedi N. Factors associated with progression to macro- albuminuria in microalbuminuric type 1 diabetic patients: the EURODIAB Prospective Complications Study. Diabetologia 2004; 47:1020e8.
  13. Hovind P, Tarnow L, Rossing P, Jensen BR, Graae M, Torp I, et al. Predictors for the development of microalbuminuria and macro- albuminuria in patients with type 1 diabetes: inception cohort study. BMJ 2004;328:1105.
  14. Gaede P, Tarnow L, Vedel P, Parving HH, Pedersen O. Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and micro- albuminuria. Nephrol Dial Transplant 2004;19:2784e8.
  15. Araki S, Haneda M, Sugimoto T, Isono M, Isshiki K, Kashiwagi A, et al. Factors associated with frequent remission of micro- albuminuria in patients with type 2 diabetes mellitus. Diabetes 2005;54:2983e7.
  16. Yamada T, Komatsu M, Komiya I, Miyahara Y, Shima Y, Matsuzaki M, et al. Development, progression, and regression of microalbuminuria in Japanese patients with type 2 diabetes under tight glycemic and blood pressure control: the Kashiwa study. Diabetes Care 2005;28:2733e8.
  17. Lane PH, Steffes MW, Mauer SM. Glomerular structure in IDDM women with low glomerular filtration rate and normal urinary albumin excretion. Diabetes 1992;41:581e6.
  18. Tsalamandris C, Allen TJ, Gilbert RE, Sinha A, Panagiotopoulos S, Cooper ME, et al. Progressive decline in renal function in diabetic patients with and without albuminuria. Diabetes 1994;43: 649e55.
  19. Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol 2013;24:302e8.
  20. Bailey RA, Wang Y, Zhu V, Rupnow MF. Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging. BMC Res Notes 2014;7:415.
  21. Mottl AK, Kwon KS, Mauer M, Mayer-Davis EJ, Hogan SL, Kshirsagar AV. Normoalbuminuric diabetic kidney disease in the U.S. population. J Diabet Complicat 2013;27:123e7.
  22. MacIsaac RJ, Tsalamandris C, Panagiotopoulos S, Smith TJ, McNeil KJ, Jerums G. Nonalbuminuric renal insufficiency in type 2 diabetes. Diabetes Care 2004;27:195e200.
  23. Dwyer JP, Parving HH, Hunsicker LG, Ravid M, Remuzzi G, Lewis JB. Renal dysfunction in the presence of normoalbuminuria in type 2 diabetes: results from the DEMAND Study. Cardiorenal Med 2012; 2:1e10.
  24. Parving HH, Lewis JB, Ravid M, Remuzzi G, Hunsicker LG. DEMAND investigators. Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: a global perspective. Kidney Int 2006;69:2057e63.
  25. Yokoyama H, Sone H, Oishi M, Kawai K, Fukumoto Y, Kobayashi M, et al. Prevalence of albuminuria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes Clinical Data Management study (JDDM15). Nephrol Dial Trans- plant 2009;24:1212e9.
  26. Thomas MC, Weekes AJ, Broadley OJ, Cooper ME, Mathew TH. The burden of chronic kidney disease in Australian patients with type 2 diabetes (the NEFRON study). Med J Aust 2006;185:140e4.
  27. Thomas MC, Macisaac RJ, Jerums G, Weekes A, Moran J, Shaw JE, et al. Nonalbuminuric renal impairment in type 2 diabetic patients and in the general population (National Evaluation of the Fre- quency of Renal Impairment cO-existing with NIDDM [NEFRON] 11). Diabetes Care 2009;32:1497e502.
  28. Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, et al. Clinical significance of nonalbuminuric renal impairment in type 2 diabetes. J Hypertens 2011;29:1802e9.
  29. Afghahi H, Miftaraj M, Svensson AM, Hadimeri H, Gudbjörnsdottir S, Eliasson B, et al. Ongoing treatment with renin- angiotensin-aldosterone-blocking agents does not predict nor- moalbuminuric renal impairment in a general type 2 diabetes population. J Diabet Complicat 2013;27:229e34.
  30. Hill CJ, Cardwell CR, Patterson CC, Maxwell AP, Magee GM, Young RJ, et al. Chronic kidney disease and diabetes in the Na- tional Health Service: a cross-sectional survey of the U.K. national diabetes audit. Diabet Med 2014;31:448e54.
  31. De Cosmo S, Rossi MC, Pellegrini F, Lucisano G, Bacci S, Gentile S, et al. Kidney dysfunction and related cardiovascular risk factors among patients with type 2 diabetes. Nephrol Dial Transplant 2014;29:657e62.
  32. Gao B, Wu S, Wang J, Yang C, Chen S, Hou J, et al. Clinical features and long-term outcomes of diabetic kidney disease -a prospective cohort study from China. J Diabet Complicat 2019;33:39e45.
  33. Rodriguez-Poncelas A, Garre-Olmo J, Franch-Nadal J, Diez-Espino J, Mundet-Tuduri X, Barrot-De la Puente J, et al. Prevalence of chronic kidney disease in patients with type 2 diabetes in Spain: PERCEDIME2 study. BMC Nephrol 2013;14:46.
  34. Bramlage P, Lanzinger S, van Mark G, Hess E, Fahrner S, Heyer CHJ, et al. Patient and disease characteristics of type-2 diabetes pa- tients with or without chronic kidney disease: an analysis of the German DPV and DIVE databases. Cardiovasc Diabetol 2019;18:33.
  35. Lee HW, Jo AR, Yi DW, Kang YH, Son SM. Prevalent Rate of Non- albuminuric Renal insufficiency and its association with cardio- vascular disease event in Korean type 2 diabetes. Endocrinol Metabol (Seoul) 2016;31:577e85.
  36. Koye DN, Magliano DJ, Reid CM, Jepson C, Feldman HI, Herman WH, et al. Risk of progression of nonalbuminuric CKD to end-stage kidney disease in people with diabetes: the CRIC (Chronic Renal Insufficiency Cohort) Study. Am J Kidney Dis 2018; 72:653e61.
  37. Drury PL, Ting R, Zannino D, Ehnholm C, Flack J, Whiting M, et al. Estimated glomerular filtration rate and albuminuria are inde- pendent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetologia 2011;54:32e43. New issues in DKD 19 Please cite this article as: Pugliese G et al., Diabetic kidney disease: New clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on "The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with..., Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/j.numecd.2019.07.017
  38. Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, et al. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol 2009;20:1813e21.
  39. Tobe SW, Clase CM, Gao P, McQueen M, Grosshennig A, Wang X, et al. Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: results from the ONTARGET and TRANSCEND studies. Circulation 2011;123:1098e107.
  40. Bakris GL, Sarafidis PA, Weir MR, Dahlöf B, Pitt B, Jamerson K, et al. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet 2010;375:1173e81.
  41. Thorn LM, Gordin D, Harjutsalo V, Hägg S, Masar R, Saraheimo M, et al. The presence and consequence of nonalbuminuric chronic kidney disease in patients with type 1 diabetes. Diabetes Care 2015;38:2128e33.
  42. Penno G, Russo E, Garofolo M, Daniele G, Lucchesi D, Giusti L, et al. Evidence for two distinct phenotypes of chronic kidney disease in individuals with type 1 diabetes mellitus. Diabetologia 2017;60: 1102e13.
  43. Pacilli A, Viazzi F, Fioretto P, Giorda C, Ceriello A, Genovese S, et al. Epidemiology of diabetic kidney disease in adult patients with type 1 diabetes in Italy: the AMD-Annals initiative. Diabetes Metabol Res Rev 2017;33(4).
  44. Lamacchia O, Viazzi F, Fioretto P, Mirijello A, Giorda C, Ceriello A, et al. Normoalbuminuric kidney impairment in patients with T1DM: insights from Annals Initiative. Diabetol Metab Syndrome 2018;10:60.
  45. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR, UKPDS Study Group. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes 2006;55:1832e9.
  46. Molitch ME, Steffes M, Sun W, Rutledge B, Cleary P, de Boer IH, et al. Development and progression of renal insufficiency with and without albuminuria in adults with type 1 diabetes in the diabetes control and complications trial and the epidemiology of diabetes interventions and complications study. Diabetes Care 2010;33: 1536e43.
  47. Krolewski AS. Progressive renal decline: the new paradigm of diabetic nephropathy in type 1 diabetes. Diabetes Care 2015;38: 954e62.
  48. Krolewski AS, Skupien J, Rossing P, Warram JH. Fast renal decline to end-stage renal disease: an unrecognized feature of nephrop- athy in diabetes. Kidney Int 2017;91:1300e11.
  49. Skupien J, Warram J, Smiles A, Stanton RC, Krolewski AS. Patterns of estimated glomerular filtration rate decline leading to end- stage renal disease in type 1 diabetes. Diabetes Care 2016;39: 2262e9.
  50. Weldegiorgis M, de Zeeuw D, Li L, Parving HH, Hou FF, Remuzzi G, et al. Longitudinal estimated GFR trajectories in patients with and without type 2 diabetes and nephropathy. Am J Kidney Dis 2018; 71:91e101.
  51. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013;3: 1e150.
  52. Krolewski AS, Niewczas MA, Skupien J, Gohda T, Smiles A, Eckfeldt JH, et al. Early progressive renal decline precedes the onset of microalbuminuria and its progression to macro- albuminuria. Diabetes Care 2014;37:226e34.
  53. Perkins BA, Ficociello LH, Ostrander BE, Silva KH, Weinberg J, Warram JH, et al. Microalbuminuria and the risk for early pro- gressive renal function decline in type 1 diabetes. J Am Soc Nephrol 2007;18:1353e61.
  54. Skupien J, Warram JH, Smiles AM, Niewczas MA, Gohda T, Pezzolesi MG, 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;82:589e97.
  55. de Boer IH, Steffes MW. Glomerular filtration rate and albumin- uria: twin manifestations of nephropathy in diabetes. J Am Soc Nephrol 2007;18:1036e7.
  56. Hoefield RA, Kalra PA, Baker PG, Sousa I, Diggle PJ, Gibson MJ, et al. The use of eGFR and ACR to predict decline in renal function in people with diabetes. Nephrol Dial Transplant 2011;26:887e92.
  57. Babazono T, Nyumura I, Toya K, Hayashi T, Ohta M, Suzuki K, et al. Higher levels of urinary albumin excretion within the normal range predict faster decline in glomerular filtration rate in diabetic patients. Diabetes Care 2009;32:1518e20.
  58. Kitai Y, Doi Y, Osaki K, Sugioka S, Koshikawa M, Sugawara A. Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic pa- tients with severely impaired renal function. Clin Exp Nephrol 2015;19:1037e43.
  59. Minutolo R, Gabbai FB, Provenzano M, Chiodini P, Borrelli S, Garofalo C, et al. Cardiorenal prognosis by residual proteinuria level in diabetic chronic kidney disease: pooled analysis of four cohort studies. Nephrol Dial Transplant 2018;33:1942e9.
  60. Provenzano M, Chiodini P, Minutolo R, Zoccali C, Bellizzi V, Conte G, et al. Reclassification of chronic kidney disease patients for end-stage renal disease risk by proteinuria indexed to esti- mated glomerular filtration rate: multicentre prospective study in nephrology clinics. Nephrol Dial Transplant 2018 Jul 23. https: //doi.org/10.1093/ndt/gfy217. · DOI
  61. Jerums G, Panagiotopoulos S, Premaratne E, Power DA, MacIsaac RJ. Lowering of proteinuria in response to antihyper- tensive therapy predicts improved renal function in late but not in early diabetic nephropathy: a pooled analysis. Am J Nephrol 2008; 28:614e27.
  62. de Boer IH, Gao X, Cleary PA, Bebu I, Lachin JM, Molitch ME, et al. Albuminuria changes and cardiovascular and renal outcomes in type 1 diabetes: the DCCT/EDIC Study. Clin J Am Soc Nephrol 2016; 11:1969e77.
  63. Jun M, Ohkuma T, Zoungas S, Colagiuri S, Mancia G, Marre M, et al. Changes in albuminuria and the risk of major clinical outcomes in diabetes: results from ADVANCE-ON. Diabetes Care 2018;41:163e70.
  64. de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, et al. Proteinuria, a target for renoprotection in pa- tients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int 2004;65:2309e20.
  65. Carrero JJ, Grams ME, Sang Y, Ärnlöv J, Gasparini A, Matsushita K, et al. Albuminuria changes are associated with subsequent risk of end-stage renal disease and mortality. Kidney Int 2017;91:244e51.
  66. Coresh J, Heerspink HJL, Sang Y, Matsushita K, Arnlov J, Astor BC, et al. Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta- analysis of observational studies. Lancet Diabetes Endocrinol 2019;7:115e27.
  67. Levey AS, Cattran D, Friedman A, Miller WG, Sedor J, Tuttle K, et al. Proteinuria as a surrogate outcome in CKD: report of a scientific workshop sponsored by the national kidney foundation and the US food and drug administration. Am J Kidney Dis 2009;54: 205e26.
  68. Gregg EW, Cheng YJ, Saydah S, Cowie C, Garfield S, Geiss L, et al. Trends in death rates among U.S. adults with and without diabetes between 1997 and 2006: findings from the National Health Interview Survey. Diabetes Care 2012;35:1252e7.
  69. Kramer H, Boucher RE, Leehey D, Fried L, Wei G, Greene T, et al. Increasing mortality in adults with diabetes and low estimated glomerular filtration rate in the absence of albuminuria. Diabetes Care 2018;41:775e81.
  70. Liu JJ, Liu S, Gurung RL, Ang K, Tang WE, Sum CF, et al. Risk of progressive chronic kidney disease in individuals with early-onset type 2 diabetes: a prospective cohort study. Nephrol Dial Trans- plant 2018 Jul 10. https://doi.org/10.1093/ndt/gfy211. · DOI
  71. Weir MR. Acute changes in glomerular filtration rate with renin- angiotensin system (RAS) inhibition: clinical implications. Kid- ney Int 2017;91:529e31.
  72. Xie X, Liu Y, Perkovic V, Li X, Ninomiya T, Hou W, et al. Renin- angiotensin system inhibitors and kidney and cardiovascular outcomes in patients with CKD: a Bayesian network meta-analysis of randomized clinical trials. Am J Kidney Dis 2016;67:728e41.
  73. Tabaei BP, Al-Kassab AS, Ilag LL, Zawacki CM, Herman WH. Does microalbuminuria predict diabetic nephropathy? Diabetes Care 2001;24:1560e6.
  74. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851e60.
  75. Afghahi H, Cederholm J, Eliasson B, Zethelius B, Gudbjörnsdottir S, Hadimeri H, et al. Risk factors for the development of albuminuria and renal impairment in type 2 diabetes-the Swedish National Diabetes Register (NDR). Nephrol Dial Transplant 2011;26: 1236e43.
  76. Ficociello LH, Rosolowsky ET, Niewczas MA, Maselli NJ, Weinberg JM, Aschengrau A, et al. High-normal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes: results of a 6- year follow-up. Diabetes Care 2010;33:1337e43.
  77. Pilemann-Lyberg S, Hansen TW, Tofte N, Winther SA, Theilade S, Ahluwalia TS, et al. Uric acid is an independent risk factor for decline in kidney function, cardiovascular event and mortality in patients with type 1 diabetes. Diabetes Care 2019;42:1088e94.
  78. Zoppini G, Targher G, Chonchol M, Ortalda V, Abaterusso C, Pichiri I, et al. Serum uric acid levels and incident chronic kidney disease in patients with type 2 diabetes and preserved kidney function. Diabetes Care 2012;35:99e104.
  79. Kim WJ, Kim SS, Bae MJ, Yi YS, Jeon YK, Kim BH, et al. High-normal serum uric acid predicts the development of chronic kidney dis- ease in patients with type 2 diabetes mellitus and preserved kidney function. J Diabet Complicat 2014;28:130e4.
  80. De Cosmo S, Viazzi F, Pacilli A, Giorda C, Ceriello A, Gentile S, et al. Serum uric acid and risk of CKD in type 2 diabetes. Clin J Am Soc Nephrol 2015;10:1921e9.
  81. Chang YH, Lei CC, Lin KC, Chang DM, Hsieh CH, Lee YJ. Serum uric acid level as an indicator for CKD regression and progression in patients with type 2 diabetes mellitus-a 4.6-year cohort study. Diabetes Metab Res Rev 2016;32:557e64.
  82. Gu L, Huang L, Wu H, Lou Q, Bian R. Serum uric acid to creatinine ratio: a predictor of incident chronic kidney disease in type 2 diabetes mellitus patients with preserved kidney function. Dia- betes Vasc Dis Res 2017;14:221e5.
  83. Coca SG, Nadkarni GN, Huang Y, Moledina DG, Rao V, Zhang J, et al. Plasma biomarkers and kidney function decline in early and established diabetic kidney disease. J Am Soc Nephrol 2017;28: 2786e93.
  84. Wang J, Yu Y, Li X, Li D, Xu C, Yuan J, et al. Serum uric acid levels and decreased estimated glomerular filtration rate in patients with type 2 diabetes: a cohort study and meta-analysis. Diabetes Metab Res Rev 2018;34:e3046.
  85. Mwasongwe SE, Fülöp T, Katz R, Musani SK, Sims M, Correa A, et al. Relation of uric acid level to rapid kidney function decline and development of kidney disease: the Jackson Heart Study. J Clin Hypertens 2018;20:775e83.
  86. Hanai K, Tauchi E, Nishiwaki Y, Mori T, Yokoyama Y, Uchigata Y, et al. Effects of uric acid on kidney function decline differ depending on baseline kidney function in type 2 diabetic patients. Nephrol Dial Transplant 2018 May 30. https://doi.org/10.1093/ndt/gfy138. · DOI
  87. Jalal DI, Chonchol M, Chen W, Targher G. Uric acid as a target of therapy in CKD. Am J Kidney Dis 2013;61:134e46.
  88. Afkarian M, Polsky S, Parsa A, Aronson R, Caramori ML, Cherney DZ, et al. Preventing early renal loss in diabetes (PERL) study: a randomized double-blinded trial of allopurinol-rationale, design, and baseline data. Diabetes Care 2019 Jun 11. https: //doi.org/10.2337/dc19-0342. · DOI
  89. Niewczas MA, Ficociello LH, Johnson AC, Walker W, Rosolowsky ET, Roshan B. Effects of uric acid on kidney function decline differ depending on baseline kidney function in type 2 diabetic patients. Serum concentrations of markers of TNFa and Fas-mediated pathways and renal function in nonproteinuric patients with type 1 diabetes. Clin J Am Soc Nephrol 2009;4: 62e70.
  90. Gohda T, Niewczas MA, Ficociello LH, Walker WH, Skupien J, Rosetti F, et al. Circulating TNF receptors 1 and 2 predict stage 3 CKD in type 1 diabetes. J Am Soc Nephrol 2012;23:516e24.
  91. Skupien J, Warram JH, Niewczas MA, Gohda T, Malecki M, Mychaleckyj JC, et al. Synergism between circulating tumor ne- crosis factor receptor 2 and HbA 1c in determining renal decline during 5-18 years of follow-up in patients with type 1 diabetes and proteinuria. Diabetes Care 2014;37:2601e8.
  92. Miyazawa I, Araki S, Obata T, Yoshizaki T, Morino K, Kadota A, et al. Association between serum soluble TNFa receptors and renal dysfunction in type 2 diabetic patients without proteinuria. Diabetes Res Clin Pract 2011;92:174e80.
  93. Niewczas MA, Gohda T, Skupien J, Smiles AM, Walker WH, Rosetti F, et al. Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes. J Am Soc Nephrol 2012;23:507e15.
  94. Pavkov ME, Nelson RG, Knowler WC, Cheng Y, Krolewski AS, Niewczas MA. Elevation of circulating TNF receptors 1 and 2 in- creases the risk of end-stage renal disease in American Indians with type 2 diabetes. Kidney Int 2015;87:812e9.
  95. Doody A, Jackson S, Elliott JA, Canavan RJ, Godson C, Slattery D, et al. Validating the association between plasma tumour necrosis factor receptor 1 levels and the presence of renal injury and functional decline in patients with type 2 diabetes. J Diabet Complicat 2018;32:95e9.
  96. Kamei N, Yamashita M, Nishizaki Y, Yanagisawa N, Nojiri S, Tanaka K, et al. Association between circulating tumor necrosis factor-related biomarkers and estimated glomerular filtration rate in type 2 diabetes. Sci Rep 2018;8:15302.
  97. Chung HF, Long KZ, Hsu CC, Al Mamun A, Jhang HR, Shin SJ, et al. Association of n-3 polyunsaturated fatty acids and inflammatory indicators with renal function decline in type 2 diabetes. Clin Nutr 2015;34:229e34.
  98. Klisic A, Kavaric N, Ninic A. Retinol-binding protein 4 versus albuminuria as predictors of estimated glomerular filtration rate decline in patients with type 2 diabetes. J Res Med Sci 2018;23:44.
  99. Nadkarni GN, Rao V, Ismail-Beigi F, Fonseca VA, Shah SV, Simonson MS, et al. Association of urinary biomarkers of inflammation, injury, and fibrosis with renal function decline: the ACCORD Trial. Clin J Am Soc Nephrol 2016;11:1343e52.
  100. Sabbisetti VS, Waikar SS, Antoine DJ, Smiles A, Wang C, Ravisankar A, et al. Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts pro- gression to ESRD in type I diabetes. J Am Soc Nephrol 2014;25: 2177e86.
  101. Nielsen SE, Reinhard H, Zdunek D, Hess G, Gutiérrez OM, Wolf M, et al. Tubular markers are associated with decline in kidney function in proteinuric type 2 diabetic patients. Diabetes Res Clin Pract 2012;97:71e6.
  102. Rotbain Curovic V, Hansen TW, Eickhoff MK, von Scholten BJ, Reinhard H, Jacobsen PK, et al. Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients. Acta Diabetol 2018;55:1143e50.
  103. Colombo M, Looker HC, Farran B, Hess S, Groop L, Palmer CNA, et al. Serum kidney injury molecule 1 and b2-microglobulin perform as well as larger biomarker panels for prediction of rapid decline in renal function in type 2 diabetes. Diabetologia 2019;62:156e68.
  104. Araki S, Haneda M, Koya D, Sugaya T, Isshiki K, Kume S, et al. Predictive effects of urinary liver-type fatty acid-binding protein for deteriorating renal function and incidence of cardiovascular disease in type 2 diabetic patients without advanced nephropa- thy. Diabetes Care 2013;36:1248e53.
  105. Kim SS, Song SH, Kim IJ, Jeon YK, Kim BH, Kwak IS, et al. Urinary cystatin C and tubular proteinuria predict progression of diabetic nephropathy. Diabetes Care 2013;36:656e61. New issues in DKD 21 Please cite this article as: Pugliese G et al., Diabetic kidney disease: New clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on "The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with..., Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/j.numecd.2019.07.017
  106. Conway BR, Manoharan D, Manoharan D, Jenks S, Dear JW, McLachlan S, et al. Measuring urinary tubular biomarkers in type 2 diabetes does not add prognostic value beyond established risk factors. Kidney Int 2012;82:812e8.
  107. Garlo KG, White WB, Bakris GL, Zannad F, Wilson CA, Kupfer S, et al. Kidney biomarkers and decline in eGFR in patients with type 2 diabetes. Clin J Am Soc Nephrol 2018;13:398e405.
  108. Kopf S, Oikonomou D, von Eynatten M, Kieser M, Zdunek D, Hess G, et al. Urinary excretion of high molecular weight adipo- nectin is an independent predictor of decline of renal function in type 2 diabetes. Acta Diabetol 2014;51:479e89.
  109. von Scholten BJ, Reinhard H, Hansen TW, Oellgaard J, Parving HH, Jacobsen PK, et al. Urinary biomarkers are associated with inci- dent cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with micro- albuminuria. Diabetologia 2016;59:1549e57.
  110. Morita M, Uchigata Y, Hanai K, Ogawa Y, Iwamoto Y. Association of urinary type IV collagen with GFR decline in young patients with type 1 diabetes. Am J Kidney Dis 2011;58:915e20.
  111. Araki S, Haneda M, Koya D, Isshiki K, Kume S, Sugimoto T, et al. Association between urinary type IV collagen level and deterio- ration of renal function in type 2 diabetic patients without overt proteinuria. Diabetes Care 2010;33:1805e10.
  112. Bhensdadia NM, Hunt KJ, Lopes-Virella MF, Michael Tucker J, Mataria MR, Alge JL, et al. Urine haptoglobin levels predict early renal functional decline in patients with type 2 diabetes. Kidney Int 2013;83:1136e43.
  113. Liu JJ, Liu S, Wong MD, Gurung RL, Lim SC. Urinary haptoglobin predicts rapid renal function decline in asians with type 2 dia- betes and early kidney disease. J Clin Endocrinol Metab 2016; 101:3794e802.
  114. Boertien WE, Riphagen IJ, Drion I, Alkhalaf A, Bakker SJ, Groenier KH, et al. Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33). Diabetologia 2013; 56:1680e8.
  115. Lee CH, Cheung CYY, Woo YC, Lui DTW, Yuen MMA, Fong CHY, et al. Prospective associations of circulating adipocyte fatty acid- binding protein levels with risks of renal outcomes and mortality in type 2 diabetes. Diabetologia 2019;62:169e77.
  116. Lee CH, Hui EY, Woo YC, Yeung CY, Chow WS, Yuen MM, et al. Circulating fibroblast growth factor 21 levels predict progressive kidney disease in subjects with type 2 diabetes and normoal- buminuria. J Clin Endocrinol Metab 2015;100:1368e75.
  117. Merchant ML, Niewczas MA, Ficociello LH, Lukenbill JA, Wilkey DW, Li M, et al. Plasma kininogen and kininogen frag- ments are biomarkers of progressive renal decline in type 1 diabetes. Kidney Int 2013;83:1177e84.
  118. Liu JJ, Pek SLT, Ang K, Tavintharan S, Lim SC, SMART2D study. Plasma leucine-rich a-2-glycoprotein 1 predicts rapid eGFR decline and albuminuria progression in type 2 diabetes mellitus. J Clin Endocrinol Metab 2017;102:3683e91.
  119. Fountoulakis N, Maltese G, Gnudi L, Karalliedde J. Reduced levels of anti-ageing hormone klotho predict renal function decline in type 2 diabetes. J Clin Endocrinol Metab 2018;103: 2026e32.
  120. Hanai K, Babazono T, Mugishima M, Yoshida N, Nyumura I, Toya K, et al. Association of serum leptin levels with progression of diabetic kidney disease in patients with type 2 diabetes. Dia- betes Care 2011;34:2557e9.
  121. Pontillo C, Zhang ZY, Schanstra JP, Jacobs L, Zürbig P, Thijs L, et al. Prediction of chronic kidney disease stage 3 by CKD273, a urinary proteomic biomarker. Kidney Int Rep 2017;2:1066e75.
  122. Zürbig P, Mischak H, Menne J, Haller H. CKD273 enables efficient prediction of diabetic nephropathy in nonalbuminuric patients. Diabetes Care 2019;42:e4e5.
  123. Lindhardt M, Persson F, Zürbig P, Stalmach A, Mischak H, de Zeeuw D, et al. Urinary proteomics predict onset of micro- albuminuria in normoalbuminuric type 2 diabetic patients, a sub-study of the DIRECT-Protect 2 study. Nephrol Dial Transplant 2017;32:1866e73.
  124. Pena MJ, Heinzel A, Heinze G, Alkhalaf A, Bakker SJ, Nguyen TQ, et al. A panel of novel biomarkers representing different disease pathways improves prediction of renal function decline in type 2 diabetes. PLoS One 2015;10:e0120995.
  125. Looker HC, Colombo M, Hess S, Brosnan MJ, Farran B, Dalton RN, et al. Biomarkers of rapid chronic kidney disease progression in type 2 diabetes. Kidney Int 2015;88:888e96.
  126. Saulnier PJ, Gand E, Velho G, Mohammedi K, Zaoui P, Fraty M, et al. Association of circulating biomarkers (adrenomedullin, TNFR1, and NT-proBNP) with renal function decline in patients with type 2 diabetes: a French prospective cohort. Diabetes Care 2017;40:367e74.
  127. Peters KE, Davis WA, Ito J, Winfield K, Stoll T, Bringans SD, et al. Identification of novel circulating biomarkers predicting rapid decline in renal function in type 2 diabetes: the Fremantle Dia- betes Study Phase II. Diabetes Care 2017;40:1548e55.
  128. Nowak N, Skupien J, Smiles AM, Yamanouchi M, Niewczas MA, Galecki AT, et al. Markers of early progressive renal decline in type 2 diabetes suggest different implications for etiological studies and prognostic tests development. Kidney Int 2018;93: 1198e206.
  129. Heinzel A, Kammer M, Mayer G, Reindl-Schwaighofer R, Hu K, Perco P, et al. Validation of plasma biomarker candidates for the prediction of eGFR decline in patients with type 2 diabetes. Diabetes Care 2018;41:1947e54.
  130. Jenks SJ, Conway BR, McLachlan S, Teoh WL, Williamson RM, Webb DJ, et al. Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes. Diabetologia 2017;60:1400e8.
  131. Chen SC, Lin TH, Hsu PC, Chang JM, Lee CS, Tsai WC, et al. Impaired left ventricular systolic function and increased brachial- ankle pulse-wave velocity are independently associated with rapid renal function progression. Hypertens Res 2011;34:1052e8.
  132. Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Car- diorenal syndrome. J Am Coll Cardiol 2008;52:1527e39.
  133. Bouchi R, Babazono T, Mugishima M, Yoshida N, Nyumura I, Toya K, et al. Arterial stiffness is associated with incident albu- minuria and decreased glomerular filtration rate in type 2 dia- betic patients. Diabetes Care 2011;34:2570e5.
  134. Fountoulakis N, Thakrar C, Patel K, Viberti G, Gnudi L, Karalliedde J. Increased arterial stiffness is an independent predictor of renal function decline in patients with type 2 diabetes mellitus younger than 60 years. J Am Heart Assoc 2017;6:e004934.
  135. Zoppini G, Targher G, Chonchol M, Ortalda V, Negri C, Stoico V, et al. Predictors of estimated GFR decline in patients with type 2 diabetes and preserved kidney function. Clin J Am Soc Nephrol 2012;7:401e8.
  136. Mantovani A, Zaza G, Byrne CD, Lonardo A, Zoppini G, Bonora E, et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: a systematic review and meta-analysis. Metabolism 2018;79:64e76.
  137. Tonneijck L, Muskiet MH, Smits MM, van Bommel EJ, Heerspink HJ, van Raalte DH, et al. Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J Am Soc Nephrol 2017;28:1023e39.
  138. Bjornstad P, Cherney DZ, Snell-Bergeon JK, Pyle L, Rewers M, Johnson RJ, et al. Rapid GFR decline is associated with renal hyperfiltration and impaired GFR in adults with type 1 diabetes. Nephrol Dial Transplant 2015;30:1706e11.
  139. Moriya T, Tanaka S, Sone H, Ishibashi S, Matsunaga S, Ohashi Y, et al. Patients with type 2 diabetes having higher glomerular filtration rate showed rapid renal function decline followed by impaired glomerular filtration rate: Japan Diabetes Complica- tions Study. J Diabet Complicat 2017;31:473e8.
  140. Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, et al. HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular Events (RIACE) Italian multi- center study. Diabetes Care 2013;36:2301e10.
  141. Porrini E, Ruggenenti P, Mogensen CE, Barlovic DP, Praga M, Cruzado JM, et al. Non-proteinuric pathways in loss of renal function in patients with type 2 diabetes. Lancet Diabetes Endocrinol 2015;3:382e91.
  142. Mise K, Hoshino J, Ueno T, Hazue R, Hasegawa J, Sekine A, et al. Prognostic value of tubulointerstitial lesions, urinary n-acetyl-b- d-glucosaminidase, and urinary b2-microglobulin in patients G. Pugliese et al. Please cite this article as: Pugliese G et al., Diabetic kidney disease: New clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on "The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with..., Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/j.numecd.2019.07.017 with type 2 diabetes and biopsy-proven diabetic nephropathy. Clin J Am Soc Nephrol 2016;11:593e601. · DOI
  143. Hwang S, Park J, Kim J, Jang HR, Kwon GY, Huh W, et al. Tissue expression of tubular injury markers is associated with renal function decline in diabetic nephropathy. J Diabet Complicat 2017;31:1704e9.
  144. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 2012;81:442e8.
  145. Kelly KJ, Dominguez JH. Rapid progression of diabetic nephrop- athy is linked to inflammation and episodes of acute renal failure. Am J Nephrol 2010;32:469e75.
  146. Chawla LS, Kimmel PL. Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney Int 2012;82: 516e24.
  147. Fiorentino M, Bolignano D, Tesar V, Pisano A, Biesen WV, Tripepi G, et al. Renal biopsy in patients with diabetes: a pooled meta-analysis of 48 studies. Nephrol Dial Transplant 2017;32: 97e110.
  148. Gesualdo L, Di Paolo S. Renal lesions in patients with type 2 diabetes: a puzzle waiting to be solved. Nephrol Dial Transplant 2015;30:155e7.
  149. Ekinci EI, Jerums G, Skene A, Crammer P, Power D, Cheong KY, et al. Renal structure in normoalbuminuric and albuminuric pa- tients with type 2 diabetes and impaired renal function. Diabetes Care 2013;36:3620e6.
  150. Shimizu M, Furuichi K, Toyama T, Kitajima S, Hara A, Kitagawa K, et al. Long-term outcomes of Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy. Diabetes Care 2013; 36:3655e62.
  151. Fioretto P, Mauer M, Brocco E, Velussi M, Frigato F, Muollo B, et al. Patterns of renal injury in NIDDM patients with micro- albuminuria. Diabetologia 1996;39:1569e76.
  152. Yagil C, Barak A, Ben-Dor D, Rosenmann E, Bernheim J, Rosner M, et al. Nonproteinuric diabetes-associated nephropathy in the Cohen rat model of type 2 diabetes. Diabetes 2005;54:1487e96.
  153. Osterby R. Glomerular structural changes in type 1 (insulin- dependent) diabetes mellitus: causes, consequences, and pre- vention. Diabetologia 1992;35:803e12.
  154. Caramori ML, Fioretto P, Mauer M. Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions. Diabetes 2003;52:1036e40.
  155. Pugliese G, Solini A, Fondelli C, Trevisan R, Vedovato M, Nicolucci A, et al. Reproducibility of albuminuria in type 2 dia- betic subjects. Findings from the renal insufficiency and cardio- vascular events (RIACE) study. Nephrol Dial Transplant 2011;26: 3950e4.
  156. Krolewski AS, Warram JH, Forsblom C, Smiles AM, Thorn L, Skupien J, et al. Serum concentration of cystatin C and risk of end-stage renal disease in diabetes. Diabetes Care 2012;35: 2311e6.
  157. Pan Y, Jiang S, Qiu D, Shi J, Zhou M, An Y, et al. Comparing the GFR estimation equations using both creatinine and cystatin c to predict the long-term renal outcome in type 2 diabetic ne- phropathy patients. J Diabet Complicat 2016;30:1478e87.
  158. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and car- diovascular risk: epidemiology, mechanisms, and prevention. Lancet 2013;382:339e52.
  159. Orchard TJ, Secrest AM, Miller RG, Costacou T. In the absence of renal disease, 20 year mortality risk in type 1 diabetes is com- parable to that of the general population: a report from the Pittsburgh Epidemiology of Diabetes Complications Study. Dia- betologia 2010;53:2312e9.
  160. Tancredi M, Rosengren A, Svensson AM, Kosiborod M, Pivodic A, Gudbjörnsdottir S, et al. Excess mortality among persons with type 2 diabetes. N Engl J Med 2015;373:1720e32.
  161. Penno G, Solini A, Bonora E, Orsi E, Fondelli C, Zerbini G, et al. Defining the contribution of chronic kidney disease to all-cause mortality in patients with type 2 diabetes: the Renal Insuffi- ciency and Cardiovascular Events (RIACE) Italian Multicenter Study. Acta Diabetol 2018;55:603e12.
  162. Astor BC, Hallan SI, Miller 3rd ER, Yeung E, Coresh J. Glomerular filtration rate, albuminuria, and risk of cardiovascular and all- cause mortality in the US population. Am J Epidemiol 2008; 167:1226e34.
  163. Chronic Kidney Disease Prognosis Consortium, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, et al. Association of estimated glomerular filtration rate and albuminuria with all- cause and cardiovascular mortality in general population co- horts: a collaborative meta-analysis. Lancet 2010;375:2073e81.
  164. Astor BC, Matsushita K, Gansevoort RT, van der Velde M, Woodward M, Levey AS, et al. Lower estimated glomerular filtra- tion rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts. Kidney Int 2011;79:1331e40.
  165. Groop PH, Thomas MC, Moran JL, Wadèn J, Thorn LM, Mäkinen VP, et al. The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes. Diabetes 2009;58:1651e8.
  166. Bruno G, Merletti F, Bargero G, Novelli G, Melis D, Soddu A, et al. Estimated glomerular filtration rate, albuminuria and mortality in type 2 diabetes: the Casale Monferrato study. Diabetologia 2007;50:941e8.
  167. de Boer IH, Katz R, Cao JJ, Fried LF, Kestenbaum B, Mukamal K, et al. Cystatin C, albuminuria, and mortality among older adults with diabetes. Diabetes Care 2009;32:1833e8.
  168. Penno G, Solini A, Orsi E, Bonora E, Fondelli C, Trevisan R, et al. Non-albuminuric renal impairment is a strong predictor of mortality in individuals with type 2 diabetes: the Renal Insuffi- ciency and Cardiovascular Events (RIACE) Italian multicentre study. Diabetologia 2018;61:2277e89.
  169. Garofolo M, Russo E, Miccoli R, Lucchesi D, Giusti L, Sancho- Bornez V, et al. Albumimuric and non-albuminuric chronic kid- ney disease in type 1 diabetes; Association with major vascular outcomes risk and all-cause mortality. J Diabet Complicat 2018; 32:550e7.
  170. Solini S, Penno G, Bonora E, Fondelli C, Orsi E, Arosio M, et al. Diverging association of reduced glomerular filtration rate and albuminuria with coronary and noncoronary events in patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicentre Study. Diabetes Care 2012;35: 143e9.
  171. Rigalleau V, Lasseur C, Raffaitin C, Beauvieux MC, Barthe N, Chauveau P, et al. Normoalbuminuric renal-insufficient diabetic patients: a lower-risk group. Diabetes Care 2007;30:2034e9.
  172. Abuelo JG. Normotensive ischemic acute renal failure. N Engl J Med 2007;357:797e805.
  173. Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, et al. Angiotensin-receptor blockade versus converting enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 2004;351:1952e61.
  174. Heart Outcomes Prevention Evaluation Study Investigators. Ef- fects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICROHOPE substudy. Lancet 2000;355:253e9.
  175. Lohr JW, Willsky GR, Acara MA. Renal drug metabolism. Phar- macol Rev 1998;50:107e41.
  176. Moen MF, Zhan M, Hsu VD, Walker LD, Einhorn LM, Seliger SL, et al. Frequency of hypoglycemia and its significance in chronic kidney disease. Clin J Am Soc Nephrol 2009;4:1121e7.
  177. Gerich JE, Meyer C, Woerle HJ, Stumvoll M. Renal gluconeogen- esis: its importance in human glucose homeostasis. Diabetes Care 2001;24:382e91. New issues in DKD 23 Please cite this article as: Pugliese G et al., Diabetic kidney disease: New clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on "The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with..., Nutrition, Metabolism & Cardiovascular Diseases, https://doi.org/10.1016/j.numecd.2019.07.017
  178. Woerle HJ, Meyer C, Popa EM, Cryer PE, Gerich JE. Renal compensation for impaired hepatic glucose release during hy- poglycemia in type 2 diabetes: further evidence for hepatorenal reciprocity. Diabetes 2003;52:1386e92.
  179. Garber AJ, Bier DM, Cryer PE, Pagliara AS. Hypoglycemia in compensated chronic renal insufficiency: substrate limitation of gluconeogenesis. Diabetes 1974;23:982e6.
  180. Ishida JH, Johansen KL. Exclusion of patients with kidney disease from cardiovascular trials. JAMA Intern Med 2016;176:124e5.
  181. Bailie GR, Eisele G, Liu L, Roys E, Kiser M, Finkelstein F, et al. Patterns of medication use in the RRI-CKD study: focus on medications with cardiovascular effects. Nephrol Dial Transplant 2005;20:1110e5.
  182. Tonelli M, Wiebe N, Guthrie B, James MT, Quan H, Fortin M, et al. Comorbidity as a driver of adverse outcomes in people with chronic kidney disease. Kidney Int 2015;88:859e66.
  183. White JR. A brief history of the development of diabetes medi- cations. Diabetes Spectr 2014;27:82e6.
  184. Neumiller JJ, Alicic RZ, Tuttle KR. Therapeutic considerations for antihyperglycemic agents in diabetic kidney disease. J Am Soc Nephrol 2017;28:2263e74.
  185. Cherney DZI, Bakris GL. Novel therapies for diabetic kidney dis- ease. Kidney Int Suppl 2018;8:18e25.
  186. Solini A, Penno G, Bonora E, Fondelli C, Orsi E, Trevisan R, et al. Age, renal dysfunction, cardiovascular disease, and anti- hyperglycemic treatment in type 2 diabetes mellitus: findings from the Renal Insufficiency and Cardiovascular Events Italian Multicenter Study. J Am Geriatr Soc 2013;61:1253e61.
  187. Salpeter S, Greyber E, Pasternak G, Salpeter E. Risk of fatal and non-fatal lactic acidosis with metformin in type 2 diabetes. Arch Intern Med 2003;163:2594e602.
  188. Duckworth WC, Bennett RG, Hamel FG. Insulin degradation: progress and potential. Endocr Rev 1998;19:608e24.
  189. de Boer IH, Zelnick L, Afkarian M, Ayers E, Curtin L, Himmelfarb J, et al. Impaired glucose and insulin homeostasis in moderate- severe CKD. J Am Soc Nephrol 2016;27:2861e71.
  190. Arnouts P, Bolignano D, Nistor I, Bilo H, Gnudi L, Heaf J, et al. Glucose-lowering drugs in patients with chronic kidney disease: a narrative review on pharmacokinetic properties. Nephrol Dial Transplant 2014;29:1284e300.
  191. Feldman JM. Glyburide: a second-generation sulfonylurea hypo- glycemic agent. History, chemistry, metabolism, pharmacokinetics, clinical use and adverse effects. Pharmacotherapy 1985;5:43e62.
  192. Rosenkranz B, Profozic V, Metelko Z, Mrzljak V, Lange C, Malerczyk V. Pharmacokinetics and safety of glimepiride at clinically effective doses in diabetic patients with renal impair- ment. Diabetologia 1996;39:1617e24.
  193. Palmer KJ, Brogden RN. Gliclazide. An update of its pharmaco- logical properties and therapeutic efficacy in non-insulin- dependent diabetes mellitus. Drugs 1993;46:92e125.
  194. Marbury TC, Ruckle JL, Hatorp V, Andersen MP, Nielsen KK, Huang WC, et al. Pharmacokinetics of repaglinide in subjects with renal impairment. Clin Pharmacol Ther 2000;67:7e15.
  195. Buse JB, DeFronzo RA, Rosenstock J, Kim T, Burns C, Skare S, et al. The primary glucose-lowering effect of metformin resides in the gut, not the circulation: results from short-term pharmacokinetic and 12-week dose-ranging studies. Diabetes Care 2016;39: 198e205.
  196. Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 2011;50:81e98.
  197. DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associ- ated lactic acidosis: current perspectives on causes and risk. Metabolism 2016;65:20e9.
  198. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med 2004;351: 1106e18.
  199. Budde K, Neumayer HH, Fritsche L, Sulowicz W, Stompôr T, Eckland D. The pharmacokinetics of pioglitazone in patients with impaired renal function. Br J Clin Pharmacol 2003;55:368e74.
  200. Joubert PH, Venter HL, Foukaridis GN. The effect of miglitol and acarbose after an oral glucose load: a novel hypoglycaemic mechanism? Br J Clin Pharmacol 1990;30:391e6.

200 of 210 shown

Authors
Pugliese, G., Penno, G., Natali, A., Barutta, F., Di Paolo, S., Reboldi, G., Gesualdo, L., & De Nicola, L.
Affiliations
  • Azienda Ospedaliera Sant'Andrea (IT)
  • University of Pisa (IT)
  • University of Turin (IT)
  • University of Perugia (IT)
  • University of Bari Aldo Moro (IT)
Corresponding author
Pugliese, Giuseppe
ORCID
Venue
Nutrition, Metabolism and Cardiovascular Diseases
Publisher
Elsevier BV
Published
2019-11
Volume
29
Issue
11
Pages
1127-1150
ISSN
0939-4753 (ISSN-L)
DOI
10.1016/j.numecd.2019.07.017
OpenAlex
W2977728615
Cited by
156
References
249
Citations by year
2026: 6 · 2025: 12 · 2024: 21 · 2023: 29 · 2022: 25 · 2021: 38 · 2020: 20 · 2019: 2 · 2018: 3
FWCI
16.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrition Metabolism and Cardiovascular Diseases (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc-nd)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by-nc-nd)
  • Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
diabetic nephropathy, type 2 diabetes, renal dysfunction, hyperglycemia treatment, non-insulin antidiabetic drugs, end-stage renal disease, estimated glomerular filtration rate decline, biomarkers, metformin, insulin secretagogues, cardiorenal protection, hypoglycemia risk, weight gain
MeSH terms
Clinical Decision-Making, Blood Glucose, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Glomerular Filtration Rate, Humans, Hypoglycemic Agents, Kidney, Kidney Failure, Chronic, Risk Factors, Biomarkers, Treatment Outcome, Disease Progression, Patient Selection, Consensus

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review