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Updating the natural history of diabetic nephropathy

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Abstract

Diabetic nephropathy (DN) is a major cause of morbidity and mortality in patients with both types of diabetes and the leading cause of end-stage renal disease (ESRD) worldwide. The classical, five-stage natural history of DN, after an initial phase of hyperfiltration, is characterized by a progressive increase of albuminuria from normoalbuminuria to proteinuria, followed by a decline of glomerular filtration rate (GFR). Accumulating evidence indicates that clinical course of DN has changed profoundly, likely as a consequence of changes in treatment. In fact, remission/regression of microalbuminuria is a common feature of both type 1 and 2 diabetes which far outweighs progression to proteinuria. Moreover, GFR loss has been shown to occur independently of albuminuria or even in the absence of it. Nonalbuminuric renal impairment probably represents a different pathway to loss of renal function, which might recognize different pathogenic mechanisms, prognostic implications, and possibly therapeutic measures, as compared with the albuminuric pathway. The nonalbuminuric phenotype might be related to macroangiopathy instead of microangiopathy and/or be the consequence of repeated and/or unresolved episodes of acute kidney injury, even of mild degree. Reduced GFR and albuminuria are both powerful risk factor for cardiovascular events, whereas albuminuria appears to predict death and progression to ESRD better than GFR loss. Finally, it is unclear whether reduced GFR and albuminuria warrant different interventions and whether GFR decline may also regress in response to treatment, as proteinuria does. Further epidemiological, pathologic, pathophysiological, and intervention studies are needed to clarify the distinctive features of nonalbuminuric renal impairment.

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Abbreviations

DN:

Diabetic nephropathy

ESRD:

End-stage renal disease

CVD:

Cardiovascular disease

GFR:

Glomerular filtration rate

BP:

Blood pressure

AER:

Albumin excretion rate

RAS:

Renin–angiotensin system

eGFR:

Estimated GFR

HbA1c :

Hemoglobin A1c

TNFR:

Tumor necrosis factor receptor

CKD:

Chronic kidney disease

NHANES:

National Health and Nutrition Examination Survey

DEMAND:

Developing Education on Microalbuminuria for Awareness of renal and cardiovascular risk in Diabetes

UKPDS:

United Kingdom Prospective Diabetes Study

DCCT/EDIC:

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications

NEFRON:

National Evaluation of the Frequency of Renal Impairment cO-existing with NIDDM

RIACE:

Renal Insufficiency And Cardiovascular Events

PERCEDIME2:

Prevalence of chronic kidney disease in patients with type 2 diabetes in Spain

ADVANCE:

Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation

FIELD:

Fenofibrate Intervention and Event Lowering in Diabetes

MDRD:

Modification of Diet in Renal Disease

CKD-EPI:

CKD-Epidemiology Collaboration

ARIC:

Atherosclerosis Risk in Communities

AKI:

Acute kidney injury

KDIGO:

Kidney Disease Improving Global Outcomes

RENAAL:

Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan

References

  1. Reutens AT, Atkins RC (2011) Epidemiology of diabetic nephropathy. Contrib Nephrol 170:1–7

    Article  PubMed  Google Scholar 

  2. Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053

    Article  PubMed  Google Scholar 

  3. Ritz E, Rychlík I, Locatelli F, Halimi S (1999) End-stage renal failure in type 2 diabetes: a medical catastrophe of worldwide dimensions. Am J Kidney Dis 34:795–808

    Article  CAS  PubMed  Google Scholar 

  4. Gregg EW, Li Y, Wang J, Burrows NR, Ali MK, Rolka D, Williams DE, Geiss L (2014) Changes in diabetes-related complications in the United States, 1990–2010. N Engl J Med 370:1514–1523

    Article  CAS  PubMed  Google Scholar 

  5. Mogensen CE (1999) Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas. Diabetologia 42:263–285

    Article  CAS  PubMed  Google Scholar 

  6. Jerums G, Premaratne E, Panagiotopoulos S, MacIsaac RJ (2010) The clinical significance of hyperfiltration in diabetes. Diabetologia 53:2093–2104

    Article  CAS  PubMed  Google Scholar 

  7. Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H (1982) Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1:1430–1432

    Article  CAS  PubMed  Google Scholar 

  8. Parving HH, Oxenbøll B, Svendsen PA, Christiansen JS, Andersen AR (1982) Early detection of patients at risk of developing diabetic nephropathy: a longitudinal study of urinary albumin excretion. Acta Endocrinol (Copenh) 100:550–555

    CAS  Google Scholar 

  9. Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311:89–93

    Article  CAS  PubMed  Google Scholar 

  10. Mathiesen ER, Oxenbøll B, Johansen K, Svendsen PA, Deckert T (1984) Incipient nephropathy in type 1 (insulin-dependent) diabetes. Diabetologia 26:406–410

    Article  CAS  PubMed  Google Scholar 

  11. Mogensen CE (1984) Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310:356–360

    Article  CAS  PubMed  Google Scholar 

  12. Tanaka Y, Atsumi Y, Matsuoka K, Onuma T, Tohjima T, Kawamori R (1998) Role of glycemic control and blood pressure in the development and progression of nephropathy in elderly Japanese NIDDM patients. Diabetes Care 21:116–120

    Article  CAS  PubMed  Google Scholar 

  13. Ravid M, Savin H, Jutrin I, Bental T, Katz B, Lishner M (1993) Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med 118:577–581

    Article  CAS  PubMed  Google Scholar 

  14. Ahmad J, Siddiqui MA, Ahmad H (1997) Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria. Diabetes Care 20:1576–1581

    Article  CAS  PubMed  Google Scholar 

  15. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS (2003) Regression of microalbuminuria in type 1 diabetes. N Engl J Med 348:2285–2293

    Article  CAS  PubMed  Google Scholar 

  16. Giorgino F, Laviola L, Cavallo Perin P, Solnica B, Fuller J, Chaturvedi N (2004) Factors associated with progression to macroalbuminuria in microalbuminuric type 1 diabetic patients: the EURODIAB Prospective Complications Study. Diabetologia 47:1020–1028

    Article  CAS  PubMed  Google Scholar 

  17. Hovind P, Tarnow L, Rossing P, Jensen BR, Graae M, Torp I, Binder C, Parving HH (2004) Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ 328:1105

    Article  PubMed Central  PubMed  Google Scholar 

  18. Gaede P, Tarnow L, Vedel P, Parving HH, Pedersen O (2004) Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria. Nephrol Dial Transplant 19:2784–2788

    Article  PubMed  Google Scholar 

  19. Araki S, Haneda M, Sugimoto T, Isono M, Isshiki K, Kashiwagi A, Koya D (2005) Factors associated with frequent remission of microalbuminuria in patients with type 2 diabetes mellitus. Diabetes 54:2983–2987

    Article  CAS  PubMed  Google Scholar 

  20. Yamada T, Komatsu M, Komiya I, Miyahara Y, Shima Y, Matsuzaki M, Ishikawa Y, Mita R, Fujiwara M, Furusato N, Nishi K, Aizawa T (2005) 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 28:2733–2738

    Article  PubMed  Google Scholar 

  21. Tabaei BP, Al-Kassab AS, Ilag LL, Zawacki CM, Herman WH (2001) Does microalbuminuria predict diabetic nephropathy? Diabetes Care 24:1560–1566

    Article  CAS  PubMed  Google Scholar 

  22. Perkins BA, Krolewski AS (2009) Early nephropathy in type 1 diabetes: the importance of early renal function decline. Curr Opin Nephrol Hypertens 18:233–240

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Perkins BA, Ficociello LH, Ostrander BE, Silva KH, Weinberg J, Warram JH, Krolewski AS (2007) Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes. J Am Soc Nephrol 18:1353–1361

    Article  CAS  PubMed  Google Scholar 

  24. Krolewski AS, Niewczas MA, Skupien J, Gohda T, Smiles A, Eckfeldt JH, Doria A, Warram JH (2014) Early progressive renal decline precedes the onset of microalbuminuria and its progression to macroalbuminuria. Diabetes Care 37:226–234

    Article  CAS  PubMed  Google Scholar 

  25. Skupien J, Warram JH, Smiles AM, Niewczas MA, Gohda T, Pezzolesi MG, Cantarovich D, Stanton R, Krolewski AS (2012) The early decline in renal function in patients with type 1 diabetes and proteinuria predicts the risk of end-stage renal disease. Kidney Int 82:589–597

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Skupien J, Warram JH, Smiles A, Galecki A, Stanton RC, Krolewski AS (2014) Improved glycemic control and risk of ESRD in patients with type 1 diabetes and proteinuria. J Am Soc Nephrol. doi:10.1681/ASN.2013091002

  27. Skupien J, Warram JH, Niewczas MA, Gohda T, Malecki M, Mychaleckyj JC, Galecki AT, Krolewski AS (2014) Synergism between circulating tumor necrosis factor receptor 2 and HbA1c in determining renal decline during 5-18 years of follow-up in patients with type 1 diabetes and proteinuria. Diabetes Care 37:2601–2608

    Article  CAS  PubMed  Google Scholar 

  28. Sabbisetti VS, Waikar SS, Antoine DJ, Smiles A, Wang C, Ravisankar A, Ito K, Sharma S, Ramadesikan S, Lee M, Briskin R, De Jager PL, Ngo TT, Radlinski M, Dear JW, Park KB, Betensky R, Krolewski AS, Bonventre JV (2014) Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. J Am Soc Nephrol. doi:10.1681/ASN.2013070758

  29. Lacquaniti A, Donato V, Pintaudi B, Di Vieste G, Chirico V, Buemi A, Di Benedetto A, Arena A, Buemi M (2013) “Normoalbuminuric” diabetic nephropathy: tubular damage and NGAL. Acta Diabetol 50:935–942

    Article  CAS  PubMed  Google Scholar 

  30. Kopf S, Oikonomou D, von Eynatten M, Kieser M, Zdunek D, Hess G, Morcos M, Forsblom C, Bierhaus A, Groop PH, Nawroth PP, Humpert PM (2014) Urinary excretion of high molecular weight adiponectin is an independent predictor of decline of renal function in type 2 diabetes. Acta Diabetol 51:479–489

    CAS  PubMed  Google Scholar 

  31. Lane PH, Steffes MW, Mauer SM (1992) Glomerular structure in IDDM women with low glomerular filtration rate and normal urinary albumin excretion. Diabetes 41:581–586

    Article  CAS  PubMed  Google Scholar 

  32. Tsalamandris C, Allen TJ, Gilbert RE, Sinha A, Panagiotopoulos S, Cooper ME, Jerums G (1994) Progressive decline in renal function in diabetic patients with and without albuminuria. Diabetes 43:649–655

    Article  CAS  PubMed  Google Scholar 

  33. Kramer HJ, Nguyen QD, Curhan G, Hsu CY (2003) Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. JAMA 289:3273–3277

    Article  PubMed  Google Scholar 

  34. MacIsaac RJ, Tsalamandris C, Panagiotopoulos S, Smith TJ, McNeil KJ, Jerums G (2004) Nonalbuminuric renal insufficiency in type 2 diabetes. Diabetes Care 27:195–200

    Article  PubMed  Google Scholar 

  35. Dwyer JP, Parving HH, Hunsicker LG, Ravid M, Remuzzi G, Lewis JB, DEMAND Investigators (2012) Renal dysfunction in the presence of normoalbuminuria in type 2 diabetes: results from the DEMAND study. Cardiorenal Med 2:1–10

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR; UKPDS Study Group (2006) Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes 55:1832–1839

    Article  Google Scholar 

  37. Molitch ME, Steffes M, Sun W, Rutledge B, Cleary P, de Boer IH, Zinman B, Lachin J, Epidemiology of Diabetes Interventions and Complications Study Group (2010) 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 33:1536–1543

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Thomas MC, Macisaac RJ, Jerums G, Weekes A, Moran J, Shaw JE, Atkins RC (2009) Nonalbuminuric renal impairment in type 2 diabetic patients and in the general population (national evaluation of the frequency of renal impairment cO-existing with NIDDM [NEFRON] 11). Diabetes Care 32:1497–1502

    Article  PubMed Central  PubMed  Google Scholar 

  39. Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Trevisan R, Vedovato M, Gruden G, Cavalot F, Cignarelli M, Laviola L, Morano S, Nicolucci A, Pugliese G, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group (2011) Clinical significance of nonalbuminuric renal impairment in type 2 diabetes. J Hypertens 29:1802–1809

    Article  CAS  PubMed  Google Scholar 

  40. Rodriguez-Poncelas A, Garre-Olmo J, Franch-Nadal J, Diez-Espino J, Mundet-Tuduri X, Barrot-De la Puente J, Coll-de Tuero G (2013) RedGDPS Study Group Prevalence of chronic kidney disease in patients with type 2 diabetes in Spain: PERCEDIME2 study. BMC Nephrol 14:46

    Article  PubMed Central  PubMed  Google Scholar 

  41. Mottl AK, Kwon KS, Mauer M, Mayer-Davis EJ, Hogan SL, Kshirsagar AV (2013) Normoalbuminuric diabetic kidney disease in the U.S. population. J Diabetes Complications 27:123–127

    Article  PubMed  Google Scholar 

  42. Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, Patel A, Cass A, Neal B, Poulter N, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Macmahon S, Chalmers J, ADVANCE Collaborative Group (2009) Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol 20:1813–1821

    Article  PubMed Central  PubMed  Google Scholar 

  43. Drury PL, Ting R, Zannino D, Ehnholm C, Flack J, Whiting M, Fassett R, Ansquer JC, Dixon P, Davis TM, Pardy C, Colman P, Keech A (2011) Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetologia 54:32–43

    Article  CAS  PubMed  Google Scholar 

  44. Rigalleau V, Lasseur C, Raffaitin C, Beauvieux MC, Barthe N, Chauveau P, Combe C, Gin H (2007) Normoalbuminuric renal-insufficient diabetic patients: a lower-risk group. Diabetes Care 30:2034–2039

    Article  CAS  PubMed  Google Scholar 

  45. Pugliese G, Solini A, Bonora E, Orsi E, Zerbini G, Giorgino F, Cavalot F, Pontiroli AE, Baroni MG, Morano S, Nicolucci A, Penno G (2011) The Chronic Kidney Disease Epidemiology Collaboration (CKD–EPI) equation provides a better definition of cardiovascular burden associated with CKD than the Modification of Diet in Renal Disease (MDRD) Study formula in subjects with type 2 diabetes. Atherosclerosis 218:194–199

    Article  CAS  PubMed  Google Scholar 

  46. Pugliese G, Solini A, Fondelli C, Trevisan R, Vedovato M, Nicolucci A, Penno G, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group (2011) Reproducibility of albuminuria in type 2 diabetic subjects. Findings from the Renal Insufficiency And Cardiovascular Events (RIACE) study. Nephrol Dial Transplant 26:3950–3954

    Article  CAS  PubMed  Google Scholar 

  47. de Boer IH, Steffes MW (2007) Glomerular filtration rate and albuminuria: twin manifestations of nephropathy in diabetes. J Am Soc Nephrol 18:1036–1037

    Article  PubMed  Google Scholar 

  48. Caramori ML, Fioretto P, Mauer M (2000) The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 49:1399–1408

    Article  CAS  PubMed  Google Scholar 

  49. Yokoyama H, Sone H, Oishi M, Kawai K, Fukumoto Y, Kobayashi M, Japan Diabetes Clinical Data Management Study Group (2009) Prevalence of albuminuria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes Clinical Data Management study (JDDM15). Nephrol Dial Transplant 24:1212–1219

    Article  CAS  PubMed  Google Scholar 

  50. Afghahi H, Cederholm J, Eliasson B, Zethelius B, Gudbjörnsdottir S, Hadimeri H, Svensson MK (2011) Risk factors for the development of albuminuria and renal impairment in type 2 diabetes–the Swedish National Diabetes Register (NDR). Nephrol Dial Transplant 26:1236–1243

    Article  PubMed  Google Scholar 

  51. Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Morano S, Cavalot F, Lamacchia O, Laviola L, Nicolucci A, Pugliese G, Renal Insufficiency And Cardiovascular Events Study Group (2013) 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 multicenter study. Diabetes Care 36:2301–2310

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Penno G, Solini A, Zoppini G, Orsi E, Zerbini G, Trevisan R, Gruden G, Cavalot F, Laviola L, Morano S, Nicolucci A, Pugliese G, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group (2012) Rate and determinants of association between advanced retinopathy and chronic kidney disease in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study. Diabetes Care 35:2317–2323

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Bash LD, Selvin E, Steffes M, Coresh J, Astor BC (2008) Poor glycemic control in diabetes and the risk of incident chronic kidney disease even in the absence of albuminuria and retinopathy: atherosclerosis Risk in Communities (ARIC) Study. Arch Intern Med 168:2440–2447

    Article  PubMed Central  PubMed  Google Scholar 

  54. Kramer CK, Leitão CB, Pinto LC, Silveiro SP, Gross JL, Canani LH (2007) Clinical and laboratory profile of patients with type 2 diabetes with low glomerular filtration rate and normoalbuminuria. Diabetes Care 30:1998–2000

    Article  CAS  PubMed  Google Scholar 

  55. Caramori ML, Fioretto P, Mauer M (2003) Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions. Diabetes 52:1036–1040

    Article  CAS  PubMed  Google Scholar 

  56. Ekinci EI, Jerums G, Skene A, Crammer P, Power D, Cheong KY, Panagiotopoulos S, McNeil K, Baker ST, Fioretto P, Macisaac RJ (2013) Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function. Diabetes Care 36:3620–3626

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. MacIsaac RJ, Panagiotopoulos S, McNeil KJ, Smith TJ, Tsalamandris C, Hao H, Matthews PG, Thomas MC, Power DA, Jerums G (2006) Is nonalbuminuric renal insufficiency in type 2 diabetes related to an increase in intrarenal vascular disease? Diabetes Care 29:1560–1566

    Article  PubMed  Google Scholar 

  58. Fioretto P, Mauer M, Brocco E, Velussi M, Frigato F, Muollo B, Sambataro M, Abaterusso C, Baggio B, Crepaldi G, Nosadini R (1996) Patterns of renal injury in NIDDM patients with microalbuminuria. Diabetologia 39:1569–1576

    Article  CAS  PubMed  Google Scholar 

  59. Romagnani P, Remuzzi G (2013) Renal progenitors in non-diabetic and diabetic nephropathies. Trends Endocrinol Metab 24:13–20

    Article  CAS  PubMed  Google Scholar 

  60. Chawla LS, Kimmel PL (2012) Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney Int 82:516–524

    Article  PubMed  Google Scholar 

  61. Coca SG, Singanamala S, Parikh CR (2012) Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 81:442–448

    Article  PubMed Central  PubMed  Google Scholar 

  62. Bucaloiu ID, Kirchner HL, Norfolk ER, Hartle JE 2nd, Perkins RM (2012) Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury. Kidney Int 81:477–485

    Article  PubMed  Google Scholar 

  63. Kline J, Rachoin JS (2013) Acute kidney injury and chronic kidney disease: it’s a two-way street. Ren Fail 35:452–455

    Article  PubMed  Google Scholar 

  64. Niewczas MA, Gohda T, Skupien J, Smiles AM, Walker WH, Rosetti F, Cullere X, Eckfeldt JH, Doria A, Mayadas TN, Warram JH, Krolewski AS (2012) Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes. J Am Soc Nephrol 23:507–515

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Solini A, Penno G, Bonora E, Fondelli C, Orsi E, Arosio M, Trevisan R, Vedovato M, Cignarelli M, Andreozzi F, Nicolucci A, Pugliese G, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group (2012) 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 multicenter study. Diabetes Care 35:143–149

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Hoefield RA, Kalra PA, Baker PG, Sousa I, Diggle PJ, Gibson MJ, O’Donoghue DJ, Middleton RJ, New JP (2011) The use of eGFR and ACR to predict decline in renal function in people with diabetes. Nephrol Dial Transplant 26:887–892

    Article  PubMed  Google Scholar 

  67. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150

    Article  Google Scholar 

  68. Evans M, Bain SC, Hogan S, Bilous RW, Collaborative Study Group participants (2012) Irbesartan delays progression of nephropathy as measured by estimated glomerular filtration rate: post hoc analysis of the Irbesartan Diabetic Nephropathy Trial. Nephrol Dial Transplant 27:2255–2263

    Article  CAS  PubMed  Google Scholar 

  69. Abuelo JG (2007) Normotensive ischemic acute renal failure. N Engl J Med 357:797–805

    Article  CAS  PubMed  Google Scholar 

  70. Jerums G, Panagiotopoulos S, Premaratne E, Power DA, MacIsaac RJ (2008) Lowering of proteinuria in response to antihypertensive therapy predicts improved renal function in late but not in early diabetic nephropathy: a pooled analysis. Am J Nephrol 28:614–627

    Article  CAS  PubMed  Google Scholar 

  71. de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM (2004) Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int 65:2309–2320

    Article  PubMed  Google Scholar 

  72. Levey AS, Cattran D, Friedman A, Miller WG, Sedor J, Tuttle K, Kasiske B, Hostetter T (2009) 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 54:205–226

    Article  PubMed  Google Scholar 

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Acknowledgments

The content of this article was the subject of the 12th Ruth Osterby Lecture, given by Professor Pugliese at the 27th Annual General Meeting of the European Diabetic Nephropathy Study Group (EDNSG), which was held in London, UK, on May 16–17, 2014. The Author thanks the RIACE Investigators for participating in the studies cited in this article. The RIACE study cited in this article was supported by the Research Foundation of the Italian Society of Diabetology (Fo.Ri.SID) and the Diabetes, Endocrinology and Metabolism (DEM) Foundation, and by unconditional grants from Eli-Lilly, Takeda, Chiesi Farmaceutici and Boehringer-Ingelheim.

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Pugliese, G. Updating the natural history of diabetic nephropathy. Acta Diabetol 51, 905–915 (2014). https://doi.org/10.1007/s00592-014-0650-7

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