Skip to main content

Screening, Early Diagnosis, Genetic Markers, and Predictors of Diabetic Nephropathy

  • Chapter
  • First Online:
Diabetes and Kidney Disease

Abstract

Early and accurate identification of diabetic nephropathy will improve patient care. Known biomarkers of diabetic nephropathy are indicators of renal tissue injury, including urinary excretion of proteins such as albumin and collagen. Azotemia confirms kidney damage and predicts future evolution. Inflammatory markers may be mechanistically relevant. Allelic variations may provide novel insights but thus far appear unsuitable as markers. Non-renal markers of diabetic nephropathy include its associated clinical features such as retinopathy, neuropathy, and non-dipping hypertension. Markers of irreversibility are needed. The best biomarkers will be cost-effective, sensitive, and specific, and their measurement will relieve illness and prolong life.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Fishberg AM. Hypertension and nephritis. Philadelphia: Lea and Febiger; 1954.

    Google Scholar 

  2. Plantinga LC, Crews DC, Coresh J, Miller 3rd ER, Saran R, Yee J, et al. Prevalence of chronic kidney disease in US adults with undiagnosed diabetes or prediabetes. Clin J Am Soc Nephrol. 2010;5(4):673–82.

    Article  PubMed Central  PubMed  Google Scholar 

  3. American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care. 2013;36 Suppl 1:S11–66.

    Article  PubMed Central  Google Scholar 

  4. 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(5):589–97.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Bright R. Cases and observations illustrative of renal disease accompanied with the secretion of albumenous urine. Guys Hosp Rep. 1836;1:338–79.

    Google Scholar 

  6. Kimmelstiel P, Wilson C. Intercapillary lesions in the glomeruli of the kidney. Am J Pathol. 1936;12:83–97.

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983;32 Suppl 2:64–78.

    Article  PubMed  Google Scholar 

  8. Groop PH, Thomas MC, Moran JL, Waden J, Thorn LM, Makinen VP, et al. The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes. Diabetes. 2009;58(7):1651–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358(6):580–91.

    Article  CAS  PubMed  Google Scholar 

  10. Macisaac RJ, Jerums G. Diabetic kidney disease with and without albuminuria. Curr Opin Nephrol Hypertens. 2011;20(3):246–57.

    Article  CAS  PubMed  Google Scholar 

  11. Magliano DJ, Polkinghorne KR, Barr EL, Su Q, Chadban SJ, Zimmet PZ, et al. HPLC-detected albuminuria predicts mortality. J Am Soc Nephrol. 2007;18(12):3171–6.

    Article  CAS  PubMed  Google Scholar 

  12. Caramori ML, Fioretto P, Mauer M. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes. 2000;49(9):1399–408.

    Article  CAS  PubMed  Google Scholar 

  13. Araki S, Haneda M, Koya D, Isshiki K, Kume S, Sugimoto T, et al. Association between urinary type IV collagen level and deterioration of renal function in type 2 diabetic patients without overt proteinuria. Diabetes Care. 2010;33(8):1805–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Ziyadeh FN. Renal tubular basement membrane and collagen type IV in diabetes mellitus. Kidney Int. 1993;43(1):114–20.

    Article  CAS  PubMed  Google Scholar 

  15. Cohen MP, Lautenslager GT, Shearman CW. Increased collagen IV excretion in diabetes. A marker of compromised filtration function. Diabetes Care. 2001;24(5):914–8.

    Article  CAS  PubMed  Google Scholar 

  16. Yamamoto T, Nakamura T, Noble NA, Ruoslahti E, Border WA. Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy. Proc Natl Acad Sci U S A. 1993;90(5):1814–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Shaker OG, Sadik NA. Transforming growth factor beta 1 and monocyte chemoattractant protein-1 as prognostic markers of diabetic nephropathy. Hum Exp Toxicol. 2013;32(10):1089–96.

    Article  CAS  PubMed  Google Scholar 

  18. Langham RG, Kelly DJ, Gow RM, Zhang Y, Cordonnier DJ, Pinel N, et al. Transforming growth factor-beta in human diabetic nephropathy: effects of ACE inhibition. Diabetes Care. 2006;29(12):2670–5.

    Article  CAS  PubMed  Google Scholar 

  19. Houlihan CA, Akdeniz A, Tsalamandris C, Cooper ME, Jerums G, Gilbert RE. Urinary transforming growth factor-beta excretion in patients with hypertension, type 2 diabetes, and elevated albumin excretion rate: effects of angiotensin receptor blockade and sodium restriction. Diabetes Care. 2002;25(6):1072–7.

    Article  CAS  PubMed  Google Scholar 

  20. Bertoluci MC, Uebel D, Schmidt A, Thomazelli FC, Oliveira FR, Schmid H. Urinary TGF-beta1 reduction related to a decrease of systolic blood pressure in patients with type 2 diabetes and clinical diabetic nephropathy. Diabetes Res Clin Pract. 2006;72(3):258–64.

    Article  CAS  PubMed  Google Scholar 

  21. Wolkow PP, Niewczas MA, Perkins B, Ficociello LH, Lipinski B, Warram JH, et al. Association of urinary inflammatory markers and renal decline in microalbuminuric type 1 diabetics. J Am Soc Nephrol. 2008;19(4):789–97.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Gohda T, Walker WH, Wolkow P, Lee JE, Warram JH, Krolewski AS, et al. Elevated urinary excretion of immunoglobulins in nonproteinuric patients with type 1 diabetes. Am J Physiol Renal Physiol. 2012;303(1):F157–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Merchant ML, Perkins BA, Boratyn GM, Ficociello LH, Wilkey DW, Barati MT, et al. Urinary peptidome may predict renal function decline in type 1 diabetes and microalbuminuria. J Am Soc Nephrol. 2009;20(9):2065–74.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Vaidya VS, Niewczas MA, Ficociello LH, Johnson AC, Collings FB, Warram JH, et al. Regression of microalbuminuria in type 1 diabetes is associated with lower levels of urinary tubular injury biomarkers, kidney injury molecule-1, and N-acetyl-beta-d-glucosaminidase. Kidney Int. 2011;79(4):464–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Nauta FL, Boertien WE, Bakker SJ, van Goor H, van Oeveren W, de Jong PE, et al. Glomerular and tubular damage markers are elevated in patients with diabetes. Diabetes Care. 2011;34(4):975–81.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Schlatzer D, Maahs DM, Chance MR, Dazard JE, Li X, Hazlett F, et al. Novel urinary protein biomarkers predicting the development of microalbuminuria and renal function decline in type 1 diabetes. Diabetes Care. 2012;35(3):549–55.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Rossing K, Mischak H, Dakna M, Zurbig P, Novak J, Julian BA, et al. Urinary proteomics in diabetes and CKD. J Am Soc Nephrol. 2008;19(7):1283–90.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. 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(6):1136–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Nielsen SE, Andersen S, Zdunek D, Hess G, Parving HH, Rossing P. Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy. Kidney Int. 2011;79(10):1113–8.

    Article  CAS  PubMed  Google Scholar 

  30. Chou KM, Lee CC, Chen CH, Sun CY. Clinical value of NGAL, L-FABP and albuminuria in predicting GFR decline in type 2 diabetes mellitus patients. PLoS One. 2013;8(1):e54863.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. 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(7):812–8.

    Article  CAS  PubMed  Google Scholar 

  32. 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(3):656–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Lurbe E, Redon J, Kesani A, Pascual JM, Tacons J, Alvarez V, et al. Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med. 2002;347(11):797–805.

    Article  CAS  PubMed  Google Scholar 

  34. Hermida RC, Ayala DE, Mojon A, Fernandez JR. Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. J Am Soc Nephrol. 2011;22(12):2313–21.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Moya A, Crespo JJ, Ayala DE, Rios MT, Pousa L, Callejas PA, et al. Effects of time-of-day of hypertension treatment on ambulatory blood pressure and clinical characteristics of patients with type 2 diabetes. Chronobiol Int. 2013;30(1–2):116–31.

    Article  CAS  PubMed  Google Scholar 

  36. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group, Nathan DM, Zinman B, Cleary PA, Backlund JY, Genuth S, et al. Modern-day clinical course of type 1 diabetes mellitus after 30 years’ duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983–2005). Arch Intern Med. 2009;169(14):1307–16.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376(9735):124–36.

    Article  PubMed  Google Scholar 

  38. El-Asrar AM, Al-Rubeaan KA, Al-Amro SA, Moharram OA, Kangave D. Retinopathy as a predictor of other diabetic complications. Int Ophthalmol. 2001;24(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  39. He F, Xia X, Wu XF, Yu XQ, Huang FX. Diabetic retinopathy in predicting diabetic nephropathy in patients with type 2 diabetes and renal disease: a meta-analysis. Diabetologia. 2013;56(3):457–66.

    Article  CAS  PubMed  Google Scholar 

  40. Amoah E, Glickman JL, Malchoff CD, Sturgill BC, Kaiser DL, Bolton WK. Clinical identification of nondiabetic renal disease in diabetic patients with type I and type II disease presenting with renal dysfunction. Am J Nephrol. 1988;8(3):204–11.

    Article  CAS  PubMed  Google Scholar 

  41. 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 multicenter study. Diabetes Care. 2013;36(8):2301–10.

    Article  CAS  PubMed  Google Scholar 

  42. Desai AS, Toto R, Jarolim P, Uno H, Eckardt KU, Kewalramani R, et al. Association between cardiac biomarkers and the development of ESRD in patients with type 2 diabetes mellitus, anemia, and CKD. Am J Kidney Dis. 2011;58(5):717–28.

    Article  CAS  PubMed  Google Scholar 

  43. 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(3):507–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. 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(3):516–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Brosius FC, Saran R. Do we now have a prognostic biomarker for progressive diabetic nephropathy? J Am Soc Nephrol. 2012;23(3):376–7.

    Article  CAS  PubMed  Google Scholar 

  46. Kanbay M, Segal M, Afsar B, Kang DH, Rodriguez-Iturbe B, Johnson RJ. The role of uric acid in the pathogenesis of human cardiovascular disease. Heart. 2013;99(11):759–66.

    Article  CAS  PubMed  Google Scholar 

  47. Johnson RJ, Nakagawa T, Jalal D, Sanchez-Lozada LG, Kang DH, Ritz E. Uric acid and chronic kidney disease: which is chasing which? Nephrol Dial Transplant. 2013;28(9):2221–8.

    Article  CAS  PubMed  Google Scholar 

  48. 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(6):1337–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Jalal DI, Rivard CJ, Johnson RJ, Maahs DM, McFann K, Rewers M, et al. Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the Coronary Artery Calcification in Type 1 Diabetes study. Nephrol Dial Transplant. 2010;25(6):1865–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Thomson SC, Vallon V, Blantz RC. Kidney function in early diabetes: the tubular hypothesis of glomerular filtration. Am J Physiol Renal Physiol. 2004;286(1):F8–15.

    Article  CAS  PubMed  Google Scholar 

  51. Zerbini G, Bonfanti R, Meschi F, Bognetti E, Paesano PL, Gianolli L, et al. Persistent renal hypertrophy and faster decline of glomerular filtration rate precede the development of microalbuminuria in type 1 diabetes. Diabetes. 2006;55(9):2620–5.

    Article  CAS  PubMed  Google Scholar 

  52. Youssef DM, Fawzy FM. Value of renal resistive index as an early marker of diabetic nephropathy in children with type-1 diabetes mellitus. Saudi J Kidney Dis Transpl. 2012;23(5):985–92.

    Article  PubMed  Google Scholar 

  53. Freedman BI, Spray BJ, Tuttle AB, Buckalew Jr VM. The familial risk of end-stage renal disease in African Americans. Am J Kidney Dis. 1993;21(4):387–93.

    CAS  PubMed  Google Scholar 

  54. Wasser WG, Tzur S, Wolday D, Adu D, Baumstein D, Rosset S, et al. Population genetics of chronic kidney disease: the evolving story of APOL1. J Nephrol. 2012;25(5):603–18.

    Article  CAS  PubMed  Google Scholar 

  55. Freedman BI, Kopp JB, Langefeld CD, Genovese G, Friedman DJ, Nelson GW, et al. The apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy in African Americans. J Am Soc Nephrol. 2010;21(9):1422–6.

    Article  CAS  PubMed  Google Scholar 

  56. Caramori ML, Canani LH, Costa LA, Gross JL. The human peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes. Diabetes. 2003;52(12):3010–3.

    Article  CAS  PubMed  Google Scholar 

  57. Grzeszczak W, Moczulski DK, Zychma M, Zukowska-Szczechowska E, Trautsolt W, Szydlowska I. Role of GLUT1 gene in susceptibility to diabetic nephropathy in type 2 diabetes. Kidney Int. 2001;59(2):631–6.

    Article  CAS  PubMed  Google Scholar 

  58. Ng DP, Tai BC, Koh D, Tan KW, Chia KS. Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects. Diabetologia. 2005;48(5):1008–16.

    Article  CAS  PubMed  Google Scholar 

  59. Currie D, McKnight AJ, Patterson CC, Sadlier DM, Maxwell AP, UK Warren 3/GoKinD Study Group. Investigation of ACE, ACE2 and AGTR1 genes for association with nephropathy in type 1 diabetes mellitus. Diabet Med. 2010;27(10):1188–94.

    Article  CAS  PubMed  Google Scholar 

  60. Hadjadj S, Belloum R, Bouhanick B, Gallois Y, Guilloteau G, Chatellier G, et al. Prognostic value of angiotensin-I converting enzyme I/D polymorphism for nephropathy in type 1 diabetes mellitus: a prospective study. J Am Soc Nephrol. 2001;12(3):541–9.

    CAS  PubMed  Google Scholar 

  61. Freedman BI, Bostrom M, Daeihagh P, Bowden DW. Genetic factors in diabetic nephropathy. Clin J Am Soc Nephrol. 2007;2(6):1306–16.

    Article  CAS  PubMed  Google Scholar 

  62. Vionnet N, Tregouet D, Kazeem G, Gut I, Groop PH, Tarnow L, et al. Analysis of 14 candidate genes for diabetic nephropathy on chromosome 3q in European populations: strongest evidence for association with a variant in the promoter region of the adiponectin gene. Diabetes. 2006;55(11):3166–74.

    Article  CAS  PubMed  Google Scholar 

  63. McKnight AJ, Patterson CC, Pettigrew KA, Savage DA, Kilner J, Murphy M, et al. A GREM1 gene variant associates with diabetic nephropathy. J Am Soc Nephrol. 2010;21(5):773–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Liu ZH, Guan TJ, Chen ZH, Li LS. Glucose transporter (GLUT1) allele (XbaI-) associated with nephropathy in non-insulin-dependent diabetes mellitus. Kidney Int. 1999;55(5):1843–8.

    Article  CAS  PubMed  Google Scholar 

  65. Janssen B, Hohenadel D, Brinkkoetter P, Peters V, Rind N, Fischer C, et al. Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1. Diabetes. 2005;54(8):2320–7.

    Article  CAS  PubMed  Google Scholar 

  66. Shimazaki A, Kawamura Y, Kanazawa A, Sekine A, Saito S, Tsunoda T, et al. Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy. Diabetes. 2005;54(4):1171–8.

    Article  CAS  PubMed  Google Scholar 

  67. Alvarez ML, DiStefano JK. Towards microRNA-based therapeutics for diabetic nephropathy. Diabetologia. 2013;56(3):444–56.

    Article  CAS  PubMed  Google Scholar 

  68. Szeto CC, Ching-Ha KB, Ka-Bik L, Mac-Moune LF, Cheung-Lung CP, Gang W, et al. Micro-RNA expression in the urinary sediment of patients with chronic kidney diseases. Dis Markers. 2012;33(3):137–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Langham RG, Kelly DJ, Cox AJ, Thomson NM, Holthofer H, Zaoui P, et al. Proteinuria and the expression of the podocyte slit diaphragm protein, nephrin, in diabetic nephropathy: effects of angiotensin converting enzyme inhibition. Diabetologia. 2002;45(11):1572–6.

    Article  CAS  PubMed  Google Scholar 

  70. Jim B, Ghanta M, Qipo A, Fan Y, Chuang PY, Cohen HW, et al. Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: a cross sectional study. PLoS One. 2012;7(5):e36041.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Wang G, Lai FM, Lai KB, Chow KM, Li KT, Szeto CC. Messenger RNA expression of podocyte-associated molecules in the urinary sediment of patients with diabetic nephropathy. Nephron Clin Pract. 2007;106(4):c169–79.

    Article  CAS  PubMed  Google Scholar 

  72. Wang G, Lai FM, Lai KB, Chow KM, Kwan BC, Li PK, et al. Urinary messenger RNA expression of podocyte-associated molecules in patients with diabetic nephropathy treated by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker. Eur J Endocrinol. 2008;158(3):317–22.

    Article  CAS  PubMed  Google Scholar 

  73. Gambara V, Mecca G, Remuzzi G, Bertani T. Heterogeneous nature of renal lesions in type II diabetes. J Am Soc Nephrol. 1993;3(8):1458–66.

    CAS  PubMed  Google Scholar 

  74. Hodgin JB, Nair V, Zhang H, Randolph A, Harris RC, Nelson RG, et al. Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli. Diabetes. 2013;62(1):299–308.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Otu HH, Can H, Spentzos D, Nelson RG, Hanson RL, Looker HC, et al. Prediction of diabetic nephropathy using urine proteomic profiling 10 years prior to development of nephropathy. Diabetes Care. 2007;30(3):638–43.

    Article  CAS  PubMed  Google Scholar 

  76. Alkhalaf A, Zurbig P, Bakker SJ, Bilo HJ, Cerna M, Fischer C, et al. Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy. PLoS One. 2010;5(10):e13421.

    Article  PubMed Central  PubMed  Google Scholar 

  77. Yoshioka K, Tohda M, Takemura T, Akano N, Matsubara K, Ooshima A, et al. Distribution of type I collagen in human kidney diseases in comparison with type III collagen. J Pathol. 1990;162(2):141–8.

    Article  CAS  PubMed  Google Scholar 

  78. Kasinath BS, Mujais SK, Spargo BH, Katz AI. Nondiabetic renal disease in patients with diabetes mellitus. Am J Med. 1983;75(4):613–7.

    Article  CAS  PubMed  Google Scholar 

  79. Haider DG, Peric S, Friedl A, Fuhrmann V, Wolzt M, Horl WH, et al. Kidney biopsy in patients with diabetes mellitus. Clin Nephrol. 2011;76(3):180–5.

    CAS  PubMed  Google Scholar 

  80. Akimoto T, Ito C, Saito O, Takahashi H, Takeda S, Ando Y, et al. Microscopic hematuria and diabetic glomerulosclerosis—clinicopathological analysis of type 2 diabetic patients associated with overt proteinuria. Nephron Clin Pract. 2008;109(3):c119–26.

    Article  PubMed  Google Scholar 

  81. Mann JF, Anderson C, Gao P, Gerstein HC, Boehm M, Ryden L, et al. Dual inhibition of the renin-angiotensin system in high-risk diabetes and risk for stroke and other outcomes: results of the ONTARGET trial. J Hypertens. 2013;31(2):414–21.

    Article  CAS  PubMed  Google Scholar 

  82. Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372(9638):547–53.

    Article  CAS  PubMed  Google Scholar 

  83. Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK, Avoid Study Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008;358(23):2433–46.

    Article  CAS  PubMed  Google Scholar 

  84. Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012;367(23):2204–13.

    Article  CAS  PubMed  Google Scholar 

  85. de Leeuw PW. Aliskiren increased adverse events in patients with diabetes and kidney disease who were receiving ACE inhibitors or ARBs. Ann Intern Med. 2013;158(6):JC7.

    Article  PubMed  Google Scholar 

  86. Bakris GL, Weir MR, Shanifar S, Zhang Z, Douglas J, van Dijk DJ, et al. Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study. Arch Intern Med. 2003;163(13):1555–65.

    Article  PubMed  Google Scholar 

  87. ACCORD Study Group, Cushman WC, Evans GW, Byington RP, Goff Jr DC, Grimm Jr RH, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575–85.

    Article  PubMed  Google Scholar 

  88. Hansen MB, Jensen ML, Carstensen B. Causes of death among diabetic patients in Denmark. Diabetologia. 2012;55(2):294–302.

    Article  CAS  PubMed  Google Scholar 

  89. Haller H, Ito S, Izzo Jr JL, Januszewicz A, Katayama S, Menne J, et al. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med. 2011;364(10):907–17.

    Article  CAS  PubMed  Google Scholar 

  90. Palmer AJ, Chen R, Valentine WJ, Roze S, Bregman B, Mehin N, et al. Cost-consequence analysis in a French setting of screening and optimal treatment of nephropathy in hypertensive patients with type 2 diabetes. Diabetes Metab. 2006;32(1):69–76.

    Article  CAS  PubMed  Google Scholar 

  91. Howard K, White S, Salkeld G, McDonald S, Craig JC, Chadban S, et al. Cost-effectiveness of screening and optimal management for diabetes, hypertension, and chronic kidney disease: a modeled analysis. Value Health. 2010;13(2):196–208.

    Article  PubMed  Google Scholar 

  92. Kessler R, Keusch G, Szucs TD, Wittenborn JS, Hoerger TJ, Brugger U, et al. Health economic modelling of the cost-effectiveness of microalbuminuria screening in Switzerland. Swiss Med Wkly. 2012;142:w13508.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eric P. Cohen M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Cohen, E.P., Krzesinski, JM. (2014). Screening, Early Diagnosis, Genetic Markers, and Predictors of Diabetic Nephropathy. In: Lerma, E., Batuman, V. (eds) Diabetes and Kidney Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0793-9_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-0793-9_7

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-0792-2

  • Online ISBN: 978-1-4939-0793-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics