Jump to ContentJump to Main Navigation
Show Summary Details

Open Medicine

formerly Central European Journal of Medicine

Editor-in-Chief: Darzynkiewicz, Zbigniew

1 Issue per year


IMPACT FACTOR increased in 2015: 0.190
5-year IMPACT FACTOR: 0.221

SCImago Journal Rank (SJR) 2015: 0.140
Source Normalized Impact per Paper (SNIP) 2015: 0.154
Impact per Publication (IPP) 2015: 0.197

Open Access
Online
ISSN
2391-5463
See all formats and pricing
Volume 8, Issue 3 (Jun 2013)

Issues

Predictors of diabetic nephropathy

Mahmoud Gaballa
  • Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, PA 19107, USA
  • Email:
/ Youssef Farag
  • Renal Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, MA 02120, USA
  • Email:
Published Online: 2013-04-17 | DOI: https://doi.org/10.2478/s11536-012-0055-3

Abstract

Diabetic nephropathy (DN) is a leading cause of morbidity and mortality in diabetic patients representing a huge health and economic burden. Alarming recent data described diabetes as an unprecedented worldwide epidemic, with a prevalence of ∼6.4% of the world population in 2010, while the prevalence of CKD among diabetics was approximately 40%. With a clinical field hungry for novel markers predicting DN, several clinical and laboratory markers were identified lately with the promise of reliable DN prediction. Among those are age, gender, hypertension, smoking, sex hormones and anemia. In addition, eccentric left ventricular geometric patterns, detected by echocardiography, and renal hypertrophy, revealed by ultrasonography, are promising new markers predicting DN development. Serum and urinary markers are still invaluable elements, including serum uric acid, microalbuminuria, macroalbuminuria, urinary liver-type fatty acid-binding protein (u-LFABP), and urinary nephrin. Moreover, studies have illustrated a tight relationship between obstructive sleep apnea and the development of DN. The purpose of this review is to present the latest advances in identifying promising predictors to DN, which will help guide the future research questions in this field. Aiming at limiting this paramount threat, further efforts are necessary to identify and control independent modifiable risk factors, while developing an integrative algorithm for utilization in DN future screening programs.

Keywords: Diabetes; Chronic kidney disease; Diabetic nephropathy; Risk factors; Predictors; Markers; Microalbuminuria

  • [1] Foley, R.N. and A.J. Collins, The growing economic burden of diabetic kidney disease. Curr Diab Rep, 2009. 9(6): p. 460–465 http://dx.doi.org/10.1007/s11892-009-0075-9 [Crossref]

  • [2] Farag, Y.M. and M.R. Gaballa, Diabesity: an overview of a rising epidemic. Nephrol Dial Transplant, 2011. 26(1): p. 28–35 http://dx.doi.org/10.1093/ndt/gfq576 [Crossref]

  • [3] Shaw, J.E., R.A. Sicree, and P.Z. Zimmet, Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract, 2010. 87(1): p. 4–14 http://dx.doi.org/10.1016/j.diabres.2009.10.007

  • [4] Plantinga, L.C., et al., Prevalence of chronic kidney disease in US adults with undiagnosed diabetes or prediabetes. Clin J Am Soc Nephrol, 2010. 5(4): p. 673–682 http://dx.doi.org/10.2215/CJN.07891109 [Crossref]

  • [5] Abougalambou, S.S.I., et al., Prevalence of Vascular Complications among Type 2 Diabetes Mellitus Outpatients at Teaching Hospital in Malaysia. J Diabet Metabol, 2011. 2:115 http://dx.doi.org/10.4172/2155-6156.1000115 [Crossref]

  • [6] Singh, D.K., P. Winocour, and K. Farrington, Oxidative stress in early diabetic nephropathy: fueling the fire. Nat Rev Endocrinol, 2010

  • [7] Fioretto, P., et al., An overview of renal pathology in insulin-dependent diabetes mellitus in relationship to altered glomerular hemodynamics. Am J Kidney Dis, 1992. 20(6): p. 549–558 [Crossref]

  • [8] Adler, S., Diabetic nephropathy: Linking histology, cell biology, and genetics. Kidney Int, 2004. 66(5): p. 2095–2106 http://dx.doi.org/10.1111/j.1523-1755.2004.00988.x [Crossref]

  • [9] Alexander, M.P., et al., Kidney pathological changes in metabolic syndrome: a cross-sectional study. Am J Kidney Dis, 2009. 53(5): p. 751–759. http://dx.doi.org/10.1053/j.ajkd.2009.01.255 [Crossref]

  • [10] Farag, Y.M., Metabolic syndrome and the nonneoplastic kidney. Adv Anat Pathol, 2011. 18(2): p. 173; author reply 174 http://dx.doi.org/10.1097/PAP.0b013e3182026d60 [Crossref]

  • [11] Nosadini, R., et al., Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate. Diabetes, 2000. 49(3): p. 476–484 http://dx.doi.org/10.2337/diabetes.49.3.476

  • [12] Keck, M., et al., Hormonal status affects the progression of STZ-induced diabetes and diabetic renal damage in the VCD mouse model of menopause. Am J Physiol Renal Physiol, 2007. 293(1): p. F193–199 http://dx.doi.org/10.1152/ajprenal.00022.2007 [Crossref]

  • [13] Mankhey, R.W., F. Bhatti, and C. Maric, 17beta-Estradiol replacement improves renal function and pathology associated with diabetic nephropathy. Am J Physiol Renal Physiol, 2005. 288(2): p. F399–405 http://dx.doi.org/10.1152/ajprenal.00195.2004 [Crossref]

  • [14] Reckelhoff, J.F., et al., Testosterone supplementation in aging men and women: possible impact on cardiovascular-renal disease. Am J Physiol Renal Physiol, 2005. 289(5): p. F941–948 http://dx.doi.org/10.1152/ajprenal.00034.2005 [Crossref]

  • [15] Mollsten, A., et al., Cumulative risk, age at onset, and sex-specific differences for developing endstage renal disease in young patients with type 1 diabetes: a nationwide population-based cohort study. Diabetes, 2010. 59(7): p. 1803–1808 http://dx.doi.org/10.2337/db09-1744 [Crossref]

  • [16] Morimoto, A., et al., Is pubertal onset a risk factor for blindness and renal replacement therapy in childhood-onset type 1 diabetes in Japan? Diabetes Care, 2007. 30(9): p. 2338–2340 http://dx.doi.org/10.2337/dc07-0043 [Crossref]

  • [17] Harvey, J.N., The influence of sex and puberty on the progression of diabetic nephropathy and retinopathy. Diabetologia, 2011. 54(8): p. 1943–1945 http://dx.doi.org/10.1007/s00125-011-2185-6 [Crossref]

  • [18] Finne, P., et al., Incidence of end-stage renal disease in patients with type 1 diabetes. JAMA, 2005. 294(14): p. 1782–1787 http://dx.doi.org/10.1001/jama.294.14.1782 [Crossref]

  • [19] Raile, K., et al., Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex. Diabetes Care, 2007. 30(10): p. 2523–2528 http://dx.doi.org/10.2337/dc07-0282 [Crossref]

  • [20] Svensson, M., et al., Age at onset of childhoodonset type 1 diabetes and the development of end-stage renal disease: a nationwide population-based study. Diabetes Care, 2006. 29(3): p. 538–542 http://dx.doi.org/10.2337/diacare.29.03.06.dc05-1531 [Crossref]

  • [21] Dahlquist, G. and S. Rudberg, The prevalence of microalbuminuria in diabetic children and adolescents and its relation to puberty. Acta Paediatr Scand, 1987. 76(5): p. 795–800 http://dx.doi.org/10.1111/j.1651-2227.1987.tb10567.x [Crossref]

  • [22] Olsen, B.S., et al., The significance of the prepubertal diabetes duration for the development of retinopathy and nephropathy in patients with type 1 diabetes. J Diabetes Complications, 2004. 18(3): p. 160–164 http://dx.doi.org/10.1016/S1056-8727(03)00073-4 [Crossref]

  • [23] Yacoub, R., et al., Association between smoking and chronic kidney disease: a case control study. BMC Public Health, 2010. 10: p. 731. http://dx.doi.org/10.1186/1471-2458-10-731 [Crossref]

  • [24] Sawicki, P.T., et al., Smoking is associated with progression of diabetic nephropathy. Diabetes Care, 1994. 17(2): p. 126–131 http://dx.doi.org/10.2337/diacare.17.2.126 [Crossref]

  • [25] Rossing, P., P. Hougaard, and H.H. Parving, Risk factors for development of incipient and overt diabetic nephropathy in type 1 diabetic patients: a 10-year prospective observational study. Diabetes Care, 2002. 25(5): p. 859–864 http://dx.doi.org/10.2337/diacare.25.5.859 [Crossref]

  • [26] Stegmayr, B.G., A study of patients with diabetes mellitus (type 1) and end-stage renal failure: tobacco usage may increase risk of nephropathy and death. J Intern Med, 1990. 228(2): p. 121–124 http://dx.doi.org/10.1111/j.1365-2796.1990.tb00204.x [Crossref]

  • [27] Chuahirun, T. and D.E. Wesson, Cigarette smoking predicts faster progression of type 2 established diabetic nephropathy despite ACE inhibition. Am J Kidney Dis, 2002. 39(2): p. 376–382 http://dx.doi.org/10.1053/ajkd.2002.30559 [Crossref]

  • [28] Orth, S.R., Smoking—a renal risk factor. Nephron, 2000. 86(1): p. 12–26 http://dx.doi.org/10.1159/000045708 [Crossref]

  • [29] Jaimes, E.A., R.X. Tian, and L. Raij, Nicotine: the link between cigarette smoking and the progression of renal injury? Am J Physiol Heart Circ Physiol, 2007. 292(1): p. H76–82 http://dx.doi.org/10.1152/ajpheart.00693.2006 [Crossref]

  • [30] Marangon, K., et al., Diet, antioxidant status, and smoking habits in French men. Am J Clin Nutr, 1998. 67(2): p. 231–239

  • [31] Cross, C.E., A. van der Vliet, and J.P. Eiserich, Cigarette smokers and oxidant stress: a continuing mystery. Am J Clin Nutr, 1998. 67(2): p. 184–185

  • [32] Hu, Y., et al., Relations of glycemic index and glycemic load with plasma oxidative stress markers. Am J Clin Nutr, 2006. 84(1): p. 70–76; quiz 266–267

  • [33] Chabrashvili, T., et al., Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney. Hypertension, 2002. 39(2): p. 269–274 http://dx.doi.org/10.1161/hy0202.103264 [Crossref]

  • [34] Gorin, Y., et al., Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney. J Biol Chem, 2005. 280(47): p. 39616–39626 http://dx.doi.org/10.1074/jbc.M502412200 [Crossref]

  • [35] Hua, P., et al., Nicotine worsens the severity of nephropathy in diabetic mice: implications for the progression of kidney disease in smokers. Am J Physiol Renal Physiol, 2010. 299(4): p. F732–739 http://dx.doi.org/10.1152/ajprenal.00293.2010 [Crossref]

  • [36] Sharma, K., P. McCue, and S.R. Dunn, Diabetic kidney disease in the db/db mouse. Am J Physiol Renal Physiol, 2003. 284(6): p. F1138–1144

  • [37] Waugh, N.R., et al., Mortality in a cohort of diabetic patients. Causes and relative risks. Diabetologia, 1989. 32(2): p. 103–104 http://dx.doi.org/10.1007/BF00505181 [Crossref]

  • [38] Sturrock, N.D., et al., Non-dipping circadian blood pressure and renal impairment are associated with increased mortality in diabetes mellitus. Diabet Med, 2000. 17(5): p. 360–364 http://dx.doi.org/10.1046/j.1464-5491.2000.00284.x [Crossref]

  • [39] Epstein, M. and J.R. Sowers, Diabetes mellitus and hypertension. Hypertension, 1992. 19(5): p. 403–418 http://dx.doi.org/10.1161/01.HYP.19.5.403 [Crossref]

  • [40] Farmer, C.K., et al., Progression of diabetic nephropathy—is diurnal blood pressure rhythm as important as absolute blood pressure level? Nephrol Dial Transplant, 1998. 13(3): p. 635–639 http://dx.doi.org/10.1093/ndt/13.3.635 [Crossref]

  • [41] Verdecchia, P., et al., Blunted nocturnal fall in blood pressure in hypertensive women with future cardiovascular morbid events. Circulation, 1993. 88(3): p. 986–992 http://dx.doi.org/10.1161/01.CIR.88.3.986 [Crossref]

  • [42] Borch-Johnsen, K., P.K. Andersen, and T. Deckert, The effect of proteinuria on relative mortality in type 1 (insulin-dependent) diabetes mellitus. Diabetologia, 1985. 28(8): p. 590–596 http://dx.doi.org/10.1007/BF00281993 [Crossref]

  • [43] Hansen, H.P., et al., Circadian rhythm of arterial blood pressure and albuminuria in diabetic nephropathy. Kidney Int, 1996. 50(2): p. 579–585 http://dx.doi.org/10.1038/ki.1996.352 [Crossref]

  • [44] Lurbe, E., et al., Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med, 2002. 347(11): p. 797–805 http://dx.doi.org/10.1056/NEJMoa013410 [Crossref]

  • [45] Lurbe, A., et al., Altered blood pressure during sleep in normotensive subjects with type I diabetes. Hypertension, 1993. 21(2): p. 227–235 http://dx.doi.org/10.1161/01.HYP.21.2.227 [Crossref]

  • [46] Moore, W.V., et al., Ambulatory blood pressure in type I diabetes mellitus. Comparison to presence of incipient nephropathy in adolescents and young adults. Diabetes, 1992. 41(9): p. 1035–1041 http://dx.doi.org/10.2337/diab.41.9.1035 [Crossref]

  • [47] Lafferty, A.R., G.A. Werther, and C.F. Clarke, Ambulatory blood pressure, microalbuminuria, and autonomic neuropathy in adolescents with type 1 diabetes. Diabetes Care, 2000. 23(4): p. 533–538 http://dx.doi.org/10.2337/diacare.23.4.533 [Crossref]

  • [48] Felicio, J.S., et al., Nocturnal blood pressure fall as predictor of diabetic nephropathy in hypertensive patients with type 2 diabetes. Cardiovasc Diabetol, 2010. 9: p. 36 http://dx.doi.org/10.1186/1475-2840-9-36 [Crossref]

  • [49] Magri, C.J., et al., Factors associated with diabetic nephropathy in subjects with proliferative retinopathy. Int Urol Nephrol, 2011

  • [50] Ip, M.S., et al., Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med, 2002. 165(5): p. 670–676 http://dx.doi.org/10.1164/ajrccm.165.5.2103001 [Crossref]

  • [51] Ozol, D., et al., Influence of snoring on microalbuminuria in diabetic patients. Sleep Breath, 2010

  • [52] Netzer, N.C., et al., Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med, 1999. 131(7): p. 485–491 http://dx.doi.org/10.7326/0003-4819-131-7-199910050-00002 [Crossref]

  • [53] Hovind, P., et al., Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study. Diabetes, 2009. 58(7): p. 1668–1671 http://dx.doi.org/10.2337/db09-0014 [Crossref]

  • [54] Kosugi, T., et al., Effect of lowering uric acid on renal disease in the type 2 diabetic db/db mice. Am J Physiol Renal Physiol, 2009. 297(2): p. F481–488 http://dx.doi.org/10.1152/ajprenal.00092.2009 [Crossref]

  • [55] Kanakamani, J., et al., Prevalence of microalbuminuria among patients with type 2 diabetes mellitus—a hospital-based study from north India. Diabetes Technol Ther, 2010. 12(2): p. 161–166 http://dx.doi.org/10.1089/dia.2009.0133 [Crossref]

  • [56] Hoefield, R.A., et al., The use of eGFR and ACR to predict decline in renal function in people with diabetes. Nephrol Dial Transplant, 2010

  • [57] Rossing, P., et al., Monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy. Diabetes Care, 2006. 29(5): p. 1024–1030 http://dx.doi.org/10.2337/dc05-2201 [Crossref]

  • [58] Phillips, A.O. and R. Steadman, Diabetic nephropathy: the central role of renal proximal tubular cells in tubulointerstitial injury. Histol Histopathol, 2002. 17(1): p. 247–252

  • [59] Kanauchi, M., H. Nishioka, and T. Hashimoto, Oxidative DNA damage and tubulointerstitial injury in diabetic nephropathy. Nephron, 2002. 91(2): p. 327–329 http://dx.doi.org/10.1159/000058412 [Crossref]

  • [60] Nielsen, S.E., et al., Urinary liver-type fatty acidbinding protein predicts progression to nephropathy in type 1 diabetic patients. Diabetes Care, 2010. 33(6): p. 1320–1324 http://dx.doi.org/10.2337/dc09-2242 [Crossref]

  • [61] Kamijo-Ikemori, A., et al., Clinical Significance of Urinary Liver-Type Fatty Acid Binding Protein in Diabetic Nephropathy of Type 2 Diabetic Patients. Diabetes Care, 2011

  • [62] Nielsen, S.E., et al., Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy. Kidney Int, 2011. 79(10): p. 1113–1118 http://dx.doi.org/10.1038/ki.2010.554 [Crossref]

  • [63] Aaltonen, P., et al., Changes in the expression of nephrin gene and protein in experimental diabetic nephropathy. Lab Invest, 2001. 81(9): p. 1185–1190 http://dx.doi.org/10.1038/labinvest.3780332 [Crossref]

  • [64] Luimula, P., et al., Nephrin in experimental glomerular disease. Kidney Int, 2000. 58(4): p. 1461–1468 http://dx.doi.org/10.1046/j.1523-1755.2000.00308.x [Crossref]

  • [65] Qipo, A., H.W. Cohen, and B. Jim, 256 Urinary Nephrin as an Early Biomarker of Diabetic Nephropathy. American journal of kidney diseases: the official journal of the National Kidney Foundation, 2011. 57(4): p. B80 http://dx.doi.org/10.1053/j.ajkd.2011.02.259 [Crossref]

  • [66] Rutter, M.K., et al., Increased left ventricular mass index and nocturnal systolic blood pressure in patients with Type 2 diabetes mellitus and microalbuminuria. Diabet Med, 2000. 17(4): p. 321–325 http://dx.doi.org/10.1046/j.1464-5491.2000.00262.x [Crossref]

  • [67] Suzuki, K., et al., Left ventricular mass index increases in proportion to the progression of diabetic nephropathy in Type 2 diabetic patients. Diabetes Res Clin Pract, 2001. 54(3): p. 173–180 http://dx.doi.org/10.1016/S0168-8227(01)00318-7 [Crossref]

  • [68] Moon, S.J., et al., The effect of anemia and left ventricular geometric patterns on renal disease progression in type 2 diabetic nephropathy. J Nephrol, 2011. 24(1): p. 50–59 http://dx.doi.org/10.5301/JN.2010.353 [Crossref]

  • [69] Rigalleau, V., et al., Large kidneys predict poor renal outcome in subjects with diabetes and chronic kidney disease. BMC Nephrol, 2010. 11: p. 3 http://dx.doi.org/10.1186/1471-2369-11-3 [Crossref]

  • [70] Zerbini, G., 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): p. 2620–2625 http://dx.doi.org/10.2337/db06-0592 [Crossref]

  • [71] Ablett, M.J., et al., How reliable are ultrasound measurements of renal length in adults? Br J Radiol, 1995. 68(814): p. 1087–1089 http://dx.doi.org/10.1259/0007-1285-68-814-1087

  • [72] Elliott J, Mishler D, Agarwal R. Hyporesponsiveness to erythropoietin: causes and management. Adv Chronic Kidney Dis. 2009 Mar;16(2):94–100 http://dx.doi.org/10.1053/j.ackd.2008.12.004

  • [73] Keithi-Reddy SR, Addabbo F, Patel TV, Mittal BV, Goligorsky MS, Singh AK. Association of anemia and erythropoiesis stimulating agents with inflammatory biomarkers in chronic kidney disease. Kidney Int. 2008

  • [74] Inrig JK, Bryskin SK, Patel UD, Arcasoy M, Szczech LA. Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors. BMC Nephrol. 2011 Dec 12;12:67 http://dx.doi.org/10.1186/1471-2369-12-67 [Crossref]

About the article

Published Online: 2013-04-17

Published in Print: 2013-06-01


Citation Information: Open Medicine, ISSN (Online) 2391-5463, DOI: https://doi.org/10.2478/s11536-012-0055-3. Export Citation

© 2013 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. (CC BY-NC-ND 3.0)

Comments (0)

Please log in or register to comment.
Log in