Clinical and Experimental Nephrology

, Volume 18, Issue 2, pp 201–205 | Cite as

Treatment and impact of dyslipidemia in diabetic nephropathy

  • Tadashi Toyama
  • Miho Shimizu
  • Kengo Furuichi
  • Shuichi Kaneko
  • Takashi Wada
Review Article WCN 2013 Satellite Symposium ‘‘Kidney and Lipids’’
First Online:
Received:
Accepted:

Abstract

Recent epidemiological research revealed that dyslipidemia is a risk factor for development and progression of diabetic nephropathy. Results from interventional studies revealed the possibility that anti-hyperlipidemic agents have a better effect on diabetic nephropathy through improvement of albuminuria and loss of renal function. In addition, dyslipidemia may be a consequence of albuminuria and renal dysfunction, thereby perpetuating kidney damage. Today, the proportion of diabetic patients receiving statins is increasing due to their beneficial effect on cardiovascular mortality. However, treatment for patients should be determined based on consideration of the risk and benefit of the treatment. More insight into the pathogenesis of diabetic nephropathy and the effects of life-style changes is required.

Keywords

Diabetic nephropathy Dyslipidemia Cardiovascular disease End-stage renal disease 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This study was supported in party by a Grant-in-Aid for Diabetic Nephropathy Research from the Ministry of Health, Labor and Welfare of Japan.

Conflict of interest

The authors have declared that no conflict of interest exists.

References

  1. 1.
    Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28:103–17.PubMedCrossRefGoogle Scholar
  2. 2.
    The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–86.Google Scholar
  3. 3.
    Fried LF. Effects of HMG-CoA reductase inhibitors (statins) on progression of kidney disease. Kidney Int. 2008;74:571–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Krysiak R, Gdula-Dymek A, Bachowski R, Okopien B. Pleiotropic effects of atorvastatin and fenofibrate in metabolic syndrome and different types of pre-diabetes. Diabetes Care. 2010;33:2266–70.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Attman PO, Knight-Gibson C, Tavella M, Samuelsson O, Alaupovic P. The compositional abnormalities of lipoproteins in diabetic renal failure. Nephrol Dial Transplant. 1998;13:2833–41.PubMedCrossRefGoogle Scholar
  6. 6.
    Jenkins AJ, Lyons TJ, Zheng D, Otvos JD, Lackland DT, McGee D, et al. Lipoproteins in the DCCT/EDIC cohort: associations with diabetic nephropathy. Kidney Int. 2003;64:817–28.PubMedCrossRefGoogle Scholar
  7. 7.
    McQueen MJ, Hawken S, Wang X, Ounpuu S, Sniderman A, Probstfield J, et al. Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. Lancet. 2008;372:224–33.PubMedCrossRefGoogle Scholar
  8. 8.
    Sniderman AD, Williams K, Contois JH, Monroe HM, McQueen MJ, de Graaf J, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4:337–45.PubMedCrossRefGoogle Scholar
  9. 9.
    Toyama T, Furuichi K, Ninomiya T, Shimizu M, Hara A, Iwata Y, et al. The impacts of albuminuria and low eGFR on the risk of cardiovascular death, all-cause mortality, and renal events in diabetic patients: meta-analysis. PLoS One. 2013;8:e71810.Google Scholar
  10. 10.
    Fox CS, Matsushita K, Woodward M, Bilo HJG, Chalmers J, Heerspink HJL, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet. 2012;380:1662–73.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Moorhead JF, Chan MK, El-Nahas M, Varghese Z. Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet. 1982;2:1309–11.PubMedCrossRefGoogle Scholar
  12. 12.
    Ruan XZ, Varghese Z, Moorhead JF. An update on the lipid nephrotoxicity hypothesis. Nat Rev Nephrol. 2009;5:713–21.PubMedCrossRefGoogle Scholar
  13. 13.
    Hartroft WS. Fat emboli in glomerular capillaries of choline-deficient rats and of patients with diabetic glomerulosclerosis. Am J Pathol. 1955;31(3):381–97.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Rutledge JC, Ng KF, Aung HH, Wilson DW. Role of triglyceride-rich lipoproteins in diabetic nephropathy. Nat Rev Nephrol. 2010;6:361–70.PubMedCrossRefGoogle Scholar
  15. 15.
    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 USA. 1993;90:1814–8.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Tojo A, Onozato ML, Kurihara H, Sakai T, Goto A, Fujita T. Angiotensin II blockade restores albumin reabsorption in the proximal tubules of diabetic rats. Hypertens Res. 2003;26:413–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, et al. Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice. Diabetologia. 2012;55:2256–66.PubMedCrossRefGoogle Scholar
  18. 18.
    Chen HC, Tan MS, Guh JY, Tsai JH, Lai YL. Native and oxidized low-density lipoproteins enhance superoxide production from diabetic rat glomeruli. Kidney Blood Press Res. 2000;23:133–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Kuwabara A, Satoh M, Tomita N, Sasaki T, Kashihara N. Deterioration of glomerular endothelial surface layer induced by oxidative stress is implicated in altered permeability of macromolecules in Zucker fatty rats. Diabetologia. 2010;53:2056–65.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    O’Seaghdha CM, Hwang S-J, Upadhyay A, Meigs JB, Fox CS. Predictors of incident albuminuria in the Framingham Offspring cohort. Am J Kidney Dis. 2010;56:852–60.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Ninomiya T, Kiyohara Y, Kubo M, Yonemoto K, Tanizaki Y, Doi Y, et al. Metabolic syndrome and CKD in a general Japanese population: the Hisayama Study. Am J Kidney Dis. 2006;48:383–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Schaeffner ES, Kurth T, Curhan GC, Glynn RJ, Rexrode KM, Baigent C, et al. Cholesterol and the risk of renal dysfunction in apparently healthy men. J Am Soc Nephrol. 2003;14:2084–91.PubMedGoogle Scholar
  23. 23.
    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.PubMedCrossRefGoogle Scholar
  24. 24.
    Raile K, Galler A, Hofer S, Herbst A, Dunstheimer D, Busch P, 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;30:2523–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Ravid M, Brosh D, Ravid-Safran D, Levy Z, Rachmani R. Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels, mean blood pressure, and hyperglycemia. Arch Intern Med. 1998;158:998–1004.PubMedCrossRefGoogle Scholar
  26. 26.
    Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS. Regression of microalbuminuria in type 1 diabetes. N Engl J Med. 2003;348:2285–93.PubMedCrossRefGoogle Scholar
  27. 27.
    Mulec H, Johnsen SA, Wiklund O, Björck S. Cholesterol: a renal risk factor in diabetic nephropathy? Am J Kidney Dis. 1993;22:196–201.PubMedGoogle Scholar
  28. 28.
    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;54:205–26.PubMedCrossRefGoogle Scholar
  29. 29.
    Ansquer J-C, Foucher C, Rattier S, Taskinen M-R, Steiner G. Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: results from the Diabetes Atherosclerosis Intervention Study (DAIS). Am J Kidney Dis. 2005;45:485–93.PubMedCrossRefGoogle Scholar
  30. 30.
    Davis TME, Ting R, Best JD, Donoghoe MW, Drury PL, Sullivan DR, et al. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia. 2011;54:280–90.PubMedCrossRefGoogle Scholar
  31. 31.
    Slinin Y, Ishani A, Rector T, Fitzgerald P, MacDonald R, Tacklind J, et al. Management of hyperglycemia, dyslipidemia, and albuminuria in patients with diabetes and CKD: a systematic review for a KDOQI clinical practice guideline. Am J Kidney Dis. 2012;60:747–69.PubMedCrossRefGoogle Scholar
  32. 32.
    Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HAW, Livingstone SJ, et al. Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS). Am J Kidney Dis. 2009;54:810–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Ruggenenti P, Cravedi P, Remuzzi G. The RAAS in the pathogenesis and treatment of diabetic nephropathy. Nat Rev Nephrol. 2010;6:319–30.PubMedCrossRefGoogle Scholar
  34. 34.
    Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377:2181–92.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Rahman M, Baimbridge C, Davis BR, Barzilay J, Basile JN, Henriquez MA, et al. Progression of kidney disease in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin versus usual care: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Am J Kidney Dis. 2008;52:412–24.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Sandhu S, Wiebe N, Fried LF, Tonelli M. Statins for improving renal outcomes: a meta-analysis. J Am Soc Nephrol. 2006;17:2006–16.PubMedCrossRefGoogle Scholar
  37. 37.
    Sharma SG, Bomback AS, Radhakrishnan J, Herlitz LC, Stokes MB, Markowitz GS, et al. The modern spectrum of renal biopsy findings in patients with diabetes. Clin J Am Soc Nephrol. 2013;8:1–7.CrossRefGoogle Scholar
  38. 38.
    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;36:3655–62.Google Scholar
  39. 39.
    Wei M, Gaskill SP, Haffner SM, Stern MP. Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study. Diabetes Care. 1998;21:1167–72.PubMedCrossRefGoogle Scholar
  40. 40.
    Robinson JG, Booth B. Statin use and lipid levels in older adults: National Health and Nutrition Examination Survey, 2001 to 2006. J Clin Lipidol. 2010;4:483–90.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Ballantyne CM, Corsini A, Davidson MH, Holdaas H, Jacobson TA, Leitersdorf E, et al. Risk for myopathy with statin therapy in high-risk patients. Arch Intern Med. 2003;163:553–64.PubMedCrossRefGoogle Scholar
  42. 42.
    Alsheikh-Ali AA, Ambrose MS, Kuvin JT, Karas RH. The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Circulation. 2005;111:3051–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ. 2013;346:f2610.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Wang K-L, Liu C-J, Chao T-F, Huang C-M, Wu C-H, Chen S-J, et al. Statins, risk of diabetes, and implications on outcomes in the general population. J Am Coll Cardiol. 2012;60:1231–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Multiple risk factor intervention trial research group. Mortality rates after 10.5 years for participants in the Multiple Risk Factor Intervention Trial. Findings related to a priori hypotheses of the trial. The Multiple Risk Factor Intervention Trial Research Group. JAMA. 1990;263:1795–801.Google Scholar

Copyright information

© Japanese Society of Nephrology 2013

Authors and Affiliations

  • Tadashi Toyama
    • 1
  • Miho Shimizu
    • 1
  • Kengo Furuichi
    • 1
  • Shuichi Kaneko
    • 2
  • Takashi Wada
    • 1
    • 3
  1. 1.Division of NephrologyKanazawa University HospitalKanazawaJapan
  2. 2.Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan
  3. 3.Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan

Personalised recommendations