Cardiovascular risk in chronic kidney disease: what is new in the pathogenesis and treatment?

Postgraduate Medicine

Volumn 130, Issue 5, 2018, Pages 461-469

  Bazyluk, Angelika ^a   Malyszko, Jolanta ^a,b   Zbroch, Edyta ^a  

^a MEDICAL UNIVERSITY OF BIALYSTOK   (Poland)

^b MEDICAL UNIVERSITY OF WARSAW   (Poland)

Author keywords

cardioprotection; Cardiovascular risk; chronic kidney disease; renoprotection

Indexed keywords

ALLOPURINOL; ANTIDIABETIC AGENT; ERYTHROPOIETIN; FENOFIBRATE; HEMOGLOBIN A1C; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYPOXIA INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITOR; INDICAN; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; UREMIC TOXIN;

ALBUMINURIA; ARTERIOSCLEROSIS; ATHEROSCLEROSIS; BLOOD PRESSURE MONITORING; BONE DEVELOPMENT; CALCIFICATION; CARDIOVASCULAR RISK; CHRONIC KIDNEY FAILURE; DIABETES MELLITUS; DIABETIC NEPHROPATHY; DNA POLYMORPHISM; ELECTROLYTE DISTURBANCE; ESTIMATED GLOMERULAR FILTRATION RATE; GLYCEMIC CONTROL; HEART PROTECTION; HUMAN; HYPERLIPIDEMIA; HYPERTENSION; INSULIN RESISTANCE; KIDNEY DISEASE; LIFESTYLE MODIFICATION; MORBIDITY; MORTALITY; NONHUMAN; PROTEINURIA; REVIEW; RISK ASSESSMENT; SLEEP DISORDERED BREATHING; SODIUM RETENTION; TRANSIENT ISCHEMIC ATTACK; WATER RETENTION; ADIPOSE TISSUE; AGING; BLOOD PRESSURE; CARDIOVASCULAR DISEASE; DIET; DISEASE EXACERBATION; DYSLIPIDEMIA; EXERCISE; GLUCOSE BLOOD LEVEL; HEMODYNAMICS; PATHOPHYSIOLOGY; PHYSIOLOGY; RISK FACTOR; SMOKING;

ADIPOSE TISSUE; AGING; ALLOPURINOL; BLOOD GLUCOSE; BLOOD PRESSURE; CARDIOVASCULAR DISEASES; DIABETES MELLITUS; DIABETIC NEPHROPATHIES; DIET; DISEASE PROGRESSION; DYSLIPIDEMIAS; EXERCISE; HEMODYNAMICS; HUMANS; RENAL INSUFFICIENCY, CHRONIC; RISK FACTORS; SMOKING;

EID: 85048359111     PISSN: 00325481     EISSN: 19419260     Source Type: Journal    
DOI: 10.1080/00325481.2018.1481714     Document Type: Review

References (102)

1. Hsu RK, Powe NR., Recent trends in the prevalence of chronic kidney disease: not the same old song. Curr Opin Nephrol Hypertens. 2017 May;26(3):187–196.
2. Manns B, Hemmelgarn B, Tonelli M, et al. Population based screening for chronic kidney disease: cost effectiveness study. BMJ. 2010;8;341:c5869.
3. Mann JFE, Dulau-Florea I, Franke J., Looking for people at high cardiovascular risk? Look at serum-creatinine. Eur Heart J. 2003 Mar;24(5):381–383.
4. Murussi M, Gross JL, Silveiro SP. Glomerular filtration rate changes in normoalbuminuric and microalbuminuric Type 2 diabetic patients and normal individuals A 10-year follow-up. J Diabetes Complications. 2006;20:210–215.
5. Nath KA. Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis. 1992;20:1–17.
6. Wali RK. Henrich WL: chronic kidney disease: a risk factor for cardiovascular disease. Cardiol Clin. 2005;23:343–362.
7. Khalique O, Aronow WS, Ahn C, et al. Relation of moderate or severe reduction in glomerular filtration rate to number of coronary arteries narrowed >50% in patients undergoing coronary angiography for suspected coronary artery disease. Am J Cardiol. 2007 Aug 1;100(3):415–416.
8. Ohtake T, Kobayashi S, Moriya H, et al. High prevalence of occult coronary artery stenosis in patients with chronic kidney disease at the initiation of renal replacement therapy: an angiographic examination. J Am Soc Nephrol. 2005;16(4):1141–1148.
9. Olechnowicz-Tietz S, Gluba A, Paradowska A, et al. The risk of atherosclerosis in patients with chronic kidney disease. Int Urol Nephrol. 2013 Dec;45(6):1605–1612.
10. Mizobuchi M, Towler D, Slatopolsky E. Vascular calcification: the killer of patients with chronic kidney disease. J Am Soc Nephrol. 2009;20:1453–1464.
11. Dc W, London GM, Parfrey PS, et al. Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial. J Am Heart Assoc. 2014 Nov 17;3(6):e001363.
12. Hayashi T, Joki N, Tanaka Y. Anaemia and early phase cardiovascular events on haemodialysis. Nephrology (Carlton). 2015 Dec;20(Suppl 4):1–6.
13. Lee JW, Bae SH, Jeong JW. Hypoxia-inducible factor (HIF-1) alpha: its protein stability and biological functions. Exp Mol Med. 2004 Feb 29;36(1):1–12.
14. Barrett TD, Palomino HL, Brondstetter TI, et al. Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor. Mol. Pharmacol. 2011;79:910–920.
15. Koury MJ, Haase VH. Anaemia in kidney disease: harnessing hypoxia responses for therapy. Nat Rev Nephrol. 2015 Jul;11(7):394–410.
16. Besarab A, Provenzano R, Hertel J, et al. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients. Nephrol Dial Transplant. 2015;30(10):1665–1673.
17. Besarab A, Chernyavskaya E, Motylev I, et al. Roxadustat (FG-4592): correction of anemia in incident dialysis patients. J Am Soc Nephrol. 2016;27(4):1225–1233.
18. U.S. National Institutes of Health. HIF inhibitor. [Cited 2017 December 6]. Available from: ClinicalTrials.gov. http://www.clinicaltrials.gov
19. Glassock RJ, Pecoits-Filho R, Barberato SH. Left ventricular mass in chronic kidney disease and ESRD. Clin J Am Soc Nephrol. 2009 Dec;4(Suppl 1):S79–S91.
20. Siedlecki AM, Jin X, Muslin AJ. Uremic cardiac hypertrophy is reversed by rapamycin but not by lowering of blood pressure. Kidney Int. 2009 Apr;75(8):800–808.
21. Lekawanvijit S, Kompa AR, Wang BH, et al. Cardiorenal syndrome: the emerging role of protein-bound uremic toxins. Circ Res. 2012 Nov 9;111(11):1470–1483.
22. Liabeuf S, Barreto DV, Barreto FC, et al. Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease. Nephrol Dial Transpl. 2010;25:1183–1191.
23. Wu IW, Hsu KH, Lee CC, et al. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol Dial Transplant. 2011 Mar;26(3):938–947.
24. Schulman G, Berl T, Beck GJ, et al. Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD. J Am Soc Nephrol. Vol. 26. 7; 2015. p. Jul.
25. Schulman G, Berl T, Beck GJ, et al. Risk factors for progression of chronic kidney disease in the EPPIC trials and the effect of AST-120. Clin Exp Nephrol Jul, 2017. 24.
26. Akizawa T, Asano Y, Morita S, et al. Study Group. Effect of a carbonaceous oral adsorbent on the progression of CKD: a multicenter, randomized, controlled trial. Am J Kidney Dis. 2009 Sep;54(3):459–467.
27. Cha RH, Kang SW, Park CW, et al. Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: post-hoc analysis of the Kremezin Study against renal disease progression in Korea. Kidney Res Clin Pract. 2017 Mar;36(1):68–78.
28. Vaziri ND, Zhao YY, Pahl MV. Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment. Nephrol Dial Transplant. 2016 May;31(5):737–746.
29. Tucker PS, Dalbo VJ, Han T, et al. Clinical and research markers of oxidative stress in chronic kidney disease. Biomarkers. 2013;18(2):103–115.
30. Silverstein DM. Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease. Pediatr Nephrol. 2009 Aug;;24(8):1445–1452.
31. Dounousi E, Papavasiliou E, Makedou A, et al. Oxidative stress is progressively enhanced with advancing stages of CKD. American Journal of Kidney Diseases. 2006;48(5):752–760.
32. Cottone S, Lorito MC, Riccobene R, et al. Oxidative stress, inflammation and cardiovascular disease in chronic renal failure. J Nephrol. 2008 Mar-Apr;21(2):175–179.
33. Drews G, Krippeit-Drews P, Düfer M. Oxidative stress and beta-cell dysfunction. Pflugers Arch. 2010 Sep;460(4):703–718.
34. Silva LA, Pinho CA, Scarabelot KS, et al. Physical exercise increases mitochondrial function and reduces oxidative damage in skeletal muscle. Eur J Appl Physiol. 2009;105:861–867.
35. Teixeira-Lemos E, Nunes S, Teixeira F, et al. Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovasc Diabetol. 2011;10:12.
36. Jain N, Reilly RF. Effects of dietary interventions on incidence and progression of CKD. Nat Rev Nephrol. 2014 Dec;10(12):712–724.
37. McMahon EJ, Bauer JD, Hawley CM, et al. A randomized trial of dietary sodium restriction in CKD. J Am Soc Nephrol. 2013 Dec;24(12):2096–2103.
38. Saran R, Padilla RL, Gillespie BW, et al. A randomized crossover trial of dietary sodium restriction in stage 3-4 CKD. Clin J Am Soc Nephrol. 2017 Mar 7;12(3):399–407.
39. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.
40. Dzau V. The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. J Hypertens Suppl. 2005 Apr;23(1):S9–S17.
41. International Diabetes Federation. IDF diabetes atlas. 8th ed. Brussels (Belgium): International Diabetes Federation; 2017.
42. Aghadavod E, Khodadadi S, Baradaran A, et al. Role of oxidative stress and inflammatory factors in diabetic kidney disease. Iran J Kidney Dis. 2016 Nov;10(6):337–343.
43. Kumar R, Sharma RK, Agarwal S. Genetic predisposition for development of nephropathy in type 2 diabetes mellitus. Biochem Genet. 2013 Dec;51(11–12):865–875.
44. American Diabetes Association Glycemic Targets: Standards of Medical Care in Diabetes—2018. Diabetes Care. 2018 Jan;41(Supplement 1):S55–S64.
45. Inaba M, Okuno S, Kumeda Y, et al. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J Am Soc Nephrol. 2007 Mar;18(3):896–903.
46. Zinman B, Wanner C, Lachin JM, et al. EMPA-REG outcome investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015 Nov 26;373(22):2117–2128.
47. Packer M, Anker SD, Butler J, et al. Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action. JAMA Cardiol. 2017 Sep 1;2(9):1025–1029.
48. Wanner C, Inzucchi SE, Lachin JM, et al. EMPA-REG outcome investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016 Jul 28;375(4):323–334.
49. Gnudi Karalliedde JL. Beat it early: putative renoprotective hae-modynamic effects of oral hypoglycaemic agents. Nephrol DialTransplant. 2016;31(7):1036–1043.
50. Neal B, Perkovic V, Dr M, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017 Nov 23;377(21):2099.
51. Jardine MJ, Mahaffey KW, Neal B, et al. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics. Am J Nephrol. 2017 Dec 13;46(6):462–472.
52. Watts NB, Bilezikian JP, Usiskin K, et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2016 Jan;101(1):157–166.
53. Kodera R, Shikata K, Kataoka HU, et al. Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes. Diabetologia. 2011 Apr;54(4):965–978.
54. Chaudhuri A, Ghanim H, Vora M, et al. Exenatide exerts a potent antiinflammatory effect. J Clin Endocrinol Metab. 2012;97:198–207.
55. Gallwitz B. Preclinical and clinical data on extraglycemic effects of GLP-1 receptor agonists. Rev Diabet Stud. 2009;6:247–259.
56. Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015 Jul 16;373(3):232–242.
57. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013 Oct 3;369(14):1327–1335.
58. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013 Oct 3;369(14):1317–1326.
59. Crowley MJ, Williams JW, Jr, Kosinski AS, et al. Metformin use may moderate the effect of DPP-4 inhibitors on cardiovascular outcomes. Diabetes Care. 2017 Dec;40(12):1787–1789.
60. Ap B, Bk B, Jb K, et al. Cost-effectiveness of intensive versus standard blood-pressure control. N Engl J Med. 2017;377:745–755.
61. James PA, Oparil S, Carter BL, et al. evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;2014(311):507–520.
62. Jessup M, Abraham WT, Casey DE, et al. Focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;2009(119):1977–2016.
63. Mancia G, Fagard R, Narkiewicz K, et al. ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;2013(31):1281–1357.
64. Whelton PK, Carey RM, Aronow WS, et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: executive Summary: a Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2017;2017(Nov):13.
65. Ku E, McCulloch CE, Mauer M, et al. Association Between Blood Pressure and Adverse Renal Events in Type 1 Diabetes. Diabetes Care. 2016 Dec;39(12):2218–2224.
66. Tsai WC, Wu HY, Peng YS, et al. Association of intensive blood pressure control and kidney disease progression in nondiabetic patients with chronic kidney disease: a systematic review and meta-analysis. JAMA Intern Med. 2017;177:792.
67. Gosmanova EO, Mikkelsen MK, Molnar MZ, et al. Association of systolic blood pressure variability with mortality, coronary heart disease, stroke, and renal disease. J Am Coll Cardiol. 2016 Sep 27;68(13):1375–1386.
68. Chang TI, Reboussin DM, Chertow GM, et al. SPRINT research group. Visit-to-visit office blood pressure variability and cardiovascular outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Hypertension. 2017 Oct;70(4):751–758.
69. AMD-Annals Study Group. Plasma triglycerides and HDL-C levels predict the development of diabetic kidney disease in subjects with type 2 diabetes. Diabetes Care. 2016 Dec;39(12):2278–2287.
70. Sacks FM, Hermans MP, Fioretto P, et al. Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case-control study in 13 countries. Circulation. 2014;129::999–1008.
71. Davis, TM, Ting R, Best, JD, et al. Fenofibrate Intervention and Event Lowering in Diabetes Study investigators 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::280–290.
72. Tu ST, Chang SJ, Chen JF, et al. Prevention of diabetic nephropathy by tight target control in an Asian population with type 2 diabetes mellitus: a 4-year prospective analysis. Arch Intern Med. 2010 Jan 25;170(2):155–161.
73. Xu J, Lee ET, Devereux RB, et al. A longitudinal study of risk factors for incident albuminuria in diabetic American Indians: the strong heart study. Am J Kidney Dis. 2008;51(3):415–424.
74. Lin J, Hu FB, Mantzoros C, et al. Lipid and inflammatory biomarkers and kidney function decline in type 2 diabetes. Diabetologia. 2010;53::263–267.
75. Herrington, WG, Emberson J, Mihaylova B, et al. Cholesterol Treatment Trialists’ (CTT) Collaboration. Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials. Lancet Diabetes Endocrinol. 2016 Oct;4(10):829–839.
76. Shepherd J, Breazna A, Deedwania PC, et al. Relation between change in renal function and cardiovascular outcomes in atorvastatin-treated patients (from the Treating to New Targets [TNT] Study). Am J Cardiol. 2016 Apr 15;117(8):1199–1205.
77. de Zeeuw D, Anzalone DA, Cain VA, et al. Renal effect of atorvastatin and rosuvastatin in patients with diabetes who have progressive renal disease (PLANET I): a randomised trial. Lancet Diabetes Endocrinol. 2015 3;Mar(3):181–190.
78. Baigent C, Landray MJ, Reith C, et al. Lancet. 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. 2011 Jun 25;377(9784):2181–2192.
79. Kuwabara M. Hyperuricemia, Cardiovascular Disease, Hypertens Pulse. 2016;3(3–4):242–252.
80. Goicoechea M, De Vinuesa SG, Verdalles U, et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010 Aug;5(8):1388–1393.
81. Golmohammadi S, Almasi A, Manouchehri M, et al. Allopurinol against progression of chronic kidney disease. Iran J Kidney Dis. 2017 Jul;11(4):286–293.
82. Shih NY, Li J, Karpitskii V, et al. Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science. 1999;286::312–315.
83. Boute N, Gribouval O, Roselli S, et al. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet. 2000;24::349–354.
84. Chuang PY, Dai Y, Liu R, et al. Alteration of forkhead box O (Foxo4) acetylation mediates apoptosis of podocytes in diabetes mellitus. PLoS ONE. 2011;6(8):e23566. Dryer SE, ed.
85. Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147::728–741.
86. Cui J, Bai X-Y, Shi S, et al. Age-related changes in the function of autophagy in rat kidneys. Age (Dordr). 2012;34:329–339.
87. Cuervo AM. Autophagy and aging: keeping that old broom working. Trends Genet. 2008 Dec;24(12):604–612.
88. Yamamoto T, Takabatake Y, Kimura T, et al. Time-dependent dysregulation of autophagy: implications in aging and mitochondrial homeostasis in the kidney proximal tubule. Autophagy. 2016 May 3;12(5):801–813.
89. Kint JA. Fabry’s disease: alpha-galactosidase deficiency. Science. 1970;167:1268–1269.
90. Cinà DP, Onay T, Paltoo A, et al. Inhibition of MTOR disrupts autophagic flux in podocytes. J Am Soc Nephrol. 2012;23:412–420.
91. Tagawa A, Yasuda M, Shinji K, et al. Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy. Diabetes. 2016 Mar;65(3):755–767.
92. The GBD 2015. Obesity collaborators; health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017 Jul 6;377(1):13–27.
93. Stefan N, Kantartzis K, Machann J, et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med. 2008;168:1609–1616.
94. Lassale C, Tzoulaki I, Moons KGM, et al. Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis. Eur Heart J. 2018 Feb 1;39(5):397–406.
95. Chandie Shaw PK, Berger SP, Mallat M, et al. Central obesity is an independent risk factor for albuminuria in nondiabetic South Asian subject. Diabetes Care. 2007;30:1840–1844.
96. Drechsler C, De Mutsert R, Grootendorst DC, et al. Association of body mass index with decline in residual kidney function after initiation of dialysis. Am J Kidney Dis. 2009;53:1014–1023.
97. Stefan N, Fritsche A, Weikert C, et al. Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes. 2008;57:2762–2767.
98. Weikert C, Stefan N, Schulze MB, et al. Plasma fetuin-A levels and the risk of myocardial infarction and ischemic stroke. Circulation. 2008;118:2555–2562.
99. Schafer C, Heiss A, Schwarz A, et al. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest. 2003;112:357–366.
100. Stefan N, Artunc F, Heyne N, et al. Obesity and renal disease: not all fat is created equal and not all obesity is harmful to the kidneys. Nephrol Dial Transplant. 2016 May;31(5):726–730.
101. Li M, Xu M, Bi Y, et al. Association between higher serum fetuin-A concentrations and abnormal albuminuria in middle-aged and elderly Chinese with normal glucose tolerance. Diabetes Care. 2010;33(11):2462–2464.
102. Wagner R, Machann J, Lehmann R, et al. Exercise-induced albuminuria is associated with perivascular renal sinus fat in individuals at increased risk of type 2 diabetes. Diabetologia. 2012 Jul;55(7):2054–2058.