Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Clinical and Experimental Nephrology
Published in: Clinical and Experimental Nephrology 1/2012

01-02-2012 | Review Article

Cardiorenal connection in chronic kidney disease

Author: Sadayoshi Ito

Published in: Clinical and Experimental Nephrology | Issue 1/2012

Login to get access

Abstract

Chronic kidney disease (CKD), as defined by reduced glomerular filtration rate (<60 ml/min/1.73 m2) and/or the presence of renal damage for >3 months, is a significant threat for public health in modern societies. Recent epidemiological studies have demonstrated that CKD is a significant risk for cardiovascular events independently of classical risk factors such as hypertension, dyslipidemia and diabetes. The mechanisms by which CKD increases the risk of cardiovascular events are currently under intensive investigation. Among various components of CKD, microalbuminuria is of particular interest, because it is a significant risk factor not only in diabetic and hypertensive subjects but also in the general population. Microalbuminuria is also closely associated with salt sensitivity of blood pressure, and the salt sensitivity is an independent risk factor for cardiovascular disease even in normotensive subjects. Several factors are likely to be involved in such associations, including the renin–angiotensin system (RAS), oxidative stress and inflammation. In addition, there may be more specific hemodynamic mechanisms in the kidney and other vital organs underlying these associations. This review describes ‘the strain vessel hypothesis’ as a possible mechanism for cerebrocardiorenal connections. In addition we discuss the significance of underlying diseases as cardiovascular risks of CKD as well as the role of RAS inhibition in the management of CKD patients.
Literature
1.
Sarnak MJ, Levey AS, Schoolwerth AC, American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Hypertension. 2003;42:1050–65.PubMedCrossRef
2.
Imai E, Horio M, Watanabe T, Iseki K, Yamagata K, Hara S, et al. Prevalence of chronic kidney disease in the Japanese general population. Clin Exp Nephrol. 2009;13(6):621–30.PubMedCrossRef
3.
Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med. 2004;164(6):659–63.PubMedCrossRef
4.
Cheung AK, Sarnak MJ, Yan G, Berkoben M, Heyka R, Kaufman A, et al. Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study. Kidney Int. 2004;65(6):2380–9.PubMedCrossRef
5.
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296–305.PubMedCrossRef
6.
Bouchi R, Babazono T, Nyumura I, Toya K, Hayashi T, Ohta M, et al. Is a reduced estimated glomerular filtration rate a risk factor for stroke in patients with type 2 diabetes? Hypertens Res. 2009;32(5):381–6.PubMedCrossRef
7.
Gerstein HC, Mann JF, Pogue J, Dinneen SF, Hallé JP, Hoogwerf B, et al. Prevalence and determinants of microalbuminuria in high-risk diabetic and nondiabetic patients in the Heart Outcomes Prevention Evaluation Study. The HOPE Study Investigators. Diabetes Care. 2000;23:B35–9.PubMedCrossRef
8.
Nakayama M, Sato T, Sato H, Yamaguchi Y, Obara K, Kurihara I, et al. Different clinical outcomes for cardiovascular events and mortality in chronic kidney disease according to underlying renal disease: the Gonryo study. Clin Exp Nephrol 2010;14:333-9.
9.
Weiner DE, Tabatabai S, Tighiouart H, Elsayed E, Bansal N, Griffith J, et al. Cardiovascular outcomes and all-cause mortality: exploring the interaction between CKD and cardiovascular disease. Am J Kidney Dis. 2006;48(3):392–401.PubMedCrossRef
10.
Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE, et al. Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? The LIFE study. Diabetes Care. 2006;29:595–600.PubMedCrossRef
11.
Hillege HL, Fidler V, Diercks GF, van Gilst WH, de Zeeuw D, van Veldhuisen DJ, Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group, et al. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation. 2002;106:1777–82.PubMedCrossRef
12.
Yuyun MF, Khaw KT, Luben R, Welch A, Bingham S, Day NE, et al. Microalbuminuria and stroke in a British population: the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study. J Intern Med. 2004;255:247–56.PubMedCrossRef
13.
Ravera M, Ratto E, Vettoretti S, Viazzi F, Leoncini G, Parodi D, et al. Microalbuminuria and subclinical cerebrovascular damage in essential hypertension. J Nephrol. 2002;15:519–24.PubMed
14.
Wada M, Nagasawa H, Kurita K, Koyama S, Arawaka S, Kawanami T, et al. Microalbuminuria is a risk factor for cerebral small vessel disease in community-based elderly subjects. J Neurol Sci. 2007;255:27–34.PubMedCrossRef
15.
Klausen KP, Scharling H, Jensen JS. Very low level of microalbuminuria is associated with increased risk of death in subjects with cardiovascular or cerebrovascular diseases. J Intern Med. 2006;260:231–7.PubMedCrossRef
16.
Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Hallé JP, HOPE Study Investigators, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286:421–6.PubMedCrossRef
17.
Fliser D, Buchholz K, Haller H, European Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis (EUTOPIA) Investigators. Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammation. Circulation. 2004;110:1103–7.PubMedCrossRef
18.
Ogawa S, Mori T, Nako K, Kato T, Takeuchi K, Ito S. Angiotensin II type 1 receptor blockers reduce urinary oxidative stress markers in hypertensive diabetic nephropathy. Hypertension. 2006;47:699–705.PubMedCrossRef
19.
Hillege HL, Janssen WM, Bak AA, Diercks GF, Grobbee DE, Crijns HJ, et al. Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med. 2001;249:519–26.PubMedCrossRef
20.
Asselbergs FW, Diercks GF, Hillege HL, van Boven AJ, Janssen WM, Voors AA, et al. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation. 2004;110:2809–16.PubMedCrossRef
21.
Satchell SC, Tooke JE. What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? Diabetologia. 2008;51:714–25.PubMedCrossRef
22.
Nosadini R, Velussi M, Brocco E, Abaterusso C, Piarulli F, Morgia G, et al. Altered transcapillary escape of albumin and microalbuminuria reflects two different pathogenetic mechanisms. Diabetes. 2005;54:228–33.PubMedCrossRef
23.
de Zeeuw D, Parving HH, Henning RH. Microalbuminuria as an early marker for cardiovascular disease. J Am Soc Nephrol. 2006;17:2100–5.PubMedCrossRef
24.
Stehouwer CD, Nauta JJ, Zeldenrust GC, Hackeng WH, Donker AJ, den Ottolander GJ. Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus. Lancet. 1992;340:319–23.PubMedCrossRef
25.
Stehouwer CD, Smulders YM. Microalbuminuria and risk for cardiovascular disease: analysis of potential mechanisms. J Am Soc Nephrol. 2006;17:2106–11.PubMedCrossRef
26.
Malik AR, Sultan S, Turner ST, Kullo IJ. Urinary albumin excretion is associated with impaired flow- and nitroglycerin-mediated brachial artery dilatation in hypertensive adults. J Hum Hypertens. 2007;21:231–8.PubMed
27.
Diercks GF, Stroes ES, van Boven AJ, van Roon AM, Hillege HL, de Jong PE, et al. Urinary albumin excretion is related to cardiovascular risk indicators, not to flow-mediated vasodilation, in apparently healthy subjects. Atherosclerosis. 2002;163(1):121–6.PubMedCrossRef
28.
Iversen BM, Amann K, Kvam FI, Wang X, Ofstad J. Increased glomerular capillary pressure and size mediate glomerulosclerosis in SHR juxtamedullary cortex. Am J Physiol. 1998;274:F365–73.PubMed
29.
Johnson RJ, Gordon KL, Giachelli C, Kurth T, Skelton MM, Cowley AW Jr. Tubulointerstitial injury and loss of nitric oxide synthases parallel the development of hypertension in the Dahl-SS rat. J Hypertens. 2000;18:1497–505.PubMedCrossRef
30.
Eng E, Veniant M, Floege J, Fingerle J, Alpers CE, Menard J, et al. Renal proliferative and phenotypic changes in rats with two-kidney, one-clip Goldblatt hypertension. Am J Hypertens. 1994;7:177–85.PubMed
31.
Mori T, Cowley AW Jr. Role of pressure in angiotensin II-induced renal injury: chronic servo-control of renal perfusion pressure in rats. Hypertension. 2004;43:752–9.PubMedCrossRef
32.
Ericson AC, Sjöquist M, Ulfendahl HR. Heterogeneity in regulation of glomerular function. Acta Physiol Scand. 1982;114:203–9.PubMedCrossRef
33.
Heyeraas KJ, Aukland K. Interlobular arterial resistance: influence of renal arterial pressure and angiotensin II. Kidney Int. 1987;31:1291–8.PubMedCrossRef
34.
Takenaka T, Suzuki H, Okada H, Hayashi K, Ozawa Y, Saruta T. Biophysical signals underlying myogenic responses in rat interlobular artery. Hypertension. 1998;32:1060–5.PubMed
35.
Ito S, Nagasawa T, Abe M, Mori T. Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk. Hypertens Res. 2009;32(2):115–21.PubMedCrossRef
36.
37.
Auer RN, Sutherland GR. Primary intracerebral hemorrhage: pathophysiology. Can J Neurol Sci. 2005;32:S3–12.PubMed
38.
Dubas F. Small vessel pathology and cerebral hemorrhage. J Neuroradiol. 2003;30:298–302.PubMed
39.
40.
Cornelissen AJ, Dankelman J, VanBavel E, Stassen HG, Spaan JA. Myogenic reactivity and resistance distribution in the coronary arterial tree: a model study. Am J Physiol Heart Circ Physiol. 2000;278(5):H1490–9.PubMed
41.
Hashimoto J, Aikawa T, Imai Y. Large artery stiffening as a link between cerebral lacunar infarction and renal albuminuria. Am J Hypertens. 2008;21(12):1304–9.PubMedCrossRef
42.
O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200–4.PubMedCrossRef
43.
Struijker Boudier HA, Cohuet GM, Baumann M, Safar ME. The heart, macrocirculation and microcirculation in hypertension: a unifying hypothesis. J Hypertens. 2003;21:S19–23.CrossRef
44.
Cubeddu LX, Hoffmann IS, Aponte LM, Nuñez-Bogesits R, Medina-Suniaga H, Roa M, et al. Role of salt sensitivity, blood pressure, and hyperinsulinemia in determining high upper normal levels of urinary albumin excretion in a healthy adult population. Am J Hypertens. 2003;16:343–9.PubMedCrossRef
45.
Nesović M, Stojanović M, Nesović MM, Cirić J, Zarković M. Microalbuminuria is associated with salt sensitivity in hypertensive patients. J Hum Hypertens. 1996;10:573–6.PubMed
46.
Campese VM. Salt sensitivity in hypertension. Renal and cardiovascular implications. Hypertension. 1994;23:531–50.PubMed
47.
Weinberger MH, Fineberg NS, Fineberg SE, Weinberger M. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans. Hypertension. 2001;37:429–32.PubMed
48.
Dickhout JG, Mori T, Cowley AW Jr. Tubulovascular nitric oxide crosstalk: buffering of angiotensin II-induced medullary vasoconstriction. Circ Res. 2002;91:487–93.PubMedCrossRef
49.
Cowley AW Jr. Long-term control of arterial blood pressure. Physiol Rev. 1992;72:231–300.PubMed
50.
Mori T, Cowley AW Jr, Ito S. Molecular mechanisms and therapeutic strategies of chronic renal injury: physiological role of angiotensin II-induced oxidative stress in renal medulla. J Pharmacol Sci. 2006;100:2–8.PubMedCrossRef
51.
Mori T, Cowley AW. Angiotensin II-NAD(P)H oxidase-stimulated superoxide modifies tubulovascular nitric oxide cross-talk in renal outer medulla. Hypertension. 2003;42:588–93.PubMedCrossRef
52.
Abe M, O’Connor P, Kaldunski M, Liang M, Roman RJ, Cowley AW Jr. Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb. Am J Physiol Renal Physiol. 2006;291:F350–7.PubMedCrossRef
53.
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329(20):1456–62.PubMedCrossRef
54.
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.PubMedCrossRef
55.
Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997;349(9069):1857–63.
56.
Agodoa LY, Appel L, Bakris GL, Beck G, Bourgoignie J, Briggs JP, et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA. 2001;285(21):2719–28.PubMedCrossRef
57.
Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med. 2001;135(2):73–87.PubMed
58.
Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE, et al. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study. Hypertension. 2005;45(2):198–202.PubMedCrossRef
59.
de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004;65(6):2309–20.PubMedCrossRef
60.
de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, et al. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation. 2004;110(8):921–7.PubMedCrossRef
61.
ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.PubMedCrossRef
62.
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.PubMedCrossRef
63.
Mann JF, Schmieder RE, Dyal L, McQueen MJ, Schumacher H, Pogue J, et al. Effect of telmisartan on renal outcomes: a randomized trial. Ann Intern Med. 2009;151(1):1–10.PubMed
64.
Ito S. Usefulness of RAS inhibition depends on baseline albuminuria. Nat Rev Nephrol. 2010;6(1):10–1.PubMedCrossRef
Metadata
Title
Cardiorenal connection in chronic kidney disease
Author
Sadayoshi Ito
Publication date
01-02-2012
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 1/2012
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-011-0493-2

Other articles of this Issue 1/2012

Clinical and Experimental Nephrology 1/2012 Go to the issue

Review Article

The role of the kidney in salt-sensitive hypertension

Review Article

Regulation and dysregulation of epithelial Na+ channels

Original Article

Significance of the duration of nephropathy for achieving clinical remission in patients with IgA nephropathy treated by tonsillectomy and steroid pulse therapy

Case report

Granulomatous interstitial nephritis associated with atypical drug-induced hypersensitivity syndrome induced by carbamazepine

Review Article

Mechanisms and interventions in peritoneal fibrosis

Review Article

The roles of V1a vasopressin receptors in blood pressure homeostasis: a review of studies on V1a receptor knockout mice

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits