Understanding the effects of chronic kidney disease on cardiovascular risk: are there lessons to be learnt from healthy kidney donors?

Moody, William E.; Chue, Colin D.; Inston, Nicholas; Edwards, Nicola C.; Steeds, Richard P.; Ferro, Charles J.; Townend, Jonathan N.

doi:10.1038/jhh.2011.46

Cited by 18 publications

(16 citation statements)

References 58 publications

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“…While data on the impact of LKD on blood pressure are inconclusive [7,32,33], donors in the present study exhibited a trend to higher systolic and diastolic blood pressures after LKD. In addition, the intake of antihypertensive medication increased after LKD.…”

Section: Discussioncontrasting

confidence: 63%

“…Kidney donors lose ~ 50% of their nephron mass by LKD, reflected by a rise in levels of serum creatinine as observed in the present study. The remaining kidney normally compensates for the nephron mass reduction by hypertrophy resulting in a glomerular filtration rate (GFR) of ~ 70% of baseline [7]. Nonetheless, a substantial proportion of kidney donors (in particular older ones) fulfill criteria for stage 3 CKD within the first months after donation [27].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, until more data regarding longterm donor safety becomes available, this new information should be integrated in the decision process before donation [6]. Arterial hypertension, increased arterial stiffness, and increased vascular calcification are discussed as mechanisms by which LKD may induce changes of cardiac morphology and function, finally contributing to an increased cardiovascular risk [7,8,9].…”

Section: Introductionmentioning

confidence: 99%

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Midterm echocardiographic follow-up of cardiac function after living kidney donation

Hewing

Dreger²,

Knebel³

et al. 2015

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Background: Living kidney donation (LKD) has become increasingly important as more patients reach end-stage renal disease. While safety of the donor is of utmost importance, recent data have suggested an increased risk for cardiovascular mortality after LKD. Therefore, we assessed the changes of cardiac structure and function after LKD by advanced echocardiographic methods. Methods: 30 living kidney donors were evaluated by medical examination, laboratory testing, and echocardiography before and after LKD (median follow-up 19.5 months). Left ventricular (LV) and right ventricular (RV) function was assessed by echocardiographic standard indices. Longitudinal 2D strain of the LV and left atrium (LA) was determined by 2D speckle tracking. Results: Serum creatinine increased significantly from 0.80 ± 0.12 mg/dL to 1.18 ± 0.21 mg/ dL (p < 0.001) after LKD. There was a trend to higher blood pressure after LKD, accompanied with significantly higher intake of antihypertensive drugs. Echocardiographic parameters of LV, LA, and RV function did not change significantly after LKD. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels remained within normal ranges after LKD. Conclusion: The rise in serum creatinine and blood pressure indicates that patients have a potentially higher cardiac risk after LKD. However, our pilot study found no evidence for detrimental effects of LKD on cardiac structure and function within a relatively short-term follow-up.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Midterm echocardiographic follow-up of cardiac function after living kidney donation

Hewing

Dreger²,

Knebel³

et al. 2015

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“…Increased urinary albumin excretion has been linked to endothelial dys- function, an important factor in microvascular damage (Stehouwer et al 2004;Stehouwer & Smulders 2006). Increased urinary albumin excretion may also be associated with renal dysfunction or chronic renal damage, which is an independent cardiovascular risk factor (Best et al 2004;Blecker et al 2011;Moody et al 2012). In the present study, the association between urinary albumin excretion and retinopathy persisted when including eGFR in the multivariable model, so endothelial dysfunction is probably the main factor.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in risk factors for retinopathy in non‐diabetic men and women: The Tromsø Eye Study

Bertelsen

Lindekleiv

Schirmer

et al. 2013

Acta Ophthalmologica

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ABSTRACT.Purpose: To determine the prevalence and risk factors for retinopathy in a nondiabetic population. Methods: The study population included 5869 participants without diabetes aged 38-87 years from the Tromsø Eye Study, a substudy of the populationbased Tromsø Study in Norway. Retinal images from both eyes were graded for retinopathy. We collected data on risk factors from self-report questionnaires, clinical examinations, laboratory measurements and case note reviews. The cross-sectional relationship between potential risk factors and retinopathy was assessed using logistic regression analysis. Results: The overall prevalence of retinopathy was 14.8%. Men had a higher prevalence of retinopathy compared with women (15.9% versus 14.0%, p = 0.04). In men, retinopathy was associated with hypertension (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.24-2.04) and HbA1c (OR per %, 1.41; 95% CI, 1.01-1.96). In women, retinopathy was associated with age (OR per 10 years, 1.32; 95% CI, 1.14-1.52), log-transformed urinary albumin excretion (OR per log unit, 1.46; 95% CI, 1.14-1.87) and hypertension (OR, 1.36; 95% CI, 1.08-1.71). In women, retinopathy was associated with very low levels of urinary albumin excretion (urinary albumin ⁄ creatinine ratio >0.43 mg ⁄ mmol). Conclusion: This study confirms results from previous studies on the strong association between blood pressure and retinopathy. A novel finding is the sex differences in risk factors for retinopathy, suggesting a sex difference in the pathogenesis leading to retinopathy.

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“…Uninephrectomy may be qualified as an “acute kidney injury,” with an immediate 50% reduction in GFR followed by an improvement related to hypertrophy in the remaining kidney—but only to 60% to 70% of baseline 6 . Up to two-thirds of donors after nephrectomy fulfil the criteria for CKD stage 3 (eGFR, 30-59 mL/min per 1.73 m 2 ) dependent on baseline age and renal function, 7 which has an approximate odds ratio for cardiovascular disease of between 2 and 4 in the general population 8 . To date, however, all studies examining the long-term consequences of kidney donation have been reassuring, often showing better health outcomes in donors compared with the general population 4,9,10 .…”

Section: Background and Rationalementioning

confidence: 99%

Effect of A Reduction in glomerular filtration rate after NEphrectomy on arterial STiffness and central hemodynamics: Rationale and design of the EARNEST study

Moody

Tomlinson

Ferro

et al. 2014

American Heart Journal

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BackgroundThere is strong evidence of an association between chronic kidney disease (CKD) and cardiovascular disease. To date, however, proof that a reduction in glomerular filtration rate (GFR) is a causative factor in cardiovascular disease is lacking. Kidney donors comprise a highly screened population without risk factors such as diabetes and inflammation, which invariably confound the association between CKD and cardiovascular disease. There is strong evidence that increased arterial stiffness and left ventricular hypertrophy and fibrosis, rather than atherosclerotic disease, mediate the adverse cardiovascular effects of CKD. The expanding practice of live kidney donation provides a unique opportunity to study the cardiovascular effects of an isolated reduction in GFR in a prospective fashion. At the same time, the proposed study will address ongoing safety concerns that persist because most longitudinal outcome studies have been undertaken at single centers and compared donor cohorts with an inappropriately selected control group.HypothesesThe reduction in GFR accompanying uninephrectomy causes (1) a pressure-independent increase in aortic stiffness (aortic pulse wave velocity) and (2) an increase in peripheral and central blood pressure.MethodsThis is a prospective, multicenter, longitudinal, parallel group study of 440 living kidney donors and 440 healthy controls. All controls will be eligible for living kidney donation using current UK transplant criteria. Investigations will be performed at baseline and repeated at 12 months in the first instance. These include measurement of arterial stiffness using applanation tonometry to determine pulse wave velocity and pulse wave analysis, office blood pressure, 24-hour ambulatory blood pressure monitoring, and a series of biomarkers for cardiovascular and bone mineral disease.ConclusionsThese data will prove valuable by characterizing the direction of causality between cardiovascular and renal disease. This should help inform whether targeting reduced GFR alongside more traditional cardiovascular risk factors is warranted. In addition, this study will contribute important safety data on living kidney donors by providing a longitudinal assessment of well-validated surrogate markers of cardiovascular disease, namely, blood pressure and arterial stiffness. If any adverse effects are detected, these may be potentially reversed with the early introduction of targeted therapy. This should ensure that kidney donors do not come to long-term harm and thereby preserve the ongoing expansion of the living donor transplant program (NCT01769924).

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Understanding the effects of chronic kidney disease on cardiovascular risk: are there lessons to be learnt from healthy kidney donors?

Cited by 18 publications

References 58 publications

Midterm echocardiographic follow-up of cardiac function after living kidney donation

Midterm echocardiographic follow-up of cardiac function after living kidney donation

Sex differences in risk factors for retinopathy in non‐diabetic men and women: The Tromsø Eye Study

Effect of A Reduction in glomerular filtration rate after NEphrectomy on arterial STiffness and central hemodynamics: Rationale and design of the EARNEST study

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