Cardiac disease in young adult patients with end-stage renal disease since childhood: a Dutch cohort study

BACKGROUND: Cardiovascular disease is the most important cause of death in patients with pediatric end-stage renal disease (ESRD). Yet, few data exist on cardiac function in these patients. We assessed the extent of cardiac abnormality and analyzed its association with potential determinants in young adult patients with pediatric ESRD in a long-term follow-up study. METHODS: All Dutch living adult patients with ESRD onset at age of 0 to 14 years between 1972 and 1992 were invited for echocardiography and blood pressure assessment. Special attention was paid to evidence of left ventricular hypertrophy (LVH), diastolic dysfunction, and aortic valve calcification. We collected data on determinants by review of all medical charts. RESULTS: Of all the 187 living patients, 140 participated in the study. Of those, 110 patients had received a transplant and 30 patients were on dialysis. Mean age was 29.2 (20.7 to 41.8) years. Left ventricular mass index (LVMI) exceeded 150 g/m2 in 47% of all male patients and 120 g/m2 in 39% of all female patients, both consistent with LVH. Diastolic dysfunction, defined as an early over atrial transmitral blood flow velocity (E/A ratio) <1, was found in 18 (13%) patients; 27 (19%) had aortic valve calcification. Multiple regression analysis revealed the following: a high LVMI was associated with a current high blood pressure (beta=0.46, P < 0.001) and male gender (beta=0.21, P=0.009), a low E/A ratio with aging (beta=-0.28, P < 0.001) and a glomerular filtration rate (GFR) <25 mL/min/1.73 m2 (beta=-0.29, P < 0.001), and aortic valve calcification with prolonged peritoneal dialysis (beta=0.36, P < 0.001). CONCLUSION: Young adult patients with pediatric ESRD are at risk for LVH caused by hypertension and for aortic valve calcification. Diastolic function decreases with age and is enhanced by a current low GFR. Prolonged peritoneal dialysis may enhance aortic valve calcification.     

Kidney transplantation improves arterial stiffness in patients with end-stage renal disease

Background

Cardiovascular disease (CVD) is the leading cause of mortality among the patients with end-stage renal disease (ESRD). Arterial stiffness is a well-accepted predictor of cardiovascular mortality in general population and ESRD patients. The aim of this study was to compare the change of arterial stiffness in kidney transplant recipients (KTRs) and ESRD patients, and further investigate the impact of kidney transplantation (KT) on arterial stiffness.

Methods

A total of 138 maintenance hemodialysis patients, 198 KTRs and 75 healthy volunteers were enrolled in this study. The carotid-femoral pulse wave velocity (CF-PWV) and carotid-radial PWV (CR-PWV) were determined, and the correlations of PWV with biochemical parameters were analyzed.

Results

CF-PWV was highest in the maintenance hemodialysis patients, but similar between KTRs and healthy volunteers. Bivariate correlation analysis among KTRs demonstrated that CF-PWV was positively correlated with high level of peripheral diastolic blood pressure, pulse pressure, mean artery pressure, BUN and HDL, but negatively correlated with albumin. Univariate polytomous logistic regression analysis showed that age, BMI, systolic blood pressure, pulse pressure, length of KT and BUN were associated with the increase of CF-PWV value.

Conclusions

Aortic stiffness could be improved after KT. Meanwhile, age, BMI, systolic blood pressure, pulse pressure, length of KT and BUN were independent predictors of the increase of CF-PWV in KTRs.

     

Quality of life in adults with end-stage renal disease since childhood is only partially impaired.

BACKGROUND: Little is known about the quality of life of adults with end-stage renal disease (ESRD) since childhood. In a long-term follow-up study, we assessed quality of life in these patients and compared their outcomes with those in the general population and in dialysis patients with adult-onset of ESRD. METHODS: All Dutch adult patients with onset of ESRD at age 0-14 years between 1972 and 1992 were asked to complete the RAND-36 questionnaire. We obtained clinical information by reviewing all available medical charts, and by current history. Patient scores were compared with those of age-matched healthy controls and with those of patients with adult onset of dialysis, of whom data were derived from a national study on the adequacy of dialysis (NECOSAD-2). RESULTS: We obtained a complete RAND-36 score in 131 of 187 surviving patients. Clinical characteristics of participants and non-participants were similar. Compared with the general population, we found a higher prevalence of impaired quality of life in dialysis patients in the following domains: physical functioning, role limitations due to physical health, social functioning (SF), general health perception (GH) and physical component summary. In other domains, impaired quality of life was equally or less prevalent (mental component summary). In transplanted patients, only impaired GH and SF were more prevalent. In dialysis patients with adult ESRD onset, impaired quality of life was more prevalent than in the general population in all domains, except in emotional role limitations. CONCLUSIONS: Dialysis patients with paediatric ESRD have an impaired physical quality of life, but in contrast to dialysis patients with adult ESRD onset, they have a normal mental quality of life.     

Successful kidney transplantation ameliorates arterial stiffness in end-stage renal disease patients

Purpose

Successful kidney transplantation (KTx) can ameliorate bodily damage caused by end-stage renal disease (ESRD). Arterial stiffness (AS) is one of the critical factors that shorten the survival of patients due to cardiovascular events. KTx may reduce AS as well; however, this has not been investigated well. We therefore conducted a retrospective study using noninvasive pulse wave velocity (PWV), which is a useful index of aortic damage.

Patients and methods

Fifty-eight consecutive kidney recipients (34 men, 24 women) were enrolled in this study. Mean age at transplantation was 40.5 ± 12.3 years and the dialysis period was 73.1 ± 95.8 months. The brachial-ankle PWV was measured preoperatively and 6 months postoperatively. First, we investigated the relationship between the PWV and the other parameters related to AS. Second, we studied the pre- to posttransplant change in PWV to evaluate the amelioration of AS after successful KTx.

Results

PWV showed significant positive correlations with age, systolic blood pressure (BP), diastolic BP, and abdominal aortic calcification index. After successful KTx, PWV significantly decreased (P < .01). In addition, systolic and diastolic BP significantly decreased (P < .01 and P < .05, respectively).

Conclusion

Successful KTx ameliorates AS in ESRD patients. This might explain the improved cardiovascular prognosis of ESRD patients who undergo KTx.     

The impact of delayed development on the quality of life of adults with end-stage renal disease since childhood

Little is known about the impact of the course of life of children with end-stage renal disease (ESRD) on their quality of life in adulthood. We therefore assessed the course of life of adult patients with onset of ESRD at an age of <15 years between 1972 and 1992 and compared it with that of the general population. Furthermore, we explored how course of life is associated with quality of life (QoL) in young adulthood. A total of 75 young adult patients who had had ESRD since childhood, aged between 20 years and 30 years, completed the RAND-36 Health Survey and a questionnaire, which retrospectively assesses the achievement of development milestones. Patients achieved fewer milestones than peers with respect to autonomy, social, and psycho-sexual development, and displayed less risk behaviour. Patients who achieved fewer social milestones while growing up experienced more emotional problems and less vitality, and they had a lesser overall mental quality of life. Paediatric nephrologists should pay more attention to the development of social and independent functioning of children with ESRD in order to prepare them for active participation in society in adult life.     

Early coronary calcification in children and young adults with end-stage renal disease

Cardiovascular disease is a major cause of morbidity and mortality in children and young adults with end-stage renal disease. In our study, we retrospectively analyzed the records of 11 patients who had undergone electron beam computerized tomography in our dialysis unit. Our patients, aged 11 to 24 years (median, 19.3 years) were on dialysis or had functioning grafts. Coronary calcification was observed in seven patients (64%) with a mean calcium score of 273.8 +/- 708 (range 0.8 to 1864) in our study population. We compared clinical characteristics like age, gender, duration of end-stage renal disease, time on hemodialysis, body mass index, and blood pressures between the patients with calcifications (group I) and those with out calcification (group II). We also compared the laboratory data including daily calcium and calcitriol intake, lipid profile, serum calcium and phosphorus levels, calcium/phosphorus products, and serum parathyroid hormone levels in the both groups. The mean daily dose of total calcium, triglyceride level, and calcium/phosphorus products were higher in the calcification group though not statistically significant. The mean daily dose of calcitriol was significantly higher in patients with calcification. Using Spearman multivariate correlation, we found a correlation between the coronary calcium scores and mean daily doses of total calcium and calcitriol (r = .750, P =.008 and r = .869, P = .001, respectively). We conclude that coronary calcification, which is a proven predictor of cardiovascular disease, begins at a very early age and that daily doses of elemental calcium and calcitriol seem to be important factors in our study population.     

Arterial stiffness and function in end-stage renal disease

Cardiovascular disease is a major cause of mortality in patients with end-stage renal disease, with damage to arteries as a major contributing factor. Arterial stiffness is a factor associated with high systolic and pulse pressure in these patients and is a strong independent factor associated with morbidity and mortality. Arterial stiffness is one of the principal factors opposing left ventricular ejection. The appropriate term to define the arterial factor(s) opposing left ventricular ejection is aortic input impedance. Aortic input impedance depends on TPR, arterial distensibility, and wave reflections. Distensibility defines the capacitive properties of arterial stiffness, whose role it is to dampen pressure and flow oscillations and to transform pulsatile flow and pressure in arteries into a steady flow and pressure in peripheral tissues. Stiffness is the reciprocal value of distensibility. These parameters are blood pressure dependent; arteries become stiffer at high pressure. While distensibility provides information about the elasticity of the artery as a hollow structure, the elastic incremental modulus characterizes the properties of the arterial wall biomaterials independent of vessel geometry. Alternatively, arterial distensibility can be evaluated by measuring pulse wave velocity, which increases with the stiffening of arteries. Arterial stiffening increases left ventricular afterload and alters the coronary perfusion. With increased pulse wave velocity, the wave reflections affects the aorta during systole, which increases systolic pressures and myocardial oxygen consumption and decreases diastolic blood pressure and coronary flow. The arterial stiffness is altered primarily in association with increased collagen content and alterations of extracellular matrix and calcification of the arterial wall. The arterial stiffening estimated by changes in aortic pulse wave velocity and intensity of wave reflections are independent predictors of survival in end-stage renal disease and in the general population. Improvement of arterial stiffening could be obtained by antihypertensive treatments as observed with calcium-channel blockers and angiotensin-converting enzyme inhibitors. Angiotensin-converting enzymes inhibitors increase AC and reduce wave reflections. It has been shown that reversibility of aortic stiffening and use of angiotensin-converting enzyme inhibitors had a favorable independent effect on survival in hypertensive patients with advanced renal disease.     

Infrainguinal arterial reconstruction in end-stage renal disease

A total of 14 infrainguinal revascularizations in 11 patients with end-stage renal disease resulting from diabetes mellitus were reviewed. Indications for surgery comprised gangrene or non-healing ulcerations in eight patients (11 limbs), ischaemic rest pain in two (two limbs) and disabling claudication in one (one limb). No graft failures occurred during the period of observation. There were two immediate postoperative deaths, one amputation, and four persistent non-healing foot ulcers. The remaining four patients showed improvement. Six deaths occurred, including two perioperative deaths. Four patients with non-healing ulcers died within 1 year and 10 months after revascularization, but their deaths were not associated with the foot ulcers. The cumulative patient survival rate was 42% at 1 year. Infrainguinal revascularization in patients with end-stage renal disease caused by diabetes mellitus is feasible when meticulous preoperative assessment and careful perioperative management are employed to minimize operative risk.     

Alterations of arterial function in end-stage renal disease

Cardiovascular disease is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Epidemiological and clinical studies have shown that this is most frequently related to damage of large conduit arteries. Macrovascular disease develops rapidly in uremic patients and is responsible for the high incidence of ischemic heart disease, sudden death, peripheral artery diseases, and congestive heart failure. The most frequent causes of these complications are occlusive lesions due to atherosclerosis. Nevertheless, atherosclerosis, a disease characterized by the presence of plaques, represents only one form of structural response to metabolic and hemodynamic alterations which interfere with the process of aging, i.e., arteriosclerosis, characterized by dilation/hypertrophy and stiffening of arteries. The vascular complications in ESRD are ascribed to two different but associated mechanisms, namely atherosclerosis and arteriosclerosis. Whereas the former principally affects the conduit function with ischemic lesions being the most characteristic consequence, the latter primarily disturbs the cushioning function of large arteries. Arteriosclerosis in ESRD patients is characterized by diffuse dilation and hypertrophy of large conduit arteries and stiffening of arterial walls and represents a clinical form of accelerated aging process. The main clinical characteristics of arterial stiffening concern changes in blood pressure with isolated increase in systolic pressure and normal or lower diastolic pressure. The consequences of these alterations are: (1) an increased left ventricular afterload with development of left ventricular hypertrophy and increased myocardial oxygen demand and (2) altered coronary perfusion and subendocardial blood flow distribution. Epidemiological studies have identified arterial remodeling and stiffening as independent predictors of overall and cardiac mortality in ESRD patients.     

Lower-extremity peripheral arterial disease among patients with end-stage renal disease.

Peripheral arterial occlusive disease (PAOD) accounts for significant morbidity and mortality among end-stage renal disease (ESRD) patients but has not been as extensively studied as other kinds of atherosclerotic disease in this population. The current epidemiology and management of PAOD in ESRD patients is here reviewed and target areas for future research are identified. The prevalence of PAOD appears to be much higher among ESRD patients than in the general population. Risk factors for disease among ESRD patients are not well understood but probably include both conventional and dialysis or uremia-associated risk factors. Standard diagnostic techniques used to identify PAOD in the general population may not be as helpful in ESRD patients because many of these tests are inaccurate in the settings of vascular calcification and small-vessel disease. Despite the fact that this is a common disease in ESRD patients, most of these patients are not screened for PAOD. Interventions that have proven effective in the prevention and treatment of PAOD in the general population, such as smoking cessation, preventive foot care, and exercise, have not been systematically applied to ESRD patients. Furthermore, the optimal management of ischemic ulceration and gangrene in ESRD patients is quite controversial, and better algorithms for the prevention and management of PAOD in ESRD patients are needed. In conclusion, PAOD is common in ESRD patients. Future research should identify risk factors for disease in this population, and efforts should be made to develop strategies for the effective prevention and management of limb ischemia in this population.     

Increased risk of hip fracture among patients with end-stage renal disease

BACKGROUND: Although patients with end-stage renal disease (ESRD) are at increased risk for bone loss, the risk of hip fracture in this population is not known. We compared the risk of hip fracture among dialysis patients with the general population. METHODS: We used data from the United States Renal Data System (USRDS) to identify all new Caucasian dialysis patients who began dialysis between January 1, 1989, and December 31, 1996. All hip fractures occurring during this time period were ascertained. The observed number of hip fractures was compared with the expected number based on the experience of residents of Olmstead County (MN, USA). Standardized incidence ratios were calculated as the ratio between observed and expected. The risk attributable to ESRD was calculated as the difference between the observed and expected rate of hip fracture per 1000 person-years. RESULTS: The number of dialysis patients was 326,464 (55.9% male and 44.1% female). There were 6542 hip fractures observed during the follow-up period of 643, 831 patient years. The overall incidence of hip fracture was 7.45 per 1000 person years for males and 13.63 per 1000 person years for females. The overall relative risk for hip fracture was 4.44 (95% CI, 4.16 to 4.75) for male dialysis patients and 4.40 (95% CI, 4.17 to 4.64) for female dialysis patients compared with people of the same sex in the general population. While the age-specific relative risk of hip fracture was highest in the youngest age groups, the added risks of fracture associated with dialysis rose steadily with increasing age. The relative risk of hip fracture increased as time since first dialysis increased. CONCLUSIONS: The overall risk of hip fracture among Caucasian patients with ESRD is considerably higher than in the general population, independent of age and gender.     

Nationwide survey of adolescents and young adults with end-stage kidney disease

Aim: To better understand the health‐care needs of adolescents and young adults (AYA) with end‐stage kidney disease (ESKD), we sought to describe the demographic characteristics of a national cohort. Methods: Data were retrieved from the Australia and New Zealand Dialysis and Transplant Registry. We included all patients aged 15–25 years, living in Australia and receiving renal replacement therapy (RRT) on 31 December 2009. Data included race, aetiology of kidney disease, postal code, transition and migration history. Results: A total of 495 AYA were receiving RRT in Australia giving a prevalence of 143 per million age‐related population. Sixty‐three per cent had a functioning transplant, 24% were receiving haemodialysis and 13% peritoneal dialysis. Median current age was 22 years (interquartile range (IQR) 19–24). The most prevalent cause of ESKD was glomerulonephritis (33%). The majority of patients lived in capital cities. Indigenous patients were more likely to live in more remote areas. Eighty‐five per cent of patients were currently receiving care at an adult unit and 35% of these patients had transitioned from a paediatric unit since starting RRT. The median number of patients per adult unit was 5 (IQR 3–10). Conclusions: The majority of Australian AYA with ESKD are managed in adult units; however, the number at any one unit is low. As most live in the capital cities there may be an opportunity to establish centralized services designed to cater for the needs of AYA patients. However, the needs of patients living in more remote areas, including a significant proportion of Indigenous patients, may not be met by such a model.     

Serum magnesium level and arterial calcification in end-stage renal disease

In this paper we examine the relationship of serum levels of Ca, P, Ca X P, P/Mg, Ca X P/Mg, alkaline phosphatase, and iPTH to the development or regression of peripheral arterial calcifications (AC) in 44 patients with end-stage renal disease being treated by continuous ambulatory peritoneal dialysis (CAPD). The average follow-up time of this longitudinal study was 27 months (range 6-67 months). The patients were divided into two groups: Group A, those showing one or more increases of AC; and Group B, patients in whom AC either did not develop or decreased during the follow-up. There was no significant difference in serum Ca, P, Ca X P, alkaline phosphatase of iPTH between the two groups. However, serum Mg was significantly lower in Group A than in Group B (2.69 +/- 0.52 and 3.02 +/- 0.51 mg/dl, respectively, P less than 0.001), while the ratios P/Mg and Ca X P/Mg were significantly higher. Our observations suggest that in end-stage renal disease hypermagnesemia may retard the development of arterial calcifications.     

Time-dependent effects of cadaveric renal transplantation on arterial compliance in patients with end-stage renal disease

BACKGROUND: Cardiovascular complications are the leading cause of mortality in patients undergoing hemodialysis. Increased arterial stiffness is a strong and independent predictor of cardiovascular risk in these patients. In the present study, we investigated the time-dependent effects of cadaveric renal transplantation on arterial elasticity in end-stage renal disease patients. METHODS: Thirty-six patients underwent successful cadaveric kidney transplantation. Pulse-wave analysis of the radial artery was performed prior to transplantation (day 0) and at six defined intervals after transplantation (day 1 to 90). Compliance of large conduit arteries (C1) and of small resistance arteries (C2) was assessed using a modified Windkessel model of the circulation. RESULTS: Both large artery and small artery compliance were transiently improved within the first four weeks posttransplant reaching a maximum of 122 +/- 42% (C1) and 147 +/- 93% (C2) between day 19 and 23. After the first month, however, elasticity gradually deteriorated to reach baseline values three months after transplantation again. CONCLUSION: The benefits of cadaveric renal transplantation on oscillatory and capacitive artery compliance are only transient. It may be speculated that the subacute and long-term vasoactive effects of calcineurin inhibitors counteract the metabolic benefits of increased renal function on the vasculature.     

Arterial and cardiac disease in young adults with childhood-onset end-stage renal disease-impact of calcium and vitamin D therapy.

BACKGROUND: Studies in patients with childhood-onset end-stage renal disease (ESRD) provide a diagnostic window to the evolution of cardiovascular disease (CVD) in this population. Hyperphosphataemia and renal osteodystrophy are particularly difficult to treat in paediatric patients, but there is only limited information regarding the effect of calcium-containing phosphate binders and vitamin D preparations on the development of CVD in the young. METHODS: We studied 40 adult patients (mean age 23.6 years) who developed ESRD at the age of 11.5 +/- 4 years and 40 matched healthy control subjects. Nine patients were on dialysis and 31 had a functioning kidney transplant. Measurements included intima-media thickness (IMT) of the common carotid artery, electron beam computed tomography (EBCT) for the detection of coronary artery calcifications (CAC), echocardiography and post-ischaemic arterial blood flow by venous occlusion plethysmography. Patient characteristics, atherosclerotic risk factors and a complete account of prescribed medications were analysed for correlations with arterial and cardiac changes. RESULTS: The IMT was not significantly different in patients and controls; four patients (10%) had coronary calcifications on EBCT. Twenty-five patients (62.5%) had left ventricular hypertrophy. Patients had a 40% reduction of post-ischaemic arterial flow. Morphological alterations of the heart and arteries were significantly correlated with the duration of ESRD and dialysis time, and with the cumulative intake of calcium-containing phosphate binders and active vitamin D preparations. Functional changes (vascular reactivity) were correlated with duration of ESRD and non-traditional risk factors. CONCLUSIONS: Young adults with ESRD since childhood have systemic CVD characterized by a decrease in arterial elasticity, the occurrence of CAC and changes in left ventricular morphology. Treatment with calcium-containing phosphate binders and active vitamin D preparations is independently associated in a dose-dependent manner with surrogate markers for CVD.     

Medical and psychosocial rehabilitation of young adults receiving renal replacement therapy since childhood: a single-centre experience

This study reviews medical and psychosocial rehabilitation of children and adolescents with end-stage renal disease (ESRD) and analyses data of young adults with ESRD from a single centre providing renal replacement therapy (RRT) for more than 20 years. Data from 30 patients, aged 25±4 (18-34) years receiving renal replacement therapy (RRT) since childhood were analysed. Medical and psychosocial rehabilitation were assessed by a medical questionnaire and by chart review. The sociological data were compared to an aged-matched control population (n=26) with long-standing diabetes mellitus type I (DM) and to the available national demographic data. Seventeen patients were treated by dialysis (D) and 13 by transplantation (TPL). The duration of RRT was 13 (1-21) years. Growth failure was pronounced in most patients, and a significant number were suffering from hypertension, left ventricular hypertrophy, anaemia, osteodystrophy, hepatitis, and phsical disabilities. Vocational training/school performance, and employment was not markedly different in patients with RRT and controls with DM. However, the type of employment was different with an overrepresentation of lower income jobs in RRT patients. Most patients with RRT were unmarried and one-third was living with their parents. These data, largely reflecting early experience of a paediatric RRT programme, indicate that young adults receiving RRT from childhood have a multitude of medical and psychosocial problems, providing a continuing challenge for centres providing RRT.     

Low protein diets delay end-stage renal disease in non-diabetic adults with chronic renal failure.

BACKGROUND: The objective of this study was to determine the efficacy of low protein diets in delaying the need to start maintenance dialysis based on an analysis of published literature. METHODS: The search strategy involved a Medline and Embase search from January 1966 through to June 1999, congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, International Society of Nephrology since 1987) and direct contacts with investigators. The selection criteria included randomized trials comparing two different levels of protein intake in adult patients suffering from moderate to severe renal failure, followed for at least 1 year. Patients with diabetic nephropathy were excluded. Seven trials were selected from 40 studies since 1975. A total of 1494 patients were analysed: 753 had received reduced protein intake and 741 a higher protein intake. The numbers of 'renal deaths' (defined as the need for starting dialysis, the death of a patient or kidney transplant during the trial) were collected. RESULTS: 242 renal deaths were recorded, 101 in the low protein diet and 141 in the higher protein diet group, giving an odds ratio of 0.61 with a 95% confidence interval of 0.46 to 0.83 (P=0.006). CONCLUSION: Reducing protein intake in patients with chronic renal failure reduces the occurrence of renal death by about 40% as compared with larger or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.