ABSTRACT
BACKGROUND: Previous reports suggest increased risk of hypertension and cardiovascular mortality after kidney donation. In this study we investigate the occurrence of ischaemic heart disease and cerebrovascular disease, diabetes and cancer in live kidney donors compared with healthy controls eligible for donation. METHODS: Different diagnoses were assessed in 1029 kidney donors and 16 084 controls. The diagnoses at follow-up were self-reported for the controls and registered by a physician for the donors. Stratified logistic regression was used to estimate associations with various disease outcomes, adjusted for gender, age at follow-up, smoking at baseline, body mass index at baseline, systolic blood pressure at baseline and time since the donation. RESULTS: The mean observation time was 11.3 years [standard deviation (SD) 8.1] for donors versus 16.4 years (SD 5.7) for controls. The age at follow-up was 56.1 years (SD 12.4) in donors versus 53.5 years (SD 11.1) in controls and 44% of donors were males versus 39.3% in the controls. At follow-up, 35 (3.5%) of the donors had been diagnosed with ischaemic heart disease versus 267 (1.7%) of the controls. The adjusted odds ratio for ischaemic heart disease was 1.64 (confidence interval 1.10-2.43; P = 0.01) in donors compared with controls. There were no significant differences for the risks of cerebrovascular disease, diabetes or cancer. CONCLUSIONS: During long-term follow-up of kidney donors, we found an increased risk of ischaemic heart disease compared with healthy controls. This information may be important in the follow-up and selection process of living kidney donors.
Subject(s)
Coronary Artery Disease , Hypertension , Kidney Transplantation , Myocardial Ischemia , Coronary Artery Disease/etiology , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Hypertension/etiology , Kidney , Kidney Transplantation/adverse effects , Living Donors , Male , Myocardial Ischemia/complications , Myocardial Ischemia/etiology , NephrectomyABSTRACT
BACKGROUND: There is no consensus on how, when, or at what intensity exercise should be performed after heart transplantation (HTx). We have recently shown that high-intensity interval training (HIT) is safe, well tolerated, and efficacious in the maintenance state after HTx, but studies have not investigated HIT effects in the de novo HTx state. We hypothesized that HIT could be introduced early after HTx and that it could lead to clinically meaningful increases in exercise capacity and health-related quality of life. METHODS: This multicenter, prospective, randomized, controlled trial included 81 patients a mean of 11 weeks (range, 7-16 weeks) after an HTx. Patients were randomized 1:1 to 9 months of either HIT (4×4-minute intervals at 85%-95% of peak effort) or moderate-intensity continuous training (60%-80% of peak effort). The primary outcome was the effect of HIT versus moderate-intensity continuous training on the change in aerobic exercise capacity, assessed as the peak oxygen consumption (Vo2peak). Secondary outcomes included tolerability, safety, adverse events, isokinetic muscular strength, body composition, health-related quality of life, left ventricular function, hemodynamics, endothelial function, and biomarkers. RESULTS: From baseline to follow-up, 96% of patients completed the study. There were no serious exercise-related adverse events. The population comprised 73% men, and the mean±SD age was 49±13 years. At the 1-year follow-up, the HIT group demonstrated greater improvements than the moderate-intensity continuous training group; the groups showed significantly different changes in the Vo2peak (mean difference between groups, 1.8 mL·kg-1·min-1), the anaerobic threshold (0.28 L/min), the peak expiratory flow (11%), and the extensor muscle exercise capacity (464 J). The 1.8-mL·kg-1·min-1 difference was equal to ≈0.5 metabolic equivalents, which is regarded as clinically meaningful and relevant. Health-related quality of life was similar between the groups, as indicated by results from the Short Form-36 (version 2), Hospital Anxiety and Depression Scale, and a visual analog scale. CONCLUSIONS: We demonstrated that HIT was a safe, efficient exercise method in de novo HTx recipients. HIT, compared with moderate-intensity continuous training, resulted in a clinically significantly greater change in exercise capacity based on the Vo2peak values (25% versus 15%), anaerobic threshold, peak expiratory flow, and muscular exercise capacity. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier NCT01796379.
Subject(s)
Heart Transplantation , High-Intensity Interval Training/methods , Transplant Recipients/statistics & numerical data , Adult , Female , Follow-Up Studies , High-Intensity Interval Training/statistics & numerical data , Humans , Male , Middle Aged , Oxygen Consumption , Prospective Studies , Quality of Life , Scandinavian and Nordic Countries/epidemiology , Spirometry , Ventricular Function, LeftABSTRACT
BACKGROUND: Patients with diabetes mellitus treated with successful pancreas transplantation (PTX) normalize hyperglycemia, but are exposed to immunosuppressive drugs that may impair endothelial function. This study aimed to evaluate endothelial function in single PTX recipients. METHODS: Flow-mediated dilatation (FMD) in the brachial artery was measured by ultrasound 8 weeks after transplantation in single PTX (n = 27) and compared with healthy controls (n = 58), simultaneous pancreas and kidney recipients (n = 9), and kidney transplant recipients with (n = 41) and without (n = 95) diabetes mellitus. Adjustments for age, gender, blood pressure, and body mass index were included in a linear regression model. Changes in FMD from before to 1 year after transplantation were assessed in a subgroup of PTX recipients (n = 9). RESULTS: Flow-mediated dilatation% in PTX recipients was not inferior to healthy controls (8.7 ± 3.6 vs 7.7 ± 3.3, P = .06) and simultaneous pancreas and kidney recipients (6.7 ± 4.5, P = .24) in an adjusted model, and superior to kidney recipients with and without diabetes (3.0 ± 3.0 and 4.8 ± 3.3, respectively, both P < .005). FMD% improved significantly from eight weeks to one year after PTX, mean 7.9 ± 4.2% vs 11.8 ± 4.8% (N = 9; P = .03). CONCLUSION: Flow-mediated dilatation is well preserved in patients undergoing pancreas transplantation and is not impaired when immunosuppressive drugs are introduced.
Subject(s)
Diabetes Mellitus, Type 1 , Kidney Transplantation , Pancreas Transplantation , Humans , Immunosuppressive Agents/therapeutic use , UltrasonographyABSTRACT
Kidney donors may be at increased risk of end-stage renal disease and premature mortality. Elevated blood pressure after donation may contribute to the increased risks. In this cohort study, we have assessed long-term risk for the development of hypertension in kidney donors compared to a control group potentially eligible as donors. Follow-up data were obtained from previous living kidney donors. A healthy control group with baseline assessment from similar time periods as the donor nephrectomies was selected. Hypertension was defined as blood pressure >140/90, use of blood pressure medication, or established diagnosis of hypertension. Stratified logistic regression was used to estimate risk of hypertension at follow-up, adjusted for systolic blood pressure at baseline, age at follow-up, time since donation/baseline, gender, smoking at baseline, and BMI at baseline. A total of 368 donors (36%) had hypertension at follow-up, and 241 of these (23%) were using blood pressure medication. In adjusted stratified logistic regression analyses, odds ratio for hypertension was significantly increased (1.25, 95% confidence interval 1.12-1.39, P < 0.001) in donors compared with controls. Kidney donors appear to be at increased long-term risk for hypertension compared with healthy controls. This finding supports regular follow-up of blood pressure in kidney donors.
Subject(s)
Hypertension , Kidney Transplantation , Cohort Studies , Follow-Up Studies , Glomerular Filtration Rate , Humans , Hypertension/epidemiology , Hypertension/etiology , Kidney , Kidney Transplantation/adverse effects , Living Donors , Nephrectomy , Retrospective StudiesABSTRACT
Purpose: Until recently, it has been believed that donating a kidney not represents any risk for development of cardiovascular disease. However, a recent Norwegian epidemiological study suggests that kidney donors have an increased long-term risk of cardiovascular mortality. The pathophysiological mechanisms linking reduced kidney function to cardiovascular disease are not known. Living kidney donors are screened for cardiovascular morbidity before unilateral nephrectomy, and are left with mildly reduced glomerular filtration rate (GFR) after donation. Therefore, they represent an unique model for investigating the pathogenesis linking reduced GFR to cardiovascular disease and cardiovascular remodelling. We present the study design of Cardiovascular rEmodelling in living kidNey donorS with reduced glomerular filtration rate (CENS), which is an investigator-initiated prospective observational study on living kidney donors. The hypothesis is that living kidney donors develop cardiovascular remodelling due to a reduction of GFR.Materials and methods: 60 living kidney donors and 60 age and sex matched healthy controls will be recruited. The controls will be evaluated to fulfil the Norwegian transplantation protocol for living kidney donors. Investigations will be performed at baseline and after 1, 3, 6 and 10 years in both groups. The investigations include cardiac magnetic resonance imaging, echocardiography, bone density scan, flow mediated dilatation, laser Doppler flowmetry, nailfold capillaroscopy, office blood pressure, 24-h ambulatory blood pressure, heart rate variability and investigation of microbiota and biomarkers for inflammation, cardiovascular risk and the calcium-phosphate metabolism.Conclusions: The present study seeks to provide new insight in the pathophysiological mechanisms linking reduced kidney function to cardiovascular disease. In addition, we aim to enlighten predictors of adverse cardiovascular outcome in living kidney donors. The study is registered at Clinical-Trials.gov (identifier: NCT03729557).
Subject(s)
Cardiovascular Diseases/physiopathology , Glomerular Filtration Rate , Kidney Diseases/physiopathology , Kidney Transplantation , Kidney/physiopathology , Living Donors , Nephrectomy/adverse effects , Vascular Remodeling , Ventricular Remodeling , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/etiology , Case-Control Studies , Humans , Kidney Diseases/diagnosis , Kidney Diseases/etiology , Longitudinal Studies , Norway , Prospective Studies , Research Design , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
There is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. A total of 1640 participants from the ALERT trial (Assessment of Lescol in Renal Transplantation), a study comparing fluvastatin with placebo in stable renal transplant recipients, were genotyped for all SNPs making up the GRS. Risk alleles were weighted by the log of odds ratios reported in genome wide association studies and summed. Associations between GRS and time from study inclusion to first major cardiovascular event (MACE) were analyzed by Cox regression. In analyses adjusted for cardiovascular risk factors, GRS was significantly associated with MACE (hazard ratio [HR] 1.81, P = .006) when comparing genetic high-risk patients (quartile 4) with genetic low-risk participants (quartile 1). A 27-SNP GRS, which predicted cardiovascular events in the nontransplant population, appears to have predictive value also in kidney allograft recipients. Refining the score to better fit the transplant population seems feasible.
Subject(s)
Cardiovascular Diseases/diagnosis , Genetic Markers , Graft Rejection/diagnosis , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Polymorphism, Single Nucleotide , Postoperative Complications , Adult , Aged , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Double-Blind Method , Female , Follow-Up Studies , Genome-Wide Association Study , Glomerular Filtration Rate , Graft Rejection/etiology , Graft Rejection/metabolism , Graft Survival , Humans , Kidney Function Tests , Male , Middle Aged , Prognosis , Risk FactorsABSTRACT
In the general population, small increases in blood pressure are associated with increased mortality. In kidney donors this association is less certain. We therefore assessed long-term overall and cardiovascular mortality in donors who were hypertensive at the time of donation compared with normotensive donors. Hypertension was defined as blood pressure >140/90 mmHg or use of antihypertensive drugs. Adequate records available in 2131 donors revealed that 140 were hypertensive and 1991 were normotensive. Multivariable regression analyses were performed for overall and cardiovascular mortality. Hypertensive donors were significantly older (mean 57.7 vs. 46.9 years), more were males (44.3% vs. 41.5%), had higher body mass index (26.4 vs. 24.7) and lower estimated glomerular filtration rate (91.8 vs. 101.2 ml/min/1.73 m2 ). After a median observation time of 20.8 years (interquartile range 11) 71 hypertensive donors had died and 26 of the deaths were cardiovascular. Multivariable analysis did not suggest a generalizable association between hypertension and long-term overall mortality [hazard ratio (HR) 1.1, 95% confidence interval (CI) 0.9-1.5, P = 0.34] or cardiovascular mortality (HR 1.1, 95% CI 0.7-1.8, P = 0.55). These data may support the use of older healthy kidney donors with hypertension at donation.
Subject(s)
Hypertension/mortality , Nephrectomy/adverse effects , Tissue Donors/statistics & numerical data , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
In stable renal transplant recipients with hyperparathyroidism, previous studies have indicated that vitamin D agonist treatment might have anti-proteinuric effects. Animal studies indicate possible anti-fibrotic and anti-inflammatory effects. Early introduction of paricalcitol in de novo renal transplant recipients might reduce proteinuria and prevent progressive allograft fibrosis. We performed a single-center, prospective, randomized, open-label trial investigating effects of paricalcitol 2 µg/day added to standard care. Participants were included 8 weeks after engraftment and followed for 44 weeks. Primary end point was change in spot urine albumin/creatinine ratio. Exploratory microarray analyses of kidney biopsies at study end investigated potential effects on gene expression. Secondary end points included change in glomerular filtration rate (GFR), pulse wave velocity (PWV), and endothelial function measured by peripheral arterial tonometry as reactive hyperemia index (RHI). Seventy-seven de novo transplanted kidney allograft recipients were included, 37 receiving paricalcitol. Paricalcitol treatment lowered PTH levels (P = 0.01) but did not significantly reduce albuminuria (P = 0.76), change vascular parameters (PWV; P = 0.98, RHI; P = 0.33), or influence GFR (P = 0.57). Allograft gene expression was not influenced. To summarize, in newly transplanted renal allograft recipients, paricalcitol reduced PTH and was well tolerated without negatively affecting kidney function. Paricalcitol did not significantly reduce/prevent albuminuria, improve parameters of vascular health, or influence allograft gene expression.
Subject(s)
Ergocalciferols/administration & dosage , Kidney Transplantation/methods , Administration, Oral , Animals , Ergocalciferols/adverse effects , Gene Expression/drug effects , Glomerular Filtration Rate/drug effects , Humans , Hyperemia/physiopathology , Hyperparathyroidism/drug therapy , Hyperparathyroidism/prevention & control , Kidney/drug effects , Kidney/pathology , Kidney/physiopathology , Parathyroid Hormone/blood , Prospective Studies , Proteinuria/prevention & control , Pulse Wave Analysis , Receptors, Calcitriol/agonistsABSTRACT
INTRODUCTION: There is an uncertainty whether total inflammation in early protocol kidney graft biopsies is associated with fibrosis progression. We investigated whether total inflammation, both in fibrotic and non-fibrotic areas, at week 6 would predict fibrosis progression at one yr post-transplant. METHODS: We included 156 single adult ABO compatible kidney recipients with adequate week 6 and one yr transplant protocol biopsies (312 biopsies). Biopsies were scored according to the current Banff criteria. In addition, fibrosis and inflammation in fibrotic and non-fibrotic areas were scored in a 10-grade semi-quantitative eyeballing system from 0% to 100%. RESULTS: Fibrosis increased significantly from week 6 to one yr both by the 10-grade scoring system from 0.69 ± 1.07 to 1.45 ± 1.86, (mean ± SD), p < 0.001 and by Banff interstitial fibrosis (ci) scoring 0.81 ± 0.65 to 1.13 ± 0.87, p < 0.001. The 10-grade scoring system detected a larger proportion of fibrosis progressors than the Banff scoring 40.4% vs. 35.5%, p < 0.001. No significant positive association was found between inflammation at week 6 and progression of fibrosis in either of the scoring systems. CONCLUSIONS: Total inflammation in kidney transplant biopsies at week 6 did not predict progression of fibrosis at one yr post-transplant.
Subject(s)
Biopsy/methods , Graft Rejection/pathology , Inflammation/pathology , Kidney Transplantation/adverse effects , Kidney/pathology , Disease Progression , Female , Fibrosis/pathology , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Period , Predictive Value of Tests , Retrospective Studies , Time Factors , Transplantation, HomologousABSTRACT
Current diagnostic criteria for post-transplantation diabetes mellitus (PTDM) are either fasting plasma glucose ≥7.0 mmol/l (≥126 mg/dl) or postchallenge plasma glucose ≥11.1 mmol/l (≥200 mg/dl) 2 h after glucose administration [oral glucose tolerance test (OGTT) criterion]. In this retrospective cohort study of 1632 renal transplant recipients (RTRs) without known diabetes mellitus at the time of transplantation, we estimated mortality hazard ratios for patients diagnosed with PTDM by either conventional glucose criteria or the proposed glycated haemoglobin (HbA1c) criterion [HbA1c ≥6.5% (≥48 mmol/mol)]. During a median follow-up of 7.0 years, 311 patients died. Compared with nondiabetic patients and after adjustment for confounders, patients diagnosed with PTDM based on chronic hyperglycaemia early after transplantation (manifest PTDM) or by the OGTT criterion at 10 weeks post-transplant suffered a higher mortality risk (HR 1.59, 95% CI 1.06-2.38, P = 0.02 and HR 1.56, 95% CI 1.04-2.38, P = 0.03, respectively). In contrast, patients diagnosed with PTDM by the HbA1c criterion at 10 weeks or between 10 weeks and 1 year post-transplant were not associated with mortality (HR 0.96, 95% CI 0.61-1.51, P = 0.86 and 1.58, 95% CI 0.74-3.36, P = 0.24 respectively). After adjustment for confounders and competing risks, only patients with manifest PTDM had a significantly higher cardiovascular mortality risk (subdistributional HR 2.31, 95% CI 1.19-4.47, P < 0.001). Since many cases with PTDM were only identified by the OGTT, we recommend monitoring fasting plasma glucose early after renal transplantation followed by an OGTT at 2-3 months post-transplant in patients without overt diabetes mellitus.
Subject(s)
Blood Glucose/analysis , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Glycated Hemoglobin/analysis , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adult , Aged , Diabetes Complications/therapy , Diabetes Mellitus/therapy , Female , Glucose Tolerance Test , Humans , Hyperglycemia/diagnosis , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/complications , Male , Middle Aged , Norway , Registries , Retrospective Studies , Risk Factors , Steroids/therapeutic use , Time Factors , Treatment OutcomeABSTRACT
The role of visceral adipose tissue (VAT) in post-transplant hyperglycaemia is not known. We evaluated 167 patients without diabetes 8-10 weeks after kidney transplantation, performing oral glucose tolerance tests and measuring VAT content from dual-energy X-ray absorptiometry scans. Median VAT weight in normal glucose tolerance patients was 0.9 kg, impaired fasting glucose patients 1.0 kg, impaired glucose tolerance patients 1.3 kg and patients with post-transplant diabetes (PTDM) 2.1 kg (P = 0.004, indicating a difference between groups). Percentage VAT of total body fat was associated with fasting (R(2) = 0.094, P < 0.001) and 2-h glucose concentration (R(2) = 0.062, P = 0.001), while BMI was only associated with 2-h glucose concentration (R(2) = 0.029, P = 0.028). An association between BMI and 2-h glucose concentration was lost in adjusted models, as opposed to the associations between VAT as percentage of total body fat and glucose concentrations (R(2) = 0.132, P < 0.001 and R(2) = 0.097, P = 0.001, respectively for fasting and 2-h glucose concentration). In conclusion, VAT is more closely related to impaired glucose metabolism than BMI after kidney transplantation. The association with central obesity should encourage additional studies on lifestyle interventions to prevent PTDM.
Subject(s)
Diabetes Mellitus/etiology , Glucose/metabolism , Insulin Resistance , Intra-Abdominal Fat/metabolism , Kidney Transplantation , Postoperative Complications/etiology , Absorptiometry, Photon , Adult , Aged , Blood Glucose/analysis , Body Composition , Body Mass Index , Cross-Sectional Studies , Diabetes Mellitus/chemically induced , Diabetes Mellitus/metabolism , Glucose Tolerance Test , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Immunoglobulins, Intravenous , Immunosuppressive Agents/adverse effects , Insulin/blood , Intra-Abdominal Fat/diagnostic imaging , Lipids/blood , Methylprednisolone/adverse effects , Middle Aged , Postoperative Complications/metabolism , Prednisolone/adverse effects , Rituximab/therapeutic use , Tissue DonorsABSTRACT
The association between serum uric acid and kidney graft and recipient survival is uncertain. During 2000-2011, we measured serum uric acid at week 10 after transplantation. Of 2748 transplanted patients, 2200 (80.1%) attended this visit. After a median follow-up of 7.4 yr, 378 patients had died, 143 from a cardiovascular cause, and 185 patients lost their graft. The third quintile of uric acid levels (357-405 µM) had the lowest mortality risk and was used as reference group. In Cox proportional hazard models adjusting for graft and patient characteristics, the fifth quintile of uric acid levels (>474 µM) was independently associated with cardiovascular mortality (hazard ratio [HR] = 2.87 [1.55-5.32], p = 0.001) and all-cause mortality (HR = 1.57 [1.09-2.25], p = 0.02). Also, the lowest quintile of uric acid levels (<309 µM) showed a trend toward increased risk of cardiovascular mortality (HR = 1.79 [0.90-3.58], p = 0.10) and all-cause mortality (HR = 1.31 [0.89-1.93], p = 0.18). The increased risk at low uric acid levels was confined to diabetic recipients. Uric acid was not associated with death-censored graft loss. In conclusion, uric acid has a J-shaped association with cardiovascular and all-cause mortality in kidney transplant recipients.
Subject(s)
Biomarkers/blood , Cardiovascular Diseases/mortality , Graft Rejection/mortality , Kidney Transplantation , Uric Acid/blood , Adolescent , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/blood , Child , Child, Preschool , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/blood , Graft Survival/physiology , Humans , Infant , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/surgery , Kidney Function Tests , Male , Middle Aged , Postoperative Complications , Prognosis , Risk Factors , Survival Rate , Young AdultABSTRACT
UNLABELLED: Uric acid is associated with increased mortality in kidney transplant recipients (KTRs), but it is uncertain if this involves endothelial dysfunction. We hypothesized, first, that there was an association between uric acid and endothelial function, and second, that there were associations between endothelial function and cardiac and mortality risk scores. METHODS: One hundred and fifty-two patients were examined 10 wk after kidney transplantation by two measures of endothelial function, the brachial artery flow-mediated dilatation (FMD) expressed as percent dilatation (FMD%), and fingertip peripheral arterial tone (PAT) expressed as log-reactive hyperemia index (LnRHI). Risk scores were calculated from a recently validated formula. Other clinical correlates of endothelial function were described in stepwise linear regression models. RESULTS: Uric acid was associated negatively with FMD% in an age- and gender-adjusted model, while not in the multivariable model. No association was shown between uric acid and LnRHI. FMD% was associated negatively with risk scores in both crude and age- and gender-adjusted models (p < 0.01). LnRHI was associated negatively with risk scores in the latter model only (p < 0.05). CONCLUSIONS: Uric acid was neither associated with FMD% nor LnRHI in KTRs. There were significant associations between endothelial function indices and cardiac and mortality risk scores.
Subject(s)
Endothelium, Vascular/pathology , Graft Rejection/diagnosis , Kidney Failure, Chronic/surgery , Kidney Transplantation , Uric Acid/blood , Vascular Diseases/diagnosis , Cross-Sectional Studies , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/blood , Graft Rejection/etiology , Graft Survival , Humans , Kidney Failure, Chronic/blood , Kidney Function Tests , Male , Middle Aged , Postoperative Complications , Prognosis , Risk Factors , Vascular Diseases/blood , Vascular Diseases/etiologyABSTRACT
BACKGROUND: It is well established that post-transplantation anemia (PTA) in renal transplant recipients (RTRs) is associated with reduced graft survival. However, there is an uncertainty of the effect of PTA on cardiovascular events and all-cause mortality. We examined prospectively in a large cohort of erythropoietin-naive patients the effects of PTA on cardiovascular morbidity, patient survival, and graft survival. METHODS: A prospective cohort study of RTRs (n = 2102) included in the ALERT study. Cox regression models were used to evaluate the impact of PTA on study endpoints: first occurrence of a major adverse cardiac event, all-cause death, and the incidence of death-censored graft loss. Mean follow-up was 6.7 yr. All endpoints were adjudicated by an independent endpoint committee. RESULTS: Twenty-nine percent of women and 30% of men were anemic. Hemoglobin levels were not associated with any effect on cardiovascular morbidity and mortality (HR 0.97 [0.90-1.05] per g/dL, p = 0.48) or all-cause death (HR 0.96 [0.90-1.03] per g/dL, p = 0.24) after extensive multivariate adjustments for clinical and demographic factors. Hemoglobin levels were negatively associated with graft loss (HR 0.86 [0.80-0.92] per g/dL, p < 0.001). CONCLUSIONS: PTA was not associated with an increased incidence of cardiovascular morbidity and mortality or all-cause mortality.
Subject(s)
Anemia/diagnosis , Cardiovascular Diseases/mortality , Kidney Failure, Chronic/diagnosis , Kidney Transplantation , Adult , Anemia/mortality , Cause of Death , Double-Blind Method , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Kidney Failure, Chronic/mortality , Kidney Function Tests , Male , Middle Aged , Postoperative Complications , Prognosis , Prospective Studies , Risk Factors , Survival RateABSTRACT
BACKGROUND: There are concerns regarding potential long-term risks to the living kidney donor. Cardiovascular mortality has not been evaluated. The aim of this study was to assess overall and cardiovascular mortality in previous kidney donors compared with a general population sample. METHODS: All live kidney donors in Norway in the period 1963-2007 were included. Controls matched 3:1 for age, gender and year of birth were provided by Statistics, Norway. Cause of death was retrieved from the death master file. Vital status as of 1 January 2010 was provided for all participants, and cause of death was available until 1 January 2008. Comparative survival analyses were performed by Kaplan-Meier curves and log-rank test. Age-stratified death rates were calculated and compared with a selected group with a health status hypothetically allowing donation. RESULTS: There were 2269 living kidney donors in the study period. At donation, mean age was 47.6 + 12.6 years, 41.3% were male. Median observation time was 14.3 years. A total of 324 donors died during the study period. Causes of death were similar for donors and controls. By Kaplan-Meier analysis, overall and cardiovascular mortality was lower for previous kidney donors than for matched controls (P < 0.001 and P = 0.004, respectively). Age-stratified death rates were elevated for the oldest group of donors. CONCLUSIONS: Overall and cardiovascular mortality results are partially reassuring. However, the seemingly elevated mortality rate among the oldest donors requires further study.
Subject(s)
Cardiovascular Diseases/mortality , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/mortality , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Living Donors , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Female , Follow-Up Studies , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Norway/epidemiology , Prognosis , Survival Rate , Young AdultABSTRACT
BACKGROUND: In patients with chronic kidney disease, vascular calcification contributes to increased cardiovascular (CV) morbidity and mortality. CV risk remains high after successful renal transplantation. Osteoprotegerin (OPG) is a glycoprotein, involved in the regulation of the vascular calcification process. Previous studies have shown that elevated OPG is predictive of mortality in high-risk populations. The aim of this study was to investigate the prognostic value of OPG for graft function, CV events and all-cause death, in a large transplant cohort. METHODS: OPG was measured at baseline in renal transplant recipients enrolled in the Assessment of Lescol in Renal Transplantation (ALERT) study, a randomized placebo-controlled intervention study comparing fluvastatin and placebo. Patients were followed for 6.7 years with evaluation of pre-specified end points, graft loss, graft function, CV events and death. RESULTS: OPG was analysed in 1889 renal transplant recipients, with a mean value of 4.69 ± 1.85 pg/L. The number of renal and CV events increased by quartiles of OPG. In the multivariate analysis, OPG in the fourth as compared to first quartile was an independent predictor of graft failure or doubling of serum creatinine [hazard ratio (HR) 2.20 (1.56-3.11), P < 0.001], major CV events [HR 2.40 (1.58-3.64), P < 0.001], cardiac mortality [HR 2.80 (1.32-5.94), P = 0.007] and all-cause mortality [HR 2.31 (1.53-3.49), P < 0.001]. CONCLUSION: In a large cohort of kidney transplant patients with long-term follow-up, OPG was independently associated with renal events, CV events and mortality.
Subject(s)
Biomarkers/metabolism , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Graft Rejection/diagnosis , Graft Rejection/mortality , Kidney Transplantation/adverse effects , Osteoprotegerin/metabolism , Adult , Aged , Anticholesteremic Agents/therapeutic use , Cardiovascular Diseases/etiology , Creatinine/blood , Enzyme-Linked Immunosorbent Assay , Fatty Acids, Monounsaturated/therapeutic use , Female , Fluvastatin , Follow-Up Studies , Graft Rejection/etiology , Humans , Indoles/therapeutic use , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/drug therapy , Kidney Failure, Chronic/mortality , Kidney Transplantation/mortality , Male , Middle Aged , Prognosis , Risk Factors , Survival Rate , Vascular Calcification/diagnosis , Vascular Calcification/etiology , Vascular Calcification/mortalityABSTRACT
Kidney transplant recipients (KTRs) are at increased risk of developing renal cell carcinoma (RCC). The cancer can be encountered at different steps in the transplant process. RCC found during work-up of a transplant candidate needs treatment and to limit the risk of recurrence usually a mandatory observation period before transplantation is recommended. An observation period may be omitted for candidates with incidentally discovered and excised small RCCs (<3 cm). Likewise, RCC in the donor organ may not always preclude usage if tumor is small (<2 to 4 cm) and removed with clear margins before transplantation. After transplantation, 90% of RCCs are detected in the native kidneys, particularly if acquired cystic kidney disease has developed during prolonged dialysis. Screening for RCC after transplantation has not been found cost-effective. Treatment of RCC in KTRs poses challenges with adjustments of immunosuppression and oncologic treatments. For localized RCC, excision or nephrectomy is often curative. For metastatic RCC, recent landmark trials in the nontransplanted population demonstrate that immunotherapy combinations improve survival. Dedicated trials in KTRs are lacking. Case series on immune checkpoint inhibitors in solid organ recipients with a range of cancer types indicate partial or complete tumor response in approximately one-third of the patients at the cost of rejection developing in ~40%.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Kidney Transplantation , Carcinoma, Renal Cell/etiology , Carcinoma, Renal Cell/therapy , Humans , Kidney Neoplasms/etiology , Kidney Neoplasms/therapy , Kidney Transplantation/adverse effects , Nephrectomy/adverse effects , Retrospective StudiesABSTRACT
BACKGROUND: Endothelial dysfunction is an early and potentially reversible stage in the atherosclerotic process. We assessed endothelial dysfunction noninvasively in kidney transplant recipients (KTRs) and evaluated the association with mortality and graft outcomes. METHODS: Flow-mediated dilation (FMD) was measured in arteria brachialis by ultrasound, with baseline diameters obtained at rest and maximal diameters obtained during reactive hyperemia occurring after 5 min of forearm occlusion. FMD% is the percentage difference of flow-mediated dilation relative to baseline. Endpoints on mortality and graft outcomes were collected from The Norwegian Renal Registry. The distribution of risk according to FMD levels was assessed in Cox regression using a restricted cubic spline function. FMD was dichotomized using receiver operating characteristic analysis to identify optimal cut points at maximal sensitivity and specificity. RESULTS: From a total of 269 KTRs in 2012, 152 (56.5%) were eligible and examined 10 wk after transplantation, and 145 had successful FMD measurements. During a mean follow-up of 6.5 y, 26 patients died, 11 lost their graft, and 34 experienced either graft loss or death. Mortality increased with lower FMD levels until about 5% dilation and did not change with further reduction in FMD% (P for nonlinearity <0.01). An optimal cut point of FMD ≤5.36% defined impaired endothelial function and FMD% below this level, was associated with fatal outcome, hazard ratio (HR), 9.80 (1.29-74.62), P = 0.03, uncensored graft loss, HR, 7.80 (1.83-33.30), P = 0.01, but an association with death-censored graft loss was lost after adjusting for pulse pressure, HR, 4.58 (0.55-37.92), P = 0.16. CONCLUSIONS: We found that impaired FMD is strongly associated with mortality in KTRs.