Changes in Blood Pressure and Arterial Hemodynamics following Living Kidney Donation.
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ABSTRACT: Background and objectives
The Effect of a Reduction in GFR after Nephrectomy on Arterial Stiffness and Central Hemodynamics (EARNEST) study was a multicenter, prospective, controlled study designed to investigate the associations of an isolated reduction in kidney function on BP and arterial hemodynamics.Design, setting, participants, & measurements
Prospective living kidney donors and healthy controls who fulfilled criteria for donation were recruited from centers with expertise in vascular research. Participants underwent office and ambulatory BP measurement, assessment of arterial stiffness, and biochemical tests at baseline and 12 months.Results
A total of 469 participants were recruited, and 306 (168 donors and 138 controls) were followed up at 12 months. In the donor group, mean eGFR was 27 ml/min per 1.73 m2 lower than baseline at 12 months. Compared with baseline, at 12 months the mean within-group difference in ambulatory day systolic BP in donors was 0.1 mm Hg (95% confidence interval, -1.7 to 1.9) and 0.6 mm Hg (95% confidence interval, -0.7 to 2.0) in controls. The between-group difference was -0.5 mm Hg (95% confidence interval, -2.8 to 1.7; P=0.62). The mean within-group difference in pulse wave velocity in donors was 0.3 m/s (95% confidence interval, 0.1 to 0.4) and 0.2 m/s (95% confidence interval, -0.0 to 0.4) in controls. The between-group difference was 0.1 m/s (95% confidence interval, -0.2 to 0.3; P=0.49).Conclusions
Changes in ambulatory peripheral BP and pulse wave velocity in kidney donors at 12 months after nephrectomy were small and not different from controls.Clinical trial registry name and registration number
NCT01769924 (https://clinicaltrials.gov/ct2/show/NCT01769924).
SUBMITTER: Price AM
PROVIDER: S-EPMC7480552 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionKidney donors have been reported to have accelerated progression of aortic stiffness and decreased glomerular filtration compared with healthy non-donors. This is a concern because increased aortic stiffness is an independent predictor of overall cardiovascular disease and all-cause mortality in the general population. To confirm if arterial stiffness increases after donation, we will systematically review all studies that evaluated indices of arterial stiffness in healthy individuals who underwent unilateral nephrectomy for kidney donation compared with age-matched healthy non-nephrectomised controls.Methods/analysisWe will comprehensively search for studies published between 1 January 1960 and 15 March 2021 in MEDLINE, EMBASE, Cochrane Central, OVID and EBM reviews. All prospective (cohort, case-control, case series and before-and-after studies) and retrospective non-randomised studies reporting indices of arterial stiffness in nephrectomised and non-nephrectomised healthy participants will be included. Primary outcome will be the difference in the functional metrics of arterial stiffness between donors and non-donors. Secondary outcomes will be the differences in systolic/diastolic blood pressures, serum creatinine, glomerular filtration, carotid artery intima-media thickness and vascular calcification. Study screening, selection and data extraction will be performed by two independent reviewers. Risk of bias will be independently assessed with the ROBINS-I tool and confidence in evidence by the Grading of Recommendations Assessment, Development and Evaluation recommendations. Qualitative and quantitative data syntheses as well as clinical and statistical heterogeneity (Forest plots, I2 and Cochran's Q statistics) will be evaluated. If clinical and statistical heterogeneity are acceptable, inverse variance-weighted effects will be analysed by random effect models.Ethics and disseminationNo ethical approval is necessary. Our results will be disseminated through peer-review publication and presentations to guide stakeholders on the evaluation and follow-up care of kidney donors.Prospero registration numberCRD42020185551.
| S-EPMC7942241 | biostudies-literature
Project description:Living kidney donation represents the optimal renal replacement therapy, but recent data suggest an increased long-term renal risk for the donor. Here, we evaluated the risk for reduced estimated glomerular filtration rate (eGFR), death, and major cardiovascular events such as nonfatal myocardial infarction or cerebrovascular event including TIA (transient ischemic attack) and stroke in 225 donors, who underwent pre-donation examinations and live donor nephrectomy between 1985 and 2014 at our center. The median follow-up time was 8.7 years (1.0-29.1). In multivariate analysis, age and arterial hypertension at baseline were significantly associated with a higher risk of adverse renal outcomes, such as (1) eGFR <60 mL/min/1.73 m2 (age per year: HR (hazard ratio) 1.05, 95% confidence interval (CI) 1.03-1.08, hypertension: HR 2.25, 95% CI 1.22-3.98), (2) eGFR <60 mL/min/1.73 m2 and a decrease of ?40% from baseline (age: HR 1.08, 95% CI 1.03-1.13, hypertension: HR 4.22, 95% CI 1.72-10.36), and (3) eGFR <45 mL/min/1.73 m2 (age: HR 1.12, 95% CI 1.05-1.20, hypertension: HR 5.06, 95% CI 1.49-17.22). In addition, eGFR at time of donation (per mL/min/1.73 m2) was associated with a lower risk of (1) eGFR <60 mL/min/1.73 m2 (HR 0.98, 95% CI 0.97-1.00) and (2) eGFR <45 mL/min/1.73 m2 (HR 0.95, 95% CI 0.90-1.00). Age was the only significant predictor for death or major cardiovascular event (HR 1.08, 95% CI 1.01-1.16). In conclusion, arterial hypertension, lower eGFR, and age at the time of donation are strong predictors for adverse renal outcomes in living kidney donors.
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Project description:BackgroundLiving kidney donation has been advocated as a means to ameliorate the chronic shortage of organs for transplantation. Significant rates of comorbidity and familial risk for kidney disease may limit this approach in the local context; there is currently limited data describing living donation in Africa.MethodsWe assessed reasons for non-donation and outcomes following donation in a cohort of 1208 ethnically diverse potential living donors evaluated over a 32-year period at a single transplant centre in South Africa.ResultsMedical contraindications were the commonest reason for donor exclusion. Black donors were more frequently excluded (52.1% vs. 39.3%; p<0.001), particularly for medical contraindications (44% vs. 35%; p<0.001); 298 donors proceeded to donor nephrectomy (24.7%). Although no donor required kidney replacement therapy, an estimated glomerular filtration rate below 60 ml/min/1.73 m2 was recorded in 27% of donors at a median follow-up of 3.7 years, new onset albuminuria >300 mg/day was observed in 4%, and 12.8% developed new-onset hypertension. Black ethnicity was not associated with an increased risk of adverse post-donation outcomes.ConclusionThis study highlights the difficulties of pursuing live donation in a population with significant medical comorbidity, but provides reassurance of the safety of the procedure in carefully selected donors in the developing world.
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Project description:BackgroundOne of the challenges in living kidney donor screening is to estimate remaining kidney function after donation. Here we developed a new model to predict post-donation measured glomerular filtration rate (mGFR) from pre-donation serum creatinine, age and sex.MethodsIn the prospective development cohort (TransplantLines, n = 511), several prediction models were constructed and tested for accuracy, precision and predictive capacity for short- and long-term post-donation 125I-iothalamate mGFR. The model with optimal performance was further tested in specific high-risk subgroups (pre-donation eGFR <90 mL/min/1.73 m2, a declining 5-year post-donation mGFR slope or age >65 years) and validated in internal (n = 509) and external (Mayo Clinic, n = 1087) cohorts.ResultsIn the development cohort, pre-donation estimated GFR (eGFR) was 86 ± 14 mL/min/1.73 m2 and post-donation mGFR was 64 ± 11 mL/min/1.73 m2. Donors with a pre-donation eGFR ≥90 mL/min/1.73 m2 (present in 43%) had a mean post-donation mGFR of 69 ± 10 mL/min/1.73 m2 and 5% of these donors reached an mGFR <55 mL/min/1.73 m2. A model using pre-donation serum creatinine, age and sex performed optimally, predicting mGFR with good accuracy (mean bias 2.56 mL/min/1.73 m2, R2 = 0.29, root mean square error = 11.61) and precision [bias interquartile range (IQR) 14 mL/min/1.73 m2] in the external validation cohort. This model also performed well in donors with pre-donation eGFR <90 mL/min/1.73 m2 [bias 0.35 mL/min/1.73 m2 (IQR 10)], in donors with a negative post-donation mGFR slope [bias 4.75 mL/min/1.73 m2 (IQR 13)] and in donors >65 years of age [bias 0.003 mL/min/1.73 m2 (IQR 9)].ConclusionsWe developed a novel post-donation mGFR prediction model based on pre-donation serum creatinine, age and sex.
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Project description:Pulse wave velocity (PWV) is a measure of arterial stiffness. We investigated PWV and blood pressure (BP) to determine to what extent BP changes contribute to arterial stiffness, and secondly, to identify influencing factors on BP in children after kidney transplantation. Seventy children ≥ 2.5 years post-transplantation with at least two PWV measurements were included. Changes of systolic (Δ SBP) and diastolic BP (Δ DBP) were classified into "stable/decreasing," "1-10 mmHg increase," and " > 10 mmHg increase." Linear mixed modeling for PWV z-score (PWVz) adjusted either for Δ SBP or Δ DBP was performed. An extended dataset with monthly entries of BP, immunosuppression, and creatinine was obtained in 35 participants over a median of 74 months to perform linear mixed modeling for SBP and DBP. PWVz increased with a rate of 0.11/year (95% CI 0.054 to 0.16). Compared to participants with stable BP, those with 1-10-mmHg SBP and DBP increase showed a higher PWVz of 0.59 (95% CI 0.046 to 1.13) and 0.86 (95% CI 0.43 to 1.30), respectively. A > 10-mmHg BP increase was associated with an even higher PWVz (SBP β = 0.78, 95% CI 0.22 to 1.34; DBP β = 1.37, 95% CI 0.80 to 1.94). Female sex and participants with lower eGFR showed higher PWVz. In the extended analysis, DBP was positively associated with cyclosporin A and everolimus trough levels. A higher increase of PWV is seen in patients with greater BP increase, with higher cyclosporin A and everolimus trough levels associated with higher BP. This emphasizes the role of BP as a modifiable risk factor for the improvement of cardiovascular outcome after transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Project description:BackgroundAs much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery.Materials and methodsMedical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients (35 years old; 95% CI 29-39). Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney.ResultsSystolic (-11?mmHg; 95% CI 6-15?mmHg), diastolic (-8?mmHg; 95% CI 4-11?mmHg), and mean arterial (-9?mmHg; 95% CI 6-12) pressures were significantly reduced after relief of the obstruction (p?<?0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37-41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction.ConclusionsIn adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis.
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Project description:In response to recent studies, a better understanding of the risks of renal complications among African American and biologically related living kidney donors is needed.We examined a database linking U.S. registry identifiers for living kidney donors (1987-2007) to billing claims from a private health insurer (2000-2007 claims) to identify renal condition diagnoses categorized by International Classification of Diseases 9th Revision coding. Cox regression with left and right censoring was used to estimate cumulative incidence of diagnoses after donation and associations (adjusted hazards ratios, aHR) with donor traits.Among 4650 living donors, 13.1% were African American and 76.3% were white; 76.1% were first-degree relatives of their recipient. By 7 years post-donation, after adjustment for age and sex, greater proportions of African American compared with white donors had renal condition diagnoses: chronic kidney disease (12.6% vs 5.6%; aHR, 2.32; 95% confidence interval [95% CI], 1.48-3.62), proteinuria (5.7% vs 2.6%; aHR, 2.27; 95% CI, 1.32-3.89), nephrotic syndrome (1.3% vs 0.1%; aHR, 15.7; 95% CI, 2.97-83.0), and any renal condition (14.9% vs 9.0%; aHR, 1.72; 95% CI, 1.23-2.41). Although first-degree biological relationship to the recipient was not associated with renal risk, associations of African American race persisted for these conditions and included unspecified renal failure and reported disorders of kidney dysfunction after adjustment for biological donor-recipient relationship.African Americans more commonly develop renal conditions after living kidney donation, independent of donor-recipient relationship. Continued research is needed to improve risk stratification for renal outcomes among African American living donors.
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Project description:BackgroundLiving kidney donors (LKDs) with obesity have increased perioperative risks and risk of end-stage renal disease after donation. Consequently, obesity serves as a barrier to donation, as many transplant centers encourage or require weight loss before donation for obese LKD candidates. Therefore, this study sought to assess patients' perspectives on weight management strategies before donation among obese LKD candidates. We hypothesized that willingness to participate in a weight loss program may be associated with donor-recipient relationship.Materials and methodsObese (BMI ≥30 kg/m2) LKD candidates evaluated at a single institution from September 2017 to August 2018 were recruited. A survey was administered to assess LKD candidates' baseline exercise and dietary habits and their interest in weight management strategies for the purpose of donation approval. Participants were grouped by relationship to the recipient (close relatives: first-degree relatives or spouses [n = 29], compared with all other relationships [n = 21]). Descriptive statistics were used to summarize the data.Results50 of 51 obese LKD candidates who were approached completed the survey. 90% of participants expressed willingness to lose weight if necessary to become eligible for donor nephrectomy. Compared with all other LKD candidates, close relatives were more likely to be interested in combined diet and exercise programs at our institution (P = 0.01).ConclusionsAmong obese LKD candidates, there was an interest in weight loss for the purposes of living kidney donation approval, particularly among close relatives of potential recipients. Future programs designed to promote weight management efforts for obese LKD candidates should be considered.
| S-EPMC6815694 | biostudies-literature
Project description:Background and objectivesPrecise BP measurement to exclude hypertension is critical in evaluating potential living kidney donors. Ambulatory BP monitoring is considered the gold standard method for diagnosing hypertension, but it is cumbersome to perform. We sought to determine whether lower BP cutoffs using office and automated BP would reduce the rate of missed hypertension in potential living donors.Design, setting, participants, & measurementsWe measured BP in 578 prospective donors using three modalities: (1) single office BP, (2) office automated BP (average of five consecutive automated readings separated by 1 minute), and (3) ambulatory BP. Daytime ambulatory BP was considered the gold standard for diagnosing hypertension. We assessed both the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) and the American College of Cardiology/American Heart Association (ACC/AHA) definitions of hypertension in the cohort. Empirical thresholds of office BP and automated BP for the detection of ambulatory BP-diagnosed hypertension were derived using Youden index, which maximizes the sum of sensitivity and specificity and gives equal weight to false positive and false negative values.ResultsHypertension was diagnosed in 90 (16%) prospective donors by JNC-7 criteria and 198 (34%) prospective donors by ACC/AHA criteria. Masked hypertension was found in 3% of the total cohort by JNC-7 using the combination of office or automated BP, and it was seen in 24% by ACC/AHA guidelines. Using Youden index, cutoffs were derived for both office and automated BP using JNC-7 (<123/82 and <120/78 mm Hg) and ACC/AHA (<119/79 and <116/76 mm Hg) definitions. Using these lower cutoffs, the sensitivity for detecting hypertension improved from 79% to 87% for JNC-7 and from 32% to 87% by ACC/AHA definition, with negative predictive values of 95% and 87%, respectively. Missed (masked) hypertension was reduced to 2% and 4% of the entire cohort by JNC-7and ACC/AHA, respectively.ConclusionsThe prevalence of hypertension was higher in living donor candidates using ACC/AHA compared JNC-7 definitions. Lower BP cutoffs in the clinic improved sensitivity and led to a low overall prevalence of missed hypertension in prospective living kidney donors.
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