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Prevalence and risk factors for tertiary hyperparathyroidism in kidney transplant recipients.
Sutton, W, Chen, X, Patel, P, Karzai, S, Prescott, JD, Segev, DL, McAdams-DeMarco, M, Mathur, A
Surgery. 2022;(1):69-76
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Abstract
BACKGROUND Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism. METHODS A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism. RESULTS Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation. CONCLUSION Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.
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Sudden cardiac death in dialysis patients: different causes and management strategies.
Genovesi, S, Boriani, G, Covic, A, Vernooij, RWM, Combe, C, Burlacu, A, Davenport, A, Kanbay, M, Kirmizis, D, Schneditz, D, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2021;(3):396-405
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Abstract
Sudden cardiac death (SCD) represents a major cause of death in end-stage kidney disease (ESKD). The precise estimate of its incidence is difficult to establish because studies on the incidence of SCD in ESKD are often combined with those related to sudden cardiac arrest (SCA) occurring during a haemodialysis (HD) session. The aim of the European Dialysis Working Group of ERA-EDTA was to critically review the current literature examining the causes of extradialysis SCD and intradialysis SCA in ESKD patients and potential management strategies to reduce the incidence of such events. Extradialysis SCD and intradialysis SCA represent different clinical situations and should be kept distinct. Regarding the problem, numerically less relevant, of patients affected by intradialysis SCA, some modifiable risk factors have been identified, such as a low concentration of potassium and calcium in the dialysate, and some advantages linked to the presence of automated external defibrillators in dialysis units have been documented. The problem of extra-dialysis SCD is more complex. A reduced left ventricular ejection fraction associated with SCD is present only in a minority of cases occurring in HD patients. This is the proof that SCD occurring in ESKD has different characteristics compared with SCD occurring in patients with ischaemic heart disease and/or heart failure and not affected by ESKD. Recent evidence suggests that the fatal arrhythmia in this population may be due more frequently to bradyarrhythmias than to tachyarrhythmias. This fact may partly explain why several studies could not demonstrate an advantage of implantable cardioverter defibrillators in preventing SCD in ESKD patients. Electrolyte imbalances, frequently present in HD patients, could explain part of the arrhythmic phenomena, as suggested by the relationship between SCD and timing of the HD session. However, the high incidence of SCD in patients on peritoneal dialysis suggests that other risk factors due to cardiac comorbidities and uraemia per se may contribute to sudden mortality in ESKD patients.
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Improvement of clinical outcomes in dialysis: No convincing superiority in dialysis efficacy using hemodiafiltration vs high-flux hemodialysis.
Abdelsalam, M, Demerdash, TM, Assem, M, Awais, M, Shaheen, M, Sabri, A, Alanany, H, Kashgary, A, Alsuwaida, A
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2021;(4):483-489
Abstract
Hemodiafiltration (HDF) is not associated with lower mortality risk compared to standard hemodialysis (HD). However, there are many critical clinical outcomes in dialysis patients in addition to mortality; the impact of HDF on these other outcomes is not clear. This retrospective study included all patients referred to DaVita Clinics in the Kingdom of Saudi Arabia. High-flux HD was the initial modality in all patients. Those who did not achieve adequacy targets or those with poorly controlled phosphorus were switched to postdilution HDF using 18 to 23 L exchange per treatment. Patients dialyzing with a central venous catheter, patients who dialyzed less than 90 days at DaVita, and those with interrupted HDF were excluded. Of the 1115 patients, 215 (19%) were on HDF and 900 on high-flux HD; the median follow-up was 6 months for all patients. The HDF group showed a significant reduction in serum phosphate (P < .001), a significant increase in serum calcium (P < .012) and a significant improvement in Kt/V (P < .0001). The HDF group had significantly higher hemoglobin levels than the HD group (P = .024), with a significant reduction in weekly erythropoiesis-stimulating agent dose after starting HDF (P < .001). A modified protocol that included prolonged dialysis duration, larger-sized dialyzer, faster blood flow rates, and adding hemofiltration fluid may be helpful in achieving the recommended targets. Thus, HDF can enable the achievement of adequate dialysis care in some patients. Randomized-controlled clinical trials are necessary to confirm these findings.
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A Scoping Review of Alternative Anticoagulation Strategies for Hemodialysis Patients with a Mechanical Heart Valve.
Thomson, BKA, Pilkey, NG, Monteith, B, Holden, RM
American journal of nephrology. 2021;(10-11):861-870
Abstract
INTRODUCTION Patients with end-stage renal disease (ESRD) have high rates of cardiac valvulopathy but can develop contraindications for vitamin K antagonist (VKA) therapy. We explored the evidence for alternative anticoagulation strategies in patients with ESRD with a contraindication for VKA therapy. METHODS A scoping review was completed, searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Conference abstracts from inception to March 30, 2021. The study population was patients with ESRD who were on VKA therapy and developed a contraindication to VKA therapy use. All data regarding studies, patient characteristics, anticoagulation strategy, and clinical outcomes were summarized. RESULTS Twenty-three articles met inclusion criteria. These articles included 57 patients. Contraindications to VKA therapy included calcific uremic arteriolopathy (CUA) (n = 55) and warfarin-induced skin necrosis (n = 2). All studies were either case reports or case series. There were 10 anticoagulation strategies identified. Continuation of VKA therapy was associated with increased death and decreased rates of CUA resolution (80.0% and 10.0%, respectively), compared to apixaban (24.0% and 70.8%), subcutaneous (SC) low-molecular-weight heparin (LMWH) (14.3%, 85.7%), and SC unfractionated heparin (0.0%, 100.0%). While only 5 patient cases were reported with mechanical heart valves, SC LMWH use has been reported in this context with good outcomes. CONCLUSIONS In patients with ESRD who develop a contraindication to VKA therapy, several alternative anticoagulation strategies have been reported with superior outcomes to VKA continuation. While outcomes appear superior to continuation of VKA therapy, more data are required before definitive recommendations can be made for the patient with ESRD and a mechanical heart valve.
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Modifiable Lifestyle Factors for Primary Prevention of CKD: A Systematic Review and Meta-Analysis.
Kelly, JT, Su, G, Zhang, L, Qin, X, Marshall, S, González-Ortiz, A, Clase, CM, Campbell, KL, Xu, H, Carrero, JJ
Journal of the American Society of Nephrology : JASN. 2021;(1):239-253
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Abstract
BACKGROUND Despite increasing incidence of CKD, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist. METHODS To evaluate the consistency of evidence associating modifiable lifestyle factors and CKD incidence, we searched MEDLINE, Embase, CINAHL, and references from eligible studies from database inception through June 2019. We included cohort studies of adults without CKD at baseline that reported lifestyle exposures (diet, physical activity, alcohol consumption, and tobacco smoking). The primary outcome was incident CKD (eGFR<60 ml/min per 1.73 m2). Secondary outcomes included other CKD surrogate measures (RRT, GFR decline, and albuminuria). RESULTS We identified 104 studies of 2,755,719 participants with generally a low risk of bias. Higher dietary potassium intake associated with significantly decreased odds of CKD (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.65 to 0.94), as did higher vegetable intake (OR, 0.79; 95% CI, 0.70 to 0.90); higher salt intake associated with significantly increased odds of CKD (OR, 1.21; 95% CI, 1.06 to 1.38). Being physically active versus sedentary associated with lower odds of CKD (OR, 0.82; 95% CI, 0.69 to 0.98). Current and former smokers had significantly increased odds of CKD compared with never smokers (OR, 1.18; 95% CI, 1.10 to 1.27). Compared with no consumption, moderate consumption of alcohol associated with reduced risk of CKD (relative risk, 0.86; 95% CI, 0.79 to 0.93). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for secondary outcomes were consistent with the primary finding. CONCLUSIONS These findings identify modifiable lifestyle factors that consistently predict the incidence of CKD in the community and may inform both public health recommendations and clinical practice.
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Novel approaches to sarcopenic obesity and weight management before and after kidney transplantation.
Tantisattamo, E, Kalantar-Zadeh, K, Halleck, F, Duettmann, W, Naik, M, Budde, K
Current opinion in nephrology and hypertension. 2021;(1):14-26
Abstract
PURPOSE OF REVIEW Although a widely recognized and complex pathophysiological condition, sarcopenic obesity remains less appreciated and may elude diagnosis and workup in both kidney transplant waitlisted candidates and kidney transplant recipients. The lack of consensus definition, and practical diagnostic tools for evaluating waitlisted candidates and transplant recipients are barriers to early detect and initiate therapeutic management for sarcopenic obesity. Although sarcopenia leads to poor clinical outcomes, posttransplant obesity yields conflicting results. Exercise and nutritional managements are common therapies for sarcopenic obese patients; however, surgery weight loss or bariatric surgery in both transplant candidates and potential living kidney donors shows promising benefits for kidney transplant access in waitlist obese candidates but may require to be selected for appropriate patients. RECENT FINDINGS Pathogenesis and management for sarcopenia and obesity are interconnected. The benefits of exercise to improve muscle mass and function is clear in waitlist kidney transplant candidates and transplant recipients. However, there are several barriers for those to increase exercise and improve physical activity including patient, provider, and healthcare or environmental factors. The advantages of fat mass reduction to lose weight can promote muscle mass and strength. However, epidemiological data regarding the obesity paradox in dialysis-dependent patients when overnutrition provides survival benefits for this population should be taken into account when performing weight loss especially bariatric surgery. SUMMARY Barriers in providing optimal care to kidney transplant waitlisted candidates and transplant recipients may partly result from underdiagnosis of sarcopenic obesity; notwithstanding that this entity has increasingly been more recognized. Mechanistic studies to better understand pathogenesis of sarcopenic obesity will help determine pathogenesis and clinical tools for diagnosis of this entity, which can facilitate further studies related to the outcomes and weight management to ultimately improve kidney transplant outcomes.
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Recent advances in treatment of haemodialysis.
Burton, JO, Corbett, RW, Kalra, PA, Vas, P, Yiu, V, Chrysochou, C, Kirmizis, D
Journal of the Royal Society of Medicine. 2021;(1):30-37
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Haemodialysis remains the most widely used treatment for patients with end-stage renal disease. Despite the progress that has occurred in the treatment of end-stage renal disease over the last six decades, there has been a failure to translate this into the desired clinical benefits, with morbidity and mortality rates among patients on haemodialysis remaining unacceptably high. Recently, however, there have been expectations that the significant advances that took place over the last few years may result in improved outcomes. New medications for the treatment of anaemia and secondary hyperparathyroidism, as well as novel trends in the areas of iron therapy, diabetes management and physical exercise are among the most important advances which, taken together, are changing the standards of care for patients on haemodialysis. The latest advances, of relevance not only to specialists in Renal Medicine but also to general practitioners caring for these patients, are reviewed in this collaborative paper.
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Using Patient-Reported Measures to Improve Outcomes in Kidney Disease.
Mclaren, S, Jhamb, M, Unruh, M
Blood purification. 2021;(4-5):649-654
Abstract
Patients with CKD and ESRD are vulnerable to increased mortality rates and other poor outcomes. Among those with ESRD, their health-related quality of life (HRQOL) is shown little to no improvement as they undergo treatments such as dialysis and providers concurrently manage other health issues that complicate their already vulnerable state. This review synthesizes evidence demonstrating that a focus on measuring and monitoring patient-reported outcomes (PRO) such as pain and depression can improve HRQOL. Patient-centered care has the potential to create an efficient way for clinicians to address specific challenges facing patients. While there is an emerging literature assessing the use of PROs in kidney research, by examining relevant research in other disciplines it is possible to generate better ways to use PROs in this high-risk population. Electronic health records as well as various other electronic methods of communication between the clinician and patient may serve to accelerate the trajectory toward patient-centered care using PROs.
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Effect of amlodipine versus bisoprolol in hypertensive patients on maintenance hemodialysis: A randomized controlled trial.
Youssef, AM, Elghoneimy, HA, Helmy, MW, Abdelazeem, AM, El-Khodary, NM
Medicine. 2021;(51):e28322
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BACKGROUND Left ventricular hypertrophy and asymmetric dimethylarginine (ADMA) are surrogate markers of cardiovascular disease (CVD) in the dialysis population. This study aimed to evaluate the effect of a calcium channel blocker-based antihypertensive regimen compared to a beta-blocker-based antihypertensive regimen on left ventricular mass index (LVMI) and ADMA levels in hypertensive patients on hemodialysis (HD). METHODS This was a parallel-design, open-label, single-center randomized controlled trial on 46 hypertensive patients on maintenance HD, with no history of CVD. Patients were randomly assigned to receive amlodipine 10 mg/d (n = 23) or bisoprolol 10 mg/d (n = 23). Office-based blood pressure (BP) was targeted to ≤ 140/ 90 mm Hg. The outcome was the change in LVMI and ADMA from baseline to 6 months. RESULTS Baseline demographic and clinical characteristics did not vary between groups. After 6 months of treatment, amlodipine-based therapy induced a greater reduction in LVMI from baseline than bisoprolol-based treatment (35 ± 34.2 vs 9.8 ± 35.9 gm/m2; P = .017). A similar reduction in the mean BP occurred with treatment in both groups. ADMA concentration decreased significantly from baseline in the amlodipine group (0.75 ± 0.73 to 0.65 ± 0.67 nmol/mL; P = .001), but increased nonsignificantly in the bisoprolol group (0.64 ± 0.61 to 0.78 ± 0.64 nmol/mL; P = .052). CONCLUSION This study showed that compared to a bisoprolol-based regimen, an amlodipine-based antihypertensive regimen resulted in a significantly greater reduction in LVMI and ADMA levels from baseline in hypertensive patients on HD despite similar BP reduction in both groups. These findings support the re-evaluation of amlodipine as a potential first-line antihypertensive treatment in patients on HD without previous CVD. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT04085562, registered September 2019.
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Novel management of diabetes in kidney transplantation.
Ong, SC, Rhee, CM
Current opinion in nephrology and hypertension. 2021;(1):5-13
Abstract
PURPOSE OF REVIEW Posttransplant diabetes mellitus (PTDM) is a prevalent complication in kidney transplant recipients, and has been associated with worse short-term and long-term outcomes. RECENT FINDINGS While hyperglycemia is frequently seen in the early posttransplant period because of surgical stress, infection, and use of high-dose steroids, the diagnosis of PTDM should be established after patients are clinically stable and on stable maintenance immunosuppression. In the early posttransplant period, hyperglycemia is typically treated with insulin, and pilot data have suggested potential benefit of lower vs. higher glycemic targets in this setting. Growing data indicate lifestyle modifications, including dietary interventions, physical activity, and mitigation of obesity, are associated with improved posttransplant outcomes. While there are limited data to support a first-line antidiabetic medication for PTDM, more established pharmacotherapies such as sulfonylureas, meglitinides, and dipetidyl peptidase IV inhibitors are commonly used. Given recent trials showing the benefits of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists upon kidney outcomes in nontransplant patients, further study of these agents specifically in kidney transplant recipients are urgently needed. SUMMARY Increasing evidence supports a multidisciplinary approach, including lifestyle modification, obesity treatment, judicious immunosuppression selection, and careful utilization of novel antidiabetic therapies in PTDM patients.