Evidences on the benefits of physical exercise in kidney transplant patients (KTx) are not conclusive and concerns on safety remain. We here gather and interpret current evidence on the benefits/harms of exercise training intervention in KTx. Systematic review of exercise training programs in KTx. A total of 24 studies including 654 KTx patients on intervention and 536 controls were evaluated. The median age was 46 years; the transplant vintage was 2 days to 10 years. The intervention was an aerobic or resistance exercise program or a combination of both; interventions consisted of 20–60 min’ sessions, 2–3 times per week repetitions and 5.5 months’ median duration. Most studies improved cardiorespiratory fitness (expressed as VO2peak) as well as maximum heart rate, which was associated with a significant increase in muscle performances and strength. No significant changes in body weight or composition were observed, but a trend towards weight reduction in overweight or obese patients on stable KTx was noted. The arterial blood pressure reduced a little after exercise when it was high at start. Exercise intervention had no clinically relevant impact on anaemia, glycaemia or lipidaemia. In contrast, exercise training improved several aspects of quality of life. No data on long-term hard outcomes or on high-risk subpopulations such comorbid or elderly patients were available. In adult kidney transplant patients, a structured physical exercise program improved the aerobic capacity and ameliorated muscle performance and quality of life. No harms were observed in the short-term, but long-term RCTs are required. Overall, in mid-age kidney transplant patients without major comorbidities, an aerobic or resistance supervised exercise lasting 3–6 months could be suggested within the comprehensive treatment of kidney transplant.

Exercise training in kidney transplant recipients: a systematic review

Patients with chronic kidney disease (CKD) are at a high risk for cardiovascular disease (CVD), and approximately half of all deaths among patients with CKD are a direct result of CVD. The premature cardiovascular disease extends from mild to moderate CKD stages, and the severity of CVD and the risk of death increase with a decline in kidney function. Successful kidney transplantation significantly decreases the risk of death relative to long-term dialysis treatment; nevertheless, the prevalence of CVD remains high and is responsible for approximately 20-35% of mortality in renal transplant recipients. The prevalence of traditional and nontraditional risk factors for CVD is higher in patients with CKD and transplant recipients compared with the general population; however, it can only partly explain the highly increased cardiovascular burden in CKD patients. Nontraditional risk factors, unique to CKD patients, include proteinuria, disturbed calcium, and phosphate metabolism, anemia, fluid overload, and accumulation of uremic toxins. This accumulation of uremic toxins is associated with systemic alterations including inflammation and oxidative stress which are considered crucial in CKD progression and CKD-related CVD. Kidney transplantation can mitigate the impact of some of these nontraditional factors, but they typically persist to some degree following transplantation. Taking into consideration the scarcity of data on uremic waste products, oxidative stress, and their relation to atherosclerosis in renal transplantation, in the review, we discussed the impact of uremic toxins on vascular dysfunction in CKD patients and kidney transplant recipients. Special attention was paid to the role of native and transplanted kidney function.

/pdf/uremic-toxins-oxidative-stress-atherosclerosis-in-chronic-2cn6u2fn0x.pdf

Uremic Toxins, Oxidative Stress, Atherosclerosis in Chronic Kidney Disease, and Kidney Transplantation.

Abstract Chronic kidney disease (CKD) is a complex condition with a prevalence of 10–15% worldwide. An inverse-graded relationship exists between cardiovascular events and mortality with kidney function which is independent of age, sex, and other risk factors. The proportion of deaths due to heart failure and sudden cardiac death increase with progression of chronic kidney disease with relatively fewer deaths from atheromatous, vasculo-occlusive processes. This phenomenon can largely be explained by the increased prevalence of CKD-associated cardiomyopathy with worsening kidney function. The key features of CKD-associated cardiomyopathy are increased left ventricular mass and left ventricular hypertrophy, diastolic and systolic left ventricular dysfunction, and profound cardiac fibrosis on histology. While these features have predominantly been described in patients with advanced kidney disease on dialysis treatment, patients with only mild to moderate renal impairment already exhibit structural and functional changes consistent with CKD-associated cardiomyopathy. In this review we discuss the key drivers of CKD-associated cardiomyopathy and the key role of hypertension in its pathogenesis. We also evaluate existing, as well as developing therapies in the treatment of CKD-associated cardiomyopathy. 

https://www.nature.com/articles/s41371-022-00751-4.pdf

Hypertension and cardiomyopathy associated with chronic kidney disease: epidemiology, pathogenesis and treatment considerations

Introduction: Lipid disorders are frequent after kidney transplantation (KT) and KT recipients are considered at high- or very-high cardiovascular risk. Among many concurring factors, a major role is played by immunosuppressants.Areas covered: General measures to manage lipid disorders first include physical activity and diet counseling. Modulating the doses of immunosuppressants also improves dyslipidemia. When lipid-lowering drugs are necessary to control elevated plasma cholesterol and/or triglycerides, statins are the cornerstone for managing hypercholesterolemia. However, side-effects (e.g. myopathy, new-onset diabetes, and kidney graft dysfunction) may occur. In these cases, ezetimibe (which does not affect kidney function) alone or on top of statins for the severe cases, is suggested by the most recent Guidelines. Proprotein convertase subtilisin/kexin type9 inhibitors are promising but expensive and their use in KT is still limited.Expert opinion: In KT recipients, statins should be used cautiously. Rather than using high-dose statin in difficult patients, an association with ezetimibe is suggested. While fibrates, niacin, and resins do not play a relevant role due to their erratic efficacy and common side-effects, new lipid-lowering drugs are emerging but their safety and efficacy in KT patients still need to be assessed.

Treatment of dyslipidemia in kidney transplantation

Kidney diseases are expected to become the fifth leading cause of death by 2040. Several physiological failures classified as pre-, intra-, and post-renal factors induce kidney damage. Diabetes, liver pathologies, rhabdomyolysis, and intestinal microbiota have been identified as pre-renal factors, and lithiasis or blood clots in the ureters, prostate cancer, urethral obstructions, prostate elongation, and urinary tract infections are post-renal factors. Additionally, the nephrotoxicity of drugs has been highlighted as a crucial factor inducing kidney injuries. Due to the adverse effects of drugs, it is necessary to point to other alternatives to complement the treatment of these diseases, such as nephroprotective agents. Plants are a wide source of nephroprotective substances and can have beneficial effects in different levels of the physiological pathways which lead to kidney damage. In traditional medicines, plants are used as antioxidants, anti-inflammatories, diuretics, and anticancer agents, among other benefits. However, the mechanism of action of some plants empirically used remains unknown and scientific data are required to support their nephroprotective effects. The present work reviewed the plants with a beneficial effect on kidney diseases. The classification of nephroprotective plants according to the clinical definition of pre-renal, intrinsic, and post-renal factors is proposed to orient their use as complementary treatments.

/pdf/nephroprotective-plants-a-review-on-the-use-in-pre-renal-and-19sx7q2a.pdf

Nephroprotective Plants: A Review on the Use in Pre-Renal and Post-Renal Diseases

Successful kidney transplantation offers patients with end-stage renal disease the greatest likelihood of survival. However, cardiovascular disease poses a major threat to both graft and patient survival in this cohort. Transplant recipients are unique in their accumulation of a wide range of traditional and non-traditional cardiovascular risk factors. Hypertension, diabetes, dyslipidaemia and obesity are highly prevalent in patients with end-stage renal disease. These risk factors persist following transplantation and are often exacerbated by the drugs used for immunosuppression in organ transplantation. Additional transplant-specific factors such as poor graft function and proteinuria are also associated with increased cardiovascular risk. However, these transplant-related factors remain unaccounted for in current cardiovascular risk prediction models, making it challenging to identify transplant recipients with highest risk. With few interventional trials in this area specific to transplant recipients, strategies to reduce cardiovascular risk are largely extrapolated from other populations. Aggressive management of traditional cardiovascular risk factors remains the cornerstone of prevention, though there is also a potential role for selecting immunosuppression regimens to minimise additional cardiovascular injury.

/pdf/cardiovascular-risk-in-renal-transplant-recipients-3quzmwhxvb.pdf

Cardiovascular risk in renal transplant recipients

Alkaline-Encrusted Pyelitis in a Renal Allograft.

Hormone therapy is widely used in prostate cancer. However, studies have raised concerns that hormone therapy, particularly the use of gonadotropin-releasing hormone agonists, could increase the risk of acute kidney injury. Men newly diagnosed with non-metastatic prostate cancer, from 2012 to 2017, were identified from the Scottish Cancer Registry. A matched comparison cohort of prostate cancer-free men was also identified. Hormone therapy use was determined from the Prescribing Information System in Scotland. The primary outcome was hospitalisations with acute kidney injury taken from Scottish hospital records (SMR01) up to June 2019. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for acute kidney injury by hormone therapy use. The prostate cancer cohort contained 10,751 patients followed for 41,997 person years, during which there were 618 hospitalisations with acute kidney injury. Prostate cancer patients had higher rates of acute kidney injury compared with cancer-free controls (adjusted HR = 1.47 95% CI 1.29, 1.69). However, prostate cancer patients currently using hormone therapy (adjusted HR = 1.14 95% CI 0.92, 1.41), including gonadotropin-releasing hormone (GnRH) agonists (adjusted HR = 1.13 95% CI 0.90, 1.40), did not appear to have a marked increase in acute kidney injury compared with prostate cancer patients not using hormone therapy after adjusting for potential confounders. In our cohort, there was little evidence that gonadotropin-releasing hormone agonists were associated with marked increases in acute kidney injury.

/pdf/hormone-therapy-use-and-the-risk-of-acute-kidney-injury-in-23283ck889.pdf

Hormone therapy use and the risk of acute kidney injury in patients with prostate cancer: a population-based cohort study.

Soluble ST2 is a novel biomarker of myocardial fibrosis with an established role in prognostication of patients with heart failure. Its role in cardiovascular risk prediction for renal transplant recipients has not been investigated despite promising results for ST2 in other populations with renal disease. In this prospective cohort study, 367 renal transplant recipients were followed up for a median of 16.2 years to investigate the association of soluble ST2 concentration with all-cause mortality. Cardiovascular mortality and major adverse cardiovascular events were secondary outcomes. Cox regression models were used to calculate hazard ratios and 95% confidence intervals for ST2 before and after adjustments. ST2 concentration was analysed both as a continuous variable and following categorisation according to the recommended cut-point of 35 ng/ml. A twofold higher ST2 concentration was associated with a 36% increased risk of all-cause mortality after adjustment for conventional cardiovascular risk factors and high-sensitivity C-reactive protein (adjusted hazard ratio 1.36; 95% confidence interval 1.06–1.75; p = 0.016). Associations with ST2 concentration were similar for cardiovascular events (adjusted hazard ratio 1.31; 95% confidence interval 1.00–1.73; p = 0.054), but were stronger for cardiovascular mortality (adjusted hazard ratio 1.61; 95% confidence interval 1.07–2.41; p = 0.022). Addition of ST2 to risk prediction models for mortality and cardiovascular events failed to improve their predictive accuracy. ST2 is associated with, but does not improve prediction of, adverse outcomes in renal transplant recipients.

https://pureadmin.qub.ac.uk/ws/files/217206291/Soluble.pdf

Association of soluble ST2 with all-cause and cardiovascular mortality in renal transplant recipients: a single-centre cohort study

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Cardiovascular risk in renal transplant recipients

Alkaline-Encrusted Pyelitis in a Renal Allograft.

Hormone therapy use and the risk of acute kidney injury in patients with prostate cancer: a population-based cohort study.

Association of soluble ST2 with all-cause and cardiovascular mortality in renal transplant recipients: a single-centre cohort study