Long-term cardio-vascular risk assessment in chronic kidney disease and kidney transplanted patients following SARS-COV-2 disease: protocol for multi-center observational match controlled trial.

BACKGROUND: The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced a pandemic since March 2020 by affecting more than 243 million people with more than 5 million deaths globally. SARS-CoV-2 infection is produced by binding to angiotensin-converting enzyme, which among other sites is highly expressed in the endothelial cells of the blood vessels, pericytes and the heart, as well as in renal podocytes and proximal tubular epithelial cells. SARS-CoV-2 and cardiovascular disease (CVD) are interconnected by risk factors association with an increased incidence of the disease and by determining de novo cardiac complications. At the same time, COVID-19 disease can lead to acute kidney injury directly, or due to sepsis, multi-organ failure and shock. Therefore, the pre-existence of both CVD and chronic kidney disease (CKD) is linked with a higher risk of severe disease and worse prognosis. METHODS: The main aim of this study is to assess the CV risk in a CKD (stage 3 to 5), dialysis and kidney transplanted population, following SARS-CoV-2 infection, with focus on the endothelial dysfunction as compared to a control group of matched patients. By using clinical evaluation, flow-mediated dilatation, carotid-femoral pulse wave velocity, intima-media thickness, echocardiographic parameters, lung ultrasound, bioimpedance spectroscopy and a series of novel biomarkers, the investigators will determine the long-term impact of this disease on CV and renal outcomes. DISCUSSION: This study will address the challenges and implications in long-term CV sequeale of COVID-19 and focus on a better understanding of the underlying mechanisms and possible therapeutic options. TRIAL REGISTRATION: Patient enrolment in the trial started in January 2021 and is expected to finish at the end of 2022. The study can be found on ClinicalTrials.gov database with NCT05125913 identifier. Registered on 18 November 2021 - Retrospectively registered.

Different aspects of frailty and COVID-19: points to consider in the current pandemic and future ones.

BACKGROUND: Older adults at a higher risk of adverse outcomes and mortality if they get infected with Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). These undesired outcomes are because ageing is associated with other conditions like multimorbidity, frailty and disability. This paper describes the impact of frailty on coronavirus disease 2019 (COVID-19) management and outcomes. We also try to point out the role of inflamm-ageing, immunosenescence and reduced microbiota diversity in developing a severe form of COVID-19 and a different response to COVID-19 vaccination among older frail adults. Additionally, we attempt to highlight the impact of frailty on intensive care unit (ICU) outcomes, and hence, the rationale behind using frailty as an exclusion criterion for critical care admission. Similarly, the importance of using a time-saving, validated, sensitive, and user-friendly tool for frailty screening in an acute setting as COVID-19 triage. We performed a narrative review. Publications from 1990 to March 2021 were identified by searching the electronic databases MEDLINE, CINAHL and SCOPUS. Based on this search, we have found that in older frail adults, many mechanisms contribute to the severity of COVID-19, particularly cytokine storm; those mechanisms include lower immunological capacity and status of ongoing chronic inflammation and reduced gut microbiota diversity. Higher degrees of frailty were associated with poor outcomes and higher mortality rates during and after ICU admission. Also, the response to COVID-19 vaccination among frail older adults might differ from the general population regarding effectiveness and side effects. Researches also had shown that there are many tools for identifying frailty in an acute setting that could be used in COVID-19 triage, and before ICU admission, the clinical frailty scale (CFS) was the most recommended tool. CONCLUSION: Older frail adults have a pre-existing immunopathological base that puts them at a higher risk of undesired outcomes and mortality due to COVID-19 and poor response to COVID-19 vaccination. Also, their admission in ICU should depend on their degree of frailty rather than their chronological age, which is better to be screened using the CFS.

Magnesium supplementation: A consideration in dialysis patients.

Even though disorders of magnesium (Mg) balance are common in dialyzed patients, this cation is often neglected. Many factors interfere with serum magnesium including diet, medications (eg, antacids or phosphate binders), and the dialysis prescription. Mg supplementation may help reduce serum phosphate concentration, PTH, and interfere with vascular calcification and bone mineralization. It could also decrease the all-cause and cardiovascular mortalities, although the results of current studies are conflicting. As with many other variables that influence hard endpoints in nephrology, additional research directly targeting the role of Mg supplementation in dialyzed patients are required. Nevertheless, a current risk/benefit assessment suggests that supplementation of Mg targeting high normal serum levels may represent a plausible option to improve the outcome of dialysis patients.

Bioimpedance-guided fluid management in maintenance hemodialysis: a pilot randomized controlled trial.

BACKGROUND: Chronic subclinical volume overload happens very frequently in hemodialysis patients and is associated directly with hypertension, increased arterial stiffness, left ventricular hypertrophy, and ultimately higher mortality. STUDY DESIGN: Randomized controlled parallel-group trial. SETTING & PARTICIPANTS: 131 patients from one hemodialysis center, randomly assigned into 2 groups. INTERVENTION: Dry weight prescription using results derived from repeated 3-month bioimpedance measurements to guide ultrafiltration for strict volume control (bioimpedance group; n=62) compared with clinical judgment without bioimpedance measures (clinical-methods group; n=69) for 2.5 years. OUTCOMES: The primary outcome was all-cause mortality over 2.5 years (the duration of the intervention). Secondary outcomes were change in relative arterial stiffness, fluid overload, and blood pressure (BP) over 2.5 years. MEASUREMENTS: Bioimpedance measurements were performed using a Body Composition Monitor device. Pulse wave velocity analysis was performed at baseline, 2.5 years (end of intervention), and 3.5 years (end of study). Relative fluid overload and BP were assessed at 3-month intervals. RESULTS: The unadjusted HR for all-cause death in the bioimpedance group (vs the clinical-methods group) was 0.100 (95% CI, 0.013-0.805; P=0.03). After 2.5 years, we found a greater decline in arterial stiffness, relative fluid overload, and systolic BP in the bioimpedance group than the clinical-methods group. Between-group differences in change from baseline to the end of intervention were -2.78 (95% CI, -3.75 to 1.80)m/s for pulse wave velocity (P<0.001), -2.99% (95% CI, -5.00% to -0.89%) for relative fluid overload (P=0.05), and -2.43 (95% CI, -7.70 to 2.84)mmHg for systolic BP (P=0.4). LIMITATIONS: Echocardiography was not performed as cardiovascular assessment and the caregivers were not masked to the intervention. CONCLUSIONS: Our study showed improvement in both surrogate and hard end points after strict volume control using bioimpedance to guide dry weight adjustment. These findings need to be confirmed in a larger trial.

Superior predictive value for NTproBNP compared with high sensitivity cTnT in dialysis patients: a pilot prospective observational study.

BACKGROUND/AIMS: The clinical utility of the new biomarker, high sensitivity cardiac T troponin (hs-cTnT) is still unclear in dialysis patients. Furthermore, the prognostic value of combining N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and hs-cTnT has not been explored so far. The objective of this pilot study was to determine the utility of hs-cTnT alone versus hs-cTnT in combination with NT-proBNP for predicting death in a stable hemodialysis cohort. METHODS: A prospective observational pilot study including 98 chronic asymptomatic hemodialysis patients with a follow up period of 24 months was designed. The cut-off values for NT-proBNP and hs-cTnT were calculated using receiver operating characteristic (ROC) analysis, using mortality as an end-point. Based on the cut-off values, the cohort was divided into four groups. Group 1--NT-proBNP < 14275 pg/ml and hs-cTnT < 69.48 ng/l; group 2--NT-proBNP < 14275 pg/ml and hs-cTnT > 69.48 ng/l; group 3--NT-proBNP > 14275 pg/ml and hs-cTnT < 69.48 ng/l; group 4--NT-proBNP > 14275 pg/ml and hs-cTnT > 69.48 ng/l. Survival for each group was determined using the Kaplan-Meier method and Cox regression analysis. RESULTS: During the follow-up period 16 patients died. According to the ROC curves analysis, the cut-off point for hs-cTnT and for NT-proBNP were 69.43 ng/l (AUC = 0.618; p = 0.04) and 14275 pg/ml (AUC = 0.722; p = 0.003), respectively. In univariate Cox analysis, both hs-cTnT (HR = 3.34; p = 0.016) and NT-proBNP (HR = 5.94; p = 0.01) were predictors of death. In the multivariable Cox proportional hazards model, only NT-pro-BNP levels above the cut-off value remained an independent predictor of all-cause mortality. The combined elevation of both biomarkers did not improve significantly the prognostic value compared with NT-proBNP alone (HR = 6.15 versus HR =4 .78; p = 0.338). CONCLUSION: NT-pro-BNP is a strong predictor of overall mortality in asymptomatic hemodialysis patients. The addition of hs-cTnT did not improve the prognostic accuracy compared with NT proBNP alone.

Predicting mortality in haemodialysis patients: a comparison between lung ultrasonography, bioimpedance data and echocardiography parameters.

BACKGROUND: The use of lung ultrasonography to evaluate extravascular lung water and its consequences has received growing attention in different clinical areas, including, in recent years, end-stage renal disease patients treated by haemodialysis (HD). Lung congestion is a direct consequence of either overall overhydration and/or cardiac dysfunction, but the exact contribution of each of these tests to mortality is unknown. METHODS: In this prospective observational study, we enrolled 96 patients from a single HD unit undergoing thrice weekly HD. We used three different methods of evaluation: lung ultrasonography (pre- and post-dialysis), bioimpedance spectroscopy (pre- and post-dialysis) and echocardiography (pre-dialysis). The objective of the study was to test for the first time the prognostic value of ultrasound lung comets (ULC) combined with bioimpedance-derived data [total body water (TBW), extravascular water, hydration status-ΔHS] and several echocardiographic parameters. Mortality was analysed after a median of 405.5-day follow-up. RESULTS: Pre-dialysis lung congestion was classified as moderate (ULC = 16-30) in 19.8% of the patients and severe in 12.5% of patients (ULC > 30), while only 19.8% appear to be hyperhydrated (ΔHS > 15%). The pre-dialysis ultrasound lung congestion score correlated significantly with all of the bioimpedance-derived parameters. In a multivariate Cox model that included ULC score, demographic, ecocardiographic and bioimpedance parameters, the factors that remained significantly associated with survival time were the pre-dialysis ULC score and left ventricular mass index. The pre-HD ULC score has a significant discriminating power for survival, while the bioimpedance-derived hydration status has no discriminatory abilities in terms of survival. CONCLUSIONS: To our knowledge, this study is the first one that compares three different strategies to predict mortality in haemodialysed patients. The lung comet score emerged as the best predictor for the relationship hydration status-mortality, independently of bioimpedance-derived parameters in this population.

Cisplatin and AKI: an ongoing battle with new perspectives-a narrative review.

Acute kidney injury (AKI) is a growing global health problem with increased mortality and morbidity. Cisplatin is achemotherapy drug first introduced in 1978, and since then, it became one of the most widely used and successful anti-cancer medication. However, there are risks associated with cisplatin administration, such as nephrotoxicity. Mechanisms of nephrotoxicity include proximal tubular injury, DNA damage, apoptosis, inflammation, oxidative stress, and vascular injury. Although various protocols are being used in clinical practice in nephrotoxicity prevention due to cisplatin, there are no clear guidelines regarding this approach. Most recommendations include hydration and avoiding additional nephrotoxic drugs. To prevent nephrotoxicity, future perspectives could rely on natural products, such as flavonoids or saponins or pharmacological products, such as aprepitant, but data are scarce in this direction. Repetitive administration of cisplatin could cause subclinical kidney injury, which over time, leads to chronic kidney disease (CKD). Therefore, more studies are needed to determine possible ways to prevent nephrotoxicity and avoid the burden of CKD worldwide.

Relationship between serum magnesium levels and cardiovascular events in chronic kidney disease patients.

BACKGROUND: Magnesium is an essential ion for all living cells because over 300 enzymes require the presence of magnesium for their catalytic action. To date, no group has evaluated magnesium as a cardiovascular risk factor in chronic kidney disease (CKD) subjects, in which closely interrelated factors and potential confounders such as endothelial dysfunction, insulin resistance (the homeostasis model assessment (HOMA) index) and inflammation (expressed as serum C-reactive protein (CRP) levels) were also considered. METHODS: Between March 2006 and December 2010, 283 CKD patients were followed up for time-to-event analysis until the occurrence of fatal or nonfatal cardiovascular events. Endothelium-dependent vasodilatation (flow-mediated dilatation; FMD) and endothelium-independent vasodilatation (nitroglycerin-mediated dilatation) of the brachial artery were assessed noninvasively using high-resolution ultrasound. RESULTS: From the univariate analysis of FMD, it appears that a higher magnesium level is associated with less endothelial dysfunction. When a multivariate analysis was performed, magnesium and estimated glomerular filtration rates (eGFR) maintained a strong positive correlation with FMD, supporting the hypothesis that higher levels of magnesium may protect against endothelial damage. In univariate Cox proportional hazards models, FMD, magnesium, high sensitivity CRP, the HOMA index, eGFR, comorbid diabetes, hypertension, smoking status, systolic blood pressure, serum phosphate and intact parathormone emerged as significant predictors for cardiovascular outcomes. Kaplan-Meier curves showed significantly higher cardiovascular mortality rates in CKD patients whose serum magnesium levels were below 2.05 mg/dl. CONCLUSIONS: This observational cohort study showed that magnesium may be an independent predictor of future cardiovascular outcomes and is the first study demonstrating such a role in etiologically diagnosed CKD patients, across different stages.

Revisiting risk prediction tools for death and end-stage renal disease in older patients with advanced chronic kidney disease: a prospective study.

BACKGROUND: Risk assessment tools for predicting mortality and end-stage renal disease (ESRD) in the elderly with CKD have received growing attention. However, integrating risk equations into a multidimensional approach of elderly with CKD stage 3b-4 is lacking. METHODS: In this prospective observational study, we enrolled CKD stage 3b-4 patients aged ≥ 65 years. Bansal score for predicting mortality risk and Kidney Failure Risk Equation (KFRE) for estimating progression to ESRD were applied. Predicted outcome was compared with actual clinical end-points. All patients underwent comprehensive geriatric assessment (CGA), which is an interdisciplinary multidimensional process for geriatric evaluation and management. RESULTS: Participants (N = 184) were divided into two groups, according to Bansal score: Group 1 (low-risk of death, Bansal score < 7, N = 69) and Group 2 (high-risk of death, Bansal score ≥ 7, N = 115). Group 2 displayed a substantially higher cardiovascular disease burden than Group 1 and was significantly more likely to be depressed and at risk of malnutrition, according to CGA. Thirty-seven patients died, and 16 started dialysis. Group 2 displayed significantly higher all-cause mortality. In the univariable Cox regression, Group 2 had a fourfold increase in the risk of all-cause mortality, as compared with Group 1 (HR = 4.29, 95% CI 1.88-10.26, P < 0.001). Multivariable stepwise Cox analysis showed that Bansal score above 7 remained significantly associated with all-cause mortality (HR = 3.96, 95% CI 1.68-9.29, P < 0.001). Group 2 also displayed higher event rates for dialysis initiation. In Group 1, only four patients started dialysis, and three out of them had a high-risk of progression at baseline, according to KFRE. CONCLUSIONS: Using risk stratification tools and CGA in a population of elderly with advanced CKD, we found that two-thirds of the patients were at high risk of death, malnutrition and depression, with multimorbidity and four times worse probability of survival than those at lower risk of death.

Evaluation of cardiovascular events and progression to end-stage renal disease in patients with dyslipidemia and chronic kidney disease from the North-Eastern area of Romania.

PURPOSE: The aim of this prospective cohort study was: to identify the association between different biomarkers [proprotein convertase subtilisin/kexin 9-PCSK9, lipoprotein(a)-Lp(a) and high-sensitivity C-reactive protein-hsCRP] and the cardiovascular events; to evaluate the relationship between the 3 biomarkers mentioned above and the renal outcomes that contributed to end-stage renal disease (ESRD). METHODS: We studied 110 patients with chronic kidney disease (CKD) stages 2 to 4. The identification of the new cardiovascular events and the renal outcomes were performed by clinical and paraclinical explorations. RESULTS: 350 patients were examined and 110 (31.4%) were included in this study. The mean age was 55.6 ± 10.9 years, with a higher number of men compared to women. The CKD patients with de novo cardiovascular events and new renal outcome during the study, had significantly increased values of total cholesterol (TC), low density cholesterol lipoprotein (LDL-C) at 6 and 12 months and higher levels of Lp(a), PCSK9, hsCRP and low ankle-brachial index (ABI) and ejection fraction (EF) values compared to patients without cardiovascular and renal events. In CKD patients, PCSK9 > 220 ng/mL was a predictor of cardiovascular events, while the EF < 50% was a predictor for renal outcomes. For CKD patients with PCSK9 > 220 ng/mL and hsCRP > 3 mg/L levels, the time-interval for the new cardiovascular and renal events occurrence were significantly decreased compared to patients displaying low values of these biomarkers. CONCLUSION: The results of this study show that PCSK9 > 220 ng/mL was predictor for cardiovascular events, while EF < 50% was predictor for CKD progression to ESRD. PCSK9 > 220 ng/mL and hsCRP > 3 mg/L were associated with the occurrence of renal and cardiovascular events earlier.

Nutrition in Chronic Kidney Disease-The Role of Proteins and Specific Diets.

Chronic kidney disease (CKD) is a global public health burden, needing comprehensive management for preventing and delaying the progression to advanced CKD. The role of nutritional therapy as a strategy to slow CKD progression and uremia has been recommended for more than a century. Although a consistent body of evidence suggest a benefit of protein restriction therapy, patients' adherence and compliance have to be considered when prescribing nutritional therapy in advanced CKD patients. Therefore, these prescriptions need to be individualized since some patients may prefer to enjoy their food without restriction, despite knowing the potential importance of dietary therapy in reducing uremic manifestations, maintaining protein-energy status.

Health-related quality of life in patients with chronic kidney disease.

Introduction: In the last three decades, health systems have continued to pay increasing attention to the quality of life (QOL) due to definitional changes in the concept of health and disease. The health-related quality of life (HRQOL) in patients with chronic kidney disease (CKD) is significantly affected, regardless of the stage of CKD. Areas covered: We attempt to thoroughly explore how CKD affects HRQOL domains with a quick primer on HRQOL assessment instruments in patients with CKD. Also, we pointed out the factors affecting HRQOL in patients with CKD as well as the clinical application of HRQOL in CKD management. Expert opinion: The general population enjoys higher HRQOL than patients with CKD in all domains. Similarly, pre-dialysis and kidney-transplant patients have better HRQOL than dialysis population. There are many factors which negatively impact HRQOL in CKD which include for example depression, anxiety, and cognitive impairment for the social domain, inactivity, and frailty for the physical domain as well as lack of social support and extroversion in the social domain. Additionally, social disparities and CKD-related factors would influence HRQOL. Of note, there is no global standard HRQOL assessment tool. Finally, HRQOL should be included in future CKD management guidelines.

A brand-new cardiorenal syndrome in the COVID-19 setting.

Coronaviruses are a major pathogen for adults, causing up to one-third of community-acquired respiratory tract infections in adults during epidemics. Although the pandemic outbreak of coronavirus disease-2019 (COVID-19) targets preferentially patient's lungs, recent data have documented that COVID-19 causes myocarditis, acute myocardial infarction, exacerbation of heart failure and acute kidney injury. Studies show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to its predecessor SARS-CoV, engages angiotensin-converting enzyme 2 (ACE2) as the entry receptor. ACE2 is also expressed in the heart, providing a link between coronaviruses and the cardiovascular system.

Evaluation of low-dose glucocorticoid regimen in association with cyclophosphamide in patients with glomerulonephritis.

BACKGROUND: The treatment of most glomerulonephritides is still based on a combination of an oral corticosteroid and an alkylating agent, with favorable outcomes, but with serious side effects. The objective of this study was to reduce the cumulative corticosteroid dose in patients with high risk of corticosteroid-related adverse events by replacing daily oral corticosteroids with intravenous (iv) methylprednisolone pulses, associated with monthly pulse i.v. cyclophosphamide (according to KDIGO guidelines) in patients with glomerulonephritis. METHODS: This was a retrospective cohort study conducted at a single nephrology centre. In the course of a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5 g per day at the end of these 6 months, received a combination of corticosteroids and cyclophosphamide. Patients were divided in two groups: group 1 (23 patients)-included patients with high risk of corticosteroid-related adverse events received monthly methylprednisolone 1 g/day, 3 days and i.v. cyclophosphamide for 6 months, and group 2 (84 patients)-received oral corticosteroids (as per KDIGO recommended dose) and i.v. cyclophosphamide. The primary outcome-time to a combined end-point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission [proteinuria < 0.3 g per 24 h (urinary protein-creatinine rate < 300 mg/g [< 30 mg/mmol]]; partial remission (proteinuria > 0.3 but < 3.5 g per 24 h or a decrease in proteinuria by at least 50% from the initial value) and adverse events. RESULTS: At 6 months, there was no difference in the primary composite end-point: 8.7% patients from the group 1 and 20.2% patients from the group 2 (P = 0.199) reached this end-point. Similar data were also recorded at 12 months. Secondary end-points were also similar between treatment groups. More patients receiving oral corticosteroids experienced infections, but without statistical significance. CONCLUSION: Our data indicate that low i.v. dose corticosteroids and cyclophosphamide administered monthly in patients with high risk of corticosteroid-related adverse events and primary glomerulonephritis are equally effective, with fewer metabolic disorders and infections.

Prospective Validation of a Screening Biomarker Approach Combining Amino-Terminal Pro-Brain Natriuretic Peptide With Galectin-3 Predicts Death and Cardiovascular Events in Asymptomatic Hemodialysis Patients.

Cardiovascular (CV) disease is a major cause of death in hemodialysis patients. Biomarkers used to identify high-risk asymptomatic patients would allow early evaluation of cardiac dysfunction and appropriate therapeutic intervention. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 (Gal-3) may serve this purpose. Plasma levels of NT-proBNP and Gal-3 were measured in 173 patients. Patients were prospectively followed for occurrences of major CV events or death. The association of NT-proBNP and Gal-3 with outcome was analyzed. The prognostic abilities for the combined outcome of Gal-3 and/or NT-proBNP were evaluated. During a median follow-up of 36 months, there were 47 incident outcomes (death and CV events). In the univariable Cox analysis, age, hypertension, albumin, phosphorus levels, and combined elevation of NT-proBNP with Gal-3 above the median (hazard ratio [HR] = 3.65, 95% confidence interval [CI] = 1.45-9.21) were associated with outcomes. In multivariable Cox analysis, both NT-proBNP and Gal-3 values above the median remained associated with outcomes (HR = 3.34, 95% CI = 1.30-8.56). In clinically asymptomatic dialysis patients, combined use of NT-proBNP and Gal-3 may improve risk stratification for death and CV events.

Bone and mineral disorders in chronic kidney disease: implications for cardiovascular health and ageing in the general population.

The patient with chronic kidney disease (CKD) represents an extreme model for arteriosclerosis, vascular calcification, and bone disorders, all of which are also associated with ageing in the general population. These pathological features are also relevant to other common chronic health disorders such as diabetes, and chronic inflammatory and cardiovascular diseases. Although management and interventions for these major risk factors are now incorporated into most public health guidelines (eg, smoking cessation and control of bodyweight and blood pressure, as well as glucose and cholesterol concentrations), some residual cardiovascular risk is not reduced by implementation of these interventions. CKD should be regarded as an atypical disease in which both traditional and novel cardiovascular risk factors have effects on outcomes. But CKD can also be viewed conceptually as an accelerator of traditional cardiovascular risk factors. Findings from research into mineral bone disorder associated with CKD (CKD-MBD) could help the medical community to better understand the vascular actions of certain molecules, such as phosphates, fibroblast growth factor 23, parathyroid hormone, sclerostin, or vitamin D and their relevance to the management of different pathologies in the general population. Importantly, these components, which are recognised in nephrology, could help to explain residual risk of cardiovascular events in the general population. Thus, achieving a better understanding of CKD-MBDs could provide substantial insight into future treatments for arteriosclerosis and osteoporosis, which are strongly associated with ageing and morbidity in the general population.

Impact of surgical parathyroidectomy on chronic kidney disease-mineral and bone disorder (CKD-MBD) - A systematic review and meta-analysis.

For more than 6 decades, many patients with advanced chronic kidney disease (CKD) have undergone surgical parathyroidectomy (sPTX) for severe secondary hyperparathyroidism (SHPT) mainly based historical clinical practice patterns, but not on evidence of outcome.We aimed in this meta-analysis to evaluate the benefits and harms of sPTX in patients with SHPT. We searched MEDLINE (inception to October 2016), EMBASE and Cochrane Library (through Issue 10 of 12, October 2016) and website clinicaltrials.gov (October 2016) without language restriction. Eligible studies evaluated patients reduced glomerular filtration rate (GFR), below 60 mL/min/1.73 m2 (CKD 3-5 stages) with hyperparathyroidism who underwent sPTX. Reviewers working independently and in duplicate extracted data and assessed the risk of bias. The final analysis included 15 cohort studies, comprising 24,048 participants. Compared with standard treatment, sPTX significantly decreased all-cause mortality (RR 0.74 [95% CI, 0.66 to 0.83]) in End Stage Kidney Disease (ESKD) patients with biochemical and / or clinical evidence of SHPT. sPTX was also associated with decreased cardiovascular mortality (RR 0.59 [95% CI, 0.46 to 0.76]) in 6 observational studies that included almost 10,000 patients. The available evidence, mostly observational, is at moderate risk of bias, and limited by indirect comparisons and inconsistency in reporting for some outcomes (eg. short term adverse events, including documented voice change or episodes of severe hypocalcaemia needing admission or long-term adverse events, including undetectable PTH levels, risk of fractures etc.). Taken together, the results of this meta-analysis would suggest a clinically significant beneficial effect of sPTX on all-cause and cardiovascular mortality in CKD patients with SHPT. However, given the observational nature of the included studies, the case for a properly conducted, independent randomised controlled trial comparing surgery with medical therapy and featuring many different outcomes from mortality to quality of life (QoL) is now very strong.

Dry weight assessment by combined ultrasound and bioimpedance monitoring in low cardiovascular risk hemodialysis patients: a randomized controlled trial.

PURPOSE: Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients. The precise assessment of hydration status in HD patients remains a major challenge for nephrologists. Our study aimed to explore whether combining two bedside methods, lung ultrasonography (LUS) and bioimpedance, may provide complementary information to guide treatment in specific HD patients. METHODS: In total, 250 HD patients from two dialysis units were included in this randomized clinical trial. Patients were randomized 1:1 to have a dry weight assessment based on clinical (control) or LUS with bioimpedance in case of clinical hypovolemia (active)-guided protocol. The primary outcome was to assess the difference between the two groups on a composite of all-cause mortality and first cardiovascular event (CVE)-including death, stroke, and myocardial infarction. RESULTS: During a mean follow-up period was 21.3 ± 5.6 months, there were 54 (21.6%) composite events in the entire population. There was a nonsignificant 9% increase in the risk of this outcome in the active arm (HR = 1.09, 95% CI 0.64-1.86, p = 0.75). Similarly, there were no differences between the two groups when analyzing separately the all-cause mortality and CVE outcomes. However, patients in the active arm had a 19% lower relative risk of pre-dialytic dyspnea (rate ratio-0.81, 95% CI 0.68-0.96), but a 26% higher relative risk of intradialytic cramps (rate ratio-1.26, 95% CI 1.16-1.37). CONCLUSIONS: This study shows that a LUS-bioimpedance-guided dry weight adjustment protocol, as compared to clinical evaluation, does not reduce all-cause mortality and/or CVE in HD patients. A fluid management protocol based on bioimpedance with LUS on indication might be a better strategy.