Severe Chronic Kidney Disease Research Articles

An Updated Review of the Management of Chronic Heart Failure in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is common in patients with heart failure (HF) and is associated with high morbidity and mortality. There has been remarkable progress in the treatment of HF over recent years with the establishment of guideline-directed medical therapies including: (1) Beta-blockers, (2) renal angiotensin aldosterone system (RAAS) inhibition (i.e., angiotensin-converting enzyme inhibitor [ACEi], aldosterone receptor blocker [ARB] or angiotensin receptor-neprilysin inhibitor [ARNI]); (3) mineralocorticoid receptor antagonists (MRA), and (4) sodium-glucose cotransporter-2 inhibitors (SGLT2i). However, there are challenges to the implementation of these medications in patients with concomitant CKD due to increased vulnerability to common side-effects (including worsening renal function, hyperkalaemia, hypotension), and most of the pivotal trials which provide evidence of the efficacy of these medications excluded patients with severe CKD. Patients with CKD and HF often have regular healthcare encounters with multiple professionals and can receive conflicting guidance regarding their medication. Thus, despite being at higher risk of adverse cardiovascular events, patients who have both HF and CKD are more likely to be under-optimised on evidence-based therapies. This review is an updated summary of the evidence available for the management of HF (including reduced, mildly reduced and preserved left ventricular ejection fraction) in patients with various stages of CKD. The review covers the evidence for recommended medications, devices such as implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy (CRT), intravenous (IV) iron, and discusses how frailty affects the management of these patients. It also considers emerging evidence for the prevention of HF in the cohort of patients with CKD. It synthesises the available evidence regarding when to temporarily stop, continue or rechallenge medications in this cohort. Chronic HF in context of CKD remains a challenging scenario for clinicians to manage, which is usually complicated by frailty, multimorbidity and polypharmacy. Treatment should be tailored to a patients individual needs and management in specialised cardio-renal clinics with a multi-disciplinary team approach has been recommended. This review offers a concise summary on this expansive topic.

Moderate and Severe Chronic Kidney Disease Predict Greater 5-Year Mortality following Major Lower-Extremity Amputation

Severe Chronic Kidney Disease (CKD) predicts greater mortality after major lower extremity amputation (LEA), but it remains poorly understood whether patients with earlier stages of CKD share similar risk. We assessed long-term postoperative outcomes for patients with CKD in a retrospective chart review of 565 patients who underwent atraumatic major LEA at a large tertiary referral center from 2015 to 2021. We stratified patients by renal function and compared outcomes including survival. Preoperative CKD diagnosis was related to many patient characteristics, co-occurred with many comorbidities, and was associated with less follow-up and survival. Kaplan-Meier and Cox Regression analyses showed significantly worse 5-year survival for major LEA patients with mild, moderate, or severe CKD compared to major LEA patients with no history of CKD at the time of amputation (P < 0.001). Severe CKD independently predicted worse mortality at 1-year (odds ratio [OR] 2.91; P = 0.003) and 5-years (OR 3.08; P < 0.001). Moderate CKD independently predicted worse 5-year mortality (OR 2.66; P = 0.029). This study demonstrates that moderate and severe CKD predict greater long-term mortality following major LEA when controlling for numerous potential confounders. This finding raises questions about the underlying mechanism if causal and highlights an opportunity to improve outcomes with earlier recognition and optimization CKD preoperatively.

Does Donor Age Have Effects on Senescence Biomarkers in Kidney-Transplanted Patients?

Renal transplantation is an effective treatment for severe chronic kidney diseases. However, young patients often face a scarcity of kidneys from donors of similar age, resulting in the transplantation of older organs, which increase the risk of graft rejection and several complications compared with older individuals who receive kidneys from donors of similar age or younger. This article focuses on studying different senescence biomarkers in donors and patients who received kidneys from various age ranges complying with the STROBE requirements. We studied 61 patients subjected to renal transplant isolating blood samples 24 h before, and 24 h, 3 days, 7 days, 3 months, and 6 months after transplant. The patients were divided into three groups: older donor than the patient (Old Donor), younger donor than the patient (Young Donor), and similar age (Matched). We studied different senescence markers such as p16, p21, interleukin 6 (IL-6), and senescence-associated secretory phenotype (SASP) release. Young patients who receive older organs showed increased mRNA and protein expression of the senescence makers. Hence, increased SASP release was also observed in patients from older donor. In contrast, older patients who receive younger organs showed a slow but consistent improvement in their initial senescent phenotype. In addition, macrophage cell model treated with blood-derived serum from patients 6 months after the transplant showed a pro-senescence environment in macrophages proposed by the SASP from the patients. These results lead the hypothesis that senolytics could reduce the presence of senescent cells and mitigate the complications associated with the transplantation of older organs in young patients.

The Role of Comorbidities in Predicting Functional Improvement After Transcatheter Aortic Valve Implantation

Patients undergoing transcatheter aortic valve implantation (TAVI) have a high comorbidity burden. We sought to stratify patients into functional outcomes using the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), a patient-reported outcome with benefits over both the New York Heart Association (NYHA) classification and the original 23-item KCCQ, and to evaluate the importance of comorbidities in predicting failure of functional improvement post-TAVI in a contemporary cohort. In total, 366 patients with severe aortic stenosis undergoing TAVI with baseline KCCQ-12 were retrospectively analysed and divided into two groups. Failure to improve was defined as a score <60 and a change in score <10 at 1 year in either overall score (KCCQ-OS) or clinical summary score (KCCQ-CSS). Failure to improve was noted in 13% of patients, who were more likely to have lower KCCQ-OS at baseline (47 [35-59] vs 56 [42-74]), chronic obstructive pulmonary disease (COPD) (19% vs 8%), severe chronic kidney disease (CKD) (13% vs 2%), a clinical frailty score (CFS) ≥5 (41% vs 14%), and lower serum albumin (36 g/L [34-38] vs 38 g/L [35-40]). On multivariate analysis, with an area under the curve of 0.71 (0.63-0.78), baseline KCCQ-OS (adjusted odds ratio [aOR] 0.3 [0.1-0.6], p=0.04), COPD (aOR 2.8 [1.2-6.5], p=0.02), and severe CKD (aOR 5.7 [1.7-18.5], p=0.004) remained independent predictors. CFS alone had a similar predictive value as the multivariable model (OR 2.0 [1.3-3.4], area under the curve 0.69 [0.59-0.80], p<0.001). KCCQ scores were effective in delineating functional outcomes, with most patients in our relatively lower surgical risk cohort showing significant functional improvements post-TAVI. Low baseline KCCQ, moderate or worse COPD, and severe CKD were associated with failure of improvement post-TAVI. Baseline CFS appears to be a good screening tool to predict poor improvement. These factors should be evaluated and weighted accordingly in pre-TAVI assessments and decision-making.

Real-world evidence of constipation and laxative use in the Korean population with chronic kidney disease from a common data model

Constipation is a highly prevalent gastrointestinal disorder in patients with chronic kidney disease (CKD). However, our understanding of its epidemiology and management in CKD is limited. We aimed to explore real-world data on constipation and laxative use in patients with CKD in a nationwide population-based cohort from the Korean Health Insurance Review and Assessment-National Patient Sample database. This study analyzed retrospective health claims data in Korea from 2012 to 2017 that were transformed into the Observational Medical Outcomes Partnership Common Data Model. The pooled proportion of constipation diagnoses was 30.5% in all patients with CKD and 15.9%, 16.5%, 17.4%, 29.9%, and 43.3% in patients with CKD stages 1–5, respectively, suggesting a higher prevalence in advanced CKD. Patients receiving peritoneal dialysis or hemodialysis had the highest prevalence of constipation, while transplant recipients showed a prevalence comparable to that of patients with early CKD. Patients with CKD had a significantly higher risk of constipation than age- and sex-matched non-CKD individuals (range of odds ratio [OR]:1.66–1.90). Laxative prescribing patterns differed by CKD severity. Osmotic agents were prescribed in more than half of patients with advanced CKD, while magnesium salts and bulking agents were prescribed less frequently. The CKD patients with constipation were more likely to be prescribed constipation-inducing medications, including antipsychotic and neurological medications. Our findings provide real-world constipation and laxative prescription status in the Korean CKD population, revealing a significantly higher risk of constipation and different laxative prescribing patterns in patients with CKD.

Dietary Intake of Antioxidant Vitamins and Its Relation to the Progression of Chronic Kidney Disease in Adults With Preserved Renal Function

It is expected that antioxidants contribute to slow the progression of chronic kidney disease (CKD). However, there are no data on the protective effect of dietary antioxidant vitamins on CKD. The purpose of study was to evaluate the renoprotective effect of dietary antioxidant vitamins in the general population. The study participants were 127,081 Korean adults with preserved renal function with estimated glomerular filtration rate ≥60mL/min/1.73m2. They were categorized into 3 groups by tertile levels of dietary antioxidant vitamins intake including vitamins C, E, and A. Cox proportional hazard assumption was used to calculate multivariable hazard ratios and 95% confidence interval for the incident moderate to severe CKD (adjusted hazard ratio [95% confidence interval]) according to tertile levels of dietary intake of antioxidant vitamins. Subgroup analysis was conducted to evaluate the risk of progression from normal to mildly decreased renal function, and from mildly decreased renal function to moderate to severe CKD. The risk of moderate to severe CKD was not significantly associated with the third tertile of dietary antioxidant vitamin intake including vitamin C (1.02 [0.78-1.34]), E (0.96 [0.73-1.27]), and A (0.98 [0.74-1.29]). Additionally, any tertile groups didn't show the significant association with the risk of moderate to severe CKD. Subgroup analysis also didn't show the decreased risk of progression from normal to mildly decreased renal function, and from mildly decreased renal function to moderate to severe CKD in any tertile groups. Dietary intake of vitamins C, E, and A was not significantly associated with the risk of CKD progression.

ASSESSMENT OF COMPLETE BLOOD COUNT AND LIVER ENZYMES IN CHRONIC KIDNEY DISEASE PATIENT

Chronic renal failure (CRF) poses a significant global health challenge, with chronic kidney disease (CKD) characterised by kidney damage or a glomerular filtration rate (GFR) persistently below 60 ml/min for over three months. This observational study, conducted in Faisalabad from January to July 2023, aimed to evaluate haematological variables and liver enzymes across different stages of CKD. Using non-probability purposive sampling, 144 CKD patient files and 48 healthy control files were collected, excluding specific conditions. CKD staging was determined using the Modification of Diet in Renal Disease (MDRD) algorithm, categorizing patients into mild (Group A), moderate (Group B), severe (Group C) CKD, and controls (Group D). Data analysis was performed using SPSS v23. Mean ± SD values were presented for each parameter across the four groups. Haemoglobin levels (Hb g/dl) exhibited a decreasing trend in CKD patients compared to the control group, with values of 13.7 ± 1.50 in controls, 11.7 ± 0.64 in Group 1, 9.7 ± 0.57 in Group 2, and 6.7 ± 1.5 in Group 3. Red blood cell count (RBCs per million/mm3) also decreased progressively in CKD patients compared to controls, with values of 5.48 ± 0.59, 4.62 ± 0.15, 3.57 ± 0.28, and 2.81 ± 0.23 in the respective groups. Conversely, white blood cell counts (WBC thousand/mm3) increased with CKD progression, showing values of 8406 ± 1383 in controls, 10674 ± 1006 in Group 1, 12028 ± 643.5 in Group 2, and 13564 ± 741.29 in Group 3. Similarly, platelet counts (lakh/ul) exhibited a decreasing trend in CKD patients compared to controls, with values of 324708 ± 112970, 235458 ± 63853, 144979 ± 6935.8, and 126333 ± 4768.3, respectively. Analysis of liver enzymes revealed a progressive decrease in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as CKD advanced. AST levels (U/L) decreased from 29.104 ± 3.130 in controls to 7.5825 ± 1.543 in Group 3, while ALT levels (U/L) decreased from 48.145 ± 4.9679 in controls to 12.270 ± 3.3500 in Group 3. Our findings demonstrate that haemoglobin, red blood cell count, platelet count, and liver enzyme levels (AST and ALT) decrease as CKD progresses while white blood cell count increases. These insights into haematological and hepatic biomarkers underscore the dynamic nature of CKD pathology and may inform clinical management strategies.

Cost-effectiveness of sodium zirconium cyclosilicate for advanced chronic kidney patients in Singapore.

Hyperkalaemia (HK) is prevalent among patients with chronic kidney disease (CKD) and chronic heart failure, especially if they are treated with renin-angiotensin-aldosterone system inhibitors (RAASi). This study evaluated the cost-effectiveness of a newly developed anti-HK therapy, sodium zirconium cyclosilicate (SZC), to the current standard of care for treating HK in advanced CKD patients from the Singapore health system perspective. We adapted a global microsimulation model to simulate individual patients' potassium level trajectories with baseline potassium ≥5.5 mmol/L, CKD progression, changes in treatment, and other fatal and non-fatal events. Effectiveness data was derived from ZS-004 and ZS-005 trials. Model parameters were localised using CKD patients' administrative and medical records at the Singapore General Hospital Department of Renal Medicine. We estimated the lifetime cost and quality-adjusted life years (QALYs) of each HK treatment, and the incremental cost-effectiveness ratio of SZC. SZC demonstrated cost-effectiveness with an incremental cost-effectiveness ratsio of SGD 45 068 per QALY over a lifetime horizon, below the willingness-to-pay threshold of SGD 90 000 per QALY. Notably, SZC proved most cost-effective for patients with less severe CKD who were concurrently using RAASi. Sensitivity analyses confirmed the robustness of the findings, accounting for alternative parameter values and statistical uncertainty. This study establishes the cost-effectiveness of SZC as a treatment for HK, highlighting its potential to mitigate the risk of hyperkalaemia and optimise RAASi therapy. These findings emphasise the value of integrating SZC into the Singapore health system for improved patient outcomes and resource allocation.

Hospital complications in patients with acute kidney injury after coronary artery bypass grafting

The aim was to assess the incidence of hospital complications in patients with acute kidney injury (AKI) after coronary artery bypass grafting (CABG).Patients and Methods. The study included 77 patients with stable angina who underwent CABG, aged 65 (61-69) years, 77,9 % men. The number of patients with arterial hypertension was 96,1 %, with carbohydrate metabolism disorders 45,5 %, with chronic kidney disease (CKD) 22,1 %, and with myocardial infarction (MI) 57,1 %. CABG on the working heart was performed in 28,6 %, bimammary CABG in 49,4 %. The duration of artificial circulation was 64 (55-82) minutes; the number of shunts implanted was 2,7+0,7 units. CKD was diagnosed when the glomerular filtration rate was less than 60 ml/min. The development of AKI was assessed according to the KDIGO criteria (2012).Results. CABG related AKI was detected in 10 (13 %) patients, of which grade 1 in 9 (11,7 %), grade 2 in 1 (1,3 %). The indicators associated with AKI after CABG were more severe initial CKD (stages 3b and 4 CKD – 20 % vs 1,5 %, p=0,043), a higher incidence of acute heart failure (in terms of adrenaline requirement – 30 % vs 5,9 %, p=0,043), more occluded coronary arteries (in the groups with and without CABG: one occlusion 70 % and 52,2 %, two occlusions 0 % and 13,4 %, three occlusions 10 % and 0 %, respectively, p=0,028). More severe CKD (stages 3b and 4) statistically significantly increased the relative risk of AKI after CABG by an average of 2,9 times. Among patients with AKI compared to patients without AKI after CABG, there was a higher incidence of cardiac death (20 % vs 0 %, p=0,015), intraoperative MI (60 % vs 8,9 %, p=0,001), acute heart failure (30 % vs 5,9 %, p=0,043).Conclusion. The incidence of AKI following CABG was 13 %. The development of AKI was associated with more severe initial CKD. Patients with postoperative AKI had a poor hospital prognosis.

Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease

IntroductionWith prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function via tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging. ObjectivesTo exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds. MethodsHybrid PMEZ scaffolds incorporating essential bioactive components, such as ricinoleic acid grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) based on biodegradable porous PLGA (P) platform was successfully manufactured. Consecutively, for functional improvements, melatonin-modulated extracellular vesicles (mEVs), derived from the human umbilical cord MSCs in chemically defined media without serum impurities, were also loaded onto PMEZ scaffolds to construct the multiplexed PMEZ/mEV scaffold. ResultsWith functionalities of Mg(OH)2 and extracellular matrix-loaded PLGA scaffolds, the continuous nitric oxide-releasing property of modified ZnO and remarkably upregulated regenerative functionalities of mEVs showed significantly enhanced kidney regenerative activities. Based on these, the structural and functional restoration has been practically achieved in 5/6 nephrectomy mouse models that mimicked severe human CKD. ConclusionOur study has proved the combinatory bioactivities of the biodegradable PLGA-based multiplexed scaffold for kidney tissue regeneration in 5/6 nephrectomy mouse representing a severe CKD model. The optimal microenvironments for the morphogenetic formations of renal tissues and functional restorations have successfully achieved the combinatory bioactivities of remarkable components for PMEZ/mEV, which could be a promising therapeutic alternative for CKD treatment.

Prevalence, patterns, and impacts of multimorbidity on adverse clinical outcomes in chronic kidney disease: A systematic review

Background: Multimorbidity is the concurrent presence of two or more long-term health conditions in the same individual. It fragments healthcare delivery and affects quality of life. Chronic kidney disease (CKD) often occurs with multimorbidity. The prevalence of CKD is rising; however, there is a lack of evidence on the prevalence, patterns, and impacts of multimorbidity on adverse clinical outcomes in patients with CKD.&#x0D; Methods: This was a systematically conducted literature review. A search was conducted in EMBASE, MEDLINE, CINAHL, and SCOPUS (2019-2023). The main search terms were “chronic kidney disease” and “multimorbidity.” The eligibility criteria were observational studies with adult participants with all stages of CKD (CKD stages 1-5, including those on renal replacement therapy). The exposure was multimorbidity quantified by measures. All-cause mortality, kidney disease progression, hospitalisation, and cardiovascular events were outcomes. The Joanna Briggs Institute (JBI) checklist was used for the risk of bias assessment. Due to heterogeneity in design and methods, Jennie Popay’s narrative synthesis was used for data synthesis.&#x0D; Results: Of 6879 papers, nine papers met the inclusion criteria. Most studies included participants with all stages of CKD (CKD stage 1-5). The prevalence of multimorbidity ranged from 86.6% to 99.1%. Hypertension was the most prevalent comorbidity. The combination of concordant multimorbidity (hypertension, diabetes, and cardiovascular diseases) was highly prevalent. Multimorbidity was significantly associated with mortality, cardiovascular events, kidney disease progression, and hospitalisation. While older people had more multimorbidity burdens, younger patients with CKD were at a higher risk of death from multimorbidity. Severe CKD with clusters of cardiovascular diseases, diabetes, chronic pain, and depression was significantly associated with all-cause mortality.&#x0D; Conclusion: There are associations between multimorbidity and adverse clinical outcomes in patients with CKD. However, there is a lack of data on Black, Asian, and Minority Ethnic participants from low- and middle-income countries. Further research is needed to investigate the high prevalence of chronic pain and depression in chronic kidney disease.

Clinical characteristics and long-term outcomes of patients with heart failure with improved ejection fraction. First Polish experience from LECRA-HF registry

PurposeHeart failure (HF) with improved ejection fraction (HFimpEF) is a new category of HF introduced in the newest European Society of Cardiology guidelines. However, clinical characteristics and long-term outcomes of HFimpEF patients remain insufficiently elucidated. We sought to characterize Polish HFimpEF patients and determine their long-term mortality. Material and methodsOf 1186 patients enrolled in the single-center Lesser Poland Cracovian Heart Failure (LECRA-HF) registry between 2009 and 2019 and hospitalized due to HF decompensation, 340 (28.7%) were those with HF with reduced ejection fraction (HFrEF). Based on follow-up echocardiography, 61 (17.9%) of them were classified as HFimpEF and the remaining as HFnon-impEF. ResultsHFimpEF patients were more frequently females (P ​< ​0.001), had higher baseline left ventricular ejection fraction (LVEF, P ​< ​0.001), had less often a history of diabetes (P ​= ​0.024), severe chronic kidney disease (P ​= ​0.026) or prior myocardial infarction (P ​= ​0.008) than HFnon-impEF patients. By multivariable analysis the HFimpEF diagnosis was independently predicted by baseline NYHA I/II (odds ratio [OR] 2.347, 95% confidence interval [95%CI] 1.020–5.405), non-ischemic etiology (OR 3.096, 95%CI 1.587–6.024), lack of diabetes mellitus (OR 2.016, 95%CI 1.059–3.846) and higher baseline LVEF (OR 1.084, 95%CI 1.042–1.126, per 1%). Within the median 49 (25–77) months all-cause mortality was lower in HFimpEF than in HFnon-impEF (10.8 vs 16.4%/year, P ​= ​0.004). ConclusionsOur findings indicate that every sixth Polish patient with HFrEF has a chance to improve LVEF during follow-up and to become a HFimpEF patient. Baseline characteristics of HFimpEF patients are different from HFnon-impEF. Simultaneously, the HFimpEF diagnosis is associated with higher long-term survival.

The Impact of Age Over 80 Years on Outcomes in Geriatric Patients with Acute Pancreatitis: A Single Center Experience

The aim of this study is to evaluate the prognosis and mortality of acute pancreatitis (AP) in older subjects and compare octogenarians (≥80 years) with nonoctogenarians (age &amp;lt;80 years). The medical records of elderly patients who were followed up with the diagnosis of AP at our clinic between January 2018 and December 2021 were retrospectively analyzed. The etiology of AP, comorbidities, laboratory parameters, intensive care unit (ICU) admission, and mortality were noted. Among survivors, one-year mortality status was also recorded. Disease severity, in-hospital mortality and one-year mortality were compared. A total of 206 older patients (60 octogenarian, 146 nonoctogenariean) were recruited to the study. Of them, 115 (56%) were female and the mean age was 76.1±7.3 years. Severity of AP didn’t differ between octogenarians and nonctogenarians (p&amp;gt;0.05). ICU admission was seen in 13% of octogenarians and 11% of nonoctogenarians (p&amp;gt;0.05). In-hospital mortality occurred in 8.3% of octogenarians and 6.8% of nonoctogenarians (p&amp;gt;0.05). After discharge, one-year mortality occurred in 20% of octogenarians and 6.6% of nonoctogenarians (p&amp;lt;0.01). In multivariate analysis severe AP (OR:24.940;%95CI:1.013–95.609; p=0.01), ICU admission (OR:10.244;%95CI:1.399–74.990; p=0.01) and chronic kidney disease(CKD) (OR:9.840;%95CI:1.013–95.609; p=0.04) were independent risk factors for in-hospital mortality, and ≥80 years (OR:2.984;%95 CI:1.116–7.980; p =0.03) and neurological disorders (OR:4.424;%95CI:1.480–13.226; p &amp;lt;0.01) were independent factors related to one-year mortality. Our results showed that advenced age has not a significant effect on the course of AP in elderly. Comorbidities play important role in short- and long-term outcomes in elderly. Larger prospective trials are needed to draw more definitive conclusions.

The impact of GLP-1 receptor agonist liraglutide on blood pressure profile, hydration, natriuresis in diabetic patients with severely impaired kidney function

Chronic treatment with GLP-1R agonists may moderately lower blood pressure due to increased natriuresis and RAAS inhibition. Short-term effect of these drugs on blood pressure may be opposite and its mechanism remains unclear. We investigated the effect of a single dose of liraglutide on diurnal blood pressure profile, natriuresis, hydration and serum concentration of renin, aldosterone and atrial natriuretic peptide (ANP) in diabetic kidney disease (DKD). 17 patients with eGFR < 30 ml/min/1.73 m2 and 17 with > 60 ml/min/1.73 m2 received in a random order a single subcutaneous dose 1.2 mg liraglutide and placebo with subsequent 24 h blood pressure and natriuresis monitoring. Before and after each medication thoracic fluid index and plasma renin, aldosterone and ANP were also assessed. The blood pressure load in the daytime and nighttime were significantly increased after liraglutide compared to placebo in patients with eGFR < 30 ml/min/1.73 m2. In patients with eGFR > 60 ml/min/1.73 m2 the changes of arterial pressure were comparable, while the morning surge was significantly reduced after liraglutide compared to placebo. After liraglutide 24 h urine sodium excretion increased in both groups vs. placebo (p < 0.001), the effect was greatest in subjects with eGFR > 60 ml/min/1.73 m2. Plasma ANP increased after liraglutide in both groups, most in patients with eGFR < 30 ml/min/1.73 m2 group. Plasma aldosterone (p = 0.013) and thoracic fluid index (p = 0.01) decreased after liraglutide compared to placebo (p = 0.013 and p + 0.01, respectively. Plasma renin concentration remained unchanged. In severe chronic kidney disease liraglutide induces a transient increase of blood pressure due to reduced natriuresis. The natriuretic effect of liraglutide in DKD may be related to increased ANP and decreased aldosterone secretion.

Left atrial appendage closure and advanced chronic kidney disease: Another string to the bow.

Key points Patients with severe chronic kidney disease (CKD) and nonvalvular atrial fibrillation are underrepresented in left atrial appendage occlusion (LAAO) studies, despite their higher fragility and greater intolerance to antithrombotic therapy. LAAO appears to be safe and effective in reducing thromboembolic and bleeding recurrences both in patients with and without advanced CKD. Despite favorable ischemic and bleeding outcomes, patients with severe CKD experienced higher mortality rate, compared to those without severe CKD

Musculoskeletal Health Worsened from Carnitine Supplementation and Not Impacted by a Novel Individualized Treadmill Training Protocol

Introduction: Chronic kidney disease (CKD) negatively affects musculoskeletal health, leading to reduced mobility, and quality of life. In healthy populations, carnitine supplementation and aerobic exercise have been reported to improve musculoskeletal health. However, there are inconclusive results regarding their effectiveness and safety in CKD. We hypothesized that carnitine supplementation and individualized treadmill exercise would improve musculoskeletal health in CKD. Methods: We used a spontaneously progressive CKD rat model (Cy/+ rat) (n = 11–12/gr): (1) Cy/+ (CKD-Ctrl), (2) CKD-carnitine (CKD-Carn), and (3) CKD-treadmill (CKD-TM). Carnitine (250 mg/kg) was injected daily for 10 weeks. Rats in the treadmill group ran 4 days/week on a 5° incline for 10 weeks progressing from 30 min/day for week one to 40 min/day for week two to 50 min/day for the remaining 8 weeks. At 32 weeks of age, we assessed overall cardiopulmonary fitness, muscle function, bone histology and architecture, and kidney function. Data were analyzed by one-way ANOVA with Tukey’s multiple comparisons tests. Results: Moderate to severe CKD was confirmed by biochemistries for blood urea nitrogen (mean 43 ± 5 mg/dL CKD-Ctrl), phosphorus (mean 8 ± 1 mg/dL CKD-Ctrl), parathyroid hormone (PTH; mean 625 ± 185 pg/mL CKD-Ctrl), and serum creatinine (mean 1.1 ± 0.2 mg/mL CKD-Ctrl). Carnitine worsened phosphorous (mean 11 ± 3 mg/dL CKD-Carn; p < 0.0001), PTH (mean 1,738 ± 1,233 pg/mL CKD-Carn; p < 0.0001), creatinine (mean 1 ± 0.3 mg/dL CKD-Carn; p < 0.0001), cortical bone thickness (mean 0.5 ± 0.1 mm CKD-Ctrl, 0.4 ± 0.1 mm CKD-Carn; p < 0.05). Treadmill running significantly improves maximal aerobic capacity when compared to CKD-Ctrl (mean 14 ± 2 min CKD-TM, 10 ± 2 min CKD-Ctrl; p < 0.01). Conclusion: Carnitine supplementation worsened CKD progression, mineral metabolism biochemistries, and cortical porosity and did not have an impact on physical function. Individualized treadmill running improved maximal aerobic capacity but did not have an impact on CKD progression or bone properties. Future studies should seek to better understand carnitine doses in conditions of compromised renal function to prevent toxicity which may result from elevated carnitine levels and to optimize exercise prescriptions for musculoskeletal health.

Blood biomarkers improve the prediction of prevalent and incident severe chronic kidney disease.

The prevalence of chronic kidney disease (CKD) is high. Identification of cases with CKD or at high risk of developing it is important to tailor earlyinterventions. The objective of this studywas to identify blood metabolites associated with prevalent and incident severeCKD, and to quantify the corresponding improvement in CKD detection and prediction. Data from four cohorts were analyzed: Singapore Epidemiology of Eye Diseases (SEED) (n = 8802), Copenhagen Chronic Kidney Disease(CPH) (n = 916), Singapore Diabetic Nephropathy (n = 714), and UK Biobank (UKBB) (n = 103,051). Prevalent CKD (stages 3-5) was defined as estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m2; incident severe CKD as CKD-related mortality or kidney failure occurring within 10years. We used multivariable regressions to identify, among 146 blood metabolites, those associated with CKD, and quantify the corresponding increase in performance. Chronic kidney disease prevalence (stages 3-5) and severe incidence were 11.4% and 2.2% in SEED, and 2.3% and 0.2% in UKBB. Firstly, phenylalanine (Odds Ratio [OR] 1-SD increase = 1.83 [1.73, 1.93]), tyrosine (OR = 0.75 [0.71, 0.79]), docosahexaenoic acid (OR = 0.90 [0.85, 0.95]), citrate (OR = 1.41 [1.34, 1.47]) and triglycerides in medium high density lipoprotein (OR = 1.07 [1.02, 1.13]) were associated with prevalent stages 3-5 CKD. Mendelian randomization analyses suggested causal relationships. Adding these metabolites beyond traditional risk factors increased the area under the curve (AUC) by 3% and the sensitivity by 7%. Secondly, lactate (HR = 1.33 [1.08, 1.64]) and tyrosine (HR = 0.74 [0.58, 0.95]) were associated with incident severe CKD among individuals with eGFR < 90mL/min/1.73m2 at baseline. These metabolites increased the c-index by 2% and sensitivity by 5% when added to traditional risk factors. The performance improvements of CKD detection and prediction achieved by adding metabolites to traditional risk factors are modest and further research is necessary to fully understand the clinical implications of these findings.

Outcomes Following Surgical Fixation of Upper Extremity Fractures in Patients with Chronic Kidney Disease

Moderate to severe (stage III-IV) chronic kidney disease (CKD) and end stage renal disease (ESRD) have been shown to be independent risk factors for sustaining a fragility fracture. High rates of complications and mortality are associated with fracture fixation in patients with CKD, but existing literature is limited. It is unknown how CKD stage III-IV or ESRD affects outcomes in upper-extremity fractures. We hypothesize that patients with CKD stage III-IV or ESRD will have high complication rates after surgical fixation of upper extremity fractures. We identified all patients between 2008 and 2018 who underwent operative fixation of an upper extremity fracture proximal to the distal radius with a diagnosis of CKD stage III-IV or ESRD at the time of injury. Those with an acute kidney injury at the time of injury or a history of a kidney transplant were excluded. Demographics, medical complications, and surgical complications were collected retrospectively. Data on readmissions within 90 days and mortality within 1 year were also collected. Thirty-five patients were identified. Three patients had ESRD. Fractures included two clavicle, twelve proximal humerus, one humeral shaft, ten distal humerus, five olecranon, two ulnar shaft, one radial shaft, and two both-bone forearm fractures. In total, 91.4% of fractures were closed injuries. Surgical complications occurred in 40% of patients. The reoperation rate was 11.4%, and all cases of reoperation involved hardware removal. The all-cause 90-day readmission rate was 34.3%. The 1-year mortality rate was 8.6%. Surgical complications occurred in 40% of patients with CKD stage III-IV or ESRD who underwent fixation for an upper extremity fracture. It is important to counsel these patients regarding their high risk for complications. Further research is needed to investigate and identify how to mitigate risk. Prognostic IV.

Increased Cardiovascular Risk in Young Patients with CKD and the Role of Lipid-Lowering Therapy.

Chronic kidney disease (CKD) is associated with a significantly increased risk of cardiovascular disease (CVD). This review summarizes known risk factors, pathophysiological mechanisms, and current therapeutic possibilities, focusing on lipid-lowering therapy in CKD. Novel data on lipid-lowering therapy in CKD mainly stem from clinical trials and clinical studies. In addition to traditional CVD risk factors, patients with CKD often present with non-traditional risk factors that include, e.g., anemia, proteinuria, or calcium-phosphate imbalance. Dyslipidemia remains an important contributing CVD risk factor in CKD, although the mechanisms involved differ from the general population. While statins are the most commonly used lipid-lowering therapy in CKD patients, some statins may require dose reduction. Importantly, statins showed diminished beneficial effect on cardiovascular events in patients with severe CKD and hypercholesterolemia despite high CVD risk and effective reduction of LDL cholesterol. Ezetimibe enables the reduction of the dose of statins and their putative toxicity and, in combination with statins, reduces CVD endpoints in CKD patients. The use of novel drugs such as PCSK9 inhibitors is safe in CKD, but their potential to reduce cardiovascular events in CKD needs to be elucidated in future studies.

Severe COVID-19 and chronic kidney disease: bidirectional mendelian randomization study

Traditional observational research has revealed an association between severe COVID-19 and chronic kidney disease (CKD). It is unclear whether there is a causative connection between them. Our goal was to determine whether genetically predicted CKD is associated with the risk of critical COVID-19. We aimed to investigate potential underlying genetic mechanisms that could explain this relationship, paving the way for personalized risk assessment and targeted interventions to mitigate the effects of COVID-19 on individuals with CKD. Using combined data from a GWAS on European ancestry and CKD (n = 117,165) and critical COVID-19 (n = 1,059,456), bidirectional Mendelian randomization analysis was performed. Four single nucleotide polymorphisms (SNPs) were chosen from the genome as CKD instrumental variables (IVs). In addition to MR‒Egger regression, weighted mode approaches, and weighted medians, we employed the inverse-variance weighted estimate as our primary analytical method. A significant association of CKD with critical COVID-19 (OR = 1.28, 95% confidence interval [CI]: 1.04–1.58, p = 0.01811) was found. However, using 6 genome-wide significant SNPs as IVs for critical COVID‐19, we could not discover a meaningful correlation between severe COVID‐19 and CKD (OR = 1.03, 95% CI: 0.96–1.10, p = 0.3947). We found evidence to support a causal relationship between CKD and severe COVID-19 in European population. This underscores the need for comprehensive monitoring and specialized care strategies for individuals with CKD to mitigate the heightened risk and severity of COVID-19 complications.