Search Results (160)

Background: Cardiovascular risk in chronic kidney disease (CKD) remains high despite frequently normal conventional lipid parameters. The extent to which lipid patterns vary across CKD severity and metabolic complications remains incompletely characterized. Therefore, this study evaluated lipid patterns and their associations with renal function and CKD-related metabolic complications. Methods: This retrospective cross-sectional study included 229 CKD patients from the nephrology clinic at King Saud Medical City. Single-time-point laboratory data and clinical variables were extracted from medical records. Patients were stratified by KDIGO eGFR stage, uremia, and phosphate status. Lipid parameters were analyzed using nonparametric tests, multivariable regression, and ROC analysis. Results: Among 229 CKD patients, the most prevalent lipid abnormalities were low HDL-C (49.8%) and elevated remnant cholesterol (RC) (31.4%). HDL-C was reduced and RC increased with declining eGFR, while TC, LDL-C, and TG remained unchanged. In uremia, HDL-C remained reduced and RC increased, with additional reductions in TC and LDL-C, whereas TG did not differ. No significant lipid changes were observed with hyperphosphatemia. In multivariable analyses, HDL-C was positively associated with eGFR (β = 48.8, q = 0.003) and inversely associated with BUN (β = −14.3, q = 0.0014), while RC showed an inverse association with eGFR (β = −19.9, q = 0.0005) and a positive association with BUN (β = 3.37, q = 0.0315). These relationships remained independent of age, sex, BMI, smoking status, hypertension, and type 2 diabetes. ROC analysis further demonstrated the moderate discriminatory ability of HDL-C and RC for identifying CKD stages and uremia. Conclusions: Alterations in HDL-C and RC were independently associated with renal function and uremic status. These findings suggest that lipoprotein composition may reflect metabolic disturbances accompanying CKD progression. Full article

Kidney transplantation (KTx) corrects many uremia-related metabolic disturbances; however, dyslipidemia remains common in kidney transplant recipients and contributes to persistent cardiovascular risk. Lipoprotein(a) [Lp(a)] is a largely genetically determined proatherogenic lipoprotein that increases in advanced chronic kidney disease (CKD) and may decrease after restoration of renal function. Autotaxin (ATX), an enzyme involved in proinflammatory lipid signaling through the ATX–lysophosphatidic acid axis, has also been implicated in cardiovascular pathology, but its early post-transplant dynamics remain poorly characterized. In addition to quantitative lipid abnormalities, CKD is associated with high-density lipoprotein (HDL) dysfunction and reduced paraoxonase-1 (PON-1) activity; however, data on early post-transplant changes in PON-1 activity are limited. In this prospective observational study, lipid profile parameters, Lp(a) concentration, ATX activity, and PON-1 activity were assessed in 55 Caucasian patients with CKD stage 5, most of whom were dialysis-dependent, before and 2–3 weeks after KTx. All recipients received tacrolimus-based maintenance immunosuppression with corticosteroids and mycophenolate mofetil. After KTx, Lp(a) levels decreased by a median of 21% and ATX activity by 28% (both p < 0.001). Lp(a) and ATX showed no cross-sectional or longitudinal association either before or after transplantation, and their percentage changes were not correlated. In contrast, conventional lipid fractions increased significantly, including total cholesterol (+22%), LDL cholesterol (+27%), HDL cholesterol (+24%), and triglycerides (+55%) (all p < 0.001). PON-1 activity increased by approximately 13% after KTx (p < 0.001), and its percentage change correlated positively with the increase in HDL cholesterol. In exploratory analyses, the magnitude of Lp(a) reduction was associated with early graft function: patients with eGFR <45 mL/min/1.73 m² exhibited a significantly smaller decline in Lp(a) than those with better graft function (−4.8% vs. −26.7%, p = 0.009). Multivariable analysis showed that demographic characteristics, body mass index, tacrolimus exposure, and post-transplant eGFR did not independently predict the magnitude of Lp(a) reduction. Tacrolimus trough concentrations and cumulative corticosteroid exposure were not associated with lipid parameters or their changes, except for a single subgroup difference in PON-1 activity of uncertain clinical significance. In summary, in the early period after KTx under tacrolimus-based immunosuppression, Lp(a) concentration and ATX activity decrease, whereas conventional lipid fractions increase and PON-1 activity improves. These changes were not associated with tacrolimus exposure or cumulative corticosteroid dose. The reduction in Lp(a) was associated with early graft function in exploratory analyses, suggesting that recovery of renal function may contribute to early post-transplant Lp(a) dynamics; however, no independent causal relationship was established, and the findings should be interpreted cautiously given the limited sample size and exploratory design. The clinical significance of these changes for long-term cardiovascular and graft outcomes requires further investigation. Full article

Background/Objectives: Posterior reversible encephalopathy syndrome (PRES) is a neurological condition characterized by acute neurological symptoms and vasogenic edema, usually affecting the posterior circulation. It is described in end-stage renal disease (ESRD), but its presentation in peritoneal dialysis (PD) is not well defined. We aimed to describe the clinical, radiological, and dialysis-related features of PRES in PD patients and highlight factors relevant for diagnosis and management. Materials and Methods: We conducted a retrospective descriptive case series of four ESRD patients on PD or recently transitioned from PD to hemodialysis (HD) who developed PRES at a single center. Clinical data, laboratory results, dialysis characteristics, and neuroimaging findings were obtained from medical records. PRES was diagnosed based on acute neurological symptoms in the setting of severe hypertension and uremia, with CT and/or MRI findings supportive of PRES when present and exclusion of alternative diagnoses. Results: All patients presented with acute neurological manifestations, including headache, visual disturbances, seizures, and/or altered consciousness, in the context of marked hypertension and uremia. Neuroimaging findings ranged from normal CT/MRI to subtle bilateral occipital hypodensities and, in one case, extensive supra- and infratentorial vasogenic edema with internal hydrocephalus and subependymal edema. In three patients, inadequate volume or solute control on PD prompted temporary or permanent transition to HD to improve blood pressure and fluid management. With antihypertensive therapy, seizure control when required, correction of metabolic disturbances, and optimization of dialysis, all patients recovered clinically, with time to PRES resolution ranging from 7 to 43 days. Conclusions: PRES should be considered in PD patients with new-onset seizures, visual symptoms, or unexplained changes in mental status, particularly during hypertensive crises and uremia. Early CT/MRI, prompt blood pressure control, and careful adjustment of dialysis modality appear important for achieving favorable neurological outcomes. Full article

Advanced chronic kidney disease (CKD) is associated with impaired humoral immunity, contributing to increased infection-related mortality and suboptimal vaccine responses, as notably observed during the COVID-19 pandemic. CKD is also marked by the accumulation of uremic toxins, but whether they directly influence T and B cell functionality remains unclear. In this translational study, we integrated clinical and biological data from 106 CKD patients with mechanistic insights from in vitro and in vivo murine models to identify the mechanisms underlying CKD-associated defects in humoral responses against T cell-dependent antigens. Contrary to our initial hypothesis, indoxyl sulfate—despite its known ability to activate Aryl hydrocarbon Receptor signaling in monocytes—did not directly impair T–B cell cooperation in coculture assays. Similarly, plasma levels of ten major uremic toxins showed no correlations with vaccine-induced antibody titers in patients. Instead, systemic inflammation emerged as the primary driver of defective humoral immunity. Murine models further confirmed that inflammation, rather than uremia alone, induces lymphopenia, disrupts lymphoid architecture, and ultimately impairs antibody production. These findings indicate that CKD-associated inflammation, rather than a direct effect of uremic toxins on adaptive immune effectors, underlies humoral immune dysfunction in CKD. Targeting inflammation may, therefore, offer a promising strategy to improve vaccine efficacy and reduce infection-related complications in this vulnerable population. Full article

Sarcopenia, the progressive loss of muscle mass and strength, is a common complication in patients with chronic kidney disease (CKD). This condition arises from a combination of factors including reduced physical activity, insufficient protein intake, hyperphosphatemia, chronic inflammation, and uremia itself; however, the underlying molecular mechanisms remain poorly understood. Proteolysis in skeletal muscle is primarily controlled by the ubiquitin–proteasome system, autophagy–lysosome system, and calpains (CAPNs) cysteine proteases, which degrade structural proteins and mediate cell signaling. This study aims to investigate the role of CAPNs in CKD-associated muscle deterioration. CKD was induced in mice through an adenine-rich diet for 2, 4 and 6 weeks. The involvement of CAPNs in CKD-related sarcopenia was assessed using mice that overexpressed the CAPNs endogenous inhibitor, calpastatin (CAST). Gastrocnemius muscle strength, structural integrity, and function were evaluated. Mice with CKD showed elevated CAPNs, particularly CAPN2, expression and activity in the gastrocnemius, in parallel with significant muscle deterioration, including strength loss, structural damage, and impaired muscle performance. Overexpression of CAST prevented muscle strength loss, improved muscle function and structure without affecting renal function, and reversed fibrosis, inflammation and adipogenesis expression markers. Targeting CAPN2 could be a promising therapeutic strategy to mitigate muscle damage and improve physical performance in CKD patients. Full article

Background: While experimental models show that leptin and adiponectin have inverse effects on the cardiovascular system, it has been suggested that the leptin-to-adiponectin (L/A) ratio may be an important predictor of cardiovascular disease and death. Higher circulating leptin and adiponectin levels are observed in uremia due to decreased renal degradation and/or clearance and increased production. We sought to examine the association between the L/A ratio and mortality in a prospective hemodialysis cohort. Methods: Among a prospective cohort of 448 hemodialysis patients from the NIH “Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease (CKD) (MADRAD) study who underwent leptin and adiponectin measurements, we examined characteristics associated with high leptin and adiponectin (defined as the highest tertile) using logistic regression. We then examined the association of L/A ratio levels (categorized as tertiles) with all-cause mortality using Cox regression. Results: Multivariable logistic regression analyses showed female sex, diabetes, presence of an arteriovenous fistula/graft, and lower serum albumin, IL-6, and adiponectin were associated with high leptin, whereas female sex, longer vintage, Black race, higher IL-6, and lower leptin were associated with high adiponectin. When examining L/A ratios, the highest tertile was associated with lower mortality in case-mix Cox models (ref: lowest tertile): HR (95% CI) 0.14 (0.06–0.35). These associations were robust in analyses that additionally adjusted for laboratory covariates: (HR 95% CI) 0.18 (0.07–0.46). Conclusions: In a prospective cohort of hemodialysis patients, inflammation and malnutrition markers were associated with lower leptin and higher adiponectin levels. Additionally, high L/A ratio levels were associated with lower mortality. Further studies are needed to determine the mechanisms relating adipocytokines, inflammation and nutrition, and survival in this population. Full article

The platelet-to-lymphocyte ratio (PLR) has been used as a marker of inflammation, endothelial damage, and a predictor of mortality. Expanded hemodialysis (HDx) using medium cut-off dialyzer (MCO) can effectively clear medium-sized uremic toxins. This study evaluated the effect of the Theranova dialyzer, a type of MCO dialyzer, on PLR and uremia-related inflammatory markers. A total of 44 patients with maintenance hemodialysis (HD) using high-flux dialyzer were randomly allocated to the Theranova or high-flux group. PLR and inflammatory markers including fibroblast growth factor 23, tumor necrosis factor-α (TNF-α), and interleukin 6 were evaluated every 4 weeks. The changes in PLR and the reduction ratio of inflammatory markers were compared between two groups during the 12-week study period. The baseline characteristics and PLR were not different between groups. After 12 weeks, the levels of PLR, and TNF-α were significantly lower in the Theranova group compared to the high-flux group (all p < 0.05). The generalized estimating equation model also revealed a significant decrease in PLR over time in the Theranova group than in the high-flux group (p = 0.04). The fold change in 12-week PLR to baseline PLR was lower in the Theranova group than in the high-flux group (p = 0.03). In the multivariable linear regression analysis, the Theranova dialyzer showed a negative correlation with the PLR fold change (β = −0.32, p = 0.04). Our results showed that HDx using the Theranova dialyzer improves PLR over time compared to the high-flux HD. The superior removal of the inflammatory uremic toxins by the Theranova dialyzer may have reduced inflammation and inflammation-related complications in HD patients. Full article

Background: Motor vehicle accidents account for the majority of abdominal trauma in pregnancy and can result in fetal morbidity and mortality. With advancing gestation, the fetus becomes more vulnerable to injury. Case presentation: A preterm neonate is born at 32 weeks’ gestation via cesarean section due to placental abruption after maternal motor vehicle accident. Initially, the infant presented with anemia, thrombocytopenia, and acute kidney injury in the setting of renal contusions. Results: Hyponatremia, acidosis, oliguria, and uremia progressed to frank anuric renal failure, requiring several months of hemodialysis before transition to peritoneal dialysis for chronic renal replacement therapy at home. Conclusions: Fetal renal injury resulting in postnatal renal failure is a rare but potentially devastating complication of blunt abdominal injury during pregnancy. Sonographic and laboratory evaluation of a neonate with suspected in utero injury after maternal motor vehicle accident is imperative, as is a high index of suspicion for neonatal renal injury. Full article

Arteriovenous (AV) access complications remain a major cause of morbidity in hemodialysis patients, influenced by multiple factors, including endothelial inflammation induced by uremia. In this study, we investigated the mechanisms underlying the upregulation of endothelial chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by indolic uremic toxins, as well as their association with AV access complications in hemodialysis patients. In cultured human endothelial cells, IL-8 and MCP-1 were upregulated by indolic uremic toxins through activation of their receptor, the aryl hydrocarbon receptor (AHR), and non-canonical TGF-β pathway involving TAK1/p38 MAPK/AP-1 signaling. In a retrospective observational study of 204 hemodialysis patients, baseline serum IL-8 or MCP-1 were positively correlated with indolic uremic toxins and TGFβ1. Additionally, serum IL-8 ≥ 40.26 pg/mL and serum MCP-1 were independently associated with an increased risk of AV access complications over a 2-year period. In conclusion, we demonstrated that indolic uremic toxins promote endothelial inflammation by inducing IL-8 and MCP-1 expression via AHR activation and non-canonical TGF-β signaling. Clinically, elevated serum IL-8 and MCP-1 were independently associated with an increased risk of AV access complications in hemodialysis patients. Full article

Background: The overall incidence of malignancy in patients with end-stage kidney disease (ESKD) is reportedly higher compared to the general population. Cancer remains one of the dominant causes of death in these patients, due in part to uremia-induced impairment of tumor immune surveillance. Malignancy is one of the major limitations in the evaluation of potential kidney transplantation. This study aimed to assess the prevalence of cancer in hemodialysis population, particularly in relation to the waiting list. Materials and Methods: From the population of 5879 prevalent hemodialysis patients (60% men), 757 of them had a history of malignancy. In this population, 449 patients were actively waitlisted, and 4619 were not considered for potential kidney transplantation. Only 54 patients had unclear status in relation to active waiting list (during evaluation/disqualification). We assessed demographic data, basal biochemical data, and comorbidities, including malignancy, in relation to age, sex, presence of metastasis, and being actively waitlisted. Results: Malignancy was reported in 13% of hemodialysis patients, 6% of which had metastatic disease. Patients with malignancy were older (p < 0.001). More cases of cancer were observed in males (p = 0.02), who also had higher Charlson Comorbidity Index scores. Moreover, in patients with cancer, cardiovascular diseases were more common. They were also more malnourished (lower albumin, hemoglobin, lean mass) and more inflamed (higher ferritin, lower phosphorus). Only 27 patients with cancer were actively waitlisted, representing only 3.8% of this population. Patients with prior cancer on the active waiting list constituted 6% of all the waitlisted patients. Patients with a history of malignancy on the active waiting list were significantly younger, healthier, with significantly lower Charlson Comorbidity Index score, significantly lower ferritin, lower prevalence of diabetes, and higher blood pressure when compared to patients with malignancy who not listed for kidney transplantation. Conclusions: As malignancy became a more common comorbidity in dialysis patients, the elderly in particular, standardized cancer screening protocols should be promoted in dialysis units. Modern oncology has made huge progress, enabling the treatment of previously incurable cancers, as malignancy after kidney transplantation is considerably increased either due to de novo cancers or the recurrence of previous malignancy. Therefore, the evaluation of potential kidney transplant recipients, with tailored cancer screening and multidisciplinary evaluation, is strongly recommended. Besides a history of malignancy, the cardiovascular status also determines the eligibility for transplantation in dialysis patients. It is of paramount importance as the main cause of death in transplant recipients is cardiovascular death followed by malignancy. Full article

Objectives: Pericardial effusion is the accumulation of excess fluid in the pericardial sac. The etiology is multi-factorial and different techniques are used for management, including subxiphoid approaches, anterior and lateral thoracotomies, video-assisted thoracic surgery (VATS), and percutaneous pericardiocentesis. We evaluate the surgical management strategies for pericardial effusion and their outcomes in this systematic review. Methods: A systematic literature review was performed to identify studies on the surgical management of pericardial effusion from inception to February 2024 using PubMed, Cochrane, and Scopus. Articles were independently assessed by two reviewers, with discrepancies resolved by the senior author. Articles were considered for inclusion if they described different pericardial effusion surgical management techniques. Baseline patient characteristics and procedural and outcome variables were extracted. Results: A total of 27 studies comprising 2773 patients were evaluated. The median age was 56.2 years (interquartile range 47–62.2). The most common etiologies of pericardial effusion were malignancy (31.0%), post-cardiac surgery (18.7%), and idiopathic (15.4%). Other causes included uremia (9.6%), infection (9.6%), and autoimmune disease (4.2%). The subxiphoid pericardial window was the most common approach (82.6%), followed by anterior and lateral thoracotomy (12.0%), and median sternotomy (0.6%). At median follow-up of 24 months, the most frequent post-procedural complications were recurrence of effusion (10.5%), arrhythmias (2.7%), and pneumonia (0.7%). Conclusions: Subxiphoid pericardial window is the most common approach for draining pericardial effusions. Prognosis depends on both the underlying etiology and the chosen drainage strategy. Treatment should be tailored to individual patients, considering patient comorbidities and the specific etiology. Full article

As a synthetic analogue of vasopressin, desmopressin or DDAVP has well established hemostatic properties. We present a review of DDAVP and summarize the clinical and laboratory evidence for its use in hemophilia A, von Willebrand disease (VWD), platelet function disorders, uremia, liver cirrhosis, and pregnancy, followed by illustrative examples of its broad efficacy from our local practice. In brief, DDAVP acts to release von Willebrand factor (VWF) and factor VIII from endogenously stored reserves, thereby correcting plasma deficiencies present in mild to moderately affected patients with hemophilia A and VWD. Thus, DDAVP represents a non-transfusional therapy for these disorders. Typically, a trial of DDAVP is arranged to assess individual responsiveness before employing DDAVP clinically, since there is individual variation in responsiveness. Thereafter, DDAVP can be utilized in responsive patients for clinical use and provides a factor replacement sparing strategy in these patients for some clinical situations. Nevertheless, DDAVP is best applied as a factor replacement sparing strategy, especially for minor procedures or short-term use. Full article

Eryptosis is a programmed cellular death involving red blood cells (RBCs). It is a physiological mechanism that leads to the removal of defective erythrocytes, similarly to apoptosis. Its typical features are cell shrinkage, cell membrane blebbing, and membrane scrambling with the consequent exposure of the aminophospholipid phosphatidylserine on the outer surface of RBCs. Different mechanisms play a role in the pathogenesis of eryptosis, such as the increase in cytosolic calcium concentration, oxidative stress, inflammation, and uremic toxins. If erythrocyte synthesis does not compensate for the accelerated eryptosis, anemia may develop. Moreover, enhanced eryptosis contributes to the pathogenesis of different clinical diseases, such as diabetes, sepsis, metabolic syndrome, and uremia. In particular, in patients with chronic kidney disease (CKD), deficiencies of erythropoietin and iron may further reduce the lifespan of RBCs. In this review, we focused on eryptosis in CKD and end-stage renal disease on peritoneal dialysis (PD) and hemodialysis (HD). Full article

Chronic kidney disease (CKD) has a high prevalence worldwide, with an increasing incidence. One of the mechanisms of CKD progression involves a disordered inter-organ relationship between the kidneys and the intestine, known as the kidney-gut axis. In CKD, two pathological gut conditions—disturbed gut microbiota composition called uremic dysbiosis and leaky gut—contribute to the progression of CKD. Dysbiosis is associated with the increased production of gut-derived uremic toxins, leaky gut, and chronic systemic inflammation, leading to worsening uremia, which in turn aggravates the gut condition. This vicious cycle should be a target of the therapeutic strategy against CKD. The modulation of uremic dysbiosis, including prebiotics, probiotics, and synbiotics, has been a typical treatment approach, although clinical evidence for their efficacy has been insufficient. Some non-antibiotic drugs have an impact on human gut bacteria that are believed to play a role in their clinical efficacy on kidney function. Nutrition therapies, including a low-protein diet, dietary fiber, a Mediterranean diet, and whole grains, positively influence gut microbiota composition and have been linked to a decreased risk of CKD. Novel strategies are currently being explored, involving the use of postbiotics, microbiome sequencing techniques, and fecal microbiota transplantation, although clinical application remains to be tested. Human trials investigating the above-mentioned interventions remain inconclusive due to several limitations, including dietary variability and genetic factors. Future research should focus on the development of more effective probiotics, prebiotics, and microbial metabolism-modifying drugs, not only for CKD but for other systemic diseases as well. Full article

Cardiovascular disease is the primary cause of mortality and morbidity in patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD) undergoing hemodialysis. This paper examines the challenges of managing acute coronary syndrome (ACS) in ESRD patients, focusing on the delicate balance between thrombotic and bleeding risks. The review explores the mechanisms underlying the increased thrombotic risk in ESRD, including elevated platelet aggregation, endothelial dysfunction, and alterations in coagulation factors. Paradoxically, ESRD patients also exhibit higher bleeding tendencies due to platelet dysfunction and other uremia-related factors. The efficacy and safety of various antiplatelet therapies, including aspirin and P2Y12 inhibitors, are evaluated in this population. While potent P2Y12 inhibitors such as ticagrelor and prasugrel have demonstrated potential in reducing ischemic events, they are associated with an increased bleeding risk. The optimal duration of anti-platelet therapy (DAPT) in ESRD patients remains controversial, with studies suggesting potential benefits of prolonged DAPT but also increased bleeding risk. This review underscores the necessity for further research and patient inclusion in clinical trials to establish evidence-based guidelines for tailoring antithrombotic therapy in this high-risk population. Full article