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Nutrients Jun 2024Gut microbiota-derived uremic toxins (UT) accumulate in patients with chronic kidney disease (CKD). Dietary phosphorus and protein restriction are common in CKD...
Gut microbiota-derived uremic toxins (UT) accumulate in patients with chronic kidney disease (CKD). Dietary phosphorus and protein restriction are common in CKD treatment, but the relationship between dietary phosphorus, a key nutrient for the gut microbiota, and protein-derived UT is poorly studied. Thus, we explored the relationship between dietary phosphorus and serum UT in CKD rats. For this exploratory study, we used serum samples from a larger study on the effects of dietary phosphorus on intestinal phosphorus absorption in nephrectomized (Nx, n = 22) or sham-operated (sham, n = 18) male Sprague Dawley rats. Rats were randomized to diet treatment groups of low or high phosphorus (0.1% or 1.2% /, respectively) for 1 week, with serum trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS) analyzed by LC-MS. Nx rats had significantly higher levels of serum TMAO, IS, and pCS compared to sham rats (all < 0.0001). IS showed a significant interaction between diet and CKD status, where serum IS was higher with the high-phosphorus diet in both Nx and sham rats, but to a greater extent in the Nx rats. Serum TMAO ( = 0.24) and pCS ( = 0.34) were not affected by dietary phosphorus levels. High dietary phosphorus intake for 1 week results in higher serum IS in both Nx and sham rats. The results of this exploratory study indicate that reducing dietary phosphorus intake in CKD may have beneficial effects on UT accumulation.
Topics: Animals; Male; Rats, Sprague-Dawley; Nephrectomy; Phosphorus, Dietary; Renal Insufficiency, Chronic; Indican; Rats; Uremic Toxins; Sulfuric Acid Esters; Methylamines; Cresols; Gastrointestinal Microbiome
PubMed: 38931160
DOI: 10.3390/nu16121807 -
Nutrients Jun 2024Patients with chronic kidney disease (CKD) suffer disproportionately from a high burden of cardiovascular disease, which, despite recent scientific advances, remains... (Review)
Review
Patients with chronic kidney disease (CKD) suffer disproportionately from a high burden of cardiovascular disease, which, despite recent scientific advances, remains partly understood. Vascular calcification (VC) is the result of an ongoing process of misplaced calcium in the inner and medial layers of the arteries, which has emerged as a critical contributor to cardiovascular events in CKD. Beyond its established role in blood clotting and bone health, vitamin K appears crucial in regulating VC via vitamin K-dependent proteins (VKDPs). Among these, the matrix Gla protein (MGP) serves as both a potent inhibitor of VC and a valuable biomarker (in its inactive form) for reflecting circulating vitamin K levels. CKD patients, especially in advanced stages, often present with vitamin K deficiency due to dietary restrictions, medications, and impaired intestinal absorption in the uremic environment. Epidemiological studies confirm a strong association between vitamin K levels, inactive MGP, and increased CVD risk across CKD stages. Based on the promising results of pre-clinical data, an increasing number of clinical trials have investigated the potential benefits of vitamin K supplementation to prevent, delay, or even reverse VC, but the results have remained inconsistent.
Topics: Humans; Vascular Calcification; Vitamin K; Renal Insufficiency, Chronic; Matrix Gla Protein; Vitamin K Deficiency; Extracellular Matrix Proteins; Calcium-Binding Proteins; Dietary Supplements; Cardiovascular Diseases; Biomarkers
PubMed: 38931153
DOI: 10.3390/nu16121798 -
Molecules (Basel, Switzerland) Jun 2024Cisplatin, a platinum-based chemotherapeutic, is effective against various solid tumors, but its use is often limited by its nephrotoxic effects. This study evaluated...
Cisplatin, a platinum-based chemotherapeutic, is effective against various solid tumors, but its use is often limited by its nephrotoxic effects. This study evaluated the protective effects of trametinib, an FDA-approved selective inhibitor of mitogen-activated protein kinase kinase 1/2 (MEK1/2), against cisplatin-induced acute kidney injury (AKI) in mice. The experimental design included four groups, control, trametinib, cisplatin, and a combination of cisplatin and trametinib, each consisting of eight mice. Cisplatin was administered intraperitoneally at a dose of 20 mg/kg to induce kidney injury, while trametinib was administered via oral gavage at 3 mg/kg daily for three days. Assessments were conducted 72 h after cisplatin administration. Our results demonstrate that trametinib significantly reduces the phosphorylation of MEK1/2 and extracellular signal-regulated kinase 1/2 (ERK1/2), mitigated renal dysfunction, and ameliorated histopathological abnormalities. Additionally, trametinib significantly decreased macrophage infiltration and the expression of pro-inflammatory cytokines in the kidneys. It also lowered lipid peroxidation by-products, restored the reduced glutathione/oxidized glutathione ratio, and downregulated NADPH oxidase 4. Furthermore, trametinib significantly inhibited both apoptosis and necroptosis in the kidneys. In conclusion, our data underscore the potential of trametinib as a therapeutic agent for cisplatin-induced AKI, highlighting its role in reducing inflammation, oxidative stress, and tubular cell death.
Topics: Animals; Cisplatin; Acute Kidney Injury; Pyridones; Oxidative Stress; Mice; Pyrimidinones; Disease Models, Animal; Inflammation; Male; Cell Death; Apoptosis; Kidney Tubules; Lipid Peroxidation; Cytokines; MAP Kinase Signaling System
PubMed: 38930946
DOI: 10.3390/molecules29122881 -
Microorganisms May 2024Upper urinary tract urolithiasis is an emerging disease in cats, with 98% of kidney stones composed of calcium oxalate. In humans, disturbances in the intestinal and...
Upper urinary tract urolithiasis is an emerging disease in cats, with 98% of kidney stones composed of calcium oxalate. In humans, disturbances in the intestinal and urinary microbiota are suspected to contribute to the formation of calcium oxalate stones. We hypothesized that similar mechanisms may be at play in cats. This study examines the intestinal and urinary microbiota of nine cats with kidney stones compared to nine healthy cats before, during, and after treatment with the antibiotic cefovecin, a cephalosporin. Initially, cats with kidney stones displayed a less diverse intestinal microbiota. Antibiotic treatment reduced microbiota diversity in both groups. The absence of specific intestinal bacteria could lead to a loss of the functions these bacteria perform, such as oxalate degradation, which may contribute to the formation of calcium oxalate stones. This study confirms the presence of a distinct urobiome in cats with kidney stones, characterized by greater richness and diversity compared to healthy cats. These findings highlight the potential of microbiota modulation as a strategy to prevent renal lithiasis in cats.
PubMed: 38930480
DOI: 10.3390/microorganisms12061098 -
Microorganisms May 2024Urinary tract infections (UTIs) rank among the most prevalent bacterial infections in children. Probiotics appear to reduce the risk of recurrence of UTIs. This study...
Urinary tract infections (UTIs) rank among the most prevalent bacterial infections in children. Probiotics appear to reduce the risk of recurrence of UTIs. This study aimed to evaluate whether probiotics containing PL1 and PM1 therapy prevent UTIs in the pediatric population compared to a placebo. A superiority, double-blind, randomized, controlled trial was conducted. In total, 54 children aged 3-18 years with recurrent UTIs or ≥one acute pyelonephritis and ≥one risk factor of recurrence of UTIs were randomly assigned (27 patients in each arm) to a 90-day probiotic or placebo arm. The age, sex, diagnosis, renal function, risk factors, and etiology of UTIs did not vary between the groups. During the intervention, 26% of children taking the probiotic had episodes of UTI, and it was not significantly less than in the placebo group. The number of UTI episodes during the intervention and the follow-up period decreased significantly in both groups, but the difference between them was insignificant. We observed a decrease in UTIs during the study of almost 50% in the probiotic group compared to the placebo group. Probiotics can be used as natural, safe prophylaxis for children with risk factors for UTIs in whom antibiotic prevention is not indicated.
PubMed: 38930419
DOI: 10.3390/microorganisms12061037 -
Journal of Clinical Medicine Jun 2024Chronic kidney disease (CKD) elevates the risk of cardiovascular disease (CVD) and mortality. Uremic cardiomyopathy, frequently observed in CKD and end-stage renal...
Chronic kidney disease (CKD) elevates the risk of cardiovascular disease (CVD) and mortality. Uremic cardiomyopathy, frequently observed in CKD and end-stage renal disease (ESRD), involves alterations in cardiac structure and function, which may reverse post-kidney transplantation, although data remain controversial. This study examines the relationship between graft function and changes in cardiac parameters pre- and post-transplantation in kidney transplant recipients. A total of 145 pediatric and adult recipients of living or deceased donor kidney transplants were enrolled at Gazi Yaşargil Training and Research Hospital. This cohort study utilized transthoracic echocardiographic (TTE) imaging pre-transplant and at least two years post-transplant. Echocardiographic parameters were analyzed using standard techniques. The mean age of the participants was 35 years, with 60% male. The average dialysis duration prior to transplantation was 27 months. Most recipients (83.4%) received kidneys from living donors. Left ventricular diastolic dysfunction increased significantly post-transplant ( < 0.05), while other cardiac dimensions and functions, such as ejection fraction and pulmonary artery pressure, showed no significant change ( > 0.05). Notably, diastolic dysfunction worsened in patients with dysfunctional grafts (GFR < 45), correlating with increased pulmonary artery pressure post-transplant. The rate of antihypertensive drug use and the prevalence of diabetes mellitus increased significantly post-transplant ( < 0.05). This study demonstrates that left ventricular diastolic dysfunction present before kidney transplantation continues to persist post-transplantation in patients with end-stage renal disease undergoing chronic kidney disease treatment. Furthermore, it shows an increased rate of pulmonary artery pressure and pericardial effusion in patients with dysfunctional grafts after transplantation. Further research is required to explore strategies to reverse uremic cardiomyopathy and reduce cardiovascular risk in these patients.
PubMed: 38930157
DOI: 10.3390/jcm13123629 -
Journal of Clinical Medicine Jun 2024Chronic Kidney Disease (CKD) is a complex health condition that interacts significantly with socioeconomic determinants, particularly income status and education. This...
Chronic Kidney Disease (CKD) is a complex health condition that interacts significantly with socioeconomic determinants, particularly income status and education. This study developed a simple indicator of socioeconomic status (SES), which is composed of income status and education in CKD patients, and evaluated its impact on health outcomes in this population. This study was conducted on 561 CKD patients, stages 2-5. The composite SES score was developed by combining the regression coefficients of income and education as predictors of the study endpoint in a multivariable Cox model, normalizing these coefficients to derive weights, and then using these weights to calculate an individual percentage score based on each person's income and education. The composed SES indicator was internally validated through bootstrap analysis. Over a median follow-up time of 36 months, we tracked all-cause death and non-fatal cardiovascular events. Both lack of income ( = 0.020) and low educational level ( = 0.034) were independently related to the combined endpoint. Based on these covariates' regression coefficients, a composite socioeconomic score considering income and educational level was generated. In a Cox regression model, a 10% increase in this composite risk score entailed a 25% increase in the hazard ratio (HR) of the combined endpoint [HR (10% increase): 1.25], and the internally validated 95% CI ranged from 1.14 to 1.41 ( < 0.001). This study underscores the significant impact of a simple, bootstrap-validated composite SES indicator on CKD patients' health outcomes. These findings highlight the importance of considering education and socioeconomic factors in managing and treating CKD patients and inform future research and policy considerations for this population.
PubMed: 38930130
DOI: 10.3390/jcm13123600 -
Journal of Clinical Medicine Jun 2024: The Hugo™ Robot-Assisted Surgery (RAS) system is a new cutting-edge robotic platform designed for clinical applications. Nevertheless, its application for cystic...
: The Hugo™ Robot-Assisted Surgery (RAS) system is a new cutting-edge robotic platform designed for clinical applications. Nevertheless, its application for cystic renal tumors has not yet been thoroughly investigated. In this context, we present an initial series of Robot-Assisted Partial Nephrectomy (RAPN) procedures carried out using the Hugo™ RAS system for cystic renal masses. : Between October 2022 and January 2024, twenty-seven RAPN procedures for renal tumors were performed at Fondazione Policlinico Universitario Campus Bio-Medico. Our prospective board-approved dataset was queried for "cystic features" (n = 12). Perioperative data were collected. The eGFR was calculated according to the CKD-EPI formula. Post-operative complications were reported according to the Clavien-Dindo classification. Computed tomography (CT) scans for follow-up were performed according to the EAU guidelines. Trifecta was defined as the coexistence of negative surgical margin status, no Clavien-Dindo grade ≥ 3 complications, and eGFR decline ≤ 30%. : All the patients successfully underwent RAPN without the need for conversion or additional port placement. The median docking and console time were 5.5 (IQR, 4-6) and 79.5 min (IQR, 58-91 min), respectively. No intraoperative complications occurred, as well as clashes between instruments or with the bedside assistant. Two minor postoperative complications were recorded (Clavien-Dindo II). At discharge, serum creatinine and eGFR were comparable to preoperative values. Only one patient (8.4%) displayed positive surgical margins. The rate of trifecta achievement was 91.7%. : RAPN for cystic renal masses using the novel Hugo™ RAS system can be safely and effectively performed. This robotic system provided satisfactory peri-operative outcomes, preserving renal function and displaying low postoperative complications and a high trifecta rate achievement.
PubMed: 38930124
DOI: 10.3390/jcm13123595 -
Journal of Clinical Medicine Jun 2024: Chronic kidney disease (CKD) is identified as a risk factor for the occurrence of ischemic stroke. There is substantial evidence that CKD is linked to a worse...
: Chronic kidney disease (CKD) is identified as a risk factor for the occurrence of ischemic stroke. There is substantial evidence that CKD is linked to a worse prognosis and higher mortality rates in stroke patients. This study aimed to evaluate the characteristics and factors affecting favorable outcomes and mortality in patients treated using mechanical thrombectomy (MT) for ischemic stroke, with particular emphasis on patients suffering from CKD. : The retrospective study included an analysis of data from 723 patients (139; 19.4% had CKD) with ischemic stroke treated with MT between March 2019 and July 2022. : Patients with CKD were significantly older (median age 76.5 vs. 65.65, < 0.001) and more often female (59.7% vs. 42.6%, < 0.001). CKD decreased the likelihood of achieving a favorable outcome (0-2 points in modified Rankin scale; OR: 0.56, CI95%: 0.38-0.81) and increased mortality (OR: 2.59, CI95%: 1.74-3.84) on the 90th day after stroke. In addition, CKD was associated with intracranial hemorrhage (ICH) in patients who underwent posterior circulation MT (13.85% vs. 50%, = 0.022). In patients with CKD, inter alia, higher levels of C-reactive protein (OR: 0.94, CI95%: 0.92-0.99) reduced the chance of a favorable outcome. In addition, the occurrence of ICH in patients with CKD increased mortality on the 90th day after stroke (OR: 4.18, CI95%: 1.56-11.21), which was almost twice as high as in patients without CKD (OR: 2.29, CI95%: 1.54-3.40). : Patients suffering from CKD had a lower probability of achieving a favorable outcome and had increased mortality following MT for ischemic stroke. It is crucial to understand the variations between patients with unimpaired and impaired renal function, as this could aid in predicting the outcomes of this method.
PubMed: 38930001
DOI: 10.3390/jcm13123469 -
Journal of Clinical Medicine Jun 2024Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the... (Review)
Review
Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the hardest challenges in clinical practice due to the lack of sensitive and specific biomarkers. Currently, neonatal AKI is defined with urinary markers and serum creatinine (sCr), with limitations in early detection and individual treatment. Biomarkers and risk factor scores were studied to predict neonatal AKI, to early identify the stage of injury and not the damage and to anticipate late increases in sCr levels, which occurred when the renal function already began to decline. Sepsis is the leading cause of AKI, and sepsis-related AKI is one of the main causes of high mortality. Moreover, preterm neonates, as well as patients with post-neonatal asphyxia or after cardiac surgery, are at a high risk for AKI. Critical patients are frequently exposed to nephrotoxic medications, representing a potentially preventable cause of AKI. This review highlights the definition of neonatal AKI, its diagnosis and new biomarkers available in clinical practice and in the near future. We analyze the risk factors involving patients with AKI, their outcomes and the risk for the transition from acute damage to chronic kidney disease.
PubMed: 38929977
DOI: 10.3390/jcm13123446