Search Results (300)

Background/Objectives: Iron deficiency without anemia (IDWA) is common among female patients with chronic kidney disease (CKD), yet the clinical implications of iron therapy in this population remain uncertain. While iron supplementation is frequently used in anemic CKD patients, evidence regarding its outcomes in non-anemic, iron-deficient individuals is limited and conflicting. Methods: This retrospective cohort study utilized the multi-institutional TriNetX database to examine the 5-year outcomes of iron therapy in adult women with stage 3 CKD, normal hemoglobin (≥12 g/dL), normal mean corpuscular volume (MCV), and low serum ferritin (<100 ng/mL). Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), pneumonia, progression to advanced CKD (estimated glomerular filtration rate ≤30 mL/min/1.73 m²), and gastrointestinal (GI) bleeding. Results: We identified 53,769 eligible non-anemic patients with stage 3 CKD, low serum ferritin levels, and normal MCV. Propensity score matching (1:1) was conducted on demographic variables to compare iron-treated (n = 6638) and untreated (n = 6638) cohorts. Over the 5-year follow-up, iron therapy in non-anemic females with stage 3 CKD, low ferritin levels, and iron supplementation was significantly associated with increased risks of MACE, AKI, pneumonia, CKD progression, and GI bleeding (log-rank p < 0.0001). No significant difference in all-cause mortality was observed. Data on transferrin saturation and the dosage of iron supplementation were unavailable. Conclusions: In non-anemic women with stage 3 CKD and low ferritin levels, iron supplementation was linked to increased MACE, renal, and pneumonia risks without evident survival benefits. These findings suggest that iron therapy in this group of patients may not confer cardiovascular benefit and may pose risks. Full article

Background/objectives: Chronic kidney disease (CKD) affects up to 15% of the global population and is driven by vascular and interstitial damage, and is most prevalent in persons with hypertension and diabetes. Vitamin K, a necessary cofactor for activation of vitamin K-dependent proteins may modulate these processes. It is well established that vitamin K deficiency is associated with CKD, but the therapeutic effects of supplementation on kidney function are still uncertain. We aimed to review the current evidence on the effect of vitamin K deficiency and supplementation on any marker of renal function and kidney disease, across general adult populations and CKD patient populations. Methods: A search was conducted in PubMed, targeting terms related to vitamin K status and CKD. Studies were included if they reported data on vitamin K status or supplementation in relation to kidney function outcomes. Results: A total of 16 studies were included. Nine interventional studies were included and confirmed that vitamin K supplementation improves biomarkers of vitamin K status but showed no consistent beneficial effects on renal function. Seven observational studies across populations found significant associations between vitamin K status and decline in kidney function; however, associations were often attenuated after adjustments. Conclusions: No clear effect of supplementation was observed on the reported kidney markers in patient populations. A clear association between low vitamin K status and impaired kidney function was confirmed. Studying heterogeneity makes the comparability and generalizability of the results difficult. Our review highlights the need for more cohort studies and clinical trials in general or patient populations. Full article

Background: Reducing cardiovascular risk markers is an essential target in chronic kidney disease (CKD). Thus, this study aimed to evaluate the effect of royal jelly plus green propolis supplementation on cardiovascular disease (CVD) risk factors in patients with CKD undergoing hemodialysis (HD). Methods: This randomized, double-blind, placebo-controlled trial involved HD patients allocated to receive either royal jelly plus green propolis EPP-AF^® (100 mg RJ + 500 mg GP) or placebo capsules daily for 2 months. Before and after the intervention period, the biochemical parameters, inflammatory cytokines, and uremic toxins were measured. Results: A total of 38 HD patients completed the 2-month supplementation study, with 19 patients in each group. After 2 months, the treated group showed a significant reduction in plasma levels of IL-6 (0.78 to 0.63 pg/mL, p = 0.008) and total cholesterol (138.60 to 111.85 mg/dL, p = 0.03), whereas no changes were observed in the placebo group. Uremic toxins did not change after intervention. Conclusion: Apitherapy with RJ + GP EPP-AF^® extract significantly reduced plasma IL-6 and total cholesterol in HD patients. This supplementation shows promise as a non-pharmacological strategy to reduce cardiovascular risk markers in this population. Full article

Fracture risk is a serious yet underrecognized complication among patients with chronic kidney disease (CKD), especially in those with stages G3-G5D. The overlap between CKD-Mineral and Bone Disorder (CKD-MBD) and osteoporosis leads to complex bone changes that increase the likelihood of fragility fractures. Studies show that 18% to 32% of CKD patients also have osteoporosis, and these individuals are more than 2.5 times as likely to suffer from fractures compared to those without CKD. In the advanced stages of the disease, fracture risk is up to four times higher than in the general population, with the femur, forearm, and humerus being the most commonly affected sites. Hip fractures are of particular concern as they are linked to longer hospital stays and higher rates of morbidity and mortality. Furthermore, dialysis patients who experience hip fractures have a mortality rate 2.4 times higher than those in the general population with similar fractures. This increased risk underscores the need for proactive bone health maintenance in CKD patients to prevent fractures and related complications. This review explores the underlying pathophysiological mechanisms, diagnostic challenges, and treatment options related to bone fragility in CKD. Diagnostic tools, such as bone mineral density (BMD) assessments, the trabecular bone score (TBS), and biochemical markers, remain underused, especially in advanced CKD stages. Recent treatment strategies emphasize a multidisciplinary, stage-specific approach, incorporating calcium and vitamin D supplements, anti-resorptive agents like denosumab, and anabolic therapies such as teriparatide and romosozumab. Effective management needs to be tailored to the patient’s bone turnover status and stage of CKD. Despite progress in understanding bone fragility in CKD, significant gaps remain in both diagnosis and treatment. Personalized care, guided by updated KDIGO recommendations and based on an interdisciplinary approach, is essential to reduce fracture risk and improve outcomes in this vulnerable population. Further research is needed to validate risk assessment tools and refine therapeutic protocols. Full article

Background: Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD), responsible for approximately 60% of cases. Diabetic kidney disease (DKD) affects 20–50% of individuals with diabetes, with diabetes-related ESKD cases rising steadily worldwide from 22.1% in 2000 to 31.3% in 2015. Methods: This review examines the literature published up to 25 February 2025, using a systematic search in PubMed and Scopus. Keywords included uremic toxins and diabetic kidney disease and/or gut microbiota, or dysbiosis or gut–kidney axis. Studies were independently assessed by a minimum of three authors, with discrepancies resolved through consensus. Results: Gut microbiota dysbiosis is a key driver of DKD progression, making the gut–kidney axis a promising therapeutic target. A “nuts and fruits” dietary pattern reduces the DKD risk by 43.3%, while an animal protein intake lowers the diabetic peripheral neuropathy risk by 42.8%. High-fiber diets and supplements like resistant starch may reduce uremic toxins through microbiota modulation. Conclusions: Microbiota-targeted interventions, including probiotics, synbiotic, and dietary modifications, show potential in reducing uremic toxin production and inflammation, though DKD-specific evidence remains limited. Lactobacillus and Bifidobacterium strains may help lower urea and creatinine levels, but outcomes vary by disease stage. Further research is needed to confirm the efficacy of dietary and probiotic approaches in DKD management. Full article

Background and Objectives: The worldwide prevalence of chronic kidney disease (CKD) continues to increase, representing a major concern for public health systems. CKD is associated with gut microbiota dysbiosis, which may exacerbate disease progression by increasing the levels of uremic toxins, systemic inflammation, and oxidative stress. Modulation of the gut microbiota through biotic supplementation has been proposed as a potential therapeutic strategy to slow CKD progression and mitigate its complications. This study aimed to evaluate the effect of 10-month synbiotic supplementation on estimated glomerular filtration rate (eGFR), circulating concentrations of indoxyl sulfate (IS), p-cresyl sulfate (p-CS), interleukin-6 (IL-6), and malondialdehyde (MDA) in patients with stage IV–V CKD not receiving dialysis, in comparison to placebo. Materials and Methods: Fifty non-dialysis CKD IV–V patients were assigned (n = 25 each) via matched, non-randomized allocation (age, sex, and primary disease) to synbiotic or placebo. This single-blind, placebo-controlled trial blinded participants and laboratory personnel. The synbiotic group received daily capsules containing Lactobacillus acidophilus La-14 (2 × 10¹¹ CFU/g) + fructooligosaccharides; controls received identical placebo. Adherence was monitored monthly (pill counts, diaries), with < 80% over two visits resulting in withdrawal. The eGFR, IS, p-CS, IL-6, and MDA were measured at baseline and month 10. Results: Forty-two patients (21/arm) completed the study; eight withdrew (4 per arm). At 10 months, the change in eGFR was −1.2 ± 2.5 mL/min/1.73 m² (synbiotic) vs. −3.5 ± 3.0 mL/min/1.73 m² (placebo); between-group difference in change was 2.3 mL/min/1.73 m² (95% CI: 0.5–4.1; p = 0.014; adjusted p = 0.07). IS decreased by −15.4 ± 8.2 ng/L vs. −3.1 ± 6.5 ng/L; between-group difference in change was −12.3 ng/L (95% CI: −17.8 to −6.8; p < 0.001; adjusted p = 0.005). No significant differences were observed for p-CS, IL-6, or MDA after correction. Conclusions: Synbiotic supplementation over a 10-month period resulted in a trend toward decreased serum IS levels in patients with advanced CKD, suggesting potential benefits of microbiota-targeted therapies. However, no significant effects were observed on renal function, inflammatory, or oxidative stress markers. Further large-scale studies are warranted to confirm these findings and explore the long-term impact of synbiotics in CKD management. Full article

Zinc is an essential trace element involved in diverse physiological processes in humans. Zinc deficiency is common in patients with chronic kidney disease (CKD), including those undergoing hemodialysis. This narrative review synthesizes both experimental and clinical findings on zinc status in CKD patients. Literature was primarily retrieved from PubMed using the keywords “zinc” AND (“CKD” OR “hemodialysis”) AND at least one of the following: “cardiovascular disease (CVD)”, “vascular calcification”, “anemia”, “blood pressure”, OR “infection”. In vitro, studies have shown that zinc suppressed phosphate-induced vascular calcification while zinc deficiency directly promoted calcification. Clinically, serum zinc levels were positively correlated with calcification propensity in patients with CKD. In vivo zinc deficiency has been implicated in elevated blood pressure, Moreover, zinc supplementation enhanced erythropoiesis and improved responsiveness to erythropoiesis-stimulating agents in both animal models and humans. We recently reported that low serum zinc levels are associated with increased mortality in hemodialysis patients with hypoalbuminemia. Previous randomized controlled trials (RCTs) suggest a daily dose of approximately 45 mg of zinc for 2 months mitigates inflammation, oxidative stress, and malnutrition in patients undergoing hemodialysis. Emerging evidence suggests that vascular calcification, hypertension, and renal anemia are newly recognized features of zinc deficiency and are established risk factors for CKD progression, CVD, and mortality. However, the impact of zinc supplementation on these clinical outcomes remains inconclusive. Further RCTs are required to establish zinc supplementation as an effective therapeutic strategy for improving various outcomes in patients with CKD including hemodialysis. Full article

Background: Diabetic kidney disease (DKD) affects 20–50% of individuals with diabetes. The aim of this review was to identify interventions that positively influence the gut microbiota in DKD. Methods: Identification of relevant studies was conducted via a systematic search of databases and registers using the PRISMA guidelines. This review examined the relevant literature published up to 5 January 2025, using a systematic search in PubMed and Scopus. The search was conducted with combinations of keywords including DKD and therapy, supplementation and gut microbiota, and supplementation or probiotics or fecal microbiota transplant. The initial search fielded 132 results from PubMed and 72 from Scopus, which was narrowed to 135 relevant studies. The exclusion criteria included non-English language studies, letters to the editor, and conference abstracts. Eligible studies were independently assessed by a minimum of three authors, with discrepancies resolved through consensus. Results: Gut microbiota-targeted interventions, including probiotics, synbiotics, and dietary modifications, show promise in modulating the gut microbiota, but evidence specific to DKD remains limited. Some natural food components such as polyphenols and anthocyanins modulate the composition of the gut microbiota translocation of uremic toxins, which slows down the progression of diabetic kidney disease. In animal models, fecal microbiota transplantation (FMT) has shown positive effects in regulating dysbiosis and beneficial effects in chronic kidney disease, but studies involving humans with DKD are insufficient. Conclusions: Lactobacillus and Bifidobacterium strains, administered at doses ranging from 0.6 to 90 billion CFU, may help lower urea and creatinine levels, but outcomes vary by disease stage, duration of therapy, and amount used. High-fiber diets (>10.1 g/1000 kcal/day) and supplements such as resistant starch and curcumin (400–1500 mg/day) may reduce uremic toxins through gut microbiota modulation and reduction in oxidative stress. The effect of sodium butyrate requires further human studies. Full article

Carnitine is essential for the mitochondrial transport of long-chain fatty acids and thus plays a pivotal role in energy metabolism, particularly in metabolically active organs, such as skeletal and cardiac muscle. In patients with dialysis, carnitine homeostasis is disrupted because of the reduced synthesis, impaired renal reabsorption, and carnitine loss during extracorporeal procedures. Carnitine deficiency is linked to a wide range of clinical manifestations, including muscle weakness, treatment-resistant anemia, intradialytic hypotension, mental disorder, and cardiovascular disease. This review provides a comprehensive overview of the physiological function of carnitine, elucidates the underlying mechanisms of carnitine deficiency in patients with dialysis, and explores the clinical consequences. Furthermore, the efficacy and limitations of L-carnitine supplementation in clinical practice are discussed based on the current literature. A better understanding of the pathophysiological and clinical relevance of carnitine deficiency may help facilitate personalized therapeutic strategies for patients with kidney diseases. Full article

Background: Acute heart failure (AHF) is a major cause of hospitalizations, posing significant challenges to healthcare systems. Despite advancements in management, the rate of poor outcomes remains high globally, emphasizing the need for timely interventions. This study aimed to identify early admission-based factors predictive of poor outcomes in hospitalized AHF patients, in order to contribute to early risk stratification and optimize patient care. Methods: This retrospective single-center study analyzed routine data of adult patients hospitalized for AHF at a public university teaching hospital in Switzerland. Outcomes included in-hospital death, intensive care (ICU) treatment, and length of hospital stay (LOHS). Potential predictors were limited to routine parameters, readily available at admission. Missing predictor data was imputed and predictors were identified by means of multivariable regression analysis. Results: Data of 638 patients (median age 84 years, range 45–101 years, 50% female) were included in the study. In-hospital mortality was 7.1%, ICU admission rate 3.8%, and median LOHS was 8 days (IQR 5–12). Systolic blood pressure ≤ 100 mmHg (Odds ratio (OR) 3.8, p = 0.009), peripheral oxygen saturation ≤ 90% or oxygen supplementation (OR 5.9, p < 0.001), and peripheral edema (OR 2.7, p = 0.044) at hospital admission were identified as predictors of in-hospital death. Furthermore, a stroke or transient ischemic attack in the patient’s history (OR 3.2, p = 0.023) was associated with in-hospital death. ICU admission was associated with oxygen saturation ≤ 90% or oxygen supplementation (OR 22.9, p < 0.001). Factors linked to longer LOHS included oxygen saturation ≤ 90% or oxygen supplementation (IRR 1.2, p < 0.001), recent weight gain (IRR 1.1, p = 0.028), and concomitant chronic kidney disease (IRR 1.2, p < 0.001). Conclusions: This study validated established predictors of AHF outcomes in a Swiss cohort, highlighting the predictive value of poor perfusion status, fluid overload, and comorbidities such as chronic kidney disease. The identified predictors imply potential for developing tools to improve rapid treatment decisions. Future research should focus on the prospective external validation of the identified predictors and the design and validation of risk scores, incorporating these parameters to optimize early interventions and reduce adverse outcomes in AHF. Full article

Dietary management is a pillar of chronic kidney disease (CKD) treatment. While some rules are the same as dietary prescriptions for the general population and those suffering from other chronic diseases (energy intake, salt intake, avoidance of ultra-processed food and limited intake of animal fats), in non-dialysis-dependent patients living with CKD, the specific focus is on protein intake. Low-protein diets (LPDs) and supplemented very low protein diets (sVLPDs) have been successfully employed to decrease the symptoms of people living with non-dialysis-dependent CKD, delay the progression of the disease and retard the need for dialysis. Randomized clinical trials have yielded conflicting results on efficacy, resulting in conflicting guidelines. Concerns about the risk of malnutrition (specifically when the main source of proteins is plant-derived), electrolyte imbalances, and energy intake, and the idea that adherence is difficult, jeopardize the use and wide application of LPDs and sVLPDs. That dietary management focuses mainly on nutrients while dietary quality occupies second place is also an erroneous concept that requires discussion. In September 2023, a group of experts composed of nephrologists and dieticians gathered in Frankfurt, Germany, to try to reconcile the different guideline indications and address most of the common doubts of final dispatchers to increase the prescription of “renal diets” and improve people living with CKD’s adherence to them. Full article

It is now widely recognized that maintaining magnesium (Mg) homeostasis is critical for health, especially in the context of chronic kidney disease (CKD). Patients with CKD commonly develop hyperphosphatemia and secondary hyperparathyroidism, which are controlled by therapies targeting intestinal phosphate absorption and circulating calcium levels or by modulating parathyroid calcium sensing. Notably, Mg supplementation may provide dual benefits by promoting bone formation and maintaining normal mineralization with slightly elevated serum levels. Importantly, low Mg levels are associated with mortality risk in CKD, highlighting the importance of maintaining adequate serum Mg levels in these patients. Particularly, kidney transplant (KT) patients have lower circulating Mg levels, likely due to interactions with immunosuppressive treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown survival benefits in CKD and increased serum Mg levels, suggesting that Mg regulation may contribute to these outcomes. Overall, Mg plays a key role in CKD-associated mineral and bone disorders (CKD-MBD). Thus, understanding the mechanisms underlying the alteration of Mg homeostasis in CKD could improve clinical outcomes. This review summarizes the basic and clinical studies demonstrating (1) the key actions of Mg in CKD-MBD, including secondary hyperparathyroidism and bone abnormalities; (2) the distinctive profile of KT patients for Mg homeostasis; and (3) the interaction between commonly used drugs, such as SGLT2 inhibitors or immunosuppressive treatments, and Mg metabolism, providing a broad understanding of both the key role of Mg in the context of CKD and the treatments that should be considered to manage Mg levels in CKD patients. Full article

Background: Renal fibrosis is a common pathological feature of all progressive chronic kidney disease (CKD). Eucommiae cortex (EC) is a valuable economic tree species endemic to China. The microbial fermentation of Chinese medicines can release their active ingredients as effectively as possible or produce new active ingredients with enhanced efficacy and reduced toxic side effects; Methods: The microbial fermentation of EC can produce pinoresinol (Pin) and dehydrodiconiferyl alcohol (DA). In this study, C57 BL/6 mice were fed a diet containing 0.2% adenine, resulting in a model of chronic kidney disease. The effects of EC and EC ferment (ECF) on CKD were explored by the exogenous supplementation of EC and ECF; Results: The results of the study showed that exogenous supplementation with EC and ECF suc-cessfully reduced creatinine and urea nitrogen levels, down-regulated the expression levels of TGF-β1, α-SMA, Smad3, and phospho-Smad3 in the TGF-β1/Smad signaling pathway, and ameliorated renal fibrosis; Conclusions: Both EC and ECF may have reno-protective effects and provide a reference for relevant clinical drug development. Full article

Recently published data indicate that elevated circulating concentrations of N1-methyl-2-pyridone-5-carboxamide (2PY, also described as Met2PY) and N1-methyl-4-pyridone-5-carboxamide (4PY, also described as Met4PY), terminal catabolites of nicotinamide adenine dinucleotide (NAD⁺), are associated with cardiovascular disease (CVD) risk in humans. Previously, we and the others have shown that patients with advanced stages of chronic kidney disease (CKD) exhibit several-fold higher circulating 2PY and 4PY concentrations compared to healthy subjects or patients in the early stages of the disease. It is also well documented that patients with advanced CKD stages exhibit markedly elevated CVD risk, which is the main cause of premature death (in these patients). Therefore, we hypothesize that high concentrations of circulating 2PY and 4PY are important factors that may contribute to cardiovascular events and, ultimately, premature death in CKD patients. However, further, accurately controlled clinical research is needed to provide definitive answers concerning the role of 2PY and 4PY in CVD risk in CKD patients. Moreover, we are dealing with some issues related to the use of NAD⁺ precursors (NAD⁺ boosters) as drugs (also in CKD patients) and/or supplements. Due to the increase in circulating 2PY and 4PY levels during treatment with NAD⁺ boosters, these precursors should be used with caution, especially in patients with increased CVD risk. Full article

Inborn errors of metabolism (IEMs) are a group of disorders resulting from defects in enzymes in metabolic pathways. These disorders impact the processing of metabolites, leading to a wide array of effects on each organ system. Advances in genetic screening have allowed for the early identification and intervention of IEMs, traditionally in the form of enzyme replacement or vitamin supplementation. However, many IEMs disrupt essential metabolic pathways where simple supplementation proves ineffective, resulting in substantial disease burden. In the case of renal IEMs, metabolic pathway disruption leads to the onset of chronic kidney disease (CKD). For these diseases, genetic therapy provides hope. Over the past few decades, the technology for genetic therapy has emerged as a promising solution to these disorders. These therapies aim to correct the source of the defect in the genetic code so that patients may live full, unencumbered lives. In this review, we searched a large database to identify IEMs that affect the kidney and investigated the current landscape and progression of gene therapy technology. Multiple promising genetic therapies were identified for IEMs affecting the kidney, including primary hyperoxaluria, argininemia, glycogen storage diseases Ia and Ib, and Fabry disease. Emerging gene therapy approaches using adeno-associated virus (AAV) vectors, lentiviral vectors, and CRISPR/Cas9 techniques hold promising potential to provide curative treatments for additional single-mutation disorders. Full article