A case report of mediastinal parathyroid carcinoma in a chronic kidney disease patient: Addressing management conundrum.

Parathyroid carcinoma is a rare malignancy; and it is rarer to find one located in an ectopic location. Ectopic parathyroid glands are a reported cause of failed primary surgery for hyperparathyroidism. We report here a 73-year-old male who previously had parathyroidectomy for primary hyperparathyroidism but then had recurrence of his symptoms with a diagnosis of a mediastinal parathyroid carcinoma on further evaluation. This presentation of complicated mediastinal parathyroid carcinoma posed significant diagnostic and management challenges due to comorbid stage IV chronic kidney disease (CKD). Secondly, due to the same comorbid condition, a more aggressive calcimimetic regimen could not be undertaken due to the risk of renal dysfunction with potential progression to dialysis status. Thirdly, he was a high-risk surgical candidate due to significant cardiovascular risks. Ideally, open surgical intervention would be recommended but due to the associated risks, he was managed with robotic-assisted thoracoscopic surgery. He subsequently developed hypocalcemia which normalized with supplemental calcium at follow-up.

Use of bailing capsules (cordyceps sinensis) in the treatment of chronic kidney disease: a meta-analysis and network pharmacology.

The Bailing Capsule is a commonly used traditional Chinese medicine for the treatment of chronic kidney disease (CKD). However, its therapeutic effects and pharmacological mechanisms have not been fully explored. In this study, we integrated meta-analysis and network pharmacology to provide scientific evidence for the efficacy and pharmacological mechanism of Bailing Capsule in treating CKD. We conducted searches for randomized controlled studies matching the topic in PubMed, the Cochrane Library, Embase, Web of Science, and the Wanfang Database, and screened them according to predefined inclusion and exclusion criteria. Dates from the included studies were extracted for meta-analysis, including renal function indicators, such as 24-h urinary protein (24UP), blood urea nitrogen (BUN), and serum creatinine (Scr), as well as inflammatory indicators like high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Network pharmacology was employed to extract biological information, including active drug ingredients and potential targets of the drugs and diseases, for network construction and gene enrichment. Our findings indicated that 24UP, BUN, and Scr in the treatment group containing Bailing Capsule were lower than those in the control group. In terms of inflammatory indicators, hs-CRP, IL-6, and TNF-α, the treatment group containing Bailing Capsule also exhibited lower levels than the control group. Based on network pharmacology analysis, we identified 190 common targets of Bailing Capsule and CKD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that the pharmacological mechanism of Bailing Capsule might be related to immune response, inflammatory response, vascular endothelial damage, cell proliferation, and fibrosis. This demonstrates that Bailing Capsule can exert therapeutic effects through multiple targets and pathways, providing a theoretical basis for its use.

Hypoxia-inducible factor prolyl hydroxylase inhibitors for anaemia in chronic kidney disease: a document by the European Renal Best Practice board of the European Renal Association.

Anaemia is a common complication of chronic kidney disease (CKD) and is associated with poor long-term outcomes and quality of life. The use of supplemental iron, erythropoiesis stimulating agents (ESAs) and blood transfusions has been the mainstay of treatment of anaemia in CKD for more than three decades. Despite available treatments, CKD patients with anaemia are undertreated and moderate-to-severe anaemia remains prevalent in the CKD population. Anaemia has consistently been associated with greater mortality, hospitalisation, cardiovascular events, and CKD progression in patients with CKD, and the risk increases with anaemia severity. Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitors have a novel mechanism of action by mimicking the body's response to hypoxia and have emerged as an alternative to ESAs for the treatment of anaemia in CKD. Their efficacy in correcting and maintaining haemoglobin has been demonstrated in over 30 phase 3 clinical trials. Additionally, HIF activation results in various pleiotropic effects beyond erythropoiesis with cholesterol reduction and improved iron homeostasis and potential anti-inflammatory effects. The long-term safety of these agents, particularly with respect to cardiovascular and thromboembolic events, and their possible effect on tumor growth requires to be fully elucidated. This document presents in detail the effects of HIF-PH inhibitors, describes their mechanisms of action and pharmacologic properties, and discusses their place in the treatment of anaemia in CKD according to the available evidence.

Stabilizing Hypoxia-Inducible Factor to Manage Anemia in Chronic Kidney Disease: From Basic Theory to Clinical Study.

Background: Anemia is one of the common complications of chronic kidney disease (CKD), and its prevalence has been arising globally. The key cause of anemia in CKD patients is the diseased kidney's reduced ability to synthesize endogenous erythropoietin (EPO), yet this is not the sole reason. Inflammatory elements, functional iron deficiency, and uremic toxins together participate in the development of anemia. According to research data, anemia is an independent risk factor for cardiovascular events, all-cause mortality, and worsening renal function and affects the clinical prognosis and quality of life of CKD patients. Regular treatments for anemia in CKD patients include the use of erythropoiesis-stimulating agents (ESAs), iron supplements, and blood transfusions. Summary: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel and small-molecule pharmacological compounds that target the hypoxia-inducible factor (HIF) pathway and are another option for improving anemia in CKD patients. HIF-PHIs simulate hypoxia, stabilize HIF protein, stimulate EPO synthesis, reduce hepcidin level, boost iron utilization, induce the creation of red blood cells, and alleviate anemia. The results of several HIF-PHI phase III trials indicated that HIF-PHIs are similarly effective as ESA at raising hemoglobin concentration. Key Messages: This article summarizes the structure of HIF and the mechanism of stabilizing HIF to improve anemia, discusses the efficacy of HIF-PHIs in CKD patients with or without dialysis, as well as emphasizes the potential safety concerns with HIF-PHIs.

Shenshuai Yingyang Jiaonang ameliorates chronic kidney disease-associated muscle atrophy in rats by inhibiting ferroptosis mediated by the HIF-1α/SLC7A11 pathway.

Objective: Shenshuai Yingyang Jiaonang (SSYYJN), a traditional Chinese medicine formula, can ameliorate muscle atrophy associated with chronic kidney disease (CKD). However, its mechanisms of action remain unclear. This study is to investigate the molecular mechanisms involved in the effects of SSYYJN in ameliorating muscle atrophy associated with CKD in rats. Methods: The chemical compounds of SSYYJN were identified by UPLC-Q-Orbitrap HRMS. Considering the dose-response relationship of the identified compounds, male SD rats were randomly divided into Sham, Model, SSYYJN, and α-Keto Acid (KA) groups. Subsequently, we assessed the therapeutic and anti-ferroptotic effects of SSYYJN. Network pharmacology studies were used to predict the molecular mechanism of SSYYJN on ferroptosis and were further verified for accuracy. Results: A total of 42 active compounds were identified from SSYYJN. SSYYJN alleviated muscle atrophy caused by CKD, as evidenced by changes in body weight, serum biochemical indices, mass and histopathology of the skeletal muscle, and the levels of MuRF1. SSYYJN reduced the levels of iron, MDA, and ROS, increased the levels of GSH, NAPDH, and Gpx4. Network pharmacology analysis indicated that SSYYJN exerted anti-ferroptotic effects that were closely related to the HIF-1α signaling pathway. Molecular protein and genetic test results showed that SSYYJN increased HIF-1α protein and increased SLC7A11. Conclusions: SSYYJN attenuates muscle atrophy in CKD by inhibiting ferroptosis through the activation of the HIF-1α/SLC7A11 pathway and might be a promising traditional Chinese medicine for muscle atrophy in CKD.

Assessment and management of vitamin status in children with CKD stages 2-5, on dialysis and post-transplantation: clinical practice points from the Pediatric Renal Nutrition Taskforce.

Children with chronic kidney disease (CKD) are at risk for vitamin deficiency or excess. Vitamin status can be affected by diet, supplements, kidney function, medications, and dialysis. Little is known about vitamin requirements in CKD, leading to practice variation.The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric kidney dietitians and pediatric nephrologists, was established to develop evidence-based clinical practice points (CPPs) to address challenges and to serve as a resource for nutritional care. Questions were formulated using PICO (Patient, Intervention, Comparator, Outcomes), and literature searches undertaken to explore clinical practice from assessment to management of vitamin status in children with CKD stages 2-5, on dialysis and post-transplantation (CKD2-5D&T). The CPPs were developed and finalized using a Delphi consensus approach. We present six CPPs for vitamin management for children with CKD2-5D&T. We address assessment, intervention, and monitoring. We recommend avoiding supplementation of vitamin A and suggest water-soluble vitamin supplementation for those on dialysis. In the absence of evidence, a consistent structured approach to vitamin management that considers assessment and monitoring from dietary, physical, and biochemical viewpoints is needed. Careful consideration of the impact of accumulation, losses, comorbidities, and medications needs to be explored for the individual child and vitamin before supplementation can be considered. When supplementing, care needs to be taken not to over-prescribe. Research recommendations are suggested.

Adenine-induced animal model of chronic kidney disease: current applications and future perspectives.

Chronic kidney disease (CKD) with high morbidity and mortality all over the world is characterized by decreased kidney function, a condition which can result from numerous risk factors, including diabetes, hypertension and obesity. Despite significant advances in our understanding of the pathogenesis of CKD, there are still no treatments that can effectively combat CKD, which underscores the urgent need for further study into the pathological mechanisms underlying this condition. In this regard, animal models of CKD are indispensable. This article reviews a widely used animal model of CKD, which is induced by adenine. While a physiologic dose of adenine is beneficial in terms of biological activity, a high dose of adenine is known to induce renal disease in the organism. Following a brief description of the procedure for disease induction by adenine, major mechanisms of adenine-induced CKD are then reviewed, including inflammation, oxidative stress, programmed cell death, metabolic disorders, and fibrillation. Finally, the application and future perspective of this adenine-induced CKD model as a platform for testing the efficacy of a variety of therapeutic approaches is also discussed. Given the simplicity and reproducibility of this animal model, it remains a valuable tool for studying the pathological mechanisms of CKD and identifying therapeutic targets to fight CKD.

Assessment of Dietary Acid Load in Children with Chronic Kidney Disease: An Observational Study.

Introduction: Dietary acid load (DAL), which reflects the balance between acid- and alkaline-forming foods, is a modifiable risk factor for metabolic acidosis in CKD. Owing to the paucity of data in the Indian context, we undertook this cross-sectional study to estimate DAL and assess acid and alkaline food consumption in children with CKD2-5D (Chronic kidney disease stage 2 to 5 and 5D-those on hemodialysis). Methods: Clinical profile, dietary assessment of energy, protein intake/deficits, and macronutrients were noted and computed using software created by the division of nutrition, St John's research institute based on Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines in clinically stable children with CKD2-5D. DAL was estimated using potential renal acid load (PRAL in mEq/day) = (0.49 × protein intake in g/day) + (0.037 × phosphorus-intake in mg/day) - (0.02 × potassium intake in mg/day) - (0.013 × calcium intake in mg/day) - (0.027 × magnesium intake in mg/day). A positive dietary PRAL (>0) favors acidic content and negative (<0) favors alkaline content. PRAL was stratified into quartiles for analysis. The association of various clinical and dietary parameters were analysed across these quartiles. Results: Eighty-one children [of mean age 122 ± 47 months; 56 (69%) boys, 29 (36%) on dialysis, 62 (77%) non-vegetarians] were studied. Twenty-eight (34%) were on bicarbonate supplements. A positive PRAL (9.97 ± 7.7 mEq/day) was observed in 74/81 (91%) children with comparable proportions in those with CKD2-5 and 5D [47/52 (90%) vs. 27/29 (93%) respectively, P > 0.05]. Protein intake was significantly higher in the highest quartile compared to the lowest quartile of PRAL in CKD2-5 (55 ± 16 g/day vs. 40 ± 14 g/day, P < 0.001) and 5D groups (47 ± 15 g/day vs. 25 ± 11 g/day, P = 0.002). A majority of the participants 60/81 (74%) consumed highly acidic and minimal alkali foods. Conclusion: In children with CKD2-5D, PRAL estimation revealed high DAL in the majority with a high consumption of acidic foods. These findings provide implications for appropriate dietary counseling in children with CKD.

Health-related quality of life for pediatric patients with end-stage kidney disease: A systematic review and meta-analysis of the Pediatric Quality of Life Inventory (PedsQL).

INTRODUCTION: Health-related quality of life (HRQoL) studies demonstrate the impact of end-stage renal disease (ESRD) on the physical and psychosocial development of children. While several instruments are used to measure HRQoL, few have standardized domains specific to pediatric ESRD. This review examines current evidence on self and proxy-reported HRQoL among pediatric patients with ESRD, based on the Pediatric Quality of Life Inventory (PedsQL) questionnaires. METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis on HRQoL using the PedsQL 4.0 Generic Core Scale (GCS) and the PedsQL 3.0 ESRD Module among 5- to 18-year-old patients. We queried PubMed, Embase, Web of Science, CINAHL, and Cochrane databases. Retrospective, case-controlled, and cross-sectional studies using PedsQL were included. FINDINGS: Of 435 identified studies, 14 met inclusion criteria administered in several countries. Meta-analysis demonstrated a significantly higher total HRQoL for healthy patients over those with ESRD (SMD:1.44 [95% CI: 0.78-2.09]) across all dimensional scores. In addition, kidney transplant patients reported a significantly higher HRQoL than those on dialysis (PedsQL GCS, SMD: 0.33 [95% CI: 0.14-0.53]) and (PedsQL ESRD, SMD: 0.65 [95% CI: 0.39-0.90]) concordant with parent-proxy reports. DISCUSSION: Patients with ESRD reported lower HRQoL in physical and psychosocial domains compared with healthy controls, while transplant and peritoneal dialysis patients reported better HRQoL than those on hemodialysis. This analysis demonstrates the need to identify dimensions of impaired functioning and produce congruent clinical interventions. Further research on the impact of individual comorbidities in HRQoL is necessary for developing comprehensive, integrated, and holistic treatment programs.

Hypomethylation of the LncRNA H19 promoter accelerates osteogenic differentiation of vascular smooth muscle cells by activating the Erk1/2 pathways.

OBJECTIVE: Vascular calcification is a common chronic kidney disease complication. This study aimed to investigate the function of long non-coding RNA (LncRNA) H19 in vascular calcification to explore new therapeutic strategies. METHODS: We induced osteogenic differentiation and calcification of vascular smooth muscle cells (VSMCs) using ß-glycerophosphate. Then, we detected the LncRNA H19 promoter methylation status and Erk1/2 pathways using methylation-specific polymerase chain reaction and western blotting, respectively. RESULTS: Compared with the control group, high phosphorus levels induced VSMC calcification, accompanied by increases in LncRNA H19 and the osteogenic marker Runx2 and reduction of the contractile phenotype marker SM22a. LncRNA H19 knockdown inhibited osteogenic differentiation and calcification of VSMCs. However, the suppressed role of VSMC calcification caused by shRNA H19 was partially reversed by simultaneous activation of the Erk1/2 pathways. Mechanically, we found that the methylation rate of CpG islands in the LncRNA H19 promoter region was significantly lower in the high-phosphorus group, and the hypomethylation state elevated LncRNA H19 levels, which in turn regulated phosphorylated Erk1/2 expression. CONCLUSIONS: LncRNA H19 promoted osteogenic differentiation and calcification of VSMCs by regulating the Erk1/2 pathways. Additionally, hypomethylation of LncRNA H19 promoter CpG islands upregulated LncRNA H19 levels and subsequently activated Erk1/2 phosphorylation.

Effectiveness of Narrowband Ultraviolet Light in Chronic Kidney Disease-Associated Pruritus.

INTRODUCTION:  Chronic kidney disease-associated pruritus (CKDaP) is a prevalent and challenging symptom in individuals suffering from advanced chronic kidney disease (CKD). Its underlying mechanism remains inadequately understood, leading to a limited array of unsatisfactory therapeutic interventions. Despite various attempts, identifying the most effective treatment remains inconclusive. Nevertheless, there is a growing interest in employing ultraviolet phototherapy, particularly for non-responsive patients, although its efficacy is not definitively established. To investigate the potential benefits of narrowband ultraviolet B (NB-UVB) phototherapy on individuals experiencing CKDaP, we report our experience with NB-UVB light in management of CKDaP in dialysis patients. MATERIALS AND METHODS: The study group consisted of patients with end-stage chronic kidney disease who underwent hemodialysis. These patients received dermatological consultations and follow-ups for itching. They were all unresponsive to the conventional treatment (emollients and antihistamines). Screening laboratory examinations, including complete blood count, liver function test, thyroid function, electrolytes, and others, were also arranged to exclude systemic etiologies. The main potential pruritogens were dosed: calcium, phosphate, and parathyroid hormone. Itch intensity was evaluated with a numerical rating scale (0-10), based on the worst level of itching in the past two weeks. They had sessions of NB-UVB light (311 nm, TL01) twice per week. After UVB exposure, patients were advised to use topical emollients. A questionnaire was employed to document the extent, intensity, frequency, and sleep disruption experienced to evaluate the efficiency of the treatment, using a scale from 0 to 10.  Results: In a group of 38 patients, the average age of the patients was 56 years (16-80); 63.2% were female and 36.8% were male. Median duration of pruritus was 4.7 years, and that of dialysis was 8.4 years. Pruritus was intermittent and diffuse in most cases, localized to the arteriovenous fistula site in two cases, and exacerbated by heat in all cases. Itch intensity was evaluated with a numerical rating scale (0-10) based on the worst level of itching in the past two weeks and showed a moderate average score (5/10). Xerosis was found in 63%, and scratch lesions such as excoriation in 34%. NB-UVB phototherapy was used twice per week on nonconsecutive days, with protection of the genital area and also the eyes using UVB-blocking goggles. The initial dose was 0.4 J/cm2 and further doses were introduced according to the erythema response until a maximum of 2 J/cm2. No sunburn, hyperpigmentation, or blistering was noted. Emollients were maintained in patients with xerosis. Average number of sessions was 13 (6-24) and reduction of itch intensity was observed starting from the sixth session. Total improvement was obtained at the end of treatment duration except for three patients who required additional sessions. One patient had recurrence one year later.  Conclusion: In conclusion, phototherapy represents a significant advancement in the treatment options for CKD-associated pruritus. Its positive impact on reducing itching and improving the quality of life for many patients is undeniable. However, to fully unlock its potential, ongoing research is needed to optimize dosing, understand relapse mechanisms, and identify the patients who will benefit most from this therapy.

The effects of omega-3 fatty acids supplementation on hemoglobin, hematocrit, and platelet levels of patients with ESRD condition undergoing dialysis.

Background: Concomitant inflammation may boost the cardiovascular complications in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). Omega-3 fatty acids may have certain health benefits in HD patients. The aim of this study was to investigate the effects of omega-3 fatty acids supplementation on hematocrit (HCT), hemoglobin (HB) level and platelet (PLT) counts of HD patients. Methods: A randomized controlled trial was conducted on HD patients at a private dialysis center in Rasht, Iran. Three omega-3 fatty acid supplement capsules (3 g/d) were administered daily for two months to patients in the intervention group (n = 55). The control group (n = 60) were given three placebo capsules containing medium chain triglyceride (MCT) oil, similar to the supplemental dose of the intervention group at the same period. Three parameters of HCT, HB and PLT were measured at baseline and after the intervention. Results: The PLT count decreased in the intervention group compared to the control group (173.38 ± 74.76 vs. 227.68 ± 86.58 103/mm3, F = 4.83, P = 0.03). No significant change was found on the levels of HCT and HB parameters between the two groups after the intervention. Conclusion: Omega-3 supplementation in HD patients may decrease the risk of forming blood clots in the blood vessels. Further studies are warranted.

Relationship between serum phosphorus and mortality in non-dialysis chronic kidney disease patients: evidence from NHANES 2001-2018.

BACKGROUND: Hyperphosphatemia is common in chronic kidney disease (CKD), associated with higher mortality in dialysis patients. Its impact in non-dialysis patients, especially those with preserved kidney function, remains uncertain. METHODS: A prospective cohort study was conducted using data from the National Health and Nutrition Examination Survey (2001-2008). Serum phosphorus was analyzed as a continuous variable, or categorized into three groups: < 3.5 mg/dL, 3.5 to < 4.5 mg/dL, and ≥ 4.5 mg/dL. Cox proportional hazards models were used to analyze the association between phosphorus with all-cause and cardiovascular disease (CVD) mortality, with or without adjustment for age, sex, race, hemoglobin, estimated glomerular filtration rate (eGFR), serum albumin, serum calcium, 25(OH)D, obesity, hypertension, diabetes, and CVD. RESULTS: A total of 7694 participants were included in the analysis, representing 28 million CKD patients in the United States. During mean 92 months of follow up, 2708 all-cause deaths (including 969 CVD deaths) were observed. Per 1 mg/dL increase in phosphorus was associated with a 13% and 24% increased risk of all-cause mortality (hazard ratio [HR], 1.13; 95%CI, 1.02-1.24) and CVD mortality (HR, 1.24; 95%CI, 1.07-1.45), respectively. Compared with the < 3.5 mg/dL, phosphorus ≥ 4.5 mg/dL was associated with a 28% and 57% increased risk of all-cause mortality (HR, 1.28; 95%CI, 1.05-1.55) and CVD mortality (HR, 1.57; 95CI, 1.19-2.08), respectively. In participants with eGFR < 60 ml/min/1.73m2, elevated phosphorus (≥ 4.5 mg/ dL) were significantly associated with increased risk of all-cause mortality (HR, 1.36; 95%CI, 1.07-1.72). No significant association was observed in eGFR ≥ 60 ml/min/1.73m2 group (HR, 1.31; 95%CI, 0.86-1.99). This correlation does not differ significantly between subgroups defined by eGFR level (P for interaction = 0.889). CONCLUSION: Serum phosphorus above 4.5 mg/dL is significantly associated with a 28% and 57% increased risk of all-cause and CVD death in non-dialysis CKD patients, respectively. This relationship still demonstrated in patients with eGFR < 60 ml/min/1.73m2. However, for population with eGFR ≥ 60 ml/min/1.73m2, further verification is needed.

Zinc Supplementation Trial in Pediatric Chronic Kidney Disease: Effects on Circulating FGF-23 and Klotho.

Background: Zinc status, its role in bone metabolism and efficacy of deficiency correction has not been well studied in children with chronic kidney disease (CKD). Objectives: The primary objective was to investigate whether 3 months of oral zinc supplementation corrects zinc deficiency in children with CKD who have native or transplanted kidneys. The secondary objective was to compare circulating intact FGF-23 (iFGF-23), c-terminal FGF-23 (cFGF-23), and Klotho between zinc-sufficient and zinc-deficient children with CKD and to assess the relationship between circulating zinc, iFGF-23, cFGF-23, Klotho, bone biomarkers, copper, and phosphate excretion pre-supplementation and post-supplementation of zinc. Methods: Forty-one children (25 male and 16 female, age 12.94 ± 4.13 years) with CKD in native or transplanted kidneys were recruited through 2 pediatric nephrology divisions in Ontario, Canada. Of those, 14 patients (9 native CKD, 5 transplant CKD) with identified zinc deficiency (64% enrollment rate) received zinc citrate supplement for 3 months: 10 mg orally once (4-8 years) or twice (9-18 years) daily. Results: Zinc deficiency (plasma concentration < 11.5 µmol/L) was found in 22 patients (53.7%). A linear regression model suggested that zinc concentration reduced by 0.026 µmol/L (P = .04) for every 1-unit of estimated glomerular filtration rate (eGFR) drop. Zinc deficiency status was associated with higher serum iFGF-23; however, this was predominantly determined by the falling GFR. Zinc deficient and sufficient children had similar circulating c-FGF-23 and alpha-Klotho. Normalization of plasma zinc concentration was achieved in 8 (5 native CKD and 3 transplant CKD) out of 14 treated patients rising from 10.04 ± 1.42 to 12.29 ± 3.77 µmol/L (P = .0038). There were no significant changes in other biochemical measures in all treated patients. A statistically significant (P = .0078) rise in c-FGF-23 was observed only in a subgroup of 11 children treated with zinc but not receiving calcitriol. Conclusions: Zinc status is related to kidney function and possibly connected to bone metabolism in patients with CKD. However, it plays a minor role in fine-tuning various metabolic processes. In this exploratory non-randomized study, 3 months supplementation with zinc corrected deficiency in just over half of patients and only modestly affected bone metabolism in asymptomatic CKD patients.

Contexte: Le statut du zinc, son rôle dans le métabolisme osseux et l'efficacité de la correction d'une carence n'ont pas encore été bien étudiés chez les enfants atteints d'insuffisance rénale chronique (IRC). Objectifs: L'objectif principal était d'examiner si une supplémentation orale en zinc pendant trois mois pouvait corriger une carence chez les enfants atteints d'IRC avec des reins natifs ou transplantés. Les objectifs secondaires étaient de comparer les taux circulants de FGF-23 intact (iFGF-23), de FGF-23 c-terminal (cFGF-23) et de Klotho d'enfants atteints d'IRC et ayant des niveaux corrects ou déficients en zinc, puis d'évaluer la relation entre le zinc circulant, l'iFGF-23, le cFGF-23, le Klotho, les biomarqueurs osseux et l'excrétion de cuivre et de phosphate avant et après la supplémentation en zinc. Méthodologie: Un total de 41 enfants (25 garçons et 16 filles, âgés de 12,94 ±4,13 ans) atteints d'IRC avec reins natifs ou transplantés ont été recrutés par deux divisions de néphrologie pédiatrique en Ontario, au Canada. De ceux-ci, 14 patients (9 avec reins natifs; 5 avec reins transplantés) qui présentaient une carence en zinc (taux d'inclusion de 64 %) ont reçu un supplément de citrate de zinc pendant trois mois à raison de 10 mg par voie orale une fois (4 à 8 ans) ou deux fois (9 à 18 ans) par jour. Résultats: Une carence en zinc (concentration plasmatique < 11,5 µmol/L) a été constatée chez 22 patients (53,7 %). Un modèle de régression linéaire a suggéré que la concentration de zinc diminue de 0,026 µmol/L (P = 0,04) pour chaque chute d'une unité de DFGe. Le statut de carence en zinc était associé à un taux sérique d'iFGF-23 plus élevé; cependant, cela était principalement déterminé par la baisse du DFG. Tous les enfants, avec ou sans carence en zinc, avaient des taux circulants similaires de c-FGF-23 et d'alpha-Klotho. La normalisation de la concentration plasmatique de zinc a été obtenue chez 8 patients (5 avec reins natifs; 3 avec reins transplantés) sur les 14 qui ont été traités, passant de 10,04 ±1,42 à 12,29 ±3,77 µmol/L (P = 0,003 8). Aucun changement significatif n'a été observé dans les autres mesures biochimiques chez les patients traités. Une augmentation statistiquement significative (P = 0,007 8) du taux de c-FGF-23 a été observée uniquement dans un sous-groupe de 11 enfants traités avec du zinc, mais ne recevant pas de calcitriol. Conclusion: Le statut du zinc est lié à la fonction rénale et peut être lié au métabolisme osseux chez les patients atteints d'IRC. Il joue toutefois un rôle mineur dans le réglage fin de divers processus métaboliques. Dans cet essai exploratoire non randomisé, une supplémentation en zinc pendant trois mois a permis de corriger la carence chez un peu plus de la moitié des patients et n'a eu qu'un effet modeste sur le métabolisme osseux chez les patients asymptomatiques atteints d'IRC.

Hirudin in the Treatment of Chronic Kidney Disease.

Chronic kidney disease (CKD) is a common public health concern. The global burden of CKD is increasing due to the high morbidity and mortality associated with it, indicating the shortcomings of therapeutic drugs at present. Renal fibrosis is the common pathology of CKD, which is characterized by glomerulosclerosis, renal tubular atrophy, and renal interstitial fibrosis. Natural hirudin is an active ingredient extracted from Hirudo medicinalis, which has been found to be the strongest natural specific inhibitor of thrombin. Evidence based on pharmacological data has shown that hirudin has important protective effects in CKD against diabetic nephrology, nephrotic syndrome, and renal interstitial fibrosis. The mechanisms of hirudin in treating CKD are mainly related to inhibiting the inflammatory response, preventing apoptosis of intrinsic renal cells, and inhibiting the interactions between thrombin and protease-activated receptors. In this review, we summarize the function and beneficial properties of hirudin for the treatment of CKD, and its underlying mechanisms.

Food to Prevent Vascular Calcification in Chronic Kidney Disease.

Vascular calcification (VC) is a consequence of chronic kidney disease (CKD) which is of paramount importance regarding the survival of CKD patients. VC is far from being controlled with actual medication; as a result, in recent years, diet modulation has become more compelling. The concept of medical nutritional therapy points out the idea that food may prevent or treat diseases. The aim of this review was to evaluate the influence of food habits and nutritional intervention in the occurrence and progression of VC in CKD. Evidence reports the harmfulness of ultra-processed food, food additives, and animal-based proteins due to the increased intake of high absorbable phosphorus, the scarcity of fibers, and the increased production of uremic toxins. Available data are more supportive of a plant-dominant diet, especially for the impact on gut microbiota composition, which varies significantly depending on VC presence. Magnesium has been shown to prevent VC but only in experimental and small clinical studies. Vitamin K has drawn considerable attention due to its activation of VC inhibitors. There are positive studies; unfortunately, recent trials failed to prove its efficacy in preventing VC. Future research is needed and should aim to transform food into a medical intervention to eliminate VC danger in CKD.

Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway.

CONTEXT: Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects. OBJECTIVE: To investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat model of MGN. MATERIALS AND METHODS: Fourty male Sprague-Dawley rats were randomized into four groups. The MGN model was established and treated with a DG dose (10 mg/kg) and a positive control (TPCA1, 10 mg/kg), while normal control and MGN groups received distilled water by gavage for four consecutive weeks. At the end of the experiment, 24 h urinary protein, biochemical indices, oxidation and antioxidant levels, inflammatory parameters, histopathological examination, immunohistochemistry and immunoblotting were evaluated. RESULTS: DG significantly ameliorated kidney dysfunction by decreasing urinary protein (0.56-fold), serum creatinine (SCr) (0.78-fold), BUN (0.71-fold), TC (0.66-fold) and TG (0.73-fold) levels, and increasing ALB (1.44-fold). DG also reduced MDA (0.82-fold) and NO (0.83-fold) levels while increasing the activity of SOD (1.56-fold), CAT (1.25-fold), glutathione peroxidase (GPx) (1.55-fold) and GSH (1.81-fold). Furthermore, DG reduced Keap1 (0.76-fold) expression, Nrf2 nuclear translocation (0.79-fold), and induced NQO1 (1.25-fold) and HO-1 (1.46-fold) expression. Additionally, DG decreased IL-2 (0.55-fold), TNF-α (0.80-fold) and IL-6 (0.75-fold) levels, and reduced protein expression of NF-κB p65 (0.80-fold), IKKß (0.93-fold), p-IKKß (0.89-fold), ICAM-1 (0.88-fold), VCAM-1 (0.91-fold), MCP-1 (0.88-fold) and E-selectin (0.87-fold), and also inhibited the nuclear translocation of NF-κB p65 (0.64-fold). DISCUSSION AND CONCLUSIONS: The results suggest a potential therapeutic benefit of DG against MGN due to the inhibition of the NF-κB pathway, supporting the need for further clinical trials.

Integrated Care Model by the Village Health Volunteers to Prevent and Slow down Progression of Chronic Kidney Disease in a Rural Community, Thailand.

INTRODUCTION: Chronic kidney disease (CKD) is a major health problem in Thailand and health behaviors are central to its risk and progression. Because of the shortage of healthcare personnel, village health volunteers (VHVs) have been collaborating in the primary health care system. However, the contribution of VHVs to CKD reduction has not been evaluated yet. This study aimed to evaluate the efficacy of the VHV-integrated model in preventing and slowing down CKD and its risk factors. METHODS: The population-based cohort study was conducted in a rural community of Thailand between 2017 and 2019. Baseline clinical and behavioral characteristics including CKD, diabetes, hypertension, and other high-risk factors of the participants were collected. The integrated care model was initiated by the multidisciplinary care team that facilitated, empowered, and trained VHVs targeting risk factors of CKD, health literacy, and health promotion. Then the participants were educated and trained for lifestyle modification and were monitored continuously for 18 months by VHVs. Changes in the CKD risk factors, and kidney functions before and after the application of integrated care model were compared. RESULTS: A total of 831 subjects participated in the study with an average age of 57.5 years, and 69.5% were female. Among them, 222 participants (26.7%) were diagnosed as having CKD, the vast majority (95%) of which were in the early stages (G1-G3 and A1-A2). CKD risk factors such as high salt intake, smoking, alcohol consumption, self-NSAID (non-steroidal anti-inflammatory drugs) use were significantly decreased after application of the care model. Also, hemoglobin A1c was significantly reduced in diabetic patients, and blood pressure was controlled better than before in the hypertensive patients. Most importantly, a decline of estimated glomerular filtration rate of the CKD group was improved and lower than the non-CKD group. CONCLUSION: The integrated care model through VHV significantly attenuated the risk factors associated with CKD in the general and high-risk population and effectively slowed down the progression of CKD.

Red ginseng ameliorates lipotoxicity-induced renal fibrosis in hyperuricemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic kidney disease can be caused by numerous diseases including obesity and hyperuricemia (HUA). Obesity may exacerbate the renal injury caused by HUA. Red ginseng, a steamed products of Panax ginseng Meyer root, is known for its remarkable efficacy in improving metabolic syndrome, such as maintaining lipid metabolic balance. However, the role of red ginseng on hyperuricemia-induced renal injury in obese cases remains unclear. AIM OF THE STUDY: This study aimed to investigate the action of red ginseng extract (RGE) on lipotoxicity-induced renal injury in HUA mice. MATERIALS AND METHODS: A high-fat diet (HFD)-induced obesity model was employed to initially investigate the effects of RGE on body weight, TC, OGTT, renal lipid droplets, and renal function indices such as uric acid, creatinine, and urea nitrogen. Renal structural improvement was demonstrated by H&E staining. Subsequently, an animal model combining obesity and HUA was established to further study the impact of RGE on OAT1 and ACC1 expression levels. The mechanisms underlying renal injury regulation by RGE were postulated on the basis of RNA sequencing, which was verified by immunohistochemical (including F4/80, Ki67, TGF-ß1, α-SMA, and E-cadherin), Masson, and Sirius red staining. RESULTS: RGE modulated HFD-induced weight gain, glucose metabolism, and abnormalities of uric acid, urea nitrogen, and creatinine. RGE alleviated the more severe renal histopathological changes induced by obesity combined with HUA, with down-regulated the protein levels of ACC1, F4/80, Ki67, TGF-ß1, and α-SMA, and up-regulated OAT1 and E-cadherin. CONCLUSIONS: RGE has ameliorative effects on chronic kidney disease caused by obesity combined with HUA by maintaining lipid balance and reducing renal inflammation and fibrosis.

The effect of oral supplementation of Paricalcitol on C-reactive protein levels in chronic kidney disease patients: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials.

BACKGROUND: Previous studies investigating the effect of oral supplementation of paricalcitol on reactive protein levels in chronic kidney disease (CKD) patients reported inconsistent findings. In this systematic review and meta-analysis, we have analyzed and interpreted the results obtained from previous randomized clinical trials on the effect of paricalcitol on C-reactive protein in CKD patients in the literature. METHODS: MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched until January 2023 and related articles were obtained through a careful screening process allowing extraction of required data from selected articles. The effect size was calculated using a random effect model and weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity among studies was evaluated using Cochran's Q test and I2. RESULTS: Amongst the 182 articles obtained from the initial search, 4 studies (6 arms) were finally included in the meta-analysis. Pooled analysis shows that C-reactive protein levels significantly decrease after oral supplementation with paricalcitol (WMD: -2.55 mg/L, 95% CI (-4.99 to -0.11; P = 0.04). The studies used in this meta-analysis showed significant heterogeneity (I2 = 66.3% and P = 0.01). CONCLUSION: Oral paricalcitol supplementation in CKD patients can significantly reduce C-reactive protein levels, which may prevent CKD progression.