Progression To Kidney Failure Research Articles

Integrated analysis of long non‑coding RNA megacluster, microRNA‑132 and microRNA‑133a and their implications for cardiovascular risk and kidney failure progression in diabetic patients.

Inefficient control of elevated blood sugar levels can lead to certain health complications such as diabetic nephropathy (DN) and cardiovascular disease (CVD). The identification of effective biomarkers for monitoring diabetes was performed in the present study. The present study aimed to investigate the implications of long non-coding RNA megacluster (lnc-MGC), microRNA (miR)-132 and miR-133a, and their correlation with lactate dehydrogenase (LDH) activity and glycated hemoglobin (HbA1C) levels to identify biomarkers for the early diagnosis of diabetes mellitus, induced DN and CVD. The present study included a total of 200 patients with type 2 diabetes, as well as 40 healthy subjects as controls. The diabetic patients were classified into six groups based on their estimated HbA1c level, glomerular filtration rate and LDH activity, while the healthy controls constituted the seventh group. Diabetic patients exhibited significant increases in parameters related to diabetes as fasting blood sugar, HbA1c levels, cardiac injury and kidney failure. Furthermore, the expression levels of TNF-α were significantly increased in the diabetic groups compared with healthy controls. Diabetic patients with cardiovascular dysfunction showed significantly increased expression levels of miR-132, miR-133a and lnc-MGC, compared with the healthy group. The expression of circulating miR-132 in blood was low in the groups of diabetic patients compared with the healthy controls, and demonstrated a negative correlation with LDH and HbA1C levels. Expression levels of miR-132, miR-133a and lnc-MGC, along with their correlations with LDH and HbA1C levels, could be used to distinguish diabetic patients with reduced CVD from those at early stage diabetes, which indicated their potential as biomarkers for CV complications associated with diabetes mellitus in the future.

Expert consensus on multidisciplinary clinical management for chronic kidney disease

Chronic kidney disease (CKD) has been a major public health challenge threatening human health worldwide. When patients with CKD eventually progress to end-stage kidney disease, it imposes a substantial burden on individuals and society. Currently, the diagnosis rate of CKD in China remains low, with an unfavorable status regarding diagnosis and treatment. Therefore, it is urgent to establish a comprehensive prevention and treatment system of CKD, that enhances the multidisciplinary clinical management pathway for CKD patients while improving physicians' co-screening and co-management capabilities across various disciplines for high-risk individuals. Based on current evidence and clinical experience, we formulate the expert consensus on multidisciplinary clinical management approach for CKD, which aims to achieve early detection, early treatment, delay the progression of kidney failure, reduce the risk of cardiovascular, cerebrovascular diseases as well as death in CKD patients, while improving the prognosis of CKD patients and alleviating the burden of CKD disease with a multidisciplinary co-screening co-management model for CKD.

Prediction of Allograft Failure in Pediatric Kidney Transplant Recipients: A Validation Study of the Four-Variable Kidney Failure Risk Equation.

Recent findings suggest that the four-variable Kidney Failure Risk Equation (KFRE) may be useful in predicting the likelihood of allograft failure in adult kidney transplant (KT) recipients. However, research on its application in pediatric patients is lacking. This study aimed to assess the accuracy of the four-variable KFRE for prediction of the two-year and five-year risk of allograft failure in a cohort of pediatric KT recipients. A retrospective observational study of patients undergoing KT in a tertiary pediatric nephrology unit between 2007 and 2017 was conducted. The KFRE risk scores were determined using data collected one-year post-transplantation. Discrimination and calibration properties of the four-variable KFRE were assessed through the area under the receiver operating characteristic curves (AUC) and calibration plots. Fifty-nine patients with a median age of 12.4 (9.1-15.7) years at KT were included. Eleven (18.6%) were living donor recipients. The median estimated glomerular filtration rate one-year post-transplantation was 62.0 (49.0-75.0) mL/min/1.73 m2. One (1.7%) and three (5.1%) patients experienced allograft failure within two and five years following the one-year post-transplantation date, respectively. The four-variable KFRE showed excellent and very good discrimination for the two-year and five-year risks, respectively (AUC 0.966, 95% confidence interval (CI) 0.914-1.000; AUC 0.887, 95% CI 0.732-1.000). Calibration plots demonstrated imprecise calibration. The four-variable KFRE shows promise in predicting kidney failure progression in pediatric KT recipients with a functioning allograft one-year post-transplantation. Larger-scale studies are essential to confirm its predictive accuracy and establish more definitive conclusions.

Urinary Growth Differentiation Factor 15 May Be a New Biomarker of Kidney Failure Progression in Diabetic Kidney Disease

Urinary Growth Differentiation Factor 15 May Be a New Biomarker of Kidney Failure Progression in Diabetic Kidney Disease

Carbamylation Is Instrumental in End-Stage Kidney Disease Coagulopathies: The Impact on von Willebrand Factor and Platelet Functionality.

Chronic kidney disease (CKD) is a progressive, irreversible, and incurable condition characterized by high morbidity and mortality, affecting approximately one-tenth of the global population. Rise of urea-derived cyanate levels in CKD patients, severalfold higher in comparison to those found in healthy individuals, leads to an increased rate of carbamylation of lysine residues of proteins and peptides. This posttranslational modification plays an important role in the progression of kidney failure but also in the onset of CKD-related complications, including previously reported coagulopathies. In this study, we have explored the impact of carbamylation on the functionality of von Willebrand factor (vWF), a pivotal player in hemostasis, and its implications for platelet adhesion. We have explored carbamylated vWF's interactions with its partner proteins via ELISA. Mass spectrometry was employed to identify modified lysine residues. Blood platelets isolated from healthy donors were carbamylated, and their activation, binding to endothelium and thromboxane release were evaluated using flow cytometry, adhesion assays and ELISA, respectively. Using mass spectrometry we detected the vWF's lysine residue smost susceptible to carbamylation. This modification has in turn affected vWF's interactions with its key binding partners: decreased binding to collagen types I/III but increased the affinity to factor FVIII, while its binding to fibrinogen remained unchanged. Carbamylation of vWF impeded vWF-blood platelet binding, but carbamylation of platelets led to their increased thrombin-dependent activation as observed by enhanced phosphatidylserine exposure, improved their binding to vascular endothelium, at the same time decreasing the production of the prothrombotic mediator, thromboxane A2. Our findings highlight the multifaceted impact of carbamylation on vWF and platelets, disturbing the delicate balance of coagulation cascade. These alterations could contribute to the complex hemostatic imbalance in ESKD, underscoring the need for further research to fully understand these mechanisms and their clinical implications.

Performance of clinical and histological prognostic scores for kidney survival in ANCA-associated vasculitis.

Integrating clinical and histological parameters into prognostic scores may enhance the prediction of progression to kidney failure in anti-neutrophil cytoplasm antibodies-associated vasculitis (AAV). This study aimed to evaluate the prognostic performance of histological classifications and scoring systems for kidney survival in AAV. This retrospective cohort study included 101 AAV patients with kidney involvement diagnosed by biopsy and followed for ≥12 months. The main outcome was the time to kidney failure. The prognostic performance of each histological and prognostic score was evaluated using Harrell's C statistic and Akaike's Information Criteria. Among the 101 patients, 37 progressed to kidney failure over a median follow-up of 75 months (IQR 39-123). The Harrell's C statistic was 0.702 (0.620-0.784), 0.606 (0.473-0.738), 0.801 (0.736-0.867), 0.782 (0.706-0.858), and 0.817 (0.749-0.885) for the EUVAS/Berden classification, Mayo Clinic Chronicity Score, Percentage of ANCA Crescentic Score (PACS), ANCA renal risk score (ARRS), and the improved ANCA kidney risk score (AKRiS), respectively. The AKRiS best discriminated the risk of kidney failure progression among subgroups. The AKRiS performance decreased with longer follow-up intervals. Adding the peak estimated glomerular filtration rate attained post-therapy improved the AKRiS performance at all follow-up intervals. Kidney relapses precipitated kidney failure in 71% of cases that progressed after the first year of follow-up. The novel AKRiS enhances the prediction of kidney failure in AAV with kidney involvement. As the prognostic yield of AKRiS decreases over time, a second calculation of AKRiS, including post-therapy kidney function, may improve its long-term performance.

#2300 Validation study of the 4-variable kidney failure risk equation for prediction of allograft loss in a group of pediatric kidney transplant recipients

Abstract Background and Aims Emerging evidence suggests that the 4-variable Kidney Failure Risk Equation (KFRE) can be used to predict the risk of graft failure in adult transplant recipients. However, research studies in pediatric patients are lacking. This study aimed to validate the 4-variable KFRE (age, sex, estimated glomerular filtration rate [eGFR], and urine albumin-to-creatinine ratio [uACR]) for prediction of the 2- and 5-year risk of graft failure in a group of pediatric transplant patients. Method A retrospective observational study involving 59 pediatric patients who underwent kidney transplant between January 2007 and December 2017 was conducted. The KFRE risk scores were calculated with data collected at 1-year post-transplantation. The area under the receiver operating characteristic curves (AUC) and calibration plots were used to assess the discrimination and calibration properties of the 4-variable KFRE in predicting the risk of graft failure at 2 and 5 years from the point of the 1-year post-transplantation measurements. Results Among the 59 patients, 41 (69.5%) were male, with median age of 12.8 years (interquartile range 9.2-15.7) at the time of the kidney transplant. Eleven (18.6%) were living donor recipients. Median eFGR at 1-year post-transplantation was 62.0 mL/min/1.73 m2 (50.0-76.5); 1 (1.7%) and 3 (5.1%) patients developed graft failure within 2 and 5 years from the point of the 1-year post-transplantation measurements, respectively. The 4-variable KFRE showed excellent discrimination for the 2-year risk (AUC 0.966, 95% confidence interval [CI] 0.914-1.000) and very good discrimination for the 5-year risk (AUC 0.887, 95% CI 0.732-1.000). Calibration plots however showed imprecise calibration. A discernible trend was apparent in this sample, suggesting that living donor recipients have increased probability of experiencing graft failure in the first 5 years (p = 0.069). Conclusion The 4-variable KFRE may be of interest in predicting kidney failure progression in pediatric kidney transplant recipients using data at 1-year post-transplant, however to substantiate these findings and ensure the robustness of conclusions, larger-scale studies should be conducted.

#2897 Urinary CD44 levels in chronic kidney disease: a validation study

Abstract Background and Aims Proteinuria is the one of the main cause of kidney failure progression. There is inadequate data about protein components in urine and CKD severity. Our recent urinary proteomics study demonstrated the higher expression of CD44 in the urine proteome of healthy participants compared to CKD patients, arguing the protective role of CD44 in kidney health. However, the validation study needed to proof those differences in CD44 levels by ELISA tests in healthy participants and CKD patients. Therefore, we aimed to investigate urinary CD44 levels in our previously studied cohort of healthy controls and CKD patients using ELISA test. Method This study included 49 healthy participants and 88 early-stage CKD patients. Along with routine laboratory tests, 24 h collected urine samples were investigated using liquid chromatography-mass spectrometry (HPLC-MS) for proteomic analysis. Exponentially Modified Protein Abundance Index (emPAI) was used to estimate peptide count of proteins. Additionally, urinary CD44 levels were measured using ELISA kit to validate findings from proteomic study. Results A brief baseline characteristics of study population presented in Table 1. CKD group represented with lower eGFR, increased creatinine and higher proteinuria compared to healthy controls. Urinary CD44 levels were significantly higher in CKD group compared to healthy controls. Both CD44 levels measured by HPLC-MS and ELISA methods significantly positively correlated with eGFR levels (Table 2). Conclusion In this validation study, we compared the levels of CD44 measured by HPLC-MS and ELISA in healthy controls and CKD patients. We demonstrated that CD44 is overexpressed in urine samples of healthy people compared to CKD patients and may play a protective role in the kidney health. Further investigations needed to explain this finding in a different cohort and large number of CKD patients.

Effect of multidisciplinary care on diabetic kidney disease: a retrospective cohort study

BackgroundDiabetic kidney disease (DKD) is the most common disease among patients requiring dialysis for the first time in Japan. Multidisciplinary care (MDC) may prevent the progression of kidney failure. However, the effectiveness and timing of MDC to preserve kidney function in patients with DKD is unclear. Therefore, the aim of this study was to investigate whether MDC for patients with DKD affects the preservation of kidney function as well as the timing of MDC in clinical practice.MethodsIn this retrospective cohort study, we identified patients with type 2 diabetes mellitus and DKD from April 2012 to January 2020 using a nationwide Japanese healthcare record database. The fee code for medical guidance to prevent dialysis in patients with diabetes was used to distinguish between the MDC and non-MDC groups. The primary outcome was a 40% decline in the estimated glomerular filtration rate, and secondary outcomes were death, hospitalization, permanent dialysis, kidney failure with replacement therapy, and emergency temporary catheterization. Propensity score matching was performed, and Kaplan–Meier and multivariable Cox regression analyses were performed.ResultsOverall, 9,804 eligible patients met the inclusion criteria, of whom 5,614 were matched for the main analysis: 1,039 in the MDC group, and 4,575 in the non-MDC group. The primary outcome did not differ between the groups (hazard ratio: 1.18, [95% confidence interval: 0.99–1.41], P = 0.07). The groups also did not differ in terms of the secondary outcomes. Most patients with DKD received their first MDC guidance within 1 month of diagnosis, but most received guidance only once per year.ConclusionsAlthough we could not demonstrate the effectiveness of MDC on kidney function in patients with DKD, we clarified the characteristics of such patients assigned the fee code for medical guidance to prevent dialysis related to diabetes.

Beta-blockers and chronic kidney disease: a literature review

Chronic kidney disease (CKD) and cardiovascular diseases are widespread throughout the world and are closely related to each other. Sympathetic hyperactivity, characteristic of CKD, increases cardiovascular risk and accelerates the progression of kidney disease by activating beta-adrenergic receptors. Beta-blockers play an important role in preventing the negative effects of in creased activity of the sympathetic nervous system on the cardiovascular system and kidneys, can slow the progression of renal disease, and have proven effective in reducing overall and cardiovascular mortality and treatment of coronary heart disease, heart failure, arterial hypertension, and arrhythmias in patients with CKD. Despite this, beta-blockers are still underused in patients with CKD, especially in its later stages, including ESRD. Although there are currently no clear recommendations for the choice of any specific beta blocker in CKD, factors such as the CKD stage, presence of diabetes mellitus or reduced insulin sensitivity, and pharmacodynamics (cardioselectivity, α1-blocking- and vasodilating properties) and pharmacokinetic properties (metabolism, routes of elimination from the body, degree of binding to plasma proteins and dualizability) should be considered. At present, along with ACE inhibitors, AT1-receptor antagonists, and SGLT2 inhibitors, beta-blockers remain indispensable drugs for treating cardiovascular diseases with proven positive effects on the progression of kidney failure in patients with CKD. Their broader use in this population is expected to further reduce cardiovascular mortality and delay the initiation of renal replacement therapy.

KFRE for predicting ESRD risk in CKD 3-4 patients

Objective: The Kidney Failure Risk Equation (KFRE) is a useful tool for predicting chronic kidney disease (CKD) progression to end-stage renalkidney disease (ESRD). It has been validated in various countries populations. This study aimed to evaluate the prognostic significance of the KFRE model in a Turkish CKD cohort. Materials and Methods: In a prior retrospective study at a single center, the 4-variable KFRE model's accuracy in predicting end-stage renal disease (ESRD) progression was assessed. Among 246 stage 3 or 4 CKD individuals, two-year risk predictions categorized participants into low-intermediate (<20%) and high (≥20%) risk groups. Results: The model showed a sensitivity of 48.9% (95% confidence interval [CI] 34.08–63.94) and a specificity of 89.45% (95% CI 84.32–93.35) in predicting kidney failure progression in the Turkish population with stage 3–4 CKD. The area under the receiver operating characteristic curve was 0.69 (95% CI 0.60–0.79, p = 0.0001). Albuminuria, glomerular filtration rate, and renin–aldosterone system blockage were independently associated with kidney failure progression according to the Cox regression analysis. Conclusion: The findings of this study have demonstrated that the Kidney Failure Risk Equation (KFRE) model shows potential utility in predicting the progression of stage 3–4 chronic kidney disease (CKD) toward the critical stage of end-stage renal disease (ESRD) for the Turkish population.

Applying stacking ensemble method to predict chronic kidney disease progression in Chinese population based on laboratory information system: a retrospective study.

Chronic kidney disease (CKD) is a major public health issue, and accurate prediction of the progression of kidney failure is critical for clinical decision-making and helps improve patient outcomes. As such, we aimed to develop and externally validate a machine-learned model to predict the progression of CKD using common laboratory variables, demographic characteristics, and an electronic health records database. We developed a predictive model using longitudinal clinical data from a single center for Chinese CKD patients. The cohort included 987 patients who were followed up for more than 24 months. Fifty-three laboratory features were considered for inclusion in the model. The primary outcome in our study was an estimated glomerular filtration rate ≤15 mL/min/1.73 m2 or kidney failure. Machine learning algorithms were applied to the modeling dataset (n = 296), and an external dataset (n = 71) was used for model validation. We assessed model discrimination via area under the curve (AUC) values, accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score. Over a median follow-up period of 3.75 years, 148 patients experienced kidney failure. The optimal model was based on stacking different classifier algorithms with six laboratory features, including 24-h urine protein, potassium, glucose, urea, prealbumin and total protein. The model had considerable predictive power, with AUC values of 0.896 and 0.771 in the validation and external datasets, respectively. This model also accurately predicted the progression of renal function in patients over different follow-up periods after their initial assessment. A prediction model that leverages routinely collected laboratory features in the Chinese population can accurately identify patients with CKD at high risk of progressing to kidney failure. An online version of the model can be easily and quickly applied in clinical management and treatment.

Acute over-additive natriuretic effects by a combination of finerenone and SGLT2 inhibition in rats with an activated renin-angiotensin-aldosterone system: a mechanistic basis for clinical outcomes?

Abstract Background Recent preclinical studies suggested an independent benefit of non-steroidal mineralocorticoid receptor (MR) antagonism by finerenone and SGLT2 inhibition in cardiorenal diseases, with a potential for combination therapy. Chronic low-dose combination of finerenone and empagliflozin in hypertensive rats revealed an early, sustained and over-additive reduction in proteinuria but the underlying mechanism(s) are not fully understood. Purpose To compare the acute glucosuric, natriuretic, kaliuretic and diuretic efficacy of individual dosages of finerenone and SGLT2 inhibitors (empagliflozin, canagliflozin or dapagliflozin) with the combined administration of both drug classes in conscious rats with an activated renin-angiotensin-aldosterone system (RAAS). Methods The RAAS was activated in male Wistar rats (body mass 250 to 500 g) by placing them on a low-salt diet containing 0.02% sodium chloride for 72 hours. In a series of three independent experiments, finerenone (1 mg/kg), SGLT2 inhibitor (3 mg/kg; either empagliflozin, canagliflozin or dapagliflozin) alone and the respective combinations were administered in 2-3 ml/kg of solvent (PEG400) by oral gavage and the animals (n=6-10 / group) were individually placed in metabolic cages on water ad libitum. The individual urine was collected for 24 hours and the concentration of glucose, sodium and potassium excreted in the urine was measured by a clinical-chemical analyzer system (ADVIA 2400). Results Administration of 1 mg/kg finerenone had no influence on urinary glucose, urinary volume and urinary potassium but caused an increase in urinary sodium excretion at least by trend. At a dose of 3 mg/kg, all SGLT2 inhibitors induced a strong increase in urinary glucose excretion but had no significant influence on urinary potassium and urinary sodium, while only dapagliflozin caused an increase in urinary volume at the tested dose. Administration of a combination of 1 mg/kg finerenone and 3 mg/kg SGLT2 inhibitor did not significantly modify urinary glucose and urinary potassium in comparison to the respective individual finerenone and SGLT2 inhibitor dosages and only the combination with empagliflozin increased urinary volume vs the respective monotherapies. Surprisingly, combination of finerenone with SGLT2 inhibition over-additively induced sodium excretion consistently in all three experiments (finerenone+empagliflozin: 171,4%; finerenone+canagliflozin: 139,6%; finerenone+dapagliflozin: 133,9%) in comparison to the calculated combination (set to 100%) of the respective individual finerenone and SGLT2 inhibitor groups. Conclusion Combination of MR antagonism by finerenone and SGLT2 inhibition revealed an acute over-additive natriuresis in a rat diuresis model. This might provide an additional mechanistic basis for near-term (e.g. hospitalization for heart failure) and long-term outcomes (e.g. blockade of the progression of kidney failure) in cardiorenal patient populations.

The child and adolescent hypertension as a world-wide problem: prevalence, risk factors including neonatal ones

The children hypertension is a serious threat to population health because uncontrolled children hypertension can result in exponential increasing of cardiovascular and cerebrovascular diseases, progression of kidney failure and premature death in adulthood. The main risk factors for primary children and adolescent hypertension are considered as cardiovascular biomarkers (fibro-blast growth), obesity, especially central obesity, overweight, low birth weight, high sodium intake, sedentary lifestyle, lack of physical activity, socioeconomic and ethnic factors, as well as family anamnesis. The special place in studying children hypertension is occupied by problem of neonatal hypertension. The most common causes of neonatal hypertension are umbilical catheter-related thrombosis, renal parenchymal disease and chronic lung disease (bronchopulmonary dysplasia), as well as low birth weight, post-menstrual age and some other maternal factors, as well as medications (inotropic medicines, caffeine) and regulation of fluid intake.

Diagnostic challenges of diabetic kidney disease.

Diabetic kidney disease (DKD) is one of the most common microvascular complications of both type 1 and type 2 diabetes and the most common cause of the end-stage renal disease (ESRD). It has been evidenced that targeted interventions at an early stage of DKD can efficiently prevent or delay the progression of kidney failure and improve patient outcomes. Therefore, regular screening for DKD has become one of the fundamental principles of diabetes care. Long-established biomarkers such as serum-creatinine-based estimates of glomerular filtration rate and albuminuria are currently the cornerstone of diagnosis and risk stratification in routine clinical practice. However, their immanent biological limitations and analytical variations may influence the clinical interpretation of the results. Recently proposed new predictive equations without the variable of race, together with the evidence on better accuracy of combined serum creatinine and cystatin C equations, and both race- and sex-free cystatin C-based equation, have enabled an improvement in the detection of DKD, but also require the harmonization of the recommended laboratory tests, wider availability of cystatin C testing and specific approach in various populations. Considering the complex pathophysiology of DKD, particularly in type 2 diabetes, a panel of biomarkers is needed to classify patients in terms of the rate of disease progression and/or response to specific interventions. With a personalized approach to diagnosis and treatment, in the future, it will be possible to respond to DKD better and enable improved outcomes for numerous patients worldwide.

IMPACT OF HEMODIALYSIS ON HEALTH-RELATED QUALITY OF LIFE OF THE PATIENT

Hemodialysis is a procedure used to clean the blood of people whose kidneys are not functioning properly. Duration of dialysis is 4-6 hours, twice or thrice a week. Hemodialysis cleans the kidneys of waste products including urea and creatinine along with free water extracorporeal, which slows the progression of kidney failure. The observational study included 80 patients who received hemodialysis.Our study was conducted on 80 patients out of which were found to be males (61.25%) and were found to be females (38.75%). The majority of the patients there (28.75%) were between the ages of 51 and 60. Among 80 patients, complications were reported in 64 (80%) patients. Commonly reported complications were weakness, muscle cramps and fever. Out of 80 patients, 16 patients (20.0%) were having long-term hypertension and 12 patients (15%) were having both hypertension and diabetes as co-morbidity. Participants in our study reported that the above-mentioned problems significantly lower the life quality in terms of the health.

Immunological Approaches for Diagnosis and Treatment of Kidney Failure: A Systematic Review

Introduction: This section provides a brief overview of the significance of kidney failure and its impact on public health. It highlights the urgent need for effective diagnostic and treatment approaches to address this growing health concern. Overview of Immunological Mechanisms in Kidney Failure: The role of immune system dysregulation in the development and progression of kidney failure is discussed in this section. Various immune cells, cytokines, and inflammatory processes are explained in relation to their contribution to renal damage. Understanding these mechanisms is crucial for developing targeted interventions. Immunological Approaches for Diagnosis: This section reviews immunological markers or techniques used for diagnosing kidney failure. The advantages, limitations, and potential clinical applications of these markers or techniques are discussed. Accurate diagnosis plays a crucial role in timely intervention and management. Immunological Approaches for Treatment: Different immunotherapeutic strategies employed in managing kidney failure are explored in this section. The mechanisms of action, efficacy, and potential side effects associated with these approaches are discussed. Advancements in immunotherapy offer hope for improved patient outcomes. Challenges and Future Directions: Existing challenges in implementing immunological approaches for kidney failure diagnosis and treatment are addressed here. Additionally, potential areas of research are suggested to overcome these challenges and enhance patient outcomes. Identifying future directions will drive innovation and progress.

In vivo evaluation of an innovative synbiotics on stage IIIb-IV chronic kidney disease patients.

Microbiota unbalance has been proven to affect chronic kidney disease (CKD) patients and, noteworthy, microbiota composition and activity are implicated in CKD worsening. The progression of kidney failure implies an exceeding accumulation of waste compounds deriving from the nitrogenous metabolism in the intestinal milieu. Therefore, in the presence of an altered intestinal permeability, gut-derived uremic toxins, i.e., indoxyl sulfate (IS) and p-cresyl sulfate (PCS), can accumulate in the blood. In a scenario facing the nutritional management as adjuvant therapy, the present study assessed the effectiveness of an innovative synbiotics for its ability to modulate the patient gut microbiota and metabolome by setting a randomized, single-blind, placebo-controlled, pilot trial accounting for IIIb-IV stage CKD patients and healthy controls. Metataxonomic fecal microbiota and fecal volatilome were analyzed at the run-in, after 2 months of treatment, and after 1 month of wash out. Significant changes in microbiota profile, as well as an increase of the saccharolytic metabolism, in feces were found for those CKD patients that were allocated in the synbiotics arm. Noteworthy, the here analyzed data emphasized a selective efficacy of the present synbiotics on a stage IIIb-IV CKD patients. Nonetheless, a further validation of this trial accounting for an increased patient number should be considered. https://clinicaltrials.gov/, identifier NCT03815786.

Association of Diet-dependent Systemic Acid Load, Renal Function, and Serum Albumin Concentration

Inflammation may be present with CKD and diet composition high in protein intake and fats may affect inflammation thereby impacting kidney health. We investigated whether acid load estimated from urine measures is associated with kidney function decline and whether the effect of acid load on an inflammatory marker, serum albumin, is a pathway to this association. We studied 188 post-menopausal women in a randomized clinical trial of potassium bicarbonate treatment for up to 36 months. 24-hr urine and arterialized blood collections were done at baseline and at subsequent follow-up visits at 3 months interval. Acid load was estimated from potential renal acid load calculated using urinary measures of chloride, phosphate, sodium, potassium, calcium, and magnesium (UPRAL). Mixed effects model with random-intercept and slope was used to estimate subjects' annual decline rate in creatinine clearance (CrCl), and the association between (i) UPRAL and serum albumin and (ii) serum albumin and CrCl, adjusting for age, body mass index, systolic BP, and glucose. A Cox proportional regression model was used to study the relative hazard (RH) for rapid progression of kidney function decline (defined as loss of ≥5 ml/min CrCl/yr based on the last CrCl in the rolling window) with UPRAL, adjusting for the potential covariates and baseline CrCl. A 25 mEq/day increase in UPRAL was inversely associated with serum albumin (Adjusted β[95% CI]: -0.02[-0.09;-0.001). During a mean follow-up of 28 months, 19 women (10%) had a rapid decline in kidney function. For each 25 mEq/day increase in UPRAL, the risk of a rapid decline in CrCl increased by 17% (95% CI: 1.06-1.28). On adjustment for potential confounders, the risk attenuated to 5% (1.02-1.14). Mediation analysis indicated that of the total effect of the association between UPRAL and CrCl, the proportion mediated by serum albumin increased to 0.346 (i.e. 34.6%). Higher UPRAL was associated with lower serum albumin as well as greater kidney function decline in post-menopausal women. Our findings suggest inflammatory response may exert a modulatory effect on the association of UPRAL and kidney function and might be a potential pathway explaining the effects of systemic acid load on progression of kidney failure.

Comparison of Gambier Extract (Uncaria Gambier Robx) and Angiotensin Receptor Blocker on Proteinuria Reduction and Antioxidants - Enhancement in Nephrotic Rat Models.

Proteinuria is a significant clinical manifestation that causes edema in several diseases, including Nephrotic Syndrome (NS). Untreated proteinuria is strongly linked to the progression of kidney failure. One of the adjuvant therapies could be used to reduce proteinuria such as Angiotensin Receptor Blocker (ARB) including Losartan®. Gambier is a traditional medicinal plant widely known for its antioxidant effects. Catechin, a compound contained in Gambier Extract (GE), has been used to reduce microalbuminuria in diabetics. However, its application in NS has not been widely studied. This study compared the effects of GE and ARB in reducing proteinuria and increasing antioxidant activity levels, as well as reported histopathological findings in the nephrotic Wistar rat model. An experimental design study with a control group and a posttest was conducted. The experimental animals were divided into four groups: the control group (K1), the group with puromycin aminonucleoside (PAN) injection (K2), the group with PAN injection + GE (K3), and the group with PAN injection + Losartan® (K4). The standard GE used was Sarie Uncariae® by Toyo Brothers, PT while the ARB (Losartan®) was obtained from Novell, PT. Protein urine, the activity level of total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were assessed using the colorimetric method. Renal histopathology was assessed based on Rollerman's criteria. Gambier extract significantly reduced proteinuria, as depicted by a decrease in protein/volume urine (p = 0.009), increased antioxidant activity, as illustrated by an elevation in T-SOD activity levels (p = 0.007), and tended to decrease MDA levels compared to Losartan®. Based on histopathological findings, GE tended to reduce the percentage of kidney damage in rats induced by puromycin. Gambier extract has been shown a higher antioxidant effect by increasing T-SOD activity levels, reducing proteinuria and also exhibiting a tendency to diminish kidney damage.