Progression To Kidney Failure Research Articles

#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.

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.

The Potential Benefits and Controversies of Probiotics Use in Patients at Different Stages of Chronic Kidney Disease.

The therapeutic modulation of the gut microbiome has been suggested to be one of the tools in the integrated management of chronic kidney disease (CKD) in recent years. Lactobacillus and Bifidobacterium genera are the two most commonly used probiotics strains. Most of the probiotics used in studies are mixed formulation. There is no consensus on the dose and duration of the probiotic administration for CKD patients Increasing evidence indicates that patients with early stage (1–2) CKD have an altered quantitative and qualitative microbiota profile. However, there was a dearth of prospective controlled studies on the use of probiotics in the early stage of the CKD population. The association between gut microbiota disturbance and advanced CKD was reported. Most randomized controlled trials on probiotic treatment used in CKD stage 3–5ND patients reported positive results. The metabolites of abnormal gut microbiota are directly involved in the pathogenetic mechanisms of cardiovascular disease and inflammation. We summarized 13 studies performed in the dialysis population, including 10 in hemodialysis (HD) patients and 3 in peritoneal dialysis (PD). Some controversial results were concluded on the decreasing plasma concentration of uremic toxin, symptoms, inflammation, and cardiovascular risk. Only three randomized controlled trials on PD were reported to show the potential beneficial effects of probiotics on inflammation, uremic toxins and gastrointestinal symptoms. There is still no standard in the dosage and duration of the use of probiotics in CKD patients. Overall, the probiotic administration may have potential benefit in improving symptoms and quality of life, reducing inflammation, and delaying the progression of kidney failure. Further research studies using a larger sample size with longer follow-up durations and a greater focus on clinical outcomes—including survival—are warranted to elucidate the significant clinical impact of the use of probiotics in CKD patients.

Effect size of Dna-j heat shock protein family B member 9 (DNAJB9) biomarker in kidney biopsy specimens on kidney outcomes in fibrillary glomerulonephritis

Background. Fibrillary glomerulonephritis is a rare glomerular disease that presents with hypertension, hematuria, nephrotic syndrome and renal insufficiency. The purpose of this research was to assess effect of DNAjB9 staining marker in kidney biopsy specimens on kidney outcomes. Materials and methods. In this analytic (experimental) clinical study with randomized clinical trial design in meta-analysis article, 72 patients with biopsy-proven fibrillary glomerulonephritis were investigated. Clinical features, laboratory data at initial presentation, management and outcomes were collected. The paper has written based on searching PubMed Central and Google Scholar to identify potentially relevant articles. Median, percentage, mean ± standard deviation (SD), two-tailed t and Chi-square, two proportion difference meta-analysis and Kaplan-Meier analysis were used for statistical evaluation. Moreover, relative risk, odds ratio, Spearman’s correlation for statistical analyses were used. Results. The median and interquartile range of age of patients with fibrillary nephropathy at the time of diagnosis were 55 and 18 years, respectively. There was no statistically significant difference between two sex groups of males and females in current research (p-value: 0.35). There was significant statistical correlation between elevated serum creatinine level and time of last serum creatinine measurement with p-value of 0.01 and confidence interval (CI) of 0.7820 to –0.1258 during follow-up. Relative risk of kidney failure progression to kidney replacement therapy (↑ ≥ 2-fold in serum creatinine or dialysis or kidney transplant) in DNAjB9-positive (group I) and DNAjB9-negative patients (group II) was assessed 2.67 with 95% CI of 1.128 to 6.3044 and p-value of 0.025. Odds ratio of kidney failure progression to kidney replacement therapy (↑ ≥ 2-fold in serum creatinine or dialysis or kidney transplant) was assessed 4.33 with 95% CI of 0.9464 to 19.8417 and p-value of 0.058. There was statistically significant difference when comparing group I and group II for mortality probability (Kaplan-Meier analysis) during follow-up (P < 0.0001). Conclusions. The present study revealed high mortality in DNAjB9-negative (8/64, 12.5%) versus DNAjB9-positive patients (0/8) with statistically significant level. Relative risk and odds ratio of kidney failure progression to kidney replacement therapy were assessed 2.67 and 4.33, respectively.

MO265: Patients with Alport Syndrome from the Radar Registry: A Natural History Study

Abstract BACKGROUND AND AIMS Alport Syndrome (AS) is the second most common genetic kidney disease and results from mutations in COL4A3, A4 or A5 genes. It is characterized by glomerulonephritis, CKD, hearing loss, and ocular lens defects. Estimated incidence is ∼ 1 in 50 000 live births with prevalence of 1 in 5000–10 000. About 80% patients reach ESKD by age 35 years. The UK Alport Registry, part of the National Registry of Rare Kidney Diseases (RaDaR), performs on-going collection of longitudinal data of AS patients. The aims of this study were to characterize demographic and lab data of AS patients and determine the proportion of AS patients at risk for rapid kidney function decline. METHOD Eligible patients had a clinical, histological or genetic diagnosis of ‘Alport syndrome’ or ‘thin basement membrane nephropathy’ by their physician and provided informed consent. Some data were entered manually, but most routine test results were collected by automatic link between RaDaR and renal IT systems. eGFR was calculated using CKD-EPI Cr equation without race adjustment (2021) or Schwartz equation for subjects ≤16 years of age at time of Cr measurement. For eGFR slope calculations, a minimum of four measurements over at least 2 years were required to be included in this analysis; subjects were censored if they reached ESKD, defined as maintenance dialysis, transplant, or ≥ 2 consecutive eGFR measurements of <15 mL/min/1.73 m2. Data are presented as percentages for categorical variables and mean ± SD for continuous variables. RESULTS Between 4 January 2013 and 29 November 2021, 887 patients were recruited. See Table 1 for summary of data stratified by age groups. Overall, 52% male versus 48% female, and in those with genotyping data, 54% had X-linked AS with a mean age of 25.8 years at diagnosis and a mean age of proteinuria onset of 29.6 years. Clinically meaningful Stage 2 CKD was already present at time of diagnosis (mean eGFR 72.7 mL/min/1.73 m2) in many of those ≥ 18 years of age. A total of 43% of this AS cohort have reached ESKD, at a mean age of 32.8 years. While 37% were on ACEi and 20% on ARB medications, only 4% were on dual RAAS blockade therapy. About 50% had documentation of eGFR loss ≥4 mL/min/1.73 m2 per year, 29% had UPCR > 2 g/g, and 50% of those age ≥ 18 years had reached ESKD. The proportion of patients with ≥1 risk factor for rapid progression of kidney failure (defined as eGFR decline ≥ 4 mL/min/1.73 m2 per year, UPCR > 2 g/g, UACR > 1 g/g or male 18–23 yrs with eGFR < 90 mL/min/1.73 m2 based on ATHENA natural history study) was 41%. CONCLUSION Demographic and genetic characteristics of AS patients in the RaDaR registry are generally comparable with previously reported data. Approximately 50% had eGFR decline ≥ 4 mL/min/1.73 m2 per year and 41% of patients had exhibited ≥ 1 risk factor for future rapid progression of kidney disease. Results should be interpreted with caution, however, in light of the considerable amount of missing data in a number of the analyses. On-going data collection in this open cohort should allow for further insights on the natural history over time as well as identify AS patients for potential enrollment into clinical trials.

S-Allylcysteine (SAC) Exerts Renoprotective Effects via Regulation of TGF- β1/Smad3 Pathway Mediated Matrix Remodeling in Chronic Renal Failure.

S-Allylcysteine (SAC), an organosulfur phytochemical sourced from aged garlic extract, is well known for its varied biomedical applications, such as anti-oxidant, anti-inflammatory, and detoxification mechanisms. Despite this, the scientific findings on the defensive impact of SAC against kidney failure (KF) are still unclear. Therefore, in the current investigation, the animal model of KF was induced by adenine in Wistar rats, and the animals were divided into four groups as control, KF induction using adenine, SAC treated KF rats for an experimental duration of 8 weeks. KF progression was assessed by various serum and tissue markers, and the results demonstrated that the renal functions' markers, KIM-1 (kidney injury molecule-1), cystatin, NGAL (neutrophil gelatinase-associated lipocalin), were found increased in adenine-treated rats compared to control. In addition, the inflammatory markers, matrix proteins, and fibrosis signatures explicated by RT-PCR, ELISA demonstrated a profound increase. On the other hand, rats received SAC mitigated KF considerably (p < 0.001) with restored cellular functions. Besides, SAC pre-treatment abrogated the cytokines and pro-inflammatory signals (COX-2 and PGE2) in a dose-dependent manner. Furthermore, the fibrosis signaling markers mediators, such as SMAD-2,-3 were increased with associated matrix proteins. Thus, the present study substantiated that SAC possesses a significant renoprotective effect that might have been demonstrated by the inhibition of the TGF-β1/Smad3 signaling pathway.

Clinical and pathologic analysis of kidney damage in patients with nephrotic syndrome in the Republic of Srpska

Background / Aim: Nephrotic syndrome (NS) is a clinical syndrome characterised by massive proteinuria &gt; 3.5 g in 24 h urine, hypoalbuminaemia, hyperlipidaemia and oedema. Aim of this study was to determine the aetiology and frequency of kidney diseases that occur as the cause of NS in adults in the Republic of Srpska and the progression of renal insufficiency, disease outcomes and efficacy of applied therapy. Methods: The retrospective study included patients aged 18 to 80 hospitalised between 2014 and 2018 due to clinically and laboratory-manifested NS. In patients with suspected primary glomerular disease, a kidney biopsy with immunofluorescent dyeing was performed. The first examination involved hospital admission and the next check-up six months after the first hospitalisation. Basic clinical parameters were followed: creatinine, clearance creatinine, albumin, total protein, cholesterol, total protein in 24 h urine and microscopy of urine during the first hospitalisation and repeated same laboratory findings on control. The progression of kidney failure during this period was assessed, as well as the efficacy of immunosuppressive therapy. Results: In primary NS category membranous glomerulonephritis (MGN) was present at 40.7 % of patients, followed by focal segmental glomerulosclerosis (FSGS) 21.7 %, membranoproliferative glomerulonephritis (MPGN) 11.9 % and IgA glomerulonephritis (IgAN) 11.9 %. Nephroangiosclerosis was verified as the most common cause of secondary NS with 28.8 % and lupus nephritis 21.2 %, followed by ANCA-associated GN (11.5 %) and diabetic nephropathy (11.5 %). Thirty-four patients (21 %) died during the follow-up. Thirty-four patients (18.6 %) progressed to end stage renal disease during the five-year follow-up. Conclusion: The pathology of kidney disease in older patients is often very complex; therefore, a kidney biopsy should be conducted at an early stage of kidney disease for the purpose of obtaining an accurate diagnosis, determining appropriate treatment and thus improving the prognosis of the patient.

Update and Perspectives in the Personalized Management of Sodium, Water, Volume and Hemodynamic Disorders of Dialysis Patients

Sodium and water-related disorders are major components of chronic kidney disease (CKD) and contribute significantly to cardiovascular (CV) complications and mortality. Usually, they are marked by gradual accumulation of sodium, water and have hemodynamic consequences (i.e., fluid overload, hypertension and cardiac disorders) along with the progression of kidney failure culminating in end stage kidney disease. Renal replacement therapy which is then required to sustain life is intended to restore sodium, fluid and pressure disorders along with the objective of reducing the uremic toxin load. Unfortunately, the intermittent nature of conventional short hemodialysis relying on a so called ‘dry weight’ probing approach, only partially restores the sodium-water overload related disorders, thereby exposing patients to further multi-organ damage through the resultant dialysis-induced systemic stress (DISS). Fluid volume management in dialysis patients has emerged as a very challenging condition that requires further attention and more precise tools. Furthermore, recent findings indicate that the physiology of sodium is more complex than that previously summarized by the kidney-centric two-compartment model (volemia and Interstitium) linked to osmotically active sodium (water-bound sodium). A third tissue compartment (skin, muscle) of sodium has now been identified, taking the form of free-water sodium [glycosaminoglycans (GAGs) or gel-like component] with newly-identified pathophysiologic metabolic consequences. All these findings suggest that restoration of sodium homeostasis in dialysis-dependent chronic kidney disease patients should encompass a more holistic approach to improve cardiac health and reduce cardiovascular burden in this highly vulnerable population. In this context, new tools for monitoring and managing dialysis patients to ensure a more precise and personalized control of their sodium and water homeostasis, volemic and hemodynamic disorders are needed. Several monitoring and management tools (e.g., bioimpedance, lung ultrasound, blood volume control, thermal balance control) are already available with potential value. The conductivity measurement-based automated sodium control module represents the latest and very appealing addition to this list of innovative tools. Although establishing the clinical value of these tools requires further outcome-based studies, current clinical use of this new tools has shown promising indications towards the goal of reducing CV morbidity and mortality in kidney dialysis patients. A brief review of these new pathophysiologic findings as well as clinical interests of these new tools is provided in this narrative review.

Temporal macular thinning: a salient sign of Alport syndrome

Alport syndrome is a hereditary, multisystemic disorder that causes abnormalities of the ear, kidney, and eye. A teenager who was suffering from end-stage renal failure and hearing problems was referred to us suspected of Alport syndrome. He did not have any ocular complaints and wore glasses for myopic astigmatism. His best-corrected visual acuity was 6/7.5 bilaterally. Anterior segment examination was unremarkable. Posterior segment examination showed perimacular dot-andfleck retinopathy with bull’s eye maculopathy. Optical coherence tomography revealed temporal macular thinning. The findings were in keeping with the diagnosis of X-linked Alport syndrome. Ocular findings can help diagnose Alport syndrome. Early detection and treatment can help delay the progression of kidney failure.

Umbilical Cord Mesenchymal Stem Cell Exosomes Alleviate the Progression of Kidney Failure by Modulating Inflammatory Responses and Oxidative Stress in an Ischemia-Reperfusion Mice Model.

The efficacy of stem cells for the treatment of renal failure is widely recognized; however, an excessive volume of stem cells can block the capillaries; thus, the potential risks should not be ignored. Stem cell exosomes are secretory extracellular vesicles with a size of 30-150 nm, which have similar functions to stem cells but are much smaller in size. This study aims to investigate the role of human umbilical cord mesenchymal stem cells (UCMSCs)-derived exosomes in the treatment of renal failure caused by ischemia-reperfusion. Fifty 8-week-old female C57 mice underwent bilateral renal ischemia-reperfusion surgery for 30 minutes. After 4 weeks, the treated group received UCMSCs-derived exosomes treatment, and the control group was solely injected with the same amount of PBS. At the age of 16 weeks, the kidney function, kidney damage, inflammatory responses and oxidative stress were measured. Moreover, the effect of UCMSCs-derived exosomes on the phenotype of M1 macrophages was also tested. The results showed that UCMSCsderived exosomes significantly reduced the levels of blood urea nitrogen (BUN), serum creatinine (SCR), and urinary albumin and creatinine (ACR) and 8-isoprostane. UCMSCs-derived exosomes also improved the atrophy of the kidney and glomerulus, decreased kidney pro-inflammatory factors expression (mRNA of II-1β, II-6, Tnf-α, and Mcp-1) and oxidative stress (malondialdehyde), and increased glutathione level. However, F4/80 immunohistochemistry did not show significant differences between the two groups. In systemic inflammation measurement, UCMSCs-derived exosomes decreased proinflammatory factors TNF-α, IL-6, and IL-1β levels, and increased anti-inflammatory factor IL-10 level. In vitro experiments showed that UCMSCs-derived exosomes decreased the protein expression level of TNF-α and increased the protein expression level of IL-10 in M1 macrophages. UCMSCs-derived exosomes reduce kidney inflammation and oxidative stress by improving systemic inflammation, and thus reduce kidney damage and improve kidney function. This study shows the potential application value of exosomes in the treatment of renal failure.