Chronic End-stage Renal Disease Research Articles

Sofosbuvir plus velpatasvir combination for the treatment of chronic hepatitis C in patients with end stage renal disease on renal replacement therapy: A systematic review and meta-analysis.

Sofosbuvir (SOF) and velpatasvir (VEL) is a pan-genotypic regimen for the treatment of Hepatitis C virus (HCV) infection. The data on the efficacy and safety of this regimen is end-stage renal disease (ESRD) is scanty. This systematic review and meta-analysis was done to ascertain the efficacy and safety of SOF and VEL in patients with chronic Hepatitis C (CHC) and ESRD on renal replacement therapy (RRT). Systematic search of Pubmed, Embase, Scopus, and Google Scholar was conducted using the search term (end-stage renal disease OR renal replacement therapy OR chronic kidney failure OR severe renal impairment OR chronic kidney disease OR haemodialysis OR dialysis OR peritoneal dialysis) AND (sofosbuvir OR velpatasvir OR NS5A inhibitors OR directly acting antivirals). Pooled sustained virologic response (SVR) and adverse event rates with 95% confidence intervals were estimated. Seven studies (410 patients with CHC and ESRD on RRT) fulfilled our eligibility criteria. The overall pooled SVR rate of SOF and VEL in patients with HCV on RRT was 97.69% (95% CI: 95.71 to 98.92). There was no significant heterogeneity (I2 : 39.3%, p-value of Cochran's Q=0.13) among the studies. The pooled estimate of efficacy of SOF-VEL combination among patients with cirrhosis was 91.94% (95% CI 77.03-98.52). Pooled SVR rates in genotype 3 infection [94.6%, (95%: CI 81.3-99.4)] was comparable to that in those with documented non-genotype 3 infection [94.63%, (95% CI 87.12-98.44)]. No serious adverse event attributable to SOF and VEL was reported in the included studies. The fixed-dose combination of SOF and VEL is effective and safe in CHC patients with ESRD on RRT.

Medical management of Stevens-Johnson syndrome/toxic epidermal necrolysis among North American dermatologists

Medical management of Stevens-Johnson syndrome/toxic epidermal necrolysis among North American dermatologists

Nuances of Arteriovenous Fistula Creation for Vascular Access in Hemodialysis.

Background With rising incidence and increased life expectancy of patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), the number of patients requiring hemodialysis has increased substantially. Vascular access is the lifeline for a patient on hemodialysis (HD), and an arteriovenous fistula (AVF) is the undisputed gold standard for HD access. An effective and long-lasting fistula serves to increase the life expectancy of ESRD patients and improves their quality of life. Learning Objectives This paper aims to give a comprehensive overview of AVF creation, including the various techniques, patient selection, troubleshooting with decision-making, and common complications. Authors share their experience from previous publications and over 2000 AVF surgeries. They have not only described a new modification of the technique of proximal fistula but have also established a direct correlation between bruit and thrill on operation table and success of fistula surgery. Conclusion A standardized, protocol-driven multidisciplinary approach with careful patient and site selection, guided by outcome predictors, is vital in AVF surgery. Knowledge about the potential complications of AVFs contributes to their timely detection and allows measures to be taken that might prevent deleterious consequences that range from loss of vascular access to serious morbidity and mortality.

Proton pump inhibitors use and risk of chronic kidney disease and end-stage renal disease.

A possible association between long-term proton pump inhibitors (PPI) use and chronic kidney disease (CKD) has been recently described. Due to the potential health risk of this association, in the absence of proper clinical trials, we have decided to carry out a systematic review followed by meta-analysis. PubMed, Cochrane Library, and Lilacs databases were searched. Studies that reported an association between PPI use and CKD or End-stage Renal Disease (ESRD) published until December 23, 2019, were included. All selected studies present high quality according to the New-Castle-Ottawa. The risk ratio (RR) and confidence interval (CI) were pooled using a random-effects model in CKD outcome analysis and fixed effects model for ESRD. A total of 10 observational studies were selected. Compared to patients who did not use PPI, the RR for CKD associated with PPI use was 1.35 (95% CI 1.15-1.56) with P<0.001, and the RR for ESRD associated with PPI use was 1.49 (95% CI 1.41-1.56) with P<0.001. This study indicates the presence of a significant association between PPI use and an increased risk of CKD and ESRD and reiterates the need for the medical prescription of this class of drugs to be made following the guidelines of the FDA.

Association of chronic kidney disease and end-stage renal disease with procedural complications and in-hospital outcomes from left atrial appendage occlusion device implantation in patients with atrial fibrillation: Insights from the national inpatient sample of 36,065 procedures.

BackgroundLeft atrial appendage occlusion (LAAO) has emerged as an alternative strategy to oral anticoagulation for mitigating ischemic stroke risk in selected patients with atrial fibrillation (AF), but safety data in patients with significant kidney disease are limited.ObjectiveTo determine the association of chronic kidney disease (CKD) and end-stage renal disease (ESRD) with procedural complications and in-hospital outcomes after LAAO in AF patients.MethodsData were extracted from National Inpatient Sample for calendar years 2015–2018. Watchman implantations were identified on the basis of International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes of 37.90 and 02L73DK. The outcomes assessed in our study included complications, inpatient mortality, and resource utilization with LAAO.ResultsA total of 36,065 Watchman recipients were included in the final analysis. CKD (9.8%, n = 3545) and ESRD (3%, n = 1155) were associated with a higher prevalence of major complications and mortality in crude analysis compared to no CKD. After multivariate adjustment for potential confounders, CKD was associated with length of stay (LOS) >1 day (adjusted odds ratio [aOR] 1.355; 95% confidence interval [CI] 1.234–1.488), median cost >$24,663 (aOR 1.267; 95% CI 1.176–1.365), and acute kidney injury (aOR 4.134; 95% CI 3.536–4.833), while ESRD was associated with in-patient mortality (aOR 7.156; 95% CI 3.294–15.544).ConclusionThe prevalence of CKD and ESRD was approximately 13% in AF patients undergoing Watchman LAAO implantations. CKD was independently associated with prolonged LOS, higher hospitalization costs, and acute kidney injury, while ESRD was independently associated with in-patient mortality.

The Loss of Mitochondrial Quality Control in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the predominant complication of diabetes mellitus (DM) and the leading cause of chronic kidney disease and end-stage renal disease worldwide, which are major risk factors for death. The pathogenesis of DKD is very complicated, including inflammation, autophagy impairment, oxidative stress, and so on. Recently, accumulating evidence suggests that the loss of mitochondrial quality control exerts critical roles in the progression of DKD. Mitochondria are essential for eukaryotic cell viability but are extremely vulnerable to damage. The mechanisms of mitochondrial quality control act at the molecular level and the organelle level, including mitochondrial dynamics (fusion and fission), mitophagy, mitochondrial biogenesis, and mitochondrial protein quality control. In this review, we summarize current knowledge of the role of disturbances in mitochondrial quality control in the pathogenesis of DKD and provide potential insights to explore how to delay the onset and development of DKD.

The Association of Chronic Kidney Disease With Outcomes Following Percutaneous Left Atrial AppendageClosure.

The aim of this study was to investigate the associations of chronic kidney disease (CKD) and end-stage renal disease (ESRD) with in-hospital and short-term outcomes using a large national database representative of contemporary clinical practice. CKD and ESRD are associated with increased risk for stroke and bleeding in patients with atrial fibrillation on oral anticoagulation. Left atrial appendage closure (LAAC) may provide a reasonable alternative for these patients; however, the impact of CKD and ESRD on in-hospital and short-term outcomes following LAAC remain largely unknown. The Nationwide Readmissions Database was used to identify LAAC procedures from 2016 to 2017 in patients with no CKD, CKD (stages I-V), and ESRD. Multivariable logistic regression models were used to assess in-hospital and short-term outcomes. The primary outcome was in-hospital mortality. Of 21,274 patients who underwent LAAC during the study period, 3,954 (18.6%) had CKD and 571 (2.7%) had ESRD. ESRD was associated with increased risk for in-hospital mortality compared with no CKD (3.3% vs 0.4%; adjusted odds ratio: 6.48; 95% confidence interval: 3.35-12.50; P< 0.001) and CKD (3.3% vs 0.5%; adjusted odds ratio: 11.43; 95% confidence interval: 4.77-27.39; P< 0.001). CKD was associated with increased risk for in-hospital acute kidney injury or hemodialysis and stroke or transient ischemic attack. ESRD and CKD were associated with increased readmissions extending to 90days compared with no CKD, and ESRD was associated with increased readmissions compared with CKD. There was no difference with respect to other in-hospital outcomes. ESRD is associated with higher in-hospital mortality, and CKD is associated with higher rates of stroke or transient ischemic attack in patients undergoing LAAC. Further research is needed to assess the impact of CKD and ESRD on long-term outcomes in these patients.

Hepatocellular carcinoma in patients with renal dysfunction: Pathophysiology, prognosis, and treatment challenges.

The population of patients with hepatocellular carcinoma (HCC) overlaps to a high degree with those for chronic kidney disease (CKD) and end-stage renal disease (ESRD). The degrees of renal dysfunction vary, from the various stages of CKD to dialysis-dependent ESRD, which often affects the prognosis and treatment choice of patients with HCC. In addition, renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes. This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction. The possible mechanisms of CKD causing HCC involve uremia itself, long-term dialysis status, immunosuppressive agents for postrenal transplant status, and miscellaneous factors such as hormone alterations and dysbiosis. The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome. Finally, we categorized the risk factors that could lead to both HCC and CKD into four categories: Environmental toxins, viral hepatitis, metabolic syndrome, and vasoactive factors. Both CKD and ESRD have been reported to negatively affect HCC prognosis, but more research is warranted to confirm this. Furthermore, ESRD status itself ought not to prevent patients receiving aggressive treatments. This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment, treatment-related adverse renal effects, and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD. Such aggressive treatments include liver resection, simultaneous liver kidney transplantation, radiofrequency ablation, and transarterial chemoembolization. Finally, focusing on patients unable to receive active treatment, this study compiled information on the latest systemic pharmacological therapies, including targeted and immunotherapeutic drugs. Based on available clinical studies and Food and Drug Administration labels, this study details the drug indications, side effects, and dose adjustments for patients with renal dysfunction. It also provides a comprehensive review of information on HCC patients with renal dysfunction from disease onset to treatment.

Patient characteristics, care patterns, and outcomes of atrial fibrillation associated hospitalizations in patients with chronic kidney disease and end-stage renal disease

Chronic Kidney Disease (CKD) and end-stage renal disease (ESRD) are associated with poor outcomes in patients with cardiovascular disease. There is a paucity of contemporary data on in-hospital outcomes and care patterns of atrial fibrillation (AF) associated hospitalizations CKD and ESRD. Outcomes and care patterns were evaluated in GWTG-AFIB database (Jan 2013-Dec 2018), including in-hospital mortality, use of a rhythm control strategy, and oral anticoagulation (OAC) prescription at discharge among eligible patients. Generalized logistic regression models with generalized estimating equations were used to ascertain differences in outcomes. Hospital-level variation in OAC prescription and rhythm control was also evaluated. Among 50,154 patients from 105 hospitals the median age was 70 years (interquartile range 61-79) and 47.3% were women. The prevalence of CKD was 36.0% while that of ESRD was 1.6%. Among eligible patients, discharge OAC prescription rates were 93.6% for CKD and 89.1% for ESRD. After adjustment, CKD and ESRD were associated with higher in-hospital mortality (odds ratio [OR] 3.08, 95% confidence interval [CI] 1.57-6.03 for ESRD and OR 2.02, 95% CI 1.52-2.67 for CKD), lower odds of OAC prescription at discharge (OR 0.59, 95% CI 0.44-0.79 for ESRD and OR 0.84, 95% CI 0.75-0.94 for CKD) compared with normal renal function. CKD was associated with lower utilization of rhythm control strategy (OR 0.92, 95% CI 0.87-0.98) with no significant difference between ESRD and normal renal function (OR 1.32, 95% CI 0.79-1.11). There was large hospital-level variation in OAC prescription at discharge (MOR 2.34, 95% CI 2.05-2.76) and utilization of a rhythm control strategy (MOR 2.69, 95% CI 2.34-3.21). CKD/ESRD is associated with higher in-hospital mortality, less frequent rhythm control, and less OAC prescription among patients hospitalized for AF. There is wide hospital-level variation in utilization of a rhythm control strategy and OAC prescription at discharge highlighting potential opportunities to improve care and outcomes for these patients, and better define standards of care in this patient population.

Coronary revascularisation in patients with chronic kidney disease and end-stage renal disease: A meta-analysis.

ObjectivesTo compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for revascularising coronary arteries in patients with chronic kidney disease (CKD) and end‐stage renal disease (ESRD). CKD is described as a continuous decrease in the glomerular filtration rate or abnormalities in kidney structure or function.MethodsPubMed, Cochrane Library and Embase databases were searched for studies on the revascularisation of coronary arteries in patients with CKD and ESRD.ResultsSince no randomised controlled trials (RCTs) have addressed this issue so far, 31 observational studies involving 74 805 patients were included in this meta‐analysis. Compared with PCI, patients undergoing CABG have significantly higher early mortality (CKD: RR = 1.62, 95% CI: 1.17‐2.25, pheterogeneity = 0.476, I 2 = 0; ESRD: RR = 1.99, 95% CI: 1.46‐2.71, pheterogeneity = 0.001, I 2 = 66.9%). Patients with ESRD undergoing CABG have significantly lower all‐cause mortality (RR = 0.95, 95% CI: 0.93‐0.96, pheterogeneity < 0.001, I 2 = 82.9%) and cardiac mortality (RR = 0.73, 95% CI: 0.58‐0.92, pheterogeneity = 0.908, I 2 = 0). The long‐term risk of repeat revascularisation (CKD: RR = 0.24, 95% CI: 0.19‐0.30, pheterogeneity = 0.489, I 2 = 0; ESRD: RR = 0.23, 95% CI: 0.15‐0.34, pheterogeneity = 0.012, I 2 = 54.4%) and myocardial infarction (CKD: RR = .57, 95% CI: 0.38‐0.85, pheterogeneity = 0.025, I 2 = 49.9%; ESRD: RR = 0.42, 95% CI: 0.40‐0.44, pheterogeneity = 0.49, I 2 = 0) remained significantly higher in the PCI group.ConclusionsPatients with ESRD, but not CKD, who underwent CABG had significantly lower all‐cause mortality and cardiac mortality. However, CABG was associated with an increased risk of early mortality in patients with CKD or ESRD. Adequately powered, contemporary, prospective RCTs are needed to define the optimal revascularisation strategy for patients with CKD and ESRD.

Design and conduct considerations for studies in patients with impaired renal function.

An impaired renal function, including acute and chronic kidney disease and end‐stage renal disease, can be the result of aging, certain disease conditions, the use of some medications, or as a result of smoking. In patients with renal impairment (RI), the pharmacokinetics (PKs) of drugs or drug metabolites may change and result in increased safety risks or decreased efficacy. In order to make specific dose recommendations in the label of drugs for patients with RI, a clinical trial may have to be conducted or, when not feasible, modeling and simulations approaches, such as population PK modeling or physiologically‐based PK modelling may be applied. This tutorial aims to provide an overview of the global regulatory landscape and a practical guidance for successfully designing and conducting clinical RI trials or, alternatively, on applying modeling and simulation tools to come to a dose recommendation for patients with RI in the most efficient manner.

Impact of polypharmacy on all-cause mortality and hospitalization in incident hemodialysis patients: a cohort study.

Polypharmacy (PP) is common in end-stage chronic renal disease patients largely due to the presence of multiple comorbid conditions. Although PP is potentially harmful, its relationship with mortality and morbidity in hemodialysis patients currently remains unclear. Study design: cohort study. participants: one hundred and fifty-two initial hemodialysis patients (male, 88 patients; mean age, 70.3years) were enrolled between February 2015 and March 2018 at Nobeoka Prefectural Hospital and Chiyoda Hospital. patients were divided into 2 groups according to PP (6 or more drug prescriptions or less) during admission and discharge for the initiation of hemodialysis. all-cause mortality and hospitalization during the mean 2.8-year follow-up. hazard ratios (HRs) were estimated using Cox's model for the relationships between PP and clinical outcomes and adjusted for potential confounders. The group with 5 or less drug prescriptions was set as a reference. The number of prescribed drugs per patient averaged 7.4 at admission and 7.0 at discharge for initial hemodialysis. One hundred (65.8%) and 94 patients (61.8%) had PP at admission and discharge, respectively. During the follow-up, 20 patients died and 71 were hospitalized. PP at admission did not correlate with outcomes, whereas that at discharge correlated with all-cause hospitalization. PP at discharge may be associated with clinical outcomes. However, it remains unclear whether PP is the direct cause of outcomes or is simply a marker for an increased risk of outcomes.

Pathophysiological Implications of Imbalances in Fibroblast Growth Factor 23 in the Development of Diabetes.

Observational studies have associated the increase in fibroblast growth factor (FGF) 23 levels, the main regulator of phosphate levels, with the onset of diabetes. These studies open the debate on the plausible existence of undescribed diabetogenic mechanisms derived from chronic supraphysiological levels of FGF23, a prevalent condition in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. These maladaptive and diabetogenic responses to FGF23 may occur at different levels, including a direct effect on the pancreatic ß cells, and an indirect effect derived from the stimulation of the synthesis of pro-inflammatory factors. Both mechanisms could be mediated by the binding of FGF23 to noncanonical receptor complexes with the subsequent overactivation of signaling pathways that leads to harmful effects. The canonical binding of FGF23 to the receptor complex formed by the receptor FGFR1c and the coreceptor αKlotho activates Ras/MAPK/ERK signaling. However, supraphysiological concentrations of FGF23 favor non-αKlotho-dependent binding of this molecule to other FGFRs, which could generate an undesired overactivation of the PLCγ/CN/NFAT pathway, as observed in cardiomyocytes and hepatocytes. Moreover, the decrease in αKlotho expression may constitute a contributing factor to the appearance of these effects by promoting the nonspecific activation of the PLCγ/CN/NFAT to the detriment of the αKlotho-dependent Ras/MAPK/ERK pathway. The description of these mechanisms would allow the development of new therapeutic targets susceptible to be modified by dietary changes or by pharmacological intervention.

Uremic Toxins and Their Relation with Oxidative Stress Induced in Patients with CKD.

The presence of toxins is believed to be a major factor in the development of uremia in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Uremic toxins have been divided into 3 groups: small substances dissolved in water, medium molecules: peptides and low molecular weight proteins, and protein-bound toxins. One of the earliest known toxins is urea, the concentration of which was considered negligible in CKD patients. However, subsequent studies have shown that it can lead to increased production of reactive oxygen species (ROS), and induce insulin resistance in vitro and in vivo, as well as cause carbamylation of proteins, peptides, and amino acids. Other uremic toxins and their participation in the damage caused by oxidative stress to biological material are also presented. Macromolecules and molecules modified as a result of carbamylation, oxidative stress, and their adducts with uremic toxins, may lead to cardiovascular diseases, and increased risk of mortality in patients with CKD.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury.

Acute kidney injury (AKI) is a common and potential life-threatening disease in patients admitted to hospital, affecting 10%–15% of all hospitalizations and around 50% of patients in the intensive care unit. Severe, recurrent, and uncontrolled AKI may progress to chronic kidney disease or end-stage renal disease. AKI thus requires more efficient, specific therapies, rather than just supportive therapy. Mesenchymal stem cells (MSCs) are considered to be promising cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to expand in vitro. Recent research indicated that the main therapeutic effects of MSCs were mediated by MSC-derived extracellular vesicles (MSC-EVs). Furthermore, compared with MSCs, MSC-EVs have lower immunogenicity, easier storage, no tumorigenesis, and the potential to be artificially modified. We reviewed the therapeutic mechanism of MSCs and MSC-EVs in AKI, and considered recent research on how to improve the efficacy of MSC-EVs in AKI. We also summarized and analyzed the potential and limitations of EVs for the treatment of AKI to provide ideas for future clinical trials and the clinical application of MSC-EVs in AKI.

1048-P: Factors Contributing to Early Mortality in Persons with Type 2 Diabetes with Lower Extremity Amputation

Introduction: Type 2 diabetes continues to be one of the most common and costly conditions in the United States. Complications and co-morbidities that develop, such as amputations, add to the financial toll and can reduce the life expectancy of these individuals. The aim of this study was to identify risk factors that lead to early mortality (12 months or less) following subacute inpatient, interdisciplinary rehabilitation at a VA Community Living Center (CLC). Methods: A retrospective medical chart review was conducted on forty-seven Veterans who had a lower extremity amputation and died between 2015-2018. Demographic variables collected included age, months between discharge and death, and social support at home. Conditions on status of hypertension, type 2 diabetes, coronary artery disease, congestive heart failure, smoking status, end-stage renal disease and chronic renal disease were gathered at date of death. Results: The mean age at CLC admission was 68 years and the average time of death was 14.2 months after discharge. It was shown that 50.5% of the patients returned home to social support. Mean HbA1c was 7.1% prior to amputation. A multiple logistic regression was performed associating status of persons with type 2 diabetes (P=.043, 95% CI = .09 - 5.25) and concurrent chronic renal disease (P=.02, 95% CI = .33 - 4.79) leading to death at less than 12 months. There was no significant relationship between hypertension, smoking, age, end-stage renal disease, congestive heart failure with mortality after discharge from the CLC. No association was found between pre-operative HbA1c status and survivorship. Conclusion: There was a relationship between those who died within 12 months and diagnosis with both type 2 diabetes and chronic renal disease after an inpatient stay at a VA Community Living Center. These results suggest diabetes along with concurrent chronic renal disease management needs to be maintained after an inpatient stay to prevent premature death. Disclosure J. Chan: None. K. Yan: None.

Prognostic evaluation model of diabetic nephropathy patients.

Diabetic nephropathy (DN) affects about 40% of diabetes mellitus (DM) patients and is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) globally, especially in advanced countries. We aimed to explore the risk factors affecting the prognosis of DN, and to establish a prognostic evaluation line map. We analyzed 471 cases of DN from December 2011 to April 2020, and extracted the basic clinical factors, including gender, age, and history of diabetes. Analysis included that of associations between DN and hypertension, creatinine (CR), body mass index (BMI), and fundus lesions. Statistical analysis was performed using R software and the related R package. The above clinical factors were analyzed by both single- and multiple-factor Cox regression. The participants were divided into two groups, including a high risk and a low risk group. A Kaplan-Meier curve was drawn for survival analysis of the high and low risk groups, and the log-rank method was used for statistical testing. A receiver operating characteristic (ROC) curve was drawn with the area under the curve (AUC) calculated to evaluate the predictive effectiveness of the line map. This study initially included 471 patients; however, 33 patients (7.0%) were lost to follow-up due to inaccessibility. A total of 93 cases (21.2%) died during the follow-up. The 3-year and 5-year renal survival rates were 74.5% and 22.6%, respectively. Single factor Cox analysis showed that the course of diabetes, fundus lesions, BMI, and grade of hypertension were risk factors for renal survival, and had adverse effects on prognosis (P<0.05). Multivariate Cox regression analysis showed that BMI and grade of hypertension were independent risk factors for survival of DKD, and had adverse effects on prognosis (P<0.05). Survival analysis showed that low risk group participants had significantly better survival rates than high risk group participants (P<0.05). The AUC was 0.742, which meant that the line map could accurately predict the survival rate of DN patients. The influence of risk factors on prognosis can be accurately evaluated by line diagram which can provide a basis for clinical decision making.

MO067DELETION AND BLOCKAGE OF KININ B1 RECEPTOR EXACERBATES CISPLATIN-INDUCED CKD

Abstract Background and Aims Kinins plays a major role in immune response, where kinin B2 receptor is constitutively expressed and kinin B1 receptor is induced under inflammatory stimuli. Kinin B1 receptor deletion and blockage has been shown to have beneficial effects in some models of renal diseases. Multiple acute renal insults, even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Our main objective was to determine the importance of kinin B1 receptor in tubulointerstitial fibrosis induced by ongoing cisplatin treatment. Method Male C57/Bl6 mice were divided in 3 groups, vehicle, cisplatin, cisplatin + R715 (kinin B1 receptor antagonist). Animals has been treated with multiple doses of cisplatin (7mg/kg i.p) once a week during 4 weeks and R715 (0.8mg/kg i.p) 48, 24 and 1 hour prior to cisplatin injections. We also used B1KO mice (C57Bl6 background) and WT mice (littermates). Mice were euthanized after 30 days of last cisplatin injection. Renal parameters, histology, real time PCR were performed to investigate renal injury, inflammation and fibrosis. Results Cisplatin treatment increases most of renal parameters, renal injury and fibrosis markers. Deletion of B1 receptor exacerbates significantly creatinine (WT CIS 0,60+0,03 B1KO 0,76+0,01 mg/dL), urea (WT CIS 111,8+5,638 B1KO CIS 240,8+28,60 mg/dL), and protein excretion (WT CIS 0,0058+0,0011 B1KO CIS 0,0121+0,0007 mg/24h). Association of cisplatin with R715 increased creatinine levels (veh 0,43+0,03 cis+R715 0,64+0,04 mg/dL), exacerbates urea (cis 95,51 + 3,926 cis+R715 158,9+14,40 mg/dL) and protein excretion (cis 0,012+0,002 cis+R715 0,018+0,003 mg/24h). Renal injury markers such as KIM-1 and TNF-a showed no significant differences. NGAL expression exacerbates (cis 2,53+0,44 cis+R715 5,66+1,34) and tubular injury score (cis 0,130+0,021 cis+R715 0,191+0,020) is higher in cisplatin+R715 group. Fibrosis markers a-SMA (cis 2,56+0,43 cis+R715 4,67+0,99), Col4 (cis 2,57+0,39 cis+R715 5,14+1,01) and Vimentin (2,69+0,31 cis+R715 4,62+0,98) were exacerbated in cisplatin treatment associated with R715. Picrosirius red staining were used to asses tubulointerstitial fibrosis, and we confirmed that R715 treatment here also exacerbates fibrosis (cis 0,225+0,025 cis+R715 0,345+0,042). Conclusion Here we show that both deletion and blockage of kinin B1 receptor has deleterious effects in renal injury and fibrosis induced by ongoing cisplatin treatment.

MO116COMPARISON OF THE CHARACTERISTICS BETWEEN UNILATERAL AND BILATERAL RENAL STONES AND THEIR ASSOCIATION WITH KIDNEY INJURY IN CHINESE POPULATION

Abstract Background and Aims Urinary stone disease (USD) has been associated with increased risk for chronic kidney disease (CKD) and end-stage renal disease (ESRD) in Western populations. However, the comparison of metabolic disorders between unilateral and bilateral renal stones and their association with CKD have not been fully examined. It is also unclear whether there is an increased risk for kidney tubular injury makers such as N-acetyl-ß-D-glucosaminidase (NAG) and alpha-1-microglobulin (α1-MG) in different stone formers. Method We performed a cross-sectional study of 10,281 participants in rural China in 2014. All subjects underwent a renal ultrasound to detect USD; stone formers were grouped into one or two sides of USD by ultrasound exams. CKD was defined as a decreased estimated glomerular filtration rate (eGFR, &amp;lt;60mL/min/1.73m2) and/or albuminuria (ACR≥30mg/g). Increased urine NAG and α1-MG were defined as the values of NAG and α1-MG above the 75th percentile of the sample distribution. Results The mean age of the study population was 55.4±10.0 years; 47.1% were males. Among all participants, 4.9% (n=507) had unilateral renal stone, and 0.7% had bilateral renal stones. The proportion of CKD in non-stone formers, unilateral and bilateral renal stones were 11.0%, 19.2%, and 29.7%, respectively (p for trend&amp;lt;0.001). Bilateral renal stone formers tend to have a higher proportion of hypertension and diabetes. In multivariate analyses after adjustment for multiple confounders, bilateral renal stones were significantly associated with an increased risk of decreased eGFR (OR 3.38; 95% CI 1.05-10.90), albuminuria (OR 3.01; 95% CI 1.76-5.13), CKD (OR 3.18; 95% CI 1.88-5.36), increased NAG (OR 1.95; 95% CI 1.21-3.16) and α1-MG (OR 2.54; 95% CI 1.56-4.12) compared with non-stone formers. Conclusion In the present study, bilateral renal stone formers tend to have a higher proportion of metabolic disorders and are also associated with a higher risk of CKD and kidney tubular injury. Further studies are needed to confirm the increased risk for ESRD.

Proteinuria and Psoriasis Risk: A Nationwide Population-Based Study.

Psoriasis, a chronic inflammatory dermatosis, has been associated with chronic kidney disease or end-stage renal disease. However, the association of the changes or amount of proteinuria with psoriasis development has not been evaluated. Using the Korean National Health Screening database, we assessed psoriasis development until 2018 in 6,576,851 Koreans who underwent health examinations in 2009 and 2011. Psoriasis was defined using the International Classification of Diseases, 10th revision (ICD-10) code L40. The risk of psoriasis was evaluated according to change in proteinuria (never [Neg (no proteinuria)/Neg], new [Neg/Pos (proteinuria present)], past [Pos/Neg] and persistent [Pos/Pos] proteinuria) and the proteinuria amount. During a median 7.23-year follow-up, 162,468 (2.47%) individuals developed psoriasis. After adjustments, the hazard ratio (HR) for psoriasis was higher in the persistent proteinuria group (1.32 [1.24–1.40]) than in the never proteinuria group. The past proteinuria group showed better renal outcome (1.03 [1.00–1.07]) than the new (1.05 [1.01–1.07]) and never proteinuria (reference, 1.00) groups did. The amount of random urine proteinuria was associated with increased HR for psoriasis. Subgroup analyses for age, sex, estimated glomerular filtration rate (eGFR), hypertension and diabetes showed that the persistent proteinuria group had a higher risk of psoriasis than the never proteinuria group, especially at eGFR < 60 mL/min/1.73 m2. Persistent proteinuria is associated with psoriasis risk, and the proteinuria amount significantly affects psoriasis development.