Risk Factor For Renal Disease Research Articles

Effects of Microplastic (MP) Exposure at Environmentally Relevant Doses on the Structure, Function, and Transcriptome of the Kidney in Mice.

As a common emerging environmental pollutant, microplastics (MPs) have been detected in a variety of environmental media and human bodies. The potential toxic effects and mechanisms of MPs need to be revealed urgently. MPs can be deposited in the kidney, and exposure to high doses of MPs can cause nephrotoxicity in experimental animals. In this study, we investigated the effects of exposure to polystyrene microplastics (PS-MPs) at environmentally relevant doses (0.1 and 1 mg/L) on kidney structure, function, and transcriptome in mice. We found that mice exposed to PS-MPs in drinking water for eight weeks had no change in body weight or kidney coefficient. PS-MPs administration decreased the levels of blood urea nitrogen (BUN) in mice, while serum creatinine (CRE) and uric acid (UA) concentrations were unaffected. Through using periodic acid-Schiff (PAS) and Masson staining, we discovered that the glomerular tuft area increased in the PS-MP-treated mice, while the degree of renal fibrosis remained unchanged. Furthermore, renal cortex transcriptomic analysis identified 388 and 303 differentially expressed genes (DEGs) in the 0.1 and 1 mg/L dose groups, respectively. The DEGs were highly enriched in mitochondrial-related terms and pathways of thermogenesis and oxidative phosphorylation. Moreover, protein-protein interaction (PPI) network analysis revealed that cytochrome b-c1 complex subunit 10 (UQCR11) and cytochrome c oxidase subunit 3 (MT-CO3) were important node proteins. These findings suggest that environmental exposure to MPs can cause abnormalities in renal structure and filtration function and that long-term exposure to MPs may be a risk factor for renal disease.

Chloroquine inhibits NLRP3 inflammasomes activation and alleviates renal fibrosis in mouse model of hyperuricemic nephropathy with aggravation by a high-fat-diet

Numerous epidemiological studies have demonstrated that hyperuricemia (HUA) is a risk factor for renal diseases and renal fibrosis. Dietary patterns can influence serum urate levels and hyperuricemic nephropathy (HN). NLRP3 inflammasomes play a crucial role in various inflammatory responses and contribute to HN progression. Chloroquine (CQ) is an anti-inflammatory and disease-modifying anti-rheumatic drug (DMARD) utilized in treating autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. In this study, we examined the effects and underlying mechanisms of CQ in a high-fat-diet (HFD) exacerbated mouse model of HN. C57BL/6 mice were randomized into either a control group or an HN group (induced by adenine/potassium oxonate treatment), followed by a normal diet or HFD, with or without CQ treatment. Our findings revealed that the HN group exhibited elevated serum levels of blood urea nitrogen (BUN) and creatinine compared to the control group. Additionally, the HN + HFD group displayed increased serum levels of uric acid, BUN, and creatinine relative to the control + HFD group. Moreover, the HFD exacerbated renal uric acid crystal deposition and fibrosis in HN mice compared to a normal diet. CQ ameliorated renal dysfunction, as evidenced by reduced serum creatinine levels, renal fibrosis, and renal tubular injury scores, and significantly decreased NLRP3, ASC, caspase-1, and IL-1β levels in HN mice. These findings suggest that CQ inhibits the activation of NLRP3 inflammasomes and may serve as a potential therapeutic strategy for HN treatment.

Association of Oxidative Stress with Kidney Injury in a Hyperandrogenemic Female Rat Model.

Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is associated with oxidative stress (OS), which is the main risk factor for renal diseases. This study aimed to investigate the mechanisms responsible for renal injury in a hyperandrogenemic female rat model. This study was conducted from December 2019 to September 2021 at Shiraz Nephro-Urology Research Centre, Shiraz University of Medical Sciences (Shiraz, Iran). Thirty female Sprague-Dawley rats were randomly divided into three groups (n=10), namely control, sham, and dehydroepiandrosterone (DHEA). Plasma total testosterone, plasma creatinine (Cr), and blood urea nitrogen (BUN) levels were measured. In addition, total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and histopathological changes in the ovaries and kidneys were determined. Data were analyzed using the GraphPad Prism software, and P<0.05 was considered statistically significant. Plasma total testosterone levels increased by nine-fold in DHEA-treated rats compared to controls (P=0.0001). Administration of DHEA increased Cr and BUN levels and caused severe renal tubular cell injury. In addition, plasma and tissue (kidney and ovary) TAC levels decreased significantly, but TOS levels and OSI values were significantly increased (P=0.019). Significant damage to both glomerular and tubular parts of the kidney and ovarian follicular structure was observed in the DHEA group. Hyperandrogenemia caused systemic abnormalities through OS-related mechanisms and damaged renal and ovarian tissues. DHEA treatment in rat models is recommended to study the mechanisms that mediate PCOS-associated renal injury.

A Review on Machine Learning Approaches for HIV Infected Patient Chronic Kidney Disease Stage Classification

Chronic kidney disease (CKD) is sometimes called chronic kidney failure. The kidneys eliminate waste and surplus fluids from the circulation and excrete them as urine. In severe chronic renal disease, fluid, electrolytes, and waste products may build up in the body. HIV patients with additional risk factors for renal disease must have kidney function evaluated annually. HIV may damage kidney filters. The filters won't work properly. CKD has five stages, with more severe symptoms from stage 1 to stage 5. If chronic kidney disease continues to stage 4 or 5, our bodies might accumulate fluid and waste. Machine learning categories HIV-positive CKD patients based on their features. Machine learning relies on feature selection. This research uses feature selection and classification to accurately predict chronic renal illness.

The laboratory and hypertension - Novel approach for diagnosis and management

Hypertension remains one of the most significant causes of mortality, affecting more than 1 billion people worldwide. It is a significant public health concern and a major risk factor for renal disease, heart failure, stroke, coronary artery disease and peripheral vascular disease. In more than 90% of hypertensive patients, the cause of blood pressure elevation is unknown. Therefore, early diagnosis and timely interventions are crucial to prevent complications. Over the last four decades, various blood biomarkers have been identified, which can help in understanding the cause of the underlying processes involved in the onset, development and progression of hypertension (HT). It is our attempt, in this review, to suggest a more robust use of circulating biomarkers that may prove to be beneficial in better elucidating the pathophysiology, development, progression and therapeutic efficacy in the management of HT.

Association of Vitamin D Receptor Genetic Polymorphisms With Nephrolithiasis and End-Stage Renal Disease: A Meta-Analysis

Our objective was to evaluate the association between vitamin D receptor (VDR) BsmI, FokI, TaqI, and ApaI gene polymorphisms and the risk of renal disease. Ameta‑analysis was conducted to determine the correlation between these VDR gene polymorphisms and the renal disease. Meta-analysis was carried out to clarify the association of BsmI (2467 cases and 2651 controls), FokI (2460 cases and 3085 controls), TaqI (3181cases and 3713 controls), and ApaI (2512 cases and 3091 controls) polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN), and end-stage renal disease (ESRD). The VDR BsmI C allele, under the allele contrast random effect model, was associated with renal diseases calculated for ESRD. Subgroup analysis revealed association of VDR FokI polymorphism with ESRD and no association with NL and DN. The VDR TaqI C allele, under the allele contrast fixed effect model, was associated with renal diseases calculated collectively for DN, ESRD, and NL. Cochran's Q test showed no evidence of heterogeneity for TaqI and ApaI polymorphisms and showed a significant heterogeneity for BsmI and FokI polymorphisms. This meta-analysis identifies BsmI, FokI, TaqI and ApaI polymorphisms of the VDR gene as risk factors for renal diseases.

HLA gene polymorphism among Bangladeshi patients with end-stage renal disease awaiting kidney transplantation

Proper matching of HLA class I and class II antigens among donor and recipient is an important prerequisite for the long survival of a transplanted organ. To reveal the HLA gene polymorphism among end-stage renal disease (ESRD) patients and their donors, a total of 180 ESRD patients and 320 donors, referred by clinicians for HLA typing, were included in this study. HLA typing was performed using Polymerase Chain Reaction-Se- quence Specific Primer (PCR-SSP). The most frequent alleles reported from both groups were, A*11, A*02 and A*33 in A locus; B*15:02, B*35 and B*52 in B locus and DRB1*15, DRB1*07 and DRB1*04 in DR locus. Frequencies of four alleles, A*26, B*57, B*40 and DRB1*11 were found to be higher in ESRD patients. The three locus haplotypes A*24, B*15:02, DRB1*15 were observed more frequently among recipients than in donors. The results were found to be in genetic equilibrium. Higher frequencies of certain alleles in recipients may be indicative of risk factor for renal disease. Further studies are needed to corroborate the findings of this study. BSMMU J 2022; 15(1): 01-10

Chronic hepatitis B virus infection increases the risk of upper urinary calculi

BackgroundAlthough hepatitis B virus (HBV) is a recognized risk factor for renal diseases, little is known about HBV infection in individuals with upper urinary calculi (UUC). We investigated the relationship between chronic HBV infection and UUC.MethodsWe retrospectively analysed data from 1399 patients who were discharged from the Department of Urology (2017–2018). The diagnosis of UUC was determined using urinary tract ultrasonography or computed tomography, and HBV infection was evaluated by a positive hepatitis B surface antigen (HBsAg) test. Data on patients with and without UUC and HBsAg-positive and HBsAg-negative patients were compared by univariate and multivariate analyses.ResultsData on chronic HBV infection and UUC were available for 1062 patients, including 514 who presented with UUC and 548 who did not. Overall, 5.8% of total patients, 8.0% of UUC patients and 3.8% of non-UUC patients had chronic HBV infection. UUC patients (41/514) had a significantly higher prevalence of HBsAg positivity (OR 2.175; 95% CI 1.267–3.734; P = 0.004) than non-UUC patients (21/548). After stratifying by sex, the relative odds of HBsAg positivity were statistically significant in men (OR 2.156; 95% CI 1.162–4.003; P = 0.015) but not in women (OR 2.947; 95% CI 0.816–10.643; P = 0.099). The incidence of urinary pH > 6 and staghorn stones was significantly higher in HBsAg-positive UUC patients than in HBsAg-negative UUC patients.ConclusionThis is the first study to demonstrate that chronic HBV infection is strongly associated with UUC, at least in men. The urinary pH > 6 and staghorn stones were more common in UUC patients with chronic HBV infection.

MO043: Role of the I416L variant of complement factor I in the occurrence of thrombotic microangiopathy among patients of African ancestry

Abstract BACKGROUND AND AIMS Complement dependent hemolytic and uremic syndrome (c-HUS) predisposes to hypertensive crisis and chronic hypertension. Reciprocally, hypertensive crisis may precipitate thrombotic microangiopathy (TMA) via endothelial shear stress. Patients of African ancestry have long been recognized for their predisposition to both chronic hypertension and chronic kidney disease (CKD). Yet, despite growing evidence meant to bridge the divide between the complement alternative pathway and hypertensive crisis [1] (i) c-HUS is only known to account for a small fraction of the cases of malignant HTA (5%) [2] or TMA (4%) [3] (ii) complement genetic investigations in the population of African ancestry are sparse. Recently, the I416L CFI variant, which is specific to patients of African ancestry, has been classified as likely pathogenic (https://databases.lovd.nl/shared/variants/0000521158#00005040). By running a query through the BIOMNIS genetic databank, we sought to identify and provide a phenotypic description of the patients carrying the I416L CFI variant. METHOD All samples were sequenced at the BIOMNIS center (Lyon, France) using the Illumina platform and subsequently processed via the in-center bioinformatics pipeline. The BIOMNIS genetic databank compiles a total of 2886 whole exome sequencing (WES) nationwide (single unrelated patients) for renal (n = 1200) and non-renal indications (n = 1686). Once patients were recognized to carry the I416 variant, deidentified clinical data was provided by the attending nephrologist. RESULTS Among 1686 WES performed for non-renal indications, three unrelated patients harbored the I416L variant. Out of the 1200 WES performed for renal indications, we identified eight unrelated patients carrying the I416L CFI variant. All patients were of African Ancestry and were heterozygous for the variant, including five males with median age of 38.5 years. They all shared a common history remarkable for hypertension of early onset at median of 33 years [21–38]. None of these patients were acknowledged to have c-HUS prior to WES. In six cases, the kidney disease was undetermined. Four patients experienced TMA: three during bouts of malignant hypertension with concurrent biological TMA. One of them exhibited signs of TMA on biopsy with superimposed signs of malignant nephrosclerosis and another on a kidney transplant. Three patients disclosed genetic risk factor for kidney disease including Apol1 pathogenic variants (G1 and/or G2) (n = 2) and URAT1-related pathogenic variant (n = 1). Five patients had at least one additional risk factor for renal disease. All but one patient progressed to CKD including end-stage CKD on four instances with a median follow-up of 6.5 years. One patient presented with TMA following kidney transplantation. Only one patient whose hypertensive crisis manifested as preeclampsia and HELLP was free of CKD on last follow-up. CONCLUSION C-HUS may go unrecognized or mimic vascular nephropathy. These results make a case for a streamlined genotyping of patients, especially patients of African ancestry with a history of hypertension of early onset. Additional triggers acting as second ‘hits’ such as hypertension, pregnancy or genetic and non-genetic renal risk factors may aggravate the course of kidney disease. Yet, further investigations are warranted to appreciate the true clinical significance of this variant as it entails momentous therapeutic and medico-economic implications, most notably the use of anti-C5 therapy.

Investigation of acute kidney injury and related risk factors in patients with COVID-19

Introduction: The 2019 recent coronavirus disease (COVID- 19) is a novel pandemic disease in the world. The main organ involved in this viral sepsis is the respiratory system. Objectives: Regarding the expression of angiotensin-converting enzyme (ACE) receptors as entering route for virus’ particles into cells, the kidney organ is another important target in this catastrophic sepsis. There is little data about renal complications and related risk factors in victims. Patients and Methods: All patients with COVID-19 admitted to a referral and tertiary center (Shohada hospital, Khorramabad, Iran) were included in the study. The research was performed from February 20 to April 19, 2020. Diagnosis of patients was confirmed by COVID-19 upper respiratory sampling using real-time PCR. Patients’ demographic data, clinical and laboratory variables were included in pre-designed questionnaires according to the considered factors; then all collected data was entered into SPSS-26 software and statistical analysis was performed. Results: All COVID-19 patients included in the study were 232 cases. Out of them, 99 cases were female (42.7%) and 133 males (57.3%). Among patients, 19 cases had AKI (acute kidney injury); of these cases. Out of AKI patients, 12 (63.2%) were admitted to the ICU, whereas the mortality rate in patients with AKI was 63.2%. AKI was significantly associated with older age, ICU admission, and lower lymphocyte count. AKI occurrence was associated with the history of hypertension, or underlying kidney disease but hadn’t a significant relationship with diabetes. Conclusion: According to this study, age is an important risk factor for renal disease and poor outcomes in COVID-19 patients. Hence, old age patients should be given more attention. Concerning more prevalence of potassium disorders, further monitoring of hypokalemia or hyperkalemia is recommended. Considering, poor outcomes in patients with COVID-19 and AKI, nephrologist’s consultation is necessary.

MO1048PHYTOTHERAPY ON RENAL HYPOXIA: THE PREVENTIVE EFFECTS OF HYDROXYTYROSOL - PRELIMINARY IN VITRO RESULTS

Abstract Background and Aims Renal hypoxia plays a key role in the pathophysiology of acute kidney injury and in the progression of chronic kidney disease, potentiating other important risk factors for renal disease, such as oxidative stress, renal fibrosis, and inflammation. Hydroxytyrosol (HT) is a phenolic compound extracted from olives and olive-derived products, that has been shown to detain potent in vitro antioxidant and anti-inflammatory activity. The aim of this study was to evaluate the preventive therapeutic potential of HT on a cellular model of renal hypoxia. Method A cell line of normal adult proximal tubular epithelium (HK-2 cell line) was used to determine the effects of the chemical induction of hypoxia with cobalt chloride (CoCl2), as well as the preventive potential of HT on the elicited effects. For this purpose, HK-2 cells were exposed for 24 h to 254 µM CoCl2, to mimic the hypoxic conditions, or pre-incubated for 1 h with 5 µM HT and further exposed to the CoCl2 for 24 h more. Cell viability was assessed by the thiazolyl blue tetrazolium bromide reduction assay. Oxidative status was evaluated by the measurement of reactive oxygen and nitrogen species (ROS and RNS) and reduced glutathione (GSH) levels, by using standardized fluorometric and colorimetric assays. The expression of several genes related to the hypoxic, inflammatory, and fibrotic responses was determined by quantitative polymerase chain reaction (PCR). Results CoCl2-exposed HK-2 cells (hypoxic conditions) showed a significant decrease in cell viability (p &amp;lt; 0.0001 vs. control), and a disruption of the oxidative status, characterized by an increase of ROS and RNS production of about 6-fold over control cells (p &amp;lt; 0.0001) and a decrease in GSH intracellular levels of nearly 50 % (p &amp;lt; 0.05). Although the pre-exposure to HT showed no significant effects on the loss of cell viability elicited by CoCl2, the presence of HT prior to induction of hypoxia reduced the generation of ROS and RNS (p &amp;lt; 0.05 for HT + CoCl2 vs. CoCl2) and prevented the GSH depletion (GSH levels for HT + CoCl2 were similar to those of control) elicited by CoCl2. When compared to control cells, CoCl2-exposed HK-2 cells also showed increased expression of genes related to hypoxia (HIF1A, p &amp;lt; 0.05; GAPDH, p &amp;lt; 0.0001), as well as of modulators of inflammation (IL6, p &amp;lt; 0.0001) and fibrosis (TGFB1, p &amp;lt; 0.05). Importantly, the expression of these genes was partially or even totally suppressed by the pre-exposure of cells to HT (GAPDH, p &amp;lt; 0.01 for HT + CoCl2 vs. CoCl2; expression of HIF1A, IL6 and TGFB1 for HT + CoCl2 was similar to that of control). Conclusion Our data supports the potential for a multiplicity of preventive effects of HT, providing antioxidant, anti-inflammatory and anti-fibrotic defenses to renal cells under hypoxic conditions. Importantly, the development of safe and effective therapeutic approaches based on phytochemicals such as HT, may present substantial advantages for renal patients over synthetic drugs, including fewer side effects, significantly lower price, and ease of administration in the form of dietary supplements. Acknowledgments This work was supported by Applied Molecular Biosciences Unit (UCIBIO), financed by national funds from FCT/MCTES (UIDB/04378/2020), by North Portugal Regional Coordination and Development Commission (CCDR-N)/NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024), and co-financed by FCT/MCTES (PTDC/OCE-ETA/32492/2017) and FEDER/COMPETE 2020 (POCI-01-0145-FEDER-032492).

Inhibition of endoplasmic reticulum stress and activation of autophagy-protect intestinal and renal tissues from western diet-induced dysbiosis and abrogate inflammatory response to LPS: role of vitamin E.

Diet pattern is an emerging risk factor for renal disease. The mechanism by which high-fat high fructose (western) diet mediates renal injury is not yet fully understood. The objective of the present study was to investigate the relationship between endoplasmic reticulum (ER) stress and autophagy in the development of renal impairment and aggravation of the inflammatory response. Eighty male rats were randomly divided into four groups as follows: a standard diet-fed (ConD), a high-fat high fructose diet fed (HFHF-V), ConD fed and orally supplemented with vitamin E (ConD-E), and HFHF fed and orally supplemented vitamin E (HFHF-E). After 12 weeks, either lipopolysaccharide (LPS) or saline was injected. We found that upregulation of endoplasmic reticulum stress-related proteins rendered the cells susceptible to injury induced by dysbiosis and microbiota-derived metabolites. A downregulation of autophagy and upregulation of caspase-12 resulted in the loss of intestinal integrity and renal tubular injury. Maintained ER stress also increased the inflammatory response to LPS. In contrast, vitamin E effectively ameliorated ER stress and promoted autophagy to protect intestinal and renal tissues. Our results provide insight into the influences of sustained ER stress activation and autophagy inhibition on the development of renal injury, which may contribute also to the enhanced inflammatory response.

Rice bran modulates renal disease risk factors in animals submitted to high sugar-fat diet.

Introduction:Obesity, diabetes, and hypertension are common risk factors for chronic kidney disease (CKD). CKD arises due to many pathological insults, including inflammation and oxidative stress, which affect renal function and destroy nephrons. Rice bran (RB) is rich in vitamins and minerals, and contains significant amount of antioxidants. The aim of this study was to evaluate the preventive effect of RB on renal disease risk factors.Methods:Male Wistar rats (±325 g) were divided into two experimental groups to received a high sugar-fat diet (HSF, n = 8) or high sugar-fat diet with rice bran (HSF + RB, n = 8) for 20 weeks. At the end, renal function, body composition, metabolic parameters, renal inflammatory and oxidative stress markers were analyzed.Results:RB prevented obesity [AI (HSF= 9.92 ± 1.19 vs HSF + RB= 6.62 ± 0.78)], insulin resistance [HOMA (HSF= 83 ± 8 vs. HSF + RB= 42 ± 11)], dyslipidemia [TG (HSF= 167 ± 41 vs. HSF + RB=92 ± 40)], inflammation [TNF-α (HSF= 80 ± 12 vs. HSF + RB=57 ± 14), IL-6 (903 ± 274 vs. HSF + RB=535 ± 277)], oxidative stress [protein carbonylation (HSF= 3.38 ± 0.18 vs. HSF + RB=2.68 ± 0.29), RAGE (HSF=702 ± 36 vs. RSF + RB=570 ± 190)], and renal disease [protein/creatinine ratio (HSF=1.10 ± 0.38 vs. HSF + RB=0.49 ± 0.16)].Conclusion:In conclusion, rice bran prevented renal disease by modulating risk factors.

Gamma-oryzanol reduces renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to high sugar-fat diet.

Introduction: The receptor for AGEs (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface receptors expressed in many organs, among them, the kidneys. When activated, RAGE leads to a sequence of signaling that results in inflammation and oxidative stress, both involved in kidney disease pathogenesis. Gamma-oryzanol (γOz) comprises a mixture of ferulic acid (FA) esters and phytosterols (sterols and triterpene alcohols) mainly found in rice, with antioxidant and anti-inflammatory activities.Aim: To evaluate the effect of γOz to reduce renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to a high sugar-fat diet.Methods: Male Wistar rats (±187g) were randomly divided into two experimental groups: control (n = 7 animals) and high sugar-fat diet (HSF, n = 14 animals) for 20 weeks. After this period, when the presence of renal disease risk factors was detected in the HSF group (insulin resistance, dyslipidemia, increased systolic blood pressure and obesity), the HSF animals were divided to begin the treatment with γOz or continue receiving only HSF for 10 more weeks.Results: No effect of γOz on obesity and metabolic parameters was observed. However, kidney inflammation and oxidative stress decreased as soon as RAGE levels were reduced in HSF + γOz.Conclusion: It is possible to conclude that the gamma- oryzanol was effective in reducing inflammation and oxidative stress in the kidney by modulating the AGEs/RAGE axis.

Acute kidney injury induced by glycerol is worsened by orchiectomy and attenuated by testosterone replacement

Although several studies have demonstrated that the male gender represents an independent risk factor for renal disease, evidence shows that androgens exert renal protective actions. The findings are controversial and no studies have evaluated the effects of orchiectomy and testosterone replacement on glycerol-induced renal injury. Male Wistar rats were submitted to orchiectomy or sham surgery and divided into four groups: SC, sham control rats injected with NaCl; SG, sham rats injected with glycerol; OG, orchiectomized rats injected with glycerol; OGT, orchiectomized rats injected with glycerol and testosterone. Testosterone was administered daily for 14 days in the OGT group. After 11 days of testosterone replacement in the OGT group, SC rats were submitted to a saline injection, while SG, OG and OGT rats received glycerol. All rats were euthanized three days after injections. OG rats presented higher serum creatinine and urea, and sodium excretion, compared to SC and SG, while testosterone attenuated these changes. Acute tubular necrosis was also mitigated by testosterone. Renal immunostaining for macrophages, lymphocytes and NF-κB was higher in OG compared to SC and SG. In addition, renal interleukin-1β, Caspase 3 and AT1 gene expression was higher in OG rats compared to SG. Testosterone attenuated these alterations, except the NF-κB immunostaining. The renal NO was lower in OG rats compared to SG. Only the OG rats presented decreases in serum NO and renal HO-1, and increased TNF-α, angiotensinogen and AT1 expression compared to SC. We conclude that orchiectomy worsened glycerol-induced kidney injury, while testosterone attenuated this renal damage.

Risk factors for renal disease and diabetes in remote Australia - findings from The Western Desert Kidney Health Project.

The Western Desert Kidney Health Project (WDKHP) aimed to determine the prevalence of type 2 diabetes (T2DM), kidney disease and associated risk factors in Aboriginal and non-Aboriginal people in a remote area of Western Australia. The project, featuring whole-of-community cross-sectional surveys and health assessments using point-of-care testing, was conducted in five small towns and six remote Aboriginal communities in the Goldfields of Western Australia between 2010 and 2014. Initial health assessments were completed by 597 adults (424 Aboriginal) and 502 children (393 Aboriginal). This included almost 80% of the Aboriginal population. All non-Aboriginal people residing in the six remote Aboriginal communities participated. Risk factors for renal disease and T2DM were present in participants of all ages, including children as young as 2 years. There was no significant difference between Aboriginal and non-Aboriginal children. Aboriginal and non-Aboriginal adult participants had twice the burden of T2DM than the standard Australian population. More than 12% of all children had elevated albumin-creatinine ratio (ACR). Adults had markers of kidney disease at higher rates than expected: 51% of Aboriginal adults and 27% of non-Aboriginal adults had at least one marker of kidney disease (haematuria, proteinuria or elevated ACR). Aboriginal women were the highest risk group (32% T2DM, 40% elevated ACR). Haematuria and low urine pH were common findings, 21% of people had haematuria (greater than trace) and 71% had urine pH of 6 or less; there was no difference in this finding between Aboriginal and non-Aboriginal people. The WDKHP found higher than expected rates of risk factors for T2DM and renal disease compared with Australian Bureau of Statistics rates for Australian Aboriginal and non-Aboriginal adults and children, with Aboriginal women the highest risk group. The rates for non-Aboriginal participants were higher than expected, suggesting exposures in common might be more important than ethnicity.The high prevalence of aciduria and haematuria found in both Aboriginal and non-Aboriginal participants in this study suggests that factors contributing to a chronic metabolic acidosis and inflammation or irritation of the urinary tract need to be explored. Drinking water quality in this remote area is known to be poor and may be an important contributing factor. Many of the contributing factors are potentially modifiable - such as water quality, food supply, exercise opportunities and living conditions - offering scope for interventions to reduce the risk and burden of these diseases.

The mechanism of Arhalofenate in alleviating hyperuricemia-Activating PPARγ thereby reducing caspase-1 activity.

Hyperuricemia (HUA) is an important risk factor for renal diseases and contributes to gout. Arhalofenate (Arha) has been proved to have uricosuric activity as an inhibitor of URAT1, organic anion transporter 4 (OAT4) and OAT10. However, the effects of Arha on HUA remain unknown. The objective of this study was to investigate whether Arha could alleviate HUA and uncovered the underlying mechanism in vitro. HK-2 cells were exposed to uric acid (UA) to simulate HUA in vitro. Then cells were treated with Arha, caspase-1 inhibitor Belnacasan (Beln), caspase-11 inhibitor Wedelolactone (Wede) and PPARγ inhibitor Mifobate, respectively. The alteration of cell proliferation, inflammation, pyroptosis and expression of related proteins were detected. Results showed that UA exposure inhibited cell viability and increased IL-1β and IL-18 generation in a concentration dependent manner. Meanwhile, UA activated the cleavage of gasdermin D (GSDMD), enhanced the protein expression of URAT1, OAT4, TLR4, caspase-1, and caspase-11 and reduced PPARγ expression. While the presence of Arha or Beln enhanced cell viability and inhibited cleavage of GSDMD. Wede slightly increased cell viability but failed to prevent GSDMD cleavage. The expression of related proteins except caspase-11was also recovered by Arha. Beln and Wede partially rescued related proteins level except PPARγ compared with model group. Besides, the co-treatment of Mifobate blunted the effects of Arha on cell viability and expression of GSDMD, TLR4, and caspase-1. In conclusion, Arha inhibited UA transport as well as preventing inflammation and pyroptosis via activating PPARγ thereby blocking caspase-1 activation of HUA in vitro.

SO020NEPHROLOGY INTERVENTION IN PATIENTS AWAITING CARDIAC SURGERY: A RANDOMISED CONTROLLED TRIAL

Abstract Background and Aims Acute kidney injury (AKI) is a frequent complication after cardiac surgery. Its incidence ranges from 19 to 44% depending on the study and which definition is used. There are some well-known risk factors associated with AKI, including baseline patient characteristics (age and comorbidities), need of perioperative blood transfusion or presence of previous chronic kidney disease. We wanted to evaluate if a nephrologist management and control of potential risk factors of renal disease can be used to prevent AKI, thereby minimizing the risk of need RRT, reducing costs and improving survival in these patients. It will be the first study focused on this intervention. The aim of this study is to assess if a nephrology intervention before cardiac surgery can reduce the postoperative incidence of AKI. Method Unicentric prospective randomized controlled trial of 298 participants from 2015 to 2019. The inclusion criteria was patients undergoing scheduled cardiac surgery of &amp;gt; 18 years old. The exclusion criteria was a requirement for renal replacement therapy before surgery. Clinical Research Ethics Committee of Bellvitge has approved the study before initiation. All patients have given written informed consent. We have done an intention-to-treat analysis, continuous variables have been compared between groups using Student's t test and categorical variables using X2. Results Nephrology intervention before surgery, included a preoperative study done minimum 1 month before the surgery to optimize the patient’ s overall condition by optimization of hydration state, remove or minimize dose of drugs that potentially deteriorate kidney function and correct metabolic disorders. No differences in the characteristics of the patients between groups was found (Table 1). The number of patients with AKI were 49 without differences between groups (0.112), with most of them presenting a stage 1 AKI, only 3 patients present a stage 3 AKI, but none of them required renal replacement therapy (Table 2). We found 1.3% of mortality (1 participant in the intervention group and 3 in control group). Data at 1 year follow-up (n= 144) showed low incidence of kidney disease (creatinine in intervention arm 91.87±30.79μmol/L and in control arm 87.08±23.58, p=0.292) without differences in albuminuria. Conclusion In summary, we did not find any difference in acute kidney injury and death when a nephrology intervention is done to cardiac surgery patients, probably it would be necessary to increase the sample size to make conclusions. The results at 1 year follow-up showed no kidney disease in these patients.

Randomized Sirolimus-based Early Calcineurin Inhibitor Reduction in Liver Transplantation: Impact on Renal Function.

The long-term use of calcineurin inhibitors (CNIs) after liver transplantation (LT) is associated with nephrotoxicity. Five-year follow-up data were retrieved from the randomized controlled multicenter SiLVER trial. Standard CNI-based mammalian target of rapamycin-free immunosuppression (group A, n = 264) was compared with a 50% reduction of CNI and introduction of the mammalian target of rapamycin inhibitor Sirolimus (SIR) within 4-6 weeks after LT (group B, n = 261). Median MELD at LT was low with 10 (7-15) (group A) and 11 (8-15) (group B) in the intention-to-treat approach. CNI dose and CNI trough were reduced by 20% and 8% (group A) versus 55% and 56% (group B) at 3 months posttransplantation. Renal function was preserved at 3 months after LT in the SIR arm (estimated glomerular filtration rate 74 [57-95] versus 67 [55-85] mL/min/1.73m2 P = 0.004) but was similarly impaired thereafter compared with group A. The per protocol analysis identified LT recipients in group B with concomitant early CNI minimization and SIR treatment ≥ year 1 with significantly superior estimated glomerular filtration rate and lowest rate of chronic kidney disease (≥stage 3) from year 1 onwards until study end. Competing risk factors for renal disease (arterial hypertension, fat metabolism disorder, and hyperglycemia) were not associated with worse kidney function. Prevention of CNI nephrotoxicity by SIR-based early CNI minimization protects renal function only short-term after LT in the intention-to-treat analysis of this low MELD cohort. Yet, selected LT recipients compliant with early CNI minimization and SIR maintenance achieved better long-term renal outcomes compared with real-world practice.

Patients with human immunodeficiency virus infection do not have inferior outcomes after dialysis access creation

ObjectiveDespite improvements in treating human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), the risk of end-stage renal disease and need for long-term arteriovenous (AV) access for hemodialysis remain high in HIV-infected patients. Associations of HIV/AIDS with AV access creation complications have been conflicting. Our goal was to clarify short- and long-term outcomes of patients with HIV/AIDS undergoing AV access creation. MethodsThe Vascular Quality Initiative registry was queried from 2011 to 2018 for all patients undergoing AV access creation. Documentation of HIV infection status with or without AIDS was recorded. Data were propensity score matched (4:1) between non-HIV-infected patients and HIV/AIDS patients. Subsequent multivariable analysis and Kaplan-Meier analysis were performed for short- and long-term outcomes. ResultsThere were 25,711 upper extremity AV access creations identified: 25,186 without HIV infection (98%), 424 (1.6%) with HIV infection, and 101 (.4%) with AIDS. Mean age was 61.8 years, and 55.8% were male. Patients with HIV/AIDS were more often younger, male, nonwhite, nonobese, and current smokers; they were more often on Medicaid and more likely to have a history of intravenous drug use, and they were less often diabetic and less likely to have cardiac comorbidities (P < .05 for all). There was no significant difference in autogenous or prosthetic access used in these cohorts. Wound infection requiring incision and drainage or explantation within 90 days was low for all groups (0.6% vs 1.9 vs 0%; P = .11) of non-HIV-infected patients vs HIV-infected patients vs AIDS patients. Kaplan-Meier analysis showed no significant difference in 1-year freedom from primary patency loss (43.9% vs 46.3%; P =.6), 1-year freedom from reintervention (61% vs 60.7%,; P = .81), or 3-year survival (83% vs 83.8%; P = .57) for those with and without HIV/AIDS, respectively. Multivariable analysis demonstrated that patients with HIV/AIDS were not at significantly higher risk for access reintervention (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.76-1.24; P = .81), occlusion (HR, 1.06; 95% CI, 0.86-1.29; P = .6), or mortality (HR, 1.08; 95% CI, 0.83-1.43; P = .57). ConclusionsPatients with HIV/AIDS undergoing AV access creation have outcomes similar to those of patients without HIV infection, including long-term survival. Patients with HIV/AIDS had fewer traditional end-stage renal disease risk factors compared with non-HIV-infected patients. Our findings show that the contemporary approach for creation and management of AV access in patients with HIV/AIDS should be continued; however, further research is needed to identify risk factors in this population.