Risk Of Renal Disease Research Articles

8. Sepsis-Associated Acute Kidney Injury and Acute Kidney Disease: A 15-Year Cohort Study of 4,226 Adult Sepsis Inpatient Survivors at a Tertiary Medical Center in Taiwan

BackgroundSepsis is the most common cause of acute kidney injury (AKI) and about one-third of patients with sepsis-associated AKI (SA-AKI) develop acute kidney diseases (SA-AKD) and may progress to unfavorable outcomes. We aimed to study the characteristics and outcomes associated with SA-AKI and SA-AKD.MethodsThis cohort study included adult inpatients with first-time sepsis who were admitted during 2003-2017, had qualifying serum creatinine (SCr) measurements at baseline (-365 to -3 days), -2 to +7 days, and +8 to +90 days of sepsis index day, and survived the first 90 days (Figure 1). Sepsis was identified using an electronic medical records-based Sepsis-3 criteria. We classified sepsis inpatients into SA-AKI(-), SA-AKD(-), SA-relapsed-AKD, and SA-nonrecovery-AKD (Figure 2). ESRD and mortality were ascertained by linking to the Catastrophic Illness records and to National Death Registry, respectively. Multivariable Cox proportional hazard model was used to evaluate the risk of mortality and end-stage renal disease (ESRD) associated with SA-AKI/AKD subtypes.Figure 1. Flowchart of the selection process of adult sepsis survivors (N = 4226 patients). Figure 2. Definitions of sepsis associated-acute kidney injury (SA-AKI) and sepsis associated-acute kidney disease (SA-AKD). ResultsOf 4,226 eligible sepsis inpatient survivors, 47.1% developed SA-AKI and 10.1% progressed to SA-AKD (5.4% relapsed and 4.7% nonrecovery). Patient with AKI and non-recovered AKD had the worst baseline renal function (SCr, 1.3 mg/dL) (Table 1). The multivariable analyses revealed that SA-relapsed AKD was significantly associated with increased risk of all-cause mortality for 1-year (aHR 1.67; 95% CI 1.25, 2.24), 3-year (aHR 1.38; 95% CI 1.11, 1.71), and overall (aHR 1.35; 95% CI 1.12, 1.61), compared with SA-AKI(-). SA-relapsed AKD and SA-nonrecovery AKD were both significantly associated with 1-year, 3-year, and overall ESRD, with the risk of about 4-fold or higher than SA-AKI(-) (Table 2).Table 1. Baseline characteristics and outcomes among adult sepsis survivors, by different SA-AKI/AKD subtypes. Table 2. Risk of all-cause mortality and end stage renal disease (ESRD) among adult sepsis survivors. ConclusionSepsis survivors who initially had AKI and developed relapsed or nonrecovery AKD tended to have worse outcomes of all-cause and ESRD, compared with those without AKI. Unexpectedly, patients with non-recovered AKD did not have a higher mortality risk, possibly because we have selected those who survived the first 90 days of sepsis. We will develop two-stage prediction models to identify sepsis patients at risk of developing AKI and SA-AKI patients at risk of developing different types of AKD. Disclosures All Authors: No reported disclosures

Four prescribed Chinese herbal medicines provide renoprotection and survival benefit without hyperkalemia risk in patients with advanced chronic kidney disease: A nationwide cohort study

BackgroundChinese herbal medicine (CHM) has been used as adjuvant treatment of chronic kidney disease (CKD) for years. Astragalus membranaceus (A. membranaceus, Huangqi [A]), Angelica sinensis (Oliv.) Diels (Danggui [S]), Rheum palmatum L. (Dahuang [R]), and Salvia miltiorrhiza Bunge (Danshen [D]) are considered as potentially renoprotective CHMs. However, there is limited evidence on whether ASRD use affects outcomes and causes hyperkalemia in patients with stage 4 and stage 5 advanced CKD. PurposeTo investigate between ASRD use (vs. nonuse) and risks of end-stage renal disease (ESRD), death, and hyperkalemia in patients with advanced CKD. Study DesignRetrospective nationwide cohort study using claims data from the Taiwan's 2005 Longitudinal Generation Tracking Database in 2000–2016. MethodsA total of 24,572 patients with advanced CKD were identified and 15,729 eligible patients were enrolled in the propensity score matching, with 1,401 incident ASRD users (8.9%) and 14,328 nonusers (91.1%). Finally, 1,076 ASRD users and 4,304 matched nonusers were subjected to analysis. We used Cox proportional hazards regression model to estimate the hazard ratios for ESRD and death and Poisson regression to estimate incidence rate ratio of hyperkalemia. The additive effect of one to four ASRD and the pooling effect of individual ASRD on risks of ESRD and death were also addressed. ResultsIn a total follow-up of 15,740 person-years, 2,703 patients (50.2%) developed ESRD and 499 (9.3%) died before progression to ESRD. As compared with nonusers, ASRD users were associated with adjusted hazard ratios of 0.83 (95% confidence interval, 0.76–0.91) for ESRD and 0.78 (0.30–0.93) for death, as well as adjusted incidence rate ratios of 0.54 (0.48–0.60) for inpatient hyperkalemia and 0.44 (0.42–0.46) for total hyperkalemia. The renal and survival benefits of ASRD use were consistent across almost patient subgroups on multivariate stratified analyses. Using all four ASRD provided the lowest risks of ESRD (0.30; 0.71–0.52) and death (0.32; 0.17–0.63). Individual use of ASRD also demonstrated comparable renal and survival benefits. ConclusionASRD use was associated with lower risks of ESRD and death among advanced CKD patients. This benefit did not increase hyperkalemia risk.

Community intervention study of viscera massage in overweight/obese type 2 diabetes high-risk population

Background:Prediabetes is an intermediate metabolic state between normoglycemia and diabetes. Without intervention, prediabetes often progresses to diabetes and prediabetes is associated with increased risk of cardiovascular disease, cancer, renal disease, and dementia. Lifestyle modification play a major role in controlling prediabetes. But lifestyle interventions are often with poor compliance and side effects of drugs are often be dislike by people. As a non-invasive therapy with no side effects, abdominal massage (AM), also called viscera massage in China, has been used to treat prediabetes and obesity-associated diseases. The gut microbiota has been recognized as an important factor in the development of metabolic diseases. Individuals with prediabetes have aberrant intestinal microbiota character. Colonic transport time and stool consistency are strongly associated with gut microbiota. Viscera massage can ease constipation by reducing colonic transport time and promoting intestinal motility. We can infer that viscera massage can modulate composition of gut microbiota affects human metabolism. So, in this trial, we will explore the mechanism of viscera massage on prediabetes from the perspective of intestinal microbiota.Methods and design:Eighty prediabetes individuals will be recruited for this study. Eighty prediabetes individuals will be divided into lifestyle intervention group and viscera massage + lifestyle intervention group by a simple random method. Each group will have 40 individuals. The manipulation of the viscera massage + lifestyle intervention group will be mainly carried out through rubbing the abdomen, kneading abdomen, vibrating abdomen, and pressing the abdomen, 30 minutes per time, once a day, with 2 days off every 5 days. Lifestyle interventions will be performed by combining pushing healthy lifestyle guidance information through Wechat application and giving face-to-face advice together daily. The lifestyle intervention group will receive healthy lifestyle intervention only. All the intervention will be conducted for 4 weeks. Weight, body mass index (BMI), waist circumference, waist-to-hip ratio, and waist-to-height ratio will be measured at the last day of every week. Triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood-glucose, 2-hour post-meal blood glucose (2hPG) and glycosylated hemoglobin, fasting insulin and insulin resistance index will be tested at the first day and last day of the intervention course. The fecal samples of subjects will be gathered at the first day and last day of the intervention course and will be performed 16S rRNA gene sequencing and metagenomic detection. Finally, the effect and potential mechanism of viscera massage on prediabetes will be discussed in combination with all the results.Discussion:The results of this study will be used to verify the effect of AM on prediabetes and explore the mechanism of AM on prediabetes from the perspective of gut microbiota.

The nephrotoxic potential of polystyrene microplastics at realistic environmental concentrations

As microplastics (MPs) dispersed into the environment, people might be exposed to MPs. Most pollutants either pass through or concentrate in the kidney. Therefore, nephrotoxicity tests are needed to verify the toxic potential of MPs. Here we used human embryonic kidney 293 (HEK293) cells to determine the association between nephrotoxicity and round-shape polystyrene MPs (PSMPs) (3.54 ± 0.39 μm) under realistic environmental exposure concentrations. Results revealed that PSMPs can adhere to the cell membrane and get entirely engulfed by HEK293 cells. PSMPs can induce cytotoxicity by oxidative stress via inhibition of the antioxidant haem oxygenase-1. Depolarisation of the mitochondrial membrane potential and formation of autophagosomes confirmed that apoptosis and autophagy can be simultaneously induced by PSMPs. The inflammatory factor was only activated (33 cytokines) by noncytotoxic concentration of PSMPs (3 ng/mL); however, the cytotoxic concentration (300 ng/mL) of PSMPs induced autophagy, which might further reduce NLRP3 expression, thus contributing to dampening inflammation (35 cytokines) in HEK293 cells. PSMPs (300 ng/mL) can impair kidney barrier integrity and increase the probability of developing acute kidney injury through the depletion of the zonula occludens-2 proteins and α1-antitrypsin. Altogether, our results demonstrated that environmental exposure to PSMPs may lead to an increased risk of renal disease.

Healthcare utilization and psychiatric and physical comorbidities before suicide mortality in patients with methamphetamine use disorder: A nationwide case–control study

BackgroundSince the late 1990s, methamphetamine use has become a considerable public health concern. Despite high suicide rates among methamphetamine users, studies exploring medical utilization and psychiatric and physical comorbidities before suicide are scant. We aim to examine the pattern of medical utilization and distribution of comorbidities shortly before suicide in methamphetamine users who died of suicide and compared these data with those of living methamphetamine users. MethodsFrom Taiwan’s National Health Insurance Research Database, we identified the cohort with methamphetamine use disorder (n = 23,248) between January 1, 2001, and December 31, 2005. We identified 5972 deceased patients (of whom 745 died of suicide) by linking each patient with the national mortality database during the study period. By conducting a nested case–control study with risk-set sampling, from the methamphetamine cohort, we selected four age- and sex-matched controls for each patient who died of suicide (cases). We applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls. ResultsCases had higher medical utilization within 3 months before suicide, particularly in the departments of psychiatry, internal medicine, emergency, and family practice. Cases had higher risks of physical comorbidities, including pneumonia and renal disease, and psychiatric comorbidities, including depressive disorder, sleep disorder, drug-induced mental disorder, schizophrenia, and bipolar disorder. ConclusionsThe findings of increased medical utilization and the higher risks of physical and psychiatric comorbidities in cases are crucial for developing specific interventions to prevent suicide in this patient population.

The role of sulfonylureas in the treatment of type 2 diabetes

ABSTRACT Introduction Type 2 diabetes (T2D) is increasingly prevalent and associated with increased risk for cardiovascular and renal disease. After lifestyle modification, metformin is usually the first-line pharmacotherapy and sulfonylureas are traditionally added after metformin failure. However, with newer glucose lowering drugs that may have less risk of hypoglycemia or that may reduce cardiovascular and renal events, the position of sulfonylureas is being reevaluated. Areas covered In this article, the authors review relevant publications related to the use of sulfonylureas. Expert opinion Sulfonylureas are potent glucose lowering drugs. The risk of hypoglycemia varies with different drugs within the class and can be minimized by using the safer drugs, possibly in lower doses. Cardiovascular events do not appear to be increased with some of the newer generation drugs. The durability of glycemic control also appears comparable to other newer agents. Sulfonylureas are the preferred treatment for some types of monogenic diabetes and selection of T2D patients who may have greater benefit from sulfonylureas based on certain phenotypes and genotypes is likely to be refined further by precision medicine. Sulfonylureas are inexpensive and readily available everywhere and they are still the most frequently used second-line treatment for T2D in many parts of the world.

Heat illness data strengthens vulnerability maps

BackgroundPrevious extreme heat and human health studies have investigated associations either over time (e.g. case-crossover or time series analysis) or across geographic areas (e.g. spatial models), which may limit the study scope and regional variation. Our study combines a case-crossover design and spatial analysis to identify: 1) the most vulnerable counties to extreme heat; and 2) demographic and socioeconomic variables that are most strongly and consistently related to heat-sensitive health outcomes (cardiovascular disease, dehydration, heat-related illness, acute renal disease, and respiratory disease) across 67 counties in the state of Florida, U. S over 2008–2012.MethodsWe first used a case-crossover design to examine the effects of air temperature on daily counts of health outcomes. We employed a time-stratified design with a 28-day comparison window. Referent periods were extracted from ±7, ±14, or ± 21 days to address seasonality. The results are expressed as odds ratios, or the change in the likelihood of each health outcome for a unit change in heat exposure. We then spatially examined the case-crossover extreme heat and health odds ratios and county level demographic and socioeconomic variables with multiple linear regression or spatial lag models.ResultsResults indicated that southwest Florida has the highest risks of cardiovascular disease, dehydration, acute renal disease, and respiratory disease. Results also suggested demographic and socioeconomic variables were significantly associated with the magnitude of heat-related health risk. The counties with larger populations working in farming, fishing, mining, forestry, construction, and extraction tended to have higher risks of dehydration and acute renal disease, whereas counties with larger populations working in installation, maintenance, and repair workers tended to have lower risks of cardiovascular, dehydration, acute renal disease, and respiratory disease. Finally, our results showed that high income counties consistently have lower health risks of dehydration, heat-related illness, acute renal disease, and respiratory disease.ConclusionsOur study identified different relationships with demographic/socioeconomic variables for each heat-sensitive health outcome. Results should be incorporated into vulnerability or risk indices for each health outcome.

Antioxidant activity, xanthine oxidase inhibition and acute oral toxicity of Dillenia philippinensis Rolfe (Dilleniaceae) leaf extract

Context: Hyperuricemia is a metabolic syndrome characterized by a high serum uric acid level with an increased risk of gout, diabetes, cardiovascular and renal disease. Allopurinol is a widely known xanthine oxidase inhibitor that lowers serum uric acid production. Documented adverse effects of the drug raise the need for a natural alternative for xanthine oxidase inhibitor that is safe and effective. This research is driven to address the need by capitalizing on previous studies made on the Dillenia species showing nephroprotective and antihyperuricemic activity. Aims: To evaluate the antioxidant capacity, xanthine oxidase inhibitory activity, and acute toxicity of Dillenia philippinensis; a plant locally known as Katmon and endemic to the Philippines. Methods: The D. philippinensis ethanolic leaf extract (DPELE) was partitioned using solvents of different polarities, hexane, ethyl acetate, and butanol. The antioxidant activity of the DPELE and the sub-extracts was assessed using nitric oxide, hydrogen peroxide, and hydroxyl radical scavenging assays against ascorbic acid, while the xanthine oxidase inhibitory activity was examined against allopurinol as a standard. The acute toxicity was performed using Sprague-Dawley rats following OECD 425 guidelines. Results: The D. philippinensis ethyl acetate fraction (DPEAF) had the highest scavenging activity of nitric oxide, hydrogen peroxide, and hydroxyl (IC50 = 210.00, 70.92 and 59.88 µg/mL) free radicals, respectively. Also, the xanthine oxidase dose-dependent inhibitory activity was observed to be highest in the DPEAF with an IC50 = 23.09 µg/mL. Lastly, neither toxicity nor mortalities were observed in rats treated with the DPELE and the DPEAF for 14 days. The approximate lethal dose for DPELE and DPEAF was higher than 2000 mg/kg BW. Conclusions: This study shows that the DPELE and DPEAF are potential sources of natural antioxidants and xanthine oxidase inhibitors, which may be used in the treatment of hyperuricemia and are presumed safe to be used orally.

Increasing urinary podocyte mRNA excretion and progressive podocyte loss in kidney contribute to the high risk of long-term renal disease caused by preterm birth

Podocyte abnormalities are common mechanism driving the progression of glomerular diseases, which account for most chronic kidney diseases (CKDs). However, the role of podocyte in the mechanism of high-risk long-term CKD caused by prematurity has not been well clarified. In present study, urine samples of 86 preterm infants and 32 full-term infants were collected, and podocyte-specific podocin mRNA levels in urine pellet were applied to indicate urinary podocyte mRNA excretion. In addition, in a preterm animal rat model, preterm rats were identified by delivery 2 days early. From the age of 3 weeks–12 months, urine samples were collected to examine podocyte mRNA excretion by measuring podocyte-specific podocin mRNA levels. Kidney samples at the age of 3 weeks, 2 months, and 12 months were collected from 8, 5 and 6 preterm rats and 9, 6 and 8 full-term rats, respectively, to examine podocyte density and podocyte area by measuring the podocyte specific nuclear marker WT-1 and the podocyte specific marker synaptopodin. As results, a more than threefold increase of urinary podocyte-specific podocin mRNA excretion rate was found in preterm infants compared with full-term infants. In addition, there was negative correlation between gestational age at birth and urinary podocin mRNA excretion. In preterm rats, a reduction in the total number of differentiated podocytes in glomeruli and an increased podocyte podocin mRNA excretion rate in urine were detected at the end of kidney differentiation. Moreover, long-term follow-up data in preterm rats showed there was an increased the risk of renal disease indicated by persistent podocyte mRNA loss, proteinuria, and enlarged glomeruli. In conclusion, increasing podocyte mRNA excretion in urine and podocyte loss in kidney led by prematurity drive the progression of long-term abnormal kidney function and could potentially explain the high risk of long-term CKD in preterm infants.

Evaluation of microalbumin, cystatin c, creatinine and uric acid levels in HIV patients in Nnamdi Azikiwe University Teaching Hospital, Nnewi

This study evaluated the microalbumin, cystatin C, creatinine and uric acid levels in HIV patients in Nnamdi Azikiwe University Teaching Hospital, Nnewi (NAUTH). A total of one hundred (100) male and female HIV positive and control participants who were aged between 18 and 60 years attending the voluntary counseling and testing unit (VCT) and antiretroviral therapy unit (ART) of NAUTH were randomly recruited for the study and grouped thus: Group A (HIV positive symptomatic participants on long term ART (HPSPLTART) (n= 25); Group B (HIV positive symptomatic participants on short term ART (HPSPSTART) (n= 25); Group C: Asymptomatic HIV positive participants NOT on ART (AHPPNART) (n=25) and Group D: control (n=25).6mls of blood sample and 10mls of freshly voided urine samples were collected from each of the participants for the evaluation of biochemical parameters using standard laboratory methods. Results showed significantly higher BMI and SBP in HPSPSTART than in control (p=0.04; 0.02). SBP was significantly higher in HPSPLTART than in AHPPNART and Control (p=0.00). DBP was significantly higher in HPSPLTART than in HPSPSTART and control respectively (p=0.00). There were significantly higher plasma creatinine and Cys-C levels in both male HIV positives and male HIV positive participants on ART than in both females respectively (p0.00; 0.02). Also, BMI, creatinine, uric acid and Cystatin C levels were significantly higher in male HIV negative participants than in female HIV negative participants (p=0.00; 0.04; 0.02; 0.01). This study has revealed greater risk for renal disease among the HIV participants studied.

Prevalences and incidences of cardiovascular and renal diseases in type 1 compared with type 2 diabetes: a nationwide observational study

Abstract Background Type 1 diabetes (T1D) and type 2 diabetes (T2D) increase risks of cardiovascular (CV) and renal disease compared with diabetes-free populations. There are only few studies comparing T1D and T2D for the risk of these clinical events. We examined these issues in a nationwide analysis in France. Methods All patients aged ≥18 seen in French hospitals in 2013 with at least 5 years of follow-up were identified and categorized by their diabetes status. A total of 50,623 patients with T1D (age 61.4±18.6, 53% male) and 425,207 patients with T2D (age 68.6±14.3, 55% male) were followed over a mean period of 4.3±2.1 years (median 5.3, interquartile 2.8–5.8 years). Prevalence and event rates of myocardial infarction (MI), heart failure (HF), ischemic stroke, chronic kidney disease (CKD), all-cause death and CV death were assessed with age stratification of 10-year intervals. Cox regression analyses were used to estimate risk with adjustment on sex and age. Results The age and sex-adjusted prevalence of CV diseases was higher in T2D for ages above 40 years whereas the adjusted prevalence of CKD was more common in T1D between ages 18 and 69 years and higher in T2D for ages above 80 years. During 2,033,239 person-years of follow-up, there were 27,497 patients with MIs (yearly rate 1.4%), 24,892 with ischemic strokes (yearly rate 1.2%), 100,769 with incident HF (yearly rate 5.4%), 65,928 with incident CKD (yearly rate 3.4%) and 197,858 deaths (yearly rate 9.7%) including 49,026 CV deaths (yearly rate 2.4%) were recorded. Age and sex-adjusted event rates comparing T1D versus T2D showed that MI risk was increased for ages above 60 (1.2-fold for T1D versus T2D) and HF between ages 18–29 and above 60 years (1.1–1.4-fold). Adjusted risk of ischemic stroke did not markedly differ between T1D and T2D. Risk of incident CKD was 1.1–2.4-fold higher in T1D between ages 18–49 and above 60 years. The all-cause death risk was 1.1-fold higher in T1D at age ≥60 years, the cardiovascular death risk being 1.1-fold higher in T1D between 60 and 69 years. Conclusions The adjusted prevalent burden and risk of incident renal disease are greater among patients with T1D compared with T2D patients across most ages. Although the prevalent burden of cardiovascular diseases may be lower in T1D than in T2D, patients with T1D may have a higher risk of incident MI, HF, all-cause death and cardiovascular death at middle-older ages, highlighting their need for improved prevention. Funding Acknowledgement Type of funding sources: None.

Comparing Oncological Outcomes and Surgical Complications of Hand-Assisted, Laparoscopic and Robotic Nephroureterectomy for Upper Tract Urothelial Carcinoma.

PurposeThis study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy.MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches.ResultsAmong the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p <0.001).ConclusionsMinimally invasive surgery can be safe and feasible. We proved that compared with the HALNU group, the LNU and RNU groups have better survival rates and fewer surgical complications. It is crucial to uphold strict oncological principles with sophisticated technique to improve outcomes. Further prospective studies are needed to validate our findings.

Hyperuricemia is a risk factor for the progression to end-stage renal disease in minimal change disease.

BackgroundMinimal change disease (MCD) is one of the most common causes of nephrotic syndrome worldwide. Hyperuricemia increases the end-stage renal disease (ESRD) risk in glomerulonephritis. In this study, we aimed to determine the effect of high serum uric acid levels on the progression to ESRD in MCD.MethodsA total of 800 patients diagnosed with MCD by kidney biopsy were retrospectively analyzed. We determined the relationship of hyperuricemia with the progression to ESRD in MCD using the Cox proportional hazard model and Kaplan-Meier survival analysis. The primary outcome was defined as the initiation of dialysis or kidney transplantation.ResultsA total of 42 patients (5.3%) progressed to ESRD during the follow-up period. In the restricted cubic spline curve, serum uric acid levels exhibited a positive correlation with ESRD progression in patients with MCD. In the fully adjusted model, the risk of MCD progression increased by 29% for every 1 mg/dL increase in the baseline serum uric acid level (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09–1.54; p = 0.004). Falling into the high uric acid group (serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women) was also a risk factor for progression of MCD to ESRD (HR, 3.40; 95% CI, 1.59–7.31; p < 0.001).ConclusionOur study shows that hyperuricemia is an independent risk factor for the progression to ESRD in patients with MCD.

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.

Abstract P184: Aging Male Offspring Of Polycystic Ovary Syndrome Rat Model Have Normal Blood Pressure And Exaggerated Pressor Response To Angiotensin II

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia and elevated blood pressure (BP). Male offspring of hyperandrogenemic female (HAF) rats, PCOS model, have low birth weight, with normal BP, but exaggerated pressor response to Angiotensin (Ang) II as adults. The present study tested the hypothesis that with aging, male HAF offspring are at increased risk of developing hypertension (HT). Methods: Hyperandrogenemia was induced in female SD rats (5α-dihydrotestosterone pellets 7.5 mg/90 d, s.c. at 4 wks of age and throughout life). HAF and controls (10-12 wks of age) were mated, allowed to deliver and lactate. HAF and control male offspring (F1 HAF and F1 Contr. ) were left untreated until 16-20 mos of age. Body composition (echoMRI) and proteinuria were measured in aging offspring. BP was measured (baseline; 9 d, enalapril (25 mg/kg/d); 7d) by telemetry. Rats were then given Ang II (50 ng/kg/min, s.c. minipumps) or saline (No Ang II) for 13 d. High salt (4%) diet (HSD) was started for both Ang II and No Ang II groups on day 8 of Ang II. Results: Aging male F1 HAF had similar fat mass, but lower lean mass (433.7 ± 6 vs 453.6 ± 7 g, p&lt; 0.05) and body weight (552.3 ± 11 vs 590.4 ± 11 g, n = 8-16, p&lt;0.05) than F1 Contr. . Despite higher proteinuria in F1 HAF (412 ± 42 mg/24h vs 292 ± 47 mg/24h, n = 11-13, p&lt;0.05), baseline mean arterial pressure (MAP) was similar between F1 HAF and F1 Contr. (130 ± 1 mmHg vs 126 ± 4 mmHg, respectively, n = 8, p=NS). Enalapril decreased MAP similarly in both F1 HAF and F1 Contr. (110 ± 2 mmHg vs 107 ± 3 mmHg, respectively). On low salt, Ang II increased MAP to higher levels in F1 HAF than F1 contr., saline-treated&gt;F1 HAF and F1 Contr. (140 ± 11 mmHg vs 119 ± 10 mmHg, 105 ± 3 mmHg and 103 ± 4 mmHg, respectively, n = 4, p&lt;0.05 F 1 HAF vs other grps). With 6 days of HSD, MAP was similar between F1 HAF and F1 Contr. not treated with Ang II (142 ± 6 mmHg and 132 ± 9 mmHg, respectively). MAP was also similar between F1 HAF and F1 Contr. with Ang II (169 ± 1 mmHg and 159 ± 9 mmHg, respectively). However, both Ang II-treated groups had significantly higher MAP compared to their respective No Ang II control groups. Conclusion: Aging male HAF offspring do not develop hypertension, but are at increased risk of renal injury and cardiovascular disease due to enhanced pressor sensitivity to Ang II.

Frailty, Age, and Postdialysis Recovery Time in a Population New to Hemodialysis.

Frailty, a phenotype characterized by decreased physiologic reserve and the inability to recover following confrontation with a stressor like hemodialysis, may help identify which patients on incident hemodialysis will experience longer postdialysis recovery times. Recovery time is associated with downstream outcomes, including quality of life and mortality. We characterized postdialysis recovery times among patients new to hemodialysis and quantified the association between frailty and hemodialysis recovery time. Among 285 patients on hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, frailty was measured using the Fried phenotype. Self-reported recovery time was obtained by telephone interview. We estimated the association of frailty (intermediately frail and frail versus nonfrail) and postdialysis recovery time using adjusted negative binomial regression. Median time between dialysis initiation and study enrollment was 3.4 months (IQR, 2.7-4.9), and that between initiation and recovery time assessment was 11 months (IQR, 9.3-15). Mean age was 55 years, 24% were >65 years, and 73% were Black; 72% of individuals recovered in ≤1 hour, 20% recovered in 1-6 hours, 5% required 6-12 hours to recover, and <5% required >12 hours to recover. Those with intermediate frailty, frailty, and age ≤65 years had 2.56-fold (95% CI, 1.45 to 4.52), 1.72-fold (95% CI, 1.03 to 2.89), and 2.35-fold (95% CI, 1.44 to 3.85) risks, respectively, of longer recovery time independent of demographic characteristics, comorbidity, and dialysis-related factors. In adults new to hemodialysis, frailty was independently associated with prolonged postdialysis recovery. Future studies should assess the effect of frailty-targeted interventions on recovery time to improve clinical outcomes.

Racial differences in all-cause mortality and future complications among people with diabetes: a systematic review and meta-analysis of data from more than 2.4 million individuals.

The aim of this work was to quantify racial/ethnic differences in risk for future diabetic complications and all-cause mortality by performing a meta-analysis of prospective studies. A systematic search in PubMed and EMBASE was performed from inception to May 2021. Prospective cohort studies that reported HRs and associated 95% CIs of diabetes complications and all-cause mortality among racial/ethnic groups, with White people as the reference group, were included. Study characteristics and HR estimates were extracted from each study. Estimates were pooled using random-effects inverse-variance model with the Hartung-Knapp-Sidik-Jonkman variance estimator. A total of 23 studies were included, comprising 2,416,516 individuals diagnosed with diabetes (White 59.3%, Black 11.2%, Asian 1.3%, Hispanic-American 2.4%, Native American 0.2%, East Asian 1.9%, South Asian 0.8%, Pacific Islander 2.3%, Māori 2.4% and others 18.2%). Compared with White individuals with diabetes, individuals of Māori ethnicity were at higher risk for all-cause mortality (HR 1.88 [95% CI 1.61, 2.21]; I2= 7.1%), Hispanic-American individuals had a significantly lower risk for CVD (HR 0.66 [95% CI 0.53, 0.81]; I2= 0%) and Black individuals had higher risk for end-stage renal disease (HR 1.54 [95% CI 1.05, 2.24]; I2= 95.4%). No significant higher risk for diabetes complications was found in other racial/ethnic groups relative to White people. Racial/ethnic differences exist in the risk for future diabetic complications and all-cause mortality. Our results support the use of such categories for international diabetes clinical guideline recommendations until better predictors become available. Efforts to identify high-risk groups and to better control cardiovascular risk factors across ethnically diverse populations are therefore needed. PROSPERO registration ID CRD42021239274.

The role of GLP-1 receptor agonists during COVID-19 pandemia: a hypothetical molecular mechanism

ABSTRACT Introduction A number of anti-diabetic treatments have been favored during the continuing spread of the current SARS-CoV-2 pandemic. Glucagon like peptide-1 receptor agonists (GLP1-RAs) are a group of antidiabetic drugs, the glucose reducing effect of which is founded on augmenting glucose-dependent insulin secretion with concomitant reduction of glucagon secretion and delayed gastric emptying. Apart from their glucose lowering effects, GLP1-RAs also exert a plethora of pleiotropic activities in the form of anti-inflammatory, anti-thrombotic and anti-obesogenic properties, with beneficial cardiovascular and renal impact. All these make this class of drugs a preferred option for managing patients with type 2 diabetes (T2D), and potentially helpful in those with SARS-CoV2 infection. Areas covered In the present article we propose a hypothetical molecular mechanism by which GLP1-RAs may interact with SARS–CoV-2 activity. Expert Opinion The beneficial properties of GLP1-RAs may be of specific importance during COVID-19 infection for the most fragile patients with chronic comorbid conditions such as T2D, and those at higher cardiovascular and renal disease risk. Yet, further studies are needed to confirm our hypothesis and preliminary findings available in the literature.

Association between Dental Scaling and Reduced Risk of End-Stage Renal Disease: A Nationwide Matched Cohort Study.

Periodontitis is prevalent in patients with chronic kidney disease (CKD) and is also associated with kidney function decline. It is unclear whether dental scaling treatment prevents the progression of CKD. In a nationwide cohort study, Taiwan’s National Health Insurance Research Database was used to select people with CKD. Propensity score-matching procedures were performed to compare the long-term risk of end-stage renal disease (ESRD) between CKD patients with and without the receipt of dental scaling. A total of 33,637 matched pairs with CKD were included, with 503,373 person-years of follow-up for analyses. Dental scaling was significantly associated with a lower risk of ESRD (adjusted hazard ratio (aHR): 0.83, 95% confidence interval (CI): 0.77–0.90). In addition, there was a dose-dependent relationship between the frequency of dental scaling and a reduced risk of ESRD. Dental scaling was also linked to reduced risks of major adverse cardiovascular events (aHR: 0.91, 95% CI: 0.87–0.95), sepsis (aHR: 0.81, 95% CI: 0.77–0.85), and all-cause mortality (aHR: 0.81, 95% CI: 0.76–0.87). Dental scaling was significantly associated with lower risks of progression to ESRD in patients with CKD. Regular dental scaling may serve as a prophylactic measure for kidney function decline.

Environmental metals and metal mixtures and renal disease in an adult population from Spain: the Aragon Workers Health Study

BACKGROUND AND AIM: Disproportionally high exposures to arsenic (As), cadmium (Cd) and lead are nephrotoxic. However, epidemiological studies evaluating low-chronic exposure, especially for other metals, are limited. We assessed the cross-sectional and prospective associations of a panel of metals, individually and as mixtures, with albuminuria and estimated glomerular filtration rate (eGFR), two well-established markers of renal function. METHODS: 1519 participants from the Aragon Worker’s Health Study had available cobalt (Co), copper (Cu), molybdenum (Mo), zinc (Zn), As, barium (Ba), Cd, chromium (Cr), antimony (Sb), titanium (Ti), uranium (U), vanadium (V) and tungsten (W) urinary measurements. In a subset of 707 participants with available follow-up, we estimated annual-average increase of urine albumin and eGFR. The joint association of metals were evaluated implementing Bayesian Kernel Machine Regression (BKMR) methods. RESULTS:Median metal levels were 0.24, 7.0, 18.6, 295, 3.1, 1.9, 0.25, 0.99, 0.20, 9.7, 0.03, 0.50, 0.22 μg/g creatinine for Co, Cu, Mo, Zn, As, Ba, Cd, Cr, Sb, Ti, U, V and W, respectively. Increased urinary Co, Cu, Zn, As, Cr, Ti, U and W were associated with higher odds of albuminuria ≥30 mg/g. In BKMR analysis, these associations seemed to be driven by W, As and Zn. In prospective analyses, increased Cu, As and Cr were also related with higher odds of annual-increase albumin excretion ≥20%. For eGFR, the prospective association with annual-eGFR change [mean difference in change (95% confidence interval)] was not statistically significant for most metals except for As [-0.35 (-0.70, -0.001)], Zn [-0.31 (-0.61, -0.01)] and Ba [0.38 (0.09, 0.67)], directionally consistent with and without urine creatinine adjustment. CONCLUSIONS:We identified W, As, Zn and Cr exposures as potential risk factors of renal dysfunction. Exposure reduction and mitigation interventions of metals may decrease renal disease risk. KEYWORDS: Heavy metals, Epidemiology, Outcomes