Risk Of Renal Disease Research Articles

Age- and oxidative stress-induced centrosome amplification and renal stones in Drosophila Malpighian tubules.

Renal diseases, including cancer, are rapidly increasing worldwide, driven by rising temperatures and changing diets, especially among younger people. Renal stones, a major risk for chronic renal disease, are increasingly common due to various health issues. Research on the underlying mechanisms, drug discovery, and the effects of aging and stress is limited. We used Drosophila, due to its similarity to the human renal system and ease of use, to identify cancer hallmarks and renal stone formation related to aging and oxidative stress. Our results indicate that centrosome amplification and stone formation increase with age and oxidative stress, and high sucrose feeding also heightens stone formation in the renal system. Our results show a close relationship between these diseases and aging, reactive oxygen species (ROS) stress, and chronic diseases. We suggest that the Drosophila renal model could be a powerful tool to study the relationship between age and age-related diseases and to discovering new agents for nephropathy.

Metabolic dysfunction-associated steatotic liver disease and risk of four intrahepatic and extrahepatic diseases: MASLD and risk of four related diseases

Introduction and ObjectivesRecently, Delphi consensus proposed an overarching term steatotic liver disease (SLD), with various subcategories such as MASLD, MetALD and ALD. Our aim was to investigate the association between MASLD/MetALD/ALD and four intrahepatic and extrahepatic diseases (liver diseases, renal diseases, cardiovascular diseases, and cancers) in the UK Biobank cohort. Patients and MethodsBy defining hepatic steatosis as image-derived phenotype (IDP)-PDFF >5.21%, we used data from the UK Biobank to diagnose MASLD/ MetALD/ALD. The odd ratio (OR) and the hazard ratio (HR) were calculated using the logistic regression modals and Cox regression models, respectively. ResultsAmong 39,230 eligible individuals, 6,865 MASLD subjects, 2,379 MetALD subjects and 884 ALD subjects were diagnosed. The last follow-up time was October 13, 2023. Consistent with the logistic analyses, MASLD/MetALD/ALD were significantly associated with a higher risk of liver diseases (HR=3.04 [95%CI:2.60∼3.56], HR = 2.69 [95% CI: 2.12∼3.42] and HR =3.99 [95%CI:2.92∼5.45], respectively). Subjects with MASLD also had an increased higher risk of renal diseases (HR = 1.40 [95%CI:1.20∼1.64]) and subjects with ALD had an increased higher risk of cancers (HR = 1.36 [95%CI:1.15∼1.60]). ConclusionIt is the first study to report the association between MASLD, MetALD, ALD and common intrahepatic and extrahepatic diseases based on magnetic resonance imaging data—PDFF. We found that MASLD, MetALD and ALD were risk factors for liver diseases. Meanwhile, MASLD was also a risk factor for renal diseases and ALD was a risk factor for cancers.

Impact of Metabolic Syndrome Traits on Kidney Disease Risk in Individuals with MASLD: A UK Biobank Study.

The impact of metabolic syndrome (MetS) traits on chronic kidney disease (CKD) risk in metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. We investigated the impact of type and number of MetS traits and liver fibrosis on prevalent CKD and incident end-stage renal disease (ESRD) risk in SLD. 234 488 UK Biobank participants' were analysed. Hepatic steatosis index (> 36 for SLD, < 30 for no SLD) and MRI-proton density fat fraction (≥ 5.56%) were used to identify SLD. MetS traits were identified using MASLD criteria. Advanced fibrosis (FIB-4 score > 2.67) was determined using FIB-4 scores. eGFR < 60 mL/min/1.73 m2 or albuminuria > 3 mg/mmol identified prevalent CKD. A validated algorithm identified incident ESRD. Binary logistic and Cox regressions were used to test associations with prevalent CKD ([adjusted odds ratios (ORs)]) and incident ESRD (adjusted hazard ratios [HRs]) respectively. 102 410 participants (41.2%) had SLD. 64.4% had MetS. 1.3% had FIB-4 score > 2.67. With SLD and only one MetS trait, hypertension (OR 1.35, 95% CI 1.35-1.72) or type 2 diabetes (T2D) (OR 1.89, 95% CI 1.06-3.38) increased risk of prevalent CKD. MetS (≥ 3 traits) increased prevalent CKD risk (OR 1.94, 95% CI 1.75-2.15), which was further increased by advanced liver fibrosis (OR 4.29, 95% CI 3.36-5.47). CKD prevalence increased with increasing MetS traits. Over 13.6 years (median follow-up), MetS was associated with increased risk of developing ESRD (HR 1.70, 95% CI 1.19-2.43). In MASLD, hypertension, and T2D, number of MetS traits and liver fibrosis increased risk of prevalent CKD and presence of MetS increased the risk of incident ESRD.

Lower risk of end stage renal disease in diabetic nurse

Lower risk of end stage renal disease in diabetic nurse

The Prevalence of Potentially Inappropriate Medications Among Patients With Diabetic Nephropathy: A Cross-Sectional Study Conducted at a Tertiary Care Hospital.

Background Diabetic nephropathy is a serious complication of diabetes that significantly increases the risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD). A critical concern in managing patients with diabetic nephropathy is the prevalence of potentially inappropriate medications (PIMs), which can exacerbate kidney dysfunction and lead to adverse health outcomes. PIMs are defined as medications whose risks outweigh their benefits, particularly when safer alternatives are available. The exact prevalence of the potentially inappropriate fraction of this as well as factors associated with the prescription of these medications remains variable. This study seeks to investigate the prevalence of PIMsin a diabetic population with CKD, aiming to identify the factors that contribute to this issue. Methods We conducted a cross-sectional study analyzing clinical and electronic data frompatients with diabetic nephropathy who were receiving care in the wards and outpatient clinics of Hamad Medical Corporation. Data were extracted from medical records, encompassing demographic information, comorbidities, prescribed medications, and kidney function, measured as estimated glomerular filtration rate (eGFR). The American Geriatrics SocietyBeers Criteriawas employed to identify PIMsin older adults. Statistical analyses included chi-square tests for categorical variables and logistic regression to identify factors associated with PIM prescriptions. Results Of the 860 patients analyzed, 248 (28.8%) were prescribed at least one PIM. The most commonly prescribed classes of PIMs were sulfonylureas and nonsteroidal anti-inflammatory drugs (NSAIDs). Significant factors associated with PIM prescriptions included older age (OR 1.52, 95% CI 1.21-1.92), lower eGFR(OR 1.67, 95% CI 1.28-2.19), and polypharmacy (OR 1.83, 95% CI 1.42-2.36). Conclusion In this examination of the combined inpatient and outpatient database of patients with diabetic nephropathy, we identified a high prevalence of PIMs, particularly in individuals of older age, those with lower eGFR, and those experiencing polypharmacy. The findings underscore the importance of addressing polypharmacy through targeted therapeutic interventions aimed at reducing the use of PIMs in this population. By implementing such strategies, we can enhance medication safety and improve overall health outcomes for patients with diabetic nephropathy.

Impact of diet on renal stone formation.

The incidence of kidney stones is increasing globally, with a preponderance in adults compared with that in adolescents and children. Dietary habits have been identified as significant contributing factors to kidney stone formation. This literature review aimed to explore the existing evidence on the impact of diet on renal stone formation. We conducted a comprehensive literature review and included 81 studies published between 1999 and 2023, limiting the search to articles published in English. The extracted data were analyzed to identify common themes, trends, and patterns related to the impact of diet on renal stone formation. We investigated the influence of dietary habits on the risk of nephrolithiasis. Although the role of fluid intake in relation to stone formation is clear, existing evidence on how different types of beverages (coffee, tea, fruit juices, and soft drinks) affect kidney stone formation is conflicting. Other factors such as protein, sodium chloride, calcium, oxalate, fat, and carbohydrate intake have also been discussed as contributors to nephrolithiasis. Thus, diet should be appropriately modified to reduce the risk of stone formation in susceptible individuals. A history of nephrolithiasis has been found to increase the risk of both chronic kidney disease and end-stage renal disease. The review acknowledges the limitations inherent in conducting a literature review, including the potential for publication bias and the reliance on available published studies. These findings highlight the importance of understanding and preventing nephrolithiasis.

The role of maintaining lower LDL-C level during statin treatment for advanced CKD patients

Background and aimsDifferent from other high cardiovascular (CV) risks populations, the evidence supporting the CV protective effect of LDL-C reduction with statins in chronic kidney disease (CKD) patients is comparatively scarce. This study is aimed to investigate the role of maintaining lower LDL-C level in advanced CKD patients. MethodsBy using Chang Gung Research Database, on the basis of Taiwan's largest healthcare group, a total of 5367 adult patients newly-diagnosed with stage 4 CKD and receiving statin were extracted and further categorized into three groups based on their LDL-C levels: <70 mg/dL, 70–100 mg/dL, and ≥100 mg/dL. The main outcome is major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiovascular death, myocardial infarction, and stroke. The inverse probability of treatment weighting was performed to achieve balance of baseline characteristics. ResultsAt 5-year follow-up, the LDL-C < 70 mg/dL group exhibited significantly lower risks of MACCEs (14.3 % vs. 18.7 %, hazard ratio [HR]: 0.77, 95 % CI: 0.69–0.86), cardiovascular death (7.1 % vs. 9.7 %, subdistribution HR [SHR]: 0.75, 95 % CI: 0.65–0.88), ischemic stroke (4.1 % vs. 5.4 %, [SHR]: 0.65, 95 % CI: 0.54–0.79), and new-onset end-stage renal disease requiring chronic dialysis (25.6 % vs. 29.4 %, SHR: 0.87, 95 % CI: 0.80–0.91) compared to LDL-C > 100 mg/dL group. In contrast, the group with LDL-C levels between 70 and 100 did not significantly differ from the group with LDL-C > 100 mg/dL in study outcomes. ConclusionsMaintaining LDL-C lower than 70 mg/dL may be beneficial for cardiovascular protection in advanced CKD patients and a lower LDL-C treatment target may be required as CKD progression.

Impact of Chronic Kidney Disease and Gout on End-Stage Renal Disease in Type 2 Diabetes: Population-Based Cohort Study.

We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status. Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD-Gout-, CKD- Gout+, CKD+Gout-, and CKD+Gout+. Patients with incident ESRD were followed up until December 2018. Among 847,884 patients, 11,825 (1.4%) experienced progression to ESRD. ESRD incidence increased in the following order: 0.77 per 1,000 person-years (PY) in the CKD-Gout- group, 1.34/1,000 PY in the CKD-Gout+ group, 8.20/1,000 PY in the CKD+Gout- group, and 23.06/1,000 PY in the CKD+Gout+ group. The presence of gout modified the ESRD risk in a status-dependent manner. Hazard ratios (HR) were 1.49 (95% confidence interval [CI], 1.32 to 1.69) and 2.24 (95% CI, 2.09 to 2.40) in patients without and with CKD, respectively, indicating a significant interaction (P<0.0001). The CKD+Gout+ group had a markedly higher risk of developing ESRD (HR, 18.9; 95% CI, 17.58 to 20.32) than the reference group (CKD-Gout-). Gout substantially enhances the risk of ESRD, even in the absence of CKD. Concurrent CKD and gout synergistically increase the risk of ESRD. Therefore, physicians should carefully screen for hyperuricemia to prevent progression to ESRD.

Lifestyle in patients with hypertension from the Shoulder to Shoulder Foundation

Introduction: Arterial hypertension (AHT) is defined as a disorder in which the blood vessels frequently have high tension, increasing the risk of cardiovascular, cerebral, and renal diseases, etc. Objective: To determine the lifestyles of patients with hypertension of the Hombro a Hombro Foundation, Santo Domingo, 2022. Methodology: The research is quantitative, data on the lifestyles of patients with arterial hypertension were collected, with a descriptive, cross-sectional level in which the collected data was stored and analyzed. The population consisted of 50 patients with arterial hypertension from the Shoulder to Shoulder Foundation. Results: Determining that within the healthy parameters are the physical condition, physical activity and sport; self-care and medical care; eating habits; the consumption of substances and some parameters on rest, although the last one could show that there is a small problem due to unhealthy practices. Conclusions: there are still patients who do not adhere to a new lifestyle, and work must continue to improve and treat as much as possible for the patient to adapt to this new stage, allowing him to be healthier

Coincidence of HCV and chronic kidney disease-a systematic review and meta-analysis

BackgroundThere are reported studies of Hepatitis C and chronic kidney disease association. However, how this liver virus infection affects the general population’s susceptibility to the onset of the kidney disease is still unknown.MethodsTo determine if a positive anti-HCV serologic status is linked to a greater incidence of chronic kidney disease in the general adult population, a systematic evaluation of the published medical literature since 2015 was conducted. A summary estimate of the relative risk of chronic kidney disease with HCV was produced using a random-effects model. Moreover, stratified analysis and meta-regression were performed.ResultsTwelve studies (n = 605858 patients) were filtered and included. Meta-analyses were conducted according to the outcome. Pooling results of longitudinal studies (n = 06 studies, n = 347120 unique patients) demonstrated an association between positive anti-HCV serologic status and increased incidence of CKD. The summary estimate for adjusted hazard ratio was 1.21 with (95% confidence interval 1.13; 1.29, P = 0.001), and between studies heterogeneity was noted (P value by Q test < 0.001). In the subset of Asian surveys, the risk of the occurrence of chronic kidney disease linked to HCV was 1.70 (95% confidence interval 1.40; 2.00) without heterogeneity (P value by Q test = 0.6).ConclusionsWe found a strong correlation between HCV infection and a higher risk of chronic renal disease in general global population.

8399 Adherens Junctions Regulate Aldosterone Production and Zona Glomerulosa Morphogenesis

Abstract Disclosure: M. Berber: None. N.A. Guagliardo: None. P.Q. Barrett: None. B. Haykir: None. V. Chortis: None. K.S. Borges: None. D.L. Carlone: None. D.T. Breault: None. Primary aldosteronism (PA) caused by the autonomous production of aldosterone by zona Glomerulosa (zG) cells of the adrenal gland is the most common cause of endocrine hypertension, which increases the risk of cardiovascular and renal disease, independent of blood pressure. Current treatments with mineralocorticoid receptor antagonists do not fully mitigate these risks. Thus, a better understanding of the mechanisms underlying PA pathogenesis is important for the development of new therapeutic strategies. zG cells are organized in multicellular rosette structures, which are the functional aldosterone-producing units. Rosettes are stabilized by intercellular adherens junctions (AJs) comprised of cadherins, beta-catenin (βCat) and alpha-catenin (αCat), which link to the actin non-muscle myosin II (NMII) network. Recent data implicate AJs and rosettes in aldosterone-producing cell clusters and an unbiased proteomic analysis of aldosterone-producing adenomas detected an upregulation of the GTPase RhoC, an important regulator of AJ stability.We hypothesized that AJs are potent modulators of aldosterone production and zG morphogenesis with important implications for PA. Using the NCI-H295R cell line with confocal microscopic and co-immunoprecipitation assays, we found that potassium (K+) and angiotensin II (AngII) stimulation markedly enhanced the formation and maintenance of AJs. In addition, treatment with inhibitors of Rho-associated kinase (ROCK) (Y-27632) and NMII (blebbistatin) largely abrogated the effects of K+ and AngII stimulation on AJs, suggesting the Rho-ROCK-NMII pathway regulates AJ stability in the zG. Moreover, disruption of AJs, using either blebbistatin or deletion of αCat using CRISPR, blunted the aldosterone response to K+ stimulation (100% and 50%, respectively). Furthermore, zG-specific deletion of αCat (αCat-LOF) in mice led to disruption of AJs, impaired rosette formation and decreased 24-hour urinary aldosterone excretion on standard (Control 5.6±1.7 ng/mg; αCat-LOF 2.9±0.7 ng/mg (aldosterone/creatinine)) or high K+ (Control: 34.7±13.7 ng/mg; αCat-LOF 19.4±9.5 ng/mg (aldosterone/creatinine)) diets. Finally, mice with zG-specific βcat-GOF demonstrated enhanced AJ stability, increased rosette size and zG hyperplasia, which was abrogated in zG-specific bigenic βCat-GOF::αCat-LOF mice, without affecting gene expression of canonical βcat targets. These data indicate that AJs modulate aldosterone production and zG morphology, revealing AJs as a novel molecular target for the treatment of high-risk patients with PA. Presentation: 6/3/2024

Association between preterm delivery and the risk of maternal renal disease: A systematic review and meta‑analysis.

The present systematic review and meta-analysis aimed to generate high-quality evidence on the association between preterm delivery (PTD) and subsequent risk of renal disease in the mother. A literature search was conducted on PubMed, Embase, CENTRAL and Scopus until the 15th of May 2023 for studies reporting an adjusted association between PTD and the risk of maternal renal disease. A total of seven studies were eligible. The pooled analysis found that women with PTD had a statistically significant increased risk of chronic kidney disease in the long term [hazard ratio (HR): 1.82 95% confidence interval (CI): 1.38, 2.40; I2=85%]. Similarly, the meta-analysis also found a statistically significant increased risk of end-stage renal disease (ESRD) amongst women with PTD as compared with those without PTD (HR: 2.22 95% CI: 1.95, 2.53; I2=0%). Overall, the pooled analysis showed a significantly higher incidence of renal disorders with PTD (HR: 1.98; 95% CI: 1.57, 2.50; I2=88%). The results were unchanged on sensitivity analysis. Women with PTD could be at increased risk of future chronic kidney disease and ESRD. The small number of studies and retrospective nature of data are important limitations. Further studies are needed to supplement the available evidence.

Effect of Occupational Noise on Employee Health: A Longitudinal Study.

This study investigated the long-term health risks associated with occupational noise exposure. By using 9 years of health examination data from a major manufacturing company in Taiwan, this study compared the health indices of employees in noise-intensive and non-noise-intensive work environments. A retrospective analysis of 6278 health examination reports spanning 9 years was conducted to compare 20 health indices among 166 employees evenly distributed between noise-intensive and non-noise-intensive workgroups. These employees were carefully matched for sex, age, and work experience. Linear regression models were used to assess the temporal impact of noise exposure on each health index by incorporating a unique range ratio to quantify index fluctuations attributable to noise. Employees exposed to occupational noise had an increase in platelet count of 16.594 K/µL, with an annual increment of 1.228 K/µL. Moreover, employees in noisy environments exhibited a significant increase in blood urea nitrogen level by 0.438 mg/dL, with an annual increase of 0.171 mg/dL. Additionally, their carcinoembryonic antigen level was significantly increased by 0.187 ng/mL on average, with the annual increase being 0.034 ng/mL. Moreover, increases in systolic blood pressure (2.015 mmHg), heart rate (4.620 beats/min), and white blood cell count (0.536 K/µL) and a decrease in red blood cell count (0.107 M/µL) were discovered to be solely attributable to noise exposure. Prolonged exposure to high occupational noise levels significantly increases the risk of cardiovascular, renal, and colorectal diseases. This longitudinal study underscores the detrimental health consequences of prolonged noise exposure in occupational settings.

Intraoperative hypotension during critical phases of liver transplantation and its impact on acute kidney injury: a retrospective cohort study

IntroductionAcute Kidney Injury (AKI) following Liver Transplantation (LT) is associated with prolonged ICU and hospital stay, increased risk of chronic renal disease, and decreased graft survival. Intraoperative hypotension is a modifiable risk factor associated with postoperative AKI. We aimed to determine in which phase of LT hypotension has the strongest association with AKI: the anhepatic or neohepatic phase. MethodsThis retrospective cohort study included adult patients undergoing LT between January 2010 and June 2022. Exclusion criteria were re-do or combined transplantations, preoperative dialysis, and early graft failure or death. Primary outcome was AKI as defined by KDIGO. Hypotension was Mean Arterial Pressure (MAP) below predefined thresholds in minutes. Risk adjusted logistic regression analysis considered hypotension in 3 periods: the total procedure, anhepatic phase, and neohepatic phase. ResultsOur cohort included 1153 patients. The median MELD-NA score was 19 (IQR 11–28), and 412 (35.9%) were living-related donations. AKI occurred in 544 patients (47.2%). The unadjusted model showed an association with AKI for MAP < 60 mmHg (OR = 1.011 [1.0, 1.022], p = 0.047) and MAP < 55 mmHg (OR = 1.023 [1.002, 1.047], p = 0.040) in the anhepatic phase, and for MAP < 60 mmHg (OR = 1.032 [1.01, 1.056], p = 0.006) in the neohepatic phase. The adjusted model did not reach significance in the subgroups but did in the total procedure: MAP < 60 mmHg (OR = 1.005 [1.002, 1.008], p < 0.001) and MAP < 55 mmHg (OR = 1.008 [1.003–1.013], p = 0.004). ConclusionIntraoperative hypotension is independently associated with AKI following LT. This association is seen during the anhepatic phase. Maintaining MAP above 60 mmHg may improve kidney function after LT.

Development and validation of a predictive model for end-stage renal disease in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) affects many populations. This study aims to develop a predictive model and create a nomogram for assessing the risk of end-stage renal disease (ESRD) in patients diagnosed with SLE. Data from electronic health records of SLE patients treated at the Affiliated Hospital of North Sichuan Medical College between 2013 and 2023 were collected. The dataset underwent thorough cleaning and variable assignment procedures. Subsequently, variables were selected using one-way logistic regression and lasso logistic regression methods, followed by multifactorial logistic regression to construct nomograms. The model's performance was assessed using calibration, receiver operating characteristic (ROC), and decision curve analysis (DCA) curves. Statistical significance was set at P < 0.05. The predictive variables for ESRD development in SLE patients included anti-GP210 antibody presence, urinary occult blood, proteinuria, white blood cell count, complement 4 levels, uric acid, creatinine, total protein, globulin, glomerular filtration rate, pH, specific gravity, very low-density lipoprotein, homocysteine, apolipoprotein B, and absolute counts of cytotoxic T cells. The nomogram exhibited a broad predictive range. The ROC area under the curve (AUC) was 0.886 (0.858-0.913) for the training set and 0.840 (0.783-0.897) for the testing set, indicating good model performance. The model demonstrated both applicability and significant clinical benefits. The developed model presents strong predictive capabilities and considerable clinical utility in estimating the risk of ESRD in patients with SLE.

Intact NOX2 in T Cells Mediates Pregnancy-Induced Renal Damage in Dahl SS Rats.

Hypertensive disorders of pregnancy are associated with increased risk for cardiovascular disease, renal disease, and mortality. While the exact mechanisms remain unclear, T cells and reactive oxygen species have been implicated in its pathogenesis. We utilized Dahl salt-sensitive (SS), SSCD247-/- (Dahl SS CD247 knockout rat; lacking T cells), and SSp67phox-/- (Dahl SS p67phox [NOX2 (NADPH [nitcotinamide adenine dinucleotide phosphate] oxidase 2)] knockout rat; lacking NOX2) rats to investigate these mechanisms in primigravida and multigravida states. We assessed blood pressure and renal damage phenotypes in SS, SSCD247-/-, and SSp67phox-/- rats during primigravida and multigravida states. To investigate the contribution of NOX2 in T cells, we performed adoptive transfers of splenocytes or cluster of differentiation (CD)4+ T cells from either SS or SSp67phox-/- donors into SSCD247-/- recipients to determine pregnancy-specific alterations in phenotype. Multigravida SS rats developed significant pregnancy-induced renal damage and renal functional impairment associated with elevated maternal mortality rates, whereas deletion of T cells or NOX2 garnered protection. During primigravida states, this attenuation in renal damage was observed, with the greatest protection in the SSp67phox-/- rat. To demonstrate that NOX2 in T cells contributes to adverse pregnancy phenotypes, adoptive transfer of SS splenocytes into SSCD247-/- rats resulted in significant pregnancy-induced renal damage, whereas transfer of SSp67phox-/- splenocytes garnered protection. Specifically, the transfer of SS CD4+ T cells resulted in pregnancy-induced proteinuria and increases in uterine artery resistance index, an effect not seen with the transfer of SSp67phox-/- CD4+ T cells. T cells and NOX2-derived reactive oxygen species, thus, contribute to end-organ damage in both primigravida and multigravida pregnancies in the SS rat leading to increases in maternal mortality.

The effects of age and frailty on the risks of end-stage renal disease, death, and severe infection in older adults with antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study

Frailty, a measure of biological age, might predict poor outcomes in older adults better than chronological age. We aimed to compare the effect of age and frailty on end-stage renal disease, death, and severe infection within 2 years of diagnosis in older adults with incident antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This retrospective cohort study included individuals aged 65 years or older from the Mass General Brigham ANCA-associated vasculitis cohort in the USA who were treated between Jan 1, 2002, and Dec 31, 2019. Individuals with a diagnosis of eosinophilic granulomatosis with polyangiitis were excluded from the analysis. Baseline frailty was measured with a claims-based frailty index using data collected in the year before the date of treatment initiation in individuals with at least one health-care encounter before baseline; individuals who did not have an encounter within the 12 months before baseline were classified as pre-frail. Incidence rates of end-stage renal disease or death and severe infections (ie, infections leading to hospital admission or death) at 2 years were estimated, and multivariable analyses were performed to compare the association of age and frailty with these outcomes. Cumulative incidence rates and an additive interaction analysis were used to assess the interaction of age and frailty groupings. Of the 234 individuals included, 136 (58%) were women, 98 (42%) were men, 198 (85%) were White, and 198 (85%) were positive for myeloperoxidase-specific ANCA. Frailty was present in 25 (22%) of 116 individuals aged 65-74 years and 44 (37%) of 118 aged 75 years or older. In the multivariable analysis, an age of 75 years or older was associated with an increased risk of end-stage renal disease or death (hazard ratio [HR] 4·50 [95% CI 1·83-11·09]), however, frailty was not (1·08 [0·50-2·36]). Both an age of 75 years or older (HR 2·52 [95% CI 1·26-5·04]) and frailty (8·46 [3·95-18·14]) were independent risk factors for severe infections. The effect of frailty on the incidence of end-stage renal disease or death was greater in individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 7·5 cases vs 2·0 cases per 100 person-years) than in those aged 75 years or older (13·5 cases vs 16·0 cases per 100 person-years). The effect of frailty on the incidence of serious infections varied by age, with large differences observed among both individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 38·9 cases vs 0·8 cases per 100 person-years) and individuals aged 75 years or older (61·9 cases vs 12·3 cases per 100 person-years). Despite the observed differences between the age groups, the additive interaction terms were not statistically significant for either frailty and end-stage renal disease or death (p for interaction=0·276) or frailty and serious infections (p for interaction=0·650). Adults with ANCA-associated vasculitis aged 75 years or older had a higher incidence of end-stage renal disease, death, and severe infections within 2 years of diagnosis than adults aged 65-74 years. Frailty, an approximation of biological age, was a risk factor for severe infection. Assessment beyond chronological age could better inform management decisions in older adults with ANCA-associated vasculitis. National Institutes of Health and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Long-Term Use of Proton Pump Inhibitors Increases the Risk of Renal Diseases

Long-Term Use of Proton Pump Inhibitors Increases the Risk of Renal Diseases

The Pattern of Practice in the Management of Early Diabetic Kidney Disease.

Background and objectives Diabetes is a leading cause of kidney failure in various regions worldwide. To detect renal disease in individuals with diabetes, screening typically involves evaluating the glomerular filtration rate and measuring albuminuria. Although there are established guidelines for these screenings, adherence to them varies. This study aims to examine the prevalence of albuminuria screening among adults with diabetes mellitus (DM) and to assess the different practices in managing these patients across primary and tertiary care settings. Methods This cross-sectional observational study involved adult patients with DM attending outpatient clinics in both primary and tertiary care settings. Patient data were gathered using a standardized form, excluding those with established chronic kidney disease (CKD) who were under nephrology care. Results The study included 1,010 patients, with 303 (30%) from primary care clinics and 707 (70%) from tertiary care clinics. The cohort comprised 582 (58%) females, with a median age of 62 years (IQR: 55-70), and approximately 990 (98%) had type 2 DM (T2DM). Annual albumin-to-creatinine ratio (ACR) screening was conducted for 498 out of 1,010 patients (49%) (95% confidence interval {CI}: 46%-52%). Screening compliance was notably higher in primary care settings compared to tertiary care clinics. Older patients (over 60 years) and those with hypertension or cardiac conditions were less likely to undergo screening. Among those screened, 185 of 498 patients (37%) (95% CI: 33%-41%) had abnormal albuminuria (ACR > 3). Conclusion Albuminuria is a significant indicator of progressing renal disease and cardiovascular risk. The annual screening rate for albuminuria in diabetic patients is inadequate. Primary care physicians show better adherence to screening guidelines compared to their tertiary care counterparts. Increasing physician awareness about the importance of screening could improve guideline compliance and mitigate the adverse effects of albuminuria.

Abstract P184: Increased Granulopoiesis, Kidney Neutrophil Infiltration, and Renal Damage in a Mouse Model of Psoriasis

Psoriasis is an autoimmune skin disease marked by T cell-mediated hyperproliferation of epidermal keratinocytes. Most psoriasis-related morbidity and mortality stems from an elevated risk of renal and cardiovascular disease, but mechanisms remain unclear. Although neutrophils are not directly targeted with current psoriasis therapies, neutrophils are increased in the skin and circulation of these patients. We hypothesized that excess skin inflammation in psoriasis drives increased G-CSF-dependent granulopoiesis leading to renal neutrophil infiltration and dysfunction. Employing a KC-Tie2 mouse model of psoriasis with keratinocyte-specific overexpression of the angiopoietin receptor Tie2 (KC-Tie2), we observed 2-3-fold elevations in multiple indices of renal damage including urine albumin, urine NGAL, and glomerulosclerosis in KC-Tie2 mice compared to littermate controls (all P&lt;0.05). KC-Tie2 mice also demonstrated 13 mm Hg higher daytime systolic blood pressure compared to littermate controls (P&lt;0.05). Using flow cytometry, we found that KC-Tie2 mice had an increase not only in cutaneous neutrophils but also an approximate 10-fold increase in renal neutrophils (P&lt;0.001). KC-Tie2 kidneys also exhibited increased vital and suicidal neutrophil extracellular trap (NET) formation, representing a potential mechanism for the observed renal damage. Interestingly, the increase in renal neutrophils was selective relative to other major immune cell populations such as dendritic cells, lymphocytes, monocytes, and macrophages. Similar selective increases in neutrophils were noted in the circulation, aorta, and spleen. We thus examined neutrophil production in the bone marrow, and observed significant increases in immature Ly6g low and Ly6g intermediate neutrophils (P&lt;0.0001) as well as total Ly6g + neutrophils (P&lt;0.05), with no change in mature Ly6g high neutrophils in the bone marrow of KC-Tie2 mice. These findings are consistent with increased granulopoiesis, prompting an examination of the key mediator of granulopoiesis, granulocyte colony-stimulating factor (G-CSF). KC-Tie2 mice exhibited marked increases in G-CSF in both the skin and plasma (P&lt;.001 for both). In conclusion, our findings demonstrate increased renal damage in a mouse model of psoriasis, concomitant with increases in granulopoiesis and total and NETotic renal neutrophils, potentially unveiling a novel link between skin inflammation and renal damage via enhanced G-CSF-mediated granulopoiesis.