Chronic Kidney Disease Factors Research Articles

Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation, fluid sheer stress, and inflammatory pathways in obesity-related glomerulopathy

Obesity-related glomerulopathy (ORG) is an independent risk factor for chronic kidney disease and even progression to end-stage renal disease. Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG, but relatively little is known about cell-specific changes in gene expression. To define the transcriptomic landscape at single-cell resolution, we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing. We report for the first time that immune cells, including T cells and B cells, are decreased in ORG patients. Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells. This gene is related to inflammation and cell proliferation. Analysis of differential gene expression in glomerular cells (endothelial cells, mesangial cells, and podocytes) showed that these cell types were mainly enriched in genes related to oxidative phosphorylation, cell adhesion, thermogenesis, and inflammatory pathways (PI3K-Akt signaling, MAPK signaling). Furthermore, we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway. Moreover, an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients, with major interactions between parietal epithelial cells and podocytes. Altogether, our identification of molecular events, cell types, and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

The Triglyceride-Glucose Index is Independently Associated with Chronic Kidney Disease in the Geriatric Population, Regardless of Obesity and Sex.

Insulin resistance (IR) negatively affects several risk factors of chronic kidney disease (CKD). This cross-sectional study investigated whether the triglyceride-glucose (TyG) index, which reflects IR, was independently associated with CKD in a geriatric population, regardless of obesity and sex. The analysis included 7,326 individuals (2,864 males and 4,462 females) aged ≥60 years. Non-obesity or obesity was evaluated using a body mass index cutoff of 25 kg/m2. The TyG index was calculated as ln [triglyceride concentration (mg/dL)×fasting plasma glucose concentration (mg/dL)]/2. All participants were categorized into three groups according to TyG tertiles. Moderate-to-severe CKD (MSCKD) was defined as an estimated glomerular filtration rate (eGFR) of <45.0 mL/min/1.73 m2. In males and females with or without obesity, a trend test showed a decreasing tendency in the eGFR from the lowest to highest TyG tertiles. Males without obesity and females with obesity in the middle and highest tertiles of the TyG index were 2.342 and 2.393, and were 2.313 and 3.516 times more likely to have MSCKD, respectively. Those with or without obesity in the highest tertile of the TyG index were 1.736 and 2.374 times more likely to have MSCKD, respectively. Geriatric populations with an increased TyG index have a high risk of MSCKD regardless of obesity and sex. Our findings suggest that increased IR is associated with CKD in the geriatric population independent of obesity and sex.

The Impact of Sedentary Behavior on Renal Function Decline in 132,123 Middle Aged and Older Adults: A Nationwide Cohort Study.

BACKGROUND Prior studies suggest that sedentary behavior is a well-known risk factor for cardiometabolic diseases. However, the longitudinal association between overall siting time and kidney function decline is not known. MATERIAL AND METHODS We performed a nationwide prospective cohort study in individuals aged more than 40 years enrolled in the China Cardiometabolic Disease and Cancer Cohort (4C) study. A total of 132 123 individuals were included in this study. Sitting time was measured with the short version of the International Physical Activity Questionnaire (IPAQ). Kidney function decline was defined as an eGFR <60 mL/min/1.73 m² or more than a 30% decrease in eGFR from baseline. Multivariate Cox proportional hazards regression analyses were conducted to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of the relation between kidney function decline and sitting time. RESULTS During a mean follow-up of 3.8 years, 3890 (2.9%) participants experienced kidney function decline. Longer sitting time was significantly associated with the risk of kidney function decline (aHR, 1.136; 95% CI, 1.036-1.247, P=0.007, comparing participants with baseline sitting time in the lowest quartile with those in the highest quartile) after adjustment for potential confounders. CONCLUSIONS Longer sitting time was independently and prospectively associated with a higher risk of kidney function decline. Sedentary behavior might represent a modifiable risk factor for chronic kidney disease (CKD) prevention.

Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio and Cardiorenal Syndrome Type 2 in the Systemic Sclerosis EUSTAR Cohort.

The aim of the study was to evaluate the association between the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio and estimated glomerular filtration rate (eGFR) and their association with mortality in the European Scleroderma Trials and Research (EUSTAR) cohort. Patients with systemic sclerosis (SSc) from the EUSTAR database with TAPSE, sPAP, and parameters required to calculate eGFR were included. Logistic regression and Cox regression analysis were performed to evaluate TAPSE/sPAP as a risk factor for chronic kidney disease (CKD) and overall survival. A total of 2,370 patients with SSc were included; 284 (12%) patients had CKD stage 3a-5. TAPSE/sPAP (odds ratio [OR] 0.479; 95% CI 0.310-0.743; P < 0.001), arterial hypertension (OR 3.118; 95% CI 2.173-4.475; P < 0.001), diastolic dysfunction (OR 1.670; 95% CI 1.148-2.428; P < 0.01), and N-terminal pro-B-type natriuretic peptide (OR 1.165; 95% CI 1.041-1.304; P < 0.01) were associated with CKD stage 3a-5. TAPSE/sPAP ≤0.32 mm/mm Hg (hazard ratio [HR] 3.589; 95% CI 2.236-5.761; P < 0.001), eGFR <60 mL/min per 1.73 m2 (HR 2.818; 95% CI 1.777-4.468; P < 0.001), and age (HR 1.782; 95% CI 1.348-2.356; P < 0.001) were the most significant predictive factors for all-cause mortality. A total of 276 patients with SSc had pulmonary hypertension (PH) confirmed by right heart catheterization, with 69 (25%) having CKD stage 3a-5. No difference was found in eGFR between patients with PH with reduced or normal cardiac index. Reduced TAPSE/sPAP ratio is independently associated with CKD. TAPSE/sPAP ratio ≤0.32 mm/mm Hg and eGFR <60 mL/min per 1.73 m2 are prognostic factors for all-cause mortality. In patients with SSc with PH, eGFR is independent by reduced cardiac output.

Clinical assessment of etiological risk factors of chronic kidney disease in patients admitted for dialysis to a tertiary care hospital

Background: Chronic kidney disease (CKD) is defined as a reduced glomerular filtration rate, increased urinary albumin excretion, or both, and it is an increasing public health problem with a prevalence of 8–16%. However, there is a paucity of such studies evaluating risk factors among dialysis patients in India and also there could be associated setting specific varied contributory factors. Hence, we have undertaken this study to assess common risk factors in CKD patients admitted for dialysis to a Tertiary Care Hospital. Aims and Objectives: To assess the clinical presentation and the common risk factors in CKD patients admitted for dialysis to tertiary care hospital. Materials and Methods: The present study was cross-sectional study in which 100 CKD patients admitted to the dialysis unit of tertiary care hospital were included on the basis of predefined inclusion and exclusion criteria and were analyzed as regards the history of illness, environment, and physical behavior was collected based on various pre-validated questionnaires (The WHO STEP wise approach to chronic disease risk factor Surveillance questionnaire for NCDs, dietary questionnaire, environmental/occupational questionnaire, and patient history questionnaire) in a face-to-face interview with participants and their family members. Etiological Risk Factors and clinical assessment of patients were studied. P&lt;0.05 was taken as statistically significant. Results: 49 (49%) of the study participants were from the age group of 41 to 60 years with the mean age of the 51.9±12.3 years. There was a male ponderance with M: F ratio being 1:0.61. The most common underlying condition responsible for end-stage renal disease (ESRD) was hypertension (25%) followed by diabetes mellitus (21%), glomerulonephritis (18%), analgesic nephropathy (15%), and renal stones (8%). CKD of unknown etiology was present among 7% and polycystic kidney 6%. Common clinical presentation in studied cases was anorexia (61%) followed by easy fatigability (58%) patients, Facial puffiness (49%), weakness (45%), and oliguria (44%). Conclusion: Male gender, advancing age, and occupational exposure to nephrotoxic metals were the baseline risk factors. Hypertension and diabetes mellitus were the two most common comorbidities among ESRD patients which are the important risk factors for progression to ESRD.

Abstract 127: Time Restricted Feeding In Diet Induced Obesity Reduces Kidney Cd8 + T Cells

Diet induced obesity (DIO) is one of the leading risk factors for chronic kidney disease. Previous studies identified a role for pro-inflammatory T cells in mediating DIO-driven renal damage. We found that time restricted feeding (TRF; food available only in 12-hr dark phase) during the final 2 weeks of a 20-week DIO model (45% fat) significantly improves renal damage compared to DIO ad libitum fed male mice. DIO+TRF also significantly reduced total T cells in the kidney adjacent to vasa recta in the outer medulla compared to DIO ad libitum mice assessed at the start of the dark phase or Zeitgeber Time (ZT) 12. We hypothesized that DIO+TRF decreases renal and circulating pro-inflammatory CD4 + and CD8 + T cells compared to DIO ad libitum in a time-of-day dependent manner . Using flow cytometry, we found that DIO significantly increases total renal T cells compared to normal diet (ND; 10% fat) at ZT13-15 (dark phase) only. DIO+TRF significantly decreases total renal T cells compared to DIO in the dark phase (n=7-14; 2-way ANOVA, Interaction: p=0.016, Effect of Time of Day: p=0.010, Effect of Diet: p=0.001). Our data showed no significant changes in renal T cell numbers in the light phase. Compared to ND, DIO increased renal CD8 + T cells at ZT13-15 and DIO+TRF normalized renal CD8 + T cells (n=7-14; 2-way ANOVA, Interaction: p=0.007, Effect of Diet: p=0.004). DIO and DIO+TRF did not alter renal CD4 + T cells at either ZT1-3 or ZT13-15 compared to ND. We further examined the kidney CD8 + T cell phenotype with DIO and TRF. We also found no significant changes in CD8 + T cell activation markers, perforin and granzyme B, CD8 + T cell development marker EOMES, or CD8 + T cell pro-inflammatory cytokines, IFNγ and TNFα. We assessed circulating CD8 + and CD4 + T cells via flow cytometry to analyze systemic effects of TRF. DIO+TRF led to a diurnal rhythm of CD8 + T cells with increased circulating CD8 + T cells in the dark phase compared to the light phase that was not observed in the ND or DIO groups (n=7-17; 2-way ANOVA, Interaction: p=0.012). No significant changes were observed in circulating CD8 + T cell activation markers or cytokines. DIO and TRF had no significant effect on numbers of circulating CD4 + T cells. We conclude that DIO+TRF influences rhythms of circulating and renal CD8 + T cells, but not CD4 + T cells.

Association of the rs5186 polymorphism of the AGTR1 gene with decreased eGFR in patients with type 2 diabetes from Mexico City

BackgroundEarly biomarkers search for Diabetic Kidney Disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM), as genetic markers to identify vulnerable carriers of the disease even before Glomerular Filtration Rate (GFR) decline or microalbuminuria development, has been relevant during the last few years.The rs5186 (A116C) polymorphism of the Angiotensin II Receptor Type I gene (AGTR1), has been associated to multiple effects of renal injury risk, commonly detected in patients with Diabetes Mellitus (DM). It has been described that rs5186 could have an effect in stability proteins that assemble Angiotensin II Receptor Type I (AT1), modifying its action, which is why it should be considered as a risk factor for Chronic Kidney Disease (CKD), characterized by a GFR progressive reduction. Even though, the association between rs5186 AGTR1 gene polymorphism and DKD in patients with T2DM has been controversial, inconclusive, and even absent. This disputable issue might be as a result of association studies in which many and varied clinical phenotypes included are contemplated as CKD inductors and enhancers. Although, the sample sizes studied in patients with T2DM are undersized and did not have a strict inclusion criteria, lacking of biochemical markers or KDOQI classification, which have hindered its examination. ObjectiveThe aim of our study was to establish an association between rs5186 AGTR1 gene polymorphism and GFR depletion, assessed as a risk factor to DKD development in patients with T2DM. MethodsWe analyzed 297 not related patients with T2DM, divided into 221 controls (KDOQI 1) and 76 cases (KDOQI 2). Arterial pressure, anthropometric and biochemical parameters were measured. rs5186 of AGTR1 genotyping was performed by TaqMan assay real-time PCR method. Allele and genotype frequencies, and Hardy-Weinberg equilibrium were measured. Normality test for data distribution was analyzed by Shapiro-Wilk test, variable comparison by Student’s t-test for continuous variables, and Chi-squared test for categorical variables; ANOVA test was used for mean comparison of more than two groups. Effect of rs5186 to DKD was estimated by multiple heritability adjustment models for risk variables of DKD. Statistical significance was indicated by p<0.05. Data was analyzed using Statistical Package STATA v11 software. ResultsDominant and Over-dominant models showed a likelihood ratio to GFR depletion of 1.89 (1.05−3.39, p=0.031) and 2.01 (1.08−3.73, p=0.023) in patients with T2DM. Risk factor increased to 2.54 (1.10−5.89) in women in Over-dominant model. ConclusionIn clinical practice, most of nephropathies progress at a slow pace into a total breakdown of renal function, even asymptomatic. This is the first study, reporting that rs5186 polymorphism of AGTR1 gene contribution to GFR depletion, and this could be evaluated as a predisposing factor for DKD in patients with T2DM.

Hepatic Fibrosis Evaluated in Patients with Type 2 Diabetes with and without Chronic Kidney Disease

Background: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population. Methods: Cross-sectional study including patients with type 2 diabetes with CKD stages 3–5 (N = 50) or without CKD (N = 50). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m² with or without proteinuria. Three methods were used to detect significant liver fibrosis defined as either ≥8 kilopascal measured by transient elastography (FibroScan®), fibrosis-4 (FIB-4) score ≥2.67, or NAFLD fibrosis score (NFS) >0.675. Results: Significant liver fibrosis was found in 38% and 28% of the patients with and without CKD, respectively, using at least one of the three methods. Both FIB-4 score and NFS were significantly higher in patients with CKD (p < 0.0009 and p < 0.0001, respectively), although insignificant after adjustments for age, sex, body mass index, and duration of diabetes. In patients without CKD, a significant association between steatosis and fibrosis was observed (p = 0.0007). Conclusion: Our data do not support any strong independent association between liver fibrosis and established CKD as assessed by FibroScan, FIB-4 score, and NFS, respectively.

Basigin is released in extracellular vesicles derived from the renal tubular epithelium in response to albuminuria.

Irrespective of the cause, albumin/proteinuria induces tubulointerstitial damage and accelerates the progression of kidney diseases. Our series of studies demonstrated that proteinuria, an independent prognostic factor for chronic kidney disease (CKD), is correlated with urinary basigin/CD147 (Bsg) levels. We examined the morphology and origin of Bsg in the tubular lumen through the effects of filtered glucose and protein solutes on the tubules. Diabetic kidney disease (DKD) patients (N = 50) were treated with spironolactone 25 mg for 4 weeks or by conservative treatment. The associations between urinary Bsg values and clinical indicators were examined. Primary-cultured proximal tubular epithelial cells (PTECs) from human adult kidneys were exposed to high glucose or bovine serum albumin (BSA). In patients with early phase DKD, urinary Bsg levels were closely correlated with proteinuria but not HbA1c. Full-length Bsg on extracellular vesicles (EVs) was investigated primarily in urine collected from DKD patients. EVs obtained from the urine of DKD patients included Bsg and SGLT2 proteins. Notably, spironolactone treatment concomitantly suppressed the release of Bsg-bearing EVs in correlation with decreased albuminuria. Exposure of PTECs to BSA (but not high glucose) enhanced the storage of supernatant Bsg in EVs despite the absence of exposure-specific changes in Bsg transcription. Proteinuria induces the release of Bsg-bearing EVs derived from PTECs into the tubular lumen.

High-Density Lipoprotein Lipidomics and Mortality in CKD

Patients with chronic kidney disease (CKD) have dysfunctional high-density lipoprotein (HDL) particles that lack cardioprotective properties; altered lipid composition may be associated with these changes. To investigate HDL lipids as potential cardiovascular risk factors in CKD, we tested the associations of HDL ceramides, sphingomyelins, and phosphatidylcholines with mortality. We leveraged data from a longitudinal prospective cohort of participants with CKD. We included participants aged greater than 21 years with CKD, excluding those on maintenance dialysis or with prior kidney transplant. HDL particles were isolated using density gradient ultracentrifugation. We quantified the relative abundance of HDL ceramides, sphingomyelins, and phosphatidylcholines via liquid chromatography tandem mass spectrometry (LC-MS/MS). Our primary outcome was all-cause mortality. We tested associations using Cox regressions adjusted for demographics, comorbid conditions, laboratory values, medication use, and highly correlated lipids with opposed effects, controlling for multiple comparisons with false discovery rates (FDR). There were 168 deaths over a median follow-up of 6.12 years (interquartile range, 3.71-9.32). After adjustment, relative abundance of HDL ceramides (HR, 1.22 per standard deviation; 95% CI, 1.06-1.39), sphingomyelins with long fatty acids (HR, 1.44; 95% CI, 1.05-1.98), and saturated and monounsaturated phosphatidylcholines (HR, 1.22; 95% CI, 1.06-1.41) were significantly associated with increased risk of all-cause mortality (FDR<5%). We were unable to test associations with cardiovascular disease given limited power. HDL lipidomics may not reflect plasma lipidomics. LC-MS/MS is unable to differentiate between glucosylceramides and galactosylceramides. The cohort was comprised of research volunteers in the Seattle area with CKD. Greater relative HDL abundance of 3 classes of lipids was associated with higher risk of all-cause mortality in CKD; sphingomyelins with very long fatty acids were associated with a lower risk. Altered lipid composition of HDL particles may be a novel cardiovascular risk factor in CKD. Patients with chronic kidney disease have abnormal high-density lipoprotein (HDL) particles that lack the beneficial properties associated with these particles in patients with normal kidney function. To investigate if small lipid molecules found on the surface of HDL might be associated with these changes, we tested the associations of lipid molecules found on HDL with death among patients with chronic kidney disease. We found that several lipid molecules found on the surface of HDL were associated with increased risk of death among these patients. These findings suggest that lipid molecules may be risk factors for death among patients with chronic kidney disease.

Factors That Influence Behavior of Chronic Kidney Disease Prevention in Medan Citizens

Chronic kidney disease is defined as the abnormality of kidney structure and function., which stays for more than 3 months long, with health implications. Today, chronic kidney disease is giving a great contribution to the world’s burden. Chronic kidney disease also affects 8%-16% of the world’s population. The huge number of chronic kidney disease cases has proven to be caused by the lack of knowledge regarding the signs and risk factors of chronic kidney disease. This is observational analytical research with a cross-sectional design. The data used in this research are primary data, obtained from questionnaire instruments on Medan citizens. The data is analyzed univariately, bivariate, and multivariately. Out of 100 respondents, it is acquired that adult (p&lt;0,001), male gender (p&lt;0,001), and higher education (p&lt;0,001) were the only factors significantly associated with good knowledge, good attitude, and positive behavior. Lastly, respondents with good knowledge (p=0,002) (PR = 8,017 (90% CI: 2,759-23,296)) and, good attitude (p&lt;0,001) (PR= 13,668 (90% CI: 4,269-43,767)) will have a positive behavior

Successful treatment of an urgent dialysis patient with uremic encephalopathy

Diabetes has become a global pandemic and is believed to be one of the most common risk factors for chronic kidney disease, which leads to end-stage renal disease, of which a significant number will develop, requiring renal replacement therapy. Uremic encephalopathy is the most frequent complication of untreated chronic kidney disease, is defined as cerebral dysfunction due to toxin accumulation. If this occurs, renal replacement therapy, which is urgent dialysis, is essential for lowering the patient's mortality. We report a 48-year-old female patient with uncontrolled type 2 diabetes who presented with delirium, poor physical performance and muscle mass loss.

Cafeteria Diet-Induced Obesity Worsens Experimental CKD.

Obesity is a significant risk factor for chronic kidney disease (CKD). This study aimed to evaluate the impact of obesity on the development of kidney fibrosis in a model of cafeteria diet rats undergoing 5/6th nephrectomy (SNx). Collagen 1, 3, and 4 expression, adipocyte size, macrophage number, and the expression of 30 adipokines were determined. Collagen 1 expression in kidney tissue was increased in Standard-SNx and Cafeteria-SNx (7.1 ± 0.6% and 8.9 ± 0.9 tissue area, respectively). Renal expression of collagen 3 and 4 was significantly increased (p < 0.05) in Cafeteria-SNx (8.6 ± 1.5 and 10.9 ± 1.9% tissue area, respectively) compared to Cafeteria (5.2 ± 0.5 and 6.3 ± 0.6% tissue area, respectively). Adipocyte size in eWAT was significantly increased by the cafeteria diet. In Cafeteria-SNx, we observed a significant increase in macrophage number in the kidney (p = 0.01) and a consistent tendency in eWAT. The adipokine level was higher in the Cafeteria groups. Interleukin 11, dipeptidyl peptidase 4, and serpin 1 were increased in Cafeteria-SNx. In the kidney, collagen 3 and 4 expressions and the number of macrophages were increased in Cafeteria-SNx, suggesting an exacerbation by preexisting obesity of CKD-induced renal inflammation and fibrosis. IL11, DPP4, and serpin 1 can act directly on fibrosis and participate in the observed worsening CKD.

Risk of Chronic Kidney Disease in Hospitalized Patients with Hidradenitis Suppurativa

Background: Hidradenitis suppurativa (HS) is associated with several comorbidities such as diabetes mellitus and cardiovascular diseases. These comorbidities are also risk factors for chronic kidney disease (CKD), yet little is known about the risk of CKD in HS patients. Objectives: The objective was to study the prevalence of CKD in HS patients. Methods: Cross-sectional population-based study using the United States National Inpatient Sample database between January 1, 2002 and December 31, 2012 was performed. Results: We identified 23,767 hospital admissions for HS patients and 95,068 admissions for age- and gender-matched controls. The prevalence of CKD in HS patients was 6.3% (1,497/23,767) compared to non-HS controls which was 4.3% (4,052/95,068). The association of CKD was strongest in HS patients, who were ≥60 years old, 16.9% (475/2,811), male 7.3% (695/9,556), obese 7.8% (407/5,209), diabetic 12.5% (890/7,105), hyperlipidemic 13.3% (416/3,126), and had cardiovascular diseases 12.5% (631/5,045). The crude odds ratio of CKD in HS patients was 1.5 (95% CI: 1.420–1.605) compared to non-HS patients. The association remained significant after adjusting for important covariates with adjusted odds ratio of CKD in HS patients of 1.1 (95% CI: 1.014–1.176) compared to non-HS patients. Conclusions: Our findings show that there is a possible association of HS with CKD. Any signs of CKD should be assessed by a nephrologist as early diagnosis can hopefully prevent further progression.

Longitudinal tracking of acute kidney injury reveals injury propagation along the nephron

Acute kidney injury (AKI) is an important risk factor for chronic kidney disease (CKD), but the underlying mechanisms of failed tubule repair and AKI-CKD transition are incompletely understood. In this study, we aimed for dynamic tracking of tubule injury and remodeling to understand if focal injury upon AKI may spread over time. Here, we present a model of AKI, in which we rendered only half of the kidney ischemic. Using serial intravital 2-photon microscopy and genetic identification of cycling cells, we tracked dynamic tissue remodeling in post- and non-ischemic kidney regions simultaneously and over 3 weeks. Spatial and temporal analysis of cycling cells relative to initial necrotic cell death demonstrated pronounced injury propagation and expansion into non-necrotic tissue regions, which predicted tubule atrophy with epithelial VCAM1 expression. In summary, our longitudinal analyses of tubule injury, remodeling, and fate provide important insights into AKI pathology.

The incidence and dynamic risk factors of chronic kidney disease among people with HIV.

We investigate the incidence of chronic kidney disease (CKD) among people with HIV (PWH) and the dynamic risk factors associated with CKD incidence. A population-based cohort study of PWH in South Carolina. Adults (age ≥18 years) PWH diagnosed between 2006 and 2019 who were CKD-free at baseline were included. The associations of HIV-related risk factors and conventional risk factors with the incidence of CKD were investigated during the overall study period and by different follow-up periods (i.e. 5, 10, and 15 years) by multivariate logistic regression. Among 9514 PWH, the incidence of CKD was 12.39 per 1000 person-years. The overall model indicated that conventional risk factors, such as hypertension, dyslipidemia, cardiovascular disease, and diabetes, were significantly associated with a higher risk of developing CKD. HIV-related characteristics, such as high percentage of days with viral suppression, recent CD4 + cell count, and percentage of retention in care, were associated with a lower risk of CKD compared with their counterparts. In the subgroup analysis, the results were similar for the 5-year and 6-10 years follow-up groups. Among patients who did not develop CKD by the 10th year, the risk factors for developing CKD within 11-15 years were dyslipidemia, diabetes, low recent CD4 + cell count, and short duration of retention in care while other predictors vanished. Diabetes, CD4 + cell count, and retention in care were persistently associated with CKD despite of follow-up duration. Closely monitoring diabetes and improving CD4 + cell count and retention in care are important to lower the risk of CKD in PWH.

Prevalence of chronic kidney disease and associated factors among patients with underlying chronic disease at Dessie Referral Hospital, East Amhara Region, Ethiopia.

Chronic kidney disease is defined as a reduction in glomerular filtration rate below 60 ml/min per 1.73 m2 and presence of albuminuria over a period of time. Globally, 10%-15% of populations are affected by chronic kidney disease. Studies conducted in Jimma, Addis Ababa, and the Tigray region were conducted on a single chronic disease and did not include human immune viruses. In addition, there has been no such study conducted in the Amhara region. Therefore, the aim of this study was to determine the magnitude and associated factors of chronic kidney disease among chronic patients who are followed up at an outpatient department. An institutional-based cross-sectional study of 480 chronic patients was conducted at Dessie Referral Hospital, Dessie, Ethiopia between 15 March and 16 April 2020. Data were entered into Epidata and exported to SPSS version 25 for analysis. Binary logistic regression models were performed to identify factors associated with chronic kidney disease. The variables with a p-value ≤0.25 were considered to be a candidate for multivariable logistic regression. A p-value ≤0.05 was considered a statistically significant association. The magnitude of chronic kidney disease among the study participants was 21.3%. Variables such as hypertension [adjusted odds ratio (AOR): 2.6, 95% CI: 1.58-4.27], use of non-steroidal anti-inflammatory drugs (AOR: 2.4, 95% CI: 1.41-3.97), smoking (AOR: 4.4, 95% CI: 2.65-7.34), routine physical activity (AOR: 0.6, 95% CI: 0.35-0.94), and obesity (AOR: 3.0, 95% CI: 1.76-5.05) were significantly associated with the chronic kidney disease. This study found that the magnitude of chronic kidney disease in the study area was high. Hypertension, use of non-steroidal anti-inflammatory drugs, smoking, routine physical activity, and obesity were found to be significant factors for chronic kidney disease.

Effect of E-Vaping on Kidney Health in Mice Consuming a High-Fat Diet.

High-fat diet (HFD) consumption and tobacco smoking are risk factors for chronic kidney disease. E-cigarettes have gained significant popularity among younger populations worldwide, especially among overweight individuals. It is unclear whether vaping interacts with HFD consumption to impact renal health. In this study, Balb/c mice (male, 7 weeks old) were fed a pellet HFD (43% fat, 20 kJ/g) for 16 weeks when exposed to nicotine or nicotine-free e-vapour from weeks 11 to 16. While HFD alone increased collagen Ia and IV depositions, it did not cause significant oxidative stress and inflammatory responses in the kidney itself. On the other hand, e-vapour exposure alone increased oxidative stress and damaged DNA and mitochondrial oxidative phosphorylation complexes without significant impact on fibrotic markers. However, the combination of nicotine e-vapour and HFD increased inflammatory responses, oxidative stress-induced DNA injury, and pro-fibrotic markers, suggesting accelerated development of renal pathology. Nicotine-free e-vapour exposure and HFD consumption suppressed the production of mitochondrial OXPHOS complexes and extracellular matrix protein deposition, which may cause structural instability that can interrupt normal kidney function in the future. In conclusion, our study demonstrated that a HFD combined with e-cigarette vapour exposure, especially when containing nicotine, can increase susceptibility to kidney disease.

Chronic environmental hypoxia attenuates innate immunity activation and renal injury in two CKD models.

Tissue hypoxia has been pointed out as a major pathogenic factor in chronic kidney disease (CKD). However, epidemiological and experimental evidence inconsistent with this notion has been described. We have previously reported that chronic exposure to low ambient Po2 promoted no renal injury in normal rats and in rats with 5/6 renal ablation (Nx) unexpectedly attenuated renal injury. In the present study, we investigated whether chronic exposure to low ambient Po2 would also be renoprotective in two additional models of CKD: adenine (ADE) excess and chronic nitric oxide (NO) inhibition. In both models, normobaric ambient hypoxia attenuated the development of renal injury and inflammation. In addition, renal hypoxia limited the activation of NF-κB and NOD-like receptor family pyrin domain containing 3 inflammasome cascades as well as oxidative stress and intrarenal infiltration by angiotensin II-positive cells. Renal activation of hypoxia-inducible factor (HIF)-2α, along with other adaptive mechanisms to hypoxia, may have contributed to these renoprotective effects. The present findings may contribute to unravel the pathogenesis of CKD and to the development of innovative strategies to arrest its progression.NEW & NOTEWORTHY Hypoxia is regarded as a major pathogenic factor in chronic kidney disease (CKD). In disagreement with this view, we show here that sustained exposure to low ambient Po2 lessened kidney injury and inflammation in two CKD models: adenine (ADE) excess and chronic nitric oxide (NO) inhibition. Together with our previous findings in the remnant kidney, these observations indicate that local changes elicited by hypoxia may exert renoprotection in CKD, raising the prospect of novel therapeutic strategies for this disease.

TJ-17 (Goreisan) mitigates renal fibrosis in a mouse model of folic acid-induced chronic kidney disease

Background and purposeTJ-17 (Goreisan), a traditional Japanese Kampo medicine, has been generally used to treat edema, such as heart failure, due to its diuretic effect. In the present study, we investigate the effects of TJ-17 on chronic kidney disease (CKD). MethodsWe the preventive action of TJ-17 against acute kidney injury (AKI) transition to CKD in vivo using a folic acid (FA)-induced mouse model. Mice were treated with food containing TJ-17 at 48 h after FA intraperitoneal injection (AKI phase). ResultsHistological analysis, as well as renal function and renal injury markers, deteriorated in mice with FA-induced CKD and were ameliorated by TJ-17 treatment. Increased levels of inflammatory cytokines and macrophage infiltration were also alleviated in mice treated with TJ-17. Renal fibrosis, a crucial factor in CKD, was induced by FA administration and inhibited by TJ-17 treatment. Pretreatment with TJ-17 did not exert an inhibitory effect on FA-induced AKI. The increase in urinary volume in FA-induced CKD mice was ameliorated by TJ-17 treatment, with a concurrent correction of reduced aquaporins expression in the kidney. ConclusionTJ-17 may have a novel preventive effect against inflammation, oxidative stress, and fibrosis, contributing to innovation in the treatment of CKD.