Risk Factors For Chronic Kidney Disease Research Articles

Metabolically healthy obesity and chronic kidney disease risk: exploring the dynamics.

Obesity represents a prevalent global health concern with significant implications for various diseases, including chronic kidney disease (CKD). Within this landscape, the phenomenon of metabolically healthy obesity has emerged, challenging traditional notions about the health risks associated with excess weight. While traditional CKD risk factors involve obesity, metabolic syndrome, diabetes, and hypertension, the metabolically healthy obese (MHO) subgroup disrupts these assumptions. Our main objective in this study is to integrate existing literature on CKD in MHO individuals. In this endeavor, we delve into the pathophysiological foundations, the transition between obesity phenotypes and their impact on renal health, examine the implications of their metabolic resilience on mortality within a renal context, and explore potential management strategies specifically designed for MHO individuals. Offering a comprehensive overview of the pathophysiology, we cover various factors contributing to the risk of CKD in the metabolically healthy obese setting, including inflammation, cytokines, hemodynamics, and the renin-angiotensin-aldosterone system, gastrointestinal microbiota, diet, exercise, adipose distribution, and lipotoxicity. Through this synthesis, we aim to provide a comprehensive understanding of the risk of CKD in those classified as MHO.

Costs and healthcare use of patients with chronic kidney disease in the Northern Territory, Australia

BackgroundThe burden of chronic kidney disease (CKD) is high in the Northern Territory (NT), Australia. This study aims to describe the healthcare use and associated costs of people at risk of CKD (e.g. acute kidney injury, diabetes, hypertension, and cardiovascular disease) or living with CKD in the NT, from a healthcare funder perspective.MethodsWe included a retrospective cohort of patients at risk of, or living with CKD, on 1 January 2017. Patients on kidney replacement therapy were excluded from the study. Data from the Territory Kidney Care database, encompassing patients from public hospitals and primary health care services across the NT was used to conduct costing. Annual healthcare costs, including hospital, primary health care, medication, and investigation costs were described over a one-year follow-up period. Factors associated with high total annual healthcare costs were identified with a cost prediction model.ResultsAmong 37,398 patients included in this study, 23,419 had a risk factor for CKD while 13,979 had CKD (stages 1 to 5, not on kidney replacement therapy). The overall mean (± SD) age was 45 years (± 17), and a large proportion of the study cohort were First Nations people (68%). Common comorbidities in the overall cohort included diabetes (36%), hypertension (32%), and coronary artery disease (11%). Annual healthcare cost was lowest in those at risk of CKD (AUD$7,958 per person) and highest in those with CKD stage 5 (AUD$67,117 per person). Inpatient care contributed to the majority (76%) of all healthcare costs. Predictors of increased total annual healthcare cost included more advanced stages of CKD, and the presence of comorbidities. In CKD stage 5, the additional cost per person per year was + $53,634 (95%CI 32,769 to 89,482, p < 0.001) compared to people in the at risk group without CKD.ConclusionThe total healthcare costs in advanced stages of CKD is high, even when patients are not on dialysis. There remains a need for effective primary prevention and early intervention strategies targeting CKD and related chronic conditions.

Air pollution aggravates renal ischaemia-reperfusion-induced acute kidney injury.

Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM2.5) and a decline in renal function. PM2.5 exerts harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischaemia-reperfusion injury (IRI) involves biological processes similar to those involved in PM2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM2.5 exposure on IRI-induced AKI. Through a unique environmentally controlled setup, mice were exposed to urban PM2.5 or filtered air for 12 weeks before IRI followed by euthanasia 48 h after surgery. Animals exposed to PM2.5 and IRI exhibited reduced glomerular filtration, impaired urine concentration ability, and significant tubular damage. Further, PM2.5 aggravated local innate immune responses and mitochondrial dysfunction, as well as enhancing cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation. This increased renal senescence and suppressed the anti-ageing protein klotho, leading to early fibrotic changes. In vitro studies using proximal tubular epithelial cells exposed to PM2.5 and hypoxia/reoxygenation revealed heightened activation of the STING pathway triggered by cytoplasmic mitochondrial DNA, resulting in increased tubular damage and a pro-inflammatory phenotype. In summary, our findings imply a role for PM2.5 in sensitising proximal tubular epithelial cells to IRI-induced damage, suggesting a plausible association between PM2.5 exposure and heightened susceptibility to CKD in individuals experiencing AKI. Strategies aimed at reducing PM2.5 concentrations and implementing preventive measures may improve outcomes for AKI patients and mitigate the progression from AKI to CKD. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Sex differences in the association of long-term exposure to heat stress on kidney function in a large Taiwanese population study.

The incidence and prevalence of dialysis in Taiwan are high compared to other regions. Consequently, mitigating chronic kidney disease (CKD) and the worsening of kidney function have emerged as critical healthcare priorities in Taiwan. Heat stress is known to be a significant risk factor for CKD and kidney function impairment. However, differences in the impact of heat stress between males and females remains unexplored. We conducted this retrospective cross-sectional analysis using data from the Taiwan Biobank (TWB), incorporating records of the wet bulb globe temperature (WBGT) during midday (11 AM-2 PM) and working hours (8 AM-5 PM) periods based on the participants' residential address. Average 1-, 3-, and 5-year WBGT values prior to the survey year were calculated and analyzed using a geospatial artificial intelligence-based ensemble mixed spatial model, covering the period from 2010 to 2020. A total of 114,483 participants from the TWB were included in this study, of whom 35.9% were male and 1053 had impaired kidney function (defined as estimated glomerular filtration rate < 60ml/min/1.73m2). Multivariable analysis revealed that in the male participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1℃ increase were significantly positively associated with eGFR < 60ml/min/1.73m2 (odds ratio [OR], 1.096, 95% confidence interval [CI] = 1.002-1.199, p = 0.044 for 1year; OR, 1.093, 95% CI = 1.000-1.196, p = 0.005 for 3years; OR, 1.094, 95% CI = 1.002-1.195, p = 0.045 for 5years). However, significant associations were not found for the working hours period. In the female participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1℃ increase were significantly negatively associated with eGFR < 60ml/min/1.73m2 (OR, 0.872, 95% CI = 0.778-0.976, p = 0.018 for 1year; OR, 0.874, 95% CI = 0.780-0.978, p = 0.019 for 3years; OR, 0.875, 95% CI = 0.784-0.977, p = 0.018 for 5years). In addition, during the working hours period, the 1-, 3-, and 5-year average WBGT values per 1℃ increase were also significantly negatively associated with eGFR < 60ml/min/1.73m2 (OR, 0.856, 95% CI = 0.774-0.946, p = 0.002 for 1year; OR, 0.856, 95% CI = 0.774-0.948, p = 0.003 for 3years; OR, 0.853, 95% CI = 0.772-0.943, p = 0.002 for 5years). In conclusion, our results revealed that increased WBGT was associated with impaired kidney function in males, whereas increased WBGT was associated with a protective effect against impaired kidney function in females. Further studies are needed to elucidate the exact mechanisms underlying these sex-specific differences.

Skipping Breakfast and Progression of Chronic Kidney Disease in the General Japanese Population: the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD)

Introduction: Breakfast-skipping habits are associated with adverse health outcomes including coronary heart disease, metabolic syndrome and diabetes mellitus. However, it remains uncertain whether skipping breakfast affects chronic kidney disease (CKD) risk. This study aimed to examine the association between skipping breakfast and progression of CKD. Methods: We retrospectively conducted a population-based cohort study using the data from the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD). Between 2008 and 2019, we included 922 participants aged 30 years or older who had CKD (estimated glomerular filtration rate &amp;lt;60 mL/min/1.73m2 and/or proteinuria) at baseline. Breakfast-skippers were defined as participants who skipped breakfast more than 3 times per week. The outcome was CKD progression defined as a decline of at least 30% in the eGFR from the baseline status. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD progression, adjusted for other CKD risk factors. Results: During a follow-up period with a mean of 5.5 years, CKD progression occurred in 60 (6.5%) participants. The incidence rate (per 1,000 person-years) of CKD progression was 21.5 in the breakfast-skipping group and 10.7 in the breakfast-eating group (p=0.029), respectively. The multivariable-adjusted HR (95% CI) for CKD progression was 2.60 (95% CI 1.29‒5.26) for the breakfast-skipping group (p=0.028) compared with the group eating breakfast. There were no clear differences in the association of skipping breakfast with CKD progression in subgroup analyses by sex, age, obesity, hypertension, diabetes mellitus, baseline eGFR and baseline proteinuria. Conclusion: Skipping breakfast was significantly associated with higher risk of CKD progression in the general Japanese population.

Associations between metabolic dysfunction-associated fatty liver disease, chronic kidney disease, and abdominal obesity: a national retrospective cohort study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD) present notable health challenges, however, abdominal obesity has received scant attention despite its potential role in exacerbating these conditions. Thus, we conducted a retrospective cohort study using the National Health and Nutrition Examination Surveys III (NHANES III) of the United States from 1988 to 1994 including 9161 participants, and mortality follow-up survey in 2019. Statistical analyze including univariable and multivariable Logistic and Cox regression models, and Mediation effect analyze were applied in study after adjustment for covariates. Our findings revealed that individuals with both abdominal obesity and MAFLD were more likely to be female, older and exhibit higher prevalence of advanced liver fibrosis (7.421% vs. 2.363%, p < 0.001), type 2 diabetes mellitus (T2DM) (21.484% vs. 8.318%, p < 0.001) and CKD(30.306% vs. 16.068%, p < 0.001) compared to those with MAFLD alone. MAFLD (adjusted OR: 1.392, 95% CI 1.013-1.913, p = 0.041), abdominal obesity (adjusted OR 1.456, 95% CI 1.127-1.880, p = 0.004), abdominal obesity with MAFLD (adjusted OR 1.839, 95% CI 1.377-2.456, p < 0.001), advanced fibrosis(adjusted OR 1.756, 95% CI 1.178-2.619, p = 0.006) and T2DM (adjusted OR 2.365, 95% CI 1.758-3.183, p < 0.001) were independent risk factors of CKD. The abdominal obese MAFLD group had the highest all-cause mortality as well as mortality categorized by disease during the 30-year follow-up period. Indices for measuring abdominal obesity, such as waist circumference (WC), waist-hip ratio (WHR), and lipid accumulation product (LAP), elucidated a greater mediation effect of MAFLD on CKD compared to BMI on CKD (proportion mediation 65.23%,70.68%, 71.98%, respectively vs. 32.63%). In conclusion, the coexistence of abdominal obesity and MAFLD increases the prevalence and mortality of CKD, and abdominal obesity serves as a mediator in the association between MAFLD and CKD.

#1117 Skipping breakfast and progression of chronic kidney disease in a general Japanese population

Abstract Background and Aims Unhealthy eating habits such as skipping breakfast are associated with adverse health outcomes including coronary heart disease, metabolic syndrome and diabetes mellitus. However, it remains uncertain whether skipping breakfast affects chronic kidney disease (CKD) risk. The aim of this study was to investigate the association between skipping breakfast and progression of CKD. Method Between 2008 and 2019, we conducted a retrospective cohort study using annual health check data in Iki City, Nagasaki, Japan. A total of 922 participants aged 30 years or older who had CKD (estimated glomerular filtration rate &amp;lt;60 mL/min/1.73 m2 and/or proteinuria) at baseline were included in the present analysis. The breakfast-skipping group was defined as participants who skipped breakfast more than 3 times per week. The outcome was CKD progression defined as a decline of at least 30% in the eGFR from the baseline status. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD progression, adjusted for other CKD risk factors. Results During a follow-up period with a mean of 5.5 years, CKD progression occurred in 60 (6.5%) participants. The incidence rate (per 1,000 person-years) of CKD progression was 21.5 in the breakfast-skipping group and 10.7 in the breakfast-eating group (p = 0.029), respectively. The multivariable-adjusted HR (95% CI) for CKD progression was 2.60 (95% CI 1.29‒5.26) for the breakfast-skipping group (p = 0.028) compared with the group eating breakfast. There were no clear differences in the association of skipping breakfast with CKD progression in subgroup analyses by sex, age, obesity, hypertension, diabetes mellitus, baseline eGFR and baseline proteinuria. Conclusion Skipping breakfast was significantly associated with higher risk of CKD progression in a general Japanese population.

#2333 Risk of NDI and CKD in individuals treated with lithium

Abstract Background and Aims Nephrogenic diabetes insipidus (NDI) is a known side effect of lithium treatment. Lithium has also been associated with the development of chronic kidney disease (CKD). The aims of this study were to examine the risk factors for NDI among persons on lithium treatment and the association of NDI and other risk factors with the development of chronic kidney disease (CKD). Method This was a retrospective cohort study of all persons in Iceland using lithium in the years 2003-2018. Lithium exposure was defined as at least one lithium prescription or at least one serum lithium measurement with a detectable lithium level. Patients with affective disorders (ICD-10 codes F30-F39) attending the outpatient clinics of Landspitali–The National University Hospital Mental Health Services in 2014-2016, without lithium exposure, served as controls. NDI was defined as concomitant serum sodium (SNa) &amp;gt;144 mmol/L and urine specific gravity (SG) &amp;lt;1.005; individuals with no SNa measurement after 2003 were excluded from the analysis. CKD stages 3-5 were defined according to the KDIGO guidelines for CKD as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated from serum creatinine (SCr) using the CKD-EPI equation. The analysis of incident CKD was limited to the period when standardized SCr measurements had become available, in 2008-2018. Individuals with &amp;lt;2 SCr measurements after 2008 and those with CKD stages 3-5 before 2008 were excluded. In addition, this analysis specifically examined the relationship between the mean serum lithium concentration and the development of CKD, comparing those not exposed to lithium to 3 groups of lithium users with a mean serum lithium concentration of 0.3-0.59, 0.6-0.79 and 0.8-0.99 mmol/L. Acute kidney injury (AKI) was defined according to the SCr component of the KDIGO criteria for AKI, and other comorbid conditions were defined based on ICD-9 and ICD-10 diagnosis codes. Multivariable Cox regression with time-dependent covariables was used for risk assessment. Results In the analysis of the development of NDI, the group exposed to lithium consisted of 2252 individuals, of whom 58 (2.6%) met the criteria for NDI compared with 13 (1.0%) of the 1272 controls. When compared with those without lithium exposure. the risk of NDI was lithium concentration dependent, with a hazard ratio (HR) of 1.22 (95% CI, 0.50–2.98), 5.52 (95% CI, 2.81–10.85) and 10.03 (95% CI, 4.51–22.27) for groups with a mean lithium concentration of 0.3–0.59, 0.6–0.79 and 0.8–0.99 mmol/L, respectively. A previous diagnosis of CKD was also a significant risk factor (HR 3.00 [95% CI, 1.50–6.12]). In the CKD analysis, the group of lithium users comprised 1401 individuals. Of those, 192 (13.7%) developed CKD, compared with 39 (2.8%) of the 1406 controls. Analysis adjusted for initial eGFR showed that NDI was a significant risk factor for CKD (HR 1.90 [95% CI, 1.03-3.54]). Other significant risk factors were mean lithium concentration with HR of 1.25 (95% CI, 0.82–1.91), 2.84 (95% CI, 1.94–4.15) and 5.11 (95% CI, 3.22–8.07) for the groups with a mean lithium concentration of 0.6–0.79 and 0.8–0.99 mmol/L, respectively. Other significant risk factors were age per year (HR 1.03 [95% CI, 1.02–1.05]), diabetes (HR 1.62 (95% CI, 1.08–2.46]) and history of AKI (HR 1.92 [95% CI, 1.33–2.77]). Conclusion Lithium use is associated with NDI in a concentration-dependent manner. Long-term lithium treatment is associated with a risk of CKD, which also is concentration dependent, in patients with bipolar and unipolar mood disorders. NDI may be an important risk factor for CKD.

#1913 Long-term trends of blood pressure and blood glucose in patients with chronic kidney disease in South Korea, 1998-2021

Abstract Background and Aims Uncontrolled hypertension and elevated blood glucose are established risk factors for the progression of chronic kidney disease (CKD) and its complications. The long-term trends in these CKD risk factors, including the coronavirus 2019 (COVID-19) pandemic, have not been thoroughly studied in South Korea. Method We used data from Korea National Health and Nutrition Examination Survey, which nationally representative survey in South Korea. Data from Korean adults from 1998 to 2021 were obtained. We defined CKD as the participant's estimated glomerular filtration rate being &amp;lt;60 mL/min/1.73 m², one-time spot proteinuria of ≥1+. The evaluated risk factors for CKD included uncontrolled blood pressure and blood glucose, defined as a mean systolic blood pressure ≥120 mmHg and a glycated hemoglobin (HbA1c) level ≥6.5%. We examined the trend in the prevalence of uncontrolled hypertension and blood glucose, conducting subgroup analysis based on socioeconomic and behavioral factors. Results The trend among a total of 4,648 CKD patients with uncontrolled hypertension gradually decreased or remained steady from 1998 to 2019, however, there was an increase observed in COVID-19 pandemic period from 2019 to 2021 (1998-2005, 75.5% [95% confidence interval (CI) 71.5–79.5]; 2016–2019, 63.6% [95% CI 60.5–66.7]; 2021, 69.4% [95% CI 63.6–75.1]; and β diff, 0.65; 95% CI 0.30 to 1.00). Moreover, in the subgroup analysis of the prevalence of uncontrolled hypertension in CKD, almost all subgroups increased during the pandemic, except for older patients (age ≥ 65) However, the overall trend difference in the prevalence of uncontrolled blood glucose among a total of 1,848 CKD patients with diabetes did not show significant changes (β diff, 2.80; 95% CI −0.11-5.71) between the periods before and during the COVID-19 pandemic. Conclusion During the COVID-19 pandemic, uncontrolled hypertension had a more significant impact on CKD patients than uncontrolled blood glucose, with an increase in the prevalence of uncontrolled hypertension. It is estimated that additional attention and policies for uncontrolled hypertension with CKD patients may be needed during periods of medical vulnerability, such as the COVID-19 pandemic.

#1082 Early-stage chronic kidney disease as a risk factor for suicide: a nationwide observational cohort study

Abstract Background and Aims Chronic kidney disease (CKD) is associated with poor psychological well-being. Whether early-stage CKD is a risk factor for suicide warrants further research. Method This nationwide, retrospective, cohort study aimed to evaluate the risk of suicide in patients with early-stage CKD and identify the associated risk factors. A total of 3 945 198 individuals aged ≥19 years who underwent the 2009 national health screening were enrolled. Among them, 202 291 patients had early-stage CKD (estimated glomerular filtration rate (eGFR) ≥30 and &amp;lt;60 mL/min per 1.73 m2 and/or dipstick albuminuria ≥1+). The study outcome was suicide as confirmed by the nationwide death register based on death certificates. Results The study population had a mean age of 59 ± 15 years, and 47% were male. We identified 930 suicides (incidence rate, 0.45 per 1 000 person-years) in the CKD group and 11 332 suicides (incidence rate, 0.27 per 1 000 person-years) in the non-CKD group. Early-stage CKD was significantly associated with an increased risk of suicide in multivariable analysis adjusted for demographic characteristics; lifestyle habits; comorbidities, including diabetes and hypertension; economic status; and depression (hazard ratio, 1.16; 95% confidence interval, 1.09‒1.25). Suicide risk was higher in individuals with proteinuria but preserved kidney function (eGFR &amp;gt;60 mL/min per 1.73 m2 and dipstick albuminuria &amp;gt;1+) than in those without CKD. In the CKD group, older males and current smokers had a higher risk of suicide. Conclusion CKD even in the early stages is associated with significantly higher risk of death from suicide. Hence, healthcare providers may need to examine the mental health of patients with early-stage CKD and other risk factors to prevent suicide.

#1966 Participation rate and yield of screening for albuminuria in the primary care setting for early identification of chronic kidney disease (SALINE)

Abstract Background and Aims Although guidelines recommend opportunistic screening for chronic kidney disease (CKD) in individuals with established risk factors, such as diabetes, hypertension, or cardiovascular disease, screening for CKD in these individuals remains suboptimal. This study aimed to evaluate the effectiveness of an additional systematic home-based albuminuria screening program in patients at risk for CKD in a primary care setting. Method A cross-sectional screening study was performed in 10 general practices and 5 pharmacies in the Netherlands between Nov 2021-Nov 2023. A random selection of patients aged 45-80 years with risk factors for CKD progression was invited for home-based albuminuria screening. These patients were registered at their general practitioner (GP) or at the pharmacy. Patients in the GP-group were identified based on the following risk factors: diabetes, cardiovascular disease, hypertension, hypercholesterolemia, or obesity. Patients were excluded in case of a normal albuminuria status (ACR (albumin-creatinine ratio) &amp;lt;3.0 mg/mmol) within 18 months prior to the screening. Patients in the pharmacy-group were identified based on drug prescriptions for the aforementioned risk factors in the last 6 months. Home-based albuminuria screening was performed using a urine collection device that was sent by post to a central laboratory for ACR measurement. If the test result was positive upon confirmation (i.e. ≥two tests ACR ≥3 mg/mmol), patients were invited for an elaborate visit in the general practice or pharmacy, to assess presence of CKD and cardiovascular risk factors. Main outcomes were participation rate and yield of the home-based albuminuria screening in the total study population and in both screening groups separately. Secondary outcomes were the yield of persistent albuminuria despite treatment with RAS-inhibition in both screening groups and the yield of previously undiagnosed albuminuria in the GP-group. Results We invited 6 380 patients (2 578 via pharmacy registries and 3 802 via GP registries), of whom 2 147 completed the home-based screening, corresponding to a participation rate of 33.7%. The participation rate among GP patients was 41.4% (1 575/3 802), compared to 22.2% (572/2 578) among pharmacy patients (P &amp;lt; .001). Albuminuria was confirmed in 8.5% (134/3 802) and 5.6% (32/2 578) of the participants in the GP- and pharmacy-group, respectively. Among participants in the GP-group, 59.7% (80/134) had a positive albuminuria test within one year prior to the screening; the remaining 40.3% either had no albuminuria test (or a normal albuminuria test within one year prior to the screening. Of those with increased albuminuria in the GP- and pharmacy-group, 85.8% (115/134) and 81.3% (26/32) attended the elaborate screening visit, respectively. In the GP-group, 72.2% (83/115) had an eGFR &amp;gt;60 and only 19.1% (22/115) an adequate blood pressure (&amp;lt;130/80 mmHg), compared to 69.2% (18/26) and 19.2% (5/26) in the pharmacy-group. Of the albuminuric participants in the GP- and pharmacy-group, respectively, 44.3% (51/115) and 23.1% (6/26) were not treated with RAS inhibition, and 94.8% (109/115) and 96.2% (25/26), respectively, were not treated with an SGLT2 inhibitor. Many patients were not aware of having albuminuria before participating in the systematic home-based screening program 42.6% (109/115) in the GP-group vs. 61.5% (16/26) in the pharmacy-group). Conclusion In conclusion, systematic albuminuria screening in the primary care setting when added to regular opportunistic screening has an acceptable participation rate and yield when performed via GPs, but is less effective when performed via pharmacies. It identifies patients with yet unknown albuminuria and most of the identified patients may benefit of initiation or optimization of albuminuria-lowering treatment. The introduction of such systematic albuminuria screening programs via GPs merits further study.

#3094 Prevalence and risk factors for progression and mortality in patients with advanced chronic kidney disease

Abstract Background and Aims Chronic kidney disease (CKD) is a growing health concern worldwide. Prevalence and risk factors for its progression are highly relevant, given that Portugal has the highest incidence and prevalence rates of dialysis in Europe. With this study, we aimed to estimate the prevalence of patients with CKD stage 4 and 5 in a tertiary center in Portugal, as well as to evaluate risk factors for progression and mortality. Method We evaluated all patients followed in the Nephrology outpatient clinic at a tertiary center in Portugal during the year 2021, and selected those with CKD stage 4 and stage 5, based on estimated glomerular filtration rate (eGFR) using CKD-EPI formula. Primary endpoints were CKD progression or mortality after 1 year of follow-up. Progression was defined as initiating renal replacement therapy (RRT) or transition from stage 4 to stage 5 CKD. Results We evaluated 4381 patients, of which 1083 (24.7%) were included with CKD stage 4 (n = 856) and CKD stage 5 (n = 227). There was a predominance of males (52.7%), with a mean age of 74.6 ± 12.5 years. We observed a high prevalence of hypertension (94%), diabetes mellitus (46.2%), dyslipidemia (81%), heart failure (34%) and past history of major cardiovascular events (21%). At one year follow-up 108 patients died, 116 lost follow-up, and 256 (26.5%) had CKD progression, of which 179 (18.5%) initiated renal replacement therapy. 33.5% of patients initiating dialysis had a definitive access, mostly in stage 5 CKD (40 vs. 25%, p &amp;lt; 0.05). Risk factors for progression (versus stability) in univariate analysis were male gender (64.5 vs. 50.1, p &amp;lt; 0.001), younger age (68 vs. 75 years, p &amp;lt; 0.001) and lower eGFR (16 vs. 22 mL/min). Progression occurred in 51% of stage 5 CKD vs. 26.5% stage 4. Worse laboratory control of anemia, hyperparathyroidism, acidosis, and albuminuria (urinary albumin/creatinine ratio 1242 vs. 302 mg/g, p &amp;lt; 0.01) were identified risk factors for progression. In multivariate analysis, predictors for CKD progression were younger age (OR: 0.97, CI: 0.95-0.99, p = 0.02), male gender (OR: 2.82, CI: 1.43-5.57, p = 0.003), lower eGFR (OR: 0.80, CI: 0.74-0.86, p &amp;lt; 0.001), lower hemoglobin levels (OR: 0.62, CI: 0.48-0.79, p &amp;lt; 0.001), and proteinuria (OR: 1.44, CI: 1.22-1.53, p 0.003). Regarding mortality, no statically significant differences were observed between CKD stage 4 and 5, and in multivariate analysis the only independent risk factors for death were older age and heart failure, which increased 3.4 times mortality risk (OR: 3.40, CI: 1.48-7.83, p = 0.04). Conclusion Our data show a high prevalence of CKD and traditional risk factors, with an annual progression rate of 26.5%. Anemia and proteinuria were identified as modifiable risk factors for progression. In older patients with heart failure, the mortality risk was found to be higher than progression risk, highlighting the importance of cardiovascular protection and consideration of conservative management in this particular subset of patients.

High body mass index and triglyceride levels at health checkups increase the risk of new-onset chronic kidney disease and worsening renal function: the TAMA MED Project-CKD.

Health checkups are important in patients with chronic kidney disease (CKD), which is not easily accompanied by subjective symptoms. CKD can be caused or aggravated by factors that have not yet been identified. This retrospective cohort study included 7 483 patients who underwent specific annual health checkups at a medical institution in Tama City, did not have CKD in 2012, and continued to undergo checkups (aged 40-74years). We examined the risk factors for new-onset CKD and 1.5-fold increase in serum creatinine levels among laboratory values from 2012 to 2020. Age, body mass index (BMI), triglyceride levels, atrial fibrillation, and medication for hypertension (HT) and diabetes mellitus were independent risk factors for proteinuria, whereas current smoking, BMI, systolic blood pressure (SBP), and medication for HT were independent risk factors for estimated glomerular filtration rate < 60mL/min/1.73m2. SBP, triglyceride levels and medication for HT were risk factors for a 1.5-fold increase in serum creatinine levels during course of the study. The cut-off values of BMI for eGFR < 60mL/min/1.73m2 were 22.2 (men 24.7, women 22.1) kg/m2 and fasting triglyceride levels for a 1.5-fold increase in serum creatinine level were 171 (men 247, women 170) mg/dL, respectively. Health checkups provide information to prevent new-onset CKD and worsening of renal function. It is necessary to increase the rate of health checkups and visits to medical institutions after health checkups as well as to use these results for health guidance.

Prevalence and risk factors for chronic kidney disease among older adult patients with schizophrenia in Taiwan.

There is an increasing incidence and prevalence of patients with chronic kidney disease (CKD) worldwide. Little is known the prevalence of CKD among older patients with schizophrenia. The purpose of this study was to investigate the prevalence of CKD and its risk factors in older adults with schizophrenia. In this cross-sectional study, a convenience sample of 240 patients with schizophrenia age 50 or older were recruited. In addition to demographic and clinical data, participants' estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation based on age, sex, ethnicity, and serum creatinine level determined from a blood sample taken from participants. The overall prevalence of CKD was 11.3%. Those with CKD group were older, had a longer duration of psychiatric illness, a higher body mass index (BMI), and diagnoses of hypertension compared to those in the non-CKD group. Independent of other risk factors, older age and BMI were significantly associated with CKD. This study found that the overall prevalence of CKD in older patients with schizophrenia was 11.3%. Risk factors for CKD in this population were older age and higher BMI. In addition to early identification and early treatment of CKD in older patients with schizophrenia, clinicians should actively manage the risk factors identified in this study, such as higher BMI and older age.

Relationship between parity and the prevalence of chronic kidney disease in Japan considering hypertensive disorders of pregnancy and body mass index.

Global studies exploring the relationship between parity and chronic kidney disease (CKD) are scarce. Furthermore, no study has examined the relationship between parity and CKD in Japan. Therefore, this study aimed to examine the relationship between parity and the prevalence of CKD in a Japanese population, considering the clinical history of hypertensive disorders of pregnancy (HDP) and current body mass index (BMI) based on menopausal status. This cross-sectional study included 26,945 Japanese multiparous women (5,006 premenopausal and 21,939 postmenopausal women) and 3,247 nulliparous women (1,599 premenopausal and 1,648 postmenopausal women). Participants were divided into two groups based on their menopausal status (premenopausal and postmenopausal women). The relationship between parity and the prevalence of CKD was evaluated using a multiple logistic regression model adjusted for several covariates, including a clinical history of HDP and current BMI. The relationship between parity and the prevalence of CKD was not statistically significant in either premenopausal or postmenopausal multiparous women. A clinical history of HDP was significantly associated with an increased risk of CKD in premenopausal and postmenopausal multiparous women. However, the relationship between a clinical history of HDP and CKD in premenopausal women was weakened after adjusting for current BMI. Furthermore, the current BMI was significantly associated with an increased risk of CKD in both premenopausal and postmenopausal women. Parity is not significantly associated with the prevalence of CKD in premenopausal and postmenopausal multiparous women. A clinical history of HDP is a risk factor for CKD in both premenopausal and postmenopausal women. Current BMI is also associated with an increased risk of CKD in premenopausal and postmenopausal women. Therefore, continuous surveillance and preventive measures against CKD should be provided to women with a clinical history of HDP. In addition, maintaining an appropriate body weight is beneficial in reducing the risk of CKD.

Neutrophil-to-lymphocyte ratio associated with renal function in type 2 diabetic patients.

Type 2 diabetes mellitus (T2DM) is a leading risk factor for the development and progression of chronic kidney disease (CKD). However, an accurate and convenient marker for early detection and appropriate management of CKD in individuals with T2DM is limited. Recent studies have demonstrated a strong correlation between the neutrophil-to-lymphocyte ratio (NLR) and CKD. Nonetheless, the predictive value of NLR for renal damage in type 2 diabetic patients remains understudied. To investigate the relationship between NLR and renal function in T2DM patients. This study included 1040 adults aged 65 or older with T2DM from Shanghai's Community Health Service Center. The total number of neutrophils and lymphocytes was detected, and NLR levels were calculated. CKD was defined as an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m². Participants were divided into four groups based on NLR levels. The clinical data and biochemical characteristics were compared among groups. A multivariate logistic regression model was used to analyze the association between NLR levels and CKD. Significant differences were found in terms of sex, serum creatinine, blood urea nitrogen, total cholesterol, and low-density lipoprotein cholesterol among patients with T2DM in different NLR groups (P < 0.0007). T2DM patients in the highest NLR quartile had a higher prevalence of CKD (P for trend = 0.0011). Multivariate logistic regression analysis indicated that a high NLR was an independent risk factor for CKD in T2DM patients even after adjustment for important clinical and pathological parameters (P = 0.0001, odds ratio = 1.41, 95% confidence intervals: 1.18-1.68). An elevated NLR in patients with T2DM is associated with higher prevalence of CKD, suggesting that it could be a marker for the detection and evaluation of diabetic kidney disease.

Possible sarcopenia and risk of chronic kidney disease: a four-year follow-up study and Mendelian randomization analysis

ABSTRACT Introduction Chronic kidney disease (CKD) is a common risk factor for sarcopenia. However, whether sarcopenia increases the risk of CKD remains unclear. To investigate the longitudinal and causal associations between possible sarcopenia and CKD, this study was performed. Methods Possible sarcopenia was defined according to the Asian Working Group for Sarcopenia in 2019. Participants aged ≥ 40 years were recruited from the baseline survey of the China Health and Retirement Longitudinal Study and followed up for four years. Binary logistic regression was used to evaluate the cross-sectional and longitudinal associations between possible sarcopenia, low muscle strength, low physical performance and CKD. Propensity score matching was used to balance the intergroup differences. Subgroup and interactive analyses were adopted to identify potential interactive effects. Mendelian Randomization analysis was used to assess the causal association between appendicular lean mass (ALM) and CKD. Results After data cleansing, a total of 7296 participants were included in the baseline survey. In the cross-sectional analyses, the odds ratios (ORs) of prevalent CKD were 1.50 (95% CI = 1.23–1.84, p < 0.001) for possible sarcopenia, 1.37 (95% CI = 1.10–1.70, p < 0.01) for low muscle strength and 1.42 (95% CI = 1.16–1.74, p < 0.001) for low physical performance in the full models. No significant interaction effects of covariates were detected (all P for interaction > 0.05). After four years of follow-up, an increased risk of incident CKD was also observed in participants with possible sarcopenia (OR = 1.66, 95% CI = 1.13–2.44, p = 0.010) and low physical performance (OR = 1.69, 95% CI = 1.16–2.45, p = 0.006), but not in participants with low muscle strength (OR = 1.19, 95% CI = 0.75–1.88, p = 0.469). In the Mendelian Randomization analysis, the inverse variance weighted estimator showed that a 1-standard deviation increase of genetically predicted ALM was associated with a lower risk of CKD (OR = 0.92, 95% CI = 0.85–0.99, p = 0.035). All the sensitivity analyses supported the main findings. Conclusions Possible sarcopenia is an independent risk factor for CKD and may serve as a predictor of CKD for early identification and intervention.

Research Progress of Drug Delivery Systems Targeting the Kidneys.

Chronic kidney disease (CKD) affects more than 10% of the global population, and its incidence is increasing, partially due to an increase in the prevalence of disease risk factors. Acute kidney injury (AKI) is an independent risk factor for CKD and end-stage renal disease (ESRD). The pathogenic mechanisms of CKD provide several potential targets for its treatment. However, due to off-target effects, conventional drugs for CKD typically require high doses to achieve adequate therapeutic effects, leading to long-term organ toxicity. Therefore, ideal treatments that completely cure the different types of kidney disease are rarely available. Several approaches for the drug targeting of the kidneys have been explored in drug delivery system research. Nanotechnology-based drug delivery systems have multiple merits, including good biocompatibility, suitable degradability, the ability to target lesion sites, and fewer non-specific systemic effects. In this review, the development, potential, and limitations of low-molecular-weight protein-lysozymes, polymer nanomaterials, and lipid-based nanocarriers as drug delivery platforms for treating AKI and CKD are summarized.

Functional Characterization of an Ammonia Transporter RhBG Mutation Identified in Diabetic Kidney Disease Patients

Metabolic acidosis is a major complication of CKD (chronic kidney disease) and DKD (diabetic kidney disease). The kidney responds to metabolic acidosis by eliminating acid, primarily by producing and excreting NH4+ in the urine. Two Rh glycoproteins, RhBG and RhCG, expressed in the collecting duct are directly involved in NH3/NH4+transport. We previously determined that RhBG transports both NH4+ and NH3 across the basolateral membrane of intercalated cells. Impaired NH3/NH4+ production and/or transport may be a factor in increasing acid load and worsening kidney disease. In type 2 diabetes, net endogenous acid production is significantly elevated, and the proportion of acid excreted as NH4+ is decreased even after accounting for diet and renal function. This is significant given that the association between acidosis and faster decline in GFR is now well established. In DKD, impaired NH4+ excretion as a potential risk factor for progression of kidney disease remains poorly understood. Specifically, the genetic risk factors contributing to DKD are unclear. Hypothesis: Defined RhBG variant(s) linked to DKD cause impaired NH3/NH4+ transport that may contribute to DKD development and progression. Methods: We conducted whole-exome sequencing (WES) analysis using data from A therosclerosis R isk i n C ommunities (ARIC) study and the C hronic R enal I nsuffciency C ohort (CRIC) study. We selected DKD patients with the most rapid GFR decline and compared them with: 1) subjects without kidney disease (healthy control); 2) diabetic patients without CKD (DM control); 3) CKD patients without diabetes (CKD control). This approach will identify single nucleotide variants (SNVs) of RhBG associated with DKD. This will also determine if the detected variants contribute to the development of kidney disease per se and whether they contribute to the development of diabetes and/or fast GFR decline. To study function, we expressed RhBG variants (and wild-type RhBG) in Xenopus oocytes by microinjecting oocytes with the respective mRNA. The effect of defined SNV of RhBG on NH3/NH4+ transport was assessed from measurements of changes in intracellular pH (pHi), membrane potential (Vm), whole cell currents (I) or surface pH (pHs) induced by exposing the oocytes to bath solutions containing NH4Cl or methyl ammonium chloride (MA/MA+). Results: We identified an SNV, rs3748569 (minor allele frequency MAF &gt; 0.05), that was significantly associated with DKD. Significance was determined compared to DM control (OR=1.38, p=0.0026) and healthy control (OR=1.26, p=0.01). This variant has also been predicted to be deleterious by 4 bioinformatic tools. Our electrophysiological measurements showed that the resultant amino acid switch, G315R, completely inhibited transport of NH3 and NH4+ (p&lt;0.001) and the transport of MA and MA+ (p&lt;0.0001), compared with RhBG-WT. Conclusions: WES results suggest that this naturally occurring RhBG mutation, G315R, contributes to DKD occurrence. This effect is through the development of kidney disease and less likely due to development of diabetes. It is therefore likely a general CKD risk factor. Inhibition of NH3/NH4+ transport by this mutation is a contributing factor to its deleterious effect. This work provides experimental validation of computational predictions concerning CKD and diabetes. NIH-U54 GM104940, Paul Teschan Research, NIH-R01, Carol Lavin Bernick, Tulane institutional. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The CKD-DETECT V2.0 study: A randomised controlled trial evaluating the effectiveness of an infographic poster compared with an e-learning program on general practice nurses’ knowledge and learning efficiency about chronic kidney disease risk factors and best practice screening procedures

Aims and objectivesTo evaluate: (a) the effectiveness of an infographic poster compared with an e-learning program on general practice nurses’ knowledge about chronic kidney disease risk factors and best practice screening procedures and (b) the effectiveness of an infographic poster compared with an e-learning program on general practice nurses’ learning time and learning efficiency. BackgroundThe screening and early detection of chronic kidney disease is essential in reducing its burden on the health system and those affected by it. General practice nurses are well-positioned to assist in its early detection. DesignParallel-group, single-blinded, pre-post interventional randomised control design. MethodThis study was reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT). Participants were registered or enrolled nurses working in general practice settings across Australia. The intervention group (n = 173) received an infographic poster about chronic kidney disease risk factors and best practice screening procedures, whereas the control group (n = 170) received an interactive e-learning program. Data were collected using an 8-item pre-post knowledge evaluation instrument. Time spent learning were collected through a self-reported log and a login/logout method. ResultsThe overall intervention effect demonstrated no statistical significance in knowledge scores from the baseline scores between the intervention and control group. The intervention group demonstrated higher learning efficiency in comparison to the control group. ConclusionThe study demonstrated an infographic poster is as effective as an e-learning program on improving knowledge scores. However, in comparison to an e-learning program, an infographic poster is a more efficient way of learning. Relevance to clinical practiceInfographic posters can be an efficient educational modality to enhance healthcare professionals’ knowledge and could be used as public health campaigns in clinical settings to educate the community.