Chronic Kidney Disease In Adults Research Articles

Factors Associated with the Development of Chronic Kidney Disease in Patients with Arterial Hypertension.

Chronic kidney disease affects a large part of the population with hypertension, diabetes mellitus as well as those over 50 years of age. Research reported that male sex and other comorbidities such as obesity and anemia are more frequent in Chronic kidney disease, as well as uncontrolled diabetes mellitus or hypertension. To determine the risk factors associated with the development of chronic kidney disease in adults with arterial hypertension. Retrospective cohort study of 455 patients with hypertension treated in a primary health care hospital. Medical records and laboratory information were reviewed for the diagnosis of chronic kidney disease and its staging. Patients aged 40 years and older, of both sexes and evaluated between the years 2015 -2017 were included. Logistic regression analysis allowed the identification of risk factors associated with the development of chronic kidney disease. 63.7% were female and 36.3% male. The average age for 2015 was 69.79 ± 9.03, more than half of participants had diabetes mellitus and controlled hypertension and the predominant nephroprotection was with Losartan (53%) that year. Male sex (OR 1.68, CI 1.03-2,76), age: 60 years or older (OR 6.38, CI 2.65-15,37) and anemia (OR 1.71, CI 1.03-2,85), were risk factors for the development of chronic kidney disease (p < 0.05), whereas nephroprotection (OR 0.39, CI 0.18-0,88) and controlled diabetes mellitus (OR: 0.18, CI 0.07-0,47) were shown to be protective factors (p < 0.05). The prevalence of chronic kidney disease between 2015 and 2017 was 19% and 45%, respectively, with predominance of category G2. The comparison group is the same cohort analyzed in each year under study. Male sex, age over 60 years, and anemia are risk factors for chronic kidney disease. Nephroprotection, controlled diabetes mellitus, and patient follow-up are factors that prevent its development.

Association between Whole Grain Intake and Chronic Kidney Disease

BackgroundThe relationship between whole grain intake and chronic kidney disease (CKD) remains uncertain. ObjectiveThis study aimed to evaluate the association between whole grain intake and risk of CKD in Chinese adults. MethodsThe present cross-sectional study used data from the China Health and Nutrition Survey conducted in 2009. Whole grain intake was measured using 3 consecutive 24-h dietary recalls and a household food inventory. A multivariable logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of CKD. In addition, a restricted cubic spline was used to investigate the dose‒response relationship between whole grain and risk of CKD. ResultsA total of 6747 participants were included, 728 of whom had CKD. Compared with those in the lowest whole grain intake group, those in the higher grain intake group had an inverse association with risk of CKD (Q2: adjusted OR 0.70, 95% CI: 0.54, 0.89; Q3: adjusted OR 0.54, 95% CI: 0.42, 0.69; and Q4: adjusted OR 0.29, 95% CI: 0.21, 0.41). The association between whole grain intake and CKD seems to be stronger for individuals who were male (P for interaction = 0.008) or smokers (P for interaction = 0.013). In addition, the restricted cubic spline suggested an obvious L-shaped correlation. ConclusionsIncreased whole grain intake was associated with a decreased risk of CKD in Chinese adults.

Epidemiology and clinical characteristics of biopsy-confirmed adult-onset IgA vasculitis in southern Sweden

ObjectiveImmunoglobulin A vasculitis (IgAV) is the most prevalent primary childhood vasculitis in Sweden, but is considerably rarer in adults. This study aims to describe the epidemiology, clinical characteristics and renal...

Association between dietary diversity and chronic kidney disease in community-dwelling older adults.

The present study examined whether dietary diversity is associated with chronic kidney disease (CKD) in community-dwelling older Japanese adults. Participants comprised 8,195 older adults (mean age was 74.0 ± 5.6years; 42.7% were men) in this cross-sectional study. In this study, CKD was defined as estimated Glomerular Filtration Rate (eGFR) < 45mL/min/1.73m2. Diet variety was assessed using the Food Frequency Score (FFS) (maximum, 30 points). The FFS assessed the one-week consumption frequency of ten foods (meat, fish/shellfish, eggs, milk, soybean products, green & yellow vegetables, potatoes, fruits, seafood, and fats & oil). Participants with an FFS of 16 or fewer points were defined as having low dietary diversity. The prevalence of CKD was 376 (4.6%), and the low dietary diversity group had higher prevalence (5.6%) compared with the high and low dietary diversity group (4.3%). Multiple logistic regression analysis revealed low dietary diversity was associated with CKD in older adults (OR 1.30, 95%CI 1.01-1.68). Stratified analysis showed that low dietary diversity was independently associated with CKD (OR 1.43, 95% CI 1.07-1.91) in older adults with hypertension, but not in adults without hypertension (OR 0.94, 95% CI 0.54-1.64). This cross-sectional study revealed that low dietary diversity was associated with CKD among older adults. Furthermore, low dietary diversity was associated with CKD among older adults with hypertension.

Association between blood metals mixture and chronic kidney disease in adults: NHANES 2013-2016

BackgroundThe association between single metal exposure and chronic kidney disease (CKD) has been established. However, there is limited research on the effects of multi-metal mixtures and their potential age-specific associations with kidney injury. This study aimed to examine the relationship between metal mixtures and kidney function in adults, while also exploring the modifying effects of age. MethodsWe included a subset (n = 4250) of a nationally representative adult population in the National Health and Nutrition Examination Survey (NHANES) 2013–2016. Kidney function was assessed using the glomerular filtration rate (eGFR) and creatinine albumin ratio (ACR). The individual and combined effects of lead (Pb), cadmium (Cd), mercury, and manganese on kidney injury and the risk of CKD were evaluated. ResultsPb and Cd were found to be positively associated with decreased kidney function. For a one Ln-unit increase in lead and cadmium, the adjusted ORs of CKD were 1.60 (95% CI: 1.35, 1.90) and 1.41 (95% CI:1.12, 1.77), respectively. We also observed an interaction between lead and cadmium for ACR. We also observed the joint effect between Pb and Cd on eGFR, ACR and CKD. Stratified analysis found a higher risk of decreased kidney function among older individuals. The quantile-g calculation model further showed that metal mixture was associated with decreased kidney function and the risk of CKD (OR = 1.53, 95% CI: 1.22, 1.90). And lead and cadmium were the main contributors. And Pb and Cd were the major components that increased the risk of CKD. ConclusionCo-exposure to metal mixture were associated with reduced kidney function in adults, especially in older. Our findings support co-exposure to lead and cadmium as risk factors of CKD in adults.

Serum vitamin C levels and their correlation with chronic kidney disease in adults: a nationwide study

Introduction Inflammation and oxidative stress play significant roles in the development of chronic kidney disease (CKD). Given the recognized antioxidant properties of vitamin C, our study aimed to explore the correlation between CKD and serum vitamin C levels. Methods Data were gathered from the 2017–2018 National Health and Nutrition Examination Survey. Participants below 18 years of age, pregnant individuals, those lacking essential data for CKD diagnosis, or individuals with incomplete serum vitamin C data were excluded. Subgroup and weighted multivariable logistic regression analyses were performed to assess the potential correlation between serum vitamin C and CKD. Results Our study comprised 4969 participants, revealing an overall CKD prevalence of 15.0%. The results indicated that individuals with reduced serum vitamin C levels were more likely to be male, possess lower educational attainment, have a diminished poverty-income ratio, engage in heavy drinking, and be current smokers. Additionally, they exhibited a higher prevalence of obesity and diabetes. Significantly, participants in the third quartile group experienced a 37.0%, 47.0%, and 46.6% decrease in the risk of developing albuminuria, low estimated glomerular filtration rate (eGFR), and CKD, respectively. Subgroup analysis demonstrated that individuals between 65 and 80 years of age showed a statistically reduced risk of developing CKD and low eGFR when their serum vitamin C levels fell in the third and fourth quartile groups. Conclusions Our findings reveal a correlation between elevated serum vitamin C levels and a decreased risk of developing albuminuria, low eGFR, and CKD. Appropriately increasing serum vitamin C levels may hold promise in protecting renal function, particularly among older individuals.

Association between dietary intake of selenium and chronic kidney disease in US adults: a cross-sectional study of NHANES 2015-2018.

Chronic kidney disease (CKD) is currently a widespread chronic illness, and its development is influenced by nutrients. Selenium plays a crucial role in the intervention and therapy of various chronic illness. In this study, we aimed to investigate the connection between dietary selenium intake and CKD in adults in the United States. We included 6,390 individuals from the datasets of the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2018. We used multiple logistic regression, restricted cubic spline regression, and forest plots to investigate the connection between dietary selenium intake and CKD. After fully adjusting the data of 6,390 individuals from NHANES between 2015 and 2018, 1,523 (23.83%) of the individuals were identified as having chronic kidney disease (CKD). The rates of CKD in participants with average selenium intakes of ≤0.072, 0.072-0.103, 0.103-0.144, and > 0.144 mg/day were 27.53, 25.11, 22.42, and 19.96%, respectively. After adjusting for potential confounding factors, the fully adjusted odds ratio (OR) values for CKD according to dietary selenium intake were 1 (reference), 0.94 (95% confidence interval (CI): 0.79-1.12, p = 0.466), 0.82 (95% CI:0.68-0.98, p = 0.033), and 0.77 (95% CI:0.63-0.95, p = 0.016) for the four selenium intake levels, respectively, with P trend = 0.007. The dietary selenium intake was negatively associated with the incidence of CKD, after adjusting for other confounding factors. The risk of CKD decreased by 7.7% for every additional 0.1 mg of dietary selenium intake. A higher dietary selenium intake correlates significantly and negatively with the incidence of CKD.

Association between serum methylmalonic acid and chronic kidney disease in adults: a cross-sectional study from NHANES 2013-2014.

Chronic kidney disease(CKD) is a global medical problem. Serum methylmalonic acid(MMA) is a serum marker associated with many diseases. This study aimed to investigate the association between MMA and CKD. Data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were downloaded and analyzed. The association between MMA and CKD was confirmed by using multiple logistic regression modeling. The smooth curve fitting method was used to investigate the nonlinear relationship between them. Subgroup analyses and interaction tests were used to verify the stability of the association between different subgroups. Threshold effect analysis was used to determine the optimal control point for MMA. There was a unique W-shaped nonlinear relationship between MMA and the risk of CKD, with a positive correlation between them (OR=1.66,95% CI:1.27, 2.17; P=0.0002). As the stage of CKD progressed, MMA levels increased. Age, hypertension, and serum vitamin B12 had significant influences on the association between MMA and the risk of CKD. Our findings revealed that serum MMA accumulation was positively associated with the risk of CKD. Serum MMA level may be a novel index to predict the development and course of CKD. This study may help in the early identification of people at risk for chronic kidney disease and provide new ideas and approaches for prevention and treatment.

Higher Arterial Stiffness Predicts Chronic Kidney Disease in Adults: The ELSA-Brasil Cohort Study.

Central Illustration : Higher Arterial Stiffness Predicts Chronic Kidney Disease in Adults: The ELSA-Brasil Cohort Study. Arterial stiffening can directly affect the kidneys, which are passively perfused by a high flow. However, whether the relation between arterial stiffness and renal function depends on diabetes and hypertension conditions, is a matter of debate. To investigate the relationship between arterial stiffening by carotid-to-femoral pulse wave velocity (cfPWV) and chronic kidney disease (CKD) incidence in individuals and verify whether this association is present in individuals without hypertension and diabetes. A longitudinal study of 11,647 participants of the ELSA-Brasil followed up for four years (2008/10-2012/14). Baseline cfPWV was grouped per quartile, according to sex-specific cut-offs. Presence of CKD was ascertained by glomerular filtration rate (eGFR-CKD-EPI) < 60 ml/min/1.73 m2 and/or albumin-to-creatinine ratio ≥ 30 mg/g. Logistic regression models were run for the whole cohort and a subsample free from hypertension and diabetes at baseline, after adjustment for age, sex, race, schooling, smoking, cholesterol/HDL ratio, body mass index, diabetes, use of antihypertensive, systolic blood pressure, heart rate, and cardiovascular disease. Statistical significance was set at 5%. The chance of CKD was 42% (CI 95%: 1.05;1.92) greater among individuals in the upper quartile of cfPWV. Among normotensive, non-diabetic participants, individuals in the 2nd, 3rd, and 4th quartiles of cfPWV presented greater chances of developing CKD, as compared to those in the lower quartile, and the magnitude of this association was the greatest for those in the upper quartile (OR: 1.81 CI 95%: 1.14;2.86). Higher cfPWV increased the chances of CKD and suggests that this effect is even greater in individuals without diabetes and hypertension.

Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults.

Studies have found a U-shaped relationship between sleep duration and chronic kidney disease (CKD) risk, but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD. We included 104 538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study, with self-reported time of daily-life behavior. Using isotemporal substitution models, we found that substituting 1 h of sleeping with sitting, walking, or moderate-to-vigorous physical activity was associated with a lower CKD prevalence. Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population. In stratified analysis, a lower CKD prevalence related to substitution toward physical activity was found in long sleepers. More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes, and they benefited from other behavior substitutions toward a more active way. The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys, in which the pernicious link with oversleep could be reversed by time reallocation to physical activity. The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.

Development of a Genetic Risk Score for Albuminuria in Pediatric Patients with Sickle Cell Anemia

Introduction Sickle cell anemia (SCA) causes progressive, age-dependent, kidney damage. Albuminuria is an early clinical biomarker for chronic kidney disease (CKD) and is associated with progressive glomerular injury. Identifying patients at risk for albuminuria is critical for early institution of renoprotective interventions to prevent progressive kidney injury. Developing a genetic risk score (GRS) to predict albuminuria is one approach to identifying high risk patients. Our prior data demonstrates that Apolipoprotein-L1 ( APOL1 G1/G2) is associated with early development of albuminuria in children with SCA (PMID:30890594). However, this gene variant does not account for all kidney disease progression. Multiple other gene variants that modify SCA-severity have been associated with CKD in adults with SCA. We hypothesized that developing a genetic risk score (GRS) will allow for identification of pediatric patients at increased risk for development and progression of kidney disease. We aimed to develop a novel pediatric GRS that can identify pediatric SCA patients at high risk for albuminuria. Methods Gene allele variants in APOL1 G1/G2, HMOX1, BCL11A and α-thalassemia (α -3.7 allele), were identified in 324 African American patients with SCA (HbSS or HbS 0-thalassemia genotypes) enrolled in the Sickle Cell Clinical Research and Intervention Program (NCT02098863), a lifespan, longitudinal cohort study. The first urine albumin to creatinine ratio (ACR) collected after birth was analyzed as a continuous variable and dichotomized by a threshold of ACR ≥30mg/g creatinine as albuminuria. We defined a GRS 3 based on established risk alleles in three genes: APOL1 (G1/G2 ), BCL11A (rs1427407), and α -3.7(PMID:27658436). High risk was defined as patients with APOL1 (G1/G1, G2/G2 or G1/G2), without α -3.7 and with wildtype BCL11A (G/G); low-risk was defined as patients negative for APOL1 G1/G2 and with α -3.7 (either α -3.7/αα or α -3.7/α -3.7) and the BCL11A T allele (either G/T or T/T). All other combinations were defined as intermediate risk. By adding HMOX1 (rs743811), C allele (TT/TC vs CC), we further refined GRS 3 as GRS 4 using the summation of the number of high-risk alleles of kidney outcomes for four variants and created four risk categories. The generalized linear regression model was used to associate additive dose-effect models for GRS 3 and GRS 4 with continuous ACR and albuminuria, adjusted for age, sex, hydroxyurea treatment, 5 principal components, and, if significant, the age-genotype interaction. ACR was log-transformed to approximate normality. As we included variants with known associations, we used a one-sided p-value for testing associations of individual variants, GRS 3, and two-sided p-values for GRS 4. P-values &amp;lt;0.05 were considered significant. Results In 324 individuals with SCA, those with albuminuria (34, 10.5%) appeared to be older than those without albuminuria (290, 89.5%) (mean 9.8 years [standard deviation ±4.4 years] vs. 8.6 [± 4.0], p=0.053). There were no significant differences between these groups by sex (female 58% vs. 49%, p=0.37), proportion on hydroxyurea (62% vs. 59%, p=0.85) or fetal hemoglobin (15.6 [± 10.61] vs. 14.8% [± 10.0], p= 0.81). All four individual genetic variants were associated with the first ACR (all p ≤ 0.028) and albuminuria (all p≤ 0.03). GRS 3 was significantly associated with the first ACR (estimate=1.4, standard error [SE]=0.5, p=0.0035) and albuminuria (odds ratio [OR]=3.0, 95% CI: 1.2-7.5, p= 0.008). After adding HMOX1 to GRS 3, GRS 4 was more significantly associated with the first ACR (estimate=0.9, SE=0.3, p=0.0005) and albuminuria (OR=2.0, 95% CI: 1.2-3.4, p=0.003). Summary We developed a GRS 3 based on three genetic variants associated with albuminuria in pediatric patients with SCA and stratified patients into different risk categories. Addition of a fourth genetic variant to create GRS 4improved the model. Our findings will need to be validated in larger longitudinal studies to further examine the association between GRS 4 and development of albuminuria and chronic kidney disease. Genetic prediction strategies using GRS has the potential to identify high risk SCA patients for whom renoprotective measures could prevent the development of albuminuria.

Persistent Albuminuria and Chronic Kidney Disease in Adults with Sickle Cell Disease: Results from a Multicenter Natural History Study

Background: Patients with sickle cell disease (SCD) are at high risk for developing kidney disease. Albuminuria, an early marker of kidney injury, may be initially transient in patients with SCD. Existing guidelines propose confirming albuminuria at multiple timepoints before intervention. A recent study suggests a urinary albumin-creatinine ratio (UACR) ≥ 100 mg/g correlates highly with persistent albuminuria and subsequent decline in estimated glomerular filtration rate (eGFR). We examined a cohort of patients with SCD to assess those characteristics associated with persistent albuminuria and chronic kidney disease (CKD). Methods During routine clinical visits, we enrolled patients with HbSS or HbSß 0 thalassemia between 18 and 65 years at 4 centers into a prospective study to assess the natural history of kidney disease in SCD. We excluded patients if they had bone marrow transplantation, cancer, connective tissue disease, diabetic nephropathy, other glomerular diseases, hepatitis (B or C), HIV, or were on dialysis. Blood and urine were collected for routine clinical laboratory assessments. Serum cystatin C was measured by commercially available ELISA, and eGFR was calculated using the CKD-EPI-2012 cystatin C equation. We defined CKD as an eGFR &amp;lt; 60 mL/min/1.73m 2 or presence of albuminuria. Glomerular hyperfiltration was defined as an eGFR&amp;gt;130 in females and &amp;gt;140mL/min/1.73m 2 in males, respectively. Persistent albuminuria was considered present if 2 or 3 UACR values were ≥30 mg/g or if initial baseline value was ≥100 mg/g (PMID: 32289161). We utilized generalized linear models adjusting for age and sex to identify characteristics associated with persistent albuminuria and CKD. For multivariable selection, we fit binomial or multinomial LASSO regression models adjusted for age, sex, hemoglobin, %Hemoglobin F, hemoglobinuria, and hydroxyurea to identify those variables associated with outcomes of interest. Results Of 284 enrolled patients, 268 had complete data for UACR, cystatin C and serum creatinine at baseline; 104 (38.8%) of these had persistent albuminuria (Table 1). CKD was present in 40.7% of patients and 26.5% exhibited hyperfiltration. In analyses adjusted for age and sex, several factors were associated with the likelihood of persistent albuminuria. Higher hemoglobin, higher %Hemoglobin F, higher serum bicarbonate and use of NSAIDs were associated with decreased likelihood of persistent albuminuria. Higher systolic and diastolic blood pressure, elevated serum alkaline phosphatase, total bilirubin, and white blood cell count (WBC) were associated with an increased likelihood of persistent albuminuria as were presence of hemoglobinuria and use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). In multivariable selection, higher systolic and diastolic blood pressure, ACEi/ARB use, leg ulcers, higher WBC, higher aspartate transaminase (AST) remained associated with higher likelihood of persistent albuminuria. Presence of avascular necrosis, NSAID use, and higher serum bicarbonate were associated with lower likelihood of persistent albuminuria. When evaluating baseline UACR, individuals with UACR≥100 mg/g had similar probability of subsequent albuminuria as compared to those with severe albuminuria (UACR≥300 mg/g) [Table 2]. Conclusion Persistent albuminuria in this cohort was associated with multiple clinical features. Lower use of NSAIDs in this cohort likely represents counseling of patients to avoid these due to their kidney disease. The relationship with serum bicarbonate suggests a propensity for metabolic acidosis in these patients which could exacerbate the underlying SCD. These data confirm the predictive value of a single UACR value ≥100 mg/g for persistent albuminuria, suggesting this may be a sufficient trigger to warrant intervention. CKD, hyperfiltration and albuminuria were extraordinarily common, consistent with prior studies and validate use of this cohort for additional longitudinal assessment of kidney disease in SCD.

MASLD, hepatic steatosis and fibrosis are associated with the prevalence of chronic kidney disease and retinopathy in adults with type 1 diabetes mellitus

AimWe examined whether metabolic dysfunction-associated steatotic liver disease (MASLD) with or without significant fibrosis (assessed by validated non-invasive biomarkers) was associated with an increased risk of prevalent chronic kidney disease (CKD) or diabetic retinopathy in people with type 1 diabetes mellitus (T1DM). MethodsWe performed a retrospective multicenter cross-sectional study involving 1,409 adult outpatients with T1DM, in whom hepatic steatosis index (HSI) and fibrosis (FIB)-4 index were calculated for non-invasively detecting hepatic steatosis (defined by HSI > 36), with or without coexisting significant fibrosis (FIB-4 index ≥ 1.3 or < 1.3). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin/creatinine ratio ≥ 3.0 mg/mmol. The presence of diabetic retinopathy was also recorded in all participants. ResultsPatients with MASLD and significant fibrosis (n = 93) had a remarkably higher prevalence of CKD and diabetic retinopathy than their counterparts with MASLD without fibrosis (n = 578) and those without steatosis (n = 738). After adjustment for sex, diabetes duration, hemoglobin A1c, hypertension, and use of antihypertensive or lipid-lowering medications, patients with SLD and significant fibrosis had a higher risk of prevalent CKD (adjusted-odds ratio 1.76, 95 % confidence interval 1.05–2.96) than those without steatosis. Patients with MASLD without fibrosis had a higher risk of prevalent retinopathy (adjusted-odds ratio 1.49, 95 % CI 1.13–1.46) than those without steatosis. ConclusionThis is the largest cross-sectional study showing that MASLD with and without coexisting significant fibrosis was associated, independently of potential confounders, with an increased risk of prevalent CKD and retinopathy in adults with T1DM.

Burden of Chronic Kidney Disease in Californians with Sickle Cell Disease

Introduction: Chronic Kidney Disease (CKD) is a known complication of sickle cell disease (SCD). Data from contemporary adult cohorts estimating prevalence and burden of CKD in the aging sickle cell population are limited. We used administrative data from the Sickle Cell Data Collection (SCDC) program to estimate the burden of CKD in adults with SCD in California over a 10-year period. We also report mortality data and examine access to specialized care (hematology and nephrology) for SCD patients with and without CKD. Methods: This is a retrospective cohort study of Medicaid-enrolled individuals with SCD in California. Data sources included Medicaid claims, Emergency Department, hospitalization data from 2011 to 2020, and vital records data obtained from the California SCDC program. Individuals aged 18 years or older in 2011, meeting either the confirmed SCD case definition, defined as the presence of laboratory confirmation of SCD, or the SCDC probable case definition of 3 or more SCD-coded encounters during any 5-year period were eligible to be included. We ascertained individuals' CKD status (none versus any, the latter encompassing stages 1 through 5, unspecified stage, and End Stage Renal Disease (ESRD)), based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10-CM diagnosis codes. Hematologist and nephrologist encounters were identified using the National Provider Identifier (NPI) of the rendering provider. Linked death records were used to identify deaths that occurred during the study period. Results: We identified 2,992 individuals with SCD who met inclusion criteria, with 2,311 (77.2%) in the non-CKD group and 681 (22.8%) in the CKD group. The mean age of the cohort at the mid-point of the study was 40.1 years. The CKD population was older in age, and the majority (67.9%) were 30-60-years of age, whereas the non-CKD cohort had majority (61.6%) in the 18-40-year age category. Males had a higher prevalence of CKD when compared to females (26.7% vs. 20.4%). The period prevalence of CKD increased from 8% in the 18-29 year group, to 17% in the 30-39 year group, 24% in the 40-49 year group, 44.6% in the 50- 59 year group and 51.1% for the &amp;gt; 60 years age group. The mean age at first recorded CKD code was 48 years, males were significantly (p&amp;lt;0.05) younger at their first recorded CKD code than females, at 46 and 49 years of age respectively. By first recorded CKD code, one third (33.4%) of individuals had stages 1-2, 39% had stages 3-5, and 4% had ESRD. In contrast, by the latest recorded CKD stage in the 10-year period, more than one-third (35%) had CKD stages 3-5, and 40% reached ESRD. By latest CKD stage, males had more ESRD (40.2%) than stage 3-5 (34.7%), while females had similar burden of ESRD and CKD 3-5 at 37.6% and 38.7% respectively. A total of 478 deaths (15.9%) occurred during the study period, with 50.8% of deaths occurring in the CKD cohort. The median age at death was 53 years for the CKD cohort and 43 years for the non- CKD cohorts, possibly indicating that CKD occurred in patients who did not die of other causes at a younger age. When examining access to care, the median number of visits per year with a hematologist was 0.11 and 0 for the CKD vs. entire cohort respectively. The median number of visits per year with a nephrologist for those with CKD was 0. The proportion of individuals with CKD who had zero visits per year with a hematologist or a nephrologist over the study period was 48% and 61% respectively. Individuals with CKD who died during the study period had a significantly lower number of mean annual visits with a hematologist than those who were alive (1.37 vs 1.23, p&amp;lt;0.001) at the end of the study period. Individuals with CKD who died during the study period had a higher number of visits with a nephrologist than those who were alive (1.56 vs. 2.23, p&amp;lt;0.05) at the end of the study period. Conclusion: CKD poses a significant burden on adults with SCD. In our cohort, males had a higher prevalence of CKD, and the prevalence of CKD increased with age. 40% of individuals with CKD had a latest recorded stage of ESRD. Half of the deaths that occurred during the study timeframe occurred in the CKD cohort. Californians with CKD and SCD had severe restrictions in access to both hematology and nephrology care. Further prospective studies are needed to understand the natural history of CKD in SCD and identify risk factors for progression.

Association of sarcopenia with rapid kidney function decline and chronic kidney disease in adults with normal kidney function.

The association between sarcopenia and kidney function remains poorly investigated. We aimed to evaluate the associations between sarcopenia status and kidney function (rapid kidney function decline and chronic kidney disease (CKD)) in middle-aged and older Chinese population. A total of 9375 participants from the China Health and Retirement Longitudinal Study 2011 were included in the cross-sectional analyses. A total of 5864 participants with eGFRcr-cys ≥ 60 ml/min per 1·73 m2 at baseline were included in the longitudinal analyses and were followed up in 2015. Sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 criteria. In the cross-sectional analyses, possible sarcopenia and sarcopenia were significantly associated with an increased risk of CKD. During the 4 years of follow-up, 359 (6·12 %) participants experienced rapid decline in kidney function and 126 (2·15 %) participants developed CKD. After multivariable adjustment of baseline eGFRcr-cys level and other risk factors, possible sarcopenia (OR, 1·33; 95 % CI 1·01, 2·12) and sarcopenia (OR, 1·49; 95 % CI 1·05, 2·12) were associated with an increased risk of primary outcome (composite of rapid decline in kidney function (annualised decline in eGFRcr-cys ≥ 5 ml/min per 1·73 m2) and progression to CKD (eGFRcr-cys < 60 ml/min per 1·73 m2). Individuals with low muscle mass or low muscle strength alone also had an increased risk of rapid decline in kidney function and progression to CKD.

THU340 Efficacy And Safety Of Low-dose Spironolactone On Chronic Kidney Disease In Adults With Type 2 Diabetes: A Multicenter, Randomized Clinical Trial

Abstract Disclosure: A. Oiwa: None. D. Hiwatashi: None. T. Takeda: None. T. Miyamoto: None. I. Kawata: None. M. Koinuma: None. S. Kubota: None. S. Takayama: None. M. Yamazaki: None. M. Komatsu: None. Objective: To evaluate the albuminuria-lowering effect and safety regarding hyperkalemia of adding low-dose spironolactone (12.5 mg/day) to the renin-angiotensin system (RAS) blockers in adults with chronic kidney disease and type 2 diabetes. Research Design and Methods: This was a multicenter, open-label, randomized controlled trial. We enrolled 130 Japanese individuals aged ≥20 years with type 2 diabetes and albuminuria (≥30 mg/gCre), estimated glomerular filtration ≥30 mL/min/1.73 m2, and serum potassium level &amp;lt;5.0 mEq/L. They were randomly assigned to the spironolactone-administered and control groups. The main outcomes were changes in urine albumin-to-creatinine ratio (UACR), serum potassium levels and renal function from baseline to the 24-week interventional period. Results: The spironolactone-administered group showed a significant reduction in UACR by a mean of 103.47 ± 340.80 mg/gCre from baseline compared with the control group that showed increased UACR by a mean of 63.93 ± 310.14 mg/gCre (p = 0.0007, Wilcoxon rank-sum test and T-test). As for serum potassium levels, although there was a statistically significant increase (p = 0.0026), none of the participants had a potassium level ≥5.5 mEq/L at 24 weeks. Further, there was a tendency that the higher the initial potassium level, the smaller the increase in serum potassium level (estimate −0.37, analysis of covariance). Conclusions: This study first demonstrated that low-dose spironolactone administration reliably reduced albuminuria and was safe against hyperkalemia. The administration of spironolactone, which is the oldest known and most cost-effective of all the other mineralocorticoid receptor antagonists, should be re-evaluated with consideration of lower doses. Presentation: Thursday, June 15, 2023

Kappa opioid agonists in the treatment of itch: just scratching the surface?

Chronic pruritus is a debilitating condition affecting 23–44 million Americans. Recently, kappa opioid agonists (KOAs) have emerged as a novel class of potent antipruritic agents. In 2021, the Food and Drug Administration approved difelikefalin (Korsuva) for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. Difelikefalin is a potent, peripherally restricted KOA that is intravenously available. Although promising, difelikefalin is currently available as an intravenous composition only, limiting the scope of use. Oral formulations of difelikefalin did not meet the primary endpoint criteria in recent phase 2 clinical trials; however, additional clinical studies are ongoing. The future for KOAs in the treatment of pruritus is encouraging. Orally active pathway-biased KOAs, such as triazole 1.1, may serve as viable alternatives with broader applications. Extended-release compositions, such as the TP-2021 ProNeura subdermal implant, may circumvent the pharmacokinetic issues associated with peptide-based KOAs. Lastly, dual-acting kappa opioid receptor agonist/mu opioid receptor antagonists are orally bioavailable and may be useful in the treatment of various forms of chronic itch. In this review, we summarize the results of KOAs in clinical and preclinical trials and discuss future directions of drug development.

Epidemiology and treatment of renal anaemia in Spain: RIKAS retrospective study

Background and objectiveStudies on the prevalence of anaemia in chronic kidney disease in adults not on dialysis (CKD-ND) and in dialysis programmes (CKD-D) in Spain are not recent or focus on certain subgroups. The aim of this study was to know the epidemiology and current treatment patterns of anaemia associated with CKD in Spain. Materials and methodsMulticentre, non-interventional, retrospective study with CKD-ND stage 3a-5 and CKD-D patients treated in Spain between 2015 and 2017 (RIKAS study). ResultsThe prevalence of anaemia in CKD-ND and CKD-D in 2015 was 33.8% and 91.5%, respectively, with similar results during 2016−2017. The prevalence of systemic inflammation in anaemic patients (18.1% and 51.8% for CKD-ND and CKD-D, respectively) was higher, especially in those treated with erythropoiesis-stimulating agents (ESA), compared to the general population with CKD-ND. After 12 months of follow-up, mean ferritin and transferrin saturation index (TSI) values in anaemic patients with CKD-ND were 187.1 ng/mL and 22.2%, respectively, while in CKD-D were 254.6 ng/mL and 20.2%. In ESA-treated patients, mean values were 190.6 ng/mL and 22.0% in ND-CKD, and 255.0 ng/mL and 20.2% in D-CKD. ConclusionsThe prevalence of anaemia and inflammation increased with the disease severity, being higher in D-CKD. Iron parameters in anaemic patients treated or not with ESA are insufficient according to the guidelines, so there is room for improvement in the treatment of anaemia associated with CKD.

Association of mitochondrial DNA copy number with chronic kidney disease in older adults

BackgroundMitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of chronic kidney disease (CKD). Estimation of mitochondrial DNA copy number (mtDNA-CN) is considered a convenient method for representing mitochondrial function in large samples. However, no study has investigated the association between mtDNA-CN and CKD in older adults with the highest prevalence. The objective is to examine cross-sectional and prospective associations between mtDNA-CN values and CKD risk in older adults to determine whether mtDNA-CN represents a novel potential biomarker for the recognition of CKD risk.Patients and methodsIn a Chinese community-based cohort of over 65-year-olds, we included 14,467 participants (52.6% females). CKD was defined by eGFR < 60 mL/min/1.73 m2 or ICD-10 codes (patients = 3831 (26.5%)). Participants had peripheral blood levels of mtDNA-CN calculated from probe intensities of the Axiom CAS Array.ResultsThe risk of CKD prevalence decreased with mtDNA-CN per 1-SD increment, independent of established risk factors for older CKD (odds ratio [OR] per SD 0.90, 95% confidence interval [CI] 0.86, 0.93, P < 0.001), and has comparable strength of association with these established risk factors. Furthermore, the progression of kidney function was stratified according to the worsening of eGFR categories. The risk of kidney function progression to a more severe stage gradually decreased as the mtDNA-CN increased (P trend < 0.001). Non-CKD participants in the highest quartile of mtDNA-CN had a lower risk of developing CKD compared to the lowest quartile within 2 years of follow-up, reducing the risk of CKD by 36% (95% CI 0.42, 0.97; P = 0.037).ConclusionsBased on the analysis of the largest sample to date investigating the association between mtDNA-CN and CKD in older adults, higher levels of mtDNA-CN were found to be associated with a lower risk of CKD, suggesting that a reduced level of mtDNA-CN is a potential risk factor for CKD.

The NOS/NO System in Renal Programming and Reprogramming.

Nitric oxide (NO) is a gaseous signaling molecule with renoprotective properties. NO can be produced in NO synthase (NOS)-dependent or -independent manners. NO deficiency plays a decisive role in chronic kidney disease (CKD). Kidney development can be affected in response to adverse intrauterine conditions that induce renal programming, thereby raising the risk of developing CKD in adulthood. Conversely, detrimental programming processes could be postponed or halted prior to the onset of CKD by early treatments, namely reprogramming. The current review provides an overview of the NOS/NO research performed in the context of renal programming and reprogramming. NO deficiency has been increasingly found to interact with the different mechanisms behind renal programming, such as oxidative stress, aberrant function of the renin-angiotensin system, disturbed nutrient-sensing mechanisms, dysregulated hydrogen sulfide signaling, and gut microbiota dysbiosis. The supplementation of NOS substrates, the inhibition of asymmetric dimethylarginine (ADMA), the administration of NO donors, and the enhancement of NOS during gestation and lactation have shown beneficial effects against renal programming in preclinical studies. Although human data on maternal NO deficiency and offspring kidney disease are scarce, experimental data indicate that targeting NO could be a promising reprogramming strategy in the setting of renal programming.