Risk Factors For Chronic Kidney Disease Research Articles

Depressive symptoms and sleep duration in relation to chronic kidney disease: Evidence from the China health and retirement longitudinal study

ObjectiveNowadays, the joint effects of depressive symptoms and sleep duration on the risk of chronic kidney disease (CKD) are still unclear. We aimed to prospectively assess the combined effect of depressive symptoms and sleep duration on the incidence of CKD in middle-aged and elderly Chinese population. MethodsA total of 10,953 participants from the China Health and Retirement Longitudinal Study (CHARLS) were included. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies Depression scale (CESD-10). Sleep duration was evaluated by self-reported. CKD events were based on self-reported physicians' diagnosis or personal estimate glomerular filtration rate level (eGFR <60 mL/min/1.73 m2). Cox regression models were established to analyze the correlation between depressive symptoms, sleep duration and the risk of CKD. ResultsOver a mean follow-up time was 6.76 ± 0.98 years, 851 (7.8%) participants had reported CKD events during the follow-up. Elevated depressive symptoms (HR = 1.65, 95% CI = 1.43–1.90) and short sleep duration (HR = 1.48, 95% CI = 1.27–1.72) were independently associated with an increased CKD risk after adjusting for potential confounding factors. Participants with short sleep duration (< 6 h)/elevated depressive symptoms (HR = 2.24, 95% CI = 1.89–2.65) were associated with the highest risk of CKD than those with normal sleep duration/low depressive symptoms. ConclusionsElevated depressive symptoms and short sleep duration were independent risk factors for CKD. There was a combined effect between depressive symptoms and sleep duration in increasing the risk of CKD.

Why is chronic kidney disease progressive? Evolutionary adaptations and maladaptations.

Despite significant advances in renal physiology, the global prevalence of chronic kidney disease (CKD) continues to increase. The emergence of multicellular organisms gave rise to increasing complexity of life resulting in trade-offs reflecting ancestral adaptations to changing environments. Three evolutionary traits shape CKD over the lifespan: 1) variation in nephron number at birth, 2) progressive nephron loss with aging, and 3) adaptive kidney growth in response to decreased nephron number. Although providing plasticity in adaptation to changing environments, the cell cycle must function within constraints dictated by available energy. Prioritized allocation of energy available through the placenta can restrict fetal nephrogenesis, a risk factor for CKD. Moreover, nephron loss with aging is a consequence of cell senescence, a pathway accelerated by adaptive nephron hypertrophy that maintains metabolic homeostasis at the expense of increased vulnerability to stressors. Driven by reproductive fitness, natural selection operates in early life but diminishes thereafter, leading to an exponential increase in CKD with aging, a product of antagonistic pleiotropy. A deeper understanding of the evolutionary constraints on the cell cycle may lead to manipulation of the balance between progenitor cell renewal and differentiation, regulation of cell senescence, and modulation of the balance between cell proliferation and hypertrophy. Application of an evolutionary perspective may enhance understanding of adaptation and maladaptation by nephrons in the progression of CKD, leading to new therapeutic advances.

Contrast-associated acute kidney injury and cardiovascular events: a secondary analysis of the PRESERVE cohort.

Contrast-associated acute kidney injury (CA-AKI) has been associated with a higher risk of cardiovascular (CV) events. We studied the risk of CV events in chronic kidney disease (CKD) patients undergoing angiography and whether biomarkers can predict such events. We also explored whether CA-AKI mediates the association of pre-angiography estimated glomerular filtration rate (eGFR) on CV events. We analysed participants from the Prevention of Serious Adverse Events following the Angiography (PRESERVE) trial. Urinary tissue inhibitor of matrix metalloproteinase [TIMP]-2 and insulin growth factor binding protein [IGFBP]-7, plasma brain-type natriuretic peptide (BNP), high sensitivity C-reactive protein (hs-CRP), and serum cardiac troponin-I (Tn-I) were assayed before and after angiography. We assessed the composite risk of CV events by day 90. Of the 922 participants, 119 (12.9%) developed CV events, and 73 (7.9%) developed CA-AKI. Most cases of CA-AKI (90%) were stage 1. There were no differences in urinary [TIMP-2]•[IGFBP7] concentrations or the proportion of patients with CA-AKI among those with and without CV events. Higher BNP, Tn-I, and hs-CRP were associated with CV events, but their discriminatory capacity was modest (AUROC <0.7). CA-AKI did not mediate the association of the pre-angiography eGFR on CV events. Most episodes of CA-AKI are stage 1 AKI and are not associated with CV events. Less severe CA-AKI episodes also did not mediate the risk of pre-angiography eGFR on CV events. Our findings suggest that most CV events after contrast procedures are due to underlying CKD and CV risk factors rather than less severe CA-AKI episodes and should help enhance the utilization of clinically indicated contrast procedures among high-risk patients with CKD. Further research is required to examine whether moderate-to-severe CA-AKI episodes are associated with CV events.

Is Climate Change Harming our Kidneys?

Chronic kidney disease (CKD) is highly prevalent and is predicted to become the fifth highest cause of premature mortality globally by 2040. There are several risk factors for CKD and the environmental conditions play an important role on the development of kidney injury. Due to increasing use of earth’s natural resources and pollutants emissions, extreme weather events are becoming more frequent and severe. These events, such as hurricanes or floods, cause infectious diseases outbreaks that increase the risk of acute kidney injury and chronic kidney disease. In addition, rising average temperatures and heat waves cause a higher incidence of acute kidney injury and nephrolithiasis. Patients with CKD are particularly prone to these events, with a special focus on patients undergoing peritoneal dialysis or hemodialysis. Mitigation plans are needed to reduce the effect of climate change on kidney health. Nephrologists have an important role in both reducing the environmental impact of nephrology and in preparing patients for the effect of climate changes on their diseases and for the accessibility problems to health institutions.

Degree of Albuminuria is Associated With Increased Risk of Fragility Fractures Independent of Estimated GFR

Fragility fractures are common in persons with chronic kidney disease (CKD); however, the association between fragility fractures and albuminuria is not well-studied. The primary objective of this study is to determine the association of albuminuria with incident risk of fragility fractures. The secondary objective is to examine the risk of fragility fracture by estimated glomerular filtration rate (eGFR) and Kidney Disease Improving Global Outcomes (KDIGO) risk categories. Community dwelling adults residing in Alberta, Canada who had at least 1 creatinine and albuminuria measurement between April 1, 2008 and March 31, 2019 participated in the study (N= 2.72 million). Incident fragility fractures were identified using Canadian Chronic Disease Surveillance Systems Osteoporosis Working Group algorithms. Albuminuria was categorized as none/mild (albumin-to-creatinine ratio [ACR]<30 mg/g, protein-to-creatinine ratio [PCR]<150 mg/g, trace/negative dipstick); moderate (ACR 30-300 mg/g, PCR 150-500 mg/g, 1+ dipstick) or severe (ACR >300 mg/g, PCR >500 mg/g,≥2+ dipstick). Multivariable analysis controlled for 42 variables. Patients with severe albuminuria had an increased risk of hip fracture (odds ratio [OR]= 1.37; 95% confidence interval [CI] 1.28, 1.47]), vertebral fracture (OR= 1.31; 95% CI 1.21, 1.41) and any-type fracture (OR= 1.22; 95% CI 1.17, 1.28) compared with patients with none/mild albuminuria. Patients in the most severe KDIGO risk category had an increased risk of hip fracture (OR= 1.22; 95% CI 1.16, 1.29), vertebral fracture (OR= 1.18; 95% CI 1.09, 1.26) and any type of fracture (OR= 1.25; 95% CI 1.21, 1.30). This study demonstrates the important role of albuminuria as a risk factor for fragility fracturesin CKD and may help inform risk stratification and prevention strategies in this high-risk population category.

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.

Association of hyperhomocysteinemia and chronic kidney disease in the general population: a systematic review and meta-analysis

BackgroundIncreasing evidence shows that an elevated homocysteine(Hcy) level is associated with an increased risk of chronic kidney disease (CKD). This study systematically evaluated the correlation between homocysteine level and the incidence of CKD reported in cohort and cross-sectional studies.MethodsWe searched electronic databases and reference lists for relevant articles. 4 cohort studies and 7 cross-sectional studies including 79,416 patients were analyzed in a meta-analysis. Hyperhomocysteinemia was defined as a Hcy level > 15 µmol/L, which was the criterium used in previous studies. Meta-analyses were conducted of literature searches from online databases such as PubMed, Embase, Cochrane and Scopus. Computed pooled adjusted odds ratios with corresponding 95% confidence intervals (95% CI) were used to estimate the risk of new-onset CKD according to Hcy levels in the general population.ResultsPeople with high Hcy levels were more likely to suffer from CKD than people with normal Hcy levels (pooled OR, 2.09; 95% CI, 1.72–2.55). This positive relationship persisted across different study types such as cohort studies (summary OR, 2.2; 95% CI, 1.55–3.13) and cross-sectional studies (summary OR, 2.07; 95% CI, 1.63–2.63).ConclusionsPeople with hyperhomocysteinemia have a higher incidence of CKD, Hyperhomocysteinemia may also be an independent risk factor for CKD in the general population.

Participation rate and yield of two home-based screening methods to detect increased albuminuria in the general population in the Netherlands (THOMAS): a prospective, randomised, open-label implementation study

Chronic kidney disease (CKD) has a rising global prevalence and is expected to become the fifth leading cause of death by 2030. Increased albuminuria defines the early stages of CKD and is among the strongest risk factors for progressive CKD and cardiovascular disease. The value of population screening for albuminuria to detect CKD in an early phase has yet to be studied. We aimed to evaluate the effectiveness of two home-based albuminuria population screening methods. Towards Home-based Albuminuria Screening (THOMAS) was a prospective, randomised, open-label implementation study that invited Dutch adults aged 45-80 years for albuminuria screening. Individuals were randomly assigned (1:1) to screening by applying either a urine collection device (UCD) that was sent by post to a central laboratory for measurement of the albumin-to-creatinine ratio (ACR) by immunoturbidimetry or to screening via a smartphone application that measures the ACR with a dipstick method at home. Randomisation was done with a four-block method via a web-based system and was stratified by age, sex, and socioeconomic status. If two or more individuals per household were invited to participate, these individuals were randomly assigned to the same group. In case of confirmed increased albuminuria at home, participants were invited for an elaborate screening in a regional hospital (Amphia Hospital, Breda, Netherlands) for CKD and cardiovascular risk factors. When abnormalities were found, participants were referred to their general practitioner for treatment. The primary outcomes were the participation rate and yield of the home-based screening and elaborate screening. Participation rate was assessed in the intention-to-screen population (ie, all participants who were invited for the home-based screening or elaborate screening). Yield was assessed in the per-protocol population (ie, all individuals who participated in the home-based screening or elaborate screening). An exploratory analysis assessed the sensitivity and specificity of both home-based screening methods. To this end, an additional quantitative ACR test was performed among people participating in the elaborate screening, and a substudy was performed among participants with a first negative home-based screening test, who were invited for an additional test. The study is registered with ClinicalTrials.gov, NCT04295889. 15 074 participants were enrolled between Nov 14, 2019, and March 19, 2021. 7552 (50·1%) were randomly assigned to home-based albuminuria screening by the UCD method and 7522 (49·9%) were assigned to albuminuria screening by the smartphone application method. The participation rate of the home-based screening was 4484 (59·4% [95% CI 58·3-60·5]) of the 7552 invited individuals for the UCD method and 3336 (44·3% [43·2-45·5]) of 7522 invited individuals for the smartphone application method (p<0·0001). Increased ACR was confirmed by home-based testing in 150 (3·3% [95% CI 2·9-3·9]) of 4484 individuals for the UCD method and 171 (5·1% [4·4-5·9]) of 3336 indivduals for the smartphone application method. 124 (82·7% [95% CI 75·8-87·9]) of 150 individuals assigned to the UCD method and 142 (83·0% [76·7-87·9]) of 171 participants assigned to the smartphone application method attended the elaborate screening. Sensitivity to detect increased ACR was 96·6% (95% CI 91·5-99·1) for the UCD method and 98·1% (89·9-99·9) for the smartphone application method, and specificity was 97·3% (94·7-98·8) for the UCD method and 67·9% (62·0-73·3) for the smartphone application method, indicating that the test characteristics of only the UCD method were sufficient for screening. Albuminuria, hypertension, hypercholesterolaemia, and decreased kidney function were newly diagnosed in 77 (62·1%), 44 (35·5%), 30 (24·2%), and 27 (21·8%) of 124 participants for the UCD method, respectively. Of the 124 participants assigned to the UCD method who completed elaborate screening, 111 (89·5%) were referred to their general practitioner for treatment because of newly diagnosed CKD or cardiovascular disease risk factors or known risk factors outside the target range. Home-based screening of the general population for increased ACR using a UCD had a high participation rate and correctly identified individuals with increased albuminuria and yet unknown or known but outside target range CKD and cardiovascular risk factors. By contrast, the smartphone application method had a lower at-home participation rate than the UCD method and the test specificity was too low to accurately assess individuals for risk factors during the elaborate screening. The UCD screening strategy could allow for an early start of treatment to prevent progressive kidney function loss and cardiovascular disease in patients with CKD. Dutch Kidney Foundation, Top Sector Life Sciences & Health of the Dutch Ministry of Economic Affairs.

Association of Plasma Biomarkers of Alzheimer Disease With Cognition and Medical Comorbidities in a Biracial Cohort.

Recent advances in blood-based biomarkers offer the potential to revolutionize the diagnosis and management of Alzheimer disease (AD), but additional research in diverse populations is critical. We assessed the profiles of blood-based AD biomarkers and their relationships to cognition and common medical comorbidities in a biracial cohort. Participants were evaluated through the Mayo Clinic Jacksonville Alzheimer Disease Research Center and matched on age, sex, and cognitive status. Plasma AD biomarkers (β-amyloid peptide 1-42 [Aβ42/40], plasma tau phosphorylated at position 181 [p-tau181], glial fibrillary acidic protein [GFAP], and neurofilament light) were measured using the Quanterix SiMoA HD-X analyzer. Cognition was assessed with the Mini-Mental State Examination. Wilcoxon rank sum tests were used to assess for differences in plasma biomarker levels by sex. Linear models tested for associations of self-reported race, chronic kidney disease (CKD), and vascular risk factors with plasma AD biomarker levels. Additional models assessed for interactions between race and plasma biomarkers in predicting cognition. The sample comprised African American (AA; N = 267) and non-Hispanic White (NHW; N = 268) participants, including 69% female participants and age range 43-100 (median 80.2) years. Education was higher in NHW participants (median 16 vs 12 years, p < 0.001) while APOE ε4 positivity was higher in AA participants (43% vs 34%; p = 0.04). We observed no differences in plasma AD biomarker levels between AA and NHW participants. These results were unchanged after stratifying by cognitive status (unimpaired vs impaired). Although the p-tau181-cognition association seemed stronger in NHW participants while the Aβ42/40-cognition association seemed stronger in AA participants, these findings did not survive after excluding individuals with CKD. Female participants displayed higher GFAP (177.5 pg/mL vs 157.73 pg/mL; p = 0.002) and lower p-tau181 (2.62 pg/mL vs 3.28 pg/mL; p = 0.001) levels than male participants. Diabetes was inversely associated with GFAP levels (β = -0.01; p < 0.001). In a biracial community-based sample of adults, we observed that sex differences, CKD, and vascular risk factors, but not self-reported race, contributed to variation in plasma AD biomarkers. Although some prior studies have reported primary effects of race/ethnicity, our results reinforce the need to account for broad-based medical and social determinants of health (including sex, systemic comorbidities, and other factors) in effectively and equitably deploying plasma AD biomarkers in the general population.

The Number and Size of Individual Kidney Medullary Pyramids is Associated with Clinical Characteristics, Kidney Biopsy Findings, and CKD Outcomes among Kidney Donors.

Segmentation of multiple structures in cross-sectional imaging is time-consuming and impractical to perform manually, especially if the end goal is clinical implementation. In this study, we developed, validated, and demonstrated the capability of a deep learning algorithm to segment individual medullary pyramids in a rapid, accurate, and reproducible manner. The results demonstrate that cortex volume, medullary volume, number of pyramids, and mean pyramid volume is associated with patient clinical characteristics and microstructural findings and provide insights into the mechanisms that may lead to CKD. The kidney is a lobulated organ, but little is known regarding the clinical importance of the number and size of individual kidney lobes. After applying a previously validated algorithm to segment the cortex and medulla, a deep-learning algorithm was developed and validated to segment and count individual medullary pyramids on contrast-enhanced computed tomography images of living kidney donors before donation. The association of cortex volume, medullary volume, number of pyramids, and mean pyramid volume with concurrent clinical characteristics (kidney function and CKD risk factors), kidney biopsy morphology (nephron number, glomerular volume, and nephrosclerosis), and short- and long-term GFR <60 or <45 ml/min per 1.73 m 2 was assessed. Among 2876 living kidney donors, 1132 had short-term follow-up at a median of 3.8 months and 638 had long-term follow-up at a median of 10.0 years. Larger cortex volume was associated with younger age, male sex, larger body size, higher GFR, albuminuria, more nephrons, larger glomeruli, less nephrosclerosis, and lower risk of low GFR at follow-up. Larger pyramids were associated with older age, female sex, larger body size, higher GFR, more nephrons, larger glomerular volume, more nephrosclerosis, and higher risk of low GFR at follow-up. More pyramids were associated with younger age, male sex, greater height, no hypertension, higher GFR, lower uric acid, more nephrons, less nephrosclerosis, and a lower risk of low GFR at follow-up. Cortex volume and medullary pyramid volume and count reflect underlying variation in nephron number and nephron size as well as merging of pyramids because of age-related nephrosclerosis, with loss of detectable cortical columns separating pyramids.

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.

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

BackgroundNonalcoholic fatty liver disease (NAFLD) is associated with impaired renal function, and both diseases often occur alongside other metabolic disorders. However, the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear. The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients. MethodsAll adults aged 18–70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study. Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase (FAST), Agile 3+ and Agile 4 scores. Impaired renal function and chronic kidney disease (CKD) were defined by an estimated glomerular filtration rate (eGFR) with value of < 90 mL/min/1.73 m2 and < 60 mL/min/1.73 m2, respectively, as estimated by the CKD-Epidemiology Collaboration (CKD-EPI) equation. ResultsAmong 529 included NAFLD patients, the prevalence rates of impaired renal function and CKD were 37.4% and 4.9%, respectively. In multivariate analysis, a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+ and Agile 4 scores were independent risk factors for CKD (P< 0.05). Furthermore, increased fasting plasma glucose (FPG) and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome (P< 0.05). Compared with patients with normoglycemia, those with prediabetes [FPG ≥ 5.6 mmol/L or hemoglobin A1c (HbA1c) ≥ 5.7%] were more likely to have impaired renal function (P< 0.05). ConclusionsAgile 3+ and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD. Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Tubular Secretory Solute Clearance and HIV Infection.

Tubular secretion is an important kidney function responsible for the clearance of numerous medications, including antibiotics and antivirals. It is unknown whether persons living with HIV have lower secretion compared with HIV-uninfected persons, which might predispose them to the risk of progressive kidney disease or adverse drug events. We evaluated a panel of 6 endogenous secretory solutes in 199 women living with HIV (WLWH) and 100 women without HIV enrolled in the Women's Interagency HIV Study. Secretory clearance was estimated as the urine-to-plasma ratio of each solute, with adjustment for urine tonicity. Using multivariable linear regression analysis, we compared differences in levels of secretory solute clearance between women with and without HIV and evaluated characteristics associated with secretion. WLWH were older (median 40 vs. 38 years) but had similar estimated glomerular filtration rate (eGFR, 96 vs. 100 mL/minute/1.73 m 2 ) compared with those without HIV. African American and Latino race, diabetes, diastolic blood pressure, smoking, hepatitis C, peak HIV viral load, and current and nadir CD4 count were associated with differences in clearance of at least 1 marker after multivariable adjustment. The secretory clearance of 3 solutes (cinnamoylglycine, kynurenic acid, and pyridoxic acid) were on average 10%-15% lower among WLWH compared with those without HIV independent of eGFR, albuminuria and chronic kidney disease risk factors, including HCV, and injection drug use. HIV is associated with reduced secretion among women with preserved eGFR. The implications of these findings for drug dosing and adverse events need to be evaluated.

Relationship between serum uric acid and estimated glomerular filtration rate in adolescents aged 12-19 years with different body mass indices: a cross-sectional study.

Globally, chronic kidney disease (CKD) is a growing public health concern. Serum uric acid (SUA) is an easily detectable and readily available biochemical indicator that has long been recognized as an independent risk factor for CKD. In addition, studies have indicated a potential relationship between SUA and body mass index (BMI). However, studies on the effect of SUA levels on the estimated glomerular filtration rate (eGFR) in adolescents with different BMIs are very rare. Weighted multiple regression analysis was used to estimate the independent relationship between SUA and log-transformed eGFR. Additionally, we used a weighted generalized additive model and smooth curve fitting to describe the nonlinear relationships in the subgroup analysis. First, SUA was negatively associated with log-transformed eGFR even after adjusting for all covariates (β=-0.0177, 95% CI: -0.0203-0.0151, P<0.0001). Second, the results of the stratified analysis found that after adjusting for all covariates, the decrease in log-transformed eGFR due to changes in per SUA levels (Per 1, mg/dL increase) was elevated in female adolescents (β=-0.0177, 95% CI: -0.0216, -0.0138, P<0.0001), adolescents aged 12-15 years (β=-0.0163, 95% CI: -0.0200, -0.0125, P<0.0001) and black (β=-0.0199, 95% CI: -0.0251, -0.0148, P<0.0001) adolescents. Furthermore, we found that adolescents with a higher BMI had higher SUA levels, and the effect of SUA on eGFR was significantly higher in underweight adolescents (β=-0.0386, 95% CI: (-0.0550, -0.0223), P<0.0001). SUA was negatively associated with the eGFR in adolescents aged 12-19 years. Furthermore, we found for the first time that SUA affects the eGFR differently in adolescents with different BMIs. This effect was particularly significant in underweight adolescents.

Renal Dysfunction after Rectal Cancer Surgery: A Long-term Observational Study.

Despite the high incidence of urinary dysfunction (UD) after rectal surgery, it remains questionable whether UD causes future chronic kidney disease (CKD). This study aimed to clarify the long-term trends in renal function and risk factors for future CKD after rectal resection. For comparison, patients who underwent rectal resection (n = 129) and colectomy (n = 127) between 2006 and 2017 were identified. The estimated glomerular filtration rate (eGFR) ratio was calculated as the ratio to the baseline. "eGFR ratio < 0.75 at 3-year" was adopted as a surrogate indicator of future CKD. eGFR ratio significantly decreased in the rectal cohort compared with the colon cohort at 1.5 years (0.9 vs. 0.95, p = 0.008) and at 3 years (0.85 vs. 0.94, p < 0.001). Although the preoperative prevalence of CKD was lower in the rectal than the colon cohort (13.9% vs. 23.6%, p = 0.055), it was similar at 3 years (29.5% vs. 30.7%). In multivariate analysis, females, and cT4 were independent risk factors for future CKD, but UD itself was not. Postoperative eGFR significantly decreased after rectal cancer surgery compared to colectomy. The prevalence of CKD more than doubled at 3 years after rectal resection. The female sex and cT4 tumor, instead of the UD, were independent risk factors for future CKD.

Burden of chronic kidney disease in Nepal: An analysis of the burden of disease from 1990 to 2019.

Chronic kidney disease (CKD) has emerged as one of the major public health concerns. The increasing prevalence of its correlates such as obesity, diabetes, and hypertension has been, due in part responsible for the increased burden. However, very few studies have presented the comprehensive data on burden of disease particularly in developing countries like Nepal. In this study, we have performed an analysis on prevalence, mortality, years lived with disability (YLDs), years of life lost (YLLs) and disability-adjusted life years (DALYs) attributable to CKD in Nepal using Global Burden of Disease (GBD) Study 2019. The GBD 2019 study provides estimation of the prevalence, mortality rates, YLDs, YLLs and DALYs due to 369 different disease and 87 risk factors for 204 countries and territories across the world. In this study, we present Nepal specific data on prevalence, mortality, YLDs, YLLs and DALYs related to CKD. In 2019, there were 1,895,080 prevalent cases of CKD with 5,108 deaths, and a total of 168,900 DALYs were attributable to CKD. Age-standardized prevalence rate of CKD increased from 5,979.1 cases per 100,000 population (95% UI: 5539.7, 6400.4) in 1990 to 7,634.1 cases per 100,000 population (95% UI: 7138.8, 8119.4) in 2019 with higher prevalence in males. Similarly, the age-standardized mortality due to CKD increased for both sexes from 0.8 deaths per 100,000 population (95% UI: 0.6, 1.0) in 1990 to 2.6 deaths per 100,000 population (95% UI: 2.0, 3.3) in 2019. The burden of CKD as a percentage of total DALYs was 0.5% (95% UI: 0.4, 0.6) in 1990 and increased to 1.8% (95% UI: 1.4, 2.2%) in 2019. Kidney dysfunction, high systolic blood pressure, high fasting plasma glucose, high body mass index, low temperature, lead exposure, diet high in sodium, and high temperature were found to be the major risk factors for CKD. The study reveals that Nepal has a high and rising burden of CKD. Innovative strategies for prevention of CKD including health system preparedness for treatment services are required to respond to the rising burden of CKD.

Metabolic disorders induced by PNPLA3 and TM6SF2 gene variants affect chronic kidney disease in patients infected with non-genotype 3 hepatitis C virus

BackgroundPatients with chronic hepatitis C virus (HCV) infections differ in their risk for metabolic disorders and chronic kidney disease (CKD). The aim of this study was to investigate the effect of metabolic disorders induced by genetic factors on CKD in HCV-infected patients.MethodsPatients with chronic non-genotype 3 HCV infection with or without CKD were examined. PNPLA3 and TM6SF2 variants were determined using high-throughput sequencing. The relationships of variants and different combinations with metabolic disorders were analyzed in CKD patients. Univariate and multivariate analyses were used to identify factors associated with CKD.ResultsThere were 1022 patients with chronic HCV infection, 226 with CKD and 796 without CKD. The CKD group had more severe metabolic disorders, and also had higher prevalences of liver steatosis, the PNPLA3 rs738409 non-CC genotype, and the TM6SF2 rs58542926 CC genotype (all P < 0.05). Relative to patients with the PNPLA3 rs738409 CC genotype, patients with the non-CC genotype had a significantly decreased eGFR and a greater prevalence of advanced CKD (CKD G4-5). Patients with the TM6SF2 rs58542926 CC genotype had a lower eGFR and a higher prevalence of CKD G4-5 than those with the non-CC genotype. Multivariable analysis indicated that multiple metabolic abnormalities, including liver steatosis and the PNPLA3 rs738409 C > G variant, increased the risk of CKD, but the TM6SF2 rs58542926 C > T variant decreased the risk of CKD.ConclusionSpecific PNPLA3 rs738409 and TM6SF2 rs58542926 variants are independent risk factors for CKD in patients with chronic HCV infections and are associated with the severity of renal injury.

#4177 PREVALENCE OF UNRECOGNIZED CHRONIC KIDNEY DISEASE IN THE LOLLAND-FALSTER HEALTH STUDY: A POPULATION-BASED STUDY IN A RURAL-PROVINCIAL AREA OF DENMARK

Abstract Background and Aims In order to improve renal and cardiovascular outcome in patients with chronic kidney disease (CKD), it is important to identify patients with CKD in early stages of the disease. Given the asymptomatic nature of early-stage CKD, the majority of the CKD patients are living with an unrecognized condition. There is limited knowledge about the Danish prevalence of CKD stage 1-4. Moreover, previous studies have shown association between CKD and low socio-economic status. This study aims to increase the insights into prevalence and risk factors of CKD in a population living in a part of Denmark where income and life expectancy is below the national average. Method Data was derived from The Lolland-Falster Health Study (LOFUS) which is a population and household-based prospective cohort study at Lolland-Falster, a mixed rural-provincial area in Denmark. Data was obtained between 2016 and 2020 from questionnaires, clinical- and paraclinical evaluation. CKD was defined according to KDIGO classification (single test) as urinary albumin-to-creatinine ratio (UACR) &amp;gt;30 mg/g and/or estimated glomerular filtration rate (eGFR) &amp;lt;60 ml/min/1.73 m2. Univariate and multiple logistic regression models were used to evaluate potential risk factors for CKD. Results The study included 16,142 adult individuals. Characteristics of the population are reported in Table 1. The median age was 58.6 years (IQR 44.7-68.6) and 53% of the population were women. The overall CKD prevalence was 17.7% and was higher in women than in men (19.2% versus 16.0%, p-value &amp;lt; 0.001). Of the 2856 participants with CKD, 71.1% had CKD based on elevated UACR, 19.0% had CKD based on reduced eGFR and 9.9% had CKD based on reduced eGFR combined with elevated UACR. Among the participants with CKD, 31.8% had CKD stage 1, 39.2% had stage 2, 28.0% stage 3, and 1.1% had CKD stage 4-5. Less than 2% (n = 207) of the total population had a self-reported kidney-related diagnosis which correspond to only 4.5% of the individuals with CKD identified in the study. Among those with CKD stage 3-5, more than 27% did not report any kidney-related diagnosis. In univariate analyses, female sex (OR 1.25, 95% CI 1.15 – 1.35), age above 55 years (OR 3.55, 95% CI 3.01 – 4.20), BMI &amp;gt; 25 kg/m2 (OR 1.02, 95% CI 1.02 – 1.03), diabetes (OR 3.38, 95% CI 2.89 – 3.95), hypertension (OR 3.34, 95% CI 3.06 – 3.65), cardiovascular disease (OR 2.28, 95% CI 1.86 – 2.79) and current or former smoking (OR 1.27, 95% CI 1.17 – 1.39) were all risk factors for CKD. In a multiple regression analysis, all risk factors but BMI were independent risk factors for CKD. Conclusion CKD is common in the LOFUS cohort with a prevalence of nearly 18%. Less than 5% are aware of their condition and therefore our data indicate a high rate of unrecognized CKD. Comorbidities such as hypertension, diabetes, and cardiovascular disease are strongly associated with CKD. In contrast to earlier findings, overweight and obesity did not seem to increase the risk of CKD in our study, when adjusted for other comorbidities. Our findings could be used to develop strategies for early identification of CKD patients, particularly in populations living in socio-economically disadvantaged areas.

Chronic kidney disease acquired knowledge in a diabetic and hypertensive population using a translated and validated questionnaire

Chronic kidney disease (CKD) is the progressive and irreversible functional and/or structural impairment of the kidney; its main etiologies include hypertension and diabetes. Mexico has the second highest prevalence of CKD worldwide with a high economic burden affecting public and private health systems. Patients with higher knowledge about CKD increase their adherence to preventive treatment. In this study we aim to describe the knowledge of CKD in a sample of Mexican high-risk population, comparing it with general Mexican population, medical students and nephrologists. A cross-sectional, observational study was performed divided in two phases: translation and validation of the knowledge questionnaire to Spanish, and cross-sectional survey to evaluate the knowledge of CKD in patients with diagnosis of diabetes and/or hypertension. We interviewed medical students, general population, and nephrologists to attain validation of the questionnaire in Spanish. The questionnaire was answered by 1,061 participants within the high-risk population. The results of the questionnaire were: 22/24, 18/24, 13.8/24, and 13.4/24 in nephrologists, medical students, normal subjects, and high-risk population, respectively. The questions with least correct answers were related to kidney functions and CKD risk factors. To our knowledge this is the first time a questionnaire for CKD knowledge is applied in Mexican population. These findings suggest poor understanding of kidney functions, risk factors, and symptoms of CKD. It is important not only to provide medical treatment to chronic illness but also awareness of the consequences of not achieving goals of treatment.

#5425 CHANGES IN SERUM CREATININE DURING AND AFTER PREGNANCY IN WOMEN WITH OR WITHOUT CHRONIC KIDNEY DISEASE: AN OBSERVATIONAL STUDY

Abstract Background and Aims In women with chronic kidney disease (CKD), kidneys may not sufficiently adapt to physiological changes during pregnancy, which may accelerate postpartum loss in renal function. We aimed to characterize pregnant women with or without renal impairment and to describe changes in renal filtration during and until one year after pregnancy. Method We performed a descriptive study using primary care data from the United Kingdom-based Clinical Practice Research Datalink (CRPD) GOLD and linked hospital data (2000–2019) in 14’401 pregnancies with ≥2 serum creatinine (SCr) measurements between the year before and after pregnancy. Pregnancies were categorized by means of the median estimated glomerular filtration rate (eGFR) during baseline (proteinuria is not reliably recorded). We captured risk factors for CKD and described changes in SCr levels over time as proxies for renal filtration. Results Of 14’401 pregnancies, 84% had a baseline eGFR [ml/min/1.73m2] of ≥90, 13% between 75–89, 13% between 60–74, and &amp;lt;1% between 15–59. Pre-existing hypertension, diabetes, and/or overweight was prevalent in 66.0% of women with an eGFR &amp;lt; 60 (versus 51.3-54.4% in eGFR ≥ 60). Preterm delivery was recorded in 30.2% of women with an eGFR &amp;lt; 60 (versus 9.4–9.8% in eGFR ≥ 60). In women with a low-normal eGFR between 75–89, median baseline SCr levels (mg/dL [μmol/L]) were 0.92 [81.33] (interquartile range (IQR) = 0.88–0.96 [77.79–84.86]), which decreased by 0.25 [22.1] by week 14/15, remained stable until week 30/31, increased to 0.94 [84.0] (IQR = 0.83–0.99 [73.37–87.52]) until week 3/4 postpartum, and decreased back to baseline by one year postpartum. In women with a moderately low baseline eGFR between 60–74, median baseline SCr levels were 1.05 [92.82] (IQR = 1.01–1.10 [89.28–97.24]) and patterns during pregnancy followed those of women with low-normal eGFR (decreased by 0.28 [24.74] until week 18/19, plateau until week 38/39). However, SCr levels increased slower in trimester 3 and early postpartum and reached baseline levels at week 9/10 postpartum. Women with a baseline eGFR between 15–59 (median baseline SCr levels = 1.43 mg/dL [126.41 μmol/L], IQR = 1.26–1.72 mg/dL [111.38–152.05 μmol/L]) showed renal adaptation in trimester 1 and 2, but increased SCr levels of 1.71 [151.16] (IQR = 1.32-2.36 [116.69–208.62]) in trimester 3, but sample size was small. Conclusion Adaptations of renal filtration were not impaired during or after pregnancy in 1’932 pregnancies of women with a low-normal eGFR between 75–89. In women with a moderately low eGFR between 60–74, the pattern was similar, but potentially prolonged hyperfiltration in trimester 3 and early postpartum requires further investigation. The pattern of renal adaptation in eGFR between 15–59 was similar in trimester 1 and 2. Increased SCr levels in trimester 3 may indicate insufficient renal function but results have to be interpreted cautiously due to small sample size and potentially selective measurements.