Incidence and Predictors of CKD and Estimated GFR Decline in Patients Receiving Immune Checkpoint Inhibitors.
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ABSTRACT:
SUBMITTER: Chute DF
PROVIDER: S-EPMC8855486 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Incidence and Predictors of CKD and Estimated GFR Decline in Patients Receiving Immune Checkpoint Inhibitors.
Chute Donald F DF Zhao Sophia S Strohbehn Ian A IA Rusibamayila Nifasha N Seethapathy Harish H Lee Meghan M Zubiri Leyre L Gupta Shruti S Leaf David E DE Rahma Osama O Drobni Zsofia D ZD Neilan Tomas G TG Reynolds Kerry L KL Sise Meghan E ME
American journal of kidney diseases : the official journal of the National Kidney Foundation 20210624 1
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Project description:BACKGROUND:Low ankle-brachial index (ABI) is associated with increases in serum creatinine level. Whether low ABI is associated with the development of rapid estimated glomerular filtration rate (eGFR) decline, stage 3 chronic kidney disease (CKD), or microalbuminuria is uncertain. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:Framingham Offspring cohort participants who attended the sixth (1995-1998) and eighth (2005-2008) examinations. PREDICTOR:ABI, categorized as normal (>1.1 to <1.4), low-normal (>0.9 to 1.1), and low (?0.9). OUTCOMES:Rapid eGFR decline (eGFR decline ?3 mL/min/1.73 m(2) per year), incident stage 3 CKD (eGFR <60 mL/min/1.73 m(2)), incident microalbuminuria. MEASUREMENTS:GFR was estimated using the serum creatinine-based CKD-EPI (CKD Epidemiology Collaboration) equation. Urinary albumin-creatinine ratio (UACR) was determined based on spot urine samples. RESULTS:During 9.5 years, 9.0% (232 of 2,592) experienced rapid eGFR decline and 11.1% (270 of 2,426) developed stage 3 CKD. Compared to normal ABI, low ABI was associated with 5.73-fold increased odds of rapid eGFR decline (95% CI, 2.77-11.85; P<0.001) after age, sex, and baseline eGFR adjustment; this persisted after multivariable adjustment for standard CKD risk factors (OR, 3.60; 95% CI, 1.65-7.87; P = 0.001). After adjustment for age, sex, and baseline eGFR, low ABI was associated with a 2.51-fold increased odds of stage 3 CKD (OR, 2.51; 95% CI, 1.16-5.44; P = 0.02), although this was attenuated after multivariable adjustment (OR, 1.68; 95% CI, 0.75-3.76; P = 0.2). In 1,902 free of baseline microalbuminuria, low ABI was associated with increased odds of microalbuminuria after adjustment for age, sex, and baseline UACR (OR, 2.81; 95% CI, 1.07-7.37; P = 0.04), with attenuation upon further adjustment (OR, 1.88; P = 0.1). LIMITATIONS:Limited number of events with low ABI. Outcomes based on single serum creatinine and UACR measurements at each examination. CONCLUSIONS:Low ABI is associated with an increased risk of rapid eGFR decline, suggesting that systemic atherosclerosis predicts a decrease in kidney function.
| S-EPMC3517695 | biostudies-literature
Project description:Rationale & objectiveDetermining whether a change in estimated glomerular filtration rate (eGFR) or albuminuria is clinically significant requires knowledge of short-term within-person variability of the measurements, which few studies have addressed in the setting of chronic kidney disease.Study designCross-sectional study with multiple collections over less than 4 weeks.Setting & participantsClinically stable outpatients with chronic kidney disease (N=50; mean age, 56.8 years; median eGFR, 40mL/min/1.73m2; median urinary albumin-creatinine ratio (UACR), 173mg/g).ExposureRepeat measurements from serially collected samples across 3 study visits.OutcomesMeasurements of urine albumin concentration (UAC), UACR, and plasma creatinine, cystatin C, β2-microglobulin (B2M), and beta trace protein (BTP).Analytical approachWe calculated within-person coefficients of variation (CVw) values and corresponding reference change positive and negative (RCVpos and RCVneg) values using log-transformed measurements.ResultsMedian CVw (RCVpos; RCVneg) values of filtration markers were 5.4% (+16%; -14%) for serum creatinine, 4.1% (+12%; -11%) for cystatin C, 7.4% (+23%; -18%) for BTP, and 5.6% (+17%; -14%) for B2M. Results for albuminuria were 33.2% (+145%; -59%) for first-morning UAC, 50.6% (+276%; -73%) for random spot UAC, 32.5% (+141%; -58%) for first-morning UACR, and 29.7% (124%; -55%) for random spot UACR. CVw values for filtration markers were comparable across the range of baseline eGFRs. CVw values for UAC and UACR were comparable across the range of baseline albuminuria values.LimitationsSmall sample size limits the ability to detect differences in variability across markers. Participants were recruited and followed up in a clinical and not research setting, so some preanalytical factors could not be controlled.ConclusionseGFR markers appear to have relatively low short-term within-person variability, whereas variability in albuminuria appears to be high, making it difficult to distinguish random variability from meaningful biologic changes.
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Project description:BackgroundSeveral reviews have recently detailed the beneficial effects of weight loss surgery for kidney function. However, these studies have a number of limitations, including small sample size, few done in chronic kidney disease (CKD) stages 3 and 4, and many not including the main bariatric surgery procedures used in the United States today.Study designThis was an observational retrospective cohort study comparing propensity score-matched bariatric surgery patients and nonsurgery control patients who were referred for, but did not have, surgery. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy were also compared using propensity matching.Setting & participantsPatients (714 surgery patients; 714 controls) were from a large integrated health care system, a mean of 58±8 (SD) years old, and mostly women (77%) and non-Hispanic whites (56%) and had diabetes mellitus (66%) and/or hypertension (91%).PredictorPredictors at the time of surgery or referral to surgery were age, sex, race/ethnicity, weight, and presence of diabetes and/or hypertension.OutcomesThe primary outcome for this study was change in estimated glomerular filtration rate (eGFR) from serum creatinine level over a median 3-year follow-up period.MeasurementsSerum creatinine was used to calculate eGFR using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation.ResultsSurgery patients had 9.84 (95% CI, 8.05-11.62) mL/min/1.73m2 greater eGFRs than controls at a median 3 years' follow-up and RYGB patients had 6.60 (95% CI, 3.42-9.78) mL/min/1.73m2 greater eGFRs than sleeve gastrectomy patients during the same period.LimitationsThis study is limited by its nonrandomized observational study design, estimation of GFR, and large changes in muscle mass, which may affect serum creatinine level independent of changes in kidney function.ConclusionsBariatric surgery, especially the RYGB procedure, results in significant improvements for up to 3 years in eGFRs for patients with CKD stages 3 and 4.
| S-EPMC6264887 | biostudies-literature
Project description:BackgroundCardiovascular immune-related adverse events (CV-irAEs) associated with immune checkpoint inhibitors (ICIs) may have been underreported given that most previous reports were retrospective. We aimed to evaluate the incidence, clinical characteristics, and predictors of CV-irAEs and determine the feasibility of serial cardiac monitoring using a combination of B-type natriuretic peptide, cardiac troponin T, and electrocardiogram for the prediction of future symptomatic (grade ≥2) CV-irAEs.Materials and methodsThis was a prospective observational study that included 129 consecutive patients with non-small-cell lung cancer who received ICI monotherapy at a single center. Serial cardiac monitoring was performed during ICI monotherapy.ResultsA total of 35 (27%) patients developed any grade ≥1 CV-irAEs with a median time of onset of 72 (interquartile range 44-216) days after ICI treatment initiation. Multivariate Fine-Gray regression analysis showed that prior acute coronary syndrome (adjusted hazard ratio [HR] 3.15 (95% [CI], 2.03-4.91), prior heart failure hospitalization (adjusted HR 1.65 [95% CI, 1.17-2.33]), and achievement of disease control (adjusted HR 1.91, [95% CI, 1.16-3.14]) were significantly associated with grade ≥1 CV-irAEs. Serial cardiac monitoring revealed that patients with preceding grade 1 CV-irAEs were associated with a significantly higher risk of onset of grade ≥2 CV-irAEs compared with those without preceding grade 1 CV-irAEs (HR: 6.17 [95% CI, 2.97-12.83]).ConclusionCV-irAEs were more common than previously recognized and have several predictors. Moreover, serial cardiac monitoring may be feasible for the prediction of future grade ≥2 CV-irAEs.
| S-EPMC9074992 | biostudies-literature
Project description:Physical activity may counteract metabolic disturbances that promote the progression of CKD. To address this concept, we performed a longitudinal cohort study of 256 participants in the Seattle Kidney Study, a clinic-based study of CKD. Participants with an estimated GFR (eGFR) of 15-59 ml/min per 1.73 m(2) at baseline were eligible for the study. Physical activity was quantified using the Four-Week Physical Activity History Questionnaire. We used generalized estimating equations to test associations of physical activity with change in eGFR determined by longitudinal measurements of serum cystatin C. Mean baseline eGFR was 42 ml/min per 1.73 m(2). During a median 3.7 years of follow-up, the mean change in eGFRcystatin C was -7.6% per year (interquartile range, -16.8%, 4.9% per year). Participants who reported >150 minutes of physical activity per week had the lowest rate of eGFRcystatin C loss (mean -6.2% per year compared with -9.6% per year among inactive participants). In adjusted analyses, each 60-minute increment in weekly physical activity duration associated with a 0.5% slower decline per year in eGFR (95% confidence interval, 0.02 to 0.98; P=0.04). Results were similar in sensitivity analyses restricted to participants without cardiovascular disease or diabetes, or to participants with moderate/high physical function. After adjustment for eGFR at the time of questionnaire completion, physical activity did not associate with the incidence of ESRD (n=34 events). In summary, higher physical activity levels associated with slower rates of eGFR loss in persons with established CKD.
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Project description:Rationale & objectivePrimary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism that results in early-onset kidney stone disease, nephrocalcinosis, and kidney failure. There is an unmet need for reliable markers of disease progression to test effectiveness of new treatments for patients with PH. In this study, we assessed the rate of estimated glomerular filtration rate (eGFR) decline across chronic kidney disease (CKD) glomerular filtration rate (GFR) categories (CKD G2-G5) in a cohort of patients with PH1.Study designRetrospective observational study.Setting & participantsPatients with PH1 enrolled in the Rare Kidney Stone Consortium (RKSC) registry who did not have kidney failure at diagnosis and who had at least 2 eGFR values recorded from within 1 month of diagnosis until their last contact date or incident kidney failure event.PredictorsCKD GFR category, baseline patient and laboratory characteristics.OutcomeAnnualized rate of eGFR decline.Analytical approachGeneralized estimating equations and linear regression were used to evaluate the associations between CKD GFR category, baseline patient and laboratory characteristics, and annual change in eGFR during follow-up.ResultsCompared with the slope in CKD G2 (-2.3 mL/min/1.73 m2 per year), the mean annual eGFR decline was nominally steeper in CKD G3a (-5.3 mL/min/1.73 m2 per year) and statistically significantly more rapid in CKD G3b and G4 (-14.7 and -16.6 mL/min/1.73 m2 per year, respectively). In CKD G2, older age was associated with a more rapid rate of eGFR decline (P = 0.01). A common PH1-causing variant of alanine glyoxylate aminotransferase, a glycine to arginine substitution at amino acid 170 (G170R), appeared to be associated with less severe annual decline in eGFR.LimitationsData at regular time points were not available for all patients due to reliance on voluntary reporting in a retrospective rare disease registry.ConclusionsThe eGFR decline was not uniform across CKD GFR categories in this PH1 population, with a higher rate of eGFR decline in CKD G3b and G4. Thus, CKD GFR category needs to be accounted for when analyzing eGFR change in the setting of PH1.
| S-EPMC9398980 | biostudies-literature
Project description: Not available
| S-EPMC11833704 | biostudies-literature
Project description:Rationale & objectiveThe prevalence of chronic kidney disease (CKD) is known to increase with age; however, creatinine may be a less reliable filtration marker in older adults. Few studies have investigated the prevalence and progression of CKD using different filtration markers for estimating glomerular filtration rate (GFR).Study designA prospective observational cohort study.Setting & participants6,393 White and African American participants aged 65-100 years from the Atherosclerosis Risk in Communities Study (ARIC) at Visit 5, followed longitudinally at Visits 6 and 7.Exposure and outcomeThe eGFR was estimated either by creatinine (eGFRcr), cystatin C (eGFRcys), creatinine and cystatin C (eGFRcr-cys), or using creatinine, cystatin C, and β-2-microglobulin (eGFRcr-cys-b2m). CKD progression was defined as 30% decline in eGFR at follow-up visits.Analytical approachLogistic regression models, adjusted for sex, race and study center, diabetes, blood pressure, body mass index, prevalent cardiovascular disease, and heart failure.ResultsAt Visit 5, the mean age in the study population was 75.8 years, and the mean eGFR ranged from 71.2 to 61.2 mL/min/1.73m2 using eGFRcr or eGFRcys, respectively. The proportion with eGFR < 60 mL/min/1.73m2 was lowest with eGFRcr and highest with eGFRcys for all age groups, and prevalence increased with age for all markers. For example, the prevalence of eGFRcr < 60 mL/min/1.73m2 in ages 70-74 years ranged from 15% to 21% and in ages 85-89 years ranged from 38% to 46% at the different visits. The proportion with a 30% eGFR decline over a mean of 8 years in people who were originally aged 65-69 years ranged from 9% (eGFRcr)-18% (eGFRcys). More people with eGFRcr ≥ 60 mL/min/1.73m2 were reclassified to < 60 mL/min/1.73m2 when using eGFRcys (33%) compared with eGFRcr-cys (12%) or eGFRcr-cys-b2m (18%). The proportion with 30% eGFR decline was lowest with eGFRcr and highest with eGFRcys, with greater incidence in older age groups for all markers.LimitationsNo direct measurement of GFR. Not all participants survived or attended subsequent follow-up visits.ConclusionsThe prevalence and progression of CKD increase with age, but estimates vary with the filtration marker used. The eGFRcr gave the lowest estimate of CKD at 15% for people aged 65-69 years at Visit 5 while eGFRcys gave the highest estimates of CKD at 26% for that same population.
| S-EPMC11420509 | biostudies-literature
Project description:BackgroundDespite cardiovascular disease (CVD) and chronic kidney disease sharing similar causes and interplay, it is unknown if a broader relationship between these diseases exists across generations. We investigated the association between parental CVD history and estimated glomerular filtration rate (eGFR) in the community.Study designCross-sectional and longitudinal analyses.Setting & participants13,241 community-based adults with serum creatinine measurement and follow-up visits (from 1-8 visits ~2 years apart) from the Aerobics Center Longitudinal Study.PredictorsPremature parental CVD history (before age 50 years).OutcomeseGFR, decreased eGFR (<60 mL/min/1.73 m(2)), and rate of eGFR decline.MeasurementsInformation for parental history was collected by protocol-standardized questionnaires. eGFR was assessed with serum creatinine.Results3,339 (25.2%) participants reported a history of parental CVD. Individuals with parental CVD had significantly lower eGFRs compared with those without parental CVD (69.4 ± 12.9 vs 74.8 ± 14.2 mL/min/1.73 m(2); P<0.001). After multivariable adjustment, parental CVD was associated independently with higher odds of having decreased eGFR (adjusted OR, 1.68; 95% CI, 1.52-1.86). Random-coefficient models showed that individuals with parental CVD had a faster decline in eGFR compared with those without parental CVD (sex- and ethnicity-adjusted annual change of -0.47 vs -0.41 mL/min/1.73 m(2); P=0.06).Limitations~70% of participants did not attend a second examination.ConclusionsParental history of CVD was associated with lower baseline eGFR, higher odds of decreased eGFR, and a nominally faster rate of eGFR decline in the offspring. Such findings may imply previously unrecognized cross-generational links between both diseases and be of support in community screening programs.
| S-EPMC4414720 | biostudies-literature
Project description:Background and objectives: Immune checkpoint inhibitor use in oncology is increasing rapidly. We sought to determine the frequency, severity, cause, and predictors of AKI in a real-world population receiving checkpoint inhibitors.Design, setting, participants, & measurements: We included all patients who received checkpoint inhibitor therapy from May 2011 to December 2016 at Massachusetts General Hospital. Baseline serum creatinine, averaged 6 months before checkpoint inhibitor start date, was compared with all subsequent creatinine values within 12 months of starting therapy. AKI was defined by Kidney Disease: Improving Global Outcomes criteria for fold changes in creatinine from baseline. Sustained AKI events lasted at least 3 days and was our primary outcome. The cause of sustained AKI was determined by chart review. Cumulative incidence and subdistribution hazard models were used to assess the relationship between baseline demographics, comorbidities, and medications, and sustained AKI and potential checkpoint inhibitor-related AKI.Results: We included 1016 patients in the analysis. Average age was 63 (SD 13) years, 61% were men, and 91% were white. Mean baseline creatinine was 0.9 mg/dl (SD 0.4 mg/dl), and 169 (17%) had CKD (eGFR<60 ml/min per 1.73 m2) at baseline. A total of 169 patients (17%) experienced AKI, defined by an increase in creatinine at least 1.5 times the baseline within 12 months; 82 patients (8%) experienced sustained AKI and 30 patients (3%) had potential checkpoint inhibitor-related AKI. The first episode of sustained AKI occurred, on average, 106 days (SD 85) after checkpoint inhibitor initiation. Sixteen (2%) patients experienced stage 3 sustained AKI and four patients required dialysis. Proton pump inhibitor use at baseline was associated with sustained AKI.Conclusions: AKI is common in patients receiving checkpoint inhibitor therapy. The causes of sustained AKI in this population are heterogenous and merit thorough evaluation. The role of PPI and other nephritis-inducing drugs in the development of sustained AKI needs to be better defined.
| S-EPMC6895474 | biostudies-literature