Cystatin C- and Creatinine-based Estimated GFR Differences: Prevalence and Predictors in the UK Biobank.

Rationale & Objective: Large differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values. Study Design: Cohort study. Setting & Participants: 468,969 participants in the UK Biobank. Exposures: Candidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors. Outcomes: eGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than -15 mL/min/1.73 m2), concordant eGFRcys and eGFRcr (eGFRdiff, -15 to < 15 mL/min/1.73 m2), and lower eGFRcr (eGFRdiff, ≥15 mL/min/1.73 m2). Analytical Approach: Multinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants. Results: Mean ± standard deviation of eGFRcys was 88 ± 16 mL/min/1.73 m2, and eGFRcr was 95 ± 13 mL/min/1.73 m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio >300 mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model's area under the curve was 0.75 in the validation set, with good calibration (1.00). Limitations: Limited generalizability. Conclusions: This study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing.

Estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine may differ substantially within an individual. Although most clinicians are aware that creatinine is influenced by muscle mass, there are additional numerous lifestyle and health characteristics that may affect serum concentrations of either biomarker. Our analyses of 468,969 individuals in the UK Biobank identified independent predictors of large differences between eGFR based on cystatin C and eGFR based on creatinine, which may inform the interpretation of discrepant eGFR values within an individual. We developed models that may be implemented at a population level to help health systems identify individuals who are likely to have large differences between eGFR based on cystatin C and eGFR based on creatinine and thus should be prioritized for cystatin C testing.

The Vitamin D Metabolite Ratio Is Associated With Volumetric Bone Density in Older Men.

CONTEXT: Serum 25-hydroxyvitamin D (25(OH)D) is the current marker of vitamin D adequacy, but its relationship with bone health has been inconsistent. The ratio of 24,25-dihydroxyvitamin D3 to 25(OH)D3 (vitamin D metabolite ratio or VMR) is a marker of vitamin D that has been associated with longitudinal changes in bone mineral density (BMD) and fracture risk. OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) provides information on bone health beyond standard dual-energy x-ray absorptiometry, in that it measures volumetric BMD (vBMD) as well bone strength. The relationship of the VMR with vBMD and bone strength remains unknown. METHODS: We evaluated the associations of the VMR and 25(OH)D3 with vBMD and bone strength in the distal radius and tibia, assessed by HR-pQCT in 545 older men participating in the Osteoporotic Fractures in Men (MrOS) Study. Primary outcomes were vBMD and estimated failure load (EFL, a marker of bone strength) at the distal radius and tibia. RESULTS: The mean age was 84 ± 4 years, 88.3% were White, and 32% had an estimated glomerular filtration rate <60 mL/min/1.73 m2. In adjusted models, each twofold higher VMR was associated with a 9% (3%, 16%) higher total vBMD and a 13% (5%, 21%) higher EFL at the distal radius. Results were similar at the distal tibia. 25(OH)D3 concentrations were not associated with any of the studied outcomes. CONCLUSION: Among older men, a higher VMR was associated with greater vBMD and bone strength while 25(OH)D3 was not. The VMR may serve as a valuable marker of skeletal health in older men.

Estimated GFR Accuracy When Cystatin C- and Creatinine-Based Estimates Are Discrepant in Older Adults.

Rationale & Objective: Serum creatinine and cystatin C are used to estimate glomerular filtration rate, but creatinine-based estimated glomerular filtration rate (eGFRcr), cystatin C-based estimated glomerular filtration rate (eGFRcys), and combined creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) are often divergent, particularly in older adults. We investigated which estimated glomerular filtration rate (eGFR) was more accurate and less biased compared with measured glomerular filtration rate (mGFR). Study Design: A diagnostic test study from the Berlin Initiative Study. Setting & Participants: The study population included 657 individuals aged 70 years or older with iohexol plasma clearance (mGFR) and serum creatinine and cystatin C measurements: 567 community-dwelling participants and 90 with a serum creatinine of ≥1.5 mg/dL. Tests Compared: We defined 3 groups on the basis of the difference eGFRcys - eGFRcr: whether < -5 mL/min/1.73 m2 (lower eGFRcys), within 5 mL/min/1.73 m2 (reference), or ≥ 5 mL/min/1.73 m2 (lower eGFRcr). eGFRcr, eGFRcys, and eGFRcr-cys were compared to mGFR to assess bias and accuracy. Outcome: Median bias (eGFR minus mGFR) with 95% CIs and accuracy (percentage of eGFR values within ±30% of mGFR). Results: The mean ± standard deviation age was 78 ± 6 years; the mean eGFRcys, eGFRcr, and eGFRcr-cys were 59 ± 23, 64 ± 20, and 61 ± 22 mL/min/1.73 m2, respectively, and the mean mGFR was 56 ± 19 mL/min. Half of the participants were in the lower eGFRcys group (n=337, 51%). Among them, the median bias for eGFRcys was the lowest (median bias, -2.7; 95% CI, -3.8 to -1.9) compared with the other eGFR equations. Conversely, in the lower eGFRcr group (n=121, 18%), the median bias for eGFRcr was the lowest compared with those for eGFRcys and eGFRcr-cys (2.9; [95% CI, 0.9-4.8] vs 13.8 [95% CI, 11.4-15.6] and 9.5 [95% CI, 7.7-11.0], respectively). Accuracy (percentage of eGFR values within ±30% of mGFR) was 93% for eGFRcr in the lower eGFRcr group and 92% for eGFRcys and 94% for eGFRcr-cys in the lower eGFRcys group. Limitations: Untested generalizability in younger populations. Conclusions: Among older adults, the lower eGFR between eGFRcys and eGFRcr was a more accurate and less biased estimate of mGFR when comparing the groups.

Anaphylaxis From Ethylene Oxide-Sterilized Dialysis Tubing and Needles: A Case Report.

Hypersensitivity reactions to ethylene oxide-sterilized dialyzers have been well described. Although ethylene oxide is no longer used to sterilize most dialyzers, it is used on other pieces of dialysis equipment. We present a case of a 78-year-old man who experienced dialysis-related anaphylaxis attributed to an IgE-mediated allergy to dialysis tubing and needles sterilized with ethylene oxide. Shortly after transitioning from a tunneled catheter to an arteriovenous fistula, he developed multiple episodes of intradialytic hypotension and syncope within minutes of starting dialysis. Laboratory evaluation revealed marked leukocytosis, eosinophilia, and elevated anti-ethylene oxide IgE antibody. After pretreatment with corticosteroids and antihistamines, the rinsing of dialysis tubing, and transition of access back to a tunneled catheter, he tolerated subsequent dialysis treatments. Review of his history revealed chronic eosinophilia since the time of hemodialysis initiation. We hypothesize his eosinophilia and mast cell degranulation began upon initial exposure to ethylene oxide and hemodialysis equipment. When use of the arteriovenous fistula was resumed, he was exposed to a higher "dose" of ethylene oxide due to the use of needles. The higher antigenic stimuli triggered a memory immune response, leading to mast cell degranulation and repeated anaphylactic episodes that were overcome by minimization of ethylene oxide-sterilized equipment, corticosteroid pretreatment, and the anti-IgE Fc monoclonal omalizumab.

Advantages, Limitations, and Clinical Considerations in Using Cystatin C to Estimate GFR.

Cystatin C has been shown to be a reliable and accurate marker of kidney function across diverse populations. The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommended using cystatin C to confirm the diagnosis of chronic kidney disease (CKD) determined by creatinine-based estimated glomerular filtration rate (eGFR) and to estimate kidney function when accurate eGFR estimates are needed for clinical decision-making. In the efforts to remove race from eGFR calculations in the United States, the National Kidney Foundation (NKF) and American Society of Nephrology (ASN) Joint Task Force recommended increasing availability and clinical adoption of cystatin C to assess kidney function. This review summarizes the key advantages and limitations of cystatin C use in clinical practice. Our goals were to review and discuss the literature on cystatin C; understand the evidence behind the recommendations for its use as a marker of kidney function to diagnose CKD and risk stratify patients for adverse outcomes; discuss the challenges of its use in clinical practice; and guide clinicians on its interpretation.

Improving chronic kidney disease detection and treatment in the United States: the chronic kidney disease cascade of care (C3) study protocol.

BACKGROUND: There are major gaps in the implementation of guideline-concordant care for persons with chronic kidney disease (CKD). The CKD Cascade of Care (C3) initiative seeks to improve CKD care by improving detection and treatment of CKD in primary care. METHODS: C3 is a multi-modal initiative deployed in three major academic medical centers within the Department of Veterans Affairs (VA) Health Care System: San Francisco VA, San Diego VA, and Houston VA. The main objective of the first phase of C3 described in this protocol is to establish the infrastructure for universal CKD detection among primary care patients at high-risk for CKD with a triple-marker screen comprising cystatin C, creatinine, and albuminuria. Across the three sites, a comprehensive educational intervention and the integration of primary care-based clinical champions will be employed with the goal of improving CKD detection and treatment. The San Francisco VA will also implement a practice-facilitation intervention leveraging telehealth and health informatics tools and capabilities for enhanced CKD detection. Parallel formative evaluation across the three sites will assess the feasibility and acceptability of integrating cystatin C as part of routine CKD detection in primary care practice. The effectiveness of the interventions will be assessed using a pre-post observational design for change in the proportion of patients tested annually for CKD. Secondary outcomes will assess change in the initiation of cardio-kidney protective therapies and in nephrology referrals of high-risk patients. DISCUSSION: The first phase of C3 is a multi-facility multi-modal initiative that aims to improve CKD care by implementing a triple-marker screen for enhanced CKD detection in primary care.

Association of Intra-individual Differences in Estimated GFR by Creatinine Versus Cystatin C With Incident Heart Failure.

RATIONALE & OBJECTIVE: Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFRcys) and creatinine (eGFRcr) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Difference in GFR estimates (eGFRdiff; ie, eGFRcys minus eGFRcr). OUTCOME: Incident HF hospitalization. ANALYTICAL APPROACH: Fine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFRdiff with incident HF. RESULTS: Of 4,512 participants, one-third had eGFRcys and eGFRcr values that differed by over 15 mL/min/1.73 m2. In multivariable-adjusted models, each 15 mL/min/1.73 m2 lower baseline eGFRdiff was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFRdiff less than -15 mL/min/1.73 m2 had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFRdiff ≥15 mL/min/1.73 m2 had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFRcys and eGFRcr. Participants with faster declines in eGFRcys relative to eGFRcr had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFRcys and eGFRcr declined in parallel. LIMITATIONS: Entry into the CRIC Study was determined by eGFRcr, which constrained the range of baseline eGFRcr-but not eGFRcys-values. CONCLUSIONS: Among persons with CKD who have large differences between eGFRcys and eGFRcr, risk for incident HF is more strongly associated with eGFRcys. Diverging slopes between eGFRcys and eGFRcr over time are also independently associated with risk of incident HF.

Cystatin C- and Creatinine-Based Glomerular Filtration Rate Estimation Differences and Muscle Quantity and Functional Status in Older Adults: The Health, Aging, and Body Composition Study.

Rationale & Objective: The difference in the estimated glomerular filtration rate based on cystatin C and that based on creatinine (eGFRDiff) is known to be associated with frailty and mortality. Creatinine is influenced by muscle mass, more so than cystatin C; we aimed to determine whether eGFRDiff is associated with muscle quantity and to what extent muscle quantity explains the relationship between eGFRDiff and poor functional status. Study Design: A cohort analysis of the health, aging, and body composition study (HABC). Setting & Participants: Overall, 2,970 HABC participants had their baseline serum creatinine level, cystatin C level, and body composition measured using imaging. Exposure: Estimated glomerular filtration rates (eGFRs) were calculated using Chronic Kidney Disease Epidemiology Collaboration equations (estimated glomerular filtration rate based on cystatin C [eGFRCys] and estimated glomerular filtration rate based on creatinine [eGFRCr]), and eGFRDiff was calculated as eGFRCys - eGFRCr. Outcomes: The total thigh muscle area was evaluated using computed tomography. The health, aging, and body composition study physical performance battery was scored on a continuous scale (standing and walking tasks); poor functional status was characterized by the lowest quartile. Analytical Approach: We used linear regression to model the cross-sectional association of eGFRDiff and muscle measures. We used logistic regression to evaluate the association of eGFRDiff with poor functional status. Results: The mean age was 74 ± 3 years; the eGFRCys, eGFRCr, and eGFRDiff was 72 ± 18, 68 ± 15, and 4 ± 14 mL/min/1.73 m2, respectively. Compared with participants in the reference group (-10 < eGFRDiff ≤ 10 mL/min/1.73 m2), those in the negative eGFRDiff group (≤-10 mL/min/1.73 m2) were more likely to have comorbidities, a slower gait, and worse functional status. They had an approximately 14-cm2 smaller thigh muscle area in a fully adjusted model. Compared with the reference group, those in the negative group had 1.89-fold higher odds of poor functional status (unadjusted). This relationship was minimally attenuated after adjustment for thigh muscle, thigh fat area, appendicular lean mass, and limb fat mass, both individually and in combination. Limitations: The functional status outcome was specific to HABC. The muscle measures did not capture dynamic turnover. Conclusions: The difference of eGFRCys - eGFRCr provides information on older adults' functional status, which is only partially explained by muscle quantity and quality.

Association of Intraindividual Difference in Estimated Glomerular Filtration Rate by Creatinine vs Cystatin C and End-stage Kidney Disease and Mortality.

Importance: As cystatin C is increasingly adopted to estimate glomerular filtration rate (eGFR), clinicians will encounter patients in whom cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) differ widely. The clinical implications of these differences, eGFRdiffcys-cr, are unknown. Objective: To evaluate the associations of eGFRdiffcys-cr with end-stage kidney disease (ESKD) and mortality among individuals with chronic kidney disease (CKD). Design, Setting, and Participants: This is a prospective cohort study of 4956 individuals with mild to moderate CKD from 7 clinical centers in the United States who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 to 2018. Statistical analyses were completed in December 2021. Exposures: eGFRdiffcys-cr (eGFRcys - eGFRcr) was calculated at baseline and annually thereafter for 3 years. Because 15 mL/min/1.73 m2 represents a clinically meaningful difference in eGFR that also distinguishes CKD stages, eGFRdiffcys-cr was categorized as: less than -15 mL/min/1.73 m2, -15 to 15 mL/min/1.73 m2, and 15 mL/min/1.73 m2 or greater. Main Outcomes and Measures: The outcomes of ESKD, defined as initiation of maintenance dialysis or receipt of a kidney transplant, and all-cause mortality were adjudicated from study entry until administrative censoring in 2018. Results: Among 4956 participants with mean (SD) age of 59.5 (10.5) years, 2152 (43.4%) were Black, 515 (10.4%) were Hispanic, and 2113 (42.6%) were White. There were 2156 (43.5%) women and 2800 (56.5%) men. At baseline, eGFRcys and eGFRcr values differed by more than 15 mL/min/1.73 m2 in one-third of participants (1638 participants [33.1%]). Compared with participants with similar baseline eGFRcys and eGFRcr (eGFRdiffcys-cr -15 to 15 mL/min/1.73 m2), those in whom eGFRcys was substantially lower than eGFRcr (eGFRdiffcys-cr < -15 mL/min/1.73 m2) had a higher risk of mortality (hazard ratio [HR], 1.86; 95% CI, 1.40-2.48) while those with eGFRdiffcys-cr of 15 mL/min/1.73 m2 or greater had lower risks of ESKD (subHR [SHR], 0.73; 95% CI, 0.59-0.89) and mortality (HR, 0.68; 95% CI, CI 0.58-0.81). In time-updated analyses, participants with eGFRdiffcys-cr less than -15 mL/min/1.73 m2 had higher risks of ESKD (SHR, 1.83; 95% CI, 1.10-3.04) and mortality (HR, 3.03; 95% CI, 2.19-4.19) compared with participants with similar eGFRcys and eGFRcr. Conversely, participants with eGFRdiffcys-cr of 15 mL/min/1.73 m2 or greater had lower risks of ESKD (SHR, 0.50; 95% CI, 0.35-0.71) and mortality (HR, 0.58; 95% CI, 0.45-0.75). Longitudinal changes in eGFRdiffcys-cr were associated with mortality risk. Compared with participants who had similar slopes by eGFRcys and eGFRcr, those with smaller eGFRcr declines had an 8-fold increased mortality risk (HR, 8.20; 95% CI, 6.37-10.56), and those with larger apparent declines by eGFRcr had a lower mortality risk (HR, 0.14; 95% CI, 0.08-0.24). Conclusions and Relevance: These findings suggest that large differences between eGFRcys and eGFRcr were common in persons with CKD. These differences and their changes over time may be informative of ESKD and mortality risks, warranting monitoring of both eGFRcys and eGFRcr in this high-risk population.

Relationship of Kidney Tubule Biomarkers with Cognition among Community-Living Elders in the Health ABC Study.

Higher baseline urinary neutrophil gelatinase-associated lipocalin was associated with worse cognitive scores at baseline.Lower concentrations of baseline serum bicarbonate (higher is better) were associated with lower cognitive scores at baseline.We found no associations with urine markers with longitudinal changes in cognition.

Marathon Runners' Knowledge and Strategies for Hydration.

OBJECTIVE: To study hydration plans and understanding of exercise-associated hyponatremia (EAH) among current marathon runners. DESIGN: Cross-sectional study. SETTING: Southern California 2018 summer marathon. PARTICIPANTS: Two hundred ten marathon runners. INTERVENTIONS: Survey administered 1 to 2 days before the race. Race times were obtained from public race website. MAIN OUTCOME MEASURES: Planned frequency of hydration; awareness of, understanding of, and preventative strategies for dehydration and EAH; resources used to create hydration plans; drink preferences. RESULTS: When the participants were split into 3 equal groups by racing speed, the slower tertile intended to drink at every mile/station (60%), whereas the faster tertile preferred to drink every other mile or less often (60%), although not statistically significant. Most runners (84%) claimed awareness of EAH, but only 32% could list a symptom of the condition. Both experienced marathoners and the faster tertile significantly had greater understanding of hyponatremia compared with first-time marathoners and the slower tertile, respectively. Less than 5% of marathoners offered "drink to thirst" as a prevention strategy for dehydration or EAH. CONCLUSION: Slower runners plan to drink larger volumes compared with their faster counterparts. Both slower and first-time marathoners significantly lacked understanding of EAH. These groups have plans and knowledge that may put them at higher risk for developing EAH. Most marathon runners did not know of the guidelines to "drink to thirst," suggesting the 2015 EAH Consensus statement may not have had the desired impact.

Physicians' Recognition and Management of Kidney Disease: A Randomized Vignette Study Evaluating the Impact of the KDIGO 2012 CKD Classification System.

RATIONALE & OBJECTIVE: The Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) classification systems published in 2002 and 2012, respectively, are recommended worldwide and based on strong epidemiologic data. However, their impact on CKD recognition and management is not well evaluated in clinical practice, and we therefore investigated whether they help physicians recognize and appropriately care for patients with CKD. STUDY DESIGN: Randomized vignette experiment with fractional factorial design based on 6 kidney-related scenarios and 3 laboratory presentation methods reflecting the CKD guidelines. Participants evaluated 1 of 3 subsets of the 18 vignettes (ie, 6 vignettes each with 4 answer alternatives). SETTING & PARTICIPANTS: 249 interns, general practitioners, and residents/fellows attending postgraduate meetings and courses in Norway and the United States. INTERVENTION: Kidney-related results (serum creatinine level and urinary albumin excretion) were presented as the "minimal data" (high/low levels), KDOQI-2002 (estimated glomerular filtration rate [eGFR] reported automatically), or KDIGO-2012 (eGFR + albuminuria categorization + risk for complications) laboratory report. OUTCOME: CKD management choice by physicians. RESULTS: When kidney laboratory data were presented as the KDOQI-2002 report (automatic eGFR calculation), there was a significantly higher odds for correct patient management decisions compared with the minimal data report (OR, 1.57; P < 0.001). Additional significant improvement was obtained with the KDIGO-2012 report (OR, 2.28 for correct answer vs minimal data report [P < 0.001]; OR, 1.45 compared to KDOQI-2002 report [P = 0.005]). The KDIGO classification system improved physician management in 4 of the 6 clinical scenarios covering a wide range of kidney-related topics. Interaction analysis showed that general practitioners and those with 1 to 3 years of internal medicine experience had the greatest improvements with the new presentation techniques. LIMITATIONS: Physicians' management was evaluated by theoretical scenarios rather than direct patient care. CONCLUSIONS: Automatic GFR estimation, albuminuria categorization, and notification of the associated risk for complications improve most physicians` recognition and management of a wide range of CKD clinical scenarios.

The Difference Between Cystatin C- and Creatinine-Based Estimated GFR and Associations With Frailty and Adverse Outcomes: A Cohort Analysis of the Systolic Blood Pressure Intervention Trial (SPRINT).

RATIONALE & OBJECTIVE: In prior research and in practice, the difference between estimated glomerular filtration rate (eGFR) calculated from cystatin C level and eGFR calculated from creatinine level has not been assessed for clinical significance and relevance. We evaluated whether these differences contain important information about frailty. STUDY DESIGN: A cohort analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: 9,092 hypertensive SPRINT participants who had baseline measurements of serum creatinine, cystatin C, and frailty. EXPOSURE: eGFRs calculated using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (eGFRcys and eGFRcr), and eGFRDiff, calculated as eGFRcys-eGFRcr. OUTCOMES: A validated 35-item frailty index that included questionnaire data for general and physical health, limitations of activities, pain, depression, sleep, energy level, self-care, and smoking status, as well as medical history, cognitive assessment, and laboratory data. We defined frailty as frailty index score>0.21 (range, 0-1). The incidence of injurious falls, hospitalizations, cardiovascular events, and mortality was also recorded. ANALYTICAL APPROACH: We used logistic regression to model the cross-sectional association of baseline eGFRDiff with frailty among all SPRINT participants. Adjusted proportional hazards regression was used to evaluate the association of eGFRDiff with adverse outcomes and mortality. RESULTS: Mean age was 68±9 (SD) years, mean eGFRcys and eGFRcr were 73±23 and 72±20mL/min/1.73m2, and mean eGFRDiff was 0.5±15mL/min/1.73m2. In adjusted models, each 1-SD higher eGFRDiff was associated with 24% lower odds of prevalent frailty (OR, 0.76; 95% CI, 0.71-0.81), as well as with lower incidence rate of injurious falls (HR, 0.84; 95% CI, 0.77-0.92), hospitalization (HR, 0.91; 95% CI, 0.88-0.95), cardiovascular events (HR, 0.89; 95% CI, 0.81-0.97), and all-cause mortality (HR, 0.71; 95% CI, 0.63-0.82); P<0.01. LIMITATIONS: Gold-standard measure of kidney function and assessment of muscle mass were not available. CONCLUSIONS: The difference between eGFRcys and eGFRcr is associated with frailty and health status. Positive eGFRDiff is strongly associated with lower risks for longitudinal adverse outcomes and mortality, even after adjusting for chronic kidney disease stage and baseline frailty.

Implementing the European Renal Best Practice Guidelines suggests that prediction equations work well to differentiate risk of end-stage renal disease vs. death in older patients with low estimated glomerular filtration rate.

Recent European guidelines suggest using the kidney failure risk equation (KFRE) and mortality risk equation for kidney disease (MREK) to guide decisions on whether elderly patients with chronic kidney disease should be referred early for dialysis preparation. However, the concurrent use of the two risk equations has not been validated. To do so we evaluated 1,188 individuals over five years with estimated glomerular filtration rate (eGFR) under 45ml/min/1.73m2 and age over 65 years from the Norwegian population based HUNT study. Forty-two patients started renal replacement therapy and 462 died as their first clinical event. The KFRE was well calibrated (mean risk estimate 4.9% vs observed 3.5%) with high diagnostic accuracy (C-statistics 0.93). The MREK underestimated death risk in those with lower risk (mean risk estimate 30.1% vs observed 38.9%) and had moderate diagnostic accuracy (C-statistics 0.71). Only 31 individuals had estimated end stage kidney disease (ESRD) risk greater than death risk, and most experienced ESRD before death. Only two of 598 patients over 80 years old, and ten of 1,063 with eGFR 25-45ml/min/1.73m2 at baseline experienced ESRD. Decision curve analysis demonstrated that for risk adverse patients, deferring ESRD preparation may be appropriate until predicted ESRD risk exceeds predicted death risk. For those preferring a more aggressive approach, referral when eGFR is under 25 ml/min/1.73m2 may be beneficial if age remains under 80 years. Thus, the risk of ESRD is low compared to the risk of death in many older patients with chronic kidney disease stage 3b or worse, and combination of predicted ESRD and death risks, eGFR levels, age, and the patient`s valuations of harm and benefit can be helpful for deciding when to start dialysis preparations.

The association of the ankle-brachial index, the toe-brachial index, and their difference, with mortality and limb outcomes in dialysis patients.

INTRODUCTION: The ankle-brachial index (ABI) is the most common test to diagnose peripheral artery disease (PAD). In dialysis patients, the ABI may under-diagnose PAD, due to a high prevalence of concomitant medial arterial calcification (MAC). The toe-brachial index (TBI) is not as susceptible to misclassification by MAC. Taking the ABI and TBI together in the form of their difference, the ABI-TBI, may provide a single measure for assessing both atherosclerosis and calcification. The relationship of these variables in dialysis patients has not been well studied. METHODS: We identified 37 dialysis patients referred for vascular studies between 2009 and 2017 in the San Diego Veterans Administration Medical Center (SDVAMC). The ABI and TBI were performed systematically for each patient, and TBI was performed regardless of ABI or waveform. We examined associations between ABI, TBI, and the difference between them (ABI-TBI) with all-cause mortality and major adverse limb events (MALE), which includes revascularizations and amputations. FINDINGS: The mean age was 65 years and 30% were African American. All patients were men, reflecting the Veterans Administration population. There were 26 deaths during follow-up and mortality was highest in patients who had low ABI and low TBI and least in those with high ABI and high TBI. Persons with TBI < 0.7 had an increased risk of all-cause mortality. The ABI-TBI, and the ABI itself, were not significantly associated with all-cause mortality although the patterns were similar. DISCUSSION: Although ABI may be an important initial risk stratification tool, the TBI may be a more informative predictor of mortality in dialysis patients. Strengths of this study include a high rate of MALE and deaths. The TBI, and the difference between ABI and TBI, should be studied further in a larger cohort of persons with advanced kidney disease.

Patients,' Nephrologists,' and Predicted Estimations of ESKD Risk Compared with 2-Year Incidence of ESKD.

BACKGROUND AND OBJECTIVES: The rate of progression to ESKD is variable, and prognostic information helps patients and physicians plan for future ESKD. We assessed the estimations of ESKD risk of patients with CKD and physicians and compared them with risk calculators and outcomes at 2 years. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This prospective observational study assessed 257 adult patients with CKD stages 3-5 and their nephrologists at University of California, San Diego and Veterans Affairs San Diego CKD clinics. Patients' and nephrologists' estimations of 2-year ESKD risk were evaluated, and objective estimation of 2-year risk was determined using kidney failure risk equations; actual incidence rates of ESKD and death were ascertained by chart review. Participants' baseline characteristics were compared across kidney failure risk equation risk levels and according to whether patients' estimations were more optimistic or pessimistic than physicians' estimations. We examined correlations between estimations and compared estimations with outcomes using c statistics and calibration plots. RESULTS: Average age was 65 (±13) years old, and eGFR was 34 (±13) ml/min per 1.73 m2. Overall, 13% reached ESKD, and 9% died. About one quarter of patients gave estimates that were >20% more optimistic than physicians, and more than one in ten gave estimates that were >20% more pessimistic. Physicians' and kidney failure risk equation estimations had the strongest correlation (r=0.72; P<0.001) compared with 0.50 (P<0.001) between physicians and patients and 0.47 (P<0.001) between patients and kidney failure risk equation. Although all three estimations provided reasonable risk rankings (c statistics >0.8), physicians and patients overestimated risk compared with actual outcomes; no patient whose physician estimated a risk of ESKD <15% reached ESKD at 2 years. The kidney failure risk equation was best calibrated to actual ESKD risk. CONCLUSIONS: Compared with actual ESKD incidence, the kidney failure risk equation outperformed patients' and physicians' estimations of ESKD incidence. Patients and physicians overestimated risk compared with the kidney failure risk equation.