Glomerular Filtration Rate Estimation Using ß2-Microglobulin and ß-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study.

RATIONALE & OBJECTIVE: ß2-Microglobulin (B2M) and ß-trace protein (BTP) are novel endogenous filtration markers that may improve the accuracy of estimated glomerular filtration rate (eGFR) beyond creatinine and cystatin C (eGFRcr-cys), but they have not been assessed in patients with cancer. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Prospective cohort of 1,200 patients with active solid tumors recruited between April 2015 and September 2017. EXPOSURE: CKD-EPI equations without race combining B2M and/or BTP with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR). OUTCOME: Performance of equations compared with eGFRcr-cys and non-GFR determinants of serum B2M and BTP (SB2M, and SBTP, respectively). Measured GFR (mGFR) was determined using the plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA). ANALYTICAL APPROACH: Bias was defined as the median of the differences between mGFR and eGFR, and 1-P30 was defined as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). Linear regression was used to assess association of clinical and laboratory variables with SB2M, and SBTP after adjustment for mGFR. RESULTS: Mean age and mGFR were 58.8±13.2 SD years and 78.4±21.7 SD mL/min/1.73m2, respectively. Performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys (lesser bias and 1-P30). Performance of 2-marker panel equations was as good as eGFRcr-cys (lesser bias and similar 1-P30). SB2M and SBTP were not strongly influenced by cancer site. LIMITATIONS: Participants may have had better clinical performance status than the general population of patients with solid tumors. CONCLUSIONS: B2M and BTP can improve the accuracy of eGFR and may be useful as confirmatory tests in patients with solid tumors, either by inclusion in a multimarker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine. PLAIN-LANGUAGE SUMMARY: The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys). We studied whether using ß2-microglobulin (B2M) and/or ß-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys. Performance of 2-marker panel equations was as good as eGFRcr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

CKD-EPI and EKFC GFR Estimating Equations: Performance and Other Considerations for Selecting Equations for Implementation in Adults.

SIGNIFICANCE STATEMENT: New eGFR equations from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) using creatinine (eGFRcr), cystatin C (eGFRcys), and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice, leading to uncertainty in selecting equations for implementation. The authors evaluated performance of equations in an independent population of 4050 adults and evaluated other considerations important for implementation. They found that CKD-EPI and EKFC equations are approaching convergence, with better performance of eGFRcr-cys equations in the overall group and fewer differences among race, sex, and age subgroups than eGFRcr equations. Larger differences among eGFRcr equations reflect regional population differences in creatinine, forcing a trade-off between accuracy and uniformity in global implementation of eGFRcr equations. More widespread use of cystatin C could avoid this trade-off. BACKGROUND: New CKD-EPI and EKFC eGFR equations using eGFRcr, eGFRcys, and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice. A better understanding of the equations, including their performance in race, sex and age subgroups, is important for selection of eGFR equations for global implementation. METHODS: We evaluated performance (bias and P 30 ) of equations and methods used for equation development in an independent study population comprising 4050 adults pooled from 12 studies. The mean (SD) measured GFR was 76.4 (29.6) ml/min per 1.73 m 2 and age 57.0 (17.4) years, with 1557 (38%) women and 579 (14%) Black participants. RESULTS: Coefficients for creatinine, cystatin C, age, and sex in the CKD-EPI and EKFC equations are similar. Performance of the eGFRcr-cys equations in the overall population (bias <±5 ml/min per 1.73 m 2 and P 30 >90%) was better than the eGFRcr or eGFRcys equations, with fewer differences among race, sex, and age subgroups. Differences in performance across subgroups reflected differences in diversity of source populations and use of variables for race and sex for equation development. Larger differences among eGFRcr equations reflected regional population differences in non-GFR determinants of creatinine. CONCLUSION: CKD-EPI and EKFC equations are approaching convergence. It is not possible to maximize both accuracy and uniformity in selecting one of the currently available eGFRcr equations for implementation across regions. Decisions should consider methods for equation development in addition to performance. Wider use of cystatin C with creatinine could maximize both accuracy and uniformity of GFR estimation using currently available equations.

A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumors.

Current guidelines recommend estimating glomerular filtration rate (eGFR) using creatinine (eGFRcr) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation as the first test for GFR evaluation, but the Cockcroft-Gault (CG) equation is still commonly used in oncology practice and clinical trials despite increasing evidence of its inaccuracy compared to measured GFR (mGFR). Guidelines recommend eGFR using cystatin C (eGFRcys) or both markers (eGFRcr-cys) as a confirmatory test, but neither was carefully evaluated in cancer patients. Therefore, we compared performance of the CKD-EPI equations and others to the CG equation in adults with a variety of solid tumors. The mGFR was determined by plasma clearance of 51Cr-EDTA. Bias was defined as the median of the differences between mGFR and eGFR while accuracy was defined as the percentage of estimates that differed by more than 30% from the measured GFR (1-P30). We prospectively recruited 1,200 patients between April 2015 and September 2017 with a mean age and mGFR of 58.8 years and 78.4 ml/min/1.73m2, respectively. Bias among eGFRcr equations varied from -8.1 to +6.1 ml/min/1.73 m2. CG was the least accurate, 1-P30 (95% confidence interval) was 24.9 (22.4- 27.3)%; CKD-EPI had 1-P30 of 19.1 (16.8-21.2)% while eGFRcr-cys had the best performance: bias -2.0 (-2.6 to -1.1) ml/min/1.73m2 and 1-P30 7.8 (6.3-9.4)%. Thus, the CG equation should not be preferred over CKD-EPI equation, and eGFRcr-cys can be used as a confirmatory test in adults with solid tumors. Hence, a major policy implication would be to adopt general practice guideline-recommended methods for GFR evaluation in oncology practice and clinical trials.

Hypoalbuminemia Is Associated with Increased 30-Day Complications following Rectourethral Fistula Repair: A National Surgical Quality Improvement Program Study.

INTRODUCTION: We sought to assess patient risk factors for 30-day postoperative complications among men undergoing surgical management of rectourethral fistula (RUF). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all male patients who underwent RUF repair (2006-2018). Hypoalbuminemia was defined as preoperative serum albumin <3.5 gm/dL. Postoperative 30-day complications included wound infection, organ space surgical site infection, urinary tract infection, sepsis, venous thromboembolism, pneumonia, cerebrovascular accident, myocardial infarction, return to operating room and mortality. The association between pre-selected patient covariates and postoperative complications was investigated using logistic regression analysis. RESULTS: A total of 250 patients were identified. Concurrent procedures during RUF repair were bowel diversion in 43/250 patients (17.2%), bowel resection (34/250, 13.6%), cystectomy (20/250, 8.0%) and urethroplasty (37/250, 14.8%). Overall, median age was 66.0 years (IQR 59.0-72.0), body mass index 26.6 kg/m2 (IQR 23.7-29.5) and 247/250 patients (98.8%) were functionally independent. Comorbidities included hypertension (140/250, 56.0%), smoking (55/250, 22.0%), diabetes (17/250, 6.8%), chronic obstructive pulmonary disease (11/250, 4.4%) and congestive heart failure (1/250, 0.4%). Hypoalbuminemia (<3.5 gm/dL) was present in 25/126 patients (19.8%). Overall, 51/250 patients (20.4%) experienced a complication within 30 days of surgery including wound infection (14/250, 5.6%), sepsis (13/250, 5.2%), organ space infection (11/250, 4.4%), urinary tract infection (8/250, 3.2%), venous thromboembolism (8/250, 3.2%) and mortality (5/250, 2.0%). After adjusting for covariates, hypoalbuminemia was associated with increased odds of a 30-day complication (OR 2.49, 95% CI 1.06-5.86, p=0.036). CONCLUSIONS: Hypoalbuminemia was associated with increased odds of short-term complications after surgical management of RUF.

New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race.

BACKGROUND: Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct. METHODS: We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations. RESULTS: In the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m2; 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m2; 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m2; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m2; 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks. CONCLUSIONS: New eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

A New Panel-Estimated GFR, Including ß2-Microglobulin and ß-Trace Protein and Not Including Race, Developed in a Diverse Population.

RATIONALE AND OBJECTIVE: Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-cys requires specification of a person's race. ß2-Microglobulin (B2M) and ß-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is. STUDY DESIGN: Study of diagnostic test accuracy. SETTING AND PARTICIPANTS: Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants. TESTS COMPARED: Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race. OUTCOMES: GFR measured as the urinary clearance of iothalamate, plasma clearance of iohexol, or plasma clearance of [51Cr]EDTA. RESULTS: Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m2, and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFRcys (percentage of estimates greater than 30% different from measured GFR [1 - P30] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFRcr-cys (1 - P30 of 8.6% vs 9.4%; P = 0.2). Results were generally consistent across subgroups. LIMITATIONS: No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe. CONCLUSIONS: The 4-marker panel eGFR is as accurate as eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

Evaluation of Screening Tests for Cognitive Impairment in Patients Receiving Maintenance Hemodialysis.

BACKGROUND: Neurocognitive testing shows that cognitive impairment is common among patients receiving maintenance hemodialysis. Identification of a well performing screening test for cognitive impairment might allow for broader assessment in dialysis facilities and thus optimal delivery of education and medical management. METHODS: From 2015 to 2018, in a cohort of 150 patients on hemodialysis, we performed a set of comprehensive neurocognitive tests that included the cognitive domains of memory, attention, and executive function to classify whether participants had normal cognitive function versus mild, moderate, or severe cognitive impairment. Using area-under-the-curve (AUC) analysis, we then examined the predictive ability of the Mini Mental State Examination, the Modified Mini Mental State Examination, the Montreal Cognitive Assessment, the Trail Making Test Part B, the Mini-Cog test, and the Digit Symbol Substitution Test, determining each test's performance for identifying severe cognitive impairment. RESULTS: Mean age was 64 years; 61% were men, 39% were black, and 94% had at least a high-school education. Of the 150 participants, 21% had normal cognitive function, 17% had mild cognitive impairment, 33% had moderate impairment, and 29% had severe impairment. The Montreal Cognitive Assessment had the highest overall predictive ability for severe cognitive impairment (AUC, 0.81); a score of ≤21 had a sensitivity of 86% and specificity of 55% for severe impairment, with a negative predictive value of 91%. The Trails B and Digit Symbol tests also performed reasonably well (AUCs, 0.73 and 0.78, respectively). The other tests had lower predictive performances. CONCLUSIONS: The Montreal Cognitive Assessment, a widely available and brief cognitive screening tool, showed high sensitivity and moderate specificity in detecting severe cognitive impairment in patients on maintenance hemodialysis.

Estimating total small solute clearance in patients treated with continuous ambulatory peritoneal dialysis without urine and dialysate collection.

BACKGROUND: International Society for Peritoneal Dialysis guidelines recommend to routinely monitor the total measured clearance (mCl) of small solutes such as creatinine; however, collection of 24-h urine and peritoneal dialysis (PD) fluid is burdensome to patients and prone to errors. We hypothesized that equations could be developed to estimate mCl (estimated clearance (eCl)) using endogenous filtration markers. METHODS: In the Guangzhou PD Study (n = 980), we developed eCl equations using linear regression in two-third and validated them in the remaining one-third. Reference tests were mCl for urea nitrogen (UN) (mClUN, ml/min) and average mCl for UN and creatinine (mClUN-cr, ml/min/1.73 m2). Index tests were various eCl equations using UN, creatinine, low-molecular-weight proteins (LMWPs) (beta-trace protein (BTP), beta-2 microglobulin (B2M), and cystatin C), demographic variables, and body size. After reexpression of the equations in the combined data set, we analyzed accuracy (eCl within ± 2.0 units of mCl) and the predictive value of eCl to detect a weekly total standard Kt/V (weekly mClUN indexed for total body water) > 1.7 using receiver operating characteristic curve. RESULTS: Mean age of the cohort was 50 ± 15 years, 53% were male; mClUN was 6.9 ± 1.8 and mClUN-cr was 7.5 ± 2.8. Creatinine but not UN contributed to eCl for both mCl. LMWP did not improve accuracy for mClUN (range 88-89%). BTP and B2M improved the accuracy for mClUN-cr (82% vs. 80%); however, differences were small. The area under the curve for predicting a weekly Kt/V > 1.7 was similar for all equations (range 0.79-0.80). CONCLUSIONS: Total small solute clearance can be estimated moderately well in continuous ambulatory PD patients using serum creatinine and demographic variables without urine and dialysate collection.

Measured and estimated glomerular filtration rate: current status and future directions.

Evaluation of glomerular filtration rate (GFR) is central to the assessment of kidney function in medical practice, research and public health. Measured GFR (mGFR) remains the reference standard, but the past 20 years have seen major advances in estimated GFR (eGFR). Both eGFR and mGFR are associated with error compared with true GFR. eGFR is now recommended by clinical practice guidelines, regulatory agencies and public health agencies for the initial evaluation of GFR, with measured GFR (mGFR) typically considered an important confirmatory test, depending on how accurate the assessment of GFR needs to be for application to the clinical, research or public health setting. Our approach is to use initial and confirmatory tests as needed to develop a final assessment of true GFR. We suggest that GFR evaluation might be improved by more complete implementation of current recommendations and by further research to improve the accuracy of mGFR and eGFR.

Development and Validation of Residual Kidney Function Estimating Equations in Dialysis Patients.

RATIONALE & OBJECTIVE: Measurement of residual kidney function is recommended for the adjustment of the dialysis prescription, but timed urine collections are difficult and prone to errors. Equations to calculate residual kidney function from serum concentrations of endogenous filtration markers and demographic parameters would simplify monitoring of residual kidney function. However, few equations to estimate residual kidney function using serum concentrations of small solutes and low-molecular-weight proteins have been developed and externally validated. STUDY DESIGN: Study of diagnostic test accuracy. SETTING & PARTICIPANTS: 823 Chinese peritoneal dialysis (PD) patients (development cohort) and 826 PD and hemodialysis patients from the Netherlands NECOSAD study (validation cohort). TESTS COMPARED: Equations to estimate residual kidney function (estimated clearance [eCl]) using serum creatinine, urea nitrogen, cystatin C, ß2-microglobulin (B2M), ß-trace protein (BTP), and combinations, as well as demographic variables (age, sex, height, and weight). Equations were developed using multivariable linear regression analysis in the development cohort and then tested in the validation cohort. Equations were compared with published validated equations. OUTCOMES: Residual kidney function measured as urinary clearance (mCl) of urea nitrogen (mClUN) and average of creatinine and urea nitrogen clearance (mClUN-cr). RESULTS: In external validation, bias (difference between mCl and eCl) was within ± 1.0 unit for all equations. Accuracy (percent of differences within ± 2.0 units) was significantly better for eClBTP, eClB2M, and eClBTP-B2M than eClUN-cr for both mClUN (78%, 80%, and 81% vs 72%; P < 0.05 for all) and mClUN-cr (72%, 78%, and 79% vs 68%; P < 0.05 for all). The area under the curve for predicting mClUN > 2.0 mL/min was highest for eClB2M (0.853) and eClBTP-B2M (0.848). Results were similar for other validated equations. LIMITATIONS: Development cohort only consisted of PD patients, no gold-standard method for residual kidney function measurement. CONCLUSIONS: These results confirm the validity and extend the generalizability of residual kidney function estimating equations from serum concentrations of low-molecular-weight proteins without urine collection.

Albuminuria and Allograft Failure, Cardiovascular Disease Events, and All-Cause Death in Stable Kidney Transplant Recipients: A Cohort Analysis of the FAVORIT Trial.

RATIONALE & OBJECTIVE: Cardiovascular disease (CVD) is common and overall graft survival is suboptimal among kidney transplant recipients. Although albuminuria is a known risk factor for adverse outcomes among persons with native chronic kidney disease, the relationship of albuminuria with cardiovascular and kidney outcomes in transplant recipients is uncertain. STUDY DESIGN: Post hoc longitudinal cohort analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial. SETTING & PARTICIPANTS: Stable kidney transplant recipients with elevated homocysteine levels from 30 sites in the United States, Canada, and Brazil. PREDICTOR: Urine albumin-creatinine ratio (ACR) at randomization. OUTCOMES: Allograft failure, CVD, and all-cause death. ANALYTICAL APPROACH: Multivariable Cox models adjusted for age; sex; race; randomized treatment allocation; country; systolic and diastolic blood pressure; history of CVD, diabetes, and hypertension; smoking; cholesterol; body mass index; estimated glomerular filtration rate (eGFR); donor type; transplant vintage; medications; and immunosuppression. RESULTS: Among 3,511 participants with complete data, median ACR was 24 (Q1-Q3, 9-98) mg/g, mean eGFR was 49±18 (standard deviation) mL/min/1.73m2, mean age was 52±9 years, and median graft vintage was 4.1 (Q1-Q3, 1.7-7.4) years. There were 1,017 (29%) with ACR < 10mg/g, 912 (26%) with ACR of 10 to 29mg/g, 1,134 (32%) with ACR of 30 to 299mg/g, and 448 (13%) with ACR ≥ 300mg/g. During approximately 4 years, 282 allograft failure events, 497 CVD events, and 407 deaths occurred. Event rates were higher at both lower eGFRs and higher ACR. ACR of 30 to 299 and ≥300mg/g relative to ACR < 10mg/g were independently associated with graft failure (HRs of 3.40 [95% CI, 2.19-5.30] and 9.96 [95% CI, 6.35-15.62], respectively), CVD events (HRs of 1.25 [95% CI, 0.96-1.61] and 1.55 [95% CI, 1.13-2.11], respectively), and all-cause death (HRs of 1.65 [95% CI, 1.23-2.21] and 2.07 [95% CI, 1.46-2.94], respectively). LIMITATIONS: No data for rejection; single ACR assessment. CONCLUSIONS: In a large population of stable kidney transplant recipients, elevated baseline ACR is independently associated with allograft failure, CVD, and death. Future studies are needed to evaluate whether reducing albuminuria improves these outcomes.

Unique metabolomic signature associated with hepatorenal dysfunction and mortality in cirrhosis.

The application of nontargeted metabolomic profiling has recently become a powerful noninvasive tool to discover new clinical biomarkers. This study aimed to identify metabolic pathways that could be exploited for prognostic and therapeutic purposes in hepatorenal dysfunction in cirrhosis. One hundred three subjects with cirrhosis had glomerular filtration rate (GFR) measured using iothalamate plasma clearance, and were followed until death, transplantation, or the last encounter. Concomitantly, plasma metabolomic profiling was performed using ultrahigh performance liquid chromatography-tandem mass spectrometry to identify preliminary metabolomic biomarker candidates. Among the 1028 metabolites identified, 34 were significantly increased in subjects with high liver and kidney disease severity compared with those with low liver and kidney disease severity. The highest average fold-change (2.39) was for 4-acetamidobutanoate. Metabolite-based enriched pathways were significantly associated with the identified metabolomic signature (P values ranged from 2.07E-06 to 0.02919). Ascorbate and aldarate metabolism, methylation, and glucuronidation were among the most significant protein-based enriched pathways associated with this metabolomic signature (P values ranged from 1.09E-18 to 7.61E-05). Erythronate had the highest association with measured GFR (R-square = 0.571, P <0.0001). Erythronate (R = 0.594, P <0.0001) and N6-carbamoylthreonyladenosine (R = 0.591, P <0.0001) showed stronger associations with measured GFR compared with creatinine (R = 0.588, P <0.0001) even after controlling for age, gender, and race. The 5 most significant metabolites that predicted mortality independent of kidney disease and demographics were S-adenosylhomocysteine (P = 0.0003), glucuronate (P = 0.0006), trans-aconitate (P = 0.0018), 3-ureidopropionate (P = 0.0021), and 3-(4-hydroxyphenyl)lactate (P = 0.0047). A unique metabolomic signature associated with hepatorenal dysfunction in cirrhosis was identified for further investigations that provide potentially important mechanistic insights into cirrhosis-altered metabolism.

Performance of glomerular filtration rate estimating equations in a community-based sample of Blacks and Whites: the multiethnic study of atherosclerosis.

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are recommended for glomerular filtration rate (GFR) estimation in the general population. They have not been evaluated in community-based populations, including Blacks at higher levels of GFR, but are commonly applied in such populations. Methods: In an ancillary study of Multi-Ethnic Study of Atherosclerosis conducted at one site, we evaluated the performance of the CKD-EPI equations for creatinine (eGFRcr), cystatin C (eGFRcys) or the combination (eGFRcr-cys) compared with GFR measured as plasma clearance of iohexol. Results: Among 294 participants, the mean age was 71 (SD 9) years, 47% were Black, 48% were women and the mean measured GFR (mGFR) was 72.6 (SD 18.8) mL/min/1.73 m2. The CKD-EPI equations overestimated mGFR with a larger median bias for eGFRcr and eGFRcr-cys than eGFRcys [-8.3 (95% confidence interval -9.7, -6.5), -7.8 (-9.2, -6.2) and -3.7 (-5.0, -1.8) mL/min/1.73 m2, respectively], with smaller bias for those with lower compared with higher eGFR and by race compared with sex. Conclusion: The small differential bias of the CKD-EPI equation between races suggests that they can be used in Blacks as well as Whites in older community-based adults. The large differential bias in women versus men in all equations is in contrast to other studies and is unexplained. Further studies are required in multiracial and multiethnic community-based cohorts, taking into account differences in GFR measurement methods.

Three sides to a story: Child, parent, and nurse perspectives on the child's experience during hematopoietic stem cell transplantation.

BACKGROUND: The experience of children undergoing hematopoietic stem cell transplantation (HSCT), including the ways in which different participants (ie, children, parents, and nurses) contribute to the overall picture of a child's experience, is poorly characterized. This study evaluated parent, child, and nurse perspectives on the experience of children during HSCT and factors contributing to interrater differences. METHODS: Participants were enrolled in a multicenter, prospective study evaluating child and parent health-related quality of life over the year after HSCT. Children (n = 165) and their parents and nurses completed the Behavioral, Affective, and Somatic Experiences Scale (BASES) at baseline (before/during conditioning), 7 days after the stem cell infusion (day+7), and 21 days after the stem cell infusion (day+21). The BASES domains included Somatic Distress, Mood Disturbance, Cooperation, and Getting Along. Higher scores indicated more distress/impairment. Repeated measures models by domain assessed differences by raters and changes over time and identified other factors associated with raters' scores. RESULTS: Completion rates were high (≥73% across times and raters). Multivariate models revealed significant time-rater interactions, which varied by domain. For example, parent-rated Somatic Distress scores increased from baseline to day+7 and remained elevated at day+21 (P < .001); children's scores were lower than parents' scores across time points. Nurses' baseline scores were lower than parents' baseline scores, although by day+21 they were similar. Older child age was associated with higher Somatic Distress and Mood Disturbance scores. Worse parent emotional functioning was associated with lower scores across raters and domains except for Cooperation. CONCLUSIONS: Multirater assessments are highly feasible during HSCT. Ratings differ by several factors; considering ratings in light of such factors may deepen our understanding of the child's experience. Cancer 2017;123:3159-66. © 2017 American Cancer Society.

Association of Preoperative Urinary Uromodulin with AKI after Cardiac Surgery.

BACKGROUND AND OBJECTIVES: AKI is a serious complication after cardiac surgery. Although high urinary concentrations of the tubular protein uromodulin, a marker of tubular health, are associated with less AKI in animal models, its relationship in humans is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A post hoc analysis of a prospective cohort study of 218 adults undergoing on-pump cardiac surgery between 2004 and 2011 was conducted. Multivariable logistic and linear regression analyses were used to evaluate the associations of preoperative urinary uromodulin-to-creatinine ratio with postoperative AKI (defined as a rise in serum creatinine of >0.3 mg/dl or >1.5 times baseline); severe AKI (doubling of creatinine or need for dialysis) and peak postoperative serum creatinine over the first 72 hours. RESULTS: Mean age was 68 years, 27% were women, 95% were white, and the median uromodulin-to-creatinine ratio was 10.0 µg/g. AKI developed in 64 (29%) patients. Lower urinary uromodulin-to-creatinine ratio was associated with higher odds for AKI (odds ratio, 1.49 per 1-SD lower uromodulin; 95% confidence interval, 1.04 to 2.13), which was marginally attenuated after multivariable adjustment (odds ratio, 1.43; 95% confidence interval, 0.99 to 2.07). The lowest uromodulin-to-creatinine ratio quartile was also associated with higher odds for AKI relative to the highest quartile (odds ratio, 2.94; 95% confidence interval, 1.19 to 7.26), which was slightly attenuated after multivariable adjustment (odds ratio, 2.43; 95% confidence interval, 0.91 to 6.48). A uromodulin-to-creatinine ratio below the median was associated with higher adjusted odds for severe AKI, although this did not reach statistical significance (odds ratio, 4.03; 95% confidence interval, 0.87 to 18.70). Each 1-SD lower uromodulin-to-creatinine ratio was associated with a higher adjusted mean peak serum creatinine (0.07 mg/dl per SD; 95% confidence interval, 0.02 to 0.13). CONCLUSIONS: Lower uromodulin-to-creatinine ratio is associated with higher odds of AKI and higher peak serum creatinine after cardiac surgery. Additional studies are needed to confirm these preliminary results.

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD.

BACKGROUND: Unlike the case with creatinine, conditions affecting the non-glomerular filtration rate (GFR) determinants of low-molecular-weight serum proteins, ß-trace protein (BTP), ß2-microglobulin (B2M), and cystatin C, are not well characterized. STUDY DESIGN: Pooled cross-sectional analysis of 3 studies. SETTING & PARTICIPANTS: 3,156 persons with chronic kidney disease from the MDRD (Modification of Diet in Renal Disease) Study, AASK (African American Study of Kidney Disease and Hypertension), and CRIC (Chronic Renal Insufficiency Cohort) Study. PREDICTORS: Demographic and clinical factors hypothesized to be associated with non-GFR determinants of the filtration markers, selected from literature review and physiologic and clinical considerations. OUTCOMES: Serum creatinine, BTP, B2M, and cystatin C levels. RESULTS: In multivariable-adjusted errors-in-variables regression models that included adjustment for measured GFR (mGFR) and mGFR measurement error, creatinine level had stronger associations with male sex, black race, and higher urine creatinine excretion than the other filtration markers. BTP was associated less strongly with age, similar in direction with sex, and opposite in direction with race than creatinine level. Like cystatin C, B2M level was associated less strongly with age, sex, and race than creatinine level. BTP, B2M, and cystatin C levels were associated more strongly than creatinine level with other factors, including urine protein excretion and weight for BTP, smoking and urine protein excretion for B2M, and smoking for cystatin C. LIMITATIONS: Findings may not be generalizable to populations without chronic kidney disease, and residual confounding with GFR due to incomplete adjustment for GFR measurement error. CONCLUSIONS: Like creatinine, serum levels of low-molecular-weight proteins are affected by conditions other than GFR. Knowledge of these conditions can aid the interpretation of GFR estimates and risk using these markers and guide the use of these filtration markers in developing GFR estimating equations.