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). OUTCOMES: Performance of equations compared to eGFRcr-cys. Non-GFR determinants of serum B2M and BTP (SB2M, and SBTP, respectively). mGFR was determined using the plasma clearance of 51Cr-EDTA. ANALYTICAL APPROACH: Bias was defined as the median of the differences between mGFR and eGFR. 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 (SD) age and mGFR were 58.8 (13.2) years and 78.4 (21.7) ml/min/1.73 m2, 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 multi-marker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine.

Evaluation of novel candidate filtration markers from a global metabolomic discovery for glomerular filtration rate estimation.

Creatinine and cystatin-C are recommended for estimating glomerular filtration rate (eGFR) but accuracy is suboptimal. Here, using untargeted metabolomics data, we sought to identify candidate filtration markers for a new targeted assay using a novel approach based on their maximal joint association with measured GFR (mGFR) and with flexibility to consider their biological properties. We analyzed metabolites measured in seven diverse studies encompasing 2,851 participants on the Metabolon H4 platform that had Pearson correlations with log mGFR and used a stepwise approach to develop models to < -0.5 estimate mGFR with and without inclusion of creatinine that enabled selection of candidate markers. In total, 456 identified metabolites were present in all studies, and 36 had correlations with mGFR < -0.5. A total of 2,225 models were developed that included these metabolites; all with lower root mean square errors and smaller coefficients for demographic variables compared to estimates using untargeted creatinine. Seventeen metabolites were chosen, including 12 new candidate filtration markers. The selected metabolites had strong associations with mGFR and little dependence on demographic factors. Candidate metabolites were identified with maximal joint association with mGFR and minimal dependence on demographic variables across many varied clinical settings. These metabolites are excreted in urine and represent diverse metabolic pathways and tubular handling. Thus, our data can be used to select metabolites for a multi-analyte eGFR determination assay using mass spectrometry that potentially offers better accuracy and is less prone to non-GFR determinants than the current eGFR biomarkers.

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.

Sustained low-efficiency extended dialysis (SLED) with single-pass batch system in critically-ill patients with acute kidney injury (AKI).

BACKGROUND: Single-pass batch dialysis (SBD) is a well-established system for treatment of end-stage renal disease. However, little evidence is available on sustained low-efficiency extended dialysis (SLED) performed with SBD in patients with acute kidney injury (AKI) in the intensive care unit (ICU). METHODS: All SLED-SBD sessions conducted on AKI patients in nine ICUs between March and June 2010 were retrospectively analyzed regarding the achieved metabolic and fluid control. Logistic regression was performed to identify the risk factors associated with hypotension and clotting during the sessions. RESULTS: Data from 106 patients and 421 sessions were analyzed. Patients were 54.2 ± 17.0 years old, 51 % males, and the main AKI cause was sepsis (68 %); 80 % of patients needed mechanical ventilation and 55 % vasoactive drugs. Hospital mortality was 62 %. The median session time was 360 min [interquartile range (IQR) 300-360] and prescribed ultrafiltration was 1500 ml (IQR 800-2000). In 272 sessions (65 %) no complications were recorded. No heparin was used in 269/421 procedures (64 %) and system clotting occurred in 63 sessions (15 %). Risk factors for clotting were sepsis [odds ratio (OR) 2.32 (1.31-4.11), p = 0.004], no anticoagulation [OR 2.94 (1.47-5.91), p = 0.002] and the prescribed time (hours) [OR 1.14 (1.05-1.24), p = 0.001]. Hypotension occurred in 25 % of procedures and no independent risk factors were identified by logistic regression. Adequate metabolic and fluid balance was achieved during SLED sessions. Median blood urea decreased from 107 to 63 mg/dl (p < 0.001), potassium from 4.1 to 3.9 mEq/l (p < 0.001), and increased bicarbonate (from 21.4 to 23.5 mEq/l, p < 0.001). Median fluid balance during session days ranged from +1300 to -20 ml/24 h (p < 0.001). CONCLUSIONS: SLED-SBD was associated with a low incidence of clotting despite frequent use of saline flush, and achieved a satisfactory hemodynamic stability and reasonable metabolic and fluid control in critically-ill AKI patients.