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Routine use of natriuretic peptides: Lessons from a big data analysis.
Goudot, FX, Msadek, S, Boukertouta, T, Schischmanoff, PO, Meune, C
Annals of clinical biochemistry. 2021;(5):481-486
Abstract
BACKGROUND Natriuretic peptides have broad indications during heart failure and the detection of left ventricular dysfunction in high-risk patients. They can also be used for the diagnosis/management of other cardiac diseases. However, very little is known regarding their use in routine practice. METHODS We examined all biological tests performed from February 2010 to August 2015 in two districts from the French Brittany, covering 13,653 km2 and including 22,265 physicians. We report the settings and conditions of N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements (the only locally natriuretic peptide available). RESULTS From a total of 3,606,432 tests requested in 557,650 adult (older than 20 years) patients, only 56,653 (1.6%) included at least one NT-proBNP measurement. NT-proBNP measurements gradually increased, from 9188 in 2011 to 12,938 in 2014 (P < 0.001). Most NT-proBNP tests were measured in urban laboratories (72.7%) and in private (62.9%) non-hospital/clinics laboratories; they were mostly ordered by general practitioners (66% compared with 11% by cardiologists). The number of NT-proBNP measurements increased with age up to 80-90 years, and 70.3% of tests were measured in ≥75 years patients. Creatinine and electrolytes were not associated with NT-proBNP in 15.8% and 19.7% of tests, respectively. CONCLUSION Among a very large cohort, we observed that natriuretic peptides remain largely undermeasured. NT-proBNP is mostly measured in elderly patients, and its interpretation may be hazardous in up to 16% of all individuals because no measurement of creatinine was associated to NT-proBNP.
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A Model-Based Approach to Assess Unstable Creatinine Clearance in Critically Ill Patients.
Ullah, S, Zoller, M, Jaehde, U, Huseyn-Zada, M, Weig, T, Fuhr, U, Arshad, U, Zander, J, Taubert, M
Clinical pharmacology and therapeutics. 2021;(5):1240-1249
Abstract
Creatinine clearance is an important tool to describe the renal elimination of drugs in pharmacokinetic (PK) evaluations and clinical practice. In critically ill patients, unstable kidney function invalidates the steady-state assumption underlying equations, such as Cockcroft-Gault. Although measured creatinine clearance (mCrCL) is often used in nonsteady-state situations, it assumes that observed data are error-free, neglecting frequently occurring errors in urine collection. In contrast, compartmental nonlinear mixed effects models of creatinine allow to describe dynamic changes in kidney function while explicitly accounting for a residual error associated with observations. Based on 530 serum and 373 urine creatinine observations from 138 critically ill patients, a one-compartment creatinine model with zero-order creatinine generation rate (CGR) and first-order CrCL was evaluated. An autoregressive approach for interoccasion variability provided a distinct model improvement compared to a classical approach (Δ Akaike information criterion (AIC) -49.0). Fat-free mass, plasma urea concentration, age, and liver transplantation were significantly related to CrCL, whereas weight and sex were linked to CGR. The model-based CrCL estimates were superior to standard approaches to estimate CrCL (or glomerular filtration rate) including Cockcroft-Gault, mCrCL, four-variable modification of diet in renal disease (MDRD), six-variable MDRD, and chronic kidney disease epidemiology collaboration as a covariate to describe cefepime and meropenem PKs in terms of objective function value. In conclusion, a dynamic model of creatinine kinetics provides the means to estimate actual CrCL despite dynamic changes in kidney function, and it can easily be incorporated into population PK evaluations.
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Severe obesity and the impact of medical weight loss on estimated glomerular filtration rate.
Rothberg, AE, McEwen, LN, Herman, WH
PloS one. 2020;(2):e0228984
Abstract
OBJECTIVE To assess the impact of obesity, glucose tolerance, and weight loss on renal function, we measured serum creatinine and cystatin C and estimated glomerular filtration rate (GFR) indexed to 1.73m2 body surface area (BSA) and GFR indexed to actual BSA in subjects with normal and abnormal glucose tolerance before and up to 2 years after medical weight loss. METHODS We studied 146 subjects at baseline and 3-to-6 months after 18% reduction in weight; 43 were also studied at 2-years. GFR was estimated using the MDRD, CKD-EPICr, CKD-EPICysCr, and the CKD-EPICys equations. RESULTS eGFR was consistently lower when creatinine-based rather than cystatin C-based estimating equations were used. eGFR was lower when creatinine-based or cystatin C-based equations were indexed to 1.73m2 BSA than when they were indexed to actual BSA. eGFR indexed to actual BSA was more likely to demonstrate hyperfiltration (eGFR ≥135 ml/min) than eGFR indexed to 1.73m2 BSA and decreased into the normal range with weight loss. eGFR was highest in subjects with impaired fasting glucose but there was little difference in the patterns of change in eGFR across groups by glucose tolerance status. CONCLUSIONS With severe obesity, high fat-free mass and BSA result in low estimates of eGFR indexed to 1.73m2 BSA, especially when creatinine-based estimating equations are used. GFR indexed to actual BSA is approximately 50% higher. When eGFR is indexed to actual BSA, many subjects display evidence of renal hyperfiltration which improves with weight loss. In subjects with severe obesity undergoing medical weight loss, estimating equations that use cystatin C and are indexed to actual BSA may provide a more accurate assessment of renal function.
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Analysis of biomarkers and metabolic pathways in patients with unstable angina based on ultra‑high‑performance liquid chromatography‑quadrupole time‑of‑flight mass spectrometry.
Liu, Y, Li, Y, Zhang, T, Zhao, H, Fan, S, Cai, X, Liu, Y, Li, Z, Gao, S, Li, Y, et al
Molecular medicine reports. 2020;(5):3862-3872
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Abstract
Unstable angina (UA) is a coronary disease with a high mortality and morbidity worldwide. The present study aimed to use non‑invasive techniques to identify urine biomarkers in patients with UA, so as to provide more information for the early diagnosis and treatment of the disease. Based on metabolomics, urine samples from 28 patients with UA and 28 healthy controls (HCs) were analyzed using ultra‑high‑performance liquid chromatography‑quadrupole time‑of‑flight mass spectrometry (UPLC‑Q‑TOF/MS). A total of 16 significant biomarkers that could distinguish between patients with UA and HCs, including D‑glucuronic acid, creatinine, succinic acid and N‑acetylneuraminic acid, were identified. The major metabolic pathways associated with UA were subsequently analyzed by non‑targeted metabolomics. The results demonstrated that amino acid and energy metabolism, fatty acid metabolism, purine metabolism and steroid hormone biosynthetic metabolism may serve important roles in UA. The results of the current study may provide a theoretical basis for the early diagnosis of UA and novel treatment strategies for clinicians. The trial was registered with the Chinese Clinical Trial Registration Center (registration no. ChiCTR‑ROC‑17013957) at Tianjin University of Traditional Chinese Medicine.
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Urine protein:creatinine ratio vs 24-hour urine protein for proteinuria management: analysis from the phase 3 REFLECT study of lenvatinib vs sorafenib in hepatocellular carcinoma.
Evans, TRJ, Kudo, M, Finn, RS, Han, KH, Cheng, AL, Ikeda, M, Kraljevic, S, Ren, M, Dutcus, CE, Piscaglia, F, et al
British journal of cancer. 2019;(3):218-221
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BACKGROUND Proteinuria monitoring is required in patients receiving lenvatinib, however, current methodology involves burdensome overnight urine collection. METHODS To determine whether the simpler urine protein:creatinine ratio (UPCR) calculated from spot urine samples could be accurately used for proteinuria monitoring in patients receiving lenvatinib, we evaluated the correlation between UPCR and 24-hour urine protein results from the phase 3 REFLECT study. Paired data (323 tests, 154 patients) were analysed. RESULTS Regression analysis showed a statistically significant correlation between UPCR and 24-hour urine protein (R2: 0.75; P < 2 × 10-16). A UPCR cut-off value of 2.4 had 96.9% sensitivity, 82.5% specificity for delineating between grade 2 and 3 proteinuria. Using this UPCR cut-off value to determine the need for further testing could reduce the need for 24-hour urine collection in ~74% of patients. CONCLUSION Incorporation of UPCR into the current algorithm for proteinuria management can enable optimisation of lenvatinib treatment, while minimising patient inconvenience. CLINICAL TRIAL REGISTRATION NCT01761266.
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Interferon Gamma-1b Does Not Increase Markers of Bone Resorption in Autosomal Dominant Osteopetrosis.
Imel, EA, Liu, Z, Acton, D, Coffman, M, Gebregziabher, N, Tong, Y, Econs, MJ
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2019;(8):1436-1445
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In autosomal dominant osteopetrosis type 2 (ADO2) CLCN7 mutations cause impaired osteoclast function. Severe consequences include skeletal fragility despite high bone mass, osteomyelitis, osteonecrosis, bone marrow failure, and severe cranial nerve impingement. There is no effective medical treatment for ADO2. We recruited subjects with ADO2 into a 14-week, open-label, pilot clinical trial of interferon gamma-1b. Doses were titrated based on tolerability and if fasting serum C-telopeptide (CTX) was <25% above baseline at week 8, targeting doses of 100 µg/m2 three times a week. The primary outcomes were change from baseline in CTX and N-telopeptide/creatinine ratio (NTX/Cr) at week 14. Secondary outcomes included changes in urine calcium/creatinine ratio, bone formation markers and tolerability. Nine adults and three children were recruited. Severe manifestations of ADO2 included histories of fractures (100%), osteomyelitis (16.7%), vision loss (50%), and anemia (58.3%). Baseline CTX and NTX/Cr were generally low-normal. Procollagen type I N-terminal propeptide was elevated or in the upper-normal range in 11 of 12 (91.6%) subjects. Elevations of aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were common. One subject withdrew due to rash. Five subjects achieved doses of 50 µg/m2 3 days a week, while six reached the full dose of 100 µg/m2 3 days a week. Only 3 of 11 (27.3%) completing subjects achieved the primary outcome of increasing CTX ≥25% above baseline at week 14. The mean ± SD change from baseline in CTX at week 14 was +2.2% ± 43.2%, p = 0.86). Likewise, there was no significant change in NTX/Cr (mean change -2.1%, p = 0.81). Interferon gamma-1b was poorly tolerated. Most subjects had adverse events, and the Mental Health and Mental Component Scales of the SF-36v2 health survey declined slightly (p < 0.05). Over 14 weeks, interferon gamma-1b failed to significantly increase bone turnover markers in ADO2 and was poorly tolerated. Consequently, interferon gamma-1b is unlikely to be effective for decreasing bone mass in ADO2. © 2019 American Society for Bone and Mineral Research.
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Serum creatinine and estimated glomerular filtration rates in HIV positive and negative adults in Ethiopia.
Yilma, D, Abdissa, A, Kæstel, P, Tesfaye, M, Olsen, MF, Girma, T, Ritz, C, Friis, H, Andersen, ÅB, Kirk, O
PloS one. 2019;(2):e0211630
Abstract
BACKGROUND Glomerular filtration rate estimating equations using serum creatinine are not validated in most African settings. We compared serum creatinine and estimated glomerular filtration rate (eGFR) in HIV positive and negative adults and assessed the performance of eGFR equations ((Cockcroft and Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) compared to 24-hour creatinine clearance in HIV positive adults. METHODS Data were collected on demographic, anthropometric, body composition, clinical parameters and serum creatinine in HIV positive and negative adults. 24-hour urine was collected from some of the HIV positive adults who volunteered. Bias was calculated as mean difference between 24-hr creatinine clearance and eGFR (eGFR- 24 hour creatinine clearance) and the accuracy of each eGFR equation was calculated as the percentage of estimates within 30% of creatinine clearance. RESULTS A total of 340 HIV positive and 100 HIV negative adults were included in this study. Creatinine clearance was determined for 46 of HIV positive adults. Serum creatinine increased with increasing age, weight, height, body surface area, fat free mass and grip strength in both HIV positive and negative adults (P<0.05). No difference was observed in eGFR between HIV positive and HIV negative adults. For all eGFR equations, the correlation between eGFR and 24-hr creatinine clearance was 0.45-0.53 and the accuracy within 30% of 24-hr creatinine clearance was 24-46%. Removing ethnic coefficient reduced the bias and improved accuracy of the CKD-EPI and the MDRD estimates. CONCLUSION Ethiopian HIV positive adults in the present study had good kidney function at the initiation of antiretroviral treatment. However, all eGFR equations overestimated 24-hr creatinine clearance in the study population. Creatinine based eGFR equations that accounts for low muscle mass and body surface area are needed.
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Kidney-protective Effect of Magnesium Supplementation in Cisplatin-containing Chemotherapy for Pediatric Cancer: A Retrospective Study.
Matsui, M, Saito, Y, Yamaoka, S, Yokokawa, Y, Morikawa, Y, Makimoto, A, Yuza, Y
Journal of pediatric hematology/oncology. 2018;(5):379-381
Abstract
In total, 158 chemotherapy courses containing cisplatin for 37 pediatric cases of newly diagnosed cancer were divided into 2 groups depending on whether magnesium (Mg) supplementation was administered (Mg+: 92 courses) or not (Mg-: 66 courses). Renal impairment was defined as grade 2 or higher creatinine elevation (CE) after each chemotherapy course. The incidence of CE in the Mg+ was significantly lower than in the Mg- (9.8% vs. 22.7%; P=0.025). Multivariate analysis revealed that Mg supplementation significantly reduced the incidence of CE (odds ratio, 0.36; confidence interval, 0.13-0.99). In pediatric patients, Mg supplementation during cisplatin-containing chemotherapy was associated with less cisplatin-induced nephrotoxicity to prevent cisplatin-induced nephrotoxicity.
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Effect of beef ingestion by humans on plasma concentrations of creatinine, urea, and cystatin C.
Toffaletti, JG, Hammett-Stabler, C, Handel, EA
Clinical biochemistry. 2018;:26-31
Abstract
PURPOSE The effect of eating meat on serum concentrations of creatinine has varied among previous reports, with some finding no effect and others finding 50-100% increases, which appears related to how the beef is cooked. For other analytes related to kidney function, urea is well known to increase following a protein meal, and the effect of eating meat on cystatin C concentrations has been studied once. METHODS We had 32 participants eat a measured amount of cooked beef (5-6 or 10-12 oz; 142-170 or 284-340 g) and collected blood for measurements at 1 h before and immediately before eating beef, then at 1, 2, and 4 h after eating the beef. We measured creatinine using both alkaline picrate and enzymatic methods, cystatin C using a nephelometric immunoassay, and urea using an enzymatic method. RESULTS For creatinine, both the picrate and enzymatic methods showed similar responses, with a peak average increases of 5.9 μmol/L (0.07 mg/dL) and 4.6 μmol/L (0.05 mg/dL), respectively, at 2 h. Cystatin C had a very slightly maximal decrease of -0.037 mg/L at 2 h. Urea had the largest change, increasing by 0.30 and 0.77 mmol/L at 2 and 4 h respectively. CONCLUSIONS Healthy individuals were found to have minor increases in serum creatinine (~5 μmol/L) following the ingestion of 5/6 or 10/12 oz of fried beef. Cystatin C appears to decrease very slightly in some people after beef ingestion, possibly due either to circadian variation or to a hormonal effect of eating. We conclude that ingesting these amounts of fried beef has a small effect on plasma creatinine concentrations. Although these increases would likely not affect the diagnosis of a kidney impairment in this population or in those with kidney disease, eating meat before collecting blood for creatinine measurement should be avoided.
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Varying Patterns of Biomarkers of Mineral and Bone Metabolism After Kidney Transplantation.
Makówka, A, Głyda, M, Majewska, ER, Nowicki, M
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2017;(8):618-624
Abstract
Sclerostin inhibits Wnt/β-catenin signaling pathway, thereby decreasing bone formation. Osteoblast stimulating actions of parathyroid hormone (PTH) are mediated by suppression of sclerostin. Thus, sclerostin may reflect both bone metabolism and parathyroid function. The study was aimed to analyze the patterns of the changes of mineral and bone biomarkers for 9 months following kidney transplantation (KTx). Thirty-five patients after KTx were included into a 9-month observational study. Serum creatinine, calcium, phosphorus, 25-OH vitamin D, PTH, fibroblast growth factor 23 (FGF-23), sclerostin, and bone-specific alkaline phosphatase (BAP) were measured before KTx, and 1, 2 weeks, and 1, 2, 3, 4, 5, 6, and 9 months thereafter. Urine sclerostin/creatinine ratio was assessed in parallel from month 1 after KTx. Following KTx most serum markers significantly decreased till the end of observation including PTH (by 58%), phosphorus (37%), sclerostin (31%), BAP (28%), and FGF-23 (82%). Most of the decrease was observed during first 2 months after KTx. Serum calcium was increased by 17%. Urine sclerostin/creatinine ratio increased from month 1 till month 6. At KTx serum FGF-23 correlated only with phosphate (r=0.62, p=0.01) and PTH with BAP (r=0.49, p=0.04) but not with sclerostin. At the end of the study neither serum sclerostin nor FGF-23 correlated with other parameters of mineral and bone metabolism. Sclerostin shows the limited utility as the marker of the resolution of bone and mineral metabolism after KTx.