-
1.
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.
-
2.
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
-
-
Free full text
-
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.
-
3.
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
-
-
Free full text
-
Abstract
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.
-
4.
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
-
-
Free full text
-
Abstract
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.
-
5.
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.
-
6.
Renal Abnormalities Among Egyptian Children With Hemophilia A Using Renal Scintigraphy: Relation to Risk Factors and Disease Severity.
Hamed, AA, Shalaby, MH, El-Kinawy, NS, Elamawy, AA, Abd El-Ghany, SM
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2017;(5):478-486
Abstract
UNLABELLED Many risk factors may contribute to renal disease in patients with hemophilia A. AIM: We aimed to evaluate functional and structural renal abnormalities among a group of Egyptian children with severe and moderate hemophilia A using technetium-99m diethylene triamine pentaacetic acid (99mTc-DTPA) and technetium-99 m dimercaptusuccinic acid (99mTc-DMSA) scan. We also aimed to determine the relation between these abnormalities and different risk factors and disease severity. PATIENTS AND METHODS Forty male patients, 16 with severe and 24 with moderate hemophilia A, were enrolled in this study. Their mean age was 10.2 ± 4.3 years (range, 5-17 years). Full history taking, clinical examination, laboratory, and radionuclide investigations including serum creatinine, blood urea nitrogen (BUN), urine analysis, creatinine clearance, 24-hour urinary protein, 99mTc-DTPA scan, and 99mTc-DMSA scan were performed to all enrolled patients. RESULTS Serum creatinine and BUN were normal in all patients, and corrected creatinine clearance was diminished in 2 patients. However, 99mTc-DTPA results yielded 19 (47.5%) patients with diminished glomerular filtration rate (GFR). Moreover, it showed that 14 (35%) had obstructive uropathy, 15 (37.5%) had obstructive nephropathy, while 11 (27.5%) patients showed normal scan. One patient had atrophy of 1 kidney on 99mTc-DMSA scan. Among our cohort, 5 (12.5%) patients were hypertensive. Microscopic hematuria was detected in 14 (35%) patients while 72.5% had proteinuria. We found an association between hematuria and hypertension with diminished GFR. CONCLUSION Despite normal kidney functions (serum creatinine and BUN), we found a high rate of diminished GFR and obstructive uropathy and nephropathy as detected by 99mTc-DTPA scan among children with hemophilia A.
-
7.
Improving the measurement of longitudinal change in renal function: automated detection of changes in laboratory creatinine assay.
Poh, N, McGovern, AP, de Lusignan, S
Journal of innovation in health informatics. 2015;(2):293-301
Abstract
INTRODUCTION Renal function is reported using the estimates of glomerular filtration rate (eGFR). However, eGFR values are recorded without reference to the particular serum creatinine (SCr) assays used to derive them, and newer assays were introduced at different time points across the laboratories in the United Kingdom. These changes may cause systematic bias in eGFR reported in routinely collected data, even though laboratory-reported eGFR values have a correction factor applied. DESIGN An algorithm to detect changes in SCr that in turn affect eGFR calculation method was developed. It compares the mapping of SCr values on to eGFR values across a time series of paired eGFR and SCr measurements. SETTING Routinely collected primary care data from 20,000 people with the richest renal function data from the quality improvement in chronic kidney disease trial. RESULTS The algorithm identified a change in eGFR calculation method in 114 (90%) of the 127 included practices. This change was identified in 4736 (23.7%) patient time series analysed. This change in calibration method was found to cause a significant step change in the reported eGFR values, producing a systematic bias. The eGFR values could not be recalibrated by applying the Modification of Diet in Renal Disease equation to the laboratory reported SCr values. CONCLUSIONS This algorithm can identify laboratory changes in eGFR calculation methods and changes in SCr assay. Failure to account for these changes may misconstrue renal function changes over time. Researchers using routine eGFR data should account for these effects.
-
8.
Creatinine-or cystatin C-based equations to estimate glomerular filtration in the general population: impact on the epidemiology of chronic kidney disease.
Delanaye, P, Cavalier, E, Moranne, O, Lutteri, L, Krzesinski, JM, Bruyère, O
BMC nephrology. 2013;:57
Abstract
BACKGROUND Chronic kidney disease (CKD) is a major issue in public health. Its prevalence has been calculated using estimation of glomerular filtration rate (GFR) by the creatinine-based equations developed in the Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study. Recently, new equations based either on cystatin C (CKD-EPI Cys) or both cystatin and creatinine (CKD-EPI mix) have been proposed by the CKD-EPI consortium. The aim of this study was to measure the difference in the prevalence of stage 3 CKD, defined as an estimated GFR less than 60 mL/min/1.73 m2, in a population using these four equations. METHODS CKD screening was performed in the Province of Liège, Belgium. On a voluntary basis, people aged over 50 years have been screened. GFR was estimated by the four equations. Stage 3 CKD was defined as a GFR less than 60 mL/min/1.73 m2. RESULTS The population screened consisted of 4189 people (47% were men, mean age 63 ± 7y). Their mean serum creatinine and plasma cystatin C levels were 0.88 ± 0.21 mg/dL and 0.85 ± 0.17 mg/L, respectively. The prevalence of CKD in this population using the MDRD, the CKD-EPI, the CKD-EPI Cys and the CKD-EPI mix equations was 13%, 9.8%, 4.7% and 5%, respectively. The prevalence of CKD was significantly higher with the creatinine-based (MDRD and the CKD-EPI) equations compared to the new cystatin C-based equations. CONCLUSIONS Prevalence of CKD varies strongly depending on the method used to estimate GFR. Such discrepancies are of importance and must be confirmed and explained by additional studies, notably by studies using GFR measured with a reference method. TRIAL REGISTRATION B70720071509.
-
9.
Spot urine osmolality/creatinine ratio in healthy humans.
Godevithanage, S, Kanankearachchi, PP, Dissanayake, MP, Jayalath, TA, Chandrasiri, N, Jinasena, RP, Kumarasiri, RP, Goonasekera, CD
Kidney & blood pressure research. 2010;(4):291-6
Abstract
BACKGROUND Spot urine albumin/creatinine ratio is a reliable estimate of 24-hour urine albumin excretion. In a pilot study, we observed that the spot urine osmolality/creatinine ratio (U(osm)/U(cr)) in healthy adults is reproducible. Therefore, we postulated that U(osm)/U(cr) of a spot urine sample may give an overall estimate of urinary excretion of solutes, renal concentrating ability and body hydration status. METHOD Early morning spot urine samples were collected from healthy humans, frozen and analyzed in batches to establish spot U(osm)/U(cr) and its variation in relation to sex, age, body weight and height. RESULTS Two hundred and twenty-nine healthy volunteers participated. They were stratified into seven age groups: (a) 1.5-5, (b) >5-10, (c) >10-20, (d) >20-30, (e) >30-45, (f) >45-60, and (g) >60 years. Fifteen males and 15 females were allocated to each age category. A spot urine sample was collected from all subjects in the morning after the first void and was analyzed for osmolality and creatinine. The influence of age, sex, body weight and height on spot U(osm)/U(cr) was investigated using multiple linear regression. Only height showed a significant correlation (R(2) = 0.02). Further analysis after excluding the 1.5-5 years age group revealed no significant correlation between age, sex, body weight and height and the U(osm)/U(cr) ratio. CONCLUSION Spot U(osm)/ U(cr) of healthy humans is a consistent index in steady state and needs no correction for sex, age and body weight above the age of 5 years.
-
10.
N-acetylcysteine effect on serum creatinine and cystatin C levels in CKD patients.
Rehman, T, Fought, J, Solomon, R
Clinical journal of the American Society of Nephrology : CJASN. 2008;(6):1610-4
-
-
Free full text
-
Abstract
BACKGROUND AND OBJECTIVES N-acetylcysteine (NAC) has been widely used as a prophylactic therapy for contrast-induced nephropathy (CIN). Its efficacy is controversial because of heterogeneity in study results and because of evidence that NAC can alter serum creatinine levels without affecting glomerular filtration rate. This confounding effect of N-acetylcysteine on serum creatinine has not been rigorously tested, however, in a population at risk for CIN and following doses of NAC currently recommended for prophylaxis of CIN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS "Double-dose" NAC was administered in the absence of iodinated contrast media to 29 stage 3 to 5 stable chronic kidney disease patients. Serum creatinine and cystatin C were measured before and 4 h and 48 h after the last dose of NAC. RESULTS There was no effect of NAC on either serum creatinine or cystatin C levels. CONCLUSION NAC, in doses currently recommended for prophylaxis of CIN, has no effect on serum creatinine or cystatin C levels. It is therefore unlikely that the heterogeneity seen in clinical trials of NAC prophylaxis for CIN is related to a confounding effect on serum creatinine.