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Weidmann L, Laux C, Castrezana Lopez K, Harmacek D, George B, von Moos S, Schachtner T. Immunosuppression and transplantation-related characteristics affect the difference between eGFR equations based on creatinine compared to cystatin C in kidney transplant recipients. Clin Kidney J 2024; 17:sfae253. [PMID: 39502371 PMCID: PMC11536772 DOI: 10.1093/ckj/sfae253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Indexed: 11/08/2024] Open
Abstract
Introduction Previous studies show heterogeneity when applying estimated glomerular filtration (eGFR) equations to kidney transplant recipients (KTRs). However, research on the impact of transplantation-related characteristics on eGFR equations using creatinine (eGFRcr) compared to cystatin C (eGFRcys) is scarce. Methods We conducted a comprehensive analysis with three eGFRcr equations (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009, European Kidney Function Consortium (EKFC) 2021, kidney recipient specific-glomerular filtration rate KRS-GFR) 2023), comparing them to two eGFRcys (CKD-EPI 2012 and EKFC 2023) in 596 KTRs. Bland-Altman plots demonstrated relative differences according to different eGFR-stages. Multivariable logistic regression identified transplantation-related characteristics independently associated with smaller or greater differences between eGFRcr and eGFRcys equations. Results 94.3% of the cohort were White individuals. Median eGFR differed as much as 9 ml/min/1.73 m2 between equations. The median relative differences (Q2) were greater (more negative) when comparing the eGFRcr equations to eGFRcys CKD-EPI 2012, than when comparing them to eGFRcys EKFC 2023 (P < .001). Better average eGFR was associated with smaller mean relative differences in all comparisons but eGFRcr CKD-EPI 2009 with eGFR EKFC 2023 and eGFRcr EKFC 2021 with eGFRcys EKFC 2023. Living kidney donation and belatacept use were independent factors associated with a smaller difference (≥Q3) between eGFRcr and eGFRcys equations, while prednisone use or higher HbA1c were independently associated with a greater difference (≤Q1) between equations. Conclusion Different eGFR-stages, donor, or recipient characteristics, along with immunosuppression such as belatacept or prednisone, contribute to differences between eGFRcr and eGFRcys. These effects need to be considered in the clinical management of KTRs.
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Affiliation(s)
- Lukas Weidmann
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
| | - Catherine Laux
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
| | | | - Dusan Harmacek
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
| | - Britta George
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
| | - Seraina von Moos
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
- Department of Nephrology, Cantonal Hospital of Lucerne, Lucerne, Switzerland
| | - Thomas Schachtner
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
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Wang S, Chen H, Chao F, Bin J. Prognostic values of blood urea nitrogen/creatinine and cystatin C in patients with radical nephrectomy for renal cell carcinoma. J Med Biochem 2024; 43:436-444. [PMID: 39139179 PMCID: PMC11318041 DOI: 10.5937/jomb0-45664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 10/27/2023] [Indexed: 08/15/2024] Open
Abstract
Background To evaluate the prognostic value of blood urea nitrogen/creatinine ratio (BUN/SCr) and cystatin C (Cys C) in patients with renal cell carcinoma (RCC) after radical nephrectomy. Methods The study analysed 348 patients with RCC who underwent radical nephrectomy. The optimal cut-off was obtained based on the ROC of specific survival outcomes and the maximum Youden index. The patients were divided into four groups: Group 1 (low BUN/SCr-low Cys C), Group 2 (low BUN/SCr-high Cys C), Group 3 (high BUN/SCr-low Cys C), and Group 4 (high BUN/SCr-high Cys C). The primary endpoint was cancer-specific survival (CSS), and the secondary endpoint was disease-free survival (DFS).
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Affiliation(s)
- SiCheng Wang
- Heping Hospital Affiliated to Changzhi Medical College, Department of Urology, Changzhi City, China
| | - HaoLong Chen
- Heping Hospital Affiliated to Changzhi Medical College, Department of Urology, Changzhi City, China
| | - Feng Chao
- Heping Hospital Affiliated to Changzhi Medical College, Department of Urology, Changzhi City, China
| | - Jia Bin
- Heping Hospital Affiliated to Changzhi Medical College, Department of Urology, Changzhi City, China
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Abuelazm MT, Ghanem A, Johanis A, Mahmoud A, Hassan AR, Katamesh BE, Amin MA, Abdelazeem B. Reno-protective effects of perioperative dexmedetomidine in kidney transplantation: a systematic review and meta-analysis of randomized controlled trials. Int Urol Nephrol 2023; 55:2545-2556. [PMID: 36997837 PMCID: PMC10499682 DOI: 10.1007/s11255-023-03568-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 03/18/2023] [Indexed: 04/01/2023]
Abstract
BACKGROUND AND OBJECTIVE There is currently no FDA-approved medical therapy for delayed graft function (DGF). Dexmedetomidine (DEX) has multiple reno-protective effects preventing ischemic reperfusion injury, DGF, and acute kidney injury. Therefore, we aimed to evaluate the reno-protective effects of perioperative DEX during renal transplantation. METHODS A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, PubMed, and CENTRAL until June 8th, 2022. We used the risk ratio (RR) for dichotomous outcomes and the mean difference for continuous outcomes; both presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022338898. RESULTS We included four RCTs with 339 patients. Pooled risk ratio found no difference between DEX and placebo in reducing DGF (RR: 0.58 with 95% CI [0.34, 1.01], p = 0.05) and acute rejection (RR: 0.88 with 95% CI [0.52, 1.49], p = 0.63). However, DEX improved short-term creatinine on day 1 (MD: - 0.76 with 95% CI [- 1.23, - 0.3], p = 0.001) and day 2 (MD: - 0.28 with 95% CI [- 0.5, - 0.07], p = 0.01); and blood urea nitrogen on day 2 (MD: - 10.16 with 95% CI [- 17.21, - 3.10], p = 0.005) and day 3 (MD: - 6.72 with 95% CI [- 12.85, - 0.58], p = 0.03). CONCLUSION Although there is no difference between DEX and placebo regarding reducing DGF and acute rejection after kidney transplantation, there may be some evidence that it has reno-protective benefits because we found statistically significant improvement in the short-term serum creatinine and blood urea nitrogen levels. More trials are required to investigate the long-term reno-protective effects of DEX.
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Affiliation(s)
| | - Ahmed Ghanem
- Cardiology Department, The Lundquist Institute, Torrance, CA, USA
| | - Amit Johanis
- Faculty of Medicine, Creighton University, Phoenix, AZ, USA
| | | | | | | | | | - Basel Abdelazeem
- Department of Internal Medicine, McLaren Health Care, Flint, MI, USA
- Department of Internal Medicine, Michigan State University, East Lansing, MI, USA
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4
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Park JH, Koo BN, Kim MS, Shin D, Kwak YL. Effects of intraoperative dexmedetomidine infusion on renal function in elective living donor kidney transplantation: a randomized controlled trial. Can J Anaesth 2021; 69:448-459. [PMID: 34931289 DOI: 10.1007/s12630-021-02173-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 07/16/2021] [Accepted: 10/27/2021] [Indexed: 10/19/2022] Open
Abstract
PURPOSE Ischemia-reperfusion injury is inevitable during donor organ harvest and recipient allograft reperfusion in kidney transplantation, and affects graft outcomes. Dexmedetomidine, an α2-adrenoreceptor agonist, has renoprotective effects against ischemia-reperfusion injury. We investigated the effects of intraoperative dexmedetomidine infusion on renal function and the development of delayed graft function after elective living donor kidney transplantation in a randomized controlled trial. METHODS A total of 104 patients were randomly assigned to receive either an intraoperative infusion of dexmedetomidine 0.4 μg·kg-1·hr-1 or 0.9% saline. The primary outcome was the serum creatinine level on postoperative day (POD) 7. Secondary outcomes were renal function and the degree of inflammation and included the following variables: serum creatinine level and estimated glomerular filtration rate up to six months; incidence of delayed graft function; and levels of serum cystatin C, plasma interleukin (IL)-1β, and IL-18 during the perioperative period. RESULTS The mean (standard deviation) serum creatinine level on POD 7 was comparable between the groups (dexmedetomidine vs control: 1.11 [0.87] mg·dL-1 vs 1.06 [0.73] mg·dL-1; mean difference, 0.05; 95% confidence interval, -0.27 to 0.36; P = 0.77). Delayed graft function occurred in one patient in each group (odds ratio, 1.020; P > 0.99). There were no significant differences in the secondary outcomes between the groups (all P > 0.05). CONCLUSIONS Intraoperative dexmedetomidine infusion did not produce any beneficial effects on renal function or delayed graft function in patients undergoing elective living donor kidney transplantation. STUDY REGISTRATION www.ClinicalTrials.gov (NCT03327389); registered 31 October 2017.
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Affiliation(s)
- Jin Ha Park
- Department of Anesthesiology and Pain Medicine, and Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea
| | - Bon-Nyeo Koo
- Department of Anesthesiology and Pain Medicine, and Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea
| | - Min-Soo Kim
- Department of Anesthesiology and Pain Medicine, and Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea
| | - Dongkwan Shin
- Department of Anesthesiology and Pain Medicine, and Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea
| | - Young-Lan Kwak
- Department of Anesthesiology and Pain Medicine, and Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. .,Yonsei Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
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Teaford HR, Barreto JN, Vollmer KJ, Rule AD, Barreto EF. Cystatin C: A Primer for Pharmacists. PHARMACY 2020; 8:E35. [PMID: 32182861 PMCID: PMC7151673 DOI: 10.3390/pharmacy8010035] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 02/22/2020] [Accepted: 03/05/2020] [Indexed: 12/20/2022] Open
Abstract
Pharmacists are at the forefront of dosing and monitoring medications eliminated by or toxic to the kidney. To evaluate the effectiveness and safety of these medications, accurate measurement of kidney function is paramount. The mainstay of kidney assessment for drug dosing and monitoring is serum creatinine (SCr)-based estimation equations. Yet, SCr has known limitations including its insensitivity to underlying changes in kidney function and the numerous non-kidney factors that are incompletely accounted for in equations to estimate glomerular filtration rate (eGFR). Serum cystatin C (cysC) is a biomarker that can serve as an adjunct or alternative to SCr to evaluate kidney function for drug dosing. Pharmacists must be educated about the strengths and limitations of cysC prior to applying it to medication management. Not all patient populations have been studied and some evaluations demonstrated large variations in the relationship between cysC and GFR. Use of eGFR equations incorporating cysC should be reserved for drug management in scenarios with demonstrated outcomes, including to improve pharmacodynamic target attainment for antibiotics or reduce drug toxicity. This article provides an overview of cysC, discusses evidence around its use in medication dosing and in special populations, and describes practical considerations for application and implementation.
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Affiliation(s)
- Hilary R. Teaford
- Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, USA; (H.R.T.); (J.N.B.)
| | - Jason N. Barreto
- Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, USA; (H.R.T.); (J.N.B.)
| | - Kathryn J. Vollmer
- College of Pharmacy and Health Sciences, Drake University, Des Moines, IA 50311, USA;
| | - Andrew D. Rule
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA;
- Division of Epidemiology, Mayo Clinic, Rochester, MN 55905, USA
| | - Erin F. Barreto
- Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, USA; (H.R.T.); (J.N.B.)
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, USA
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Foster M, Weiner D, Bostom A, Carpenter M, Inker L, Jarolim P, Joseph A, Kusek J, Pesavento T, Pfeffer M, Rao M, Solomon S, Levey A. Filtration Markers, Cardiovascular Disease, Mortality, and Kidney Outcomes in Stable Kidney Transplant Recipients: The FAVORIT Trial. Am J Transplant 2017; 17:2390-2399. [PMID: 28257169 PMCID: PMC5573607 DOI: 10.1111/ajt.14258] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 02/09/2017] [Accepted: 02/11/2017] [Indexed: 01/25/2023]
Abstract
Cystatin C and beta-2-microglobulin (B2M) are filtration markers associated with adverse outcomes in nontransplant populations, sometimes with stronger associations than for creatinine. We evaluated associations of estimated glomerular filtration rate from cystatin C (eGFRcys ), B2M (eGFRB2M ), and creatinine (eGFRcr ) with cardiovascular outcomes, mortality, and kidney failure in stable kidney transplant recipients using a case-cohort study nested within the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial. A random subcohort was selected (N = 508; mean age 51.6 years, median transplant vintage 4 years, 38% women, 23.6% nonwhite race) with enrichment for cardiovascular events (N = 306; 54 within the subcohort), mortality (N = 208; 68 within the subcohort), and kidney failure (N = 208; 52 within the subcohort). Mean eGFRcr , eGFRcys , and eGFRB2M were 46.0, 43.8, and 48.8 mL/min/1.73m2 , respectively. After multivariable adjustment, hazard ratios for eGFRcys and eGFRB2M <30 versus 60+ were 2.02 (95% confidence interval [CI] 1.09-3.76; p = 0.03) and 2.56 (1.35-4.88; p = 0.004) for cardiovascular events; 3.92 (2.11-7.31) and 4.09 (2.21-7.54; both p < 0.001) for mortality; and 9.49 (4.28-21.00) and 15.53 (6.99-34.51; both p < 0.001) for kidney failure. Associations persisted with additional adjustment for baseline eGFRcr . We conclude that cystatin C and B2M are strongly associated with cardiovascular events, mortality, and kidney failure in stable kidney transplant recipients.
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Affiliation(s)
- M.C. Foster
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | - D.E. Weiner
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | | | - M.A. Carpenter
- Department of Biostatistics, University of North Carolina, Chapel Hill, NC
| | - L.A. Inker
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | - P. Jarolim
- Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - A.A. Joseph
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | - J.W. Kusek
- National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
| | - T. Pesavento
- The Ohio State University Medical Center, Columbus, OH
| | - M.A. Pfeffer
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - M. Rao
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | - S.D. Solomon
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - A.S. Levey
- Division of Nephrology, Tufts Medical Center, Boston, MA
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7
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Steubl D, Block M, Herbst V, Schlumberger W, Nockher A, Angermann S, Schmaderer C, Heemann U, Renders L, Scherberich J. Serum uromodulin predicts graft failure in renal transplant recipients. Biomarkers 2016; 22:171-177. [PMID: 27790922 DOI: 10.1080/1354750x.2016.1252957] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE AND METHODS Test the ability of serum uromodulin concentrations 1-3 months after renal transplantation to predict all-cause mortality (ACM) and graft loss (GL) in 91 patients. RESULTS uromodulin predicted GL equivalently to the other markers studied: the risk for GL was reduced by 0.21 per one standard deviation (SD) increase (cystatin C: hazard ratio [HR] 4.57, creatinine: HR 4.53, blood-urea-nitrogen [BUN]: HR 2.50, estimated glomerular filtration rate [eGFR]: HR 0.10). In receiver-operating-characteristic (ROC) analysis, uromodulin predicted GL with an area-under-the curve of 0.782 at an optimal cut-off (OCO) of 24.0 ng/ml with a sensitivity of 90.0% and a specificity of 70.2%. CONCLUSION Serum uromodulin predicted GL equivalently compared to conventional biomarkers of glomerular filtration.
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Affiliation(s)
- Dominik Steubl
- a Department of Nephrology, Klinikum rechts der Isar , Technische Universität , München , Germany
| | - Matthias Block
- b Research&Development Department, Euroimmun Medizinische Labordiagnostika AG , Lübeck , Germany
| | - Victor Herbst
- b Research&Development Department, Euroimmun Medizinische Labordiagnostika AG , Lübeck , Germany
| | - Wolfgang Schlumberger
- b Research&Development Department, Euroimmun Medizinische Labordiagnostika AG , Lübeck , Germany
| | - Andreas Nockher
- c Institute of Laboratory Medicine and Pathobiochemistry , Universitätsklinikum Marburg, Philipps-Universität Marburg , Marburg , Germany
| | - Susanne Angermann
- a Department of Nephrology, Klinikum rechts der Isar , Technische Universität , München , Germany
| | - Christoph Schmaderer
- a Department of Nephrology, Klinikum rechts der Isar , Technische Universität , München , Germany
| | - Uwe Heemann
- a Department of Nephrology, Klinikum rechts der Isar , Technische Universität , München , Germany
| | - Lutz Renders
- a Department of Nephrology, Klinikum rechts der Isar , Technische Universität , München , Germany
| | - Jürgen Scherberich
- d Department of Nephrology and Clinical Immunology, Klinikum München-Harlaching , Teaching Hospital of the Ludwig-Maximilian-Universität , München , Germany
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Santos J, Martins LS. Estimating glomerular filtration rate in kidney transplantation: Still searching for the best marker. World J Nephrol 2015; 4:345-53. [PMID: 26167457 PMCID: PMC4491924 DOI: 10.5527/wjn.v4.i3.345] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 05/06/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
Kidney transplantation is the treatment of choice for end-stage renal disease. The evaluation of graft function is mandatory in the management of renal transplant recipients. Glomerular filtration rate (GFR), is generally considered the best index of graft function and also a predictor of graft and patient survival. However GFR measurement using inulin clearance, the gold standard for its measurement and exogenous markers such as radiolabeled isotopes ((51)Cr EDTA, (99m)Tc DTPA or (125)I Iothalamate) and non-radioactive contrast agents (Iothalamate or Iohexol), is laborious as well as expensive, being rarely used in clinical practice. Therefore, endogenous markers, such as serum creatinine or cystatin C, are used to estimate kidney function, and equations using these markers adjusted to other variables, mainly demographic, are an attempt to improve accuracy in estimation of GFR (eGFR). Nevertheless, there is some concern about the inability of the available eGFR equations to accurately identify changes in GFR, in kidney transplant recipients. This article will review and discuss the performance and limitations of these endogenous markers and their equations as estimators of GFR in the kidney transplant recipients, and their ability in predicting significant clinical outcomes.
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