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Gembillo G, Soraci L, Santoro D. Chronic kidney disease in geriatric patients: Estimating glomerular filtration rate in older patients with comorbidities. World J Nephrol 2025; 14:105803. [DOI: 10.5527/wjn.v14.i2.105803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/07/2025] [Accepted: 03/21/2025] [Indexed: 04/09/2025] Open
Abstract
Aging is an inevitable process that is usually measured by chronological age, with people aged 65 and over being defined as "older individuals". There is disagreement in the current scientific literature regarding the best methods to estimate glomerular filtration rate (eGFR) in older adults. Several studies suggest the use of an age-adjusted definition to improve accuracy and avoid overdiagnosis. In contrast, some researchers argue that such changes could complicate the classification of chronic kidney disease (CKD). Several formulas, including the Modification of Diet in Renal Disease, CKD-Epidemiology Collaboration, and Cockcroft-Gault equations, are used to estimate eGFR. However, each of these formulas has significant limitations when applied to older adults, primarily due to sarcopenia and malnutrition, which greatly affect both muscle mass and creatinine levels. Alternative formulas, such as the Berlin Initiative Study and the Full Age Spectrum equations, provide more accurate estimates of values for older adults by accounting for age-related physiological changes. In frail older adults, the use of cystatin C leads to better eGFR calculations to assess renal function. Accurate eGFR measurements improve the health of older patients by enabling better medication dosing. A thorough approach that includes multiple calibrated diagnostic methods and a detailed geriatric assessment is necessary for the effective management of kidney disease and other age-related conditions in older adults.
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Affiliation(s)
- Guido Gembillo
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina 98125, Sicilia, Italy
| | - Luca Soraci
- Unit of Geriatric Medicine, Italian National Research Center on Aging (IRCCS INRCA), Cosenza 87100, Calabria, Italy
| | - Domenico Santoro
- Unit of Nephrology and Dialysis, AOU "G. Martino", University of Messina, Messina 98125, Sicilia, Italy
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Roberts GW, De Menezes Caceres V, Damiani A, Scarfo N, Williams DB, Russell PT. Determination of the optimal obesity-adjusted dosing weight for enoxaparin. Br J Clin Pharmacol 2025; 91:1182-1190. [PMID: 39568413 DOI: 10.1111/bcp.16338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 09/26/2024] [Accepted: 10/26/2024] [Indexed: 11/22/2024] Open
Abstract
AIMS The ideal dosing weight metric for enoxaparin remains elusive. Dosing remains focused on actual body weight, which may inadvertently increase the risk of bleeding in those with obesity, or ideal weight, which may underdose those with obesity. Our aim was to determine the optimal obesity-adjusted enoxaparin dosing weight. METHODS Multisite retrospective data were collected over a 2.0-year period for those with minimum 48 h of in-hospital twice-daily enoxaparin and factor anti-Xa level 3-5 h postdose (n = 220). Multiple linear regression calculated the associated variance between a range of nominal dosing weights and factor anti-Xa levels, adjusted for renal function. Dosing weights were calculated as ideal body weight (IBW) and then adjusted for increasing percentages of weight above IBW, i.e. IBW + 10% above IBW, IBW + 20% etc. up to actual body weight. A similar approach was used for lean body weight (LBW). RESULTS For body mass index ≥30 kg/m2 optimal variance explained by dosing weight metrics was at IBW + 40% (23%) and similarly for LBW + 40% (23%). Using actual body weight (ABW) had lowest associated variance with factor anti-Xa levels (18%) followed by unadjusted IBW (13%) or unadjusted LBW (19%). In those with body mass index <30 kg/m2 there was similar associated variance in the ranges of IBW + 20-50% and LBW 10-40% (21%). CONCLUSION Compared to IBW + 40% or LBW + 40% use of ABW to calculate dose was poorly associated with factor anti-Xa levels, as was IBW or LBW. IBW + 40% and LBW + 40% require further study as a dosing weight metric and may provide a more consistent factor anti-Xa response in those with obesity.
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Affiliation(s)
- Gregory W Roberts
- SA Pharmacy, Southern Adelaide Local Health Network, Adelaide, South Australia, Australia
| | - Viviane De Menezes Caceres
- Allied Health and Human Performance, University of South Australia, Adelaide, South Australia, Australia
| | - Anthony Damiani
- SA Pharmacy, Central Adelaide Local Health Network, Adelaide, South Australia, Australia
| | - Nicholas Scarfo
- SA Pharmacy, Southern Adelaide Local Health Network, Adelaide, South Australia, Australia
| | - Desmond B Williams
- Pharmacy and Biomedical Sciences, University of South Australia, Adelaide, South Australia, Australia
| | - Patrick T Russell
- Department of Internal Medicine, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, South Australia, Australia
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Damiani A, De Menezes Caceres V, Roberts G, Coddo J, Scarfo N, Willliams DB, Tharmathurai V, Tadros R, Fitzgerald S, O'Connell A, Kaur Sandhu A, Vanlint A, Mangoni AA, Hofmann D, Bony H, Faunt J, Boey JP, Farinola N, Wells R, Hedger S, Hewage U, Sharma Y, Jabbar Z, Thomas J, Flabouris K, Gilbert T, Thompson C, Russell P. A Clinical Practice-Based Comparison of Conventional and Individualized Dosing Strategies for Therapeutic Enoxaparin. Pharmacol Res Perspect 2025; 13:e70039. [PMID: 39853909 PMCID: PMC11760983 DOI: 10.1002/prp2.70039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 11/02/2024] [Accepted: 11/02/2024] [Indexed: 01/26/2025] Open
Abstract
To understand differences in anti-factor-Xa levels produced by two different dosing strategies (conventional and individualized) for therapeutic enoxaparin in a cohort of hospital inpatients. A multicenter, retrospective cohort study over a two- and a half-year period for inpatients with stable renal function and on therapeutic enoxaparin. Anti-factor-Xa levels were taken 3-5 h after enoxaparin administration and a minimum of 48 h of dosing. The final analysis included 278 patients from five hospitals: conventional dosing was used for 141, while 137 were given an unconventional dose, that is, individualized for their renal function and weight. Out-of-range levels were frequent (35% to 40% of all inpatients). After adjustment for age, renal function, and body mass index (BMI), the conventional group was more likely to experience above-range levels (> 1.0 IU/mL; OR 2.50 [95% CI 1.38-4.56], p < 0.003) than the individualized group. Individualized dosing was independently associated with higher odds of a below-range anti-Xa level (< 0.5 IU/mL) compared to conventional dosing (OR 2.27 [95% CI 1.07-4.76], p = 0.03). Within the conventional group, above-range levels were significantly and independently associated with decreasing renal function (OR 0.97, 95% CI 0.96-0.99, p = 0.004) and with increasing BMI (OR 1.06, 95% CI 1.01-1.10, p = 0.02). No such associations were seen with an individualized approach. Clinical event rates were low and not different between groups (p > 0.24). Conventional therapeutic dosing of enoxaparin exposed people with obesity or renal impairment to more frequent above-range anti-factor-Xa levels; individualizing the dose could improve this but might expose people to subtherapeutic levels. More research is needed.
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Affiliation(s)
- Anthony Damiani
- SA PharmacyCentral Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | | | - Greg Roberts
- SA PharmacySouthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Jessica Coddo
- SA PharmacySouthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Nicholas Scarfo
- SA PharmacySouthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Desmond B. Willliams
- Pharmacy and Biomedical SciencesUniversity of South AustraliaAdelaideSouth AustraliaAustralia
| | - Vinosshini Tharmathurai
- Department of Internal MedicineRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Rami Tadros
- Department of Internal MedicineRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Stephen Fitzgerald
- Department of Internal MedicineRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Alice O'Connell
- Department of Internal MedicineRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Amrit Kaur Sandhu
- Department of Internal MedicineRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Andrew Vanlint
- Medical Services DivisionNorthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Arduino A. Mangoni
- Department of Clinical PharmacologyFlinders University and Flinders Medical CentreAdelaideSouth AustraliaAustralia
| | - Dirk Hofmann
- Department of General Internal MedicineNoarlunga Hospital, Southern Adelaide Local Health Network AdelaideSouth AustraliaAustralia
| | - Hosam Bony
- SA PharmacySouthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Jeff Faunt
- Department of Internal MedicineRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Jir Ping Boey
- Department of Internal Medicine Flinders Medical CentreSouthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Nicholas Farinola
- Department of Clinical PharmacologyRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Rachel Wells
- Department of Internal MedicineRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Stephen Hedger
- Department of Internal Medicine Flinders Medical CentreSouthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Udul Hewage
- Department of Internal Medicine Flinders Medical CentreSouthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Yogesh Sharma
- Department of Internal Medicine Flinders Medical CentreSouthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
- College of Medicine & Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
| | - Zuhair Jabbar
- Department of Internal Medicine Flinders Medical CentreSouthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Josephine Thomas
- Department of Internal MedicineRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Katerina Flabouris
- Department of Internal MedicineRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
- Medical Services DivisionNorthern Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Toby Gilbert
- Discipline of MedicineThe University of AdelaideAdelaideSouth AustraliaAustralia
| | - Campbell Thompson
- Discipline of MedicineThe University of AdelaideAdelaideSouth AustraliaAustralia
| | - Patrick Russell
- Department of Internal MedicineRoyal Adelaide Hospital, Central Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
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Bukhari R, Hasan H, Aljefri D, Rambo R, AlSenaini G, Alzahrani YA, Alzahrani AM. Comparing Actual and Rounded Serum Creatinine Concentration for Assessing the Accuracy of Vancomycin Dosing in Elderly Patients: A Single-Center Retrospective Study. Healthcare (Basel) 2024; 12:1144. [PMID: 38891219 PMCID: PMC11171742 DOI: 10.3390/healthcare12111144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 05/21/2024] [Accepted: 05/30/2024] [Indexed: 06/21/2024] Open
Abstract
Prescribers often face the challenge of predicting creatinine clearance (CrCl) in elderly patients who are 65 years or older and have serum creatinine (SCr) concentrations below 1 mg/dL. Studies have shown that utilizing rounded SCr would underestimate CrCl in this population, which could lead to the under-dosing of some medications like vancomycin. The current study aimed to compare the accuracy of vancomycin dosing using actual SCr versus rounded SCr to 1 mg/dL in elderly patients. A total of 245 patients were included. The therapeutic trough level (10-20 mg/L) was achieved in 138 (56.3%) patients using actual SCr. Sub-therapeutic (<10 mg/L) and supra-therapeutic (>20 mg/L) trough levels were observed in 32 (13.1%) and 75 (30.6%) patients, respectively. The predictive performance of different vancomycin doses based on actual SCr and rounded SCr compared to the targeted maintenance dose (TMD) showed a stronger correlation of dosing based on actual SCr with TMD (r = 0.55 vs. 0.31) compared to rounded SCr dosing; both doses showed similar precision, with ranges of ±552 mg/day for the dosing based on actual SCr and ±691 mg/day for the dosing based on rounded SCr. Furthermore, the dosing based on actual SCr showed a lower error percentage (69%) and a higher accuracy rate (57.6%) within ±10% of the TMD compared to the dosing based on rounded SCr, which had an error percentage of (92.3%) and an accuracy rate of (40%). The prevalence of vancomycin-associated nephrotoxicity (VAN) was seen in 44 (18%) patients. Patients between 75 and 84 years of age, those who were bedridden, and those with vancomycin trough concentrations greater than 20 mg/L had a higher risk of developing VAN. In conclusion, in elderly patients, estimating vancomycin dosing based on actual SCr was more accurate compared to rounded SCr to 1 mg/dL. The efficacy of vancomycin could be negatively affected by rounding up SCr, which could underestimate CrCl and result in the under-dosing of vancomycin.
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Affiliation(s)
- Rawan Bukhari
- Pharmaceutical Care Department, Ministry of National Guard—Health Affairs, Jeddah 22384, Saudi Arabia; (R.B.); (H.H.); (R.R.); (G.A.)
- King Abdullah International Medical Research Center, Jeddah 21423, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah 22384, Saudi Arabia
| | - Hani Hasan
- Pharmaceutical Care Department, Ministry of National Guard—Health Affairs, Jeddah 22384, Saudi Arabia; (R.B.); (H.H.); (R.R.); (G.A.)
- King Abdullah International Medical Research Center, Jeddah 21423, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah 22384, Saudi Arabia
| | - Doaa Aljefri
- Pharmaceutical Care Division, King Faisal Specialist Hospital & Research Centre, Jeddah 23433, Saudi Arabia;
| | - Rawan Rambo
- Pharmaceutical Care Department, Ministry of National Guard—Health Affairs, Jeddah 22384, Saudi Arabia; (R.B.); (H.H.); (R.R.); (G.A.)
- King Abdullah International Medical Research Center, Jeddah 21423, Saudi Arabia
| | - Ghusun AlSenaini
- Pharmaceutical Care Department, Ministry of National Guard—Health Affairs, Jeddah 22384, Saudi Arabia; (R.B.); (H.H.); (R.R.); (G.A.)
- King Abdullah International Medical Research Center, Jeddah 21423, Saudi Arabia
| | - Yahya A. Alzahrani
- Drug Information Center, Department of Pharmacy, East Jeddah Hospital, Ministry of Health, Jeddah 22253, Saudi Arabia;
| | - Abdullah M. Alzahrani
- Pharmaceutical Care Department, Ministry of National Guard—Health Affairs, Jeddah 22384, Saudi Arabia; (R.B.); (H.H.); (R.R.); (G.A.)
- King Abdullah International Medical Research Center, Jeddah 21423, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah 22384, Saudi Arabia
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Wenzel M, Yu H, Uhlig A, Würnschimmel C, Wallbach M, Becker A, Fisch M, Chun FKH, Meyer CP, Leitsmann M. Cystatin C predicts renal function impairment after partial or radical tumor nephrectomy. Int Urol Nephrol 2021; 53:2041-2049. [PMID: 34269968 PMCID: PMC8463386 DOI: 10.1007/s11255-021-02957-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 07/09/2021] [Indexed: 11/28/2022]
Abstract
Purpose To test the value of preoperative and postoperative cystatin C (CysC) as a predictor on kidney function after partial (PN) or radical nephrectomy (RN) in renal cell carcinoma (RCC) patients with normal preoperative renal function. Methods From 01/2011 to 12/2014, 195 consecutive RCC patients with a preoperative estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73m2 underwent surgical RCC treatment with either PN or RN. Logistic and linear regression models tested for the effect of CysC as a predictor of new-onset chronic kidney disease in follow-up (eGFR < 60 ml/min/1.73m2). Moreover, postoperative CysC and creatinine values were compared for kidney function estimation. Results Of 195 patients, 129 (66.2%) underwent PN. In postoperative and in follow-up setting (median 14 months, IQR 10–20), rates of eGFR < 60 ml/min/1.73m2 were 55.9 and 30.2%. In multivariable logistic regression models, preoperative CysC [odds ratio (OR): 18.3] and RN (OR: 13.5) were independent predictors for a reduced eGFR < 60 ml/min/1.73m2 in follow-up (both p < 0.01), while creatinine was not. In multivariable linear regression models, a difference of the preoperative CysC level of 0.1 mg/dl estimated an eGFR decline in follow-up of about 5.8 ml/min/1.73m2. Finally, we observed a plateau of postoperative creatinine values in the range of 1.2–1.3 mg/dl, when graphically depicted vs. postoperative CysC values (‘creatinine blind area’). Conclusion Preoperative CysC predicts renal function impairment following RCC surgery. Furthermore, CysC might be superior to creatinine for renal function monitoring in the early postoperative setting.
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Affiliation(s)
- Mike Wenzel
- Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany. .,Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, QC, Canada.
| | - Hang Yu
- Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Annemarie Uhlig
- Department of Urology, University Medical Center Göttingen, Göttingen, Germany
| | - Christoph Würnschimmel
- Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, QC, Canada.,Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Manuel Wallbach
- Department of Nephrology, University Medical Center Göttingen, Göttingen, Germany
| | - Andreas Becker
- Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany
| | - Margit Fisch
- Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Felix K H Chun
- Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany
| | - Christian P Meyer
- Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marianne Leitsmann
- Department of Urology, University Medical Center Göttingen, Göttingen, Germany
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Gelsomino S, Bonacchi M, Lucà F, Barili F, Del Pace S, Parise O, Johnson DM, Gulizia MM. Comparison between three different equations for the estimation of glomerular filtration rate in predicting mortality after coronary artery bypass. BMC Nephrol 2019; 20:371. [PMID: 31619211 PMCID: PMC6796478 DOI: 10.1186/s12882-019-1564-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Accepted: 09/26/2019] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND This study was undertaken to compare the accuracy of chronic kidney disease-epidemiology collaboration (eGFRCKD-EPI) to modification of diet in renal disease (eGFRMDRD) and the Cockcroft-Gault formulas of Creatinine clearance (CCG) equations in predicting post coronary artery bypass grafting (CABG) mortality. METHODS Data from 4408 patients who underwent isolated CABG over a 11-year period were retrieved from one institutional database. Discriminatory power was assessed using the c-index and comparison between the scores' performance was performed with DeLong, bootstrap, and Venkatraman methods. Calibration was evaluated with calibration curves and associated statistics. RESULTS The discriminatory power was higher in eGFRCKD-EPI than eGFRMDRD and CCG (Area under Curve [AUC]:0.77, 0.55 and 0.52, respectively). Furthermore, eGFRCKD-EPI performed worse in patients with an eGFR ≤29 ml/min/1.73m2 (AUC: 0.53) while it was not influenced by higher eGFRs, age, and body size. In contrast, the MDRD equation was accurate only in women (calibration statistics p = 0.72), elderly patients (p = 0.53) and subjects with severe impairment of renal function (p = 0.06) whereas CCG was not significantly biased only in patients between 40 and 59 years (p = 0.6) and with eGFR 45-59 ml/min/1.73m2 (p = 0.32) or ≥ 60 ml/min/1.73m2 (p = 0.48). CONCLUSIONS In general, CKD-EPI gives the best prediction of death after CABG with unsatisfactory accuracy and calibration only in patients with severe kidney disease. In contrast, the CG and MDRD equations were inaccurate in a clinically significant proportion of patients.
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Affiliation(s)
- Sandro Gelsomino
- Cardiothoracic Department, Maastricht University Hospital, Florence, Italy.
- Department of Cardiothoracic Surgery, Cardiovascular Research Institute Maastricht University, Universiteitssingel 50, 6229, ER, Maastricht, The Netherlands.
| | - Massimo Bonacchi
- Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
| | - Fabiana Lucà
- Cardiothoracic Department, Maastricht University Hospital, Florence, Italy
- ANMCO Research Center of Heart Care, Florence, Italy
| | - Fabio Barili
- Department of Cardiovascular Surgery, S. Croce Hospital, Cuneo, Italy
| | - Stefano Del Pace
- Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
| | - Orlando Parise
- Cardiothoracic Department, Maastricht University Hospital, Florence, Italy
| | - Daniel M Johnson
- Cardiothoracic Department, Maastricht University Hospital, Florence, Italy
| | - Michele Massimo Gulizia
- ANMCO Research Center of Heart Care, Florence, Italy
- Cardiology Garibaldi-Nesima Hospital, Catania, Italy
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Sáez Fernández EM, Pérez-Blanco JS, Lanao JM, Calvo MV, Martín-Suárez A. Evaluation of renal function equations to predict amikacin clearance. Expert Rev Clin Pharmacol 2019; 12:805-813. [PMID: 31242039 DOI: 10.1080/17512433.2019.1637253] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Objective: To evaluate the predictive performance of eight renal function equations to describe amikacin elimination in a large standard population with a wide range of age. Methods: Retrospective study of adult hospitalized patients treated with amikacin and monitored in the clinical pharmacokinetics laboratory of a pharmacy service. Renal function was calculated as Cockcroft-Gault with total, adjusted and ideal body weight, MDRD-4, CKD-EPI, rLM, BIS1, and FAS. One compartment model with first-order elimination, including interindividual variability on clearance and volume of distribution and combined residual error model was selected as a base structural model. A pharmaco-statistical analysis was performed following a non-linear mixed effects modeling approach (NONMEM 7.3 software). Results: 198 patients (61 years [18-93]) and 566 measured amikacin plasma concentrations were included. All the estimated glomerular filtration rate and creatinine clearance equations evaluated described properly the data. The linear relationship between clearance and glomerular filtration rate based on rLM showed a statistically significant improvement in the fit of the data. rLM must be evaluated carefully in renal failure for amikacin dose adjustment. Conclusions: Revised Lund-Malmö (rLM) and CKD-EPI showed the superior predictive performance of amikacin drug elimination comparing to all the alternative metrics evaluated.
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Affiliation(s)
- Eva María Sáez Fernández
- a Pharmacy Service, University Hospital of Salamanca , Salamanca , Spain.,b Department of Pharmaceutical Sciences, Pharmacy Faculty, University of Salamanca, Campus Miguel de Unamuno , Salamanca , Spain.,c Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca. Hospital Virgen de la Vega , Salamanca , Spain
| | - Jonás Samuel Pérez-Blanco
- b Department of Pharmaceutical Sciences, Pharmacy Faculty, University of Salamanca, Campus Miguel de Unamuno , Salamanca , Spain.,c Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca. Hospital Virgen de la Vega , Salamanca , Spain
| | - José M Lanao
- b Department of Pharmaceutical Sciences, Pharmacy Faculty, University of Salamanca, Campus Miguel de Unamuno , Salamanca , Spain.,c Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca. Hospital Virgen de la Vega , Salamanca , Spain
| | - M Victoria Calvo
- a Pharmacy Service, University Hospital of Salamanca , Salamanca , Spain.,b Department of Pharmaceutical Sciences, Pharmacy Faculty, University of Salamanca, Campus Miguel de Unamuno , Salamanca , Spain.,c Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca. Hospital Virgen de la Vega , Salamanca , Spain
| | - Ana Martín-Suárez
- b Department of Pharmaceutical Sciences, Pharmacy Faculty, University of Salamanca, Campus Miguel de Unamuno , Salamanca , Spain.,c Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca. Hospital Virgen de la Vega , Salamanca , Spain
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8
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Wood S, Petty D, Glidewell L, Raynor DT. Application of prescribing recommendations in older people with reduced kidney function: a cross-sectional study in general practice. Br J Gen Pract 2018; 68:e378-e387. [PMID: 29686132 PMCID: PMC5916085 DOI: 10.3399/bjgp18x695993] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 12/21/2017] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Kidney function reduces with age, increasing the risk of harm from increased blood levels of many medicines. Although estimated glomerular filtration rate (eGFR) is reported for prescribing decisions in those aged ≥65 years, creatinine clearance (Cockcroft-Gault) gives a more accurate estimate of kidney function. AIM To explore the extent of prescribing outside recommendations for people aged ≥65 years with reduced kidney function in primary care and to assess the impact of using eGFR instead of creatinine clearance to calculate kidney function. DESIGN AND SETTING A cross-sectional survey of anonymised prescribing data in people aged ≥65 years from all 80 general practices (70 900 patients) in a north of England former primary care trust. METHOD The prevalence of prescribing outside recommendations was analysed for eight exemplar drugs. Data were collected for age, sex, actual weight, serum creatinine, and eGFR. Kidney function as creatinine clearance (Cockcroft-Gault) was calculated using actual body weight and estimated ideal body weight. RESULTS Kidney function was too low for recommended prescribing in 4-40% of people aged ≥65 years, and in 24-80% of people aged ≥85 years despite more than 90% of patients having recent recorded kidney function results. Using eGFR overestimated kidney function for 3-28% of those aged ≥65 years, and for 13-58% of those aged ≥85 years. Increased age predicted higher odds of having a kidney function estimate too low for recommended prescribing of the study drugs. CONCLUSION Prescribing recommendations when kidney function is reduced are not applied for many people aged ≥65 years in primary care. Using eGFR considerably overestimates kidney function for prescribing and, therefore, creatinine clearance (Cockcroft-Gault) should be assessed when prescribing for these people. Interventions are needed to aid prescribers when kidney function is reduced.
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Affiliation(s)
- Su Wood
- Academic Unit of Primary Care, Institute of Health Sciences, University of Leeds, Leeds
| | - Duncan Petty
- School of Pharmacy and Medical Sciences, University of Bradford, Bradford
| | - Liz Glidewell
- Academic Unit of Primary Care, Institute of Health Sciences, University of Leeds, Leeds
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9
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Poli D, Antonucci E, Zanazzi M, Grifoni E, Testa S, Ageno W, Palareti G. Impact of glomerular filtration estimate on bleeding risk in very old patients treated with vitamin K antagonists. Thromb Haemost 2017; 107:1100-6. [DOI: 10.1160/th11-10-0721] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2011] [Accepted: 04/09/2012] [Indexed: 12/26/2022]
Abstract
SummaryVitamin K antagonists (VKA) therapy is increasingly used in elderly for prevention of venous thromboembolism (VTE) and of stroke in atrial fibrillation (AF). Glomerular filtration rate (GFR), usually estimated from different equations, decreases progressively with age and it is a risk factor for bleeding. In the frame of the EPICA study, a multicentre prospective observational study including 4,093 patients ≥80 years naïve to VKA treated for AF or after VTE, we performed this ancillary study to evaluate the prevalence of chronic kidney diseases (CKD) by estimated GFR (eGFR). Incidence of bleedings was recorded and bleeding risk was evaluated in relation to eGFR calculated by Cockroft-Gault (C-G); Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. In addition, the agreement among the three eGFR formulas was evaluated. We recorded 179 major bleedings (rate 1.87 x100 patient-years [py]), 26 fatal (rate 0.27 x100 py). Moderate CKD was detected in 69.3%, 59.3% and 47.0% and severe CKD in 5.8%, 7.4% and 10.0% of cases by C-G, MDRD and CKD-EPI, respectively. Bleeding risk was higher in patients with severe CKD irrespective of the applied equation. This study confirms that CKD represents an independent risk factor for bleeding and that a wide proportion of elderly on VKA had severe or moderate CKD, suggesting the need for frequent monitoring. Although the different available equations yield different eGFR, all appear to similarly predict the risk of major bleeding.
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10
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Chi XH, Li GP, Wang QS, Qi YS, Huang K, Zhang Q, Xue YM. CKD-EPI creatinine-cystatin C glomerular filtration rate estimation equation seems more suitable for Chinese patients with chronic kidney disease than other equations. BMC Nephrol 2017; 18:226. [PMID: 28693441 PMCID: PMC5504640 DOI: 10.1186/s12882-017-0637-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Accepted: 06/26/2017] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND The aim of this study was to identify the optimal equation that accurately estimates the glomerular filtration rate (GFR) and the chronic kidney disease (CKD) stage in the Chinese population. METHODS A total of 1296 Chinese patients aged 18-65 years old were enrolled in this study. The estimated GFRs (eGFRs) calculated separately by three Diet in Renal Disease (MDRD) equations and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were compared with the reference GFR (rGFR) measured by the 99Tcm-DTPA renal dynamic imaging method. RESULTS By Bland-Altman analysis, eGFRcys and eGFRscr_cys performed similarly, showing the tightest limits of agreement among the six equations. They also achieved the first and second highest 30% and 50% accuracies. Using a combination of the serum creatinine and cystatin C levels (eGFRscr_cys) could improve the bias (-0.3 for eGFRscr_cys) of the equation and achieve the highest diagnostic accuracy for renal insufficiency (AUC60, 0.953; P < 0.05, except for eGFR_MDRD). All equations predicted stage 3 CKD with moderate accuracy (49.7-51.4%) and stage 5 CKD with good accuracy (90.2-96.4%). For stage 1 CKD, eGFRcys showed a higher percentage of misclassification than the other equations. All equations seemed to perform poorly at predicting stage 2 and 4 CKD, as compared to the other CKD stages. eGFRscr_cys was the best-performing equation in terms of accurate classification of the CKD stage based on the overall performance (kappa value, 0.423). CONCLUSION For a Chinese population, the CKD-EPIscr_cys equation seems more suitable for estimating the GFR than the other equations. Each equation had its own advantages in predicting different CKD stages.
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Affiliation(s)
- Xiao-Hua Chi
- Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Gui-Ping Li
- Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Quan-Shi Wang
- Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Yong-Shuai Qi
- Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Kai Huang
- Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Qian Zhang
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Yao-Ming Xue
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
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11
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Barber KE, Bell AM, Stover KR, Wagner JL. Intravenous Vancomycin Dosing in the Elderly: A Focus on Clinical Issues and Practical Application. Drugs Aging 2016; 33:845-854. [PMID: 27878526 PMCID: PMC5122618 DOI: 10.1007/s40266-016-0420-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The elderly population can be divided into three distinct age groups: 65-74 years (young-old), 75-84 years (middle-old), and 85+ years (old-old). Despite evidence of a shift in leading causes for mortality in the elderly from infectious diseases to chronic conditions, infections are still a serious cause of death in this population. These patients are at increased risk due to weakened immune systems, an increased prevalence of underlying comorbidities, and decreased physiologic reserves to fight infection. Additionally, elderly patients, especially adults in institutional settings, are at an increased risk of colonization and subsequent infection with methicillin-resistant Staphylococcus aureus at a rate that is five times higher than in younger individuals, causing an increase in empiric and definitive vancomycin use. Elderly patients have unique characteristics that make dosing vancomycin a challenge for clinicians, such as increased volume of distribution and decreased renal function. Using the best available evidence, it is recommended to initiate lower empiric maintenance doses and monitor vancomycin serum concentrations earlier than steady state to accurately calculate drug elimination and make appropriate dose adjustments.
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Affiliation(s)
- Katie E Barber
- Department of Pharmacy Practice, University of Mississippi School of Pharmacy, 2500 N. State Street, Jackson, MS, 39216, USA
| | - Allison M Bell
- Department of Pharmacy Practice, University of Mississippi School of Pharmacy, 2500 N. State Street, Jackson, MS, 39216, USA
| | - Kayla R Stover
- Department of Pharmacy Practice, University of Mississippi School of Pharmacy, 2500 N. State Street, Jackson, MS, 39216, USA
- Department of Medicine-Infectious Diseases, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA
| | - Jamie L Wagner
- Department of Pharmacy Practice, University of Mississippi School of Pharmacy, 2500 N. State Street, Jackson, MS, 39216, USA.
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12
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Delanaye P, Flamant M, Cavalier É, Guerber F, Vallotton T, Moranne O, Pottel H, Boffa JJ, Mariat C. [Dosing adjustment and renal function: Which equation(s)?]. Nephrol Ther 2015; 12:18-31. [PMID: 26602880 DOI: 10.1016/j.nephro.2015.07.472] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 07/28/2015] [Accepted: 07/29/2015] [Indexed: 12/18/2022]
Abstract
While the CKD-EPI (for Chronic Kidney Disease Epidemiology) equation is now implemented worldwide, utilization of the Cockcroft formula is still advocated by some physicians for drug dosage adjustment. Justifications for this recommendation are that the Cockcroft formula was preferentially used to determine dose adjustments according to renal function during the development of many drugs, better predicts drugs-related adverse events and decreases the risk of drug overexposure in the elderly. In this opinion paper, we discuss the weaknesses of the rationale supporting the Cockcroft formula and endorse the French HAS (Haute Autorité de santé) recommendation regarding the preferential use of the CKD-EPI equation. When glomerular filtration rate (GFR) is estimated in order to adjust drug dosage, the CKD-EPI value should be re-expressed for the individual body surface area (BSA). Given the difficulty to accurately estimate GFR in the elderly and in individuals with extra-normal BSA, we recommend to prescribe in priority monitorable drugs in those populations or to determine their "true" GFR using a direct measurement method.
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Affiliation(s)
- Pierre Delanaye
- Service de néphrologie, dialyse et transplantation, CHU Sart-Tilman, université de Liège, 4000 Liège, Belgique
| | - Martin Flamant
- Service d'explorations fonctionnelles, hôpital Bichat, AP-HP, université Paris Diderot, Paris, France
| | - Étienne Cavalier
- Service de chimie clinique, CHU Sart-Tilman, université de Liège, 4000 Liège, Belgique
| | - Fabrice Guerber
- Laboratoire Oriade-Vizille, 75, chemin de la Terrasse, 38220 Vizille, France
| | - Thomas Vallotton
- Laboratoire Vialle, Bastia et Syndicat des jeunes biologistes médicaux, 20600 BastiaFrance
| | - Olivier Moranne
- EA 2415, biostatistique, épidémiologie et santé publique, institut universitaire de recherche clinique, université de Montpellier, 34093 Montpellier, France
| | - Hans Pottel
- Department of Primary Care and Public Health at Kulak, KU Leuven Kulak, 8500 Kortrijk, Belgique
| | - Jean-Jacques Boffa
- Inserm 1155, service de néphrologie et dialyse, hôpital Tenon, AP-HP, université Pierre-et-Marie-Curie, 75020 Paris, France
| | - Christophe Mariat
- Service de néphrologie, dialyse et transplantation, hôpital Nord, CHU de Saint-Étienne, université Jean-Monnet, 42055 Saint-Étienne, France.
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13
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Romijn MDM, van Marum RJ, Emmelot-Vonk MH, Verhaar HJJ, Koek HL. Mild chronic kidney disease is associated with cognitive function in patients presenting at a memory clinic. Int J Geriatr Psychiatry 2015; 30:758-65. [PMID: 25366465 DOI: 10.1002/gps.4226] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 09/09/2014] [Accepted: 09/25/2014] [Indexed: 10/24/2022]
Abstract
OBJECTIVE In dialysis-dependent and severe chronic kidney disease (CKD) patients, cognitive impairment is found in 16-29%. In community-dwelling population without dementia mixed results have been observed. We investigated the relationship between renal function and cognition in patients from a memory clinic. METHODS We performed a cross-sectional study of consecutive patients from a memory clinic between 2005 and 2009. Renal function was estimated with the Modification of Diet in Renal Diseases (MDRD) and Cockcroft-Gault (CG) formulas, and categorized into ordinal groups: reference ≥ 60 ml/min/1.73 m(2), mild CKD 45-59 ml/min/1.73 m(2) and moderate CKD <45 ml/min/1.73 m(2). Cognitive function was dichotomized (Mini-Mental State Examination (MMSE) ≥ 24 vs. <24). We performed multiple logistic regression analyses with adjustment for potential confounders. RESULTS The cohort comprised 581 patients (mean age 77 ± 10 years). With the MDRD, there were 74 (12%) cases with moderate CKD and 108 (18%) with mild CKD. With the CG, these prevalences were 144 (30%) and 130 (27%). In mild CKD patients, a significant relationship was found between cognitive function and CKD according to the MDRD-formula [adjusted OR 2.10; 95%CI 1.09-4.05]. In moderate CKD patients, no significant adjusted associations were found. In patients without dementia, significant adjusted associations were found between CKD and MMSE (MDRD: mild CKD [OR 5.09; 95%CI 1.17-22.14] and moderate CKD [OR 5.03; 95%CI 1.10-22.98]; CG: mild CKD [OR 6.16; 95%CI 1.17-32.50] and moderate CKD [OR 5.60; 95%CI 1.01-30.91]). CONCLUSION This study showed a significant association between mild CKD and impaired cognitive function in patients from a memory clinic, especially in patients without dementia.
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Affiliation(s)
- Marloes D M Romijn
- Department of Geriatric Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.,Department of Geriatrics, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands
| | - Rob J van Marum
- Department of Geriatrics, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands
| | - Mariëlle H Emmelot-Vonk
- Department of Geriatric Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Harald J J Verhaar
- Department of Geriatric Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Huiberdina L Koek
- Department of Geriatric Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands
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14
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Frisse S, Röhrig G, Franklin J, Polidori MC, Schulz RJ. Prescription errors in geriatric patients can be avoided by means of a computerized physician order entry (CPOE). Z Gerontol Geriatr 2015; 49:227-31. [PMID: 26062963 DOI: 10.1007/s00391-015-0911-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 04/23/2015] [Accepted: 05/05/2015] [Indexed: 11/26/2022]
Abstract
BACKGROUND The implementation of a computerized physician order entry (CPOE) can help reduce prescription errors in clinical practice. OBJECTIVE The aim of this study was to evaluate the effects of a CPOE for geriatric patients with the two most common conditions for drug-induced iatrogenic diseases, dysphagia and renal failure. SUBJECTS AND METHODS A retrospective analysis of actual drug prescriptions versus CPOE recommendations in the geriatric department of the St. Marien Hospital in Cologne, Germany was carried out. Actual drug prescriptions were collected for 26 patients with dysphagia (15 female, 11 male, average age 82.3 ± 8.0 years) and 35 patients with renal failure (23 female, 12 male, average age 80.5 ± 6.7 years) which were compared with recommended prescriptions by means of a CPOE and discrepancies were statistically analyzed. RESULTS Prescription errors for at least 1 drug were detected in 46 % of patients with renal failure and the administration of at least 1 drug with inadequate crushing was observed in 77 % of dysphagia patients. CONCLUSION Prescription errors appear to be frequent to highly frequent in the medical routine even in a highly specialized geriatric setting. Inaccuracies might be reduced by the implementation of a CPOE and even more if coupled to a decision support system. Drug-drug or drug-disease interactions, which are particularly high risks in patients with multimorbidities, multidrug therapy, renal failure or malnutrition, might be kept under control through careful verification of medication indications, organ function status as well as drug administration and preparation in cases of tube feeding.
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Affiliation(s)
- S Frisse
- Department of Geriatrics, St. Marien Hospital, Cologne, Germany
| | - G Röhrig
- Department of Geriatrics, St. Marien Hospital, Cologne, Germany.
- Ageing Clinical Research Department II of Internal Medicine, University Hospital Cologne, Herderstrasse 52, 4th floor, 50937, Cologne, Germany.
| | - J Franklin
- Institute of Medical Statistics, Informatics and Epidemiology (IMSIE), University of Cologne, Cologne, Germany
| | - M C Polidori
- Department of Geriatrics, St. Marien Hospital, Cologne, Germany
- Ageing Clinical Research Department II of Internal Medicine, University Hospital Cologne, Herderstrasse 52, 4th floor, 50937, Cologne, Germany
| | - R-J Schulz
- Department of Geriatrics, St. Marien Hospital, Cologne, Germany
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15
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Martus P, Ebert N, van der Giet M, Jakob O, Schaeffner ES. An efficient approach for glomerular filtration rate assessment in older adults. Br J Clin Pharmacol 2015; 78:384-92. [PMID: 24472092 DOI: 10.1111/bcp.12331] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 01/17/2014] [Indexed: 11/27/2022] Open
Abstract
AIMS Assessment of glomerular filtration rate (GFR) is crucial because the GFR value defines the stage of chronic kidney disease and determines the adjustment of drug dosage. The aim was to investigate a new method for the accurate determination of GFR in older adults based on the combination of an exogenous filtration marker, iohexol, and an endogenous marker, serum creatinine or cystatin C. METHODS We combined variables for the estimation of GFR with a reduced set of measurements of the marker iohexol. In a population-based sample of 570 subjects (≥70 years old) from the Berlin Initiative Study (BIS), we investigated the following: (i) the BIS1 and BIS2 equations based on age, gender and serum creatinine with or without serum cystatin C; (ii) equations based on one or two iohexol measurements; and (iii) equations based on the combination of variables from BIS1 or BIS2 with iohexol measurements. The reference standard was based on eight iohexol measurements. The cut-off value of 60 ml min(-1) (1.73 m)(-2) was chosen to assess accuracy. Equations were constructed using a learning sample (n = 285) and an independent validation sample (n = 285). RESULTS Misclassification rates were 17.2% (BIS1), 11.6% (BIS2), 14.7% [iohexol measurement at 240 min (iohexol240 )], 7.0% (iohexol240 combined with variables included in BIS1) and 6.7% (iohexol240 combined with variables included in BIS2). Misclassification rates did not decrease significantly after inclusion of two or three iohexol measurements. CONCLUSIONS Combined strategies for the determination of GFR lead to a relevant increase of diagnostic validity.
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Affiliation(s)
- Peter Martus
- Institute of Clinical Epidemiology and Medical Biostatistics, UKT Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany
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16
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Eppenga WL, Kramers C, Derijks HJ, Wensing M, Wetzels JFM, De Smet PAGM. Individualizing pharmacotherapy in patients with renal impairment: the validity of the Modification of Diet in Renal Disease formula in specific patient populations with a glomerular filtration rate below 60 ml/min. A systematic review. PLoS One 2015; 10:e0116403. [PMID: 25741695 PMCID: PMC4351004 DOI: 10.1371/journal.pone.0116403] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Accepted: 12/09/2014] [Indexed: 01/20/2023] Open
Abstract
Background The Modification of Diet in Renal Disease (MDRD) formula is widely used in clinical practice to assess the correct drug dose. This formula is based on serum creatinine levels which might be influenced by chronic diseases itself or the effects of the chronic diseases. We conducted a systematic review to determine the validity of the MDRD formula in specific patient populations with renal impairment: elderly, hospitalized and obese patients, patients with cardiovascular disease, cancer, chronic respiratory diseases, diabetes mellitus, liver cirrhosis and human immunodeficiency virus. Methods and Findings We searched for articles in Pubmed published from January 1999 through January 2014. Selection criteria were (1) patients with a glomerular filtration rate (GFR) < 60 ml/min (/1.73m2), (2) MDRD formula compared with a gold standard and (3) statistical analysis focused on bias, precision and/or accuracy. Data extraction was done by the first author and checked by a second author. A bias of 20% or less, a precision of 30% or less and an accuracy expressed as P30% of 80% or higher were indicators of the validity of the MDRD formula. In total we included 27 studies. The number of patients included ranged from 8 to 1831. The gold standard and measurement method used varied across the studies. For none of the specific patient populations the studies provided sufficient evidence of validity of the MDRD formula regarding the three parameters. For patients with diabetes mellitus and liver cirrhosis, hospitalized patients and elderly with moderate to severe renal impairment we concluded that the MDRD formula is not valid. Limitations of the review are the lack of considering the method of measuring serum creatinine levels and the type of gold standard used. Conclusion In several specific patient populations with renal impairment the use of the MDRD formula is not valid or has uncertain validity.
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Affiliation(s)
- Willemijn L. Eppenga
- Radboud University Medical Center, Radboud Institute for Health Sciences, IQ Healthcare, Nijmegen, The Netherlands
- * E-mail:
| | - Cornelis Kramers
- Radboud University Medical Center, Department of Pharmacology and Toxicology, Nijmegen, The Netherlands
- Department of Clinical Pharmacy, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Hieronymus J. Derijks
- Hospital Pharmacy ‘ZANOB’, ‘s-Hertogenbosch, The Netherlands
- Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands
| | - Michel Wensing
- Radboud University Medical Center, Radboud Institute for Health Sciences, IQ Healthcare, Nijmegen, The Netherlands
| | - Jack F. M. Wetzels
- Radboud University Medical Center, Department of Nephrology, Nijmegen, The Netherlands
| | - Peter A. G. M. De Smet
- Radboud University Medical Center, Radboud Institute for Health Sciences, IQ Healthcare, Nijmegen, The Netherlands
- Radboud University Medical Center, Department of Pharmacy, Nijmegen, The Netherlands
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17
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Kaatz S, Mahan CE. Stroke prevention in patients with atrial fibrillation and renal dysfunction. Stroke 2014; 45:2497-505. [PMID: 24968930 DOI: 10.1161/strokeaha.114.005117] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Scott Kaatz
- From the Hurley Medical Center, Flint, MI (S.K.); and New Mexico Heart Institute, Albuquerque, NM (C.E.M.)
| | - Charles E Mahan
- From the Hurley Medical Center, Flint, MI (S.K.); and New Mexico Heart Institute, Albuquerque, NM (C.E.M.).
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18
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Sohn HS, Kwon JW, Kim HS, Kim H. Implications of using Cockcroft–Gault and Modification of Diet in Renal Disease Study equations to estimate renal function in ethnic Korean patients. Am J Health Syst Pharm 2014; 71:1009-18. [DOI: 10.2146/ajhp130492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Hyun Soon Sohn
- College of Pharmacy, Ajou University, Suwon, Republic of Korea
| | - Jin-Won Kwon
- College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea
| | - Hun-Sung Kim
- College of Medicine, The Catholic University of Korea, Seoul
| | - Hyunah Kim
- College of Pharmacy, Sookmyung Women’s University, Seoul
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19
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Huang DL, Abrass IB, Young BA. Medication safety and chronic kidney disease in older adults prescribed metformin: a cross-sectional analysis. BMC Nephrol 2014; 15:86. [PMID: 24906409 PMCID: PMC4057526 DOI: 10.1186/1471-2369-15-86] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 05/01/2014] [Indexed: 11/28/2022] Open
Abstract
Background Medication safety in patients with chronic kidney disease (CKD) is a growing concern. This is particularly relevant in older adults due to underlying CKD. Metformin use is contraindicated in patients with abnormal kidney function; however, many patients are potentially prescribed metformin inappropriately. We evaluated the prevalence of CKD among older adults prescribed metformin for type 2 diabetes mellitus using available equations to estimate kidney function and examined demographic characteristics of patients who were potentially inappropriately prescribed metformin. Methods We conducted a cross-sectional analysis of older adults aged ≥65 years prescribed metformin from March 2008-March 2009 at an urban tertiary-care facility in Seattle, Washington, USA. CKD was defined using National Kidney Foundation-Kidney Disease Outcomes Quality Initiative criteria. Creatinine clearance was calculated using the Cockcroft-Gault equation; estimated glomerular filtration rate was calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) and CKD-Epidemiology (EPI) Collaboration equations. Regression analyses were used to determine the associations between demographic characteristics and prevalent CKD. Results Among 356 subjects (median age 69 years, 52.5% female, 39.4% non-Hispanic black), prevalence of stage 3 or greater CKD calculated by any of the equations was 31.4%. The Cockcroft-Gault equation identified more subjects as having CKD (23.7%) than the abbreviated MDRD (21.1%) or CKD-EPI (21.7%) equations (P < 0.001). Older age (OR = 1.13, 95% CI 1.08-1.19) and female sex (OR = 2.51, 95% CI 1.44-4.38) were associated with increased odds of potentially inappropriate metformin prescription due to CKD; non-Hispanic black race was associated with decreased odds of potentially inappropriate metformin prescription due to CKD (OR = 0.41, 95% CI 0.23-0.71). Conclusions CKD is common in older adults prescribed metformin for type 2 diabetes, raising concern for potentially inappropriate medication use. No single equation to estimate kidney function may accurately identify CKD in this population. Medication safety deserves greater consideration among elderly patients due to the widespread prevalence of CKD.
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Affiliation(s)
- Deborah L Huang
- Division of General Internal Medicine, University of Washington, Box 354765, 4245 Roosevelt Way NE, Seattle, WA 98105, USA.
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20
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Drenth-van Maanen AC, Jansen PAF, Proost JH, Egberts TCG, van Zuilen AD, van der Stap D, van Marum RJ. Renal function assessment in older adults. Br J Clin Pharmacol 2013; 76:616-23. [PMID: 23802656 PMCID: PMC3791984 DOI: 10.1111/bcp.12199] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2013] [Accepted: 06/12/2013] [Indexed: 11/26/2022] Open
Abstract
AIMS The Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formulae are often used to estimate glomerular filtration rate (GFR). The objective was to determine the best method for estimating GFR in older adults. METHODS A cross-sectional study was conducted at the geriatric wards of two hospitals in The Netherlands. Patients aged 70 years or above with an estimated (e)GFR below 60 ml min⁻¹ 1.73 m⁻² were included. The CG, CG calculated with ideal bodyweight (IBW), MDRD and CKD-EPI formulae were compared with a criterion standard, sinistrin clearance. Renal function was classified into five stages according to the National Kidney Foundation Disease Outcomes Quality Initiative chronic kidney disease classification, as follows (in ml min⁻¹ 1.73 m)⁻²: stage 1, eGFR ≥ 90; stage 2, eGFR of 60-89; stage 3, eGFR of 30-59; stage 4, eGFR of 15-29; and stage 5, eGFR < 15. RESULTS Sixteen patients, 50% male, with a mean age of 82 years (range 71-87 years) and mean body mass index 26 kg m⁻² (range 18-36 kg m⁻²), were included. On average, all formulae slightly overestimated GFR, as follows (in ml min⁻¹ 1.73 m⁻²: CG +0.05 [95% confidence interval (CI) -28 to +28]; CG with IBW +0.03 (95% CI -20 to +20); MDRD +9 (95% CI -16 to +34); and CKD-EPI +5 (95% CI -20 to +29). They classified kidney disease correctly in 68.8% (CG), 75% (CG with IBW), 43.8% (MDRD) and 68.8% (CKD-EPI) of the participants, respectively. CONCLUSIONS The CG, CG with IBW, MDRD and CKD-EPI formulae estimate the mean GFR of a population rather well. In individual cases, all formulae may misclassify kidney disease by one stage.
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Affiliation(s)
- A Clara Drenth-van Maanen
- Department of Geriatrics, University Medical Center Utrecht, Utrecht, The Netherlands; Expertise Centre Pharmacotherapy in Old persons (Ephor), Utrecht, The Netherlands
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Chin PKL, Florkowski CM, Begg EJ. The performances of the Cockcroft-Gault, modification of diet in renal disease study and chronic kidney disease epidemiology collaboration equations in predicting gentamicin clearance. Ann Clin Biochem 2013; 50:546-57. [PMID: 24045301 DOI: 10.1177/0004563213492320] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND It is unclear which renal function equation, employing an isotope dilution mass spectrometry (IDMS)-aligned creatinine assay, best predicts gentamicin clearance. METHODS The performances of the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) Study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations for predicting gentamicin clearances were assessed retrospectively in 240 patients treated with gentamicin during 2011-2012, when the local creatinine assay was IDMS-aligned. Comparisons were based on the percentage within 30% of gentamicin clearance (P 30) and the root-mean-square error (RMSE) of each equation. Gentamicin clearance was calculated from plasma concentrations using a one-compartment model. RESULTS The Cockcroft-Gault equation and the CKD-EPI equation corrected for individual body surface area (BSA) were associated with the highest P 30 (69% and 67%, respectively) and lowest RMSE (39 and 36 mL/min, respectively) in the 240 patients. Correction for individual BSA improved the performances of the MDRD Study and CKD-EPI equations in patients with body mass indices <18.5 or ≥30 kg/m(2). The equations systematically underestimated gentamicin clearance as gentamicin clearance increased, with performance being inferior with gentamicin clearance ≥90 versus <90 mL/min. CONCLUSIONS The CKD-EPI equation corrected for individual BSA, and the Cockcroft-Gault equation, provided the best estimates of gentamicin clearance. The CKD-EPI and MDRD Study equations should be corrected for individual BSA at the extremes of body size, if used for guiding gentamicin therapy. The performances of the equations were inferior in patients with higher values of gentamicin clearance.
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Affiliation(s)
- P K L Chin
- Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand
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22
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Zhang L, Xu N, Xiao S, Arya V, Zhao P, Lesko LJ, Huang S. Regulatory Perspectives on Designing Pharmacokinetic Studies and Optimizing Labeling Recommendations for Patients With Chronic Kidney Disease. J Clin Pharmacol 2013; 52:79S-90S. [DOI: 10.1177/0091270011415410] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Lei Zhang
- Office of Clinical Pharmacology, Office of Translational Sciences, Food and Drug Administration, Silver Spring, Maryland
- Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
| | - Nancy Xu
- Office of Drug Evaluation I, Office of New Drugs, Food and Drug Administration, Silver Spring, Maryland
- Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
| | - Shen Xiao
- Office of Drug Evaluation I, Office of New Drugs, Food and Drug Administration, Silver Spring, Maryland
- Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
| | - Vikram Arya
- Office of Clinical Pharmacology, Office of Translational Sciences, Food and Drug Administration, Silver Spring, Maryland
- Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
| | - Ping Zhao
- Office of Clinical Pharmacology, Office of Translational Sciences, Food and Drug Administration, Silver Spring, Maryland
- Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
| | - Lawrence J. Lesko
- Office of Clinical Pharmacology, Office of Translational Sciences, Food and Drug Administration, Silver Spring, Maryland
- Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
| | - Shiew‐Mei Huang
- Office of Clinical Pharmacology, Office of Translational Sciences, Food and Drug Administration, Silver Spring, Maryland
- Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
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Lee JP, Wang YJ. Testing the predictive ability of the “spinal cord injury equation” in estimating vancomycin clearance. Am J Health Syst Pharm 2013; 70:669-74. [DOI: 10.2146/ajhp120329] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
| | - Yi-Jiun Wang
- Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA
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Lilly CM, Welch VL, Mayer T, Ranauro P, Meisner J, Luke DR. Evaluation of intravenous voriconazole in patients with compromised renal function. BMC Infect Dis 2013; 13:14. [PMID: 23320795 PMCID: PMC3584958 DOI: 10.1186/1471-2334-13-14] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2012] [Accepted: 01/08/2013] [Indexed: 11/16/2022] Open
Abstract
Background Incorporation of the solubilizing excipient, sulfobutylether-β-cyclodextrin (SBECD), in the intravenous (IV) formulation of voriconazole has resulted in the recommendation that this formulation be used with caution in patients with creatinine clearances (Clcr) < 50 mL/min. This study evaluated the safety of IV voriconazole compared with two other IV antifungals not containing SBECD in patients with compromised renal function. Methods A total of 128 patients aged 11–93 years who had a baseline Clcr < 50 mL/min between January 1, 2007 and December 31, 2010 were identified from a database of a university-affiliated inpatient healthcare system; of these, 55 patients received caspofungin, 54 patients received fluconazole, and 19 patients received voriconazole. Changes in serum creatinine (Scr) and Clcr levels while on therapy were compared with baseline values and between groups. Results The groups had similar characteristics apart from the larger proportion of females that received fluconazole. Baseline Scr was higher in those receiving caspofungin, but maximal increases of Scr and decreases in Clcr were greatest for the fluconazole group. Acute kidney injury (AKI), assessed by RIFLE criteria, was more frequent in the fluconazole vs. the caspofungin group (p < 0.01); incidence of AKI in the voriconazole group was not significantly different than found in the other two groups. The infecting organism was a predictor of AKI and formulation with SBECD was not. Conclusions Treatment of fungal infections in patients with compromised renal function with an SBECD-containing antifungal agent was not associated with AKI in clinical practice. Since the infecting organism was associated with AKI, decision on which antifungal to use should be determined by susceptibilities to the organism and not the incorporation of SBECD in the IV formulation.
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Affiliation(s)
- Craig M Lilly
- University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Similar risk of renal events among patients treated with tenofovir or entecavir for chronic hepatitis B. Clin Gastroenterol Hepatol 2012; 10:941-6; quiz e68. [PMID: 22507876 DOI: 10.1016/j.cgh.2012.04.008] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2011] [Revised: 03/17/2012] [Accepted: 04/04/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Tenofovir is a nucleotide reverse-transcriptase inhibitor approved for treatment of human immunodeficiency virus infection, as well as chronic hepatitis B (CHB). We evaluated nephrotoxicity among patients with CHB treated with tenofovir. METHODS We performed a community-based, retrospective cohort study of 80 patients with CHB who received tenofovir, alone or in a combination regimen; they were matched for age and sex with 80 CHB patients who received only entecavir. Incidences of serum creatinine (SCr) increase ≥0.2 mg/dL and new SCr levels of 1.5, 2.0, or 2.5 mg/dL were assessed. Patients with an estimated glomerular filtration rate (eGFR) <60 mL/min, calculated using the Modification of Diet in Renal Disease or Cockcroft-Gault formula, or who had ≥20% decrease in eGFR were also recorded. RESULTS More patients given entecavir had increases in SCr ≥2.5 mg/dL (1 vs 6; P = .053), whereas more patients given tenofovir had a new Cockcroft-Gault eGFR of <60 mL/min (15 vs 6; P = .022) and at least 1 dose adjustment (13 vs 4; P = .021). By multivariate analysis, the only significant factors associated with an increase in SCr were a history of organ transplantation (adjusted odds ratio, 6.740; 95% confidence interval, 1.799-28.250; P = .005) and pre-existing renal insufficiency (adjusted odds ratio, 10.960; 95% confidence interval, 2.419-48.850; P = .002). No factors, including therapy assignment, were associated with a new eGFR <60 mL/min. CONCLUSIONS Markers of renal function indicated that patients who received tenofovir were no more likely to have changes in renal function than patients treated with entecavir. History of transplant and pre-existing renal insufficiency were the only factors independently associated with increases in SCr.
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26
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Pan SW, Kao HK, Yu WK, Lien TC, Chen YW, Wang JH, Kou YR. Synergistic impact of low serum albumin on intensive care unit admission and high blood urea nitrogen during intensive care unit stay on post-intensive care unit mortality in critically ill elderly patients requiring mechanical ventilation. Geriatr Gerontol Int 2012; 13:107-15. [PMID: 22672187 DOI: 10.1111/j.1447-0594.2012.00869.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
AIMS To identify intensive care unit (ICU) risk factors for post-ICU 6-month (PI6M) mortality in critically ill elderly patients requiring mechanical ventilation (MV). METHODS The present study was a retrospective observational study carried out in a respiratory ICU from December 2008 to December 2009. Medical records of patients aged ≥70 years and receiving MV were reviewed. Risk factors of PI6M mortality were assessed by multivariate Cox regression. RESULTS Of 120 patients enrolled, 46 (38%) died in the PI6M period. As compared with survivors, non-survivors had lower serum albumin levels on ICU admission, lower estimated glomerular filtration rate, higher peak blood urea nitrogen (BUN) levels during ICU stay (ICU-peak BUN), a higher ratio of prolonged steroid use and longer MV length in ICU. Independent risk factors of PI6M mortality were low albumin on admission (hazard ratio [HR] 3.53 per g/dL decrease, 95% CI [1.97-6.33], P<0.001) and high ICU-peak BUN (HR 1.11 per 10-mg/dL increase, [1.04-1.18], P=0.001). The HR for PI6M mortality was 7.88 [2.97-20.91] for patients with both risk factors (albumin ≤2.8 g/dL and ICU-peak BUN >72 mg/dL) as compared with those without. For patients with high ICU-peak BUN (>72 mg/dL), PI6M survival was better for those with a reduction in BUN level to ≤72 mg/dL at ICU discharge than those without. CONCLUSIONS Low serum albumin level on ICU admission and high BUN level during ICU stay are two independent risk factors, especially their combination, of PI6M mortality in critically ill elderly patients requiring MV. Furthermore, patients with a reduction in high BUN have a better PI6M survival.
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Affiliation(s)
- Sheng-Wei Pan
- Department of Respiratory Therapy, Taipei Veterans General Hospital, Taipei, Taiwan
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Rothenbacher D, Klenk J, Denkinger M, Karakas M, Nikolaus T, Peter R, Koenig W. Prevalence and determinants of chronic kidney disease in community-dwelling elderly by various estimating equations. BMC Public Health 2012; 12:343. [PMID: 22574773 PMCID: PMC3490787 DOI: 10.1186/1471-2458-12-343] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Accepted: 04/27/2012] [Indexed: 11/30/2022] Open
Abstract
Background Chronic kidney disease (CKD) represents a global public health problem. Few data exist in the elderly. The objective of the current study is to estimate the prevalence of CKD by means of various established and new equations and to identify the main determinants of CKD in elderly. Methods The ActiFE Ulm (Activity and Function in the Elderly in Ulm) study is a population-based cohort study in people of 65 years and older. Kidney function was assessed by means of estimated glomerular filtration rate (eGFR) based on two creatinine- (Cr-; MDRD, CKD-EPI) and one cystatin C - (CysC-) based method. The relationship between various potential risk factors and CKD was quantified using unconditional logistic regression. Results A total of 1471 subjects were in the final analysis (mean age 75.6 years, SD 6.56). Overall, prevalence of CKD (eGFR < 60 mL/min/1.73 m2) was 34.3% by MDRD, 33.0% by CKD-EPI, and 14.6% by the CysC-based eGFR. All eGFRs showed statistically significant correlations with C-reactive protein, uric acid, as well as with lipid values. In multivariable analysis age was clearly related to prevalence of CKD and the risks were highest with the CysC-based equation. Females had a higher risk for CKD stages 3–5 with MDRD (OR 1.63; 95% CI: 1.23–2.16) whereas the OR was 1.23 (95% CI 0.92–1.65) with the CKD-Epi and OR = 0.89 (95% CI 0.58–1.34) with the CysC-based equation after multivariable adjustment. Although the cystatin C based definition of CKD resulted in a lower prevalence compared to the creatinine based ones, other measures of renal damage such as albuminuria were more prevalent in those defined by CysC-eGFR. Conclusions Prevalence of CKD is very variable based on the used estimating equation. More work is needed to evaluate the various estimating equations especially in elderly before we are able to assess the practical consequences of the observed differences.
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Affiliation(s)
- Dietrich Rothenbacher
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Helmholtzstr 22, D-89081, Germany.
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Nyman HA, Dowling TC, Hudson JQ, Peter WLS, Joy MS, Nolin TD. Comparative evaluation of the Cockcroft-Gault Equation and the Modification of Diet in Renal Disease (MDRD) study equation for drug dosing: an opinion of the Nephrology Practice and Research Network of the American College of Clinical Pharmacy. Pharmacotherapy 2012; 31:1130-44. [PMID: 22026399 DOI: 10.1592/phco.31.11.1130] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Accurate assessment of kidney function is an important component of determining appropriate drug dosing regimens. Nearly all manufacturer-recommended dosage adjustments are based on creatinine clearance ranges derived from clinical pharmacokinetic studies performed during the drug development process. The Cockcroft-Gault (CG) equation provides an estimate of creatinine clearance and is the equation most commonly used to determine drug dosages in patients with impaired kidney function. The Modification of Diet in Renal Disease (MDRD) study equation has also been proposed for this purpose. Published studies report that drug dosages determined by the two equations do not agree in 10-40% of cases. However, interpretation and comparison of these studies are complicated by the variable creatinine methods used for calculating CG and MDRD estimates, the patient populations studied, and a lack of outcomes data demonstrating the clinical significance of dosing discrepancies. Moreover, the impact of reporting standardized serum creatinine values on the accuracy of the CG equation and corresponding drug dosing regimens have been questioned. Currently, no prospective pharmacokinetic studies have been conducted with use of the MDRD equation to generate dosing recommendations, and limited data are available to support its use in some patient populations representing demographic extremes. Collectively, these issues have resulted in considerable confusion among clinicians and have fueled a healthy debate on whether or not to use the MDRD equation to determine drug dosages. Each of these issues is reviewed, and a proposed algorithm for using creatinine-based kidney function assessments in drug dosing is provided. Knowledge of the advantages, limitations, and clinical role of each equation will facilitate their safe and effective use in drug dosing.
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Affiliation(s)
- Heather A Nyman
- University of Utah Hospitals and Clinics, Salt Lake City, Utah, USA
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Comparison of four renal function estimation equations for pharmacokinetic modeling of gentamicin in geriatric patients. Antimicrob Agents Chemother 2012; 56:1862-9. [PMID: 22290966 DOI: 10.1128/aac.05634-11] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Most aminoglycoside pharmacokinetic models include an index of renal function, such as creatinine clearance, to describe drug clearance. However, the best clinical descriptor of renal function for the pharmacokinetic modeling of aminoglycosides has not been established. This analysis was based on 412 gentamicin concentrations from 92 geriatric patients who received intravenous gentamicin for various infectious diseases. Four two-compartment population models were fitted to gentamicin concentrations in a learning set of 64 patients using the nonparametric adaptive grid (NPAG) algorithm. Each model included an index of renal function, namely, the Cockcroft-Gault (CG), Jelliffe (JEL), modification of diet in renal disease (MDRD), or modified MDRD (MDRDm; adjusted to individual body surface area) equation as a covariate influencing gentamicin serum clearance. Goodness of fit and predictive performance of the four models were compared using standard criteria in both the learning set and in a validation set of 28 patients. A final analysis was performed to estimate the population pharmacokinetic parameter values of the entire 92-patient group. In the learning set, the CG-based model best fit the data, followed by JEL-, MDRD-, and MDRDm-based models, with relative reductions of the Akaike information criterion of 29.4, 20.2, 14.2, and 4.2, respectively. Bias and precision of population predictions were significantly different among the four models. In the validation set, individual predictions from the four models showed marginally different biases. The final estimation confirmed the previous results. Specifically, the CG-based model showed predictive performance that was comparable to or better than that of the MDRD-based model at each stage of the analysis. This study shows that methods used to estimate renal function should not be considered interchangeable for the model-based estimation of gentamicin concentrations.
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30
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Hanlon JT, Aspinall SL. Renal Function Equations to Use to Guide Prescribing of Primarily Renally Cleared Medications for Older Adults. J Am Med Dir Assoc 2012. [DOI: 10.1016/j.jamda.2011.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Taylor LA, Mauro VF. Incidence of bleeding in renally impaired patients receiving incorrectly dosed eptifibatide or bivalirudin while undergoing percutaneous coronary intervention. Ann Pharmacother 2011; 46:35-41. [PMID: 22170973 DOI: 10.1345/aph.1q402] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Limited data are available regarding adverse bleeding events associated with antithrombotic agents incorrectly dosed based on renal function in patients receiving percutaneous coronary intervention (PCI). OBJECTIVE To compare the incidence of bleeding during their hospital stay in patients with reduced renal function receiving incorrect doses of bivalirudin or eptifibatide to the incidence of correct doses, based on manufacturer recommendations; secondary objectives were to determine the incidence of correct dosing based on manufacturer recommendations and the incidence of TIMI (Thrombolysis in Myocardial Infarction) major bleeding. METHODS A chart review over a 32-month period showed that patients with reduced renal function who received either eptifibatide or bivalirudin during PCI were evaluated for correct dosing based on manufacturer recommendations, bleeding incidence according to the TIMI criteria, and extent of bleeding according to the TIMI and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) criteria. RESULTS One hundred ninety patients met inclusion criteria, 56 who received eptifibatide and 134 who received bivalirudin. Eptifibatide was dosed incorrectly in 64% of the patients. Patients receiving incorrectly dosed compared to correctly dosed eptifibatide experienced significantly more bleeding (64% vs 35%, respectively, p = 0.04), a greater extent of bleeding based on the TIMI and GUSTO criteria (p = 0.03 and p = 0.009, respectively), and had more TIMI major bleeding (19% vs 5%, respectively). Bivalirudin was dosed incorrectly in 28% of the patients. Patients receiving incorrectly dosed compared to correctly dosed bivalirudin experienced a significantly greater extent of bleeding based on the GUSTO criteria (p = 0.01). There was no significant difference between the incidence of bleeding (37% vs 21%, respectively; p = 0.06), extent of bleeding based on the TIMI criteria (p = 0.058), or incidence of TIMI major bleeding (5% vs 3%). CONCLUSIONS Patients receiving incorrectly dosed eptifibatide and bivalirudin are susceptible to adverse bleeding events. The occurrence of incorrect dosing offers an opportunity for pharmacist-driven institutional improvement.
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Use of estimated glomerular filtration rate for drug dosing in the chronic kidney disease patient. Curr Opin Nephrol Hypertens 2011; 20:482-91. [PMID: 21709552 DOI: 10.1097/mnh.0b013e328348c11f] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
PURPOSE OF REVIEW Assessment of kidney function is necessary to stage chronic kidney disease (CKD) and appropriately dose medications. The Cockcroft-Gault equation provides an estimate of creatinine clearance (eClCr) and is the method commonly referenced in pharmacokinetic studies. The Modification of Diet in Renal Disease (MDRD) and CKD-Epidemiology Collaboration (EPI) equations provide an estimate of glomerular filtration rate (eGFR), with the MDRD eGFR now automatically reported by most clinical laboratories. This review describes the differences in the Cockcroft-Gault, MDRD, and CKD-EPI equations and considerations when applying estimates from these equations for drug dosing. RECENT FINDINGS Studies evaluating drug-dosing regimens using eClCr and eGFR differ in their results depending on the population in which the equation is applied, the adjustment factors used to account for body size, and the number of dosing levels for a particular medication. The largest study to evaluate drug regimen design by method concluded that either the eGFR or Cockcroft-Gault estimates could be used for drug dosing. Differences in methodology among studies are a key factor in evaluating these results and will be highlighted in this review. SUMMARY The Cockcroft-Gault, MDRD, and CKD-EPI equations provide reasonable estimates of kidney function; however, clinicians must understand the limitations when using these estimates for drug regimen design.
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Iliadis F, Didangelos T, Ntemka A, Makedou A, Moralidis E, Gotzamani-Psarakou A, Kouloukourgiotou T, Grekas D. Glomerular filtration rate estimation in patients with type 2 diabetes: creatinine- or cystatin C-based equations? Diabetologia 2011; 54:2987-94. [PMID: 21947381 DOI: 10.1007/s00125-011-2307-1] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2011] [Accepted: 08/16/2011] [Indexed: 10/17/2022]
Abstract
AIMS/HYPOTHESIS It is argued that GFR estimation (eGFR) using cystatin C-based equations (eGFRcys) is superior to that using creatinine-based equations (eGFRcre). We investigated whether eGFRcys are superior to eGFRcre in patients with type 2 diabetes. METHODS GFR was measured in 448 type 2 diabetic patients using (51)Cr-EDTA-measured GFR (mGFR) as the reference standard. Bias, precision and accuracy of eGFRcys and eGFRcre were compared. RESULTS The most accurate eGFRcre equation (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]), which produced the highest proportion of estimates that were within 30% and 10% of the reference standard (80.7% and 38.0% of samples, respectively) had a bias of 7.1 and precision of 12.0 ml min(-1) 1.73 m(-2). The calibrated eGFRcys with the highest accuracy (Tan-C), which produced the highest proportion of estimates that were within 30% (78.8%) and within 10% (39.0%) of the reference standard had a bias of -3.5 and precision of 18.0 ml min(-1) 1.73 m(-2). Moreover, the areas under the receiver operating curve were higher with eGFRcre (CKD-EPI and Modification of Diet in Renal Disease [MDRD]) than with eGFRcys for the diagnosis of mild (mGFR <90 ml min(-1) 1.73 m(-2)) and moderate (mGFR <60 ml min(-1) 1.73 m(-2)) chronic kidney disease. In patients with mGFR ≥90 ml min(-1) 1.73 m(-2), CKD-EPI was the least biased, the most precise and the most accurate equation. CONCLUSIONS/INTERPRETATION In patients with type 2 diabetes, eGFRcys do not currently provide better eGFR than eGFRcre. At present, compared with eGFRcys, eGFRcre are better at predicting the stage of chronic kidney disease. In addition, CKD-EPI seems to be the best equation for eGFR in patients with normal renal function.
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Affiliation(s)
- F Iliadis
- First Propedeutic Department of Internal Medicine, University General Hospital AHEPA, S. Kyriakidi Street 1, 54636 Thessaloniki, Greece.
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Glomerular filtration rate estimation in patients with type 2 diabetes: creatinine- or cystatin C-based equations? Diabetologia 2011. [PMID: 21947381 DOI: 10.1007/200125-011-2307-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
AIMS/HYPOTHESIS It is argued that GFR estimation (eGFR) using cystatin C-based equations (eGFRcys) is superior to that using creatinine-based equations (eGFRcre). We investigated whether eGFRcys are superior to eGFRcre in patients with type 2 diabetes. METHODS GFR was measured in 448 type 2 diabetic patients using (51)Cr-EDTA-measured GFR (mGFR) as the reference standard. Bias, precision and accuracy of eGFRcys and eGFRcre were compared. RESULTS The most accurate eGFRcre equation (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]), which produced the highest proportion of estimates that were within 30% and 10% of the reference standard (80.7% and 38.0% of samples, respectively) had a bias of 7.1 and precision of 12.0 ml min(-1) 1.73 m(-2). The calibrated eGFRcys with the highest accuracy (Tan-C), which produced the highest proportion of estimates that were within 30% (78.8%) and within 10% (39.0%) of the reference standard had a bias of -3.5 and precision of 18.0 ml min(-1) 1.73 m(-2). Moreover, the areas under the receiver operating curve were higher with eGFRcre (CKD-EPI and Modification of Diet in Renal Disease [MDRD]) than with eGFRcys for the diagnosis of mild (mGFR <90 ml min(-1) 1.73 m(-2)) and moderate (mGFR <60 ml min(-1) 1.73 m(-2)) chronic kidney disease. In patients with mGFR ≥90 ml min(-1) 1.73 m(-2), CKD-EPI was the least biased, the most precise and the most accurate equation. CONCLUSIONS/INTERPRETATION In patients with type 2 diabetes, eGFRcys do not currently provide better eGFR than eGFRcre. At present, compared with eGFRcys, eGFRcre are better at predicting the stage of chronic kidney disease. In addition, CKD-EPI seems to be the best equation for eGFR in patients with normal renal function.
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Lee JP, Dang AT. Evaluation of methods to estimate glomerular filtration rate versus actual drug clearance in patients with chronic spinal cord injury. Spinal Cord 2011; 49:1158-63. [DOI: 10.1038/sc.2011.82] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Launay-Vacher V, Zimner-Rapuch S, Amet S, Janus N, Deray G. La formule aMDRD est la formule de choix pour évaluer la fonction rénale, y compris chez les patients de plus de 80ans : commentaire sur l’article de Andro et al. Rev Med Interne 2011; 32:391-2; author reply 393. [DOI: 10.1016/j.revmed.2011.03.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2011] [Accepted: 03/12/2011] [Indexed: 10/28/2022]
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Hanlon JT, Wang X, Handler SM, Weisbord S, Pugh MJ, Semla T, Stone RA, Aspinall SL. Potentially inappropriate prescribing of primarily renally cleared medications for older veterans affairs nursing home patients. J Am Med Dir Assoc 2011; 12:377-83. [PMID: 21450179 PMCID: PMC3102140 DOI: 10.1016/j.jamda.2010.04.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2010] [Revised: 04/19/2010] [Accepted: 04/19/2010] [Indexed: 01/08/2023]
Abstract
BACKGROUND Inappropriate prescribing of primarily renally cleared medications in older patients with kidney disease can lead to adverse outcomes. OBJECTIVES To estimate the prevalence of potentially inappropriate prescribing of 21 primarily renally cleared medications based on 2 separate estimates of renal function and to identify factors associated with this form of suboptimal prescribing in older VA nursing home (NH) patients. DESIGN Longitudinal study PARTICIPANTS Participants were 1304 patients, aged 65 years or older, admitted between January 1, 2004, and June 30, 2005, for 90 days or more to 1 of 133 VA NHs. MAIN MEASURES Potentially inappropriate prescribing of primarily renally cleared medications determined by estimating creatinine clearance using the Cockcroft Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations and applying explicit guidelines for contraindicated medications and dosing. KEY RESULTS The median estimated creatinine clearance via CG was 67 mL/min, whereas it was 80 mL/min/1.73m(2) with the MDRD. Overall, 11.89% patients via CG and only 5.98% via MDRD had evidence of potentially inappropriate prescribing of at least 1 renally cleared medication. The most commonly involved medications were ranitidine, glyburide, gabapentin, and nitrofurantoin. Factors associated with potentially inappropriate prescribing as per the CG were age older than 85 (adjusted odds ratio [AOR] 4.24, 95% confidence interval [CI] 2.42-7.43), obesity (AOR 0.26, 95% CI 0.14-0.50) and having multiple comorbidities (AOR 1.09 for each unit increase in the Charlson comorbidity index, 95% CI 1.01-1.19). CONCLUSIONS Potentially inappropriate prescribing of renally cleared medications is common in older VA NH patients. Intervention studies to improve the prescribing of primarily renally cleared medications in nursing homes are needed.
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Affiliation(s)
- Joseph T Hanlon
- Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
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Hilmer SN, Tran K, Rubie P, Wright J, Gnjidic D, Mitchell SJ, Matthews S, Carroll PR. Gentamicin pharmacokinetics in old age and frailty. Br J Clin Pharmacol 2011; 71:224-31. [PMID: 21219402 DOI: 10.1111/j.1365-2125.2010.03825.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIMS Frailty, a syndrome of decreased physiological reserve that is prevalent in old age, impacts on clinical pharmacology. The aims of the study were to (1) determine whether frailty affects the pharmacokinetics of gentamicin and (2) assess the accuracy of different estimates of body size and renal clearance as estimates of gentamicin pharmacokinetics in older inpatients. METHODS This was an observational study of gentamicin pharmacokinetics in a cohort of Australian hospital inpatients aged ≥65 years, who were administered prophylactic intravenous gentamicin. RESULTS Of the 31 participants, 14 were frail and 17 non frail on the Reported Edmonton Frail Scale. The mean volume of distribution of gentamicin was 14.8 ± 1.4 l in frail participants and 15.3 ± 2.2 l in non frail (NS). Volume of distribution correlated best with lean bodyweight. Gentamicin clearance was significantly lower in frail participants (46.6 ± 10.7 ml min(-1)) than in non frail (58.2 ± 12.4 ml min(-1), P=0.01). The Cockcroft Gault estimate of creatinine clearance calculated using ideal bodyweight gave the best estimate of gentamicin clearance (mean error -0.15 ml min(-1), 95% CI -2.67, 2.39). The Cockcroft Gault creatinine clearance calculated using actual bodyweight and the estimated glomerular filtration rate from the modified diet in renal disease equation overestimated gentamicin clearance, with mean errors of -10.15 ml min(-1) (95%CI -13.60, -6.71) and -18.86 ml min(-1) (95% CI -22.45, -15.27), respectively. The Cockcroft Gault creatinine clearance calculated using lean bodyweight underestimated gentamicin clearance (mean error 6.54 ml min(-1), 95% CI 4.18, 8.90). CONCLUSIONS Frail older people have significantly lower gentamicin clearance than non frail. The best estimate of gentamicin clearance is obtained from the Cockcroft Gault creatinine clearance calculated using ideal bodyweight.
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Affiliation(s)
- Sarah N Hilmer
- Sydney Medical School, University of Sydney, Sydney, Australia.
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Delanghe JR, Cobbaert C, Harmoinen A, Jansen R, Laitinen P, Panteghini M. Focusing on the clinical impact of standardization of creatinine measurements: a report by the EFCC Working Group on Creatinine Standardization. Clin Chem Lab Med 2011; 49:977-82. [PMID: 21428858 DOI: 10.1515/cclm.2011.167] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
The recent campaign for standardization of creatinine measurements has been promoted to allow the widespread use of formulas for estimating the glomerular filtration rate (GFR). However, studies on trueness verification and measurement interferences still show disappointing interassay variation of serum creatinine results. Creatinine recalibration has major clinical consequences. In particular, in pediatrics where reference ranges for serum and plasma creatinine are low, calculation of the GFR is problematic when based on alkaline picrate methods because of method non-specificity and the lack of appropriate GFR estimating formulas. Therefore, enzymatic creatinine assays are preferred. In the near future, cystatin C might offer an interesting alternative for GFR estimation. For the calculation of drug doses, the Modification of Diet in Renal Disease study formula generally offers reliable data. However, attention has to be paid to the elderly. Also, the calculation of the Model for End-Stage Liver Disease score, which is used to prioritize patients for liver transplantation, may significantly be influenced by recalibration of creatinine assays. Creatinine restandardization may also affect the current guidelines for referral of chronic kidney disease patients to nephrologists.
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Affiliation(s)
- Joris R Delanghe
- Department of Clinical Chemistry, University Hospital, Gent, Belgium.
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40
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Andro M, Estivin S, Comps E, Gentric A. [Assessment of renal function in elderly after eighty years: Cockroft and Gault or Modification of diet in renal disease equation?]. Rev Med Interne 2011; 32:698-702. [PMID: 21277052 DOI: 10.1016/j.revmed.2010.12.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2010] [Revised: 11/15/2010] [Accepted: 12/20/2010] [Indexed: 10/18/2022]
Abstract
Assessment of renal function is essential in the management of hospitalised patients, particularly in geriatric practice. Impairment of renal function is common in the elderly, aged of 80 years and over, and should be taken into account before prescribing drugs eliminated through the kidneys or performing investigations requiring iodine injection. Renal failure is also a predictor of mortality. In clinical practice, creatinine-based equations are recommended to assess kidney function. The most widely used equations are the Cockroft and Gault (CG) and the simplified Modification of diet in renal disease (MDRD) formulas. The former estimates the clearance of creatinine in millilitres per minute, the latter estimates the glomerular filtration rate in millilitres per minute per 1.73 m(2). In 2002, the French high authority for health recommended the use of the CG formula, but no recommendation was given for the elderly. In the literature, no study has compared CG and MDRD formulas with a reference method in this very old population. In the octogenarians, two studies have compared these formulas with the creatinine clearance calculated on the basis of a 24-hour urine collection and four studies have compared the formulas head to head. All these studies showed that the results obtained with the MDRD formula are higher from 10 to 30 mL/min/1.73 m(2) than the results obtained with the CG formula. Studies simulating drug prescription showed that the use of the MDRD formula would lead to a risk of drug over dosage in 20 to 36% of the elderly. Also, two studies have suggested that only creatinine clearance measured by the CG formula is a predictor of mortality in the very old population. In conclusion, in the octogenarian, none of these two formulas is ideal. However, based on the results of studies targeted to this elderly population, the best solution seems to be the use of the CG formula expecting new methods of evaluation of renal function.
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Affiliation(s)
- M Andro
- Service de médecine interne gériatrique, CHU La Cavale Blanche, Brest, France.
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Gauzit R. Actualités en antibiothérapie — Aminosides toujours et encore: bon usage et suivi thérapeutique. ACTA ACUST UNITED AC 2010. [DOI: 10.1007/s13546-010-0106-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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