METHODS: MEDLINE and Embase databases were searched from inception up to September 2019 to identify all studies that compared the predictive performance of cystatin C- and/or creatinine-based eGFR in predicting the clearance of vancomycin. The prediction errors (PEs) (the value of eGFR equations minus vancomycin clearance) were quantified for each equation and were pooled using a random-effects model. The root mean squared errors were also quantified to provide a metric for imprecision.
RESULTS: This meta-analysis included evaluations of seven different cystatin C- and creatinine-based eGFR equations in total from 26 studies and 1,234 patients. The mean PE (MPE) for cystatin C-based eGFR was 4.378 mL min-1 (95% confidence interval [CI], -29.425, 38.181), while the creatinine-based eGFR provided an MPE of 27.617 mL min-1 (95% CI, 8.675, 46.560) in predicting clearance of vancomycin. This indicates the presence of unbiased results in vancomycin clearance prediction by the cystatin C-based eGFR equations. Meanwhile, creatinine-based eGFR equations demonstrated a statistically significant positive bias in vancomycin clearance prediction.
CONCLUSION: Cystatin C-based eGFR equations are better than creatinine-based eGFR equations in predicting the clearance of vancomycin. This suggests that utilising cystatin C-based eGFR equations could result in better accuracy and precision to predict vancomycin pharmacokinetic parameters.
METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.
RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.
CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.
MATERIALS AND METHODS: An e-mail invitation to participate in an online survey was sent to hospital laboratories in Malaysia (n=140). Questions regarding methods for measuring creatinine, equations for calculating eGFR, eGFR reporting, the terminology used in reporting urine albumin, types of samples and the cut-off values used for normal albuminuria.
RESULTS: A total of 42/140 (30%) laboratories answered the questionnaire. The prevalent method used for serum creatinine measurement was the Jaffé method (88.1%) traceable to isotope-dilution mass spectrometry. eGFR was reported along with serum creatinine by 61.9% of laboratories while 33.3% of laboratories report eGFR on request. The formula used for eGFR reporting was mainly MDRD (64.3%) and results were reported as exact numbers even when the eGFR was <60 ml/min/1.73m2. The term microalbumin is still used by 83.3% of laboratories. There is a large heterogeneity among the labs regarding the type of sample recommended for measuring urine albumin, reference interval and reporting units.
CONCLUSION: It is evident that the laboratory assessment of chronic kidney disease in Malaysia is not standardised. It is essential to provide a national framework for standardised reporting of eGFR and urine albumin. Recommendations developed by the MACB CKD Task Force, if adopted by all laboratories, will lead to a reduction in this variability.
METHODS: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution.
RESULTS: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug-specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50-5.69) (gentamicin), 7.77 L/h (95% CI 7.26-8.19) (amikacin) and 4.70 L/h (95% CI 4.61-4.80) (vancomycin).
CONCLUSIONS: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention.
Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals.
Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported.
Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.
Results: Prior to total hip arthroplasty, 20% of all patients met the chronic renal dysfunction criterion of glomerular filtration rates <60ml/min/1.73m2 (glomerular filtration rate categories G3a-G5). Incidence rates of acute kidney injury and acute deterioration of kidney function after total hip arthroplasty were 0.49% and 6.9%, respectively. Multivariate regression analysis showed that diabetes mellitus and use of nonsteroidal anti-inflammatory drugs before total hip arthroplasty were significant risk factors for acute deterioration of kidney function. Advanced age, preoperative renal dysfunction, antihypertensive, diuretics, or statin use, operation time, total blood loss, type of anesthetic, and body mass index were not significant risk factors.
Conclusion: Diabetes mellitus and use of nonsteroidal anti-inflammatory drugs were controllable risks, and multidisciplinary approaches are a reasonable means of minimising peri-operative acute kidney injury or acute deterioration of kidney function.
METHODS: Planned analysis of data was collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Patients missing preoperative creatinine data were excluded. We used multivariable logistic regression to examine the relationships among preoperative creatinine-based estimated glomerular filtration rate (eGFR), postoperative AKI, and hospital mortality, accounting for the effects of age, major comorbid diseases, and nature and severity of surgical intervention on outcomes. We similarly modeled preoperative associations of AKI. Data are presented as n (%) or odds ratios (ORs) with 95% confidence intervals.
RESULTS: A total of 36,357 patients were included, 743 (2.0%) of whom developed AKI with 73 (9.8%) deaths in hospital. AKI affected 73 of 196 (37.2%) of all patients who died. Mortality was strongly associated with the severity of AKI (stage 1: OR, 2.57 [1.3-5.0]; stage 2: OR, 8.6 [5.0-15.1]; stage 3: OR, 30.1 [18.5-49.0]). Low preoperative eGFR was strongly associated with AKI. However, in our model, lower eGFR was not associated with increasing mortality in patients who did not develop AKI. Conversely, in older patients, high preoperative eGFR (>90 mL·minute·1.73 m) was associated with an increasing risk of death, potentially reflecting poor muscle mass.
CONCLUSIONS: The occurrence and severity of AKI are strongly associated with risk of death after surgery. However, the relationship between preoperative renal function as assessed by serum creatinine-based eGFR and risk of death dependent on patient age and whether AKI develops postoperatively.
Methods: We evaluated commonly used surrogate and imputed baseline creatinine values against a "reference" creatinine measured during follow-up in an adult clinical trial cohort. Known AKI incidence (Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was compared with AKI incidence classified by (1) back-calculation using the Modification of Diet in Renal Disease (MDRD) equation with and without a Chinese ethnicity correction coefficient; (2) back-calculation using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation; (3) assigning glomerular filtration rate (GFR) from age and sex-standardized reference tables; and (4) lowest measured creatinine during admission. Back-calculated distributions were performed using GFRs of 75 and 100 ml/min.
Results: All equations using an assumed GFR of 75 ml/min underestimated AKI incidence by more than 50%. Back-calculation with CKD-EPI and GFR of 100 ml/min most accurately predicted AKI but misclassified all AKI stages and had low levels of agreement with true AKI diagnoses. Back-calculation using MDRD and assumed GFR of 100 ml/min, age and sex-reference GFR values adjusted for good health, and lowest creatinine during admission performed similarly, best predicting AKI incidence (area under the receiver operating characteristic curves [AUC ROCs] of 0.85, 0.87, and 0.85, respectively). MDRD back-calculation using a cohort mean GFR showed low total error (22%) and an AUC ROC of 0.85.
Conclusion: Current methods for estimating baseline creatinine are large sources of potential error in acute infection studies. Preferred alternatives include MDRD equation back-calculation with a population mean GFR, age- and sex-specific GFR values corrected for "good health," or lowest measured creatinine. Studies using surrogate baseline creatinine values should report specific methodology.
DESIGN AND SETTING: Retrospective study at Hospital Universiti Sains Malaysia (HUSM).
METHODS: This was an analysis based on medical records of adult patients at HUSM. Data regarding demographics, laboratory investigations, attributable causes and CKD stage were gathered.
RESULTS: A total of 851 eligible cases were included. The patients' mean age was 61.18 ± 13.37 years. CKD stage V was found in 333 cases (39.1%) whereas stages IV, IIIb, IIIa, and II were seen in 240 (28.2%), 186 (21.9%), 74 (8.7%) and 18 (2.1%), respectively. The percentage of CKD stage V patients receiving renal replacement therapy was 15.6%. The foremost attributable causes of CKD were diabetic nephropathy (DN) (44.9%), hypertension (HPT) (24.2%) and obstructive uropathy (9.2%). The difference in the prevalence of CKD due to DN, HPT and glomerulonephritis between patients ≤ 50 and > 50 years old was statistically significant.
CONCLUSION: Our results suggest that DN and HPT are the major attributable causes of CKD among patients at a Malaysian tertiary-care hospital. Furthermore, the results draw attention to the possibility that greater emphasis on primary prevention of diabetes and hypertension will have a great impact on reduction of hospital admissions due to CKD in Malaysia.
OBJECTIVE: The aim of this review is to examine studies that focused on the different types of samples which may serve as a good and promising biomarker for early diagnosis of CKD or to detect rapidly declining renal function among CKD patient.
METHOD: The review of international literature was made on paper and electronic databases Nature, PubMed, Springer Link and Science Direct. The Scopus index was used to verify the scientific relevance of the papers. Publications were selected based on the inclusion and exclusion criteria.
RESULT: 63 publications were found to be compatible with the study objectives. Several biomarkers of interest with different sample types were taken for comparison.
CONCLUSION: Biomarkers from urine samples yield more significant outcome as compare to biomarkers from blood samples. But, validation and confirmation with a different type of study designed on a larger population is needed. More comparison studies on different types of samples are needed to further illuminate which biomarker is the better tool for the diagnosis and prognosis of CKD.
MATERIALS AND METHODS: The CKD-CHECK (CKD-CHECK EGFR Chart in Kidney disease) is a toolkit that was developed to auto-generate patients' eGFR trend using a line graph, displaying the trend visually over a year. It identifies patients with rapid CKD progression, triggers the doctors to order appropriate tests (proteinuria quantification or renal imaging) and helps in decision making (continued monitoring at primary care level or referral to nephrologist). The toolkit was piloted among medical officers practising in a hospital-based primary care clinic treating patients with eGFR<60ml/min/1.73m2 using an interventional before-after study design from February to May 2022. In the preintervention period, the CKD patients were managed based on standard practice. The doctors then used the CKDCHECK toolkit on the same group of CKD patients during the intervention period. The feasibility and acceptability of the toolkit was assessed at the end of the study period using the Acceptability of Intervention Measure (AIM) and Feasibility of Intervention Measure (FIM) questionnaires. All patients' clinical data and referral rate were collected retrospectively through medical files and electronic data systems. Comparison between the pre- and post-intervention group were analysed using paired t-test and McNemar test, with statistical significance p value of <0.05.
RESULTS: A total of 25 medical officers used the toolkit on 60 CKD patients. The medical officers found the CKD-CHECK toolkit to be highly acceptable and feasible in primary care setting. The baseline characteristics of the patients were a mean age of 72 years old, predominantly females and Chinese ethnicity. Majority of the CKD patients had diabetes mellitus, hypertension and dyslipidemia. The numbers of CKD rapid progressors was similar (26.7% in the preintervention group vs 33.3% in the post-intervention group). There were no significant differences in terms of proteinuria assessment and ultrasound kidney for CKD rapid progressors before and after the intervention. However, a significant number of CKD rapid progressors were referred to nephrologists after the use of CKD-CHECK toolkit (p=0.016).
CONCLUSIONS: CKD-CHECK toolkit is acceptable and feasible to be used in primary care. Preliminary findings show that the CKD-CHECK toolkit improved the primary care doctor's referral of rapid CKD progressors to nephrologists.
METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD).
RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use.
CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.