Background: To assess the performance of different GFR estimating equations, test the diagnostic value of serum cystatin-C, and compare the applicability of cystatin-C based equation with serum creatinine based equation for estimating GFR (eGFR) in comparison with measured GFR in the elderly Malaysian patients.
Methods: A cross-sectional study recruiting volunteered patients 65 years and older attending medical outpatient clinic. 51 chromium EDTA (51Cr-EDTA) was used as measured GFR. The predictive capabilities of Cockcroft-Gault equation corrected for body surface area (CGBSA), four-variable Modification of Diet in Renal Disease (4-MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using serum creatinine (CKD-EPIcr) as well as serum cystatin-C (CKD-EPIcys) were calculated.
Results: A total of 40 patients, 77.5% male, with mean measured GFR 41.2 ± 18.9 ml/min/1.73 m2 were enrolled. Mean bias was the smallest for 4-MDRD; meanwhile, CKD-EPIcr had the highest precision and accuracy with lower limit of agreement among other equations. CKD-EPIcys equation did not show any improvement in GFR estimation in comparison to CKD-EPIcr and MDRD.
Conclusion: The CKD-EPIcr formula appears to be more accurate and correlates better with measured GFR in this cohort of elderly patients.
Study site: medical outpatient clinic. University of Malaya Medical Centre (UMMC)
This study aimed to investigate the relationship between soluble RAGE and estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD) after controlling for the potential confounding factors such as medication usage and enzymatic antioxidants.
Kinetic estimate of GFR (keGFR) is a more accurate estimate of GFR in the
acute settings with rapidly changing kidney functions. It takes into account the changes
of creatinine over time, creatinine production rate, and the volume of distribution,
however needs serial measurement of creatinine. We evaluated which methods of the
conventional eGFR measurement best correlates with keGFR. This could assist clinicians
in using a simpler method of calculation and is useful in the absence of serial plasma
creatinine. (Copied from article).
AIM: To validate the accuracy of estimated glomerular filtration rate (eGFR) equations in Malay population attending our hospital in comparison with radiolabeled measured GFR.
METHODS: A cross-sectional study recruiting volunteered patients in the outpatient setting. Chromium EDTA (51Cr-EDTA) was used as measured GFR. The predictive capabilities of Cockcroft-Gault equation corrected for body surface area (CGBSA), four-variable Modification of Diet in Renal Disease (4-MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were calculated.
RESULTS: A total of 51 subjects were recruited with mean measured GFR 42.04 (17.70-111.10) ml/min/1.73 m(2). Estimated GFR based on CGBSA, 4-MDRD, and CKD-EPI were 40.47 (16.52-115.52), 35.90 (14.00-98.00), and 37.24 (14.00-121.00), respectively. Higher accuracy was noted in 4-MDRD equations throughout all GFR groups except for subgroup of GFR ≥ 60 ml/min/1.73 m(2) where CGBSA was better.
CONCLUSIONS: The 4-MDRD equation seems to perform better in estimating GFR in Malay CKD patients generally and specifically in the subgroup of GFR < 60 ml/min/1.73 m(2) and both BMI subgroups.
Study site: University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Plasma Cystatin C (CysC) is as an early functional marker for acute kidney
injury. Estimates of glomerular filtration rate using CysC (eGFRCysC) has been used in
some clinical setting. We evaluated the utility of CysC and eGFRCysC in diagnosing acute
kidney injury (AKI) and predicting death in critically ill patients with sepsis. (Copied from article).
Creatinine clearance is calculated from 24 hour urine creatinine excretion. This method of measuring creatinine clearance is cumbersome. Many formulae have been proposed as an alternative method of obtaining predicted creatinine clearance and they have all shown satisfactory results. From our study using 4 formulae, the correlation coefficient using these formulae rangedfrom 0.71 - 0.75. The correlation clearance was even better at > 0.90. We therefore advocate the routine use of these formulae for predicting creatinine clearance by clinicians.
Study site: Nephrology clinic, Universiti Kebangsaan Malaysia unit at Hospital Kuala Lumpur, Malaysia
This study examines the rate of decline of estimated glomerular filtration rate (eGFR) over a 10-year period and the associated risk factors in type 2 diabetes mellitus (T2DM) patients. Medical records of T2DM patients were randomly selected. The rate of fall in eGFR (simplified modification of diet in renal disease formula) was used as a measure of decline. Univariate and multivariate analysis were performed to determine the factors associated with decline of kidney function. A total of 504 patients were selected. Mean age was 57.8 ± 9 years; 65.3% were females. The mean decline rate of eGFR was 0.89 ± 2.16 mL/min/1.73 m(2)/y. Baseline proteinuria, glycosylated hemoglobin level, duration of T2DM, and Malay race were associated with faster decline in eGFR. The expected greater deterioration in kidney function in this cohort was not seen. Treatment of proteinuria and glycemia should be optimized early to retard the decline in kidney function in patients with T2DM.
Obesity and overweight are strong independent risk factors for chronic kidney disease (CKD). Using serum creatinine-based estimated glomerular filtration rate (eGFR) equations in these subjects may be inaccurate. On the other hand, cystatin C-based eGFR equations may overestimate CKD prevalence as recent findings suggest an association of cystatin C with obesity. The objective of this study was to assess the accuracy of a cystatin C-based eGFR equation compared to two creatinine -based eGFR equations in overweight and obese subjects.
The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.
Optimization of an artificial neural network model through the use of optimization algorithms is the common method employed to search for an optimum solution for a broad variety of real-world problems. One such optimization algorithm is the kidney-inspired algorithm (KA) which has recently been proposed in the literature. The algorithm mimics the four processes performed by the kidneys: filtration, reabsorption, secretion, and excretion. However, a human with reduced kidney function needs to undergo additional treatment to improve kidney performance. In the medical field, the glomerular filtration rate (GFR) test is used to check the health of kidneys. The test estimates the amount of blood that passes through the glomeruli each minute. In this paper, we mimic this kidney function test and the GFR result is used to select a suitable step to add to the basic KA process. This novel imitation is designed for both minimization and maximization problems. In the proposed method, depends on GFR test result which is less than 15 or falls between 15 and 60 or is more than 60 a particular action is performed. These additional processes are applied as required with the aim of improving exploration of the search space and increasing the likelihood of the KA finding the optimum solution. The proposed method is tested on test functions and its results are compared with those of the basic KA. Its performance on benchmark classification and time series prediction problems is also examined and compared with that of other available methods in the literature. In addition, the proposed method is applied to a real-world water quality prediction problem. The statistical analysis of all these applications showed that the proposed method had a ability to improve the optimization outcome.
INTRODUCTION: Clinical practice guidelines recommend using creatinine-based equations to estimate glomerular filtration rates (GFRs). While these equations were formulated for Caucasian-American populations and have adjustment coefficients for African-American populations, they are not validated for other ethnicities. The Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) recently developed a new equation that uses both creatinine and cystatin C. We aimed to assess the accuracy of this equation in estimating the GFRs of participants (healthy and with chronic kidney disease [CKD]) from a multiethnic Asian population.
METHODS: Serum samples from the Asian Kidney Disease Study and the Singapore Kidney Function Study were used. GFR was measured using plasma clearance of 99mTc-DTPA. GFR was estimated using the CKD-EPI equations. The performance of GFR estimation equations were examined using median and interquartile range values, and the percentage difference from the measured GFR.
RESULTS: The study comprised 335 participants (69.3% with CKD; 38.5% Chinese, 29.6% Malays, 23.6% Indians, 8.3% others), with a mean age of 53.5 ± 15.1 years. Mean standardised serum creatinine was 127 ± 86 µmol/L, while mean standardised serum cystatin C and mean measured GFR were 1.43 ± 0.74 mg/L and 67 ± 33 mL/min/1.73 m2, respectively. The creatinine-cystatin C CKD-EPI equation performed the best, with an estimated GFR of 67 ± 35 mL/min/1.73 m2.
CONCLUSION: The new creatinine-cystatin C equation estimated GFR with little bias, and had increased precision and accuracy in our multiethnic Asian population. This two-biomarker equation may increase the accuracy of population studies on CKD, without the need to consider ethnicity.
Keywords: Asian, chronic kidney disease, creatinine, cystatin C, glomerular filtration rate
Functional renal reserve is a measure of the capacity of the kidney to increase the glomerular filtration in response to the stimulus of a protein meal or amino acid infusion. The aim of this study was to evaluate the usefulness of protein meal test to measure functional renal reserve in normal subjects and various groups of renal patients. One hundred and twenty five subjects from the Nephrology Clinic, Kuala Lumpur General Hospital were subjected to a protein loading test to measure their renal reserve. Each subject had to eat a 100 gram cooked chicken meat and timed 2 hours urine collections before and after the test meal were done to measure the creatinine clearances. The 62 healthy subjects showed a mean renal reserve (creatinine clearance after protein loading-baseline creatinine clearance) of 31.0 ml/min. The 31 subjects with various kidney diseases showed a mean renal reserve of 13.5 ml/min. The 19 renal transplant recipients showed renal reserve of 13.2 ml/min. The 12 nephrectomised donors showed renal reserve of 5.4ml/min. Renal reserve may be used to assess suitability of living related transplant donor for nephrectomy.
Study site: Nephrology Clinic, Kuala Lumpur General Hospital
Standard renal clearance techniques were used to compare the effects of intravenous infusions of L-arginine, D-lysine and glycine on urinary calcium excretion in the rat. A significant calciuric response was evident following the infusion of all three amino acids in all the animals. The maximal effect was evident in rats receiving L-arginine. The mechanism for the increased urinary calcium excretion in rats infused with L-arginine and D-lysine appeared more due to a decreased fractional reabsorption of this cation as no significant changes in the glomerular filtration rate (GFR) were evident in these two groups. The calciuria in rats receiving glycine appears due to increased filtered load secondary to the increased GFR, suggesting that the mechanism for calciuria evident following protein ingestion or amino acid infusion may vary and may be dependent upon the amino acid ingested or infused.
BACKGROUND: Accurate measurement of renal function is important: however, radiolabelled gold standard measurement of GFR is highly expensive and can only be used on a very limited scale. We aim to compare the performance of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations in the multi-ethnic population attending University Malaya Medical Centre (UMMC).
METHODS: This is a cross-sectional study recruiting patients, who attend UMMC Nephrology clinics on voluntary basis. 51-Chromium EDTA (51Cr-EDTA) plasma level was used to measure the reference GFR. The serum creatinine was determined by IDMS reference modified Jaffe kinetic assay (CrJaffe). The predictive capabilities of MDRD and CKD-EPI based equations were calculated. Data was analysed using SPSS version 20 and correlation, bias, precision and accuracy were determined.
RESULTS: A total of 113 subjects with mean age of 58.12 ± 14.76 years and BMI of 25.99 ± 4.29 kg/m2 were recruited. The mean reference GFR was 66.98 ± 40.65 ml/min/1.73m2, while the estimated GFR based on MDRD and CKD-EPI formula were 62.17 ± 40.40, and 60.44 ± 34.59, respectively. Both MDRD and CKD-EPI were well-correlated with reference GFR (0.806 and 0.867 respectively) and statistically significant with p
There is substantial heterogeneity in literature regarding the epidemiology for chronic kidney disease (CKD) in different Asian populations. We aimed to assess the prevalence and risk factors of CKD in a multi-ethnic Asian population in Singapore.
Augmented renal clearance (ARC) refers to increased solute elimination by the kidneys. ARC has considerable implications for altered drug concentrations. The aims of this study were to describe the prevalence of ARC in a select cohort of patients admitted to a Malaysian intensive care unit (ICU) and to compare measured and calculated creatinine clearances in this group. Patients with an expected ICU stay of <24 hours plus an admission serum creatinine concentration <120 µmol/l, were enrolled from May to July 2013. Twenty-four hour urinary collections and serum creatinine concentrations were used to measure creatinine clearance. A total of 49 patients were included, with a median age of 34 years. Most study participants were male and admitted after trauma. Thirty-nine percent were found to have ARC. These patients were more commonly admitted in emergency (P=0.03), although no other covariants were identified as predicting ARC, likely due to the inclusion criteria and the study being under-powered. Significant imprecision was demonstrated when comparing calculated Cockcroft-Gault creatinine clearance (Crcl) and measured Crcl. Bias was larger in ARC patients, with Cockcroft-Gault Crcl being significantly lower than measured Crcl (P <0.01) and demonstrating poor correlation (rs=-0.04). In conclusion, critically ill patients with 'normal' serum creatinine concentrations have varied Crcl. Many are at risk of ARC, which may necessitate individualised drug dosing. Furthermore, significant bias and imprecision between calculated and measured Crcl exists, suggesting clinicians should carefully consider which method they employ in assessing renal function.
An episode of clinically recovered acute kidney injury (r-AKI) has been identified as a risk factor for future hypertension and cardiovascular disease. Our objective was to assess whether r-AKI was associated with future preeclampsia and other adverse pregnancy outcomes and to identify whether severity of AKI or time interval between AKI and pregnancy was associated with pregnancy complications. We conducted a retrospective cohort study of women who delivered infants between 1998 and 2016 at Massachusetts General Hospital. AKI was defined using the 2012 Kidney Disease Improving Global Outcomes laboratory criteria with subsequent clinical recovery (estimate glomerular filtration rate, >90 mL/min per 1.73 m2 before conception). AKI was further classified by severity (Kidney Disease Improving Global Outcomes stages 1-3) and time interval between AKI episode and the start of pregnancy. Women with r-AKI had an increased rate of preeclampsia compared with women without previous r-AKI (22% versus 9%; P<0.001). Infants of women with r-AKI were born earlier (gestational age, 38.2±3.0 versus 39.0±2.2 weeks; P<0.001) and were more likely to be small for gestational age (9% versus 5%; P=0.002). Increasing severity of r-AKI was associated with increased risk of preeclampsia for stages 2 and 3 AKI (adjusted odds ratio, 3.5; 95% confidence interval, 2.1-5.7 and adjusted odds ratio, 6.5; 95% confidence interval, 3.5-12.0, respectively), but not for stage 1 (adjusted odds ratio, 1.7; 95% confidence interval, 0.9-3.2). A history of AKI before pregnancy, despite apparent full recovery, was associated with increased risk of pregnancy complications. Severity and timing of the AKI episode modified the risk.
Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred. Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia. Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured.
Combination of cyclosporine (CsA) and tacrolimus immunosuppression post-liver transplantation (LT) and the chemotherapeutic drugs used to treat hepatoblastoma (HB), are nephrotoxic. We aimed to determine the severity and duration of nephrotoxicity in children following LT for unresectable HB. We reviewed all children undergoing LT for unresectable HB at the Liver Unit, Birmingham Children's Hospital, UK, from 1991 to July 2000. Thirty-six children undergoing LT for biliary atresia, matched for age and sex, were selected as controls to compare pre- and post-LT renal function. Renal function was determined by estimation of glomerular filtration rate (eGFR) derived from plasma creatinine using Schwartz's formula. Twelve children with HB (mean age of diagnosis 33 months) who underwent LT (mean age 47 months) and 36 controls (mean age of LT 34 months) were studied. CsA was the main immunosuppressive drug used in each group. The median eGFR before, and at 3, 6, 12, 24 and 36 months after LT in HB group was significantly lower than controls (93 vs. 152, 66 vs. 79, 62 vs. 86, 66 vs. 87, 64 vs. 94, 53 vs. 90 mL/min/1.73 m2, respectively; 0.01 < p < 0.03). The reductions in the median eGFR of both the HB group and controls before and at 36 months after LT were 49 and 41%, respectively. At 36 months after LT, there was a trend for partial recovery of the eGFR in the controls but not in the HB group. Children who underwent LT for unresectable HB had renal dysfunction before transplantation that persisted for 36 months after LT.
The aim of the study was to determine the effect of pro-phylactic low dose dopamine infusion on renal function in ventilated premature newborns with respiratory dis-tress syndrome (RDS). A prospective, randomised con-trolled trial was conducted, using low dose dopamine [2.5μg/kg/min] in the treatment of preterm babies with gestational age 28-36 weeks requiring mechanical ventilation for RDS within six hours of age. Thirty-six babies were enrolled and 19 babies were randomly assigned to the treatment groups. The renal function after 72 hours for the treatment and control groups respectively were: urine output (ml/kg/hour) 3.3±0.4 and 3.0±0.3 [p=0.55], urine specific gravity 1006±0.6 and 1006±1.0 [p=0.68], fractional excretion of sodium 4.1±0.8 and 2.6±0.4 [p=0.10], fractional excretion of potassium 37.44 ± 5.6 and 16.49 ± 2.2 [p=0.001], glomerular filtration rate (ml/day/1.72m2) 16±2.6 and 25.6±4.5 [p=0.06]. There were no significant differ-ences in the frequency of hypotension, oliguria and sep-sis between the two groups. There were seven deaths (36.8%) in the treatment group (six due to sepsis and one due to prematurity) and two deaths (11.8%) in the control group (both due to sepsis) (p = 0.13). In con-clusion prophylactic low-dose dopamine infusion did not improve the renal function in ventilated premature babies with respiratory distress syndrome. The results of this study do not support the routine use of prophylac-tic low-dose dopamine in ventilated preterm babies with respiratory distress syndrome.