Marker Of Glomerular Filtration Rate Research Articles

Iohexol clearance for determination of glomerular filtration rate in rats induced to acute renal failure.

IntroductionThe glomerular filtration rate (GFR) is considered an especially important tool for the measurement of renal function. Inulin clearance (InCl) is the classic reference method for this purpose, although it is associated with a number of disadvantages; thus, other markers have been proposed, including iohexol. Determination of iohexol clearance (IoCl) has been established for clinical use; however, its application as a GFR marker in experimental rat models has not been reported.ObjectivesThis study aims to standardize a methodology for the measurement of iohexol clearance and to evaluate its applicability as a marker of GFR in rats with induced toxic acute renal failure (ARF), using InCl as the gold standard.Materials and MethodsTwenty-six Wistar male rats (200–300 g) were divided into the following two groups: a control group (n=7) and an ARF group (n=19). ARF was induced by the subcutaneous administration of cisplatin (5 mg/kg); IoCl and InCl were determined simultaneously, and plasma creatinine (pCreat) dosage was measured colorimetrically.ResultsThe pCreat, InCl and IoCl levels were consistent with the expected values for the renal function ranges of the evaluated animals, and the IoCl and InCl levels were significantly correlated (r=0.792). An inverse moderate linear correlation between the IoCl and pCreat measurements (r=-0.587) and between the InCl and pCreat measurements (r=-0.722) were observed.ConclusionThese results confirm a correlation between IoCl and the gold standard of GFR, InCl measurement. IoCl offers a relevant advantage over InCl because determination of the former allows the animal to live after the procedure.

Association of definition of acute kidney injury by cystatin C rise with biomarkers and clinical outcomes in children undergoing cardiac surgery.

Research has identified improved biomarkers of acute kidney injury (AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum creatinine (SCr) and may improve AKI definition. To determine if defining clinical AKI by increases in CysC vs SCr alters associations with biomarkers and clinical outcomes. Three-center prospective cohort study of intensive care units in New Haven, Connecticut, Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18 years or younger without preoperative AKI or end-stage renal disease who were undergoing cardiac surgery. The study dates were July 1, 2007, through December 31, 2009. For biomarker vs clinical AKI associations, the exposures were first postoperative (0-6 hours after surgery) urine interleukin 18, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and liver fatty acid-binding protein. For clinical AKI outcome associations, the exposure was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or CysC). Clinical AKI, length of stay, and length of mechanical ventilation. We determined areas under the receiver operating characteristic curve and odds ratios for first postoperative biomarkers to predict AKI. The SCr-defined vs CysC-defined AKI incidence differed substantially (43.6% vs 20.6%). Percentage agreement was 71% (κ = 0.38); stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined AKI. For interleukin 18 and kidney injury molecule 1, the areas under the receiver operating characteristic curve were 0.74 and 0.65, respectively, for CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs first) quintile concentrations of both biomarkers were more strongly associated with CysC-defined AKI. For interleukin 18 and kidney injury molecule 1, the odds ratios were 16.19 (95% CI, 3.55-73.93) and 6.93 (95% CI, 1.88-25.59), respectively, for CysC-defined AKI vs 6.60 (95% CI, 2.76-15.76) and 2.04 (95% CI, 0.94-4.38), respectively, for SCr-defined AKI. Neutrophil gelatinase-associated lipocalin and liver fatty acid-binding protein associations with both definitions were similar. The CysC definitions and SCr definitions were similarly associated with clinical outcomes of resource use. Compared with the SCr-based definition, the CysC-based definition is more strongly associated with urine interleukin 18 and kidney injury molecule 1 in children undergoing cardiac surgery. Consideration should be made for defining AKI based on CysC in clinical care and future studies.

Mechanisms underlying early rapid increases in creatinine in paraquat poisoning.

BackgroundAcute kidney injury (AKI) is common after severe paraquat poisoning and usually heralds a fatal outcome. The rapid large increases in serum creatinine (Cr) exceed that which can be explained by creatinine kinetics based on loss of glomerular filtration rate (GFR).Methods and FindingsThis prospective multi-centre study compared the kinetics of two surrogate markers of GFR, serum creatinine and serum cystatin C (CysC), following paraquat poisoning to understand and assess renal functional loss after paraquat poisoning. Sixty-six acute paraquat poisoning patients admitted to medical units of five hospitals were included. Relative changes in creatinine and CysC were monitored in serial blood and urine samples, and influences of non-renal factors were also studied.ResultsForty-eight of 66 patients developed AKI (AKIN criteria), with 37 (56%) developing moderate to severe AKI (AKIN stage 2 or 3). The 37 patients showed rapid increases in creatinine of >100% within 24 hours, >200% within 48 hours and >300% by 72 hours and 17 of the 37 died. CysC concentration increased by 50% at 24 hours in the same 37 patients and then remained constant. The creatinine/CysC ratio increased 8 fold over 72 hours. There was a modest fall in urinary creatinine and serum/urine creatinine ratios and a moderate increase in urinary paraquat during first three days.ConclusionLoss of renal function contributes modestly to the large increases in creatinine following paraquat poisoning. The rapid rise in serum creatinine most probably represents increased production of creatine and creatinine to meet the energy demand following severe oxidative stress. Minor contributions include increased cyclisation of creatine to creatinine because of acidosis and competitive or non-competitive inhibition of creatinine secretion. Creatinine is not a good marker of renal functional loss after paraquat poisoning and renal injury should be evaluated using more specific biomarkers of renal injury.

Influence of cancer cachexia on drug liver metabolism and renal elimination in rats.

BackgroundBody wasting and cachexia change body composition and organ function, with effects on drug pharmacokinetics. The aim of this study was to investigate how cancer and cancer cachexia modify liver metabolism and renal drug elimination in rats.MethodsNine male Wistar-Han rats received a single oral dose of midazolam and propranolol (markers of hepatic metabolism), and 10 rats received single intravenous dose of iohexol, a marker of glomerular filtration rate. After drug delivery, multiple dried blood samples were obtained within 2 h post-dose to evaluate drug pharmacokinetic profiles. After baseline sampling (D0), rats were injected with tumour cells. Drug application and blood sampling were repeated when rats developed tumours (Day 5—D5), and when rats were severely cachectic (Day 10—D10). Clearance (CL) and volume of distribution (Vd) of drugs were assessed with non-linear mixed effects modelling. Weight and body composition were measured on D0 and D10 and were related to pharmacokinetic parameters.ResultsAll three drugs showed non-significant trend towards increased CL and Vd on D5. On D10, midazolam and propranolol CL and midazolam Vd significantly decreased from baseline (−80.5%, −79.8%, and −72.0%, respectively, P < 0.05 for all). Iohexol CL decreased by 29.8% from baseline value on D10, which was related to body weight loss (Pearson's r = 0.837, P = 0.019).ConclusionsHepatic metabolism and renal drug elimination are significantly reduced in cachexia, which could increase risk of dose-related adverse events.

Transcutaneous measurement of glomerular filtration rate in small rodents: through the skin for the win?

Rodent models of renal physiology and pathology are crucial to our understanding of the molecular, histological and functional sequelae that contribute to kidney diseases. One of the most important measures of renal function is glomerular filtration rate (GFR). While the accurate determination of GFR is pivotal to understanding the progression of disease and/or the benefits of treatment strategies, in rodents the conventional methods for assessment of GFR are inconvenient and cumbersome, not the least because they involve stress and often anaesthesia. The legitimacy of assay-based assessment of plasma and urine markers of GFR in mice has also been heavily scrutinized for their insensitivity to minor declines in GFR and inaccurate detection of renal biomarkers. While infusion-based clearance methods of GFR assessment are thus the gold standard in terms of accuracy, they are limited by the fact that they are primarily non-recovery procedures. This presents a dilemma when trying to document the progression of renal disease, as these measures cannot be taken in the same experimental subject. Here we review a technique of transcutaneous measurement of fluorescein isothiocyanate-labelled sinistrin to calculate GFR in small rodents, using a non-invasive clearance device (NIC-Kidney Device). This is a recently validated non-invasive technique for measuring GFR in small rodents that allows for the real-time measurement of GFR in conscious animals, without the need for plasma and urine assays.

0356: Is cystatin C a predictive factor of cardiovascular events in acute coronary syndrome?

Serum cystatin C has been proposed as a better marker of glomerular filtration rate than serum creatinine. This study aims to evaluate the relationship between cystatinC, BNP and acute coronary syndrome. A total of 127 consecutive patients with acute coronary syndrome (ACS) were enrolled in this study. All patients had a normal glomerular filtration rate (GFR) estimated using the MDRD (Modification of Diet in Renal Disease) equation.Serum cystatin C and brain natriuretic peptide (BNP) were determined in all subjects. All patients were followed up for 12 months and adverse cardiovascular events were recorded. Serum Cys C levels were significantly higher in patients with multi-vessel coronary artery disease (1.17±0.47 mg/L vs. 0.93±0.24 mg/L, P<0.01). BNP concentrations were significantly associated to left ventricular ejection fraction (LVEF). Patients with systolic heart failure (LVEF < 50%) had higher BNP levels (343.3 pg/ml vs. 212.7 pg/ml; P<0.001). Serum Cys C and BNP levels were significantly associated to mortality and morbidity post ACS. Receiver operator characteristic (ROC) analyses identified cys C as being the best marker in predicting major adverse cardiac and cerebrovascular events (MACCE: heart failure hospitalizations, recurrent ischemic events and mortality) (AUC=0.622). For high Cys C levels (>1.2 mg/L), the risk of occurrence of MACCE was multiplied by 3.35 for BNP levels exceeding 350pg/mL. ROC analyses identified BNP as the best predictor of LV systolic dysfunstion (AUC = 0.784). A BNP value exceeding 133pg/mL had a sensibility of 83% and a specificity of 67% for predicting LV systolic dysfunction during follow-up. Cystatin C and BNP are strong predictors for risk of cardiovascular events in acute coronary syndrome.

Can cystatin C become an easy and reliable tool for anesthesiologists to calculate glomerular filtration rate?

Background and Aims:The aim was to evaluate the role of cystatin C as a noninvasive and easy marker of glomerular filtration rate (GFR) estimation in voluntary kidney donors.Materials and Methods:We retrospectively evaluated 40 voluntary kidney donors. They underwent complete biochemical and nuclear tests as a part of transplant workup. Serum cystatin C, serum creatinine, and Tc-99m diethylene-triamine-penta-acetic acid (DTPA) were used in our study. We calculated GFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) formula based on creatinine only (GFR-CKD-EPI-creat), CKD-EPI formula using creatinine and cystatin C (GFR-CKD-EPI-cyst-creat), and modification of diet in renal disease (MDRD) and CKD-EPI cystatin C equation (2012) (GFR-cyst).Data was evaluated using the SPSS software (version 11.5). The correlation analysis and analysis of variance was used for statistical computation. Agreement was determined using analyze-it version 2.30 for MS-Excel 12+.Results:The mean age of the donors in our study was 49.83 ± 13.06. The mean cystatin C in females was 0.72 ± 0.12, the mean cystain C in males was 0.87 ± 0.23. On correlating GFR-cyst with GFR-DTPA the Pearson correlation coefficient (ρ) was found to be 0.388 this correlation was significant with P < 0.05. While comparing with DTPA the correlation coefficient of GFR-CKD-EPI-creat group was 0.587 which was significant with P < 0.01. The correlation coefficient of GFR-CKD-EPI-cyst-creat group compared with GFR-DTPA group was 0.543 which was also significant at P < 0.001. GFR-CKD-EPI-creat gave the highest correlation with DTPA in our study. The correlation coefficient of GFR-MDRD group with DTPA group was 0.576 this correlation was also significant with P < 0.01. The results obtained were further statistically analyzed by Bland-Altman analysis the percentage error for GFR-DTPA versus GFR-cyst-creat is 29.72%; for GFR-DTPA versus GFR-EPI-creat is 30.73%; or GFR-DTPA versus MDRD is 31.63% and for GFR-DTPA versus GFR-cyst is 34.37%.Conclusion:Cystatin C is a good endogenous marker for calculating GFR as it correlates very well with DTPA and CKD-EPI equation based GFR.

CYSTATIN C - MORE THAN THE MARKER OF THE GLOMERULAR FILTRATION RATE.

Cystatin C is one of biomarkers that meet the conditions necessary for an endogenous substance to be a marker of the glomerular filtration rate. Cystatin c – properties. Cystatin C is produced in the nucleated cells in a constant amount, and its serum concentration does not depend on muscle mass and protein intake. The catabolism of cystatin C is mostly done in the kidneys. Determination of cystatin c level. Cystatin C may be determined in the serum, plasma, capillary blood and urine. The laboratory methods which are mainly used to determine its level are neplielometric and turbidimetric immunoassays. Cystatin c as a marker of glomerular filtration rate. Cystatin C is superior to creatinine as a marker of kidney function, especially in the early stages of chronic kidney disease. Several formulas are available for calculating the glomerular filtration rate from serum cystatin C. Cystatin c in various physiological/pathophysiological conditions. The level of cystatin C should be interpreted carefully because there are factors that can affect its level regardless of the renal function (thyroid dysfunction, glucocorticoids use, malignancies etc.). Higher cystatin C concentrations in general population are associated with an increased cardiovascular risk, as well as with preecampsia in pregnant women. The significant advantages of cystatin C as a kidney function marker are its use in the creatinine "blind" area, in pediatric and the elderly population. In addition, cystatin C could be used as a marker for cardiovascular risk assessment, in predicting and detecting preeclampsia, in patients with malignant diseases, etc.

Clinical Significance of Cystatin C-Based Estimates of Renal Function in Type 2 Diabetic Patients: Review

Chronic kidney disease (CKD) is a common and serious complication of diabetes associated with increased risk of mortality, progression to kidney failure, cardiovascular disease (CVD) and hospitalizations. Accurate estimation of glomerular filtration rate (GFR) is essential for the diagnosis, staging, and management of CKD. Serum creatinine (SCr) level, which is the most commonly used endogenous GFR marker in clinical practice, appears to be influenced by non-renal factors such as age, sex, race and muscle mass, and is not sufficiently sensitive for detecting early renal impairment in diabetics. Serum cystatin C, an alternative endogenous marker less influenced by non-renal factors, has been recently suggested as an early serum marker of detecting changes in GFR and assessing renal impairment at earlier stage. The levels of cystatin C in serum or urine may be elevated in diabetic patients even before the appearance of traditional CKD markers, and it can be used as useful marker for detecting nephropathy in patients with normoalbuminuria (early nephropathy). Moreover, cystatin C-based estimates of renal function may improve risk prediction in diabetics than the commonly used creatinine-based estimates. In this paper we In this paper, we review from recent literatures the clinical efficiency and relevance of cystatin C as an endogenous renal marker for detecting early renal impairment and for predicting adverse outcomes in type 2 diabetic patients

Cystatin C and body surface area are major determinants of the ratio of N-terminal pro-brain natriuretic peptide to brain natriuretic peptide levels in children

BackgroundProduction of N-terminal pro-brain natriuretic peptide (NT) and BNP is equimolar. Although NT clearance occurs only in the kidneys, BNP clearance occurs in the kidneys and other organs. This study tested the hypothesis that NT/BNP ratio in children may be independently related to cystatin C (CysC), a glomerular filtration rate marker, when diastolic function and age/body size are taken into consideration. MethodsThe study included 430 children (5.3±4.9 years) with heart disease who had undergone cardiac catheterization and simultaneous BNP, NT, and CysC measurements. Pulmonary capillary wedge pressure (PCWP) was used as a ventricular diastolic stretch marker. Variables showing skewed distribution were transformed into a common logarithm. ResultsUnivariate regression revealed that logNT/BNP was affected by PCWP (r=−0.12) and logCysC (r=0.57). When age and the log of body surface area (BSA) were added to the stepwise regression, age was not adopted because of multicollinearity to logBSA, but PCWP (β=−0.10), logCysC (β=0.22), and logBSA (β=−0.66) were independent factors of logNT/BNP. ConclusionsRenal dysfunction independently increased NT/BNP, whereas high BSA decreased it and is the greatest determinant of NT/BNP. The observation that high PCWP decreased NT/BNP may suggest that worsening heart failure slows BNP clearance from other organs, a compensatory pathway of heart failure. These factors need to be considered when assessing BNP and NT.

Applicability of various estimation formulas to assess renal function in Chinese children.

This study was to evaluate the relative applicability of the most commonly used estimation formulas for renal glomerular filtration rate (GFR) of Chinese children with chronic kidney disease (CKD). One hundred CKD patients of less than 17 years old were divided into two groups by sex which was further categorized into five subgroups based on CKD staging according to the "reference" GFR (rGFR) determined by Tc-99m-DTPA renal dynamic imaging. Four GFR markers including serum cystatin C (CysC), β2-microglobulin, creatinine, and blood urea nitrogen were measured. Among all four markers, CysC best reflected the extent of glomerular damages for CKD stage 1. The value for estimation of GFR (eGFR) was derived from five different formulas either over-estimated or underestimated GFR as referenced to rGFR, and the extent of deviations was dependent on gender, age and CKD stage. The Counahan-Barratt formula and the Schwartz formula gave the most accurate estimations of GFR for CKD stages 1 and 2-3, respectively regardless of gender and age differences. Receiver operating characteristic analyses indicated that the Counahan-Barratt formula has the highest diagnostic accuracy. The Counahan-Barratt formula provides the best approximation to rGFR, thereby the highest applicability to Chinese children with CKD of different genders, ages and CKD stages.

Effects of bed-rest on urea and creatinine: correlation with changes in fat-free mass.

BackgroundBed-rest experiments are designed for investigation on catabolic effects of hypokinetic conditions and/or for microgravity simulation in on-ground aerospace research. Bed-rest effects include a reduction in fat-free mass and muscle mass. Urea and creatinine are catabolites of endogenous protein and of muscular energetic metabolism which are excreted mainly by the kidney. The study investigated on urea, creatinine, and kidney function during bed-rest.MethodsTwenty healthy young men underwent a 7-day adaptation period (day-6 to day-0) and a 35-day bed-rest experiment (day1 to day35) during normocaloric diet. Urine were collected from day-3 to day0 (baseline) and from day1 to day35. Blood samples and anthropometrical data were collected at day0 (baseline) and bed-rest days 7, 14, 21, 28, and 35.ResultsBed-rest reduced plasma volume, weight, fat-free mass, and muscle mass (P<0.001). During bed-rest there was a transient increase in plasma and urinary urea, a decrease in plasma creatinine, and no change in urinary creatinine. The overall integral of changes from day0 to day35 was on average +101.7 mg/dL for plasma urea (95%CI = +43.4/+159.9), +82.2 g/24 h for urinary urea (95%CI = +55.8/+108.7), −2.5 mg/dL for plasma creatinine (95%CI = −3.1/−1.9). Bed-rest reduced plasma cistatyn C also, which was used as mass-independent marker of glomerular filtration rate (−13.1%, P<0.05). Correlations with final reduction in fat-free mass and muscle mass were significant for the overall integral of changes in urinary urea from day0 to day35 (R = 0.706, P<0.001) and for early changes in urinary urea and plasma urea from day0 to day7 (R = 0.566, P = 0.009 and R = 0.715, P<0.001, respectively).ConclusionsStudy results shows that urea is a marker of catabolic conditions secondary to hypokinetic conditions.

Iontophoretic transdermal sampling of iohexol as a non-invasive tool to assess glomerular filtration rate.

To explore the potential of non-invasive reverse iontophoresis transdermal extraction of iohexol as a marker of glomerular filtration rate. A series of in vitro experiments were undertaken to establish the feasibility of iohexol reverse iontophoresis and to determine the optimal conditions for the approach. Subsequently, a pilot study in paediatric patients was performed to provide proof-of-concept. The iontophoretic extraction fluxes of iohexol in vitro were proportional to the marker subdermal concentration and the reverse iontophoretic technique was able to track changes dynamically in simulated pharmacokinetic profiles. Reverse iontophoresis sampling was well tolerated by the four paediatric participants. The deduced values of the iohexol terminal elimination rate constant from transdermal reverse iontophoresis sampling agreed with those estimated by conventional blood sampling. Reverse iontophoretic transdermal extraction fluxes mirrored the subdermal concentration profiles of iohexol, a relatively large neutral marker of glomerular filtration both in vitro and in vivo. The efficiency of extraction in vivo was well predicted by the in vitro model used.

Looking for a Better Creatinine

Our kidneys maintain a constant internal environment and circulatory volume through a combination of filtration, selective reabsorption and secretion, and production of several key hormones. Young, healthy individuals filter >100 L of blood each day; however, their kidneys then reabsorb most of this for a mean urine output of only 1.5 L/day. This filtration process is necessary to eliminate byproducts of ongoing metabolism (so-called uremic toxins). Indeed, a minimum amount of kidney function is essential for life, and one can demonstrate increased morbidity and mortality when the glomerular filtration rate (GFR)3 chronically dips low enough. Thus, GFR is widely considered the single most important and useful indicator of overall kidney function. It is possible to directly measure GFR by administration of small molecules that are freely filtered by the kidneys and neither metabolized, secreted, nor reabsorbed. Examples include inulin, iothalamate, and iohexol, for which the renal clearance of these molecules equals GFR. However, protocols that use these exogenous agents to measure GFR require some combination of intravenous or subcutaneous administration of the marker, multiple blood draws, and carefully timed urine collections. Thus, direct measurement of GFR is not practical for most routine situations. For these reasons, several methods of GFR estimation have been developed on the basis of endogenous molecules. The best example is creatinine, a byproduct of muscle metabolism that is freely filtered, produced in a relatively consistent manner, and not reabsorbed. Although some creatinine is secreted, this amount is usually small enough that creatinine remains a useful marker of GFR. A bigger problem, however, is that muscle mass (and consequently serum creatinine) varies widely between individuals. Thus, although serum creatinine goes up as GFR goes down, the GFR for a given serum creatinine can vary widely between individuals. For example, a “normal” serum creatinine of 1.0 mg/dL …

Clinical value of cystatin C and beta-trace protein in glomerular filtration rate in renal transplant cases with stable renal graft functions

The aim of this study was to investigate the value of cystatin C and beta-trace protein (BTP) levels in determination of the glomerular filtration rate (GFR) by accepting the technetium-99m diethylenetriamine pentaacetic acid (Tc-DTPA) method as the gold standard for GFR measurement in renal transplant patients with stable renal functions and to investigate the value of cystatin C and BTP levels in the determination of GFR in cases with or without renal tubular injury. A total of 89 (60 men and 29 women) renal transplant patients aged 19-67 years (mean 38.15 years) with stable graft functions were included in the study. GFR was calculated using three different methods: (a) the Tc-DTPA two plasma sample method; (b) eight different formulas containing cystatin C; and (c) three different formulas containing BTP. In addition, the cases were divided into two groups on the basis of N-acetyl-β-D-glucosaminidase and β2 microglobulin levels showing tubular damage. GFR values obtained with cystatin C had a better correlation with the gold standard method compared with those obtained with BTP, and the GFR value obtained with cystatin C had the most reliable consistency. We found that cystatin C provided more accurate results in GFR follow-up in renal transplant patients with no tubular injury compared with those with tubular injury. Cystatin C is a good marker of GFR in renal transplant patients, especially in those with no tubular injury; however, BTP is not as good as cystatin C in that regard.

Measuring GFR: A Systematic Review

No comprehensive systematic review of the accuracy of glomerular filtration rate (GFR) measurement methods using renal inulin clearance as reference has been published. Systematic review with meta-analysis of cross-sectional diagnostic studies. Published original studies and systematic reviews in any population. Index and reference measurements conducted within 48 hours; at least 15 participants studied; GFR markers measured in plasma or urine; plasma clearance calculation algorithm verified in another study; tubular secretion of creatinine had not been blocked by medicines. Endogenous creatinine clearance; renal or plasma clearance of chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA), diethylenetriaminepentaacetic acid (DTPA), iohexol, and iothalamate; and plasma clearance of inulin. Renal inulin clearance measured under continuous inulin infusion and urine collection. Mean bias <10%, median bias <5%, the proportion of errors in the index measurements that did not exceed 30% (P30) ≥80%, and P10 ≥50% were set as requirements for sufficient accuracy. Based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the quality of evidence across studies was rated for each index method. Renal clearance of iothalamate measured GFR with sufficient accuracy (strong evidence). Renal and plasma clearance of 51Cr-EDTA and plasma clearance of iohexol were sufficiently accurate to measure GFR (moderately strong evidence). Renal clearance of DTPA, renal clearance of iohexol, and plasma clearance of inulin had sufficient accuracy (limited evidence). Endogenous creatinine clearance was an inaccurate method (strong evidence), as was plasma clearance of DTPA (limited evidence). The evidence to determine the accuracy of plasma iothalamate clearance was insufficient. With the exception of plasma clearance of inulin, only renal clearance methods had P30 >90%. The included studies were few and most were old and small, which may limit generalizability. Requirements for sufficient accuracy may depend on clinical setting. At least moderately strong evidence suggests that renal clearance of 51Cr-EDTA or iothalamate and plasma clearance of 51Cr-EDTA or iohexol are sufficiently accurate methods to measure GFR.

Beta-trace protein as a marker of GFR — History, indications, and future research

ObjectivesRecent findings suggest that beta-trace protein (BTP), a small molecular weight protein, is at least equal if not superior to serum creatinine as a marker of glomerular filtration rate (GFR), particularly since it is independent from height, gender, age, and muscle mass. The authors sought to summarize knowledge on BTP and its use as a marker of GFR using the most recent literature available. Design and methodsThe authors compiled key articles and all relevant recent literature on this topic. Physical and chemical features of the molecule are described, as well as factors that may affect its expression. The use of BTP in estimating GFR as a whole and in specific patient groups, including pregnant women, neonates and infants, children and adolescents, and patients who have undergone renal transplantation is discussed. The use of BTP as a marker for cardiovascular risk factors is also briefly addressed. ResultsAlthough its performance in the general population is marginally inferior to cystatin C, studies have suggested that it may be superior in accurately estimating GFR in select patient groups such as pregnant women and neonates. ConclusionsThis novel marker shows promise, but further research is required to clarify findings from available data.

Cystatin C: a new renal marker and its potential use in small animal medicine.

The occurrence of chronic kidney disease is underestimated in both human and veterinary medicine. Glomerular filtration rate (GFR) is considered the gold standard for evaluating kidney function. However, GFR assessment is time‐consuming and labor‐intensive and therefore not routinely used in practice. The commonly used indirect GFR markers, serum creatinine (sCr) and urea, are not sufficiently sensitive or specific to detect early renal dysfunction. Serum cystatin C (sCysC), a proteinase inhibitor, has most of the properties required for an endogenous GFR marker. In human medicine, numerous studies have evaluated its potential use as a GFR marker in several populations. In veterinary medicine, this marker is gaining interest. The measurement is easy, which makes it an interesting parameter for clinical use. This review summarizes current knowledge about cystatin C (CysC) in humans, dogs, and cats, including its history, assays, relationship with GFR, and biological and clinical variations in both human and veterinary medicine.

English

There was a good correlation between Glomerular Filtration Rate (GFR) values estimated by any of the 3 methods. Crcl correlated better with Cockcroft-Gault (CG eGFR) than Modification of Diet in Renal Disease (MDRD eGFR) and there was also a very good correlation between CG eGFR and MDRD eGFR. Based on this result we feel that in advanced CKD all 3 methods give similar GFR estimates but in earlier stages of Chronic Kidney Disease (CKD) Creatinine clearance (Crcl) gives higher estimate of GFR. Thus use of Crcl may wrongly classify patients into less severe stages of CKD which might lead to delay in initiation of proper treatment. MATERIALS AND METHODS: CKD patients were selected on the basis of serum creatinine levels. S.C > 2.5 mg/dl values were considered to be having CKD. 75 Samples were tested. Both males & females patients are taken in this study. Serum Creatinine & Urinary Creatinine by Jaffe's method, Blood Urea by Urease method, Urinary Protein by Pyrogallol red method, estimation of GFR by three methods. Creatinine Clearance &eGFR by using Cockcroft- Gault& MDRD equations. RESULT: A total of 75 patients attending the nephrology department (P.E.S Medical College, Kuppam)for treatment and monitoring for chronic kidney disease where included in the present study. Serum creatinine, serum urea and creatinine clearance were measured in all these patients as per methods described under materials and methods. Estimated GFR (eGFR) using CG (Cock croft) and MDRD (Modification of Diet in renal disease) formulae were calculated. Majority of the cases were complications due to long standing diabetes mellitus or hypertension. CONCLUSION: Creatinine Clearance over estimates GFR in early stages of CKD. Use of Crcl to assess GFR may not be proper to classify CKD into different stages. Any of the 3 methods (Crcl, CG eGFR and MDRD eGFR) can be used as markers of GFR in advanced stages of CKD. MDRD eGFR is a better indicator of eGFR for staging CKD in early stages of CKD. All patients included in the present study had gross proteinuria even in early stages of CKD. There was no correlation between protein: creatinine ratio and CKD stages. We recommend a larger study reporting eGFR using MDRD equation along with serum creatinine for evaluation of renal function and confirm our findings. Estimated Glomerular Filtration Rate (eGFR), Glomerular Filtration Rate (GFR), Cockcroft-Gault (CG eGFR), Modification of Diet in Renal Disease (MDRD eGFR), Creatinine clearance (Crcl), Chronic Kidney Disease (CKD).

Estimating and measuring glomerular filtration rate

Glomerular filtration rate (GFR) is the best overall measure of kidney function. Reference GFR measurements (e.g. inulin clearance) are laborious. Estimation of GFR using equations based on endogenous filtration markers is simpler, cheaper and easy to apply in practice but suffers from limited accuracy and reproducibility. This review summarizes the recent studies comparing measured and estimated GFR in various populations and disease settings. We consider the utility of newer estimating equations based on standardized methodology, including those incorporating cystatin C. Equations proposed by the Chronic Kidney Disease-Epidemiology (CKD-EPI) Consortium slightly improve the accuracy of GFR estimation compared with those used formerly. The black ethnicity coefficient in the CKD-EPI equation may not be transferable across other black populations and the equations require further validation in other ethnic groups. All currently reported equations fall short of ideal. Incorporation of cystatin C into the CKD-EPI equation improves precision and offers hope of a GFR estimate that may not require ethnic adjustment. The ideal biomarker and equation to estimate GFR would provide reproducible and accurate results across the entire range of GFRs, populations and diseases. Newer GFR markers and equations are required to fulfil this holy grail of research.