Measurement Of Filtration Rate Research Articles

Pre-dialysis decline of measured glomerular filtration rate but not serum creatinine-based estimated glomerular filtration rate is a risk factor for mortality on dialysis.

Monitoring of renal function is important in patients with chronic kidney disease progressing towards end-stage renal failure, both for timing the start of renal replacement therapy and for determining the prognosis on dialysis. Thus far, studies on associations between estimated glomerular filtration rate (eGFR) measurements in the pre-dialysis stage and mortality on dialysis have shown no or even inverse relations, which may result from the poor validity of serum creatinine-based estimation equations for renal function in pre-dialysis patients. As decline in renal function may be better reflected by the mean of the measured creatinine and urea clearance based on 24-h urine collections (mGFR by C Cr-U ), we hypothesize that in patients with low kidney function, a fast mGFR decline is a risk factor for mortality on dialysis, in contrast to a fast eGFR decline. For 197 individuals, included from the multicentre NECOSAD cohort, pre-dialysis annual decline of mGFR and eGFR was estimated with linear regression, and classified according to KDOQI as fast (>4 mL/min/1.73 m 2 /year) or slow (≤4 mL/min/1.73 m 2 /year). Cox regression was used to adjust for potential confounders. Patients with a fast mGFR decline had an increased risk of mortality on dialysis: crude hazard ratio (HR) 1.84 (95% confidence interval: 1.13-2.98), adjusted HR 1.94 (1.11-3.36). In contrast, no association was found between a fast eGFR decline in the pre-dialysis phase and mortality on dialysis: crude HR 1.20 (0.75-1.89), adjusted HR 1.14 (0.67-1.94). This study demonstrates the importance of mGFR decline (by C Cr-U ) as opposed to eGFR decline in patients with low kidney function, and gives incentive for repeated mGFR measurements in patients on pre-dialysis care.

P32 - Glomerular filtration rate measurement in HIV infected patients: useful and acceptable

P32 - Glomerular filtration rate measurement in HIV infected patients: useful and acceptable

Type 2 diabetic patients with diabetic retinopathy and concomitant microalbuminuria showed typical diabetic glomerulosclerosis and progressive renal dysfunction

AimsTo determine whether or not diabetic retinopathy (DR) in type 2 diabetic patients can predict the renal functional decline. MethodsWe examined 32 normo-microalbuminuric type 2 diabetic patients by renal biopsy (23 men, age 49±10yrs) divided into two groups according to the presence (n=19) or absence (n=13) of DR. Electron microscopic morphometry including mesangial fractional volume [Vv(Mes/glom)] were performed and light microscopic tissues were categorized as: C1, normal/near normal renal structure; C2, typical diabetic glomerulopathy; C3, atypical injury patterns. Patients were followed up for 7.1±3.8years, and glomerular filtration rate (GFR) and urinary albumin excretion (UAE) measurements were taken annually. ResultsVv(Mes/glom) was larger in DR+ than that in DR–. Vv(Mes/glom) positively correlated with the UAE if patients had DR. The patients with DR had a significant higher rate of C2 pattern compared to those in DR–. Among patients with DR and C2, GFR in microalbuminuria (n=7) decreased while GFR in normoalbuminuria (n=5) did not change during the observation. ConclusionsType 2 diabetic patients with DR and C2 showed progressive renal dysfunction after they had microalbuminuria. DR and albuminuria should be considered to determine renal function decline in type 2 diabetic patients.

Conservative management of chronic kidney disease stage 5: role of angiotensin converting enzyme inhibitors.

Benefits and risks of angiotensin converting enzyme inhibitors (ACE-I) in advanced chronic kidney disease (CKD) are controversial. We tested the role of ACE-I in slowing the progression of renal damage in a real-world elderly population with CKD stage 5. We evaluated all patients consecutively referred to our CKD stage 5 outpatient clinic from January 2002 to December 2013. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15ml/min/1.73m2. We retrieved parameters of interest at baseline and assessed eGFR reduction rate during follow-up. We estimated GFR by the 4-variable Modification of Diet in Renal Disease (MDRD) formula. Mean age of the 342 subjects analyzed was 72years and eGFR 10ml/min/1.73m2. In the 188 patients on ACE-I at baseline, the subsequent annual rate of eGFR reduction was less than a third of that found in the 154 patients off ACE-I. Across phosphate quartiles, baseline eGFR significantly decreased while its annual reduction rate significantly increased. Of the original cohort, 60 patients (17%) died, 201 (59%) started dialysis and 81 (24%) were still in conservative treatment at the end of the study. Multivariate analysis identified age, phosphate, proteinuria, baseline eGFR and its rate of progression as independent risk factors directly or inversely predictive of progression to dialysis. ACE-I use significantly reduced by 31% the risk of dialysis. Our study shows that proteinuria independently predicts further renal damage progression even in end-stage renal disease patients not yet in dialysis. In our cohort of elderly patients with very advanced CKD, ACE-I was effective in slowing down further renal damage progression.

Development and validation of the Korean version of CKD-EPI equation to estimate glomerular filtration rate

BackgroundThe Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was derived mostly from Caucasian, African-American, and Hispanic populations, whereas Asian populations were excluded. The aim of this study was to develop and validate a Korean version of the CKD-EPI equation. MethodsThe study enrolled 960 individuals 18years old and older who underwent chromium-51-ethylenediaminetetraacetic-acid-based glomerular filtration rate (GFR) measurements. They were divided randomly into two groups: a development set (n=768, 80%) and a validation set (n=192, 20%). The Korean CKD-EPI equation was developed using a non-linear mixed-effect model. The performance of the equation was evaluated by calculating the bias (estimated GFR–measured GFR). The ±10% (P10) and ±30% (P30) accuracies and root mean square errors (RMSEs) of the original and Korean CKD-EPI equations were compared. ResultsThe Korean CKD-EPI equation was as follows: male, serum creatinine (Scr) ≤80μmol/L, GFR=141×(Scr/0.9)−0.642×(0.993)Age; male, Scr>80μmol/L, GFR=141×(Scr/0.9)−1.128×(0.993)Age; female, Scr≤62μmol/L, GFR=144×(Scr/0.7)−0.465×(0.993)Age; female, Scr>62μmol/L, GFR=144×(Scr/0.7)−1.382×(0.993)Age. The mean bias (mL/min/1.73m2) of the original CKD-EPI equation was −3.0±13.5 and that of the Korean CKD-EPI equation −2.3±13.3. The P10 and P30 of the original CKD-EPI equation were 33.9% and 82.8%; for the Korean CKD-EPI equation, the corresponding values were 35.4% and 85.9%. The RMSEs of the original and Korean CKD-EPI equations were 13.7 and 13.5, respectively. ConclusionsThe overall analytical performance of the Korean CKD-EPI equation was equivalent to that of the original CKD-EPI equation. The original CKD-EPI equation is therefore also valid for the Korean population.

The Variability of Estimated Glomerular Filtration Rate Decline in Alport Syndrome.

Background:A progressive trajectory toward renal failure is common in patients with Alport syndrome. Genotype-phenotype correlations have been well described; however, the natural history of the trajectory toward renal failure is not well described.Objective:The objective of this study is to describe the natural history of renal function decline in a cohort of Alport syndrome patients.Design:Retrospective observational cohort study.Setting:British Columbia, Canada, chronic renal disease registry 1995-2012.Patients:37 biopsy proven Alport syndrome or hematuria with family history of Alport syndrome.Measurements:Serial estimated glomerular filtration rate (eGFR) Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient’s eGFR measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2 /y decline), stable state (0-2 mL/min/1.73 m2 /y decline), and regressors (>2 mL/min/1.73 m2 /y incline).Methods:In this retrospective observational cohort study, participants were identified through a chronic renal disease registry in British Columbia, Canada, from 1995 to 2012. Inclusion criteria were biopsy proven or hematuria with a family history of Alport syndrome. Individual patients and family group members were studied. Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient’s serial estimated glomerular filtration rate (eGFR) measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2/y decline), stable state (0-2 mL/min/1.73 m2/y decline), and regressors (>2 mL/min/1.73 m2/y incline).Limitations:Histological or genetic evidence of Alport syndrome is not available in all patients.Results:Median follow-up time was 48.2 months of 37 patients (78% male), with a median age of 36 (interquartile range [IQR], 18-47) and a median age of renal replacement therapy commencement (n = 23) of 38 (IQR = 20-52). Renal function changes were found to be heterogeneous overall, intra-individual and within families. Portion of progressors in eGFR 45-60 mL/min/1.73 m2 was 73.7% (SD, 10.3), whereas 23.6% (SD, 11.0) remained stable. Within eGFR 30-45 mL/min/1.73 m2, 45.6% (SD, 7.0) were progressors, whereas 53.4% (SD, 7.4) remained stable. A large portion of eGFR 15-30 mL/min/1.73 m2 patients were stable (54.8%; SD, 8.4), whereas 25.7% (SD, 7.1) progressed and 19.5% (SD, 5.6) regressed.Conclusions:The renal decline in Alport syndrome patients is heterogeneous which has implications for designing clinical trials of interventions.

Comparison of Serum Vitamin D Levels Among Patients With Chronic Kidney Disease, Patients in Dialysis, and Renal Transplant Patients

ObjectiveVitamin D is a hormone with a variety of functions, and its deficiency and insufficiency are commonly seen both in the general population and in patients with chronic renal disease. The aim of this study was to compare vitamin D levels in patients with chronic renal disease who are on hemodialysis, peritoneal dialysis, or no renal replacement therapy and patients who underwent renal transplantation. MethodsA total of 169 patients who had not used vitamin D for ≥1 year and who had no diabetes mellitus or proteinuria were included in the study. These included: 40 patients with renal transplantation, 40 patients on hemodialysis, 49 patients on peritoneal dialysis, and 40 patients with chronic renal failure stage 1, 2, 3, or 4. 25-Hydroxy vitamin D levels were evaluated in the sera of the patients. Results25-Hydroxy vitamin D levels in patients with renal transplantation and in predialysis patients were 12.74 ± 10.24 ng/mL and 11.16 ± 12.25 ng/mL, respectively. The levels were 7.77 ± 6.71 ng/mL and 5.96 ± 4.87 ng/mL in patients on hemodialysis and peritoneal dialysis, respectively. ConclusionsVitamin D levels are lower in patients on hemodialysis and peritoneal dialysis compared with the patients with renal transplantation for a variety of reasons. In this study, objective results were obtained supporting the administration of vitamin D supplements without glomerular filtration rate measurement in all patient groups with the diagnosis of chronic renal failure in accordance with the guidelines.

Feasibility study of high-resolution DCE-MRI for glomerular filtration rate (GFR) measurement in a routine clinical modal

Dynamic contrast enhanced (DCE) MR renography has been identified as an interesting tool to determine single-kidney GFR. However, a fundamental issue for the applicability of MR-based estimate of single-kidney GFR is selecting a balance between spatial and temporal resolution of DCE-MRI data. The purpose is to assess the feasibility of GFR estimate from high-resolution (HR) dynamic contrast-enhanced (DCE) MRI in a routine clinical modal. Standard MR renography (2.4s/phase, total 4min; 4-ml Gd) and five-phase, HR-based imaging protocol (0, 30, 70, 120, and 240s; 0.05mmol/kg Gd) were prospectively performed in twelve volunteers who were scheduled for routine renal MRI. Data were plotted with Patlak, two-compartment modified Tofts model (2CTM), and two-compartment filtration model (2CFM) for GFR estimate. During all the measurements, only the signal intensities in the aorta and whole kidney parenchyma were considered. Standard 2CFM and 2CTM produced lower residuals over the fitted interval than HR-based measures (p<0.05); and HR-bases 2CFM and 2CTM did not reflect significant correlation to standard values. Standard Patlak plots with 0–240s data points produced significantly lower GFR and higher residuals than that plots with 0–120s data points (p<0.05). HR-based Patlak plots with 0, 30, 70, and 120s data points significantly correlated with reference values (Pearson ρ=0.97, p<0.01), and produced a 33.2% underestimation of reference value, which was better than that plots with 0, 30, 70, 120, and 240s data points (ρ=0.92, p<0.01; 58.6% underestimation of reference value). It concludes that it is feasible to estimate GFR with HR-based DCE-MRI and appreciate kinetic model. Patlak plots from 0, 30, 70, and 120s data points is better than plots from 0, 30, 70, 120, and 240s data points.

Circulating Lipocalin 2 Levels Predict Fracture-Related Hospitalizations in Elderly Women: A Prospective Cohort Study.

Lipocalin 2 (LCN2) or neutrophil gelatinase-associated lipocalin (NGAL) is expressed in a wide range of cells and pathological states. Mounting evidence suggests lipocalin 2 may be an important regulator of bone homeostasis. Recently it has been suggested LCN2 is a novel mechanoresponsive gene central to the pathological response to low mechanical force. We undertook a prospective study of 1009 elderly women over 70 years of age to study the association between circulating LCN2 and potential associated variables, including estimated glomerular filtration rate, physical activity, and baseline measures of hip bone density and heel bone quality. Osteoporotic fractures requiring hospitalizations were identified from the Western Australian Data Linkage System. Over 14.5 years, 272 (27%) of women sustained an osteoporotic fracture-related hospitalization; of these, 101 were hip fractures. Circulating LCN2 levels were correlated with body mass index and estimated glomerular filtration rate (r = 0.249, p < 0.001 and r = -0.481, p < 0.001, respectively) that modified the association with hip and heel bone measures. Per standard deviation increase in LCN2, there was a 30% multivariable-adjusted increase in the risk of any osteoporotic fracture (hazard ratio [HR] = 1.30, 95% confidence interval [CI] 1.13-1.50, p < 0.001). In participants with elevated LCN2 levels above the median (76.6 ng/mL), there was an 80% to 81% increase in the risk of any osteoporotic or hip fracture (HR = 1.81, 95% CI 1.38-2.36, p < 0.001 and HR = 1.80, 95% CI 1.16-2.78, p = 0.008, respectively). These associations remained significant after adjustment for total hip bone mineral density (p < 0.05). In conclusion, we have demonstrated that circulating LCN2 levels predict future risk of osteoporotic fractures requiring hospitalization. Measurement of LCN2 levels may improve fracture prediction in addition to current fracture risk factors in the elderly, particularly in those with impaired renal function.

Rapid determination of X-ray contrast agent iomeprol in human plasma by on-line solid-phase extraction coupled with phase optimized liquid chromatography.

Phase optimized liquid chromatography (POPLC) allows for the optimized combination of column segments of any length and stationary phases with different functionalities. In this study, a simple and rapid method using POPLC coupled with on-line solid-phase extraction (SPE) for the analysis of X-ray contrast media agent iomeprol (IOM) in human plasma was developed. Because the phenyl (PH) stationary phase has strong hydrophobic and π-π interactions with IOM and iopromide (IOP, internal standard), the best separation efficiency was achieved with a 250mm×3mm homogenous PH POPLC-column. Different kinds of on-line SPE sorbents were studied, including restricted access material-alkyl diol silica (ADS), LiChrolut EN with excellent absorption capacity and hydrophilic-lipophilic-balanced Oasis HLB. The most efficient on-line sample clean-up was carried out using a fast-flow on-line purification approach with an Oasis HLB pre-column ((20mm×2mm, 30μm). This pre-column showed excellent durability and reproducibility. At least 400 samples could be analyzed with one pre-column. Each plasma sample was directly injected and analyzed within 15min. The calibration curves were linear in the range of 10-1000μg/mL. The limit of quantitation was 2.26μg/mL. The inter-day precision of this method was excellent and less than 1.44%, and the intra-day precision was less than 4.44%. The inter-day and intra-day accuracy ranged from 94.33% to 104.36% and 94.60% to 101.71%, respectively. This validated method is expected to be useful in the analysis of human plasma samples for glomerular filtration rate (GFR) measurements and assessment of kidney function.

Application of plasma clearance of iohexol in evaluating renal function in chinese children with chronic kidney disease.

To evaluate the accuracy of plasma clearance of iohexol (PCio) for glomerular filtration rate (GFR) measurement in Chinese children with chronic kidney disease (CKD) and assess the feasibility of single-blood-sample method or dried capillary blood spots in determining the PCio. Totally 45 CKD children were included,in whom the (99m) Technetium-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) plasma clearance and iohexol plasma clearance were simultaneously determined. Blood samples were obtained 2,4,and 5 hours after injection. In addition, we also evaluated the efficacy of single blood sample method and dried blood spots method in iohexol plasma clearance. Forty-five CKD children completed the iohexol plasma clearance and thirty-six children completed the (99m)Tc-DTPA plasma clearance at the same time among them. Thirteen children finished the iohexol dried blood spot clearance. The correlation coefficient between (99m)Tc-DTPA plasma clearance and iohexol plasma clearance was 0.941 and the bias was (6.53 ± 11.6) ml/ (min·1.73 m²), and the intraclass correlation coefficient (ICC) was high (ICC=0.947). The correlation between iohexol single-sample plasma clearance and double samples was also strong (r=0.958), with the bias being (4.26 ± 9.06)ml/(min·1.73 m²) and the ICC being 0.970. The iohexol clearance by dried blood spots showed a good correlation with the serum iohexol clearance (r=0.950), with the bias still being small [(0.48 ± 10.89)ml/(min·1.73 m²)]. Iohexol plasma clearance has satisfactory agreement with (99m)Tc-DTPA plasma clearance and can be used as an ideal method to measure GFR in CKD children. The single-sample method and dried blood spots method make iohexol plasma clearance more convenient and practical.

Comparison of glomerular filtration rate measurements with two plasma and single plasma sample methods in renal transplant cases with stable renal graft functions

This study was planned to determine the efficacies of single plasma sample methods (SPSMs) in indicating glomerular filtration rate (GFR) by taking two plasma sample method (TPSM) as reference in the determination of the GFR in cases with clinically stable renal transplantation. Ninety-six renal transplantation cases (33 female, 63 male; age interval 18-67, mean age 37.46±11.81years) progressing stably clinically and as laboratory, with minimum 6months after transplantation were included in the study. The GFR values of the cases were measured with SPSM and TPSM. It is observed that all SPSMs have a strong correlation with TPSM. Highest correlation was observed between Groth&Aasted SPSM and TPSM GFR (intraclass correlation coefficient: 0.965). In the analyses performed by using the Bland-Altman analysis, GFR values calculated by all SPSMs were concordant to the TPSM which is the gold standard method in 95% confidence interval (average±1.96 standard deviation) and were within the clinically acceptable limits. The narrowest concordance interval was obtained between Groth&Aasted Tc-99m DTPA SPSM and Tc-99m DTPA TPSM..Besides, we have obtained the minimum bias and precision value by the Groth&Aasted method. As a result; we can see that all the SPSMs give reliable results in measuring GFR in cases with renal transplantation; besides, we suggest Groth&Aasted method as the first option.

Validation and impact of a new technique for assessment of glomerular filtration rate in patients with liver disease.

Previously we have proposed a technique for the measurement of plasma clearance in patients with ascites. The impact of using the technique was assessed and the results compared with those from a reference technique in 111 patients having glomerular filtration rate measurements as part of their workup for liver transplantation. Results of calculations using the new technique were compared with plasma clearance measurements obtained using a conventional slope-intercept technique and with clearance measurements based on urine collection. Discrepancies between the results of plasma clearance and urinary clearance assessments were investigated by using an uncollimated gamma camera to measure the total retention of the tracer. Conventional slope-intercept calculations overestimated clearance compared with the new technique by more than 20% in 21% of the patients. Significant differences between the results of the two methods were more likely in patients with more severe ascites. Results of urine collection-based measurements of Cr-51 EDTA clearance were frequently significantly lower than measurements using the new technique, whereas measurements of urinary clearance of creatinine were higher. Gamma camera measurements suggest that discrepancies between total and urinary clearance of Cr-51 EDTA are due to incomplete urine collection. The new technique is a practical method for assessment of kidney function and should be used in patients with liver disease who have or may have ascites.

Joint modelling of repeated measurement and time-to-event data: an introductory tutorial.

The term 'joint modelling' is used in the statistical literature to refer to methods for simultaneously analysing longitudinal measurement outcomes, also called repeated measurement data, and time-to-event outcomes, also called survival data. A typical example from nephrology is a study in which the data from each participant consist of repeated estimated glomerular filtration rate (eGFR) measurements and time to initiation of renal replacement therapy (RRT). Joint models typically combine linear mixed effects models for repeated measurements and Cox models for censored survival outcomes. Our aim in this paper is to present an introductory tutorial on joint modelling methods, with a case study in nephrology. We describe the development of the joint modelling framework and compare the results with those obtained by the more widely used approaches of conducting separate analyses of the repeated measurements and survival times based on a linear mixed effects model and a Cox model, respectively. Our case study concerns a data set from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS). We also provide details of our open-source software implementation to allow others to replicate and/or modify our analysis. The results for the conventional linear mixed effects model and the longitudinal component of the joint models were found to be similar. However, there were considerable differences between the results for the Cox model with time-varying covariate and the time-to-event component of the joint model. For example, the relationship between kidney function as measured by eGFR and the hazard for initiation of RRT was significantly underestimated by the Cox model that treats eGFR as a time-varying covariate, because the Cox model does not take measurement error in eGFR into account. Joint models should be preferred for simultaneous analyses of repeated measurement and survival data, especially when the former is measured with error and the association between the underlying error-free measurement process and the hazard for survival is of scientific interest.

Neutrophil Gelatinase-Associated Lipocalin: A New Marker of Renal Function in C-Related End Stage Liver Disease.

Background/Aims. Renal impairment is a common complication of cirrhosis. Serum creatinine is less sensitive in these patients. Measurement of the glomerular filtration rate (GFR) is the gold standard but time consuming. The aim is to validate plasma NGAL (pNGAL) and urinary NGAL (uNGAL) as markers of renal function in patients with HCV related cirrhosis. Patient and Methods. One hundred HCV related end stage liver cirrhosis patients were randomized into two groups: Group I (n = 35), patients with GFR < 60 mL/m measured by isotope scanning of the kidney (Renogram), and Group II (n = 65), patients with GFR ≥ 60 mL/m. The pNGAL and uNGAL were measured within 2 days of the Renogram. Results. Both groups were matched with age, sex, and Child Pugh score. There was statistically significant difference between both groups regarding serum creatinine (1.98 ± 1.04 versus 1.38 ± 0.88 mg/dL; p = 0.003) and pNGAL level (5.79 ± 2.06 versus 7.25 ± 3.30 ng/dL; p = 0.019). Both groups were comparable (p > 0.05) for the uNGAL (6.00 ± 0.78 versus 6.03 ± 0.96 ng/mL). Unlike uNGAL, the pNGAL positively correlated with total GFR by Renogram (r = 0.3; p = 0.001). With a cutoff ≥4 ng/mL, pNGAL had 94.3% sensitivity and 1.5% specificity and PPV = 34, NPV = 33.3, LR+ = −175.1, and LR− = −60.6. Conclusion. The pNGAL is a promising marker of the renal function in patients with cirrhosis.

The 99mTc-DTPA Urinary Clearance Method May Be Preferable to the Plasma Disappearance Method for Assessing Glomerular Filtration Rate in Diabetic Nephropathy

Background: Isotopic glomerular filtration rate (iGFR) measurement is comparable to the inulin method. In this study, we compared urinary and plasma iGFR methodologies in patients with diabetic nephropathy. Methods: A total of 147 patients from 3 sites in the Diabetic Intervention with Vitamins to Improve Nephropathy (DIVINe) trial provided 213 sets of urine and blood collections, at baseline, 18 and 36 months. Results: The mean (with standard deviation) plasma iGFR of 60.7 (24.9) ml/min/1.73 m² compared to urinary iGFR of 52.0 (28.0) ml/min/1.73 m² was statistically significant (p value <0.001). Although plasma and urinary iGFRs were highly related (R² = 0.86), plasma iGFR increasingly overestimated urinary iGFRs at lower GFRs. In contrast to the cross-sectional analyses, the two measures of iGFR were weakly related (R² = 0.32) in regard to patients' change over 18 months of follow-up. Conclusion: Plasma iGFR may not be a suitable method for accurately measuring GFR in patients with advancing degrees of chronic kidney disease from diabetic nephropathy.

A pilot study to assess the feasibility of transcutaneous glomerular filtration rate measurement using fluorescence-labelled sinistrin in dogs and cats.

In dogs and cats an assessment of renal function is often needed, however, existing methods including urine and plasma clearances are invasive, cumbersome and time consuming. This pilot study evaluated the feasibility of a transcutaneous glomerular filtration rate (GFR) measurement in dogs and cats. Additionally the optimal dose and location for the transcutaneous measurement device were investigated. Renal elimination of fluorescein-isothiocyanate-labelled sinistrin (FITC-S) was measured transcutaneously for 4 hours. The procedures were performed in awake, freely moving animals using escalating doses of FITC-S (10 mg/kg, 30 mg/kg, 50 mg/kg) with a wash-out period of at least 24 h in between. Multiple devices were placed on each animal. The resulting FITC-S disappearance curves were visually assessed to determine the most suitable location and the appropriate dose to reach an adequate transcutaneous peak signal for kinetic analysis. In both species 30 mg/kg were adequate for kinetic calculation. The most suitable place for the device was the lateral thoracic wall in dogs and the ventral abdominal wall in cats, respectively. Transcutaneous FITC-S clearance was then repeated using the optimal dose and location and in parallel with an additional plasma sinistrin clearance. Plasma elimination half-lives [min] were 26, 31 and 35, and corresponding transcutaneous elimination half-lives [min] were 26, 34 and 55, respectively in the dogs. Plasma elimination half-lives [min] were 51, 60 and 61, and corresponding transcutaneous elimination half-lives [min] were 75, 96 and 83, respectively in the cats. In conclusion, transcutaneous FITC-S clearance is a feasible method for the assessment of GFR in awake dogs and cats. It is noninvasive, well tolerated and easy to perform even in a clinical setting with results being readily available. A dose of 30 mg/kg of FITC-S seems adequate for kinetic assessment. Further studies are now needed to establish reference values and evaluate transcutaneous renal clearance in various conditions.

UK audit of glomerular filtration rate measurement from plasma sampling in 2013.

An audit was carried out into UK glomerular filtration rate (GFR) calculation. The results were compared with an identical 2001 audit. Participants used their routine method to calculate GFR for 20 data sets (four plasma samples) in millilitres per minute and also the GFR normalized for body surface area. Some unsound data sets were included to analyse the applied quality control (QC) methods. Variability between centres was assessed for each data set, compared with the national median and a reference value calculated using the method recommended in the British Nuclear Medicine Society guidelines. The influence of the number of samples on variability was studied. Supplementary data were requested on workload and methodology. The 59 returns showed widespread standardization. The applied early exponential clearance correction was the main contributor to the observed variability. These corrections were applied by 97% of centres (50% - 2001) with 80% using the recommended averaged Brochner-Mortenson correction. Approximately 75% applied the recommended Haycock body surface area formula for adults (78% for children). The effect of the number of samples used was not significant. There was wide variability in the applied QC techniques, especially in terms of the use of the volume of distribution. The widespread adoption of the guidelines has harmonized national GFR calculation compared with the previous audit. Further standardization could further reduce variability. This audit has highlighted the need to address the national standardization of QC methods. Radionuclide techniques are confirmed as the preferred method for GFR measurement when an unequivocal result is required.

Glomerular Filtration Rate Estimation in Prospective Living Kidney Donors: Preliminary Study

IntroductionKidney transplantation prolongs life expectancy in end-stage renal disease patients at a lesser cost than dialysis. Estimation of kidney function is crucial in the evaluation of prospective living kidney donors. Although unsurpassed in their precision methods of glomerular filtration rate (GFR) measurement with exogenous substances are invasive, expensive, and carry a risk for anaphylactic reactions. Alternatively, kidney function can also be assessed by GFR estimation formulas based on serum creatinine or novel markers such as cystatin C or β-trace protein (BTP). The aim of this study was to compare the performance of GFR estimation methods with reference scintigraphy-measured GFR in population of living kidney donor candidates. MethodsWe included 25 prospective kidney donors (aged 28–64 years) and measured GFR with the following equations: Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Mayo Clinic, Nankivell, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; including cystatin C), and BTP based. GFR were assessed by 99mTc-DTPA for reference. All estimation methods were compared with a reference by general linear models. ResultsThe precision of GFR estimation by all methods is unsatisfactory (30% margin of reference held in <50% of cases). Direction of regression coefficients is negative for some of the methods even when adjusted for body mass index (BMI). Of the study subjects, 64% were overweight/obese. BMI value is significantly correlated with measured GFR (P < .01). CKD-EPI estimation equations are the most precise methods of GFR estimation in this analysis; in addition, CKD-EPI cystatin C and combined creatinine/cystatin C estimators are robust to overweight/obesity. ConclusionsThe precision of GFR estimation is unsatisfactory, in part because of overweight, which adversely influences measured GFR, but also renders estimation methods unusable, except for CKD-EPI cystatin C and combined creatinine/cystatin C formulae. GFR measurement with exogenous substances remains the method of choice in the assessment of kidney function in prospective kidney donors. In addition, it provides useful information on differential (split) renal function.

Agreement among measurements and estimations of glomerular filtration in children with cancer

Glomerular filtration is an important route of elimination for many types of chemotherapy. Accurate estimation of glomerular filtration at the bedside is essential in the management of children with cancer. Bedside formulae for the estimation of glomerular filtration have not been validated in children with cancer. We investigated the accuracy of three formulae (the original Schwartz, Counahan-Barratt, and revised Schwartz equations) against measurement of the glomerular filtration rate (GFR) in a cohort of children with cancer. This was a retrospective review of existing data from a single institution. The electronic medical record was queried for subjects meeting inclusion criteria during a 3.5 year time frame. Bland-Altman analyses were used to assess agreement among current formulae and estimating the GFR compared to the measured, or index GFR. Logistic regression was performed to identify potential variables with an effect on the estimation of GFR. None of the three estimation formulae provided a reliable estimate of the index GFR. The mean difference was lowest between the revised Schwartz and the index GFR compared to the other two formulae and the index GFR. For the original Schwartz equation, age and prior receipt of chemotherapy were significant predictors of under- and overestimation. For the revised Schwartz equation, one age group (6-12 years) and a diagnosis of neuroblastoma actively receiving chemotherapy were positive risk factors for overestimation of the GFR. Currently available estimation formulae for GFR may not be appropriate for children with cancer.