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The New England Journal of Medicine May 2006Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of cyst-filled kidneys.
BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of cyst-filled kidneys.
METHODS
In a three-year study, we measured the rates of change in total kidney volume, total cyst volume, and iothalamate clearance in patients with ADPKD. Of a total of 241 patients, in 232 patients without azotemia who were 15 to 46 years old at baseline we used magnetic-resonance imaging to correlate the total kidney volume and total cyst volume with iothalamate clearance. Statistical methods included analysis of variance, Pearson correlation, and multivariate regression analysis.
RESULTS
Total kidney volume and total cyst volume increased exponentially, a result consistent with an expansion process dependent on growth. The mean (+/-SD) total kidney volume was 1060+/-642 ml at baseline and increased by a mean of 204+/-246 ml (5.27+/-3.92 percent per year, P<0.001) over a three-year period among 214 patients. Total cyst volume increased by 218+/-263 ml (P<0.001) during the same period among 210 patients. The baseline total kidney volume predicted the subsequent rate of increase in volume, independently of age. A baseline total kidney volume above 1500 ml in 51 patients was associated with a declining glomerular filtration rate (by 4.33+/-8.07 ml per minute per year, P<0.001). Total kidney volume increased more in 135 patients with PKD1 mutations (by 245+/-268 ml) than in 28 patients with PKD2 mutations (by 136+/-100 ml, P=0.03).
CONCLUSIONS
Kidney enlargement resulting from the expansion of cysts in patients with ADPKD is continuous and quantifiable and is associated with the decline of renal function. Higher rates of kidney enlargement are associated with a more rapid decrease in renal function.
Topics: Adult; Analysis of Variance; Disease Progression; Female; Glomerular Filtration Rate; Humans; Kidney; Longitudinal Studies; Magnetic Resonance Imaging; Male; Mutation; Organ Size; Polycystic Kidney, Autosomal Dominant; Regression Analysis
PubMed: 16707749
DOI: 10.1056/NEJMoa054341 -
Journal of Veterinary Internal Medicine 1998Glomerular filtration rate (GFR) is estimated by means of clearance, defined as the volume of plasma that has been cleared of a particular substance per unit time.... (Review)
Review
Glomerular filtration rate (GFR) is estimated by means of clearance, defined as the volume of plasma that has been cleared of a particular substance per unit time. Glomerular filtration rate may be estimated by measuring the renal clearance of a filtration marker using data from both urine and plasma or by plasma clearance using only plasma data. Several alternative pharmacokinetic models are used for the calculation of clearance using various filtration markers with slightly different pharmacokinetic properties. The purpose of this article is to discuss how the choice of marker and pharmacokinetic model may influence estimated GFR values and to elucidate commonly used methods and reported GFR values in the dog.
Topics: Animals; Biomarkers; Creatinine; Dogs; Edetic Acid; Female; Glomerular Filtration Rate; Inulin; Iothalamic Acid; Kidney; Male; Metabolic Clearance Rate; Models, Biological; Pentetic Acid; Sex Characteristics
PubMed: 9857332
DOI: 10.1111/j.1939-1676.1998.tb02143.x -
Journal of the American Society of... Jul 2016Measured GFR (mGFR) has long been considered the gold standard measure of kidney function, but recent studies have shown that mGFR is not consistently superior to eGFR... (Comparative Study)
Comparative Study
Measured GFR (mGFR) has long been considered the gold standard measure of kidney function, but recent studies have shown that mGFR is not consistently superior to eGFR in explaining CKD-related comorbidities. The associations between longitudinal changes in mGFR versus eGFR and adverse outcomes have not been examined. We analyzed a subset of 942 participants with CKD in the Chronic Renal Insufficiency Cohort Study who had at least two mGFRs and two eGFRs determined concurrently by iothalamate and creatinine (eGFRcr) or cystatin C, respectively. We compared the associations between longitudinal changes in each measure of kidney function over 2 years and risks of ESRD, nonfatal cardiovascular events, and all-cause mortality using univariate Cox proportional hazards models. The associations for all outcomes except all-cause mortality associated most strongly with longitudinal decline in eGFRcr. Every 5-ml/min per 1.73 m(2) decline in eGFRcr over 2 years associated with 1.54 (95% confidence interval, 1.44 to 1.66; P<0.001) times higher risk of ESRD and 1.23 (95% confidence interval, 1.12 to 1.34; P<0.001) times higher risk for cardiovascular events. All-cause mortality did not associate with longitudinal decline in mGFR or eGFR. When analyzed by tertiles of renal function decline, mGFR did not outperform eGFRcr in the association with any outcome. In conclusion, compared with declines in eGFR, declines in mGFR over a 2-year period, analyzed either as a continuous variable or in tertiles, did not consistently show enhanced association with risk of ESRD, cardiovascular events, or death.
Topics: Cohort Studies; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Prognosis; Renal Insufficiency, Chronic
PubMed: 26604213
DOI: 10.1681/ASN.2015040341 -
Clinical Journal of the American... Sep 2016eGFR equations have been evaluated in kidney transplant recipients with variable performance. We assessed the performance of the Modification of Diet in Renal Disease...
BACKGROUND AND OBJECTIVES
eGFR equations have been evaluated in kidney transplant recipients with variable performance. We assessed the performance of the Modification of Diet in Renal Disease equation and the Chronic Kidney Disease Epidemiology Collaboration equations on the basis of creatinine, cystatin C, and both (eGFR creatinine-cystatin C) compared with measured GFR by iothalamate clearance and evaluated their non-GFR determinants and associations across 15 cardiovascular risk factors.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
A cross-sectional cohort of 1139 kidney transplant recipients >1 year after transplant was analyzed. eGFR bias, precision, and accuracy (percentage of estimates within 30% of measured GFR) were assessed. Interaction of each cardiovascular risk factor with eGFR relative to measured GFR was determined.
RESULTS
Median measured GFR was 55.0 ml/min per 1.73 m(2). eGFR creatinine overestimated measured GFR by 3.1% (percentage of estimates within 30% of measured GFR of 80.4%), and eGFR Modification of Diet in Renal Disease underestimated measured GFR by 2.2% (percentage of estimates within 30% of measured GFR of 80.4%). eGFR cystatin C underestimated measured GFR by -13.7% (percentage of estimates within 30% of measured GFR of 77.1%), and eGFR creatinine-cystatin C underestimated measured GFR by -8.1% (percentage of estimates within 30% of measured GFR of 86.5%). Lower measured GFR associated with older age, women, obesity, longer time after transplant, lower HDL, lower hemoglobin, lower albumin, higher triglycerides, higher proteinuria, and an elevated cardiac troponin T level but did not associate with diabetes, smoking, cardiovascular events, pretransplant dialysis, or hemoglobin A1c. These risk factor associations differed for five risk factors with eGFR creatinine, six risk factors for eGFR Modification of Diet in Renal Disease, ten risk factors for eGFR cystatin C, and four risk factors for eGFR creatinine-cystatin C.
CONCLUSIONS
Thus, eGFR creatinine and eGFR creatinine-cystatin C are preferred over eGFR cystatin C in kidney transplant recipients because they are less biased, more accurate, and more consistently reflect the same risk factor associations seen with measured GFR.
Topics: Adult; Aged; Contrast Media; Creatinine; Cross-Sectional Studies; Cystatin C; Female; Glomerular Filtration Rate; Humans; Immunoturbidimetry; Iothalamic Acid; Kidney; Kidney Transplantation; Male; Mathematical Concepts; Middle Aged; Risk Factors
PubMed: 27340283
DOI: 10.2215/CJN.11741115 -
Kidney International. Supplement Feb 2003The Pima Indians of Arizona not only have a much higher incidence of nephropathy due to type 2 diabetes than Caucasians, but they also lose their renal function at an... (Review)
Review
The Pima Indians of Arizona not only have a much higher incidence of nephropathy due to type 2 diabetes than Caucasians, but they also lose their renal function at an accelerated rate after they develop diabetic nephropathy. This rapid loss of renal function occurs despite a younger age of onset of nephropathy and lower blood pressures and lipid levels, all of which would seem to predict a slower rate of progression of nephropathy. These findings suggest that other factors contribute to the rapid progression of renal disease in this population. In particular, glomerulomegaly in this population may contribute to the high rate of glomerular filtration rate (GFR) loss during the terminal, clinically manifest phase of nephropathy, because of the greater incremental loss of single-nephron GFR (SNGFR) with each nephron lost to sclerosis. In nine Pima Indians with type 2 diabetic nephropathy who underwent renal biopsy followed by serial iothalamate clearances for up to ten years, we examined the relationship between glomerular tuft volume at initial biopsy and the rate of GFR loss during the terminal phase. By multivariate analysis, significant independent effects of both glomerular volume (P=0.006) and podocyte density (P=0.043) were evident in these individuals. The effect of glomerular volume may result from a greater loss of intrinsic filtration capacity with each glomerulus lost, while the effect of podocyte density may reflect the destabilizing influence of "podocyte insufficiency" on the glomerular tuft. Similar factors may play a role in the rapid loss of GFR associated with progressive glomerular diseases in other indigenous populations in whom glomerulomegaly and glomerulopenia coexist.
Topics: Arizona; Diabetic Nephropathies; Disease Progression; Glomerular Filtration Rate; Humans; Indians, North American
PubMed: 12864873
DOI: 10.1046/j.1523-1755.63.s83.9.x -
Clinical Journal of the American... Jun 2013Although iothalamate clearances have been widely used to measure GFR, the need for transportation of plasma samples under refrigerated conditions obviates its use in...
BACKGROUND AND OBJECTIVES
Although iothalamate clearances have been widely used to measure GFR, the need for transportation of plasma samples under refrigerated conditions obviates its use in resource-poor situations. Spots of blood or plasma dried on filter paper may provide a solution.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Using a validated HPLC technique, iothalamate in dried blood spots of different hematocrits was measured. GFR was measured over 5 hours in 10 subjects with CKD using dried plasma spots and standard methods.
RESULTS
Lower hematocrit produced greater area of blood spreading and lowered the recovery of iothalamate from dried blood spots. However, the relationship between iothalamate concentrations in dried plasma spots and plasma showed a regression slope of 0.95 (95% confidence interval=0.92-0.98, P<0.001). Bland-Altman plot of paired sample points (n=116) showed a bias of -4 μg/ml and limits of agreement of -38 to +30 μg/ml. The relationship between GFRs using dried plasma spots and plasma methods also showed an excellent relationship (slope of 0.95, 95% confidence interval=0.82-1.17). Bland-Altman plot of paired GFRs showed a bias of 2 ml/min, with limits of agreement of -6 to +10 ml/min. Precision was generally between 5% and 10%, and accuracy was within 5%.
CONCLUSIONS
Although dried blood spots are unsuitable for studies among those patients with very low hematocrit, dried plasma spots correct for this limitation, and this small pilot study shows that it is a reasonably reliable method for quantifying iothalamate and subsequently, determining GFR.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chromatography, High Pressure Liquid; Dried Blood Spot Testing; Female; Glomerular Filtration Rate; Hematocrit; Humans; Iothalamic Acid; Kidney; Male; Middle Aged; Pilot Projects; Predictive Value of Tests; Renal Insufficiency, Chronic; Reproducibility of Results; Spectrophotometry, Ultraviolet; Time Factors
PubMed: 23411426
DOI: 10.2215/CJN.10471012 -
JAMA Network Open Jul 2021This diagnostic/prognostic study examines the estimated glomerular filtration rates (eGFR) and iothalamate clearance glomerular filtration rates (iGFR) and the Chronic...
This diagnostic/prognostic study examines the estimated glomerular filtration rates (eGFR) and iothalamate clearance glomerular filtration rates (iGFR) and the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation race coefficient in the Chronic Renal Insufficiency Cohort study.
Topics: Cohort Studies; Contrast Media; Correlation of Data; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Humans; Iothalamic Acid; Kidney Function Tests; Male; Middle Aged; Prognosis; Renal Insufficiency, Chronic; Statistics as Topic
PubMed: 34264332
DOI: 10.1001/jamanetworkopen.2021.17080 -
Clinical Journal of the American... Jan 2009Measurement of GFR is important for the management of chronic kidney disease (CKD). Although bolus administration of radiocontrast agents is commonly used to measure...
BACKGROUND AND OBJECTIVES
Measurement of GFR is important for the management of chronic kidney disease (CKD). Although bolus administration of radiocontrast agents is commonly used to measure GFR, the optimal duration of sampling to assess their plasma clearance is unknown. The purpose of this study was to evaluate whether the duration of plasma sampling influences precision and estimation of GFR.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
GFR was measured by sampling plasma 12 times over 5 h in 56 patients with CKD (mean age 64 yr, 98% men, 79% Caucasian, 34% diabetics, estimated GFR 31.8 +/- 14.2 ml/min/1.73 m(2)). In a subset of 12 patients we measured GFR by sampling plasma 17 times over 10 h.
RESULTS
Short sampling intervals considerably overestimated GFR measured using total plasma iothalamate clearance, especially in larger patients. In the higher estimated GFR group (>30 ml/min/1.73 m(2)), the 5-h GFR was 17% higher and 2-h GFR 54% higher compared with the 10-h GFR, which averaged 40.3 ml/min/1.73 m(2). In the lower estimated GFR group (<30 ml/min/1.73 m(2)), the 5-h GFR was 36% higher and 2-h GFR 126% higher compared with the 10-h GFR, which averaged 22.2 ml/min/1.73 m(2). Short sampling duration also reduced the precision of the estimated GFR from 1.67% for 10-h GFR, to 3.48% for 5-h GFR, and to 7.07% for 2-h GFR.
CONCLUSIONS
GFR measured over a longer duration with multiple plasma samples spanning the distribution and elimination phases may improve precision and provide a better measure of renal function.
Topics: Aged; Chronic Disease; Contrast Media; Female; Glomerular Filtration Rate; Humans; Injections, Intravenous; Iothalamate Meglumine; Kidney; Kidney Diseases; Male; Middle Aged; Models, Biological; Predictive Value of Tests; Reproducibility of Results
PubMed: 19005012
DOI: 10.2215/CJN.03720708 -
Bioengineering (Basel, Switzerland) Jun 2023An accurate estimate of glomerular filtration rate (eGFR) is essential for proper clinical management, especially in patients with kidney dysfunction. This prospective...
An accurate estimate of glomerular filtration rate (eGFR) is essential for proper clinical management, especially in patients with kidney dysfunction. This prospective observational study evaluated the real-world performance of the nuclear magnetic resonance (NMR)-based GFR equation, which combines creatinine, cystatin C, valine, and myo-inositol with age and sex. We compared GFR performance to that of the 2021 CKD-EPI creatinine and creatinine-cystatin C equations (CKD-EPI and CKD-EPI), using 115 fresh routine samples of patients scheduled for urinary iothalamate clearance measurement (mGFR). Median bias to mGFR of the three eGFR equations was comparably low, ranging from 0.4 to 2.0 mL/min/1.73 m. GFR outperformed the 2021 CKD-EPI equations in terms of precision (interquartile range to mGFR of 10.5 vs. 17.9 mL/min/1.73 m for GFR vs. CKD-EPI; = 0.01) and accuracy (P15, P20, and P30 of 66.1% vs. 48.7% [ = 0.007], 80.0% vs. 60.0% [ < 0.001] and 95.7% vs. 86.1% [ = 0.006], respectively, for GFR vs. CKD-EPI). Clinical parameters such as etiology, comorbidities, or medications did not significantly alter the performance of the three eGFR equations. Altogether, this study confirmed the utility of GFR for accurate GFR estimation, and its potential value in routine clinical practice for improved medical care.
PubMed: 37370648
DOI: 10.3390/bioengineering10060717 -
Chemistry Central Journal 2016Glomerular filtration rate (GFR) is usually determined by estimation of iothalamate (IOT) clearance. We have developed and validated an accurate and robust method for...
Glomerular filtration rate (GFR) is usually determined by estimation of iothalamate (IOT) clearance. We have developed and validated an accurate and robust method for the analysis of IOT in human plasma and urine. The mobile phase consisted of methanol and 50 mM sodium phosphate (10:90; v/v). Flow rate was 1.2 mL/min on a C18 reverse phase column, Synergi-hydro (250 × 4.6 mm) 4 µm 80 Å, with an ultraviolet detector set to 254 nm. Acetonitrile was used for the deproteination and extraction of IOT from human plasma and urine. Precision and accuracy were within 15% for IOT in both plasma and urine. The recoveries of IOT in urine and plasma ranged between 93.14% and 114.74 and 96.04-118.38%, respectively. The linear range for urine and plasma assays were 25-1500 and 1-150 µg/mL respectively. The lower limits of detection were 0.5 µg/mL for both urine and plasma, with no interference from plasma and urine matices. This method has been fully validated according to FDA guidelines and the new HPLC assay has been applied to a new formulation of IOT (Conray™ 43), to calculate GFR in healthy volunteers. The new method is simple, less expensive and it would be instrumental in future clinical and pharmacokinetic studies of iothalamate in kidney patients.
PubMed: 28028385
DOI: 10.1186/s13065-016-0227-3