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PubMed2006

Bias and precision of estimated glomerular filtration rate in children.

Determining true glomerular filtration rate (GFR) using an exogenous marker is time-consuming and cumbersome. Therefore, creatinine-based estimates of GFR are used. Recent papers using new population-specific/local parameters in their prediction equations, standardizing creatinine determination or adding other endogenous surrogate markers of GFR, like cystatin C, could demonstrate an improvement of bias inherent in the results of the prediction equations. Precision, however, is still poor. Currently, we have to accept a precision (as defined in the so-called Bland-Altman plot) of +/-20% in adults and +/-30-40% in children. This problem of poor precision/uncertainty is especially bothering in the higher, near normal GFR range. Caution should be exercised when applying prediction equations in individuals in need of an accurate GFR determination. In that case, a real clearance procedure has to be performed. In the long run, the true clearance procedure should be simplified using new exogenous GFR markers and developing new devices, allowing GFR measurements to be performed, for example, transcutaneously. Such a procedure would be more acceptable for both patients and physicians.

Adolescent↗

PubMed1978

Determination of glomerular filtration rate in advanced renal insufficiency.

The glomerular filtration rate (GFR) has been determined in 17 patients with advanced renal insufficiency (GFR less than 15 ml/min) by different clearance techniques using creatinine, inulin and 51Cr-EDTA as filtration markers. With renal inulin clearance as reference method for GFR, endogenous renal creatinine clearance overestimated GFR by an average of 30%. Renal clearance of 51Cr-EDTA and inulin were closely correlated and thus 51Cr-EDTA is a suitable GFR marker even at low filtration rates. However, it was found that the plasma clearance of 51Cr-EDTA overestimated the GFR often by more than 100% in the range 2.6--11.2 ml/min. Renal clearance measured during 24 h was lower than 4 h renal clearance with the patient well hydrated and resting in bed. It is concluded that the precise measurement of low glomerular filtration rates requires the use of renal clearance techniques. Four-hour 51Cr-EDTA renal clearance is a suitable method for measuring and following the development of renal function in advanced renal insufficiency.

Adult↗

PubMed1991

Evolution of glomerular filtration rate in proteinuric NIDDM patients.

OBJECTIVE: To evaluate, by means of a precise method, the rate of decline of glomerular filtration rate in proteinuric non-insulin-dependent diabetic (NIDDM) patients. RESEARCH DESIGN AND METHODS: The study was comprised of seven NIDDM patients who visited an outpatient clinic and had a 24-h urinary protein excretion rate greater than or equal to 500 mg in the absence of heart failure, urinary tract infection, or other nephropathies. RESULTS: Glomerular filtration rate (51Cr-labeled EDTA, single-injection protocol) and 24-h proteinuria (turbidimetric method) were assessed at periodic intervals (2-6 mo). Correlation of the measurements with time (Pearson's r, with Student's t test used to assess the significance, alpha = 0.05) was used to evaluate the trend of evolution of glomerular filtration rate. Renal biopsies were performed in four patients. In three of four patients, renal histopathology was consistent with the diagnosis of diabetic nephropathy (in the 4th patient measurements were not satisfactory). Neither glomerular filtration rate nor proteinuria correlated significantly with time, except in one patient who had multiple myeloma. CONCLUSIONS: The decline of glomerular filtration rate in proteinuric NIDDM patients is different from that observed in insulin-dependent diabetic patients, which is probably much slower.

Aged↗

PubMed1987

Difficulties in estimating glomerular filtration rate in the elderly.

Estimates of glomerular filtration rate are generally obtained by measuring or estimating endogenous creatinine clearance. However, it may sometimes be difficult to obtain the necessary urine collections. Most of 19 healthy, reliable elderly outpatients were found unable to provide satisfactory 24-hour urine collections. To judge whether formulas estimating creatinine clearance from serum creatinine levels are reliable, we also compared 24-hour creatinine clearances measured in 50 inpatients with values calculated by the Cockroft-Gault equation. Only a moderate correlation was found, which may be unacceptable in the clinical situations for which the equation is used, such as drug dosing. For reasons including uncertainties in the validity of predictive formulas and unreliability of urine collections, we conclude that no acceptable method now exists for bedside estimation of glomerular filtration rate and that drug levels should be measured whenever possible in elderly patients and in those with renal insufficiency.

Aged↗

PubMed1981

Strain differences in kidney function of inbred rats: 1. Glomerular filtration rate and renal plasma flow.

Bodyweight, kidney weight and glomerular filtration rate showed significant differences between strains--70% of the total variance was ascribed to the between-strain variance component--while the renal plasma flow showed only a slight strain difference due to a high within-strain variance component (63%). Heritability in the broad sense was 0.78 for bodyweight, 0.85 for kidney weight, 0.66 for glomerular filtration rate and 0.35 for renal plasma flow. There were significant genetic correlations between bodyweight and kidney weight (0.90), bodyweight and glomerular filtration rate (0.73), and between glomerular filtration rate and renal plasma flow (0.71), but not between kidney weight and kidney functions. Significant environmental correlations could be calculated only between bodyweight and all other variables, so that for comparison between strains it seems better to correct renal functions for bodyweight than for kidney weight, which would increase the variation of glomerular filtration rate.

Animals↗

PubMed1985

Short-term inhibition of prostaglandin synthesis has no effect on the elevated glomerular filtration rate of early insulin-dependent diabetes.

Glomerular filtration rate and renal plasma flow (constant infusion technique using 125I-iothalamate and 131I-hippuran) were measured twice within a 1-week interval in nine young males with insulin-dependent diabetes of short duration (2-5 years). The study was performed in a randomized double-blind design, with the patients receiving either indomethacin (150 mg/day) or placebo for 3 days before the study. Measures of metabolic control did not change. No differences were found in glomerular filtration rate (144 +/- 9 versus 144 +/- 9 ml/min X 1.73 m2, mean +/- S.E.M.) or renal plasma flow (579 +/- 43 versus 560 +/- 52 ml/min X 1.73 m2), when measured during placebo or indomethacin treatment, respectively. It is concluded that the steady-state enhancement of glomerular filtration rate and renal plasma flow found in early insulin-dependent diabetes is not due to an excessive activity of the prostaglandin system.

Adult↗

PubMed1992

Practical approach for determining glomerular filtration rate by single-injection inulin clearance.

We compared the glomerular filtration rate as measured by a single-injection inulin clearance with that measured by a standard isotope method with 99mTc-labeled diethylenetriaminopentaacetic acid in 21 subjects with glomerular filtration rates greater than 35 mL/min. After a bolus injection of 5 g of inulin, blood samples were taken 20, 45, 90, 120, 145, 180, and 240 min afterwards. Inulin was measured by optimized chemical or enzymatic methods of high analytical sensitivity to determine inulin at low concentrations. We used the one-compartment model and inulin concentrations measured at two sampling times to calculate the glomerular filtration rate from the data of the disappearance curve of inulin. Inulin concentrations at 20 and 240 min after injection of the inulin bolus were suited to estimate glomerular filtration rate by this procedure, resulting in values (y) comparable with those obtained by isotope technique (x). The relationship to the isotope technique was characterized by the equation y = +4.80 mL/min + 0.92x (r = 0.97). The single-injection inulin clearance determination can detect a decrease of glomerular filtration rate at the beginning of kidney damage, given that our study included subjects with glomerular filtration rates greater than 35 mL/min. We conclude that the glomerular filtration rate can be determined by analyzing only two blood samples after a bolus injection of inulin.

Adult↗

PubMedDate not supplied

Does increased glomerular filtration rate or disturbed tubular function early in the course of childhood type 1 diabetes predict the development of nephropathy?

To clarify whether glomerular hyperfiltration or disturbances in renal tubular function may be early markers of the later development of nephropathy a follow-up study was performed in 34 young Type 1 diabetic patients, who had originally been investigated 12 years previously. The initial median age was 14 (range 7-18) years and median diabetes duration 7 (2-14) years. At initial examination only one of the 34 diabetic patients exhibited increased urinary albumin excretion rate. The median glomerular filtration rate was increased (136 vs 107 ml min-1 1.73 m-2; p less than 0.0001) and median threshold concentration of phosphate per litre of glomerular filtrate was decreased (1.27 vs 1.76 mmol l-1; p less than 0.0001) in the diabetic group as compared to that of 28 healthy children. At follow-up 17 patients showed increased urinary albumin excretion rate and the median glomerular filtration rate in this group was significantly lower than that of 17 patients with normal urinary albumin excretion rate (108 vs 125 ml min-1 1.73 m-2; p less than 0.05). However, no relationships were found between the increased urinary albumin excretion (incipient and/or overt diabetic nephropathy) at follow-up to either the initial glomerular filtration rate (134 vs 137 ml min-1 1.73 m-2; p greater than 0.05) or to renal tubular function assessed from urinary excretion rate of beta 2-microglobulin (0.059 vs 0.069 microgram min-1; p greater than 0.05) and the renal threshold concentration of phosphate per litre of glomerular filtrate (1.29 vs 1.22 mmol l-1; p greater than 0.05).

Adolescent↗

PubMed1999

[Measurement of glomerular filtration rate in connection with 99Tc-DTPA renography].

Glomerular filtration rate (GFR) was measured in two groups of cancer patients. In 20 patients, glomerular filtration rate was measured simultaneously with 51Cr-EDTA, 99mTc-DTPA and the X-ray contrast agent iohexol as markers, and with a complete set of eight blood samples during 24 hours. In a second group of 120 patients, we used 99mTc-DTPA only and tested various simplified methods, based on one or two blood samples. Glomerular filtration rate was also calculated from serum creatinine. There was excellent agreement between the values measured with the three markers, and, in the same group of patients, very good agreement with the results of simplified methods. The larger study carried out with 99mTc-DTPA on the second group of patients, confirmed a very good agreement between methods based on the slope of the plasma curve and a method based on one blood sample only. The correlation was worse between the values obtained by any of the radionuclide methods and those calculated from serum creatinine. The latter method should therefore not be used for determination of renal function.

Chromium Radioisotopes↗

PubMed1981

Radioactive chromium-ethylenediaminetetraacetic acid for determination of glomerular filtration rate in rabbits.

Simultaneous determination of the glomerular filtration rate was made by the insulin clearance technique and by analysis of the plasma disappearance curve of radioactive chromium-ethylenediaminetetraacetic acid (51Cr-EDTA) following an intravenous injection in 28 anaesthetized rabbits. In some rabbits, the renal function was reduced by previous surgery. The insulin clearances ranged from 2.7 to 17 ml/minute. By a double-exponential analysis of the plasma disappearance curve, the total plasma clearance of 51Cr-EDTA was found to exceed the inulin clearance by 12%. By the simpler slope-intercept analysis requiring only two blood samples, this value was 32%. The renal clearance of 51Cr-EDTA was 97% of inulin clearance. In nephrectomized rabbits, plasma clearance of 51Cr-EDTA was 0.7 ml/minute. At all levels of renal function, measurement of the plasma clearance rate of 51Cr-EDTA by the single injection technique allowed a fairly reliable estimate of the glomerular filtration rate.

Animals↗

PubMed1999

Creatinine clearance as a substitute for the glomerular filtration rate in the assessment of glomerular hemodynamics.

A method for the clinical assessment of glomerular hemodynamics has been published previously. We here examined whether, when using this method, renal creatinine clearance (Ccr) can be substituted for the glomerular filtration rate (GFR). The study subjects comprised 57 inpatients from Osaka City General Hospital: 30 with type 2 diabetes mellitus and 27 with chronic glomerulonephritis. During the 2-wk study, patients received a high-salt diet for 1 wk and a low-salt diet for 1 wk. Urinary sodium excretion and systemic blood pressure were measured daily. The renal plasma flow, Ccr, and plasma total protein concentration were also evaluated simultaneously on the last day of the high-salt diet. The GFR was also calculated from the fractional renal accumulation of 99mTc-diethylenetriaminepentaacetic acid (DTPA). Glomerular hemodynamics, represented by the glomerular capillary hydraulic pressure and the resistance of afferent and efferent arterioles, were calculated using the renal clearance, the plasma total protein concentration, and the pressure-natriuresis relationship. Values for renal hemodynamics with the Ccr-derived GFR were compared with those from the 99mTc-DTPA-derived GFR. Ccr values of 53 to 169 ml/min correlated with the 99mTc-DTPA-derived clearance of 39 to 179 ml/min (n=57, r=.71, p<.001). Values for the glomerular pressure and the resistances of afferent and efferent arterioles calculated using the Ccr-derived GFR correlated significantly with those calculated using the 99mTc-DTPA-derived GFR (r=.99, p<.001 and r=.99, p<.001, respectively). These results indicate that the Ccr is an accurate representation of the GFR for use in glomerular hemodynamic analysis of the pressure-natriuresis relationship.

Chronic Disease↗

PubMed1992

Expressing glomerular filtration rate in terms of extracellular fluid volume.

Glomerular filtration rate (GFR) is routinely calculated from the second exponential of the bi-exponential plasma clearance of filtration markers such as Cr-51 EDTA and Tc-99m DTPA. By ignoring the first exponential, true GFR is overestimated, an error which increases with increasing GFR. The rate constant, lambda 2, of the second exponential represents the rate at which glomerular filtration 'turns over' the extracellular fluid (ECF) and so closely approximates GFR/ECF volume. Again, the error in the estimation of this ratio increases with increasing GFR, although in this case it underestimates the true ratio. Expressing GFR in terms of ECF volume, rather than in terms of body surface area, offers considerable technical and physiological advantages. The relationship between GFR/ECF volume and lambda 2, over a wide range of renal function, expressed as a second order polynomial, was GFR/ECF volume = -0.093 + 1.06 lambda 2 + 0.009 lambda 2(2) ml.min-1.l-1. The corresponding relationship between 'true' GFR (C1) and approximate GFR (i.e. based only on the second exponential--C2) was C1 = -0.58 + 1.012C2 -0.0011 C2(2) ml.min-1 For any level of renal function, the error in GFR/ECF volume, expressed as lambda 2, is less than the error in GFR expressed as C2. Since GFR may change as a direct result of a change in ECF volume, it is physiologically more relevant, and technically very much easier, to express GFR in terms of ECF volume rather than body surface area.

Adult↗

PubMed1988

Model for evaluating avian renal hemodynamics and glomerular filtration rate autoregulation.

Multiple vascular connections in normal avian kidneys make it difficult to experimentally manipulate renal blood flow patterns and perfusion pressures. In this study, hemostatic clips were used to obstruct the ureter of one kidney at the level of the ischiadic artery (IA) in anesthetized 3-wk-old chicks (Gallus domesticus). Kidney tissue upstream from the ureteral obstruction degenerated, leaving an intact caudal renal division with one route of arterial inflow branching from the IA. Renal function studies were conducted, using general anesthesia, when the birds reached 12-15 wk of age. A snare placed around the IA was used to unilaterally decrease renal arterial perfusion pressure (RAPP) for the experimental kidney. Under control conditions (snare loose), urine flow rates (UFR), glomerular filtration rates (GFR), clearance of p-aminohippuric acid, and fractional excretion of Na, K, Ca, and PO4 did not differ significantly, per gram of kidney weight, when experimental and intact contralateral kidneys were compared. Gradual tightening of the IA snare reduced RAPP stepwise. UFR decreased significantly from the initial control value when RAPP reached 40 mmHg, and urine flow ceased completely when RAPP reached 30-35 mmHg. In four of five birds, GFR did not decrease significantly between 110 and 60 mmHg but did decrease significantly below 60 mmHg. Urine osmolality was inversely correlated with UFR. Clearance of PAH did not decrease significantly from control values as RAPP ranged from 100 to 37 mmHg, possibly caused by increased renal portal blood flow. Overall, these results provide the first direct demonstration that in domestic fowl GFR is autoregulated at reduced RAPP.

Animals↗

PubMed1986

Accuracy and reproducibility of a new contrast clearance method for the determination of glomerular filtration rate.

A new method for determining the glomerular filtration rate was analysed prospectively. The method uses an x ray fluorescence technique to measure disappearance from the plasma of injected non-ionic iodinated contrast media. Eighty seven patients were studied. Fifty four had an intravenous dose of 100 ml iohexol (Omnipaque) and 33 had 50 ml iohexol. Clearances of chromium-51 labelled edetic acid (51Cr-EDTA) were measured simultaneously. In the patients given 100 ml iohexol there was excellent correlation with 51Cr-EDTA clearance (r = 0.90). The correlation using 50 ml iohexol was also good (r = 0.85). Correlation between creatinine clearance and clearance of 51Cr-EDTA in 33 patients was less satisfactory (r = 0.69). There were no adverse reactions to the contrast media. The equipment used for measuring contrast clearance was robust and simple to operate. Freezing plasma samples in 10 studies and re-examining them weekly for six weeks showed no significant variation in results; hence reproducibility was good. This new and accurate method for determining the glomerular filtration rate merits further study and might find a useful place in routine clinical practice.

Adolescent↗

PubMed1980

Mechanism of reduced glomerular filtration rate in chronic malnutrition.

To determine the physiological basis for the low glomerular filtration rate in chronic malnutrition, micropuncture studies were performed in Munich-Wistar rats chronically pair-fed isocaloric diets of either low (group 1, nine rats) or high protein content (group 2, nine rats). Despite the absence of hypoalbuminemia, average values for single nephron and total kidney glomerular filtration rate were nearly 35% lower in group 1 than in group 2. Mean values for glomerular capillary and Bowman's space hydraulic pressures were essentially identical in the two groups, thereby excluding glomerular transcapillary hydraulic pressure difference as the cause for the low filtration rates in group 1 animals. On the other hand, average glomerular capillary plasma flow rate and glomerular capillary ultrafiltration coefficient were significantly lower (by approximately 25 and approximately 50%, respectively) in group 1 than in group 2. The fall in glomerular capillary plasma flow rate was the consequence of increased afferent and efferent arteriolar resistances. Plasma and erythrocyte volumes were found to be equal in five additional pairs of group 1 and group 2 rats. Thus, the substantial alterations in the ultrafiltration coefficient, glomerular capillary plasma flow rate, and renal arteriolar resistances responsible for the low filtration rate in group 1 animals were not merely a consequence of decreased circulating blood or plasma volumes. Mean values for glomerular cross sectional area were significantly lower in group 1 than in group 2 despite similar values for kidney weight in the two groups. This reduction in glomerular cross sectional area in group 1 rats is presumed to reflect a decrease in effective filtration surface area and therefore likely accounts, at least in part, for the decline in ultrafiltration coefficient observed in this group.Finally, since the daily caloric intake of group 2 animals was restricted because of pair feeding requirements tied to the group 1 rats, we studied a third group of seven rats (group 3) allowed an ad lib. intake of the same high protein diet as given to group 2 rats. Average values for single nephron glomerular filtration rate and its determinants were found to be indistinguishable between groups 2 and 3. These results suggest that low protein intake, rather than calorie deficiency per se, is primarily responsible for the reduction in filtration rate seen in this experimental model of chronic malnutrition.

Animals↗

PubMed1975

Glomerular filtration rate in sick elderly inpatients.

The glomerular filtration rate was measured in the sick elderly patients using the single shot 51Cr EDTA method. As would be expected, such patients have worse renal function than the fit elderly. The filtration rate can be usefully predicted from either blood urea or serum creatinine, but a superior prediction is obtained when these factors are combined using a formula derived from multiple regression analysis.

Aged↗

PubMed1981

Glomerular filtration rate after jejunoileal bypass for obesity.

Glomerular filtration rate (GFR), concentration of total cortisol in plasma, and urinary excretion rate of free cortisol were determined in five females 1-5 years after jejunoileal bypass operation for obesity. The overweight of the patients had decreased from 97 per cent (range 82-147 per cent) to 25 per cent (range 0-39 per cent). The measured values were compared to previously published results in 16 female obese patients (median overweight 86 per cent) and in 16 female controls with normal body weight, all comparable with respect to age and height. Median GFR in the jejunoileal bypass patients (100 ml/min) was significantly (P less than 0.006) decreased compared to median GFR in the obese patients (129 ml/min), but did not differ significantly from that in the controls with normal body weight (104 ml/min). The median values of plasma cortisol and urinary excretion rate of free cortisol in the bypass patients were lower than those in the obese females, but the differences were not significant. The present results suggest that the increased GFR in obese subjects is related to the state of obesity.

Adult↗

PubMed1987

Three-hour volume of distribution method: an accurate simplified method of glomerular filtration rate measurement.

Eight hundred studies of glomerular filtration rate (GFR) measurements were performed by the standard slope-intercept method using [99mTc]DTPA and results were compared with a simultaneous measurement of the 3-hr tracer volume of distribution. A wide range of human renal function was studied and a nonlinear relationship between GFR and the volume of distribution resulted with an excellent correlation (r = 0.989). Agreement between the two measured parameters was not constant for all levels of renal function with the greatest accuracy being found for GFR = 60 to 100 ml/min.

Blood Volume↗