Clearances Of 51Cr-EDTA Research Articles

Comparison of 51Cr-EDTA and 99mTc-DTPA for glomerular filtration rate measurement.

The production of 51Cr-labelled ethylenediaminetetraacetic acid (51Cr-EDTA), a validated and widely used radio-isotopic tracer for glomerular filtration rate (GFR) measurement in Europe, was recently halted by the manufacturer. Technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance has so far mostly been restricted to assessment of separate renal function by scintigraphy, but scarcely used and validated for GFR measurement. We compared the performances of 51Cr-EDTA and 99mTc-DTPA for GFR and extracellular fluid measurement. In a multi-centre prospective study, 51Cr-EDTA and 99mTc-DTPA were simultaneously injected into 88 patients, and their urinary and plasma clearances, as well as their volumes of distribution, were measured during seven 30-min periods after a 90-min equilibrium time. Mean age was 52.2 ± 14.5years, 59% were men. Urinary clearances of 51Cr-EDTA and 99mTc-DTPA were 64.1 ± 27.6 and 66.1 ± 28.0mL/min, respectively, with a mean bias of 2.00 ± 2.25mL/min, an accuracy within 10% of 95% [95% CI 91-99], and a coefficient of determination (R2) of 0.994. Plasma clearances of 51Cr-EDTA and 99mTc-DTPA were 66.1 ± 25.8 and 68.1 ± 26.6mL/min, respectively, with a mean bias of 1.96 ± 3.32mL/min, an accuracy within 10% of 91% [95% CI 85-97] and a R2 of 0.985. Distribution volumes were 17.3 ± 4.6 L for 51Cr-EDTA and 16.6 ± 4.6 L for 99mTc-DTPA (R2 0.930). The accuracy and precision of 99mTc-DTPA clearance, compared to 51Cr-EDTA clearance, was excellent for both urinary and plasma clearance methods, despite an approximate 2mL/min overestimation, showing that the tracer is a reliable alternative to 51Cr-EDTA for GFR measurement.

Endogenous Markers for Estimation of Renal Function in Peritoneal Dialysis Patients

This method comparison study, conducted at the peritoneal dialysis (PD) outpatient clinic of the Department of Renal Medicine, Aarhus University Hospital, Denmark, set out to evaluate the accuracy and reproducibility of methods for estimating glomerular filtration rate (GFR) based on endogenous markers in PD patients. The 12 consecutive patients included in the study were examined twice while in a stable condition. All patients finished the study. Inclusion criteria were age 18 years or older, ability to collect 24-hour urine, and urine production greater than 300 mL in 24 hours. The methods for estimating GFR using endogenous markers included the average of urinary clearances of creatinine and urea [U-Cl(crea-urea)] and two equations using the serum concentration of cystatin C [eGFR(CysC)]. The resulting GFR estimates were compared with those obtained using urinary and corrected plasma clearances of (51)Cr-EDTA [U-Cl(EDTA) and cP-Cl(EDTA)], the corrected plasma clearance being plasma clearance minus dialysate clearance. Compared with the U-Cl(EDTA), the U-Cl(crea-urea) GFR estimate was 12% higher [95% confidence limits (CL): 3%, 21%]. Although significantly different (p = 0.01), the latter two methods showed the best agreement. The estimates obtained using the eGFR(CysC) methods were skewed from y = x compared with the estimates obtained using other methods, indicating strong bias, probably because of extrarenal elimination. The cP-Cl(EDTA) estimate was 34% (95% CL: 26%, 42%), higher than the U-Cl(EDTA) estimate (p < 0.001). The reproducibility (coefficients of variation) differed significantly between methods: cP-Cl(EDTA), 7%; U-Cl(EDTA), 14%; U-Cl(crea-urea), 18%; and both eGFR(CysC) methods, 3%. In PD patients, GFR may be estimated as U-Cl(crea-urea) when complete urine collection is performed, taking into account an overestimation of approximately 12%. The available equations for eGFR(CysC) seem to be inaccurate; further development and validation is desirable. Omitting the eGFR(CysC) methods, cP-Cl(EDTA) was the most reproducible method and might be useful in certain situations.

Reliability of 51Cr-EDTA plasma and urinary clearance as a measure of residual renal function in dialysis patients

Purpose: In dialysis patients, longer survival is associated with a higher residual renal function. Randomized controlled trials are conducted to clarify how residual renal function can be preserved. However, existing methods for measuring residual renal function are uncertain and there is a need for establishing a standard for measurements of glomerular filtration rate (GFR) in dialysis patients. Methods: 51Cr-EDTA clearances in plasma, urine, and dialysate were evaluated in a sample of 12 hemodialysis and 12 peritoneal dialysis patients. The patients’ condition was generally stable, and all patients were investigated twice within 4–10 days. Results: Plasma clearances of 51Cr-EDTA for all patients ranged between 2.1 and 30.8 mL/min/1.73m2, whereas urinary 51Cr-EDTA clearances ranged from 0.7–20.0 mL/min/1.73m2. This difference was statistically significant (p < 0.001). Week-to-week reproducibility expressed as coefficients of variation were below or equal to 10% for plasma clearances and 13% for urinary clearances in hemodialysis patients and 14% in peritoneal dialysis patients. Conclusions: This study demonstrated a difference between 51Cr-EDTA plasma and urinary clearances in dialysis patients. Plasma clearance of 51Cr-EDTA had the best reproducibility. For repeated measurements as in clinical prospective trials, we recommend 51Cr-EDTA plasma clearance based on blood sampling at 5 + 24 hours with subtraction of 51Cr-EDTA dialysate clearance in peritoneal dialysis patients. Further studies are needed to corroborate our findings.

Extracellular fluid volume and glomerular filtration rate

The slope-only technique for measuring glomerular filtration rate (GFR) relies on extracellular fluid volume (ECV) remaining within narrow limits. Although this requirement is met in healthy individuals, ECV may deviate or vary more in patients with abnormal renal function. We examined the correlation between surface area-scaled ECV and GFR, and their coefficients of variation (CVs), measured from simultaneous, multisample clearances of 51Cr-EDTA and iohexol in 20 healthy volunteers and 60 patients with a range of renal functions. We also compared scaled GFR and ECV, and their CVs, measured from three-sample, slope-intercept clearance of 51Cr-EDTA in 921 patients routinely referred for GFR measurement. In the 80 participants undergoing multisample, dual-indicator clearance, there was no correlation between GFR measured with one indicator and ECV measured with the other. CVs of GFR in the 60 patients were 48.1 and 44.6% for 51Cr-EDTA and iohexol, respectively, but the CVs of ECV were only 12.3 and 15.4%. These differences were less marked in the healthy participants with corresponding CVs of 13.9 and 14.9% for GFR, and 11.7 and 12.2% for ECV. There was no correlation between scaled GFR and ECV in patients having slope-intercept clearance; CVs of GFR and ECV were 32.4 and 17.8%, respectively. In unselected patient populations, there is no correlation between GFR and ECV. The CV of ECV is slightly higher in patients than healthy individuals but, in both, is less than the CV of GFR. These data do not detract from the use of slope-only GFR.

Natriuretic effect of caffeine: assessment of segmental sodium reabsorption in humans.

In order to assess the intrarenal mechanisms responsible for the natriuretic action of caffeine, the renal clearances of (51)Cr-EDTA [used as a measure of glomerular filtration rate (GFR)] and lithium (used as an index of end-proximal fluid delivery) were measured in eight healthy males before (control period) and immediately after (experimental period) a 400 mg oral dose of caffeine (given over 90 min) or placebo. In caffeine-treated subjects, the fractional excretion of sodium rose from 1.00+/-0.25% in the control period to 1.47+/-0.18% in the experimental period, while corresponding values on the placebo day were 1.04+/-0.16% and 0.70+/-0.07% respectively. GFR was unchanged following either caffeine or placebo. When compared with the placebo day, caffeine caused increases in lithium clearance (experimental period values: caffeine, 37+/-1 ml/min; placebo, 28+/-2 ml/min; P <0.001), the fractional excretion of lithium (caffeine, 34+/-1%; placebo, 26+/-2%; P <0.001) and the sodium/lithium clearance ratio (used as an index of the fraction of sodium delivered to the distal nephron that escapes reabsorption therein: caffeine, 4.4+/-0.3%; placebo, 2.8+/-0.2%; P <0.001). These results suggest that reduced fractional sodium reabsorption in both the proximal tubule and the distal nephron contributes to the acute natriuretic effect of caffeine. The data also confirm the importance of controlling caffeine intake when investigating renal function using lithium clearance.

55Co-EDTA for renal imaging using positron emission tomography (PET): a feasibility study

The feasibility of imaging renal function with 55Co-ethylene diamine tetraacetic acid (EDTA) and dynamic positron emission tomography was investigated. A group of normal Wistar rats was injected intravenously with 55Co-EDTA and underwent dynamic positron emission tomography (PET) imaging in order to study the biodistribution. The time–activity curves of the heart (blood pool), both kidneys, liver, and bladder were observed. In two animals, blood and urinary clearances of 55Co-EDTA were compared with those for 51Cr-EDTA. In one animal, unilateral reduction in kidney function was induced and the right/left ratio for the kidneys was determined. The time–activity curves showed that 55Co-EDTA cleared rapidly from the blood pool (heart), whereas prompt and high target-to-background ratios for both kidneys were obtained. The entire tracer was cleared from the renal parenchyma by urinary excretion and collection of the activity in the bladder. No specific activity uptake was noticed in any other organ or tissue. The clearances of 55Co-EDTA and 51Cr-EDTA in blood were not significantly different, showing that the nature of the M ++ has no influence on the in vivo behavior of EDTA. 55Co can be produced easily by cyclotron irradiation and 55Co-EDTA is a promising physiological tracer for nephrological research using PET.

Assessment of renal function by 51Cr‐EDTA and endogenous creatinine clearances in the pig

In anaesthetized pigs, clearances of 51Cr-EDTA (EDTA) and endogenous creatinine were compared with renal clearance of inulin measured during constant infusion after bolus injection. Creatinine was determined by enzymatic (Kodak Ektachem) as well as conventional (Jaffé) methods. In saline-loaded pigs, renal clearance of constantly infused EDTA was 97.0 +/- 6.7 mL min-1 and identical to the clearance of inulin (94.1 +/- 9.1 mL min-1). There was good agreement between individual clearances. The extraction fractions of the two markers were indistinguishable (0.26 +/- 0.02 and 0.28 +/- 0.03, respectively). In other experiments the clearance of EDTA calculated from the first 4 h of the time course of the plasma concentration after single injection was 64.4 +/- 3.7 mL min-1, correlating well with inulin clearance (63.0 +/- 1.2 mL min-1). When calculated only from the monoexponential phase of the disappearance curve ('slope clearance'), significantly higher results were obtained (+33%, P < 0.001). Renal clearance of EDTA after single injection was 7.5 +/- 1.5 mL min-1 (approximately 12%) lower than inulin clearance (P < 0.001). Values of creatinine clearances determined by the two analytical methods showed a poor agreement with inulin clearance. It is concluded that, in pigs, glomerular filtration rate may be estimated by the clearance of EDTA using constant infusion or single injection of EDTA and that the renal clearance of endogenous creatinine is a less useful a measure of GFR.

Clearance of iohexol, 51Cr-EDTA and endogenous creatinine for determination of glomerular filtration rate in pigs with reduced renal function: A comparison between different clearance techniques

In order to simplify and/or improve determination of glomerular filtration rate (GFR) the clearances of iohexol, 51Cr-EDTA and endogenous creatinine were simultaneously determined with different techniques in 21 anesthetized landrace pigs. Their GFR had been reduced to about 1/3 or less of normal GFR. After an intravenous bolus of the GFR markers, their plasma concentration curves were followed for 6 hours with 16 plasma samples. A bladder catheter collected urine during six 60-min periods. The plasma clearance was calculated by dividing “dose of marker” with “area under the plasma concentration curve” (AUC) from the time of injection to infinity using a one- (Clprovisional) and a three-compartment (CIAUC-3comp) model. The renal clearance of iohexol and 51Cr-EDTA was calculated by dividing the amount of marker excreted in the urine in a period by AUC in the same period. The AUC was for iohexol and 51Cr-EDTA determined by integrating the total area in the period (Clren adv)—our reference method representing the “true” GFR and for creatinine determined by using the arithmetic mean of the plasma concentration of the marker at the start and at the end of the urine collection period (Clren simple). Renal clearance of creatinine was significantly lower than renal clearance of iohexol (p = 0.0019) and 51Cr-EDTA (p = 0.0001). There were no significant differences between the renal clearances (Clren adv) of iohexol and 51Cr-EDTA or between their plasma clearances (ClAUC.3comp). For iohexol the median overestimation of the “true” GFR with Clprovisional was higher when “early” plasma samples (30–120 min) were used (4.5 ml min−1 10 kg−1) than when late samples (180–360 min) were used (1.9 ml min−1 10 kg−1). Subtraction of the median extrarenal clearance (known from a study of nephrectomized pigs) from the plasma clearances (CIAUC3comp) of iohexol and 51Cr-EDTA in pigs with reduced renal function decreased the median overestimation of the “true” GFR from 1.9 to 1.0 ml min−1 10 kg−1 with iohexol and from 1.7 to 0.9 ml min−110 kg−1 with 51Cr-EDTA. The plasma clearance technique may be improved in pigs with reduced GFR by (i) including a “late” plasma sample in three- and one-compartment models, which tends to increase the AUC; (ii) introducing a correction formula by normalizing the GFR values of the one-compartment model to those of the three-compartment model, thereby compensating for the rapid early changes in plasma concentration of marker after the bolus injection of the marker; or (iii) subtracting a median (or mean) extrarenal clearance of the marker in pigs from the plasma clearance [according to (i) or (ii)]. The plasma clearance one-compartment technique may be improved in pigs with various levels of GFR values by normalizing the plasma clearance values to the renal clearance values, thereby compensating for both the early changes in plasma concentration of marker and the extrarenal clearance of marker.

Clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and creatinine for determining the glomerular filtration rate in pigs with normal renal function: Comparison of different clearance techniques

We wanted to improve determination of the glomerular filtration rate (GFR) with plasma clearance techniques because the alternative-renal clearance techniques-may involve inaccurate urine sampling or risk of urinary tract infection when bladder catheterization becomes necessary. Therefore, we compared the renal and plasma clearances of iohexol and chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), as well as endogenous creatinine clearance, in 19 normal pigs using different techniques. After an intravenous bolus injection of the GFR markers, 16 plasma samples were used to plot the marker concentrations versus time for 4.5 hr. Urine was collected during nine 30-min periods. Plasma clearance was calculated by dividing the dose of marker with the area under the plasma concentration curve (AUC) from the time of injection to infinity using one-compartment (ClAUC-slope) and three-compartment (ClAUC-3comp) models. The renal clearance was calculated by dividing the amount of marker excreted in the urine in a period with the AUC in the same period. This AUC was determined by integrating the total area in the period (Clren adv)--our reference method representing the "true" GFR--or by using the arithmetic mean of the plasma concentrations of the marker at the beginning and end of the urine collection period (Clren simple). Creatinine clearance was determined according to Clren simple. Renal clearances of iohexol and 51Cr-EDTA were significantly higher than creatinine clearance (P = .0002). There was no significant difference between the renal clearances of iohexol and 51Cr-EDTA or between their plasma clearances. The two mathematical methods of calculating the renal clearance of iohexol were highly correlated (rs = .99), as were the two methods of calculating its plasma clearance (rs = .95). Because of the extrarenal clearance of the markers, the plasma clearance methods for iohexol and 51Cr-EDTA always overestimated the true GFR. ClAUC-3comp was the method closest to the true GFR. For iohexol, the median overestimation of the GFR was higher with ClAUC-slope when early plasma samples (30-120 min) after injection of the marker were used (5.5 ml.min-1.10 kg-1) than when late samples (180-270 min) were used (4.0 ml.min-1.10 kg-1). After subtracting the median extrarenal clearances of iohexol and 51Cr-EDTA (previously determined in nephrectomized pigs) from their plasma clearances (ClAUC-3comp), the median overestimation of the true GFR was reduced from 2.0 to 1.1 ml.min-1.10 kg-1 with iohexol and from 2.1 to 1.3 ml.min-1.10 kg-1 with 51Cr-EDTA. GFR determination with plasma clearance techniques can be improved in three- and one-compartment models by taking late plasma samples and by subtracting the extrarenal plasma clearance of the species. One-compartment models can be improved by determining a correction formula in the species for the early parts of the decay curve of the plasma concentration of the marker.

Extrarenal plasma clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and inulin in anephric pigs

To improve the measurement of the glomerular filtration rate (GFR), we determined the extrarenal plasma clearance of the GFR markers iohexol, chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), and inulin using 11 anephric pigs. After an intravenous (i.v.) bolus injection of the markers, the decay curves of their plasma concentrations were monitored for 29 hr by 16 plasma samples. The area under the curve (AUC; concentration of marker versus time) was calculated according to one- and three-compartment kinetics. The extrarenal clearance was calculated by dividing the dose of marker by the AUC. In the three-compartment model, the median of the extrarenal clearances of iohexol, 51Cr-EDTA, and inulin were 0.87 ml.min-1.10 kg-1 (range = 0.62-1.26 ml.min-1.10 kg-1), 0.79 ml.min-1.10 kg-1 (range = 0.61-1.04 ml.min-1.10 kg-1), and 0.83 ml.min-1.10 kg-1 (range = 0.65-1.17 ml.min-1.10 kg-1). The extrarenal clearance of 51Cr-EDTA was slightly lower than that of iohexol and inulin when measured with the three-compartment model (p = .015). There was no statistically significant difference between the two models of kinetics in calculating clearance of the same marker. Our results indicate that subtracting the median values of the extrarenal clearance of the markers from the total plasma clearance will provide GFR values closer to the "true" GFR. This technique might prove useful in GFR calculations in patients with a very low GFR (e.g., residual GFR in patients on dialysis).

Stimulatory effect of insulin on tubular sodium reabsorption in normotensive subjects with a positive family history of hypertension

Insulin resistance and hyperinsulinaemia has been suggested as a pathogenetic mechanism in hypertension. In this investigation the renal response to insulin was studied in normotensive subjects with a positive family history of hypertension in two generations (n = 14), in one weight-matched (n = 11) and one lean (n = 13) control group. During hyperinsulinaemia (euglycaemic hyperinsulinaemic clamp technique) we determined renal haemodynamics (clearances of 51Cr-EDTA and PAH) and urinary sodium excretion. Lithium clearance was used to estimate the segmental tubular reabsorption of sodium. In subjects with a positive family history of hypertension, hyperinsulinaemia did not influence renal plasma flow (RPF) or glomerular filtration rate (GFR) but urinary sodium excretion decreased by 50%. Estimated proximal tubular sodium reabsorption was unaffected by insulin while estimated distal fractional sodium reabsorption increased, P < 0.01. At the end of the clamp a low-dose infusion of angiotensin II (0.1 ng/kg per min) was superimposed. GFR and RPF then decreased significantly concomitant with urinary excretion of sodium. In control subjects hyperinsulinaemia caused an unchanged GFR in both groups, increased RPF in the lean control group and 15-25% reduction in sodium excretion. No alteration was seen in estimated proximal tubular sodium reabsorption, but estimated distal tubular sodium reabsorption increased (P < 0.05) in the lean control group. Angiotensin II elicited a further increase in distal fractional tubular sodium reabsorption in both groups (P < 0.05). In normotensive subjects with a positive family history of hypertension, in contrast to control subjects without such history, hyperinsulinaemia caused a marked decrease in urinary sodium excretion in presence of unchanged RPF and GFR indicating a renal tubular effect of insulin located at distal site of the renal tubules. Angiotensin II caused further sodium retention, probably due to an effect on renal haemodynamics.

Aspects of osseous, peritoneal and renal handling of bisphosphonate during peritoneal dialysis: a methodological study

The accumulation of methylene bisphosphonate (MBP) in increased bone turnover is an index of the total skeletal turnover. Accordingly, a model has been described where uptake of the osseous tracer can be estimated, regardless of renal function. In the present study, the model was adapted to continuous ambulatory peritoneal dialysis (CAPD). The aims were: to assess the kinetics of 99m-technetium MBP (99mTc-MBP) in CAPD, and to evaluate the correctness of the assumption that the peritoneal and renal clearances of 99mTc-MBP equal the total plasma clearance of 51-chromium ethylenediamine tetra-acetic acid (51Cr-EDTA). Eight patients on CAPD were studied cross-sectionally. The mean plasma clearances of 99mTc-MBP and 51Cr-EDTA in the steady state (4h) were 38.2 and 12.2 ml min-1 (p < 0.01), the peritoneal clearances (0-4 h) were 5.2 and 7.2 ml min-1 (p < 0.01), and the renal clearances (0-4 h) were 2.5 and 2.8 ml min-1 (not significant), respectively. The bone bisphosphonate clearance (BBC) at steady state was 26.0 ml min-1, a value which was significantly higher than that at infinity (16.5 ml min-1, p < 0.01). We conclude that the assumption that the sum of peritoneal and renal clearances of 99mTc-MBP equal the clearances of 51Cr-EDTA is correct from a clinical point of view. We found that the uptake of the tracers in soft tissue and the renal handling of 51Cr-EDTA and 99mTc-MBP are also similar. The differences between the clearance values for 51Cr-EDTA and 99mTc-MBP may be explained by their different molecular weight. The differences in the BBCs at infinity and at steady state are most probably due to late recirculation of MBP from the bone compartment. Hence, the BBC technique can be applied in the CAPD setting.

Luminal glutamine perfusion alters endotoxin-related changes in ileal permeability of the piglet.

The objective of this study was to investigate whether luminal perfusion with glutamine or with oxygenated glutamine solutions prevents endotoxin-induced changes in mucosal permeability. Three 15-cm segments of distal ileum were isolated in anesthetized 21-day-old piglets (n = 4) and perfused (50 mL/h) with Ringer's lactate solution, Ringer's lactate solution with 2% glutamine (wt/vol), glutamine, or glutamine purged with oxygen at 37 degrees C for 280 minutes. Plasma-to-lumen clearances of 51Cr-EDTA and urea were measured to assess mucosal permeability. At time 0 minutes, loading and maintenance IV infusions of markers were begun. Baseline permeabilities were obtained from time 60 to 80 minutes, and IV endotoxin (50 micrograms/kg) was introduced from time 80 to 140 minutes. Results are expressed as the ratio of the clearances of the two probes (CEDTA/CUREA). Permeability increased from baseline in loops perfused with Ringer's lactate solution vs loops perfused with glutamine purged with oxygen and with glutamine alone (p < .01). Saturation with oxygen was without effect inasmuch as glutamine alone negated permeability increases. Intestinal myeloperoxidase activity did not differ with perfusate (p > .05). These data suggest that endotoxin-induced permeability changes can be prevented or delayed by the supply of luminal glutamine at the time of insult.

On determinants of glomerular filtration rate after inhibition of proximal tubular reabsorption.

The carbonic anhydrase inhibitor acetazolamide (ACZ) inhibits the absolute rate of proximal reabsorption (APR), causes a reduction in glomerular filtration rate (GFR), and activates the tubuloglomerular feedback mechanism (TGF) resulting in afferent vasoconstriction. The quantitative importance of the afferent vasoconstriction for the reduced GFR was tested by addition of a vasodilator during continuous infusion of ACZ. Dopamine caused an increase in renal blood flow (RBF) to pre-ACZ levels. Glomerular capillary pressure (Pgc) and proximal tubular pressure (Pprox) increased in parallel (by 3.1 and 3.0 mmHg, respectively) leaving pressure gradient (delta P) unchanged. APR, as estimated from the clearances of 51Cr-EDTA and lithium, remained unchanged. Urine flow almost doubled. GFR was only modestly reversed (pre-ACZ/ACZ/ACZ+dopamine: 100/77/83%). It is concluded that relieving the afferent vasoconstriction seen after carbonic anhydrase inhibition fails to restore GFR to its control value. This is due to the high flow resistance in the distal nephron segments during the increased tubular flow rates seen after ACZ. The high distal flow resistance causes a parallel change in Pgc and Pprox and thus leaves delta P nearly unchanged. The present study highlights the importance of the distal flow resistance in determining delta P and therefore GFR during conditions where tubular flow rate is increased.

Dynamics of intrarenal pressures and glomerular filtration rate after acetazolamide

The dynamics of intrarenal pressures, early distal tubular fluid conductivity (EDC), and renal flood flow (RBF) were studied in rats given acetazolamide (ACZ), an inhibitor of proximal reabsorption. Glomerular filtration rate (GFR) and end-proximal flow were estimated by clearances of 51Cr-EDTA and lithium. Proximal tubular pressure (Pprox) increased initially by 1.7 +/- 0.1 mmHg after ACZ, causing a decrease in the hydrostatic pressure difference across the glomerular membrane (delta P). EDC increased, and then RBF, glomerular capillary pressure (Pgc), Pprox, and star vessel pressures (Psv) dropped as a result of afferent vasoconstriction. Pprox decreased less than Pgc, resulting in a further decrease in delta P, which after 25-30 s reached a constant level 3-4 mmHg below control. After a transient increase the pressures declined to a new steady state, in which Pprox was equal to control, Pgc was decreased, and distal tubular pressure, end-proximal flow, and EDC were increased. GFR was depressed by 29%. The results indicate that the tubuloglomerular feedback mechanism controls Pgc and Pprox by afferent vasoconstriction, as well as efferent vasodilation. The data also indicate that proximal reabsorption rate is important in determining the changes in delta P by its effect on Pprox at least in the early transient phase.

Atrial natriuretic peptide and renal adaptation to contralateral nephrectomy in healthy man

Atrial natriuretic peptide (ANP), angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined in 12 healthy renal transplant donors before and 5, 12, 26, 54 days after uninephrectomy (Nx) in order to study the possible role of these hormones in functional adaptation to acute reduction in renal mass. Glomerular and tubular function was studied by measurements of the clearances of 51Cr-EDTA, lithium, sodium, potassium, and albumin. ANP was 7.4 +/- 3.1 pmol l-1 (mean +/- SD) before Nx and 8.7 +/- 6.1 pmol l-1 at 5 days after Nx and remained at this level through the observation period. Aldo showed a non-significant transient fall at 5 days after Nx. AII and AVP remained normal after Nx. At 5 days after Nx glomerular filtration rate (GFR) of the remaining kidney had risen from 45 +/- 7 ml min-1 before Nx to 57 +/- 8 ml min-1 (p less than 0.01), lithium clearance had risen from 13 +/- 2 ml min-1 before Nx to 20 +/- 7 ml min-1 (p less than 0.01), and sodium and water balance was normal. To conclude, plasma ANP, AII, Aldo and AVP do not appear to be responsible for the hyperfiltration and depression of fractional proximal sodium and water reabsorption observed in recently uninephrectomized man with normal sodium and water balance.

51Cr-EDTA/99Tcm-MDP ratio: a simple non-invasive method for assessing renal osteodystrophy

We have used 99Tcm-MDP to develop a measure of overall skeletal activity for use in renal disease. The method utilizes the relative clearances of 99Tcm-MDP and 51Cr-EDTA from the blood after simultaneous injection. This is expressed as a ratio and the upper limit in normals is 1.4. This ratio has been evaluated in 42 patients with chronic renal failure and compared with appearances of left-hand radiographs. The ratio was elevated in these patients and the level corresponded to the degree of severity of the subperiosteal resorption. Similarly, there was a close correlation between the ratio values and the serum alkaline phosphatase measurements and parathyroid hormone values. Thirty-three patients had sequential studies performed at intervals of up to 2 years. Twenty-one patients showed no change on clinical, biochemical or bone scan evaluation. Of these, only one patient showed a change in ratio value of greater than 20%. Twelve patients showed evidence of change based either on clinical, biochemical or bone scan alteration and all 12 patients showed changes in ratio values greater than 20%. The 51Cr-EDTA/99Tcm-MDP ratio appears to offer not only a single plasma sample method for the detection and evaluation of renal bone disease, but our results also suggest that it may be valuable in the follow-up of these patients.

The renal handling of sodium and water is not affected by the standard-dose Cisplatin treatment for testicular cancer

Renal clearances of 51Cr-EDTA, lithium, sodium and potassium were measured before and after each of four consecutive treatment series with cisplatin in 15 men with testicular cancer. Since lithium is reabsorbed like sodium and water in the proximal tubules, but not reabsorbed to any measurable degree in the remainder of the nephron, lithium clearance equals the amount of fluid delivered from the end of the proximal straight segment to the thin descending limb of the loop of Henle. From the clearances of lithium and sodium, distal tubular reabsorption can be calculated. Lithium clearance and all other parameters of glomerular filtration and renal sodium handling remained normal throughout the study (with the exception of a fall in fractional sodium excretion after the first treatment series). Plasma magnesium declined during all four treatment periods, signifying renal magnesium wasting.

The glomerular filtration rate in unrestrained rabbits determined by means of an implanted telemetrical device.

An implanted radio-telemetrical device, which consists of a Geiger-Müller detector, a high voltage supply and a FM transmitter, incapsulated in araldite (weight 130 g) was used to measure the body disappearance rate of 125I-iothalamate following a single i.v. bolus in unrestrained and undisturbed rabbits. The disappearance curve is practically monoexponential from 10 to 60 minutes after administration of the indicator and the disappearance rate constant (Ke) is closely correlated to the "final slope" of the plasma disappearance curve of 125I-iothalamate (kp) r=0.99). A linear correlation was also found between Ke and GFR measured simultaneously by constant infusion clearance technique, using an indicator not detected by the Geiger-Müller detector (51Cr-EDTA) (r=0.98). The ratios between the renal clearances of 125I-iothalamate, 51Cr-EDTA and inulin were determined by constant infusion clearance technique in a separate series of experiments since no data were available in the present literature. The results show that GFR can be determined by means of the telemetrical method and in a series of experiments in undisturbed rabbits GFR was found to be on average 4.7 ml . min-1 . kg-1 (expressed as inulin clearance). Using the same technique in lightly pentobarbital anesthetized rabbits GFR was on average 3.5 ml . min-1 . kg-1.

Renal function and digoxin clearance during quinidine therapy.

To investigate further the handling of digoxin by the kidneys during quinidine therapy, clearances of digoxin, 51Cr-EDTA, PAH and endogenous creatinine were measured together with beta 2-microglobulin in the urine before and during quinidine therapy in 10 patients on maintenance digoxin therapy. Renal clearance of digoxin (corrected for 30% plasma binding) decreased on the average by 55% (137 +/- 73 to 73 +/- 25 ml/min, mean +/- SD). The steady state plasma concentration of digoxin increased more than twofold (1 . 0 +/- 0 . 34 to 2 . 5 +/- 0 . 79 nmol/L, mean +/- SD). The clearances of 51Cr-EDTA and PAH were not altered during quinidine therapy, indicating that neither glomerular filtration nor total renal blood flow changed when quinidine was added. The ratio of the renal clearance of unbound digoxin to that of the glomerular filtration rate was above one for all 10 patients before quinidine, indicating the involvement of tubular secretion in the renal elimination of digoxin. After the administration of quinidine this ratio decreased in all patients (from 1 . 51 +/- 0 . 30 to 0 . 83 +/- 0 . 38, mean +/- SD). Some patients had ratios well below one suggesting re-absorption of digoxin. Beta 2-microglobulin excretion was unchanged during treatment with quinidine. It is concluded that a significant portion of the renal elimination of digoxin in man results from tubular secretion and that this excretory mechanism is inhibited by quinidine.