Prediction of glomerular filtration rate from serum creatinine concentration in advanced chronic renal failure.

In 85 patients with established chronic renal failure, as manifested by serum creatinine concentration ([Cr]) > 0.177 mM (> 2 mg/dl), urinary clearance of 99mTc-DTPA (GFR) and [Cr] were determined one to four times and averaged. GFR was expressed per 3 m2 of height2 rather than in terms of 1.73 m2 of surface area because weight changes but height does not. GFR in these patients averaged 13 ml/min/3 m2 (range 2 to 37). The following equations were derived for predicting GFR from [Cr]-1 (mM-1), age (years) and weight (kg): males, GFR = 7.57 [Cr]-1 - 0.103 age + 0.096 weight - 6.66; females, GFR = 6.05 [Cr]-1 - 0.08 age + 0.08 weight - 4.81. These equations predict GFR in this series with a root mean square error of 3.0 ml/min and account for 89% of the observed variation in GFR. They are applicable only to patients with [Cr] > 0.177 mM (2 mg/dl). More precise estimates can be obtained by including a value for 24-hour urinary urea N, as a measure of protein intake. Less precise but simpler estimates can be obtained from [Cr]-1 alone: males, GFR = 7.58 [Cr]-1 - 4.29; females, GFR = 6.11 [Cr]-1 - 3.8. Expressing [Cr] in mg/dl, the latter equations become: males, GFR = 86 [Cr]-1 - 4.29; females, GFR = 69 [Cr]-1 - 3.8.

Estimating renal function from the visual analysis of Tc-99m DTPA images.

Eleven visual parameters of Tc-99m DTPA imaging studies were evaluated to identify scintigraphic findings that best detect changes in renal function, to determine at which GFR levels they appear, and to establish criteria for visual estimation of renal function. Visual parameters were compared to in vitro GFR determinations in 41 patients. Three visual parameters offered best discrimination. The first one appeared at GFR values below 70 mL/min (sensitivity: 76%). The renal peak activity on the flow study (normally equal or greater than aortic) no longer reached the intensity of the aortic peak (pK < pA). The second parameter appeared at GFR values below 50 mL/min (sensitivity: 85%). The estimated kidney-to-liver ratio in the 2-minute image (usually 3 or greater) decreased to values less than 3. The third scintigraphic finding, pelvicalyceal system nonvisualization, appeared at GFR levels below 20 mL/min (sensitivity 100%). Use of these 3 scintigraphic findings allows categorization of patients into four functional groups: 1) severe dysfunction (GFR: 0-20 mL/min), 2) moderate to severe dysfunction (GFR: 21-50 mL/min), 3) moderate dysfunction (GFR: 50-70 mL/min), and 4) Normal study (GFR > 70 mL/min). Visual analysis of Tc-99m DTPA images does not identify patients with mildly decreased renal function (GFR: 70-90 mL/min).

Diagnostic and functional implications of pelvocalyceal system nonvisualization on [99m]Tc-DTPA renal images.

Most functional abnormalities observed on 99mTc-DTPA renal images probably reflect GFR changes and the functional consequences of these changes. We have noted an unexplained failure of the pelvocalyceal system to visualize in some patients during the renal imaging sequence. This led us to study the relationship between pelvocalyceal nonvisualization and GFR, and to search for plausible explanations of the absent visualization. In 41 patients with combined renal imaging and GFR determinations, pelvecalyceal nonvisualization was seen only with GFR values below 20 ml/min. The sign was 100% sensitive and 100% specific predicting GFR less than 20 and serum creatinine above 2.9 mg/dl. In vitro studies revealed markedly reduced amounts of DTPA chelate in the urine of patients with GFR less than 20, but in addition they had decreased tubular water reabsorption leading to dilution of the already reduced urine chelate contents. The reduced amounts of 99mTc-DTPA per ml of pelvocalyceal urine may account for the nonvisualization of this system. It may be that the intensity of the pelvocalyceal system reflects the adequacy of both the GFR, and the water reabsorptive function of the renal tubules.

Reciprocal creatinine slopes often give erroneous estimates of progression of chronic renal failure.

In 10 of 22 observation periods (lasting an average of 15 months) in 17 patients with moderate to severe chronic renal failure (GFR 4 to 23 ml/min), rates of progression as estimated from the linear regression on time of reciprocal plasma creatinine concentration (multiplied by average 24 hr creatinine excretion) (b2) differed significantly from rates of progression as estimated from the regression on time of urinary clearance of 99mTc-DTPA (b1), during all or part of the period of observation, b2 exceeded b1 in six cases and was less than b1 in the other four. Owing to these changes, measurements of reciprocal creatinine concentration gave erroneous impressions of the rate or existence of progression, during all or a portion of the period of observation, in nearly half of these patients. However, in the 22 studies as a group, using the entire periods of observation, b2 indicated nearly the same mean rate of progression as b1, and had the same variance. We conclude that sequential plasma or serum creatinine measurements in individual patients are often misleading as measures of progression and should, when feasible, be replaced by urinary clearances of isotopes in following patients with chronic renal failure.

Radioisotopic measurement of glomerular filtration rate in severe chronic renal failure.

In order to determine the best method for routine measurement of glomerular filtration rate (GFR) in severe renal failure, we compared simultaneously the urinary clearances of [99mTc] diethylenetriaminepentaacetic acid (DTPA) (UD), [125I]iothalamate (UI), 24-hr creatinine clearance (UC) and plasma clearance of [99mTc]DTPA (PD), based on three plasma samples. In 60 studies in 22 patients with serum creatinine values of 2 to 8 mg/dl, UD and UI were almost identical: UD = 0.358 +/- 0.976 UI +/- 0.87 ml/min, r = 0.990. However, PD overestimated UD by a large and variable extent: PD = 11.3 +/- 0.843 UD +/- 5.5 ml/min, r = 0.694, and was inconsistent in sequential measurements in individual patients. UC also overestimated urinary isotope clearance: UC = 4.2 + 0.95 UI +/- 3.9 ml/min, r = 0.865. Sequential measurements of GFR in five patients with severe but stable renal failure (mean GFR 5.9 ml/min) showed an average standard deviation of only 0.83 ml/min. Thus both UD and UI appear to be reliable and precise measures of GFR in severe renal failure.

Creatinine measurements often yielded false estimates of progression in chronic renal failure.

In 9 of 22 observation periods (lasting an average of 15 months) in 17 patients with moderate to severe chronic renal failure (GFR 4 to 23 ml/min), rates of progression as estimated from the linear regression on time of 24-hour creatinine clearance (b1) differed significantly from rates of progression as estimated from the regression on time of urinary clearance of 99mTc-DTPA (b2), during all or part of the period of observation. b1 exceeded b2 in four cases and was less than b2 in the other five. Thus there were gradual changes in the fractional tubular secretion of creatinine in individual patients, in both directions. Owing to these changes, measurements of creatinine clearance gave erroneous impressions of the rate or existence of progression during all or a portion of the period of observation in nearly half of these patients. In the 22 studies as a group, using the entire periods of observation, b1 indicated significantly more rapid progression (by 0.18 +/- 0.06 ml/min/month, P less than 0.01) than did b2, and had a significantly greater variance. Measurements of progression based on the rate of change of reciprocal plasma creatinine (multiplied by an average rate of urinary creatinine excretion in each study) were equally misleading, even though less variable. We conclude that sequential creatinine measurements are often misleading as measures of progression and should, when feasible, be replaced by urinary clearance of isotopes in following patients with chronic renal failure.