Göran Granerus

Reference values for 51Cr-EDTA clearance as a measure of glomerular filtration rate.

Reference values for glomerular filtration rate (GFR) were defined using eight reports including epidemiological studies and studies in kidney donors. Studies using both inulin and 51Cr-EDTA were included. GFR decreased with age, by 4 ml/min decade below the age of 50, and 10 ml/min decade above 50 years of age. No sex difference was found. +/- 2 SD was equal to 25 ml/min at all ages. Based on these findings a nomogram for GFR is presented. Emphasis is given to the use of plasma clearance of 51Cr-EDTA estimated with single injection technique as the new reference method for GFR measurement.

Estimation of renal function in diabetic nephropathy. Comparison of five methods.

Plasma as well as renal clearance of 51Cr-EDTA, serum creatinine, plasma beta-2-microglobulin and endogenous creatinine clearance were compared and evaluated in patients with diabetic nephropathy and in control patients with renal disease of other origin. The difference between the plasma clearance and the renal clearance of 51Cr-EDTA, that is the extrarenal clearance, was found to be higher in diabetics than in control patients (7.0 vs. 3.5 ml/min; p less than 0.001). The serum creatinine correlated well with the glomerular filtration rate (GFR), but in the individual case the GFR was not at all predictable from serum creatinine. The plasma beta-2-microglobulin did not correlate better than serum creatinine to 51Cr-EDTA clearance, and did not permit an earlier diagnosis of renal insufficiency. Endogenous creatinine clearance overestimated GFR by 0-180%. Due to residual urine, the coefficient of variation was higher in diabetic patients than in controls, but the effect of this imperfection was reduced by using multiple collection periods. In conclusion, the renal clearance of 51Cr-EDTA was found to be preferable to the other methods.

Cardiac output in normal pregnancy measured by impedance cardiography.

Impedance cardiography was used to study cardiodynamic changes throughout normal pregnancy. Stroke volume, heart rate and cardiac output were determined in fourteen normal primigravidae from early pregnancy until 6-25 weeks after delivery. To elucidate the influence of the patients position on cardiac output, measurements were made in the supine as well as in the left and right lateral positions. Stroke volume and cardiac output increased up to the 28th week of pregnancy and then decreased during late pregnancy. These changes seemed to be independent of the patients position. After delivery a further reduction in cardiac output due to a significant decrease in heart rate was found. No significant differences in cardiac output were found between right and left lateral position. However, during pregnancy as well as after delivery, cardiac output measured by impedance cardiography was significantly higher in the supine position than in the lateral positions. Thus, the impedance method does not seem to be reliable in measuring absolute values of stroke volume and cardiac output but may be used for relative measurements during pregnancy.

Systemic and renal hemodynamic effects of single oral doses of felodipine in patients with refractory hypertension receiving chronic therapy with β-blockers and diuretics

Summary: In 12 patients with primary hypertension (World Health Organization stage 2) inadequately controlled by chronic standard triple therapy, hydralazine was replaced by felodipine, a new vasodilating dihydropyridine derivative, and the acute effects of the drug on central and renal hemodynamics were monitored. Following baseline measurements, an oral solution of felodipine (0.075–0.1 mg/kg) was given. Fifteen minutes after intake of felodipine, a significant hypotensive response was observed, and the maximal response (23% reduction of mean arterial pressure) occurred after 30 min. There was a linear relationship between the changes in mean arterial pressure and log plasma concentration of felodipine. Cardiac output (dye dilution) increased during maximal blood pressure reduction, from 5.3 ± 1.0 to 6.6 ± 2.4 L/min (p < 0.01), partly because of increased heart rate from 57 ± 4 to 65 ± 9.1 beats/min (p < 0.01) and partly because of increased stroke volume from 93 ± 14 to 104 ± 33 ml (p < 0.05). Renal plasma flow (paraaminohippuric acid clearance) increased significantly (p < 0.05) from 343 ± 138 to 391 ± 154 ml/min, while glomerular filtration rate ([51Cr]EDTA clearance) did not change. Arteriovenous noradrenaline difference increased 36% during felodipine therapy, when corrected for blood flow increase. We conclude that felodipine is a calcium inhibitor with potent vasodilating properties.

A Simple Method of Background Subtraction in Two-Detector Renography

To increase the accuracy in the routine measurement of the side distribution of kidney function from 131I-Hippuran renograms, a simple method of background subtraction has been developed. Principally a background curve was adapted to the renogram on each side, assuming an initial amplitude corresponding to the amplitude of phase I of the renogram. The amplitudes of the renogram over background after 2 min is recognized as a measured of kidney function and a background quotient was calculated by dividing the background curve amplitude at 2 min with its initial amplitude. Mean values of the background quotient recorder over thorax was 0.62 and over an empty kidney region 0.73. It was found that a quotient of 0.70 could be used generally, thus omitting the need for a background curve registration at each renographic examination.

Evaluation of unilateral kidney function in children. A comparison between renography and separate clearance.

Unilateral kidney function in children was evaluated by determination of 51Cr-EDTA-clearance combined with estimation of side distribution of kidney function by renography. As reference, separate clearance of 51Cr-EDTA, determined by sequential external ureteral occlusions on both sides, was used. A comparison between these two methods was made in 28 patients with varying degrees of unilateral kidney function impairment. A significant correlation was found when the renograms were corrected for extrarenal background activity. Thus, renography in combination with determination of the glomerular filtration rate with 51Cr-EDTA is a valuable method for evaluating separate kidney function in children, both methods being easily performed and requiring small radiation doses.

Diabetic cystopathy—A risk factor in diabetic nephropathy?

Twenty-seven patients with Type I diabetes and diabetic nephropathy were repeatedly tested (mean, 6 times per patient) for residual urine volumes with a noninvasive technique. Results in 43 of 162 investigations (27%) were abnormal, with residual volumes of greater than 15 ml. Twelve of 162 (7%) showed a residual volume greater than 100 ml. In any individual patient the occurrence of residual volumes was not a consistent finding, and the volumes varied. Pathologic residual volumes were more common in men, but all those with bacteriuria were women. All patients with residual volumes (N = 16) were given voiding instructions. There was no increase in residual volumes during the observation period (mean, 32 months), the median residual volume being 8 ml at the first observation and 5 ml at the last observation. The occurrence of residual urine could not be shown to correlate with progression of renal insufficiency. It is suggested that all patients with long-standing Type I diabetes should be tested by a noninvasive technique for residual urine volume and given voiding instructions to avoid acute retention episodes and complete atony of the bladder.

Kidney Split Function in Children a Comparative Study Between Renography and Planimetry from Urography

The suitability of the background-subtracted renogram as a method for separate kidney function in children was evaluated by comparison with planimetry of the individual renal parenchymal area measured from urography. In different groups of renal disorders the total kidney function as reflected by the glomerular filtration rate has been compared with the sum of right and left renal parenchymal areas. The percentage side distribution of kidney function estimated from the renogram combined with measurements of total glomerular filtration rate has been correlated to individual renal parenchymal area. A good correlation was found for both total and separate measurements. A moderate scatter around the regression lines has to be taken into consideration when kidney function is judged from planimetry. A highly significant correlation was observed between renography and planimetry for the percentage distribution of kidney function, indicating that both methods are well suited for determining the side distribution of kidney function. For calculation of individual kidney function, combination of renography and 51Cr-EDTA-clearance offers a reliable method with a modest dose of irradiation.

Felodipine in Combination with a β-Blocker and a Diuretic in Chronic Treatment of Patients with Refractory Primary Hypertension

SummaryThe acute antihypertensive effects of the dihydropyridine calcium antagonist, felodipine, were investigated in 12 male patients aged 43 to 64 years with uncontrolled blood pressure on combined treatment with a thiazide diuretic, a β-blocker and hydralazine. Central and renal haemodynamics were monitored after acute oral administration (0.075 mg/kg) of felodipine in combination with the β-blocker and diuretic. Six patients were continued on long term oral felodipine (mean dose 20 ± 24 mg/day) in combination with the other drugs for 6 to 18 months. Ambulatory blood pressure was measured repeatedly and renal function re-examined once during long term felodipine therapy.In the 6 patients on long term therapy, systolic blood presure was reduced from 190 ± 17 to 149 ± 24mm Hg and diastolic blood pressure from 116 ± 12 to 89 ± 14mm Hg (p < 0.001). No significant change in heart rate was observed (65 ± 4 vs 62 ± 10 beats/min). Renal plasma flow significantly increased from 284 ± 97 to 425 ± 131 ml/min/m2 (p < 0.01) but glomerular filtration rate was unchanged (72 ± 20 vs 80 ± 22 ml/min/m2). Hence, the filtration fraction was significantly reduced and normalised in all patients (0.26 ± 0.04 vs 0.20 ± 0.03) [p < 0.05]. Bodyweight was unchanged. It is concluded that felodipine is a highly potent vasodilator with a favourable effect on renal function and is suitable for long term therapy in patients with severe primary hypertension.

Time as a Risk Factor in Diabetic Nephropathy

Eighteen individuals with IDDM (type I) and diabetic nephropathy in whom the initial glomerular filtration rate (GFR) was reduced but not below 60 ml/min per 1.73 m2 were observed for an average of 3 yr. The rate of further decline of GFR was found to range between −2 and 21 ml/min/yr. The duration of diabetes until the GFR was first found to be reduced varied between 14 and 33 yr and was not correlated to the ensuing rate of decline in GFR (r = −0.13). In 10 individuals who developed uremia 40 yr or more after onset of IDDM, the development of persistent ptoteinuria was followed by hypertension and increased serum creatinine 2 yr later and by terminal uremia after an average of 8 yr. This is also the normal time span for individuals who develop terminal uremia after shorter duration of diabetes. We conclude that the course of clinical diabetic nephropathy is not more favorable in individuals with late onset of this complication and that there is no point at which a person with diabetes can be considered to be spared from developing diabetic nephropathy.