Individual Kidney Function Research Articles

Kidney-to-Liver Ratio A Simple Scintigraphic Parameter for Routine Individual Renal Function Assessment in Children

DTPA renography is commonly used for measuring relative renal function. However, in patients with bilateral renal disease or solitary kidneys, split function studies are of no value. Available techniques to quantify individual renal function are either time consuming or inaccurate. The authors validate the kidney-to-liver ratio at 3 minutes (K3/L3) as an index of renal function, showing excellent correlation with GFR. Normal K3/L3 ranges were then computed in 113 pediatric kidneys (age 2 days to 16 years) and 24 adults. Indicative of renal maturation, the K3/L3 rapidly rose from a value of 1.32 at birth to 2.02 at 6 months. Subsequently, it increased slowly to reach a peak of 2.34 at age 2, followed by gradual decline to adult values after age 5. This decrease is due likely to continued growth of the hepatic blood pool after renal maturation. GFR followed the same maturation pattern to reach a plateau around 2 years of age. K3/L3 reflects individual kidney function, and it requires no blood sampling or urine collection. By establishing normal values at different stages of maturity, this method provides identification and quantification of renal dysfunction in infants, children, and adults.

Functional changes in the pig kidney following irradiation with fractionated doses of fast neutrons (42 MeVd-->Be).

The right kidney of female Large White pigs, approximately 14 weeks old, was irradiated with fractionated doses of fast neutrons (42 MeVd-->Be). The total doses used were 6.6-9.2 Gy. Changes in kidney function, assessed as the functional index (FI, where FI = irradiated kidney function/unirradiated kidney function) or as individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), were serially determined up to 104 weeks after irradiation using 99Tcm-DTPA and 131I-hippuran renography. The animals were then euthanized, the kidneys removed and weighed. A dose-dependent reduction in FI was seen within 13 weeks of irradiation. Measuring individual kidney function revealed a hyperaemic response in both irradiated and unirradiated kidney 4 weeks after irradiation. This was followed by a dose-dependent reduction in irradiated kidney GFR and particularly ERPF. The ED50 value for the impairment in ERPF, assessed as the percentage of irradiated kidneys exhibiting a > or = 50% reduction in ERPF, was significantly lower than that for GFR, i.e. 7.20 +/- 0.10 Gy compared with 8.44 +/- 0.07 Gy (p < 0.001). A dose-related reduction in irradiated kidney weight was also observed. These fast neutron-induced changes in renal function and weight are qualitatively similar to those observed following photon irradiation of the pig kidney.

12. The 123I-OIH accumulation index (AI) in initial staging and follow-up of individual kidney function in neonates with urinary tract disorders

12. The 123I-OIH accumulation index (AI) in initial staging and follow-up of individual kidney function in neonates with urinary tract disorders

Age Factor in Compensatory Hypertrophy of the Kidney Evaluated by99mTc-DTPA Renography

Unilateral nephrectomy initiates a growth response in the contralateral kidney to compensate for the loss of a renal mass. The events which regulate this process are not very clear. We used a newly developed method, 99mTc-DTPA gamma-camera renography, to evaluate the individual kidney function for detection of the change of it. This method is simple, reliable and requires neither blood nor urine samples. Two groups of rabbits were used in the study. Those of 1.5-2 months of age were taken as the young aged group and those of 2 years of age as the old aged group. Kidney weight, glomerular filtration rate (GFR), and effective renal plasma flow (ERPF) were detected both before and 3 weeks after unilateral nephrectomy. After unilateral nephrectomy in both young and old age groups, the kidney weight increased by 119 and 38%, the GFR by 71 and 44%, and the ERPF by 116 and 35%. We conclude that nephrectomy at a young age where there is fast growth would cause the remaining kidney a compensatory hypertrophy which is much better than that in nephrectomy at an old age. The difference of glomerular filtration rate was less apparent than that of the kidney weight and renal plasma flow in both groups of rabbits.

Technical and operative factors in infrarenal aortic reconstruction and their effect on the Glomerular Filtration Rate in the immediate postoperative period and 6 months later

Renal failure is an important cause of postoperative morbidity and mortality in infrarenal aortic reconstruction. Several mechanisms for this postoperative renal dysfunction have been suggested. However, biochemical testing of renal function is insensitive since it shows only gross renal changes. This study examined prospectively the effects of the technical and operative factors on renal function using radionuclide tests. The authors measured the total Glomerular Filtration Rate (GFR) using 51Cr-EDTA clearance in 59 patients undergoing elective infrarenal aortic reconstruction. We also examined the individual kidneys using 99mTc-DTPA renography and 99mTc-DMSA renal scanning. Renal scanning gives the percentage of function of each kidney, while renography gives a graphic assessment of individual renal perfusion and clearance. All tests were carried out preoperatively, 2 weeks postoperatively and 6 months later. Twelve technical factors including aortic cross clamping time, type of aortic anastomosis, forced diuresis, division of left renal vein and various others were recorded to study their effect on the GFR and the individual kidney function. The effect on renal function of these operative factors has not previously been described. GFR showed no change in the immediate postoperative period. Six months later GFR decreased, the mean decrease was 9 ml/min. (P = 0.007 Wilcoxon rank). Some of our patients showed an increased GFR, a phenomenon that was recognised recently. None of the factors studied, except division of the left renal vein, had any effect on the changes in the GFR in the immediate postoperative period or 6 months later.

Extreme Unilateral Hydronephrosis with Normal Glomerular Filtration Rate: Physiological Studies in a Case of Obstructive Uropathy

A 30-year-old man presented with massive left hydronephrosis caused by congenital stricture of the ureteropelvic junction. Glomerular filtration rate of the post-released kidney (inulin clearance and creatinine clearance) was preserved completely. Simultaneous individual kidney function tests showed the following values expressed as the ratio of post-obstructed to normal kidney: inulin clearance 142 per cent, urine flow rate 475 per cent, sodium clearance 221 per cent and urinary excretion of prostaglandin E2 617 per cent. Urinary osmolality was 257 and 791mOsm./kg. in the obstructed and normal kidneys, respectively. Administration of indomethacin, a cyclo-oxygenase inhibitor, caused decreased urinary excretion of prostaglandin E2 in both kidneys, with drastic antinatriuresis manifested predominantly in the normal kidney.We conclude that the glomerular filtration rate may be preserved despite huge hydronephrosis, which suggests that the human kidney is salvageable even after a prolonged period of unilateral ureteral obstruction, and the contralateral normal kidney mitigates the volume losses from the obstructed kidney.

Techniques for the quantitative measurement of individual kidney function in the pig

A prerequisite for elucidating the effect of radiation on porcine renal function is the development of non-invasive methods for accurate quantification of unilateral glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The techniques presented here are (a) measurement of unilateral kidney filtration fraction (FF) determined by analysis of the early rise of the kidney's time-activity curves following the injection of tubular ([ 131I]hippuran) and glomerular ([ 99mTc]DTPA) tracers, and (b) deconvolution of the respective renogram. Unilateral FF values are obtained by calculating the ratio of glomerular to tubular clearances. Results for 23 female large white pigs indicate a highly significant correlation ( r=0.91, P<0.001) between computed FF values and those obtained from the plasma disappearance curves of [ 99mTc]DTPA and [ 131I]hippuran. Deconvolution of the renogram allows estimation of the mean transit time (MTT) for [ 99mTc]DTPA and [ 131I]hippuran, these are 6.94±1.87 and 6.86±1.44 min respectively. In addition, FF values calculated from the H 0 values are significantly correlated ( r=0.7, P<0.05) with estimates from plasma disappearance curves of the tracers. Therefore these techniques appear to provide accurate non-invasive methods for determing individual porcine kidney function.

Modern drug analysis in biological fluids suitable for clinical pharmacokinetics

Therapeutic drug monitoring can provide valuable information to guide clinicians in achieving optimal treatment with selected therapeutic agents. Large intersubject variations in drug response are common. There are many factors that may cause variability in drug disposition and drug plasma levels using standard dosage regimens: (1) Biometric factors: age, height, weight; (2) Absorption and patient compliance; (3) Distribution, cardiac failure; (4) Elimination: hepatic and/or renal failure; (5) Individual capacity in metabolizing drugs; (6) Drug-drug interactions. All these factors demand dosage adjustments for the individual patient and contribute to the observation that the correlation between drug plasma level and response is much better than that between the total dose and response among a given patient population. Pharmacokinetic-pharmacodynamic studies yield information on the therapeutic plasma concentration range of a drug that should be maintained during therapy to achieve maximum benefits. This leads to the concept of the ‘target level’ of a particular drug in plasma, which is important for the application of clinical pharmacokinetics in drug therapy. There are two ways by which ‘target levels’ can be utilized to optimize the individual drug dosage regimen: first, calculation of the dose based on predictive pharmacokinetic models for the individual patient; and second, inclusion of drug level monitoring to correct the predictive model for unaccountable intersubject variation. Predictive pharmacokinetic models are particularly useful for drugs that are mainly eliminated by renal excretion, since good correlations between clinical kidney function tests and drug clearance have been established. Thus dosage adjustments, based on individual kidney functions, are an integral part of modern drug therapy with drugs like

Evaluation of 99mTc-Dimercaptosuccinic Acid Renal Uptake as an Index of Individual Kidney Function after Acute Ureteral Obstruction and Desobstruction

The evolution of the 99mTc-dimercaptosuccinic acid (DMSA) renal uptake is followed after ligation of the right ureter in rats. The DMSA uptake falls rapidly from 35% before ligation to 13% after 24 h, and decreases further to 1.5% after 31 days. The ligated ureter was desobstructed after 10, 17, 24 and 31 days, respectively, DMSA uptake was controlled 4, 11 and 18 days after desobstruction. In the first group, deobstruction after 10 days, the DMSA uptake rose from 7 to 15%, while in the fourth group it rose from 1.5 to 2%. It is concluded that DMSA uptake provides a reliable index for renal function after acute urinary tract obstruction in rats. If the DMSA uptake has fallen below 4% very little renal function can be expected to be regained, whereas above 4% the function can improve considerably.

Radionuclide Determination of Individual Kidney Function in the Treatment of Chronic Renal Obstruction

Differential radionuclide renal scans can be useful in the management of patients with chronic partial obstruction of 1 kidney. The 99mtechnetium diethylenetriaminepentaacetic acid perfusion scan can be used to assess glomerular blood flow. The 131iodine orthoiodohippurate renal scan provides qualitative functional information from scintigrams and quantitative evaluation of effective renal plasma flow to each kidney, as well as a total excretory index. Sequential 99mtechnetium diethylenetriaminepentaacetic acid and 131iodine orthoiodohippurate renal scans were used to assess individual renal function before and after surgical correction of unilateral chronic renal obstruction in 31 patients.The preservation of cortical perfusion on 99mtechnetium diethylenetriaminepentaacetic acid scans indicated that potential existed for partial recovery of renal function. Effective renal plasma flow and excretory index determined in conjunction with the 131iodine orthoiodohippurate scans provided a quantitative assessment of preoperative renal function, an evaluation of the effect of surgery and a sensitive method for long-term evaluation of differential renal function. Correction of ureteropelvic junction obstruction usually resulted in improvement in unilateral renal function. Neither nephrolithotomy nor extended pyelolithotomy diminished renal function in the kidney subjected to an operation and often improved it. Patients with long-standing distal ureteral obstruction had the least improvement in renal function postoperatively.

Anatrophic Nephrolithotomy: Preservation of Renal Function Demonstrated by Differential Quantitative Radionuclide Renal Scans

Differential quantitative radionuclide renal scans have been used to confirm that early removal of staghorn calculi by anatrophic nephrolithotomy preserves renal parenchyma without significant renal damage by the surgical procedure. The 99mtechnetium diethylenetriaminepentaacetic acid scan was useful in predicting recovery of function in the involved kidney, while the 131iodine orthoiodohippurate scan provided a quantitative evaluation of the effect of the surgical procedure on. individual kidney function. All of 13 consecutive evaluated by 131iodine orthoiodohippurate renal scans had stable or improved effective renal plasma flow to the involved kidney and an unchanged or improved total excretory index 6 months after nephrolithotomy.

Bilateral renal function responses to converting enzyme inhibitor (SQ 20,881) in two-kidney, one clip Goldblatt hypertensive rats.

SUMMARY The influenc of the renln-angiotensie n system on individual kidney function of two-kidney, oneclip Goldblatt hypertensive (GH wa) rats evaluates bdy determining renal functional responses during intra-venous infusio on f converting enzyme inhibitor (CEI) (SQ 20,881 0J rag/100, g-hr for) 3.5 bourn. Rats weremade hypertensiv be y placing a 0.25 mm silver clip on the right renal arter 3-y4 weeks prior to study. Normalrats and GH rats were prepare tdo allow urine collections from each kidney. Mean arteria of Gl pressurH erats fell significantly from preinfusio of 15n level3 ± 7s to 126 ± 4 mm Hg during CEI infusion. Despite thisdecrease in arterial pressure, the nondipped kidneys with reduced renal renin activit ± 5 vs 29y (13 ±4 40 ngAl/mg-hr in th clippee d kidney) exhibited dramati in gtomerulac increaser filtrations (GFR rat (fro)e m1.45 ± 0.06 to 2.56 ± 0.3 ml/mln)5 , urine (4.8 flow2 ± 0.71 to 9.11 ± 1.1 ^il/mln)9 , sodium excretion(0.10 ± 0.02 to 1.15 0.3 ± 9 MEq/mln), fractional sodium excretion (0.05 ± 0.02% % to 0.43 ±% 0.18%), andpotassium excretion (0.9 ±4 0.08 to 2.50 ± 0.55 /<Eq/mln). Significant arterial-pressure-associated decreasesIn GFR, urin e flow, and salt excretion were observe in th clippee d d kidney In. normal rats CE,I infusionproduced reduction isn arterial pressure and increase in GFRs , urine flow, and sodium excretion that o werf esmaller magnitude than thos ie observen th nondippee d d kidney of GsH rats. Plasma renin wa activits ysignificantly highe inr GH rats than in normal rats (24.0 ± 2.7 vs 12.8 ± 3.4 n AI/mMir)g . The augmentedrenal response tos CE I by the nondipped kidney suggest that elevated circulating angiotensi a n levels exertsubstantial influence on hemodynamic and excretory functio of thesne kidneys even though intrarenal renin ac-tivity is markedly reduced. This influence may lea tod fluid and electrolyte retention and may partially explainthe apparent failur of the nondippee d kidne toy preven tht e development of hypertension.(Hypertension 3: 285-293, 1981)KEY WORDS • renal hypertensio • glomerulan filtration rate •r sodium • excretionrenin-angiotensin • urine flow

Renal scintigraphy: Quantitative assessment of upper urinary tract dilatation in children

A standard method of Tc-DTPA renal scintigraphy has been used to examine 426 dilated upper urinary tracts in children aged 2 days-16 yr. The method provides an accurate estimate of individual kidney function and defines the extent of dilatation. Renogram analysis and frusemide-induced diuresis have been applied in an attempt to distinguish between the obstructed upper tract and the dilated upper tract without obstruction. In 304 upper tracts, obstruction was predicted with an overall sensitivity of 0.87. The sensitivity for diagnosis of pelviureteric junction obstruction was 0.93. The value of scintigraphy in excluding significant obstruction and in follow-up studies is emphasized. This is a noninvasive, low-radiation investigation which plays an important role in the assessment of obstructive uropathy in childhood and represents a major advance in diagnostic facilities.

Intravenous Radionuclide Cystography for the Detection of Vesicorenal Reflux

Intravenous radionuclide cystography using a single intravenous injection of 99mtechnetium diethylenetriaminepentaacetic acid, provides information on individual kidney function, coarse anatomy and vesicorenal reflux. This study investigates the effectiveness of intravenous radionuclide cystography in detecting reflux. In 58 children intravenous radionuclide cystography detected 53 ureters with reflux compared to 32 detected by voiding cystography. This difference was investigated further with patients in whom other tests suggested reflux. While there was no statistically significant difference for patients having pyelonephritis or hydronephrosis, intravenous radionuclide cystography detected significantly more ureters with reflux in patients with abnormal ureteral orifices or infected urine and, therefore, predisposed to reflux. Intravenous radionuclide cystography is a more comprehensive and sensitive test for vesicorenal reflux than voiding cystography.

INDIVIDUAL KIDNEY GLOMERULAR FILTRATION RATE USING RADIONUCLIDES

The accuracy of a simple new method for glomerular filtration rate (GFR) was assessed by comparing it with the established multiple plasma sampling method in 101 consecutive children having a renal scan and serum B2 microglobulin assay (B2M). A. Multiple plasma sampling method (M Plasm). Following a measured IV dose of technetium DTPA, this was calculated conventionally following samples at 120, 150 & 180 minutes. B. Following the same dose of radionuclide, the information from a gamma camera viewing kidneys and precordium was captured onto a digital computer. From this information counts accumulating in the individual kidneys due to GFR were computed. A single plasma sample taken 20 minutes after injection furnished the plasma counts. From these two parameters individual kidney GFR was calculated. C. B2M was measured by radioimmunoassay using Phadebas B2M kit. The new method correlated well with M Plasm (r=0.80) and with B2 microglobulin (r= -0.86). The correlation between M Plasm and B2M was also good (r= -0.92). This new method is inherently attractive because: 1. It can be performed during the course of a normal renal scan without added radiation or trauma to the patient. 2. It is completed in 20 minutes. 3. It is theoretically applicable to patients with oedema or localised effusions. 4. It provides information with respect to individual kidney function.

Validity of 99mTc Dimercaptosuccinic Acid Renal Uptake for an Assessment of Individual Kidney Function

99mTc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a 131I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. 99mTc dimercaptosuccinic acid scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.

Total and individual kidney function assessment with iodine-123 ortho-iodohippurate.

A simple and reliable method of preparing 123l o-iodohippurate (l-123 OIH) is described. The agent was used to evaluate renal function in 329 patients; its use results in significant dose reduction for those with obstruction, hypertension, or transplant. Images from l-123 OIH provide 2.4 times more detectable photons per mCi administered to the patient than images obtained from l-131 OIH. Diagnoses are expected to be more reliable with l-123 OIH due to the decreased random variation of each data point.

Renal intracortical blood flow distribution, function and sodium excretion in response to saline loading of anesthetized and unanesthetized dogs.

In order to study the effect of anesthesia on the canine response to saline loading, experiments were performed on 10 dogs, first while awake and then during pentobarbital anesthesia. Individual kidney function and intrarenal blood flow response to saline loading (7.5% body weight) were measured in each condition and all data are reported as the average of a single kidney. CIN is considerably reduced under anesthesia (24.7 +/- 3.2 vs. 43.2 +/- 3.9 ml/min, P less than 0.01). A directionally similar reduction of PAH clearance was noted (89 +/- 17 vs. 122 +/- 13 ml/min). The natriuretic response to saline loading of the dogs reached 290 +/- 61 muEq/min while awake, but only 70 +/- 27 muEq/min while anesthetized. No measurable increase of CIN or CPAH occurred in response to saline loading either in the anesthetized or unanesthetized state. The natriuresis was entirely due to a rise of CNA/GFR in both circumstances. The change of CNA/GFR in response to saline load was also appreciably larger while awake (1.2 leads to 4.7% vs. 0.7 leads to 1.8%). Although the fraction of blood flow to the outermost quarter of the kidney was initially the same (31 +/- 3 vs. 29 +/- 3%) awake or anesthetized, the changes with saline loading were in the opposite direction and the values reached were significantly different (37 +/- 3, awake, vs. 27 +/- 3%, P less than 0.05). We conclude that while increased outer cortical blood flow is not necessary for natriuresis, it may occur during sodium loading and may facilitate sodium excretion.

Enhanced tubular reabsorption of phosphate

Individual kidney functions were studied during water diuresis in eight patients, following the relief of unilateral ureteral obstruction. Fractional excretion of phosphate was diminished in four of the patients, presumably due to enhanced tubular reabsorption of phosphate in the diseased side. Glomerular underperfusion may be the main factor responsible for the hypophosphaturia in the postobstructive kidney. Fractional excretion of sodium and water was increased in the obstructed side in six of the eight patients. In two of the four patients with hypophosphaturia, there was enhanced fractional sodium excretion, suggesting a dissociation of renal handling of sodium and phosphate in some patients with this condition.

Enhanced Tubular Reabsorption of Phosphate

Individual kidney functions were studied during water diuresis in eight patients, following the relief of unilateral ureteral obstruction. Fractional excretion of phosphate was diminished in four of the patients, presumably due to enhanced tubular reabsorption of phosphate in the diseased side. Glomerular underperfusion may be the main factor responsible for the hypophosphaturia in the postobstructive kidney. Fractional excretion of sodium and water was increased in the obstructed side in six of the eight patients. In two of the four patients with hypophosphaturia, there was enhanced fractional sodium excretion, suggesting a dissociation of renal handling of sodium and phosphate in some patients with this condition.