131I Hippuran Research Articles

Quality controls of radiolabeled compounds 131I–Hippuran as PSTNT-BATAN product using electrophoresis method

The labeled compound 131I-Hippuran has been known for a long time and was still being used by some hospitals as a medical kit for the study of dynamics kidney function. The application of Labelled compound 131I-Hippuran begins by intravenous injection to the patients, then monitor the process of biodistribution, secretion, and excretion of Labelled compound 131I-Hippuran using Renographs. The Bandung TRIGA 2000 reactor has obtained an operating license from BAPETEN in 2017, and has been operating at 800 kW to irradiate various elements including Tellurium to produce radioisotope Iodine-131. Iodine-131 was used as a radioisotope material in Labelled compound 131I-Hippuran, which was produced to fulfill the requests from An-Nur Hospital, Yogyakarta. Labeled compound 131I-Hippuran used in hospitals must meet the requirements of Indonesian Pharmacopeia, one of the parameters tested is radiochemical purity. The method used to determine the radiochemical purity is the paper electrophoresis method with phosphate buffer electrolyte pH 9, at a voltage of 300 volts for 1 hour. The radiochemical purity of 131I-Hippuran using the column chromatography method obtained yield more than 70% with radiochemical purity of 98.81 ± 1.06%. Based on these data, the radiochemical purity of the 131I-Hippuran kit has met the requirements set by Pharmacopoeia Indonesia V that is >90%.

Kidney preservation by hypothermic perfusion with albumin versus plasma and with pulsatile versus non-pulsatile flow.

Abstract Four groups of canine kidneys were preserved by hypothermic perfusion for 24 hours in an attempt to compare the relative merits of using cryoprecipitated plasma or albumin as perfusates and of using pulsatile or non-pulsatile flow. All the kidneys were subsequently autotransplanted At 0, 3 and 24 hours during preservation the following parameters were measured: perfusate and urine flow, renal vascular resistance, perfusate serum glutamic oxaloacetic transamianase, lactic dehydrogenase, acid and alkaline phosphatases, ammonia, free fatty acids, clearances of creatinine, 131I hippuran, Na+ and K+. After reimplantation similar renal clearance studies were carried out. After transplantation overall kidney viability was assessed by recipient survival and by serum creatinine levels. The results obtained were subjected to statistical analysis and compared between the groups. It was found that perfusion with albumin solution gave a significantly higher perfusate flow rate (P<0·02) and lower vascular resistance (P< 0·001) than perfusion with plasma. With albumin as the perfusate there was no significant difference in perfusion characteristics or in the post-implantation renal clearances regardless of whether pulsatile or non-pulsatile flow was used. With plasma as the perfusate there was significantly higher perfusate flow (P<0·01), lower vascular resistance and higher post-implantation creatinine and hippuran clearances (P<0·02, P<0·001) with pulsatile than with non-pulsatile flow. In 24-hour renal preservation overall recipient survival and graft function after transplantation were similar regardless of the nature of the perfusate or the type of perfusion.

A porcine model of systemic and renal haemodynamic responses to infrarenal aortic cross-clamping

Objectives: cross-clamping of the infrarenal aorta is associated with complex haemodynamic disturbances. Several experimental models of aortic cross-clamping (AXC) have been described with heterogeneous results. The main purpose of this study was to establish an animal model in which infrarenal AXC could reproduce similar systemic and renal haemodynamic changes to those observed in humans. Methods: eleven anaesthetised pigs underwent AXC just below the renal arteries. Renal blood flow was measured using clearance of 131I hippuran. Systemic and renal parameters were collected at 3 consecutive 30-min periods. Results: AXC did not alter the extraction fraction of 131I hippuran but was accompanied by significant (13%) decrease in cardiac index (p = 0.005) and a 23% increase in mean arterial pressure (p = 0.005). AXC induced significant 135% increase in renal vascular resistance (p = 0.012) and a 35% decrease in renal blood flow (p = 0.016). This worsened after removal of the aortic clamp, whereas systemic variables returned to baseline levels. Conclusions: this AXC animal model reproduces the changes observed in humans. It provides a reliable animal model which allows to investigate the underlying mechanisms of renal vasoconstriction and the effect of new drugs.Eur J Vasc Endovasc Surg 25, 72–78 (2003)

SYSTEMIC AND RENAL HEMODYNAMIC PROFILES OF NEORAL® ONCE VERSUS TWICE DAILY DOSING - RESULTS FROM OLN-453 STUDY

789 Chronic use of cyclosporine (CSA) is associated with systemic and intrarenal vasoconstriction. To evaluate the hemodynamic differences between two Neoral® CSA dosing regimens, we perform a prospective, randomized, pilot study comparing de-novo adult renal transplant patients, assigned to once (QD, n=10) vs twice-daily (BID, n=7) dosing. Groups were comparable in terms of age, gender, CSA and prednisone dose, cadaveric and regrafts, and HLA mismatches distribution. Total daily doses were similar during the twelve weeks. Pharmacokinetic studies and 12 hs ambulatory blood pressure monitoring were done at weeks 2, 4 and 12 after starting CSA. Additionally, GFR (Tc-99m DTPA) and ERPF(I-131 Hippuran) were measured 12 hs after the last CSA dose, at the same timepoints. Results at week 12 were: (Table) and (Figure)TableFigureAdditionally, the incidence of adverse effects (including the number of acute rejections) within the first 12 weeks was comparable between groups. Conclusions- Our pilot study showed that the use of Neoral® CSA once daily is associated with favorable (yet not statistically significant) systemic and renal hemodynamic profiles, when compared with a twice daily dosing regimen. Larger studies are needed to confirm these findings. The use of CSA once daily is currently not approved by the FDA. Study sponsored by Novartis Pharmaceuticals Co, East Hanover, NJ, USA.

Radiation dose to patients from radiopharmaceuticals: (Addendum 2 to ICRP Publication 53) ICRP Publication 80 Approved by the Commission in September 1997

A joint Task Group of ICRP Committees 2 (Doses from Radiation Exposures) and 3 (Protection in Medicine; lead Committee for this report) has prepared a compilation of data on radiation dose to patients from radiopharmaceuticals. The report provides biokinetic models, absorbed doses, and effective doses, using ICRP Publication 60 dosimetry, for 10 new radiopharmaceuticals: [Methyl- 11C]thymidine; [2- 11C]thymidine; 14C urea (incl. carbon dioxide and bicarbonate); 15O water; 99mTc HIG, Pertechnegas, Technegas, and tetrofosmin; and 111In HIG and octreotide. It also provides recalculated dose data for the 19 most frequently used radiopharmaceuticals from ICRP Publication 53, using ICRP Publication 60 dosimetry, viz. 18F FDG; 51Cr EDTA; 67Ga citrate; 75Se SeHCAT; 99mTc DMSA, DTPA, RBC, IDA, large colloids, WBC, MAA, non-absorbable markers, pertechnetate, and phosphates and phosphonates; 123I Hippuran and MIBG; 131I Hippuran and NP59; and 201Tl thallous ion. Printing errors detected in ICRP Publication 53 are also listed. Furthermore, the report reproduces with minor corrections and updates, and therefore supersedes, the information on 6 radiopharmaceuticals given in Addendum 1 to ICRP Publication 53: 3H neutral fat and fatty acids; 14C neutral fat and fatty acids; 68Ga EDTA; and 99mTc HM-PAO, MAG3, and MIBI. There is an integrated index to all radiopharmaceuticals treated in ICRP publications so far, including a listing of effective doses per unit activity administered to adults. This issue of the Annals of the ICRP also includes an Addendum to ICRP Publication 72 concerning age-dependent doses to members of the public from intakes of radionuclides.

Can Continuous Intraperitoneal Infusion of 125I-Iothalamate and 131I-Hippuran Be Used for Measurement of GFR in Conscious Rats?

We previously described a method to measure GFR in conscious spontaneously voiding rats. This method circumvents the need for anesthesia and for bladder instrumentation. It's main principle is the correction of renal 125I-iothalamate clearance for incomplete urine collection by the ratio of plasma and renal clearance of co-infused 131I Hippuran. A disadvantage of this technique is the requirement of an intra-arterial catheter for infusion of the renal function tracers. We therefore tested whether intraperitoneal infusion of 125I-Iothalamate and 131I-Hippuran can be used for such a GFR measurement in conscious spontaneously voiding rats.We found that during intraperitoneal administration, stable plasma levels of 131I-Hippuran could be obtained. However, urinary recovery of 131I-Hippuran was incomplete (66 ± 32%), leading to a significant overestimation of GFR by 140 ± 113% in comparison with the GFR measured by the intra-arterial technique. Thus intraperitoneal infusion of renal function tracers cannot replace intra-arterial infusion.

No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients.

Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.

Pair-tested renal reserve filtration capacity in kidney recipients and their donors.

Subjects after kidney donation manifest an adaptive rise in GFR. In uninephrectomized rats, progressive glomerulosclerosis, which is induced by the compensatory glomerular hyperfiltration, develops. It has been assumed that testing the existence of renal reserve filtration capacity (RRFC) might be used to demonstrate such glomerular hyperfiltration in humans. In a paired way, the RRFC of 15 kidney recipients and their donors were investigated long term (4.9 +/- 0.8 (SE) yr) after surgery. Continuous infusions of (125I)iothalamate and (131I)hippuran were used to measure GFR and effective RPF (ERPF). RRFC was tested by the infusion of dopamine, amino acids, and a combined infusion of these agents. The GFR, ERPF, and RRFC of the recipients did not differ from that of their donors. RRFC had also been tested in 12 donors, before and short term (1.3 +/- 0.3 (SE) months) after the kidney donation. Thus, the RRFC of the kidney donors could be monitored longitudinally. GFR measured short term after kidney donation amounted to 62% (+/- 2.1% SE) of the value before donation and to 68% (+/- 1.7% SE; P < 0.005) of the value long term after donation. Short- and long-term ERPF both amounted to 68% of the value before donation. The RRFC tested with the amino acids of the donors before kidney donation did not differ from that either short-term or long term after donation. Likewise, the RRFC tested with the amino acids of the recipients was similar to that of the donors before kidney donation. In contrast, in kidney recipients and donors, both short and long term after donation, RRFC tested with dopamine was approximately halved compared with that of the donors before donation. It was concluded, first, that testing RRFC cannot be used to test the existence of maladaptive glomerular hyperfiltration in subjects with a single kidney: Second, GFR increases for years after kidney donation, probably because of the compensatory hypertrophy of the remaining kidney.

Tc-99m MAG3 as an Alternative to Tc-99m DTP A and I-131 Hippuran for Renal Transplant Evaluation

This study investigated the new radiopharmaceutical, Tc-99m mercaptoacetyltriglycine (MAG3), as a possible alternative to Tc-99m DTPA and I-131 Hippuran for renal transplant evaluation. Tc-99m MAG3 and I-131 Hippuran were used sequentially in 19 consecutive patient studies and compared qualitatively and quantitatively. Serum creatinine values ranged from 1.6 mg/dL to 10.3 mg/dL (mean, 5.4 mg/dL). The Tc-99m MAG3 images and time-activity curves were of superior quality (3+) compared to I-131 Hippuran (1-2+). Quantitative analysis of the time to peak activity (Tmax) demonstrated a high correlation and no significant difference for Tc-99m MAG3 (mean, 11.4 min) compared to I-131 Hippuran (mean, 11.2 min). The percentage of peak activity retained at 20 minutes (T20) also showed a high correlation between the two agents; however, Tc-MAG3 showed a significantly slower clearance (T20 mean, 77%) than I-131 Hippuran (mean, 71%). Flow images were judged to be of good quality; however, the first-pass time-activity curves were often different from that seen with Tc-99m DTPA. Interpretation of delayed Tc-99m MAG3 images, for example to diagnose a slow urinary leak, were sometimes complicated by bowel clearance. In conclusion, Tc-99m MAG3 is superior to I-131 Hippuran for evaluation of renal transplant function. Tc-99m is the agent of choice for evaluation of renal transplant blood flow and function.

Acute renal dysfunction during interleukin-2 treatment: suggestion of an intrinsic renal lesion.

Adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has been effective in treating some advanced malignancies in animals and humans. One complication of this treatment is a reversible, oliguric, acute renal failure, which has been ascribed to renal hypoperfusion and resultant prerenal azotemia. We serially studied renal function in 10 patients receiving high-dose regimens of recombinant interleukin-2 (rIL-2) to attempt to delineate further the nature of the renal dysfunction caused by IL-2 treatment. Renal plasma flow was computed from iodine 131 (I-131 Hippuran; Mediphysics, Paramus, NJ) orthoiodohippurate, excretion curves, and glomerular filtration rate (GFR) was determined by creatinine clearance. Studies done prior to and on day 4 of treatment showed that GFR fell in nine of 10 patients, with a mean decrease of 43% +/- 8%, and renal plasma flow fell in five of the 10 patients with a mean decrease of 5% +/- 10%. The average pretherapy filtration fraction was calculated to be 23% +/- 1% and after 4 days of treatment, decreased to a mean value of 15 +/- 2%. The BUN to creatinine ratio also declined in all patients. These findings collectively suggest that IL-2 nephrotoxicity may result from an intrarenal defect in addition to the previously described prerenal azotemia. Additionally, radionuclide studies of renal function are a reliable and reproducible noninvasive method of assessing these changes in renal function.

Low-Dose Captopril Scintigraphy in the Evaluation of Renovascular Hypertension

This study compared the results of renal scintigraphy with simultaneous administration of Tc-99m DTPA and I-131 Hippuran (before and after 25 mg of oral captopril) with the results of the renal arteriogram and renal vein renins (before and after the administration of 25 mg of oral captopril) to evaluate the sensitivity and specificity of renal scintigraphy in the diagnosis of renovascular hypertension. The results of 21 consecutive patients suspected of having renovascular hypertension who underwent scintigraphy and renal arteriography were analyzed. Renal scintigraphy postcaptopril detected all the cases of renovascular hypertension (eight patients) plus two additional patients who had significant renovascular stenosis but no renin overproduction. The results indicate that the renal scintigram, before and after the administration of captopril, is an accurate and sensitive test for the detection of renovascular hypertension and should be used as a screening procedure before arteriography is considered.

Mechanism, Pathophysiology, Diagnosis, and Management of Renal Transplant Rejection

In recent years, there has been a steady progress in basic research (immunogenetics and cellular immunology) that helped us in understanding the mechanisms underlying allograft rejection. Several laboratory tests were developed, and the results were shown to correlate with clinical rejection. However, most of these studies have not found a place in clinical practice because of their nonspecificity, lack of sensitivity, time lag, added expense, and inconvenience. The commonly employed diagnostic tests (i.e., renal transplant ultrasound and 131I hippuran scintigram) are helpful in differentiating rejection from other causes of graft malfunction. The specific renal parenchymal disease, such as acute or chronic rejection or de novo or recurrent glomerular disease, contributing to graft malfunction can only be diagnosed by renal histopathologic study. Because hyperacute and accelerated acute rejections are irreversible and necessitate graft nephrectomy, measures should be taken to prevent this problem. High-dose corticosteroids still remain the mainstay of therapy for acute cellular rejection. In the case of steroid-resistant rejections, treatment with ALG or OKT3 appears promising. As there is no effective therapy for chronic allograft rejection, usual measures of delaying the progression of chronic renal failure should be employed, and patients should be advised to return to maintenance dialysis before they develop uremic symptoms. If current experiments demonstrating selective immunosuppression with monoclonal antibodies are found successful in human trials, one can expect further improvement in the outcome of renal transplantation.

Comparison of Tc-99m MAG3 and Tc-99m DTPA in Renal Transplant Patients with Impaired Renal Function

Tc-99m mercaptoacetyltriglycine (MAG3) is a new Tc-99m renal agent that compares favorably to I-131 Hippuran in animal models, normal volunteers, and patients. Based on the fact that Tc-99m MAG3 has a much more rapid clearance than Tc-99m DTPA and a smaller volume of distribution, it was postulated that the image quality of Tc-99m MAG3 studies should be superior to scans obtained using Tc-99m DTPA, particularly in patients with impaired renal function. To test this hypothesis, Tc-99m DTPA and MAG3 images were obtained in three transplant patients during periods of stable but impaired renal function. In one study, the Tc-99m DTPA study was potentially misleading, whereas the Tc-99m MAG3 examination assessed the clinical situation correctly. In all three cases, the Tc-99m MAG3 images were superior.

ACUTE EFFECTS OF INTRAVENOUS CYCLOSPORINE ON BLOOD PRESSURE, RENAL HEMODYNAMICS, AND URINE PROSTAGLANDIN PRODUCTION OF HEALTHY HUMANS

The acute renal failure associated with cyclosporine may result from vasoconstriction of intrarenal arterioles. To evaluate the mechanism of cyclosporine-induced nephrotoxicity, we acutely administered cyclosporine to eight healthy female volunteers with normal blood pressure and renal function. Cyclosporine (4 mg/kg) in 250 ml of 5% dextrose in water (D5W) was administered as a steady intravenous infusion over 6 hr. Glomerular filtration rate and renal plasma flow were measured by serum disappearance of 99m TcDTPA and 131I hippuran, respectively, during the last 3 hr of the infusion. D5W was given to the patients on separate days before the cyclosporine infusion to obtain control data. Systolic and diastolic blood pressure measured every hour during the infusions and renal vascular resistance were slightly higher during cyclosporine administration, but the increases were not statistically significant. Renal plasma flow was not affected by cyclosporine, being 479.6 +/- 24.9 ml/min during the control infusion and 463.3 +/- 12.7 ml/min during the cyclosporine infusion. However, glomerular filtration rate was reduced by cyclosporine in all patients (control, 108.8 +/- 2.5 ml/min, vs. cyclosporine, 91.1 +/- 2.2 ml/min, P less than .01), except one who demonstrated no significant change. Urinary excretion of thromboxane B2 during cyclosporine administration was markedly increased in all patients, being 39.9 +/- 8.2 ng/hr in the control period and 85.8 +/- 22.3 ng/hr during cyclosporine infusion (P less than .05), except for the one patient in whom no decrease in GFR was noted. There was no significant change in the urinary excretion rate for 6-keto-prostaglandin F1a or prostaglandin E during cyclosporine infusion. Serum averaged levels of peripheral renin activity, angiotensin II, and aldosterone did not change during with the cyclosporine administration compared with the control. All patients demonstrated a decrease in 24-h urinary excretion of sodium and potassium on the day of the cyclosporine infusion. Verapamil SR (240 mg daily for 7 days prior to cyclosporine infusion) did not reverse the reduction in glomerular filtration rate induced by cyclosporine; however, a significant reduction in renal vascular resistance and an increase in renal plasma flow (P less than .05) were noted when the volunteers were treated with both verapamil and cyclosporine compared with cyclosporine alone. Intravenous infusion of Cremophor EL, the vehicle to dissolve cyclosporine, demonstrated no significant effects on blood pressure, renal hemodynamics or urinary prostaglandin excretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Pretransplant assessment of renal viability by phosphorus-31 magnetic resonance spectroscopy. Clinical experience in 40 recipient patients.

A group of 40 cadaveric kidneys was studied just prior to planned transplantation to further assess the applicability of 31P-MRS in the analysis of clinical renal transplant viability. Renal intracellular high-energy phosphorus metabolites (ATP [or NADP], phosphomonoester [PME] and inorganic phosphate [Pi]) and pH were measured noninvasively with MRS surface coils external to cold storage containers. Pretransplant MRS parameters were correlated with subsequent renal function in recipient patients (measured one week postoperatively by the need of dialysis, drop in serum creatinine, urine output, and 123I or 131I Hippuran assessed renal tubular function). ATP and NADP was detected in eleven kidneys and was significantly (P less than 0.001) associated with the best renal function posttransplantation. These kidneys also had the highest PME/Pi ratios (1.66-0.54), while lower ratios (0.36-0.10) were associated with prolonged acute tubular necrosis. The PME/Pi ratios significantly (P less than 0.0001) correlated with subsequent clinical renal function, whereas cold storage times (37 +/- 10 hr) or intracellular renal pH (6.53-7.91) did not. These preliminary data suggest that MRS is a noninvasive, nondestructive and sterile method for assessing clinical viability during hypothermic storage of human cadaver kidneys and the subsequent recovery of renal function postrenal transplantation.

Estimation of ERPF in adults from plasma clearance of 131I—hippuran using a single injection and one or two blood samples

The plasma clearance of [ 131I] o-iodohippurate, which is an estimate of effective renal plasma flow, can be measured from one or two blood samples drawn after an i.v. bolus of tracer. The most widely used method is based on a single sample. Here, it is shown that the error (relative to a complete curve of six or more blood samples) can be halved by using two samples rather than one. Since the one-sample method is satisfactory for most clinical purposes, the two-sample method is recommended only when special accuracy is needed.

The significance of poor renal transplant concentrating ability as assessed by I-131 Hippuran imaging.

A pattern of very poor renal allograft concentration of I-131 Hippuran and good bladder activity has been observed by the authors. The kidneys are typically barely visualized and the renogram curve is flat. The significance of this particular finding has not been described in the literature. Accordingly, a retrospective review of all patients exhibiting this scan pattern was performed and the authors attempted to correlate it with clinical, laboratory, and pathological findings at the time of study. Of 11 patients exhibiting this scan pattern, three had very high urine outputs at the time of study. Of the remaining eight patients, five had chronic rejection. In the remaining three patients, the diagnosis was: one each, acute rejection, mixed acute and chronic rejection, and cyclosporine toxicity. The authors conclude that although this pattern is non-specific, if the patient is not in a high output state, it is usually related to chronic rejection.

Flip-flop phenomenon seen in 131I hippuran renal scintigraphy

Flip-flop phenomenon seen in 131I hippuran renal scintigraphy

Validity of renal split function by single probe renography in hypertensive patients

Single kidney function was determined both by single probe renography (131I hippuran) and gamma camera scintigraphy (99Tc111 DMSA) in the sitting position in 42 consecutive patients who were referred to renography as a part of the workup of their hypertension. the positioning of the detectors turned out to be satisfactory in 83 per cent of the patients when compared with the determination of the split function at scintigraphy. This might be explained by the small 100 per cent isocount area of the probe (avoiding the effect of mobile kidneys) and by the 4-channel localization system

Validity of Renal Split Function by Single Probe Renography in Hypertensive Patients

Single kidney function was determined both by single probe renography (131I hippuran) and gamma camera scintigraphy (99Tcm DMSA) in the sitting position in 42 consecutive patients who were referred to renography as a part of the workup of their hypertension. The positioning of the detectors turned out to be satisfactory in 83 per cent of the patients when compared with the determination of the split function at scintigraphy. This might be explained by the small 100 per cent isocount area of the probe (avoiding the effect of mobile kidneys) and by the 4-channel localization system.