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PubMed1992

Renal cortical scintigraphy in the diagnosis of acute pyelonephritis.

Comparative clinical studies have shown renal cortical scintigraphy, using technetium-99m (99mTc)-labeled glucoheptonate or dimercaptosuccinic acid (DMSA), to be significantly more sensitive than either intravenous pyelography or renal sonography in the diagnosis of acute pyelonephritis. However, due to uncertainties about the diagnostic accuracy of the clinical and laboratory parameters used in these studies, true sensitivity of renal cortical scintigraphy was unknown. Therefore, we evaluated the accuracy of [99mTc]DMSA scintigraphy in the diagnosis of experimentally induced acute pyelonephritis in piglets using strict histopathologic criteria as the standard of reference. The sensitivity and specificity of the DMSA scan for the diagnosis of acute pyelonephritis were 91% and 99%, respectively, with an overall 97% agreement between the scintigraphic and histopathologic findings. Based on the results of this experimental study, we used the [99mTc]DMSA scan as the standard of reference for the diagnosis of acute pyelonephritis, and conducted a prospective clinical study of 94 children hospitalized with the diagnosis of acute febrile urinary tract infection (UTI). The aims of this study were (1) to determine the relationship among vesicoureteral reflux, P-fimbriated Escherichia coli, acute pyelonephritis, and renal scarring, and (2) to evaluate the diagnostic reliability of the clinical and laboratory parameters commonly used in the diagnosis of acute pyelonephritis. We documented acute pyelonephritis in 62 (66%) of 94 patients. Vesicoureteral reflux was demonstrated in 29 (31%) of the total group and in only 23 (37%) of 62 patients with acute pyelonephritis. The prevalence of P-fimbriae in the E coli isolates was 64% in the patients with acute pyelonephritis and 78% in those with a normal DMSA scan. Even in patients without reflux, P-fimbriae were found in 71% of isolates from the patients with acute pyelonephritis and in 75% of those with a normal renal scan. Follow-up DMSA scans were obtained in 33 patients with acute pyelonephritis in 38 kidneys. We found complete resolution of the acute inflammatory changes in 58% of the involved kidneys and renal scarring in the remaining 42%, including 40% of the kidneys associated with reflux and 43% of those without reflux.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1992

Renal single photon emission computed tomography: should we do it?

Although single photon emission computed tomography (SPECT) imaging has established a place for itself in clinical nuclear medicine for heart and brain studies, its place in renal imaging is not yet clear. Renal SPECT has been subject to limitations imposed by the efficiency of imaging equipment, and has been confined to use with static imaging agents such as technetium-99m (99mTc) dimercaptosuccinate (DMSA). SPECT has been used to investigate space-occupying lesions and anatomical abnormalities, and for quantitative studies of renal uptake and volume. In these areas, it has provided little advantage over conventional imaging, but it has been helpful in individual cases. High-resolution SPECT is a promising new development, which may have applications in detecting and classifying renal scarring. It deserves careful evaluation.

Humans↗
PubMed1982

Renal radiopharmaceuticals--an update.

Noninvasive radionuclide procedures in the evaluation of renal disease have been accepted increasingly as effective and valuable alternatives to older clinical methods. The development of suitable radiopharmaceuticals labeled with high photon intensity radionuclides and with 99mTc in particular has stimulated this modality during the last few years. Currently several nearly ideal agents are available for anatomical and functional studies of kidney imparting very low absorbed radiation doses. These include 99mTc-GHA and 99mTc-DMSA for renal morphology and differential function evaluation, 99mTc-DTPA for GFR and 123I orthoiodohippurate for ERPF measurements. A suitable agent as a replacement for the latter labeled with 99mTc is actively being sought. Computer-assisted processing of dynamic renal function studies enables the observer to obtain a wealth of information related to the renal extraction, uptake, parenchymal transit and pelvic transit parameters of the agent administered into the bloodstream. Each of these parameters either globally or differentially contributes to a detailed evaluation of renal disease states. Several of these procedures have been validated against classical techniques clinically but more detailed information is being sought with the recently introduced radiopharmaceuticals. With the detailed validation and increasing recognition of the clinical utility of several of the radionuclidic procedures at many centers, it is hoped that radionuclide assessment of renal disorders ultimately will be made available routinely at all medical facilities.

Carbon Radioisotopes↗
PubMed1982

Nuclear renal imaging in acute pyelonephritis.

Patients with acute pyelonephritis may present with a spectrum of clinical signs and symptoms. There are few noninvasive diagnostic studies, however, to confirm or exclude this diagnosis. A small number of patients, generally those with severe disease, will demonstrate radiographic changes on excretory urography, but the lack of sensitivity of the IVP in early, acute pyelonephritis is well documented. Several radionuclide techniques have been proposed to assist in the earlier detection of this clinical problem including imaging with Mercury-197 chlormerodrin, Gallium-67 citrate, Technetium-99m glucoheptonate. Technetium-99m DMSA, and, more recently, Indium-111 labeled white blood cells. The success of the renal cortical imaging agents as well as those which localize in infection are described in this report. There appears to be a complimentary role or the cortical imaging agents and the radiopharmaceuticals which localize in bacterial infection. Cortical agents offer the advantage of specific assessment of functioning renal tissue and a convenient, rapid method for following the response to treatment in a noninvasive manner. A pattern is described which may be diagnostic; correlation with Gallium-67 citrate of Indium-111 WBCs may increase the probability of infection as the cause for the cortical abnormality. The measurement of differential renal function using cortical agents provides additional information to assist the clinician in predicting the late effects of infection. Improved sensitivity and specificity, and a reproducible method for following the response to therapy in patients with acute pyelonephritis are the advantages of the techniques described.

Acute Disease↗
PubMed1982

Radionuclides in the evaluation of urinary obstruction.

Radionuclide renography and renal scanning techniques are ideally suited to the initial and follow-up evaluation of patients with obstructive uropathy. While other modalities are superior in their ability to provide anatomic information, the radionuclide study yields functional information for each kidney without the necessity to resort to invasive studies. In addition, the Nuclear Medicine study is well suited to the evaluation of obstruction where serial studies often are required because of a lower radiation burden compared to urography. This lower radiation dose is especially important in obstruction because of the recurrent nature of several kinds of obstructive uropathy and because of the high incidence in the pediatric age group. The ability to control urine flow rate during the procedure through dehydration or administration of diuretics is an additional benefit. Increasing availability of computerization of nuclear medicine procedures as well as interest in studies employing physiologic intervention (including the diuresis renogram) have assured an important place for radionuclide studies in the evaluation of patients with urinary obstruction.

Adult↗
PubMed1982

Nuclear medicine in acute and chronic renal failure.

The diagnostic value of renal scintiscans in patients with acute or chronic renal failure has not been emphasized other than for the estimation of renal size. 131I OIH, 67gallium, 99mTcDTPA, glucoheptonate and DMSA all may be valuable in a variety of specific settings. Acute renal failure due to acute tubular necrosis, hepatorenal syndrome, acute interstitial nephritis, cortical necrosis, renal artery embolism, or acute pyelonephritis may be recognized. Data useful in the diagnosis and management of the patient with obstructive or reflux nephropathy may be obtained. Radionuclide studies in patients with chronic renal failure may help make apparent such causes as renal artery stenosis, chronic pyelonephritis or lymphomatous kidney infiltration. Future correlation of scanning results with renal pathology promises to further expand nuclear medicine's utility in the noninvasive diagnosis of renal disease.

Acute Kidney Injury↗
PubMed1983

Renal trauma.

Renal injuries are classified as minor, major, and critical/catastrophic for purposes of management. The radionuclide renal scintigram is a safe, simple, and extremely sensitive means of establishing the presence of an injury and monitoring kidney function during conservative management, which is utilized in the vast majority of cases. The information that may be obtained from radionuclide imaging is the state of overall and regional blood transit, overall and regional parenchymal function, and urinary extravasation.

Adolescent↗
PubMed2003

Interaction of dimercaptosuccinic acid (DMSA) with angiotensin II on calcium mobilization in vascular smooth muscle cells.

Dimercaptosuccinic acid (DMSA) was shown to lower blood pressure in rat models of arterial hypertension. Thus, there is evidence that-besides its chelating properties-DMSA has a direct vascular effect, e.g. through scavenging of reactive oxygen species (ROS). We speculated that, in addition, intracellular calcium mobilization may be involved in this action. Therefore, the present study examined the effects of DMSA on Ca(2+) mobilization in cultured vascular smooth muscle cells (VSMCs) from rat aorta. Intracellular free Ca(2+) concentration ([Ca(2+)](i)) was measured with fura-2 AM. In a first series of experiments DMSA, 10(-11) to 10(-6)M, induced an immediate dose-dependent up to 4-fold rise of [Ca(2+)](i) (P<0.001) which was almost completely blunted by the calcium channel blocker verapamil or the intracellular calcium release blocker TMB-8. In a second series of experiments, when VSMCs were exposed acutely to DMSA (10(-11) to 10(-6)M), the angiotensin (ANG) II (10(-8)M)-induced rise in [Ca(2+)](i) to 295+/-40nM was attenuated at the average by 49% independent of the dose of DMSA. Preincubation of VSMCs with DMSA (10(-6)M) for 60min reduced basal [Ca(2+)](i) by 77% (P<0.001) and dose-dependently attenuated the ANG II (10(-8)M)-induced rise in [Ca(2+)](i) between 28 and 69% at concentrations between 10(-9) and 10(-5)M DMSA, respectively (P<0.05 and <0.01). In the presence of TMB-8, which attenuated the ANG II (10(-8)M)-induced rise in [Ca(2+)](i) by 66%, DMSA (10(-6)M) had no additional suppressive effect on [Ca(2+)](i). The results suggest that DMSA acutely raises [Ca(2+)](i) by stimulating transmembrane calcium influx via L-type calcium channels and by calcium release from intracellular stores followed by a decrease in [Ca(2+)](i) probably due to cellular calcium depletion. Thus, in addition to its action as scavenger of ROS, which in part mediate the vasoconstrictor response, e.g. to ANG II, DMSA may exert its hypotensive effect through decreasing total cell calcium, thereby attenuating the vasoconstrictor-induced rise in [Ca(2+)](i) in VSMCs.

Angiotensin II↗
PubMed2003

Beneficial effect of combined administration of some naturally occurring antioxidants (vitamins) and thiol chelators in the treatment of chronic lead intoxication.

Ameliorative effects of few naturally occurring antioxidants like ascorbic acid (vitamin C), alpha-tocopherol (vitamin E) either alone or in combination with meso-2,3-dimercaptosuccinic acid (DMSA) or monoisoamyl DMSA (MiADMSA), on parameters indicative of oxidative stress in the liver, kidney, brain and blood of lead-exposed rats were studied. Male Wistar rats were exposed to 0.1% lead acetate in drinking water for 3 months and treated thereafter with DMSA or its analogue MiADMSA (50 mg/kg, intraperitoneally), either individually or in combination with vitamin E (5 mg/kg, intramuscularly) or vitamin C (25 mg/kg, orally) once daily for 5 days. The effects of these treatments in influencing the lead-induced alterations in haem synthesis pathway, hepatic, renal and brain oxidative stress and lead concentration from the soft tissues were investigated. Exposure to lead produced a significant inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity from 8.44+/-0.26 in control animals to 1.76+/-0.32 in lead control, reduction in glutathione (GSH) from 3.56+/-0.14 to 2.57+/-0.25 and an increase in zinc protoporphyrin level from 62.0+/-3.9 to 170+/-10.7 in blood, suggesting altered haem synthesis pathway. Both the thiol chelators and the two vitamins were able to increase blood ALAD activity towards normal, however, GSH level responded favorably only to the two thiol chelators. The most prominent effect on blood ALAD activity was, however, observed when MiADMSA was co-administered with vitamin C (7.51+/-0.17). Lead exposure produced a significant depletion of hepatic GSH from 4.59+/-0.78 in control animals to 2.27+/-0.47 in lead controls and catalase activity from 100+/-3.4 to 22.1+/-0.25, while oxidized glutathione (GSSG; 0.34+/-0.05 to 2.05+/-0.25), thiobarbituric acid reactive substance (TBARS; 1.70+/-0.45 to 5.22+/-0.50) and glutathione peroxidase (GPx) levels (3.41+/-0.09 to 6.17+/-0.65) increased significantly, pointing to hepatic oxidative stress. Altered, reduced and oxidized GSH levels showed significant recovery after MiADMSA and DMSA administration while, vitamins E and C were effective in reducing GSSG and TBARS levels and increasing catalase activity. Administration of MiADMSA alone and the combined administration of vitamin C along with DMSA and MiADMSA were most effective in increasing hepatic GSH levels to 4.88+/-0.14, 4.09+/-0.12 and 4.30+/-0.06, respectively. Hepatic catalase also reached near normal level in animals co-administered vitamin C with DMSA or MiADMSA (82.5+/-4.5 and 84.2+/-3.5, respectively). Combined treatments with vitamins and the thiol chelators were also able to effectively reduce lead-induced decrease in renal catalase activity and increase in TBARS and GPx level. Combination therapy, however, was unable to provide an effective reversal in the altered parameters indicative of oxidative stress in different brain regions, except in catalase activity. The result also suggests a beneficial role of vitamin E when administered along with the thiol chelators (particularly with MiADMSA) in reducing body lead burden. Blood lead concentration was reduced from 13.3+/-0.11 in lead control to 0.3+/-0.01 in MiADMSA plus vitamin E-treated rats. Liver and kidney lead concentration also showed a most prominent decrease in MiADMSA plus vitamin E co-administered rats (5.29+/-0.16 to 0.63+/-0.02 and 14.1+/-0.21 to 1.51+/-0.13 in liver and kidney, respectively). These results thus suggest that vitamin C administration during chelation with DMSA/MiADMSA was significantly beneficial in reducing oxidative stress however, it had little or no additive effect on the depletion of lead compared with the effect of chelators alone. Thus, the co-administration of vitamin E during chelation treatment with DMSA or MiADMSA could be recommended for achieving optimum effects of chelation therapy.

Animals↗
PubMed1989

Intramuscular administration of iron during long-term chelation therapy with 2,3-dimercaptosuccinic acid in a man with severe lead poisoning.

2,3-Dimercaptosuccinic acid (DMSA) an investigational chelant structurally similar to dimercaptopropanol (BAL), offers the advantage of not depleting iron stores on which basis it would not seem to form a toxic chelate with iron. We report the case of a man with a formidable body burden of lead (Pb) and depleted iron stores who was given iron intramuscularly during a defined period of long-term retreatment with DMSA. Initiation of retreatment with DMSA, 30 mg/kg/day given orally in three divided doses for the first 7 days markedly enhanced Pb diuresis, entailed a pronounced fall in blood Pb and abolished symptoms of Pb poisoning. Continuation of retreatment with two-thirds the initial DMSA dose for an added 15 days maintained blood Pb at sustained low levels. Iron sorbitol administered intramuscularly during this period in individual doses of 100 mg of elemental iron given 3 days apart to a conservative total of 400 mg produced no untoward effects, suggesting that a toxic chelate between iron and DMSA was not formed. Serum ferritin entered the normal range and there was virtually an immediate significant decrease in erythrocyte protoporphyrin. Together with discernible increases in haemoglobin, haematocrit and MCV, this pointed to enhanced iron utilization. Since iron utilization is curtailed by high concentrations of Pb, the immediacy and magnitude of the post-chelation rebound in blood Pb precluded iron administration at any other stage. From these data, DMSA emerges as a uniquely versatile new chelant. Suitable for long-term administration, it permits the simultaneous parenteral administration of iron during dose-related sustained decreases in blood Pb.

Adult↗
PubMed1993

Can ultrasound reliably detect renal scarring in children with urinary tract infection?

One hundred children with a proven urinary tract infection were studied prospectively using both ultrasound (US) and 99mTc dimercaptosuccinic acid (DMSA) scintigraphy to assess the efficacy of US in the detection of renal scarring. Sixty-nine girls and 31 boys with an age range of 0.5-11.8 years were studied. DMSA scintigraphy detected 19 scarred kidneys in 17 children. Scarring was classified as mild, moderate or gross. US detected a total of seven of the scarred kidneys (sensitivity 37%). US detected 0/6 kidneys with mild scarring, 1/7 kidneys with moderate scarring and 6/6 kidneys with gross scarring. Four kidneys with scarring on DMSA showed abnormalities other than scarring on US. 8/19 scarred kidneys were thought to be normal on US. It is important to detect renal scarring in young children and US cannot be relied upon for this purpose. It should therefore be supplemented with DMSA scintigraphy.

Child↗
PubMed1994

Does routine ultrasound have a role in the investigation of children with urinary tract infection?

The results of investigations in children with urinary tract infection (UTI) were studied in a district general hospital in order to assess the relative value of the two most widely used screening tests, namely ultrasound (US) and 99mTc dimercaptosuccinic acid (DMSA) scintigraphy. A total of 193 children had undergone both US and DMSA scintigraphy as part of an investigation of proven single or multiple urinary tract infections over a 27 month period. DMSA scintigraphy revealed abnormalities in 22 of the children (11%). The abnormalities ranged from cortical defects to congenital anatomical abnormalities. US revealed abnormalities in six children (3%) but did not contribute any additional information in any. In our institution, the DMSA scintigram alone would have been an adequate screening test for children with UTI. Hydronephrosis is a common abnormality detected by US. Although none were seen in the study group, several children were examined during the study period with dilated collecting systems detected at ante-natal US. No cases of hydronephrosis presented as UTI. We question whether the use of routine US is justifiable in the investigation of children with UTI, and discuss whether a more selective investigation protocol should be adopted.

Adolescent↗
PubMed1994

Isotope renography in childhood enuresis.

A retrospective review was performed of 100 enuretic children who underwent isotope renography during the period 1981-1989. Studies performed were Tc99mDMSA studies for renal size and to detect renal scarring and renography using Tc99mDTPA or MAG3 to evaluate excretion and detect vesicoureteric reflux. Fifty-five children had microbiological evidence of urinary tract infection (UTI), and 16 (29%) of these had abnormalities on their isotope studies. Forty-five had sterile urine and all had normal isotope studies. Thus despite recent reports of urodynamic abnormalities and increased incidence of reflux in patients with enuresis, our findings indicate that standard nuclear medicine renal studies show few abnormalities in patients with monosymptomatic enuresis. The 29% incidence of abnormal studies in patients with enuresis and UTIs suggests that the presence of infection should be an indication for further investigation in this subgroup of enuretic children.

Adolescent↗
PubMed1988

The investigation of painless haematuria--a comparison of intravenous urography and DMSA scintigraphy.

In order to test in a prospective study the suggestion that there should be a shift from the intravenous urogram to DMSA scintigraphy for the diagnosis of suspected renal masses, both investigations were performed in 63 patients with painless haematuria. While the sensitivity of both investigations was similar in renal lesions, specificity was slightly less for scintigraphy. These findings, together with the intrinsic limitations of the DMSA scintigram in detecting lesions elsewhere in the urinary tract, lead us to conclude that the intravenous urogram should remain the initial investigation for painless haematuria unless there are specific contraindications.

Hematuria↗
PubMed1998

Improved ultrasound detection of renal scarring in children following urinary tract infection.

A system for defining renal scarring on ultrasound is proposed and compared with DMSA scintigraphy. Renal scarring was assessed with ultrasound in children following urinary tract infection (UTI) using the following criteria: (1) proximity of sinus echoes to cortical surface; (2) loss of pyramids; (3) irregularity of outline; (4) loss of definition of capsular echo; and (5) calyceal dilatation. Three hundred and thirty-nine consecutive ultrasound scans (US) and DMSA scintigrams, comprising 648 kidneys, were performed and reported blindly and the results were compared. Using DMSA scintigraphy as the gold standard, ultrasound had a positive predictive value of 93% and a negative predictive value of 95%. Ultrasound disagreed with DMSA scintigraphy in 5.2% of kidneys. On review of the cases of disagreement where arbitration was possible by comparison with other imaging, ultrasound was incorrect in 10 kidneys and DMSA was incorrect in 13. We conclude that the sensitivity in the ultrasound detection of renal scarring can be greatly improved using this method. If no scars were detected at ultrasound an alternative explanation for an abnormal DMSA scintigram should be sought.

Adolescent↗
PubMed2004

2,3-Dimercaptopropanol, 2,3-dimercaptopropane-1-sulfonic acid, and meso-2,3-dimercaptosuccinic acid inhibit delta-aminolevulinate dehydratase from human erythrocytes in vitro.

The effects of dithiol chelating agents meso-2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane-1-sulfonic acid (DMPS), and 2,3-dimercaptopropanol (BAL) on delta-aminolevulinate dehydratase (delta-ALA-D) from human erythrocytes were evaluated. Furthermore, possible protective effects of zinc chloride (ZnCl(2)), dithiothreitol (DTT), and cysteine were studied. delta-ALA-D activity from human erythrocytes was inhibited by dithiol chelating agents in a concentration-dependent manner. Cysteine, at all concentrations tested, did not protect the inhibitory effect of 1 and 4 mM DMPS and DMSA, but protected 1 mM BAL inhibition. Dithiotreitol was able to protect the inhibition caused by 1 mM BAL (28%), DMPS (56%), and DMSA (40%) in a concentration-dependent manner. Zinc chloride protected and restored 1 mM BAL inhibitory effect on delta-ALA-D. Zinc chloride at 500 microM and 1 mM, respectively, protected inhibitory effects of DMPS and DMSA (1 and 4 mM), but did not reverse its effects. The preincubation of dithiol chelating agents with enzyme demonstrated that DMSA was the most potent delta-ALA-D inhibitor of human erythrocytes. These data are in agreement with delta-ALA-D activity from purified enzyme. ZnCl(2) (1 microM) added, in the reaction mixture, increased enzyme activity and DTT (100 microM) totally restored the enzyme activity for all chelating agents tested.

Chelating Agents↗