The DMSA scan and intravenous urography in the detection of renal scarring.
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Child, Preschool↗
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Update on dimercaptosuccinic acid renal scanning in children with urinary tract infection.
The dimercaptosuccinic acid (DMSA) renal scan is a method for assessing kidney function. Indications for DMSA scanning in children with urinary tract infection (UTI), as well as timing, have changed. Pitfalls in interpreting DMSA scans include: (1) acute pyelonephritis (APN), (2) tubular dysfunction, (3) hypertension, (4) use of captopril in patients with renovascular hypertension and (5) duplex kidneys. Interpretation of DMSA scans in children with UTI vary according to timing and clinical setting. During the course of a febrile UTI a DMSA scan may reveal a normal kidney, APN or a non-functioning, small and/or ectopic kidney. In the absence of UTI (up to 6 months) in children with vesicoureteric reflux a DMSA scan may indicate a normal kidney, renal scarring (reflux nephropathy), occult duplex kidney and allows the progression of scarring and hypertrophy of normal areas of the kidney to be followed anatomically. The DMSA renal scan in now the most reliable test for the diagnosis of APN. The transient abnormalities due to APN can occur in normal or scarred kidneys. Lesions due to reflux nephropathy (defined as a defect in the renal outline or contraction of the whole kidney) are permanent. Intravenous urography reveals renal abnormalities later than the DMSA scan. If abnormalities are seen on a DMSA scan performed during the course of APN it is impossible to predict the outcome: they can progress to permanent scarring or heal completely. An abnormal DMSA scan during a febrile UTI allows the identification of children at risk of developing renal scars. These children should be carefully investigated, maintained on long-term quimioprophylaxis and followed.
Acute Disease↗
99mTechnetium dimercaptosuccinic acid scintigraphy in the diagnosis of acute pyelonephritis in rats.
The use of 99mtechnetium dimercaptosuccinic acid (99mTc-DMSA) scintigraphy for the early diagnosis of pyelonephritis has been evaluated in a study performed on adolescent female Sprague-Dawley rats exposed to an ascending Escherichia coli infection. The rats were studied with DMSA scintigraphy either before and 5 days after the infection or 5 and 28 days after the infection. One group of rats received anti-microbial treatment during days 6-11. After the last DMSA scintigraphy the rats were sacrificed and the kidneys prepared for light microscopy study. Kidney morphology was normal and DMSA uptake was high and homogeneous in all control rats. The majority of the rats exposed to E. coli developed inflammatory changes, on light microscopy which extended to various degrees in the renal parenchyma. Five days after the infection the DMSA uptake was consistently reduced, if the inflammatory lesion on light microscopy involved more than 15% of the renal cortex. Twenty-eight days after infection the inflammatory changes were less extensive than at 5 days. The DMSA uptake had usually improved. At this time, however, areas of decreased DMSA uptake could be detected even if the light microscopy changes involved less than 15% of the parenchyma. Microscopical lesions were less frequent and less extensive in the treated than in the untreated rats. The complete return to normal of previously abnormal DMSA uptake was only observed in treated rats. In a few untreated rats cortical scars had formed by day 28. The scars appeared in areas with decreased DMSA uptake at 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Functional parameters and 99mtechnetium-dimercaptosuccinic acid scan in acute pyelonephritis.
The diagnostic value of 99mtechnetium-dimercaptosuccinic acid (DMSA) scintigraphy, ultrasonography and renal functional parameters [urine N-acetyl-beta-D-glucosaminidase (NAG)/creatinine and urine albumin/creatinine quotients] in acute pyelonephritis (APN) were studied in 39 children (28 girls, 11 boys, median age 9 months, range 2 weeks to 9.4 years, 28 patients < 1 year, 11 patients > 1 year) with first-time urinary tract infection. Ultrasonography of the urinary tract was performed on admission and together with DMSA scintigraphy (< 10 days from admission). Urine NAG/creatinine and urine albumin/creatinine quotients were measured daily and after 6-8 weeks. Ultrasonography revealed abnormalities in 12 of 39 (31%) patients [11/32 patients (34%) with positive DMSA scintigraphy], while DMSA uptake defects were present in 32 of 39 (82%) patients [21/28 < 1 year (75%), 11/11 > 1 year (100%), P = 0.08]. Urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in children < 1 year with APN, as well as in non-renal fever controls, than in older children. However, in both age groups the urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in APN than in non-renal fever. The urine NAG and albumin excretion decreased rapidly after the initiation of antimicrobial therapy and had normalized at 6-8 weeks. The size and grade of the DMSA uptake defect (DMSA score) did not correlate with duration of disease at admission, maximum C-reactive protein or maximum fever. The urine NAG/creatinine quotient in the children < 1 year showed, however, a significant correlation with the DMSA score (r = 0.58, P < 0.05), while no correlation was found in the older children. We conclude that DMSA scintigraphy is a sensitive method to confirm the clinical diagnosis of APN, although a substantial number of infants appear to have normal scans. Early determination of the urine NAG/creatinine and albumin/ creatinine quotients may further improve the diagnostics in the infant.
Acetylglucosaminidase↗
99mTechnetium-dimercaptosuccinic acid scan in the diagnosis of acute pyelonephritis in children: relation to clinical and radiological findings.
Seventy-two children, 59 girls and 13 boys, 0.1-15.9 (median 1.1) years of age, with acute pyelonephritis (APN) were investigated with the aid of a dimercaptosuccinic acid (DMSA) scan, renal ultrasonography (US) and a desmopressin test within 5 days of admission. Sixty-two children were reinvestigated approximately 2 months later when intravenous urography (IVU) and micturition cysto-urethrography were also performed. During infection, 92% of the children showed changes in the DMSA scan with 69% by US, and the two investigations agreed in 58% of the kidneys. At follow-up, 68% showed changes in the DMSA scan, 47% by US and 48% by IVU. The DMSA scan and IVU agreed in 60% of the kidneys. Twenty-nine percent of the children had vesico-ureteric reflux (VUR). The presence of grade greater than or equal to 3 VUR was associated with greater defects on the DMSA scan during infection, and at follow-up with a higher frequency of persistent changes compared with no VUR (P less than 0.02 and 0.01, respectively). During infection the size of the defect on the DMSA scan correlated with renal volume and C-reactive protein and inversely with the glomerular filtration rate, and at follow-up it correlated inversely with the renal concentration capacity. The DMSA scan is a sensitive method for diagnosing and localizing APN in children, and findings on DMSA scan show a weak but significant correlation with routine clinical and radiological parameters. It is suggested that persistent renal damage after APN in children without VUR may be more common than previously assumed.
Acute Disease↗
Clinical quiz. Tuberous sclerosis.
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Diagnosis, Differential↗
Lower urinary tract function after exstrophy closure.
Twenty-eight children with bladder exstrophy, prior to surgery for continence, underwent a urodynamic evaluation, cystogram, ultrasound and dimercaptosuccinic acid scan, to define parameters of lower urinary tract function that are a risk for upper tract damage and/or impair development of bladder capacity. The bladders in 7 of 28 demonstrated no storage function [leak pressure)LP) = 0]; but storage parameters could be measured in the other 21. Their LP was 10-35 cm H2O; 17 of 21 revealed involuntary contractions and 7 of 21 had an end-fill pressure greater than 10 cm H2O. Bladder capacity was better in those with a higher LP and those with no involuntary contractions. The 4 patients with bilateral hydronephrosis (3 of whom also had bilateral multiple scars) were among the 6 with LP greater than 30 cm H2O. Of the 7 with an end-fill pressure greater than 10 cm H2O, 5 had upper tract damage. Involuntary contractions may impair development of capacity. A LP of greater than 30 cm H2O is a risk factor for upper tract damage and an end-fill pressure greater than 10 cm H2O may also be a factor.
Bladder Exstrophy↗
In vitro oxidative inactivation of glutathione S-transferase from a freeze tolerant reptile.
We have previously reported that when garter snakes. Thamnophis sirtalis parietalis, a freeze tolerant species, were exposed to 5 h freezing at -2.5 degrees C organs showed increases in the activities of anti-oxidant enzymes, especially catalase in skeletal muscle. This was interpreted to be an adaptation to deal with the potentially injurious postischemic situation of thawing. The present work analyzes in vitro oxidative inactivation of a possible target of postischemic-induced free radical damage, the secondary anti-oxidant defense glutathione-S transferase, and the protective role of endogenous catalase. Approximately 50% of GST activity from snake muscle homogenates was lost within 2 min after addition of H2O2 plus Fe(II) (0.4-2 mM) in media containing azide whereas addition of iron alone resulted in no damaging effects. The opposing effects of dimethyl sulfoxide and EDTA in modifying this process strongly suggested the involvement of .OH radicals in the GST inactivation. A partial recovery of the activity was promoted by mercaptoethanol, indicating that sulphydryl groups oxidation participate in the mechanism of GST inactivation. Pre-incubation of the reaction media containing H2O2 caused protection of the GST activity only in the absence of azide, indicating that endogenous catalase modulates the extent of oxyradical damage. The protective pre-incubation effect was more efficacious when employing homogenates from lung and liver, organs that have higher catalase activities, as well as homogenates from freezing-exposed muscle (that show an 80% increase in catalase activity, compared with control). The protection against GST inactivation observed in muscle from frozen snakes demonstrates that increased anti-oxidant defenses during freezing exposure can be a key factor in controlling in vitro oxyradical damage. The implications for natural freeze tolerance are discussed.
Adaptation, Physiological↗
Methods for measuring the renal uptake rate of 99mTc-dimercaptosuccinic acid (DMSA): a comparative study.
A comparative study of the renal uptake rate of 99mTc-dimercaptosuccinic acid (DMSA) was performed using a phantom study and clinical data from 100 patients (200 kidneys) with a variety of renal diseases. The measurement methods for renal uptake rate studied here include a posterior-view method, a conjugate-view method, and a method using single photon emission computed tomography (SPECT). The renal uptake rates obtained by the posterior-view method significantly (P less than 0.001) depended on kidney depth correction. With the SPECT method, the cut-off level for delineating the kidney was changed according to the background count ratio using the results of the phantom study. The renal uptake rates obtained by the SPECT method correlated significantly (P less than 0.001) with those obtained by other methods, and there were no significant differences as compared with those obtained by the conjugate-view method. An analysis of error with the above methods indicated that the error relating to the sensitivity to body thickness was smallest for the SPECT method and greatest for the posterior-view method. In terms of measurement of renal uptake rate only, the conjugate-view method is considered the most useful because it needs no kidney depth correction and requires very little additional effort or examination time.
Female↗
N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA) increases polonium-210 excretion.
Polonium-210 is one of the most hazardous radionuclides. As recently as 1988, there have been concerns regarding accidental exposures of humans to it. Yet, there have been no studies on the effectiveness of the newer dithiol chelating agents in increasing the excretion of this radioactive heavy metal. In order to accomplish this, a safe and effective method for determining the radioactivity of polonium-210, an alpha emitter, in the feces was developed. The excretion of polonium-210 was studied by giving male Sprague-Dawley rats 210Po (3.33 x 10(7) cpm/kg, intraperitoneal); 1 h later they were given either 5% sodium bicarbonate, N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA) or meso-dimercaptosuccinic acid (DMSA) (0.20 mmol/kg, subcutaneous). Treatment was repeated daily for 12 days. DMPA and DMSA increased the urinary excretion of 210Po, as compared to control animals, 8-fold and 5-fold, respectively. DMPA increased the fecal excretion of 210Po compared to the other treatments and also decreased the level of 210Po in the spleen, a radiosensitive organ. DMPA (0.20 mmol/kg, intravenous) increased biliary levels of 210Po 5-fold compared to controls. The results indicate that DMPA has greater specificity in chelating and increasing the excretion of 210Po than DMSA.
Animals↗
In vitro and in vivo studies with pentavalent technetium-99m dimercaptosuccinic acid.
The purpose of this investigation was to characterise the in vivo chemistry and binding mechanisms of technetium-99m dimercaptosuccinic acid [99mTc(V)DMSA]. Biodistribution was studied in mice by frozen section whole-body autoradiography and microautoradiography in selected tissues. Binding to bone mineral analogues was studied in vitro using various forms of calcium phosphate and hydroxyapatite under varied conditions. Similar studies with 99mTc-hydroxymethylene diphosphonate (HDP) were also carried out for comparison. The in vivo stability of 99mTc(V)DMSA was monitored by high-performance liquid chromatographic analysis of blood and urine samples taken over 24 h from patients injected with the tracer. Whole-body autoradiography shows that 99mTc(V)DMSA has highest affinity for bone (cortical rather than medullary) in mice. Substantial uptake of the tracer was also observed in the kidney (cytoplasm of cortical renal tubular cells). No specific localisation was observed in the liver at either the microscopic or the macroscopic level. While 99mTc-HDP bound strongly to calcium phosphates under all conditions, 99mTc(V)DMSA binding was inhibited in the presence of phosphate and was stronger at pH 6.0 than at pH 7. 4. In non-phosphate buffers, however, the binding of 99mTc(V)DMSA remained high across the pH range 4-7.4. 99mTc(V)DMSA binds to calcium phosphates chemically unaltered, and no radioactive species other than the three isomers of 99mTc(V)DMSA were detected in blood or urine samples taken from patients up to 24 h after injection. 99mTc(V)DMSA is stable in vivo, and no conversion of the complex to other chemical species needs to be invoked to explain its uptake in bone metastases or soft tissue tumour. Bone affinity may be due to reversible binding of the unaltered complex to the mineral phase of bone.
Animals↗
Comparison of 99mTc(V)-DMSA, 201Tl and 99mTc-MIBI imaging in the follow-up of patients with medullary carcinoma of the thyroid.
Radionuclide scanning with tumour-seeking agents such as pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA], thallium-201 and technetium-99m sestamibi (MIBI) has been reported to be useful in the detection of medullary thyroid carcinoma (MTC). We undertook a study in 14 MTC patients to determine the comparative imaging potential of 201Tl, MIBI and 99mTc(V)-DMSA in the detection of recurrent or metastatic MTC. All patients underwent total thyroidectomy and had persistently elevated serum calcitonin levels after the surgery. Scintigraphic studies were carried out 20 min after the injection of 111 MBq of 201Tl or 555 MBq of MIBI and 2 h following the injection of 370 MBq of 99mTc(V)-DMSA. All scintigraphic findings were correlated with contemporaneous CT or MRI studies. CT, MRI and bone scans showed 42 (26 bone, 16 soft tissue) metastatic sites in 11 of the 14 patients. In the remaining three patients no lesions were detected during diagnostic evaluation. 99mTc(V)-DMSA showed all of the soft tissue metastases but could not show two bone lesions. On the other hand, MIBI imaging was false-negative in 22 (52%) sites and 201Tl was false-negative in 34 (80%) sites. Overall, lesion detection sensitivities for 99mTc(V)-DMSA, MIBI and 201Tl were 95%, 47% and 19% respectively. We conclude that 99mTc(V)-DMSA is clearly superior to MIBI and 201Tl in the follow-up of MTC patients.
Adult↗
A practical approach to evaluating urinary tract infection in children.
All children with urinary tract infections should be investigated by either excretory urography or abdominal X-ray, ultrasonography and technetium 99m - dimercaptosuccinic acid scintigraphy. Patients in the following categories should also have micturating (voiding) cystourethrography to diagnose or exclude vesico-ureteral reflux: infants aged less than 1 year, children with recurrent (second or subsequent) infections, children with clinically diagnosed acute pyelonephritis and those with a family history of reflux or chronic pyelonephritis. Cystography can safely be omitted in children over 1 year of age with unscarred kidneys and none of the additional risk factors listed. They should be followed for 1-2 years following the first infection for evidence of recurrence.
Child↗
Renal uptake of dimercaptosuccinic acid and glomerular filtration rate in chronic nephropathy at angiotensin converting enzyme inhibition.
Glomerular filtration rate (GFR) and renal uptake of dimercaptosuccinic acid (DMSA) were measured in 31 patients with progressive chronic nephropathy before and immediately after the start of treatment with angiotensin converting enzyme (ACE) inhibitor in order to control adverse effects on kidney function. Scintigrams of the kidneys showed an unaltered distribution of DMSA during treatment. GFR estimated by 51Cr-EDTA plasma clearance fell by 14% (P less than 0.01), but renal uptake of 99mTc-DMSA increased by 10% (P less than 0.01). It is concluded that DMSA in chronic renal failure is mainly taken up by the tubular cells from the peritubular capillaries since the uptake was unaffected by the acute decrease in GFR.
Adult↗
Regulation of human globin gene expression in mouse erythroleukemia x human fibroblast hybrid cells.
A somatic cell hybrid, XX-8, was obtained from a fusion of tetraploid mouse erythroleukemia cells with human Lesch-Nyhan skin fibroblasts. This hybrid cell was previously shown (1) to produce human beta- but no human gamma-globin mRNA sequences after induction with dimethylsulfoxide. In this study we show that: (a) human beta- and gamma-globin genes are present in XX-8 cells in approximately equal numbers; (b) no human gamma-globin mRNA sequences can be detected in either the cytoplasmic or nuclear RNA fractions even with several different inducers; (c) after induction the human beta-globin gene is converted from a DNase I insensitive or closed structure to a DNase I open configuration, while the human gamma-globin gene remains closed; and (d) no human beta-globin polypeptide can be detected in the intact induced cells, indicating that fibroblast globin genes, even when induced to make mRNA in an erythroid environment, do not synthesize an RNA that is translated efficiently.
Acetamides↗
A kinetic model for 99mTc-DMSA in the rat.
A pharmacokinetic model was developed for the renal imaging agent 99mTc-DMSA in anesthetized rats, which incorporated data from serial measurements of blood and urine simultaneously with dynamic images obtained over an 8-h period. Animals which received a 10 mg/kg dose of unlabeled DMSA immediately before 99mTc-DMSA injection had a significantly reduced kidney accumulation and greater urinary elimination of 99mTc than animals which received the radiopharmaceutical alone. The kidney clearance was also significantly lower in rats receiving unlabeled DMSA, but no significant difference was determined between the urine clearance estimates of the two animal groups. Because the increase in the amount eliminated in the urine was not coupled with a significant change in urine clearance, it would appear that unlabeled DMSA saturated the kidney uptake mechanism(s) of 99mTc-DMSA without modifying the urinary clearance process. This interpretation is consistent with the hypothesis that renal handling of 99mTc-DMSA is governed by both glomerular filtration and peritubular capillary uptake. The simultaneous acquisition of blood, urine and non invasive image data allows for a comprehensive and informative model of the physiological disposition of 99mTc-DMSA.
Animals↗
Chelation in metal intoxication XXI: Chelation in lead intoxication during vitamin B complex deficiency.
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Aminolevulinic Acid↗