The evaluation of acute pyelonephritis and renal scarring with technetium 99m-dimercaptosuccinic acid renal scintigraphy: evolving concepts and future directions

Technetium 99m-dimercaptosuccinic acid (DMSA) scintigraphy has emerged as the imaging agent of choice for the detection and evaluation of acute pyelonephritis and renal cortical scarring in children. Consequently, DMSA scintigraphy provides a unique opportunity to study the progression of renal damage and functional loss from the initial insult of acute pyelonephritis to the subsequent development of irreversible renal scarring. Over the last few years, clinical and experimental investigations using DMSA renal scintigraphy have provided new insights into the etiology, pathophysiology, and clinical outcome of acute pyelonephritis in children. These studies have confirmed the primary role of the acute inflammatory response, associated with both reflux and nonreflux pyelonephritis, in the etiology of irreversible renal scarring. Furthermore, several studies have shown that renal scarring can be prevented or diminished by the early diagnosis and treatment of pyelonephritis. This review highlights these recent observations and makes recommendations regarding current clinical and future research applications. Received April 10, 1996; received in revised form August 5, 1996; accepted August 9, 1996     

Power Doppler ultrasonography in the diagnosis of acute childhood pyelonephritis

In the absence of specific symptomatology in children, the early diagnosis of acute pyelonephritis (APN) is a challenge, particularly during infancy. In an attempt to differentiate APN from lower urinary tract infection (UTI), we evaluated the ability of power Doppler ultrasonography (PDU) to predict renal parenchymal involvement, as assessed by dimercaptosuccinic acid (^99m Tc-DMSA) scintigraphy. The study comprised 62 patients, 46 girls and 16 boys, aged 2 weeks to 5 years, admitted to the pediatric department with febrile UTI. All children were examined by PDU and DMSA scintigraphy within the first 3 days of admission. In the group of 31 patients with one or more DMSA scan abnormalities, the PDU showed a matching perfusion defect in 27 (87%). Of 26 children with normal DMSA scintigraphy, the PDU evaluation was also normal in 24. The sensitivity and specificity of PDU for the detection of affected kidneys were 87% and 92.3%, and the positive predictive value and negative predictive value were 93.1% and 85.7%, respectively. These data indicate the PDU has a high sensitivity and specificity for differentiating APN from lower UTI and may be a useful and practical tool for the diagnosis of APN in infants and children.     

Acute renal cortical scintigraphy in children with a first urinary tract infection

This prospective study, performed in 101 children with a first symptomatic urinary tract infection (UTI), evaluates the diagnostic value of clinical, biological, and ultrasound parameters in detecting children with acute renal infection documented by dimercaptosuccinic acid (DMSA) scintigraphy. In children with a positive DMSA scan, mean C-reactive protein (CRP) was higher than in children with a normal DMSA scan (114±64 vs. 67±38 mg/dl, mean±SD, P=0.0002). The sensitivity and specificity of CRP was 64% and 68%, respectively. In children with severe kidney involvement, mean CRP and white blood count (WBC) were higher than in children with mild/moderate disease (151±83 vs. 92±55 mg/dl for CRP, P=0.0149; 20,100±6,854 vs. 15,023±6,145 WBC/ mm³ for WBC, P=0.0131). The sensitivity and specificity was 85% and 20% for CRP, and 77% and 18% for WBC, respectively. One or more areas of abnormal cortical echogenicity were documented in 3% of kidneys with positive DMSA scans. Dilatation of the collecting system was observed in 24% of kidneys. The sensitivity and specificity of ultrasonography was 27% and 89%, respectively. In conclusion, clinical, biological, and ultrasound parameters do not accurately distinguish cystitis from pyelonephritis in children with UTI and do not identify children with severe renal damage. Accordingly, we recommend that DMSA scan should be added to the initial work-up of children with UTI. Received: 5 June 2000 / Revised: 9 May 2001 / Accepted: 9 May 2001     

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>-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<0.02 and 0.01, respectively). During infection the size of the defect on the DMSA scan correlated with renal vooume 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.     

Technetium-99m-dimercaptosuccinic acid renal scintigraphy in children over 5 years

We retrospectively evaluated the frequency of renal scintigraphic abnormalities in children over 5 years admitted with a first symptomatic urinary tract infection (UTI). Among 261 children investigated, we found only 23 over 5 years having had technetium-99m-dimercaptosuccinic acid scintigraphy during the acute phase of a first UTI. Obvious scintigraphic abnormalities were detected in 14 children (15 kidneys): 12 kidneys showed focal cortical defects and 3 were small and deformed. Ultrasound was normal in 7 of the 15 kidneys with abnormal scintigraphy and in all the kidneys with normal scintigraphy. Among the 12 kidneys with focal cortical lesions, 8 kidneys returned to normal or improved considerably 2 – 12 months after initial work-up. In conclusion, in children over 5 years admitted with a first symptomatic UTI, the frequency of scintigraphic abnormalities is high and a strategy based only on ultrasound data would miss about 50% of the abnormal kidneys. Received July 8, 1997; received in revised form January 14, 1998; accepted January 22, 1998     

Power Doppler sonographic evaluation of acute childhood pyelonephritis

Urinary tract infection is common in children. The available gold standard methods for diagnosis, Tc-99m dimercaptosuccinic acid (DMSA) scan and computed tomography (CT) are invasive and expensive. This study was performed to assess the role of power Doppler ultrasound (PDU) for diagnosis of acute pyelonephritis (APN) compared with Tc-99m DMSA scan. A prospective study was conducted in 34 children with the mean age of 2.8±2.7 years who were hospitalized with the first episode of febrile urinary tract infection. All children were examined in the first 3 days of admission by PDU and Tc-99m DMSA scan. Patients with congenital structural anomaly were excluded. Each kidney was divided into three zones. The comparison between PDU and DMSA scan was performed on the basis of patients and renal units. According to the patient’s number, sensitivity, specificity, positive and negative predictive values, and accuracy of PDU were 89%, 53%, 70%, 80%, and 74%, respectively, but based on the renal units, changed to 66%, 81%, 46%, 91%, and 79%, respectively. Although PDU has the potential for identifying APN in children, it is still soon to replace DMSA scan.     

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 ascendingEscherichia 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 toE. 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. The results imply that DMSA scintigraphy is a valuable method for the early diagnosis and for the localization of pyelonephritis.     

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.     

Procalcitonin as a marker of acute pyelonephritis in infants and children

In the absence of specific symptomatology in children, the early diagnosis of acute pyelonephritis is a challenge, particularly during infancy. In an attempt to differentiate acute pyelonephritis from lower urinary tract infection (UTI), we measured serum procalcitonin (PCT) levels and compared these with other commonly used inflammatory markers. We evaluated the ability of serum PCT levels to predict renal involvement, as assessed by dimercaptosuccinic acid (DMSA) scintigraphy. Serum C-reactive protein (CRP), leukocyte counts, and PCT levels were measured in 64 children admitted for suspected UTI. Renal parenchymal involvement was assessed by ^99mTc-DMSA scintigraphy in the first 7 days after admission. In acute pyelonephritis, the median PCT level was significantly higher than in the lower UTI group (3.41, range 0.36–12.4 μg/l vs. 0.13, range 0.02–2.15 μg/l, P<0.0001). In these two groups, respectively, median CRP levels were 120 (range 62–249 mg/l) and 74.5 (range 14.5–235 mg/l, P=0.012) and leukocyte counts were 15,910/mm³ (range 10,200–26,900) and 14,600/mm³ (range 8,190–26,470, P=0.34). For the prediction of acute pyelonephritis, the sensitivity and specificity of PCT were 94.1% and 89.7%, respectively; CRP had a sensitivity of 100%, but a specificity of 18.5%. We conclude that serum PCT may be an accurate marker for early diagnosis of acute pyelonephritis. Received: 11 July 2001 / Revised: 25 October 2001 / Accepted: 18 November 2001     

Correlation of renal ultrasonographic findings with inflammatory volume from dimercaptosuccinic acid renal scans in children with acute pyelonephritis

PURPOSE: We correlated abnormal findings on renal ultrasonography (US) and inflammatory volume (Volume) on technetium dimercaptosuccinic acid renal single photon emission computerized tomography (DMSA) in children with acute pyelonephritis (APN) with renal scars. MATERIALS AND METHODS: A total of 31 males and 14 females (9 days to 9.8 years old) who fulfilled diagnostic criteria for APN and who underwent initial DMSA between January 1995 and July 2002 and followup DMSA at least 6 months later were enrolled in the study. APN was diagnosed by initial DMSA, and placement in the scar or scar-free group was determined by followup DMSA. Photopenic areas on initial DMSA were calculated as Volume, and were compared to US findings. RESULTS: Ultrasound demonstrated 35 abnormal kidneys (38.9%) among these children with APN. Significant differences in age, Volume (11.19 +/- 2.52 ml vs 3.02 +/- 0.75 ml, p <0.005), C-reactive protein (CRP) and photopenic lesion on initial DMSA were found between children with abnormal and normal US. Of 65 children with initial APN foci 33 (50.8%) recovered, and the others had development of scars. The sensitivity of US for detecting APN (identified by DMSA scan) was 49.2%, and the specificity was 88% (OR 7.1, 95% CI 2.18 to 24.41). The sensitivity of US for predicting renal scarring was 59.4%, and the specificity was 60.6% (OR 2.3, 95% CI 0.82 to 7.65). Patients with abnormal US findings and high serum CRP (greater than 70 mg/l) had a large Volume (10.96 +/- 3.05 ml) and a 76.2% chance of being in the scar group. CONCLUSIONS: US findings are significantly correlated to Volume in APN. Along with a high level of CRP, US is helpful in predicting development of renal scarring.     

Role of Tc-99m DMSA scintigraphy in the diagnosis of culture negative pyelonephritis

The aim of this work was to evaluate prospectively the proportion of children with a clinical and biological presentation of acute pyelonephritis, abnormal Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy and negative or equivocal urine cultures. All patients aged 6 weeks to 15 years suspected of acute pyelonephritis (APN) were admitted to the Paediatric Department and underwent Tc-99m DMSA scintigraphy within 3 days after admission and at 6 months. Of 166 patients enrolled in the study, 15 (9%) had negative or equivocal urine culture despite clinical and scintigraphic evidence of APN. Of these 15 children, renal ultrasound was normal in 7 patients and vesicoureteric reflux was found in 9 patients. Control DMSA 6 months after acute episode showed the disappearance of cortical lesions in eight and partial improvement in four patients. In this prospective series, as many as 9% of patients with APN would have been missed on the basis of equivocal or negative urine cultures. It is suggested that Tc-99m DMSA scintigraphy should be performed in children with severe infection without clear aetiology, especially in those with abnormal urinalysis. Received: 9 August 2000 / Revised: 12 January 2001 / Accepted: 25 January 2001     

Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux

Acute pyelonephritis (APN) may produce permanent renal damage (PRD), which can subsequently lead to diverse complications. We prospectively evaluated 147 females and 122 males (mean age 3.5 years) with APN in order to analyze the relationship between the presence of PRD, at the time of cortical renal scintigraphy, and age, gender, episodes of urinary tract infection (UTI), and presence of vesicoureteral reflux (VUR). There were 152 children studied after the first proven UTI. VUR was present in 150 children. PRD was observed in 170 children. There were no significant differences between boys and girls. PRD was found in 36.4% of children younger than 1 year and in 70.1% of those older than 1 year (P<0.0001). Of children with VUR, 72% had PRD compared with 52% of children without VUR (P<0.0001). Of children with a first episode of UTI, 55.9% developed PRD as did 72.6% of those with recurrent UTI (P=0.004). Our results showed that PRD in children with APN is important, especially in the presence of VUR, recurrent UTI, and older age.     

The etiology of renal scars in infants with pyelonephritis and vesicoureteral reflux

We aimed to investigate, by means of dimercaptosuccinic acid (DMSA) scan, the relations between vesicoureteral reflux (VUR) and its degree, pyelonephritis during infancy, and renal parenchymal findings. Seventy-four infants with pyelonephritis, 44 girls and 30 boys (mean age at their first pyelonephritic episode 4.12 months, median 3 months), were enrolled in the study. Voiding cystourethrography (VCU) and ultrasonography (US) were performed within 6 weeks following the infection. DMSA was performed at least 4 months after the urinary tract infection (UTI). The renal parenchymal pathology was defined as focal or multifocal defects or as a split renal uptake of less than 45%. DMSA scintigraphy revealed that 19% (14/74) of the children had renal damage. Renal parenchymal findings were observed only when VUR was present, and its grade was above 3/5. No abnormality was found in 51 renal units without reflux, 9 with VUR grade 1/5, and 54 with grade 2/5. Renal pathology was observed in 9/24 renal units with VUR grade 3, 3/8 with grade 4, and 2/2 with grade 5. No correlation was found between renal parenchymal defects and clinical presentation of the pyelonephritis, type of the microorganism, presence of bacteremia, or the number of recurrent infections. In adequately treated infants, renal damage is probably due to a reflux-associated, preexisting, congenital renal parenchymal pathology and not to the inflammatory process. We suggest that DMSA scintigraphy should not be performed routinely in every infant with UTI and should be reserved primarily for children with VUR grade 3 and above. Received: 17 February 1999 / Revised: 30 June 1999 / Accepted: 7 July 1999     

Age-related radiological imaging in children with acute pyelonephritis

Accurate diagnosis of acute pyelonephritis (APN) using clinical and laboratory parameters is often difficult in children. The aims of this retrospective study were twofold. Firstly, to correlate the clinical and laboratory manifestations of APN with the results of the dimercaptosuccinic acid (DMSA) renal scan in different age groups. Secondly, to compare the DMSA renal scan, renal ultrasonography (RUS), and voiding cystourethrography (VCUG) in patients with clinical APN. The DMSA renal scan was utilized as the gold standard for renal involvement. We determined the sensitivity of these tests in febrile urinary tract infections (UTI) in three age groups: group I less than 2 years; group II 2–8 years; group III older than 8 years. During the period January 1992 through December 1998, 222 children presented with a febrile UTI. All patients had a DMSA renal scan, 208 had contrast VCUG, and 163 had RUS. The clinical and laboratory manifestation of pyelonephritis correlated better with a positive DMSA renal scan in the older children than in the younger children; 85% of the DMSA renal scans were positive in group III; 69% in group II; 48% in group I (P<0.001). Vesicoureteral reflux detected by contrast VCUG was more prevalent in the younger age groups. Although high grades of reflux (grade IV–V) correlated better with a positive DMSA renal scan, it did not reach a level of statistical significance (P>0.05). RUS did not correlate with a positive DMSA renal scan in any age group. Received: 13 July 2000 / Revised: 6 June 2001 / Accepted: 9 June 2001     

Diagnostic significance of clinical and laboratory findings to localize site of urinary infection

The aim of this study was to define in children younger than 2 years of age the diagnostic significance of clinical and laboratory findings to localize site of febrile urinary tract infection. We reviewed the records of 185 children younger than 2 years of age admitted to hospital with febrile urinary tract infection. Patients were divided into having either acute pyelonephritis or acute cystitis according to the presence or absence of acute lesions on dimercaptosuccinic acid (DMSA) renal scintigraphy. Clinical and laboratory [white blood cell count (WBC), urinalysis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)] findings were compared between the two groups using Student’s t test, chi-square test, and multivariate analysis. Patients with pyelonephritis had statistically significant higher age, WBC, ESR, and CRP than those with cystitis. Although the sensitivity of the tests was 80–100%, their specificity was <28%. On multivariate analysis, 33% of patients with cystitis were diagnosed as having pyelonephritis, whereas 22% of those with pyelonephritis were considered to have cystitis. Given the low specificity of clinical findings and available laboratory tests to define the site of urine infection in this age group, we recommend DMSA renal scintigram as the test of choice to make the diagnosis of acute pyelonephritis in these patients.     

Treatment of children with acute pyelonephritis: a prospective randomized study

The aim of this study was to compare, in children with acute pyelonephritis, the efficacy of 7 days’ (group A) and 3 days’ (group B) intravenous antibiotics, both followed by an oral treatment. Children were randomized after 3 days of intravenous treatment. Technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy was performed within the first days after admission and repeated 6 months later. Total or partial persistence of renal abnormalities on the 6-month DMSA scintigraphy was used as the endpoint of the study. Among the 92 children included in the study, 87 were followed for at least 6 months (43 in group A and 44 in group B) and were eligible for analysis. Late DMSA was abnormal in 9 kidneys of group A and 12 kidneys of group B, representing respectively 24% and 44% of kidneys with abnormalities on the initial DMSA (difference statistically not significant). When the patients were stratified according to the delay of treatment, the percentage of patients with sequelae in group A was comparable, whether the delay was less or more than 1 week. In group B, the percentage of patients with sequelae was significantly higher (P<0.01) when the delay was more than 1 week. Received: 2 January 2001 / Revised: 29 June 2001 / Accepted: 1 July 2001     

Prognostic value of the acute DMSA scan in children with first urinary tract infection

We attempted to verify in a group of 101 children with first urinary tract infection whether it was possible to identify groups of patients with different risks of developing renal scarring by taking into account both the extent of kidney involvement documented in the acute phase of infection using a dimercaptosuccinic acid (DMSA) scan, and the presence or absence of vesicoureteral reflux (VUR). The frequency of persistent lesions in kidneys with mild-moderate lesions (less than 50% of kidney involvement) in the presence of VUR or in non-refluxing kidneys was similar (P=0.1447), while the frequency of persistent lesions in kidneys with severe lesions in the presence of VUR was significantly higher than the frequency of persistent lesions in non-refluxing kidneys (P=0.0089). The extent of kidney involvement and the presence of VUR make possible the identification of different categories of risk of scarring: in the ”low risk group” (normal kidney with/without VUR) the risk of scarring is 0%; in the ”intermediate risk group” (mild lesions with/without VUR; extensive lesions without VUR) the risk of scarring is between 14% and 38%, while in the ”high risk group” (extensive lesions with VUR) the risk of scarring is 88%. Quantifying the risk of scarring could help in planning the treatment or in modifying the later strategy. Received: 5 June 2000 / Revised: 23 January 2001 / Accepted: 24 April 2001     

Proinflammatory cytokines and procalcitonin in children with acute pyelonephritis

This prospective study, performed in 76 children with a urinary tract infection (UTI), evaluates the diagnostic value of procalcitonin (PCT) and proinflammatory cytokines (IL-1, IL-6 and TNF-) in children with acute pyelonephritis documented by dimercaptosuccinic acid scintigraphy (DMSA). Renal parenchymal involvement was assessed by ^99m Tc-DMSA scintigraphy within 7 days of admission. The diagnosis of acute pyelonephritis was confirmed only in patients with reversible lesions on scintigraphy. According to DMSA scan results, patients were divided into two groups, lower UTI or acute pyelonephritis. In acute pyelonephritis, serum PCT level was found to be significantly higher than it is in the lower UTI (p <0.001). Also, significantly higher serum proinflammatory cytokines (IL-1, IL-6 and TNF-) levels were detected in those with acute pyelonephritis than those with lower UTI (p <0.001). We conclude that both serum PCT and proinflammatory cytokine levels may be used as accurate markers for diagnosis of acute pyelonephritis.