Asymptomatic hematuria in children: Korean Society of Pediatric Nephrology recommendations for diagnosis and management.

Hematuria is a relatively common condition among school-aged children. Because international guidelines for asymptomatic hematuria in children are unavailable, developing practical guidelines for the diagnosis and management of asymptomatic hematuria based on scientific evidence while considering real-world practice settings, values, and patient and physician preferences is essential. The Korean Society of Pediatric Nephrology developed clinical guidelines to address key questions regarding the diagnosis and management of asymptomatic hematuria in children.

Genotype-phenotype correlations in children with Gitelman syndrome.

BACKGROUND: This study aimed to analyze genotype-phenotype correlations in children with Gitelman syndrome (GS). METHODS: This multicenter retrospective study included 50 Korean children diagnosed with SLC12A3 variants in one or both alleles and the typical laboratory findings of GS. Genetic testing was performed using the Sanger sequencing except for one patient. RESULTS: The median age at the diagnosis was 10.5 years (interquartile range, 6.8;14.1), and 41 patients were followed up for a median duration of 5.4 years (interquartile range, 4.1;9.6). A total of 30 different SLC12A3 variants were identified. Of the patients, 34 (68%) had biallelic variants, and 16 (32%) had monoallelic variants on examination. Among the patients with biallelic variants, those (n = 12) with the truncating variants in one or both alleles had lower serum chloride levels (92.2 ± 3.2 vs. 96.5 ± 3.8 mMol/L, P = 0.002) at onset, as well as lower serum potassium levels (3.0 ± 0.4 vs. 3.4 ± 0.3 mMol/L, P = 0.016), and lower serum chloride levels (96.1 ± 1.9 vs. 98.3 ± 3.0 mMol/L, P = 0.049) during follow-up than those without truncating variants (n = 22). Patients with monoallelic variants on examination showed similar phenotypes and treatment responsiveness to those with biallelic variants. CONCLUSIONS: Patients with GS who had truncating variants in one or both alleles had more severe electrolyte abnormalities than those without truncating variants. Patients with GS who had monoallelic SLC12A3 variants on examination had almost the same phenotypes, response to treatment, and long-term prognosis as those with biallelic variants.

Clinical relevance of blood urea nitrogen to serum albumin ratio for predicting bacteremia in very young children with febrile urinary tract infection.

Background: Urinary tract infections (UTIs) are one of the most common bacterial infections in febrile children and a common cause of hospitalization, especially in very young children. We examined the clinical characteristics and predictive factors of concomitant bacteremia in pediatric patients with febrile UTI aged ≤24 months. Methods: This retrospective multicenter study reviewed medical data from 2,141 patients from three centers from January 2000 to December 2019. Enrolled cases were classified into the bacteremic UTI and non-bacteremic UTI groups according to the presence of blood culture pathogens. Results: Among 2,141 patients with febrile UTI, 40 (1.9%) had concomitant bacteremia. All patients in the bacterial group were aged ≤6 months. Multivariate analysis revealed that younger age, lower blood lymphocyte counts and serum albumin levels, higher C-reactive protein (CRP) levels, blood urea nitrogen (BUN) levels, and BUN/serum albumin ratio were independent risk factors of concomitant bacteremia. The area under the receiver-operating characteristic curves predicting bacteremia were 0.668 for CRP, 0.673 for lymphocytes, and 0.759 for the BUN/albumin ratio. Conclusion: The present study identified the BUN/albumin ratio and lower blood lymphocyte counts as novel predictive factors for bacteremia in young infants with febrile UTI in addition to the previously identified factors of younger age and higher CRP levels. Our findings could help to identify patients at high risk of bacteremia and benefit decision-making in the management of infants with febrile UTI.

Genotype-phenotype correlation of X-linked Alport syndrome observed in both genders: a multicenter study in South Korea.

The genotype-phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype-phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P < 0.001, hazard ratio (HR) 2.8) and splicing and truncating groups (P = 0.002, HR 3.1). Sensorineural hearing loss was detected in 65.1% of male patients, while hearing survival periods showed a highly significant difference between the non-truncating and truncating groups (P < 0.001, HR 5.1). In female patients, approximately 20% developed kidney failure at the median age of 50.2 years. The kidney survival was significantly different between the non-truncating and truncating groups (P = 0.006, HR 5.7). Our findings support the presence of genotype-phenotype correlation not only in male patients but also in female patients with XLAS.

Korean Society of Nephrology 2022 Recommendations on Controversial Issues in Diagnosis and Management of Hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Korean Society of Nephrology 2022 recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Korean Society of Nephrology 2022 Recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

High Glycated Hemoglobin Instead of High Body Mass Index Might Increase the Urine N-Acetyl-ß-D-glucosaminidase Con-Centration in Children and Adolescents with Diabetes Mellitus.

Children with diabetes, and particularly those with obesity, have poor glycemic control. They are thus at higher risk of early microvascular complications. Renal tubulointerstitial markers are integral to evaluating diabetic nephropathy. Various biomarkers have been proposed, but their role in the obese pediatric population is uncertain. We investigated renal injury markers in children with diabetes, according to obesity, and determined their role as early predictors of diabetic nephropathy. Fifty-three children and adolescents, diagnosed with either type 1 or 2 diabetes mellitus, and 43 control children, aged 7-18 years, were included. Clinical and laboratory characteristics, including six renal injury markers, were compared among subjects according to body mass index and presence of diabetes mellitus. Urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and N-acetyl-ß-D-glucosaminidase (NAG) showed significant difference between controls and diabetic children, whereas urine NAG was the only biomarker that was significantly lower either in non-obese or obese controls as compared to diabetic children. Urine NGAL, KIM-1, and NAG showed significant correlations with both HbA1c and urine ACR, whereas only urine NAG was significantly correlated with HbA1c even when groups were subdivided based on the presence of either obesity or diabetes. After adjusting for age, sex, body mass index, duration of known diabetes, and urine albumin-to-creatinine ratio, HbA1c remained a significant risk factor for elevated urine NAG. Urine NAG could be a useful indicator of tubulointerstitial damage in children with diabetes in the pre-albuminuric state. Tighter glycemic control appears to be crucial for avoiding early progression to diabetic nephropathy.

Clinical Significance of the Fetuin-A-to-Adiponectin Ratio in Obese Children and Adolescents with Diabetes Mellitus.

Fetuin-A and adiponectin are inflammatory cytokines associated with obesity and insulin resistance. This study aimed to examine the fetuin-A-to-adiponectin ratio (FAR) in diabetic children and to determine the role of FAR. A total of 54 children and adolescents with diabetes mellitus (DM) and 44 controls aged 9-16 years were included in this study. Clinical characteristics, including plasma fetuin-A and adiponectin levels, were compared with respect to body mass index (BMI) and diabetes type. Of 98 children, 54.1% were obese, whereas 18.4% were obese and diabetic. FAR was higher in obese children with DM than in non-obese children and also in type 2 DM children than in type 1. FAR showed a stronger association with BMI than with fetuin-A and adiponectin individually, and its association was more prominent in diabetic children than in controls. BMI was a risk factor for increased FAR. Plasma fetuin-A was elevated in obese children, and its association with insulin resistance and ß cell function seemed more prominent in diabetic children after adjustment for adiponectin. Thus, FAR could be a useful surrogate for the early detection of childhood metabolic complications in diabetic children, particularly those who are obese.

Characteristics of pediatric rhabdomyolysis and the associated risk factors for acute kidney injury: a retrospective multicenter study in Korea.

BACKGROUND: The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. METHODS: This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. RESULTS: Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53.6%) and infection (39.0%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. CONCLUSIONS: Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

Poor Glycemic Control Can Increase the Plasma Kidney Injury Molecule-1 Concentration in Normoalbuminuric Children and Adolescents with Diabetes Mellitus.

Diabetic nephropathy (DN) is a serious microvascular complication in childhood diabetes and microalbuminuria has been a solid indicator in the assessment of DN. Nevertheless, renal injury may still occur in the presence of normoalbuminuria (NA) and various tubular injury biomarkers have been proposed to assess such damage. This case-controlled study aimed to evaluate plasma and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 (KIM-1) levels in diabetic children particularly in those with normo- and high-NA stages and determine their role in predicting DN. Fifty-four children/adolescents with type 1 and 2 diabetes and forty-four controls aged 7-18 years were included. The baseline clinical and laboratory characteristics including plasma and urinary biomarkers were compared. The plasma KIM-1 levels were significantly higher in diabetic children than in the controls and in high-NA children than normo-NA children. Glycosylated hemoglobin (HbA1c) was identified as a significant risk factor for increased plasma KIM-1. The optimal cutoff for HbA1c when the plasma KIM-1 was > 23.10 pg/mL was 6.75% with an area under the curve of 0.77. For diabetic children with mildly increased albuminuria, the plasma KIM-1 complementary to MA may help increase the yield of detecting DN. Our findings also suggested an HbA1c cutoff of 6.75% correlated with increased plasma KIM-1.

New susceptible locus, rs9428555, is associated with pediatric-onset immunoglobulin A nephropathy and immunoglobulin A vasculitis in Koreans.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is one of the most common primary forms of glomerulonephritis, while IgA vasculitis (IgAV) is the most common systemic vasculitis in children. OBJECTIVE: Herein we aimed to uncover single nucleotide polymorphism (SNP) markers associated with these two related diseases by applying association tests and Sanger sequencing. METHODS: Within the discovery stage, genomic DNA in blood samples from 101 enrolled patients were genotyped by the Korean Biobank Array. Association tests were performed with 397 Korean reference genomes. In the validation stage, 26 independent samples were genotyped by Sanger sequencing. RESULTS: Four SNPs were identified (P < 5 × 10-8) in the discovery stage. To determine whether the genotypes determined by SNP array were accurate, additional genotyping via Sanger sequencing was performed. As a result, only one SNP, rs9428555, was properly genotyped. In the validation stage, the minor allele (A > G) was found in as many as 15 out of 26 samples (minor allele frequency = 0.288), even though this minor allele is rare in East Asians (< 3%). CONCLUSIONS: We found rs9428555 as a novel susceptible locus associated with the development of both IgAN and IgAV in Koreans. Though we cannot conclude rs9428555 is the unique susceptible locus of IgAN and IgAV, it is likely a good marker as the minor allele of this SNP occurred much more often in the patient group here versus within East Asians as a whole.

Lower albumin level and longer disease duration are risk factors of acute kidney injury in hospitalized children with nephrotic syndrome.

BACKGROUND: Children with nephrotic syndrome (NS) are at an increased risk of acute kidney injury (AKI) and the incidence of AKI in this population is reportedly increasing. This study aimed to investigate the incidence, clinical profiles, and risk factors of AKI in hospitalized children with NS through a nationwide study. METHODS: This retrospective multicenter study included 14 pediatric nephrology centers in Korea. From 2013 to 2017, a total of 814 patients with idiopathic NS were cared for at participating centers. Among them, 363 patients were hospitalized for NS and investigated in this study. RESULTS: A total of 363 children with NS were hospitalized 574 times. AKI occurred in 93 admissions (16.2%) of 89 patients: 30 (32.3%) stage 1; 24 (25.8%) stage 2; and 39 (41.9%) stage 3. Multivariate logistic regression analysis showed that longer disease duration, lower albumin level, and methylprednisolone pulse treatment were significantly associated with AKI development in hospitalized children with NS. AKI was associated with a longer hospital stay than non-AKI (median 10 vs. 7 days, P = 0.001). Among 93 admissions, 85 (91.4%) episodes recovered from AKI without complication, whereas 6 (6.5%) progressed to advanced chronic kidney disease (CKD). CONCLUSIONS: AKI is not uncommon in hospitalized children with NS, and its incidence in this nationwide study was 16.2%. Risk factors for AKI in hospitalized children with NS include longer disease duration, lower albumin level, and methylprednisolone pulse therapy. Pediatric NS patients with these characteristics should be under more strict scrutiny for the occurrence of AKI. Graphical abstract.

Remission of Proteinuria May Protect against Progression to Chronic Kidney Disease in Pediatric-Onset IgA Nephropathy.

Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulopathies diagnosed in children and adolescents. This study aimed to evaluate the clinical features in and outcomes of pediatric IgAN over the last 30 years. Patients who were diagnosed before age of 18 at 20 centers in Korea were evaluated retrospectively. Of the 1154 patients (768 males, 386 females) with a median follow-up of 5 years, 5.6% (n = 65) progressed to stage 3-5 chronic kidney disease (CKD). The 10- and 20-year CKD-free survival rates were 91.2% and 75.6%, respectively. Outcomes did not differ when comparing those in Korea who were diagnosed prior to versus after the year 2000. On multivariate analysis, combined asymptomatic hematuria and proteinuria as presenting symptoms and decreased renal function at the time of biopsy were associated with progression to CKD, while remission of proteinuria was negatively associated with this outcome. Patients who presented with gross hematuria or nephrotic syndrome tended toward positive outcomes, especially if they ultimately achieved remission. While remission of proteinuria might imply that the disease is inherently less aggressive, it also can be achieved by management. Therefore, more aggressive management might be required for pediatric-onset IgAN.

Genetic variations in MicroRNA genes and cancer risk: A field synopsis and meta-analysis.

BACKGROUND: Cancer risk has been associated with certain gene variations in microRNA (miRNA), but conflicting evidence warrants re-assessing of significant results in meta-analyses. We summarized published meta-analyses that assess the associations between miRNA polymorphism and cancers to show the validity of the findings. METHOD: We searched PubMed and investigated the results of meta-analyses published through November 2018. We re-assessed the results based on false-positive report probability (FPRP) to test the noteworthiness of the associations. RESULTS: Sixty-eight miRNA polymorphisms in 45 meta-analyses associated with cancer were included. Four (7.4%) and sixteen (25.0%) single nucleotide polymorphisms (SNPs) were noteworthy (FPRP < 0.2) at a prior probability of 0.001 for interesting candidate genes and a statistical power to detect an odds ratio (OR) of 1.1 and 1.5, respectively. The four miRNA SNPs noteworthy at an OR of 1.1 were as follows: miR-146a/rs2910164 Cvs.G; miR-27a/rs895819 Cvs.T; miR-423/rs6505162 Cvs.A; and miR-605/rs2043556 Cvs.T. The 16 SNPs noteworthy at an OR of 1.5 include the four genotype comparisons at an OR of 1.1, and the additional 12 genotype comparisons were as follows: miR-196a2/rs11614913 Tvs.C; miR-27a/rs895819 GGvs.AA + AG; miR-196a2/rs11614913 C vs.T; miR-146a/rs2910164 Gvs.C; miR-196a2/rs11614913 Tvs.C; miR-146a/rs2910164 Cvs.G; miR-499/rs3746444 homozygous model; miR-146a/rs2910164 CCvs.GG + GC; miR-499/rs3746444 TCvs.TT; miR-499/rs3746444 GAvs.AA; miR-146a/rs2910164 CCvs.GG; and miR-499/rs3746444 Gvs.A. No association was noteworthy at a prior probability of 0.000001. CONCLUSION: Out of 68 published associations of miRNA polymorphisms with cancer, sixteen have shown noteworthiness in our re-assessing meta-analysis. Our findings summarize the results of meta-analyses on the association of cancer with SNPs and underline the importance of interpreting results with caution.

Changes in clinical features in Henoch-Schönlein purpura during three decades: an observational study at a single hospital in Korea.

OBJECTIVE: It is unknown whether epidemiological or clinical characteristics of Henoch-Schönlein purpura (HSP) have changed over time. This study aimed at evaluating the epidemiological and clinical changes of HSP during 3 decades. METHODS: We retrospectively analyzed the data of 515 children with HSP (0-15 years of age) between 1987 and 2015. We compared the two HSP patient groups: those admitted from 1987 to 1996 (group A, 238 cases) and those admitted from 2006 to 2015 (group B, 98 cases), apart a decade. RESULTS: In total 515 patients, the mean age was 6.5 ± 3.0 years and the male-to-female ratio was 1.2:1 (278:237). The age distribution showed a peak at age 5 with a bell-shaped distribution pattern. The annual number of cases varied in each year with a trend of reduced cases in the recent decade. There were less cases during the summer season. Purpura, gastrointestinal involvement, joint involvement, and renal involvement were found in 100%, 56%, 38%, and 18% of the patients, respectively. In comparison between the two groups, there were similar findings in mean age, age distribution, and seasonal distribution. However, the hospitalization stay was longer, and the proportion of recurrent cases (14 cases vs. 0 case) and proteinuria (15% vs. 3%) were higher in the group A than in the group B. CONCLUSIONS: Long-term epidemiologic features of HSP were similar to those in other countries. Clinical manifestations of HSP showed a trend towards a less severe clinical phenotype over time in Deajeon, Korea. Key Points • It is unknown whether epidemiological and clinical traits of Henoch-Schönlein purpura (HSP) have changed over time. • We reported that clinical manifestations of HSP have changed to milder phenotype through a long-term observation of three decades at a single hospital in Daejeon, South Korea. • Clinical phenotype of infection-related diseases, including HSP, may be changed over time, and the etiology and the reason of clinical changes over time remain to be solved.

Small Red Blood Cell Fraction on the UF-1000i Urine Analyzer as a Screening Tool to Detect Dysmorphic Red Blood Cells for Diagnosing Glomerulonephritis.

BACKGROUND: Dysmorphic red blood cells (dRBCs) are first-line biomarkers for detecting glomerulonephritis (GN) in patients with hematuria. The UF-1000i system (Sysmex, Kobe, Japan), based on flow cytometry, provides small red blood cell (RBC) values (UF-1000i [UF]-%sRBCs). We evaluated the clinical application of UF-%sRBCs for detecting %dRBCs and GN. METHODS: Urine samples of 103 patients (47 with GN; 56 without GN [NGN]) were analyzed using UF-1000i urinalysis, phase-contrast microscopy (PCM), and urine chemistry. Serum creatinine (mg/dL), serum albumin (g/dL), serum protein (mg/dL), urine protein (mg/dL), and urea nitrogen (mg/dL) levels were measured using an automated chemical analyzer. To determine the cut-off level of predicting GN, ROC curve was analyzed. RESULTS: UF-%sRBCs, %dRBCs, urine protein, serum creatinine, and estimated-glomerular filtration rate differed between the GN and NGN groups, with the greatest differences detected for UF-%sRBCs and %dRBCs (P<0.0001). In ROC curve analysis, urine protein had the highest area under the curve (0.828), followed by %dRBCs (0.771) and UF-%sRBCs (0.745). To screen for GN, the best cut-off values of UF-%sRBCs and %dRBCs were >40.5% and >6.7%, respectively. %dRBCs (P=0.0001) and UF-%sRBCs (P=0.0006) differed between the GN and NGN groups in patients with isolated hematuria but without proteinuria. CONCLUSIONS: UF-%sRBCs had similar diagnostic power to %dRBCs determined by PCM for identifying patients with GN. UF-%sRBCs may be more useful for diagnosing GN in patients with isolated hematuria. Predicting %dRBCs using UF-1000i will provide information on possible GN in patients presenting with asymptomatic hematuria.

Prediction of vesicoureteral reflux in children with febrile urinary tract infection using relative uptake and cortical defect in DMSA scan.

BACKGROUND: Vesicoureteral reflux (VUR) is an important urologic anomaly that causes renal injury in children with febrile urinary tract infection (UTI). The present study aimed to evaluate the associations of abnormalities detected on technetium-99m-labeled dimercaptosuccinic acid (DMSA) scans, focusing on the association with VUR of the levels of relative decrease in kidney function and cortical defects after a first febrile UTI in children. METHODS: All 171 children underwent ultrasonography, DMSA scan and voiding cystourethrography (VCUG). The features of ultrasound and DMSA scans were compared between patients with (n = 48) and without VUR (n = 123). The relative uptake (RU) by each kidney was derived from the absolute value of the differences between the value for RU of radionuclide in the right kidney and that in the left kidney. The extent of cortical defects (ECD) was graded according to the number of compartments that contained cortical defect in both kidneys (right upper/right lower, left upper/left lower). Receiver operating characteristic curves were constructed to examine the diagnostic value of these parameters of ultrasound and DMSA scans for predicting VUR. RESULTS: The ratio of patients having hydronephrosis on ultrasound or cortical defects on DMSA scan did not differ significantly between VUR and non-VUR groups. However, the absolute values of the RU and the scores for ECD were significantly higher in the VUR group than in the non-VUR group. The area under the curves for these two parameters were higher than those for the presence of hydronephrosis or the presence of cortical defects or both. CONCLUSION: Decreased relative function and increased extents of cortical defects on DMSA scan may be associated with the presence of VUR. These findings may assist pediatricians to decide whether febrile UTI children need to undergo VCUG.