Joo Hoon Lee

Nonrefluxing Neonatal Hydronephrosis and the Risk of Urinary Tract Infection

PURPOSE The aim of this study was to assess the relationship between prenatally diagnosed nonrefluxing hydronephrosis and urinary tract infection. MATERIALS AND METHODS We reviewed patients who were born at our institution between March 1989 and February 2006. Those who were diagnosed with fetal hydronephrosis confirmed on postnatal sonography were enrolled in the study. Hydronephrosis was graded according to the Society for Fetal Urology classification. Obstructive uropathy was diagnosed with (99m)technetium mercaptoacetyltriglycine renal scan and clinical courses. Voiding cystourethrography was done to exclude patients with vesicoureteral reflux. The prevalence of urinary tract infection was checked at 1-year followup. RESULTS A total of 430 patients without reflux were enrolled in the study. Male-to-female ratio was 351:79. Urinary tract infection developed in 83 patients (19%), with first infection occurring at age 4.1 +/- 2.7 months overall and before age 6 months in 70 patients (84% of subgroup). Frequency of urinary tract infection was 1.4 +/- 0.7 (range 1 to 4) episodes during the first year. Urinary tract infection developed in 50 of 128 patients with obstructive uropathy (39%), compared to 33 of 302 patients without obstructive uropathy (11%, p <0.001). High grade hydronephrosis was associated with an increased incidence of urinary tract infection-38 of 96 patients (40%) with grade IV hydronephrosis had urinary tract infection, compared to 26 of 79 (33%) with grade III, 13 of 94 (14%) with grade II and 6 of 161 (4%) with grade I disease (p <0.001). Urinary tract infection occurred more frequently in patients with vs without hydroureter (37 of 78, or 47%, vs 46 of 352, or 13%; p <0.001). CONCLUSIONS Neonates with obstructive uropathy, severe hydronephrosis or hydroureteronephrosis have increased risk of urinary tract infection even without reflux, and antibiotic prophylaxis may be recommended.

Pharmacokinetics of drugs in rats with diabetes mellitus induced by alloxan or streptozocin: comparison with those in patients with type I diabetes mellitus

Objectives In rats with diabetes mellitus induced by alloxan (DMIA) or streptozocin (DMIS), changes in the cytochrome P450 (CYP) isozymes in the liver, lung, kidney, intestine, brain, and testis have been reported based on Western blot analysis, Northern blot analysis, and various enzyme activities. Changes in phase II enzyme activities have been reported also. Hence, in this review, changes in the pharmacokinetics of drugs that were mainly conjugated and metabolized via CYPs or phase II isozymes in rats with DMIA or DMIS, as reported in various literature, have been explained. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized in the kidney, and that were excreted mainly via the kidney or bile in DMIA or DMIS rats were reviewed also. For drugs mainly metabolized via hepatic CYP isozymes, the changes in the total area under the plasma concentration–time curve from time zero to time infinity (AUC) of metabolites, AUCmetabolite/AUCparent drug ratios, or the time‐averaged nonrenal and total body clearances (CLNR and CL, respectively) of parent drugs as reported in the literature have been compared.

Mutational analysis of idiopathic renal hypouricemia in Korea

Idiopathic renal hypouricemia is a hereditary disease characterized by abnormally high renal uric acid clearance. Most patients are clinically silent, but acute renal failure (ARF), urolithiasis, or hematuria may develop. A defect in the SLC22A12 gene, which encodes the renal uric acid transporter, URAT1, is the known major cause of this disorder. We performed a mutational analysis of the SLC22A12 gene in five Korean patients with idiopathic renal hypouricemia in this study. Two patients presented with microscopic hematuria, one with uric acid urolithiasis, and one with exercise-induced ARF. One patient was asymptomatic. Three different mutations, W258X, R90H and R477H, were detected in four of the patients. However, no mutation was found in the fifth ARF patient. This is the first study of SLC22A12 mutations in a country other than Japan. W258X was found to be the predominant SLC22A12 mutation in Korean renal hypouricemia patients, as has been reported in Japan.

WT1 and NPHS2 mutations in Korean children with steroid-resistant nephrotic syndrome

Although several genetic causes of steroid-resistant nephrotic syndrome (SRNS) have been identified, occurrence of these genetic abnormalities appears to be influenced by race. Seventy Korean children (39 girls, 31 boys) with SRNS underwent analysis for mutations of WT1 and NPHS2. Although NPHS2 mutations were not present in any of the patients, two different intronic mutations of WT1, IVS9+4 C>T and IVS9+5 G>A, were detected in four patients (three girls, one boy). Among the four patients with mutation, two girls with a karyotype of 46,XY had complete XY gonadal dysgenesis, one girl with a karyotype of 46,XX had normal genitalia, and one boy with a karyotype of 46,XY had hypospadia. A kidney biopsy conducted in three of the four patients revealed focal segmental glomerulosclerosis. The incidence of WT1 mutations observed in this study was similar to that of previous reports. However, the incidence of NPHS2 mutations seems to be very rare in Korean children. Genetic diagnosis of WT1 mutations should be recommended for children with SRNS, especially in cases involving a female phenotype or males with genital anomalies.

Risk Factors for Renal Scar Formation in Infants With First Episode of Acute Pyelonephritis: A Prospective Clinical Study

PURPOSE We prospectively determined the risk factors for renal scar formation after the first episode of acute pyelonephritis as confirmed on dimercapto-succinic acid scintigraphy in children younger than 1 year. MATERIALS AND METHODS A total of 213 infants with acute pyelonephritis were enrolled in the study. Infants with urological abnormalities other than vesicoureteral reflux were excluded from analysis. Followup scanning was performed 6 months after acute pyelonephritis and voiding cystourethrography was performed after the acute phase of infection. Possible risk factors were evaluated including gender, peak fever, duration of fever before and after treatment with antibiotics, white blood cell count, C-reactive protein concentration, presence of vesicoureteral reflux and reflux grade. RESULTS Six months after acute pyelonephritis 37 of 213 (17.4%) infants and 41 of 248 (16.5%) renal units with acute photon defects on initial dimercapto-succinic acid scintigraphy had renal scars. The rates of scar formation were significantly higher in infants with vesicoureteral reflux than in those without (39.4% vs 7.5%, p <0.001, OR 9.433) and in renal units with vesicoureteral reflux than in those without (39.4% vs 8.2%, p <0.001, OR 7.237). Renal scar formation was related to reflux grade (none-8.2%, grade I-20%, grade II-22.7%, grade III-40%, grade IV-70%, grade V-55.6%, p <0.001) but not to any other clinical or laboratory variables. CONCLUSIONS The presence of vesicoureteral reflux was the only independent risk factor for renal scar formation after acute pyelonephritis in infants. The prevalence of renal scarring was significantly correlated with reflux grade. Voiding cystourethrography is necessary in infants after the first acute pyelonephritis episode is confirmed on dimercapto-succinic acid renal scintigraphy.

Ifosfamide nephrotoxicity in pediatric cancer patients.

Abstract. The renal functions in pediatric cancer patients who received ifosfamide (IFO) treatment were evaluated and the risk factors related to IFO nephrotoxicity were determined. The medical records of all children treated with IFO were reviewed, and 62 with normal renal function before IFO treatment were selected. Nephrotoxicity was diagnosed by measuring urine β2-microglobulin and glucose, and serum phosphate, bicarbonate, and creatinine. Forty-eight (77.4%) had a history of previous cisplatin treatment. Nephrotoxicity was detected in 20 patients (32.3%). β2-Microglobulinuria was observed in all 20, hypophosphatemia in 10 (16.1%), hypocarbia in 2 (3.2%), glucosuria in 5 (8.1%), and decreased creatinine clearance in 7 (11.3%). The cumulative dose of IFO and a history of previous cisplatin therapy were related to nephrotoxicity. Among the 20 patients with nephrotoxicity, the median cumulative dose of IFO in patients with a low (<500 mg/m2) and high (>500 mg/m2) cumulative dose of previous cisplatin was 80 g/m2 (73–102 g/m2) and 45 g/m2 (11–76 g/m2), respectively. Most of the nephrotoxicity persisted after cessation of IFO treatment. In conclusion, close monitoring of IFO nephrotoxicity should be started earlier in patients with high-dose cisplatin pretreatment. Tubular proteinuria, as indicated by β2-microglobulinuria, was the most-sensitive marker for IFO nephrotoxicity. Long-term follow-up study for reversibility of IFO nephrotoxicity is in progress.

Quality of life in children with end-stage renal disease based on a PedsQL ESRD module.

BackgroundHealth-related quality of life (HRQOL) is an essential subject for children with end-stage renal disease (ESRD) and their families.MethodsWe performed a cross-sectional investigation of HRQOL in children undergoing renal replacement therapies, such as dialysis and renal transplantation, using the 34-item Pediatric Quality of Life Inventory 3.0 End-Stage Renal Disease (PedsQL 3.0 ESRD) module. We assessed 92 ESRD patients aged 2–18 from four Korean university hospitals.ResultsThe male:female ratio was 44:48, and the most common cause of ESRD was chronic glomerulonephritis. Fifty-five children were treated by dialysis, and 37 received renal transplantation. Transplant patients had better HRQOL than dialysis patients in two domains in parent proxy reports: “About my kidney disease” and “Worry.” In child self-reports, transplant patients had better HRQOL than dialysis patients in one domain: Treatment problems. However, there were no significant differences in total QOL scores between peritoneal dialysis (PD) and transplant patients in child self-reports. In addition, there were differences in the ESRD module scores between child self- and parent proxy reports. Children usually reported better QOL than their parents. Child self-reports showed significantly higher QOL scores than parent proxy reports in the domains of General fatigue, Family & peer interaction, and Worry. Children on PD self-reported a significantly higher QOL than children on hemodialysis (HD).ConclusionsThe PedsQL 3.0 ESRD module may be useful as an ESRD-specific instrument to evaluate HRQOL in children; however, a larger, longitudinal prospective study is warranted.

Renal manifestations of patients with MYH9-related disorders

MYH9-related disorders are a group of autosomal, dominantly inherited disorders caused by mutations of the MYH9 gene, which encodes the non-muscle myosin heavy chain IIA (NMMHC-IIA). May–Hegglin anomaly and Sebastian, Fechtner, and Epstein syndromes belong to this group. Macrothrombocytopenia is a common characteristic associated with MYH9-related disorders, and basophilic cytoplasmic inclusion bodies in leukocytes (Döhle-like bodies), deafness, cataracts, and glomerulopathy are also found in some patients. In this study, renal manifestations of 7 unrelated Korean patients with MYH9-related disorders were analyzed. Of a total of 7 patients, 4 had disease-related family histories. One familial case had a mutation in the tail domain of NMMHC-IIA and showed milder renal involvement with preserved renal function by his 30s. Among the 3 familial cases without renal involvement, 2 had mutations in the tail domain of NMMHC-IIA and 1 had a mutation in the motor domain. The remaining 3 sporadic cases had severe renal involvement with rapid progression to end-stage renal disease and mutations located in the motor domain. In summary, mutations in the motor domain of NMMHC-IIA and negative family history were associated with severe renal involvement in patients with MYH9-related disorders. These results are in agreement with those of previous reports.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis associated with CLDN16 mutations

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), an autosomal recessive renal tubular disorder, is characterized by the impaired tubular reabsorption of magnesium and calcium in the thick ascending limb of the loop of Henle and an eventual progression to end-stage renal disease. Recent studies have reported that this disease is caused by mutations in the CLDN16 gene, which encodes the tight junction protein, paracellin-1. Paracellin-1 belongs to the claudin family and regulates the paracellular transport of magnesium and calcium. Here, we report on two Korean siblings with typical clinical features of FHHNC in association with compound heterozygous mutations, G233C and 800delG, in CLDN16. Their parents were asymptomatic heterozygous carriers of the single mutations. This is the first report of FHHNC in Korea, and the mutations reported are novel.

Atypical hemolytic uremic syndrome: Korean pediatric series.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes.