Min Hyun Cho

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.

Previous ischemia and reperfusion injury results in resistance of the kidney against subsequent ischemia and reperfusion insult in mice; a role for the Akt signal pathway

BACKGROUND Kidneys previously exposed to ischemia and reperfusion (I/R), pre-conditioned by I/R, are less susceptible to subsequent I/R injury. Here, we investigated the role for protein kinase B (Akt) survival signaling pathways including anti-apoptosis pathways in the reduced susceptibility of I/R-pre-conditioned kidneys. METHODS Mice were exposed to either a single I/R pre-conditioning event (SIRPC, 30 min of bilateral renal ischemia followed by 8 days of reperfusion) or sham-operation (non-SIRPC) and then subjected to either 30 min of bilateral renal ischemia or sham-operation (sham). Some of the mice received intra-peritoneal administrations of wortmannin, which is an inhibitor of phosphatidylinositol-3 kinase, PI3K. RESULTS Thirty minutes of bilateral renal ischemia in non-SIRPC mice induced a dramatic increase in plasma creatinine (PCr) levels, but this was not observed in the SIRPC mouse. Consistent with the PCr results, tubular damage and apoptotic tubular cell death were more severe in the non-SIRPC mouse kidney than in the SIRPC mice. SIRPC increased the levels of phosphorylated-Akt and -Bad expression as well as the ratio of Bcl-2 to Bax expression in the kidney. I/R resulted in greater increases of phosphorylated-Akt and -Bad, Bcl-xL and Bcl-2, but a lower level of increase of Bax, in the SIRPC mouse kidneys than those in the non-SIRPC-mouse kidneys. Treatment with wortmannin during the SIRPC period inhibited SIRPC-induced increase in phosphorylated-Akt and -Bad expressions and eliminated tolerance of SIRPC mice kidneys to I/R insult. CONCLUSION Ischemic pre-conditioning confers renal resistance to I/R-induced apoptosis via activation of the Akt signal pathway.

Pathophysiology of minimal change nephrotic syndrome and focal segmental glomerulosclerosis

SUMMARY:  Minimal change nephrotic syndrome (MCNS) is the most common cause of the nephrotic syndrome in children, accounting for 90% of cases under the age of 10 years and more than 50% in older children. It has been proposed that MCNS reflects a disorder of T‐lymphocytes. These T cells are thought to release a cytokine – so‐called permeability factor – that injures the glomerular epithelial cells. The identity of this permeability factor is still uncertain. Epithelial cell damage may lead to albuminuria in MCNS by altering the metabolism of polyanions, such as heparan sulphates, that constitute most of the normal charge barrier to the glomerular filtration of macromolecules such as albumin. In contrast, in focal segmental glomerulosclerosis (FSGS) the proteinuria is primarily due to an increased number of large pores in the glomerular basement membrane, leading to an impairment in size selectivity. It has been documented by repeated renal biopsies that some patients with apparent MCNS at the initial biopsy progress to FSGS. Morphological signs which have been proposed to identify the high‐risk subset of MCNS include widespread IgM deposits (IgM nephropathy) and diffuse mesangial hypercellularity. It has been also documented that the initial biopsy of paediatric patients who subsequently showed FSGS had larger glomeruli from children with MCNS and healthy controls. Therefore, the presence of glomerular hypertrophy in biopsies of apparent MCNS appeared to be a high specific indicator of increased risk for progression to FSGS. In comparison with MCNS, a higher proportion of patients with mild mesangial hypercellularity are initial non‐responder. More severe degree of mesangial hypercellularity, as seen in patients with diffuse mesangial hypercellularity, was associated with an even poorer initial response to steroid. Accordingly, it appears that mesangial proliferative glomerulonephritis is a more severe form of MCNS in which the initial injury is greater, leading to mesangial dysfunction and a slower rate of recovery, and this disorder is a part of the MCNS‐FSGS spectrum. In this viewpoint, it can also be said that FSGS is the most severe form of MCNS in which the initial injury is the greatest, so the majority of patients with FSGS are non‐responders to steroid and progress to chronic renal failure. In summary, documents define the risk for progressive renal disease based on the presence of mesangial hypercellularity and glomerular hypertrophy in renal biopsies of patients with MCNS, thus directing vigilant follow up and more aggressive treatment of high‐risk patients.

Interleukin-8 and Tumor Necrosis Factor-Alpha Are Increased in Minimal Change Disease but Do Not Alter Albumin Permeability

Aims: Minimal change disease (MCD) is the most common primary nephrotic syndrome in children. Some suggested that interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) are involved in the pathogenesis of MCD. This study was done to see changes of plasma and urinary IL-8, TNF-α, and their effects on determination of permeability of glomerular basement membrane (BM) contributed by heparan sulfate proteoglycan (HSPG). Methods: Study patients consisted of 19 biopsy-proven MCD children aged 2–15 years old. Both plasma, urinary IL-8 and TNF-α were measured. Employing the Millicell system, IL-8 and TNF-α were screened for the permeability factors. We examined whether IL-8 and TNF-α regulated BM HSPG gene expression and HS synthesis in the glomerular epithelial cells (GECs). Results: Urinary IL-8 during relapse was significantly increased when compared with that of during remission or controls (13,996 ± 2,811 vs. 2,941 ± 373, 5,331 ± 640 ng/mg·cr) (p < 0.05). Urinary TNF-α during relapse was also significantly increased (364.4 ± 51.2 vs. 155.3 ± 20.8, 36.0 ± 4.5 ng/mg·cr) (p < 0.05). Plasma IL-8 during relapse was significantly increased compared to that during remission(1.19 ± 0.62 vs. 0.51 ± 0.42 ng/ml) (p < 0.05). However, the negative results were obtained in the permeability assay using the Millicell system. No difference was seen in BM HSPG gene expression and HS synthesis in the GECs. Conclusion: Therefore, it seems that both IL-8 and TNF-α may not play a disease-specific role in the pathogenesis of MCD.

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.

Orchiectomy attenuates kidney fibrosis after ureteral obstruction by reduction of oxidative stress in mice.

Background/Aims: Men are generally more prone to chronic kidney disease and progression to end-stage renal disease than women. However, the underlying mechanisms remain unclear. In this study, we investigated the role of reactive oxygen species and testosterone in the progression of renal fibrosis in mice with unilateral ureteral obstruction (UUO). Methods: Mice were subjected to either orchiectomy or sham operation 14 days before either UUO or sham surgery. Harvesting of the kidney was performed 7 days after the UUO surgery to measure the production of reactive oxygen species and expression of antioxidants such as catalase, copper-zinc superoxide dismutase, and manganese superoxide dismutase, as well as fibrosis markers including α-smooth muscle actin (α-SMA) and collagen. Results: UUO resulted in increased expression of α-SMA and collagen deposition in the kidneys of both female and male mice. These increases were significantly greater in males than females. Orchiectomy significantly reduced increases in α-SMA expression and collagen deposition when compared with intact male. UUO increased the production of hydrogen peroxide and lipid peroxidation along with the decreases in expression of manganese superoxide dismutase, copper-zinc superoxide dismutase, and catalase. These changes induced by UUO were significantly attenuated by orchiectomy. Conclusion: Males are more susceptible to UUO-induced kidney fibrosis compared with females, and the higher susceptibility of males is obviated by orchiectomy along with reduction in oxidative stress.

Virologic responses to add-on adefovir dipivoxil treatment versus entecavir monotherapy in children with lamivudine-resistant chronic hepatitis B.

Purpose: The aim of the study was to compare the virologic response to adefovir (ADV) add-on therapy with switching to entecavir (ETV) monotherapy in children and adolescents with chronic hepatitis B (CHB) who have developed lamivudine (LAM) resistance during LAM treatment. Methods: Twenty-seven consecutive patients with CHB who had developed LAM resistance during LAM treatment were included. Of these 27 patients, 8 patients were treated with the addition of ADV to ongoing LAM and 8 patients were treated by switching to ETV monotherapy and each of these 16 patients were compared with the 11 patients who were treated by switching to ADV alone, as a historical control. Therapeutic responses to treatment were evaluated at 12, 24, 36, and 48 weeks from the initiation of therapy by measuring the decrement of hepatitis B virus (HBV)-DNA titers. Results: The therapeutic period for HBV-DNA titer decrement (>2 log10 IU/mL) was significantly shorter in both the LAM+ADV group and the ETV group than in the ADV group (P = 0.008); however, there was no significant difference between the LAM+ADV group and the ETV group. The rate of virologic response, defined as decrement in HBV-DNA titer to undetectable levels at 24 weeks, was significantly higher in both the LAM+ADV group and the ETV group than in the ADV group (P = 0.029). Conclusions: Both the LAM+ADV combination therapy and ETV monotherapy exhibited significantly more effective virologic responses compared to the ADV monotherapy in children and adolescents with LAM-resistant CHB, although there was no significant difference between the LAM+ADV group and the ETV group.

Neurologic Complications and Outcomes of Pandemic (H1N1) 2009 in Korean Children

Neurologic complications of children with influenza A H1N1 2009 pandemic, diagnosed in two consecutive influenza seasons were retrospectively reviewed to seek better outcomes in future outbreaks. Patient demographics, clinical manifestations and neurologic outcomes were reviewed. A total of 1,389 children were diagnosed with influenza A H1N1 by real-time reverse transcriptase-polymerase chain reaction. Of these, 23 (1.7%) patients had neurologic involvement. Their mean age was 5.9 ± 3.6 yr (range, 6 months to 11 yr) and 16 (69.9%) were boys. None of the 23 patients had been vaccinated for influenza A H1N1 and seasonal influenzas. Twenty-two of the 23 patients presented with seizures. Clinical features included febrile convulsion (n = 19), afebrile convulsion (n = 1), aseptic meningitis (n = 1), encephalopathy (n = 1), and acute necrotizing encephalopathy (n = 1). They all were treated with Oseltamivir twice daily for 5 days immediately after nasal and throat swab testing. Twenty-one of the subjects recovered fully, but the youngest two infants experienced severe neurological sequelae. The results indicate that neurologic complications associated with influenza A H1N1 2009 pandemic were mostly mild, but rarely were serious. Prompt intervention leads to a better outcome and vaccination may prevent the disease, thus staving off serious neurological complications following influenza, especially in young infants.

Clinical Spectrum and Prognostic Factors of Acute Necrotizing Encephalopathy in Children

This study was conducted to investigate the etiology, the clinical characteristics and prognosis of acute necrotizing encephalopathy (ANE) in Korean children. Six children (1 yr to 7 yr) patients with ANE were enrolled. They were diagnosed by clinical and radiological characteristics and their clinical data were retrospectively analyzed. In a search of clinically plausible causes, brain MRI in all patients, mitochondrial DNA studies for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and myoclonus epilepsy and ragged red fibers (MERRF) in four patients, and genomic typing on HLA DRB/HLA DQB genes in three patients were performed. All had precedent illnesses and the main initial symptoms included mental change (83%), seizures (50%), and focal deficits (50%). MRI revealed increased T2 signal density in the bilateral thalami and/or the brainstem in all patients. Mitochodrial DNA studies for MELAS and MERRF were negative in those children and HLA-DRB1*1401, HLA-DRB3*0202, and HLA-DQB1*0502 seemed to be significant. A high dose steroid was given to all patients, which seemed to be partly effective except for 2 patients. In conclusion, ANE is relatively rare, but can result in serious neurological complication in children. Early detection and appropriate treatment may lead to a better neurological outcome.

Long-term Effectiveness and Tolerability of Topiramate in Children with Epilepsy under the Age of 2 Years: 4-Year Follow-up

This is a long-term, open label, observational study aimed to broaden our clinical experiences in managing infants and toddlers with epilepsy. The long-term retention rate and side effects of topiramate (TPM) in them were evaluated and compared with carbamazepine (CBZ). A total of 146 children were involved in the study (TPM=41, CBZ=105). The retention rates at 24 , 36, and 48 months were 46.3%, 34.1%, 26.8% for TPM and 36.2%, 23.8%, 13.3% for CBZ, respectively. At 6 months after starting antiepileptic drugs (AED), the seizure freedom or clinical efficacy (seizure reduction rate more than 50 percent) were 73.2% for TPM and 62.9% for CBZ. The major side effects led to discontinuation included psychomotor slowing, poor oral intake from TPM and sleepiness and skin rash from CBZ. TPM was discontinued due to side effects in one case (2.4%) and lack of efficacy in five cases (12.2%), whereas CBZ was discontinued due to lack of efficacy (22.9%) and side effects (6.7%). As compared with CBZ, TPM showed the same long-term retention rate in children under the age of 2 yr, and no serious side effects. It is therefore concluded that TPM can be considered as a major AED for treating children with epilepsy under the age of 2 yr.