• Journal of Yeungnam Medical Science
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• v.28 no.1
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• pp.60-69
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• 2011

Due to its efficacy and tolerability, low dose oral methotrexate (MTX) therapy has been widely used for treatment of rheumatoid arthritis (RA). However, it can rarely cause serious, life-threatening hematologic toxicities, such as pancytopenia. We report here on two patients with chronic kidney disease (CKD), who developed severe pancytopenia after 5 years (cumulative dose 1,240 mg) and 4 years (cumulative dose 1,320 mg) of low dose MTX therapy for treatment of RA, respectively. Both patients presented with renal insufficiency, hypoalbuminemia, concurrent use of nonsteroidal anti-inflammatory drugs, and elevated mean corpuscular volume of red blood cells (RECs), all of which are known as risk factors of MTX-induced pancytopenia. Despite receiving treatment, which included REC and platelet transfusions, antibiotic therapy, granulocyte colony stimulating factor, and leucovorin rescue, one patient died of sepsis. Based on our case study, prompt investigation of risk factors associated with MTX toxicity is required for all patients receiving MTX therapy. MTX treatment, even at a low dose, should be discontinued in patients with advanced CKD.

• Childhood Kidney Diseases
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• v.28 no.1
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• pp.44-50
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• 2024

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that affects multiple organs. More than half of the patients with SLE have kidney involvement, and up to 10% of patients with lupus nephritis develop end-stage renal disease (ESRD). Central nervous system (CNS) involvement in SLE occurs in 21% to 95% of patients. Severe neurological manifestations such as seizures, cerebrovascular disease, meningitis, and cerebrovascular accidents can develop in childhood-onset SLE, but cerebral infections, such as brain abscess and hemorrhage, are seldom reported in lupus nephritis, even in adults. Here, we report a rare case of childhood-onset SLE with ESRD, cerebral abscess, and hemorrhage. A 9-year-old girl diagnosed with lupus nephritis was administered high-dose steroids and immunosuppressant therapy to treat acute kidney injury (AKI) and massive proteinuria. The AKI deteriorated, and after 3 months, she developed ESRD. She received hemodialysis three times a week along with daily peritoneal dialysis to control edema. She developed seizures, and imaging showed a brain abscess. This was complicated by spontaneous cerebral hemorrhage, and she became unstable. She died shortly after the hemorrhage was discovered. In conclusion, CNS complications should always be considered in clinical practice because they increase mortality, especially in those with risk factors for infection.

• BMB Reports
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• v.56 no.3
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• pp.196-201
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• 2023

Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

• Childhood Kidney Diseases
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• v.28 no.1
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• pp.1-7
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• 2024

Antenatally diagnosed urinary tract dilatation (UTD), previously referred to as antenatal hydronephrosis, is the most commonly detected abnormality by prenatal ultrasonography. Several grading systems have been developed for the classification of antenatal UTD using prenatal and postnatal ultrasonography. UTD comprises a wide variety of congenital abnormalities of the kidney and urinary tract ranging from transient UTD to more significant abnormalities such as vesicoureteral reflux, ureteropelvic junction obstruction, ureterocele, ureterovesical junction obstruction, posterior urethral valves, and non-refluxing megaureter. Optimizing the evaluation of antenatally detected UTD is essential to recognize children with important disorders while avoiding excessive investigations. Conservative approach with close follow-up is increasingly accepted as an appropriate treatment option for patients with asymptomatic vesicoureteral reflux and ureteropelvic junction obstruction in recent years. However, predicting permanent kidney damage in an unselected group of children with antenatal UTD is still challenging. The management and follow-up of children with UTD should be individualized based on recommendations from a pediatric nephrologist, a pediatric urologist, or both. Future research directed at predicting long-term outcomes of children diagnosed with UTD from mild findings to severe disease is needed to refine management for those at higher risk of kidney disease progression.

• Childhood Kidney Diseases
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• v.18 no.2
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• pp.64-70
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• 2014

Purpose: The aims of this study were to assess the clinical and laboratory profiles of chronic kidney disease-mineral bone disorder (CKD-MBD) and to assess the effects of treatment of active vitamin D analogs on severe hyperparathyroidism (SHPT) in pediatric patients on chronic peritoneal dialysis. Methods: This is a retrospective study included 53 patients who had been undergoing dialysis for more than 1 year, between January 2003 and December 2012. Results: Even after treatment with phosphate binders and active vitamin D analogs, the $mean{\pm}standard$ deviation of the percentage of time during peritoneal dialysis that the patients' serum concentrations of phosphorus, corrected total calcium, and parathyroid hormone (PTH) fell within the Kidney Disease Outcomes Quality Initiative recommended ranges was $25.06{\pm}17.47%$, $53.30{\pm}23.03%$, and $11.52{\pm}9.51%$, respectively. Clinical symptoms or radiological signs of CKD-MBD were observed in 10 patients (18.9%). There were significant differences in percentage of time that the serum intact PTH concentration was outside of the recommended range between patients with and without symptoms or signs of CKD-MBD (below recommended range, $11.74{\pm}7.37%$ vs. $40.77{\pm}25.39%$, P <0.001; above the recommended range, $63.79{\pm}27.86%$ vs. $37.09{\pm}27.76%$, P =0.022). Of the 25 patients with SHPT, high-dose alfacalcidol treatment was required in 13 patients that controlled SHPT in 7 of these patients, without marked complications. Conclusion: Despite our efforts to manage CKD-MBD, patients' met the recommended ranges from relevant guidelines at a low frequency. The treatment of high-dose active vitamin D analogs was required in about half of the patients with SHPT and effective in about half of them.

• Investigative and Clinical Urology
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• v.59 no.6
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• pp.376-382
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• 2018

Purpose: The authors performed this study to investigate the risk factors for predicting stent failure and to evaluate its impact on prognosis. Materials and Methods: Between January 2002 and March 2017, we retrospectively reviewed 117 consecutive patients who underwent retrograde ureteral stenting and exchanging at least once every 3 months for malignant ureteral obstruction. The patients were classified according to their pre-stenting chronic kidney disease (CKD) stage. The factors affecting stent failure were analyzed using a logistic regression model. Overall survival (OS) was estimated, and the prognostic significance of each variable was estimated using Cox proportional-hazards regression modeling. Results: Before stenting, 91 patients were CKD stages 1-3 and 26 patients were CKD stages 4-5. These two groups differed significantly only in pre-stenting estimated glomerular filtration rate (eGFR), bilateral obstruction, and pre-stenting pyuria. Among the 117 patients, stent failure occurred in 30 patients (25.6%), and there were no differences between the groups. Pre-stenting pyuria and post-stenting complications were significant predictors of stent failure. There were 79 deaths in total, including 56 in the CKD stages 1-3 group and 23 in the CKD stages 4-5 group. In the multivariate analysis predicting patient OS, pre-stenting eGFR and post-stenting disease progression were significant factors. Conclusions: Internal ureteral stenting was effective for maintaining renal function in malignant ureteral obstruction. However, it did not restore renal function, which is related to the prognosis of the patients. Therefore, to improve patients' renal function and prognosis, patients who require stenting must be quickly recognized and treated.

• Kidney Research and Clinical Practice
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• v.37 no.4
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• pp.373-383
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• 2018

Background: Several epidemiologic studies have suggested that the urine sodium excretion (USE) can be estimated in lieu of performing 24-hour urine collection. However, this method has not been verified in patients with chronic kidney disease (CKD) or in an interventional study. The purpose of this study was to evaluate the usefulness of estimating USE in a prospective low-salt diet education cohort (ESPECIAL). Methods: A new formula was developed on the basis of morning fasting urine samples from 228 CKD patients in the ESPECIAL cohort. This formula was compared to the previous four formulas in the prediction of 24-hour USE after treatment with olmesartan and low-salt diet education. Results: Most previously reported formulas had low predictability of the measured USE based on the ESPECIAL cohort. Only the Tanaka formula showed a small but significant bias (9.8 mEq/day, P < 0.05) with a low correlation (r = 0.34). In contrast, a new formula showed improved bias (-0.1 mEq/day) and correlation (r = 0.569) at baseline. This formula demonstrated no significant bias (-1.2 mEq/day) with the same correlation (r = 0.571) after 8 weeks of treatment with olmesartan. Intensive low-salt diet education elicited a significant decrease in the measured USE. However, none of the formulas predicted this change in the measured urine sodium after diet adjustment. Conclusion: We developed a more reliable formula for estimating the USE in CKD patients. Although estimating USE is applicable in an interventional study, it may be unsuitable for estimating the change of individual sodium intake in a low-salt intervention study.

• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.318-323
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• 2016

Background: Multidisciplinary team care (MTC) is a collaborative approach to treatment plan and ongoing care. We aimed to evaluate the clinical effect of MTC on the regulation of chronic kidney disease-mineral and bone disorder (CKD-MBD) complications in dialysis patients. Methods: This retrospective observational study was approved by the institutional review board. Among patients who have undergone dialysis at admission, the patients admitted to the nephrology ward were allocated to MTC group, and the others to usual care (UC) group. The MTC group had collaborative care by nephrologists, nurses, pharmacists, and nutritionists. The endpoints were the regulation of corrected calcium (cCa) and phosphate (P), the percent of patients in target level of cCa-P product ($cCa{\times}P$), and the prescription rate of non-calcium based P-binders. Results: A total of 163 patients were included from January to December 2009. A significant difference was shown in the percentage of patients in target $cCa{\times}P$ level at admission (MTC vs. UC, 81.40% vs. 91.67%; P = 0.038), but there was no significant difference at discharge. During admission, the cCa and P levels of patients in only UC group were significantly changed. In addition, compared with UC group, patients in MTC group were more likely prescribed appropriate P-binders, when they had higher $cCa{\times}P$ levels than $55mg^2/dL^2$ (P <0.001). Conclusion: It was found that MTC had beneficial effect on improving the regulation of CKD-MBD and the appropriate phosphate binder uses. Therefore, application of the MTC is anticipated to enhance quality of clinical care in chronic diseases.

• Childhood Kidney Diseases
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• v.26 no.2
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• pp.80-85
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• 2022

Purpose: To determine the prevalence, clinical manifestations, and outcomes of renal involvements in pediatric Alagille syndrome (ALGS). Methods: A total of 21 patients diagnosed with ALGS at age under 18 years who visited Samsung Medical Center from March 1999 to March 2022 were enrolled. ALGS was diagnosed either by clinical manifestations, targeted JAG1 sequencing, and/or liver biopsy. Medical records including sex, age, renal manifestations, urinalysis, serum creatinine, JAG1 sequencing, and ultrasonography were retrospectively reviewed. Results: The male to female ratio was 9:12. The mean age of patients at confirmative diagnosis of ALGS was 18.4 months. Sanger sequencing was performed for 17 patients. Sixteen of 21 patients (76.1%) showed JAG1 mutations. Renal involvement was found in 10 patients (47.6%). The most common type of anomaly was renal dysplasia (40%). One patient having renal dysplasia was pathologically confirmed with glomerular lipid deposition. Two patients (20%) manifested nephrocalcinosis/nephrolithiasis. Among eight renal-involved patients who survived, four (50%) progressed to chronic kidney disease stage 3. Two of these chronic kidney disease patients were diagnosed with hepatorenal syndrome. The other four patients had renal functions preserved, including two without any interventions and two who underwent urological interventions. Conclusions: The current study revealed a high prevalence of renal involvement in Korean pediatric ALGS with diverse phenotypes.

• Journal of Yeungnam Medical Science
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• v.30 no.2
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• pp.145-148
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• 2013

Thoracic endometriosis is an uncommon disease that has four main forms: catamenial pneumothorax, hemothorax, hemoptysis, and pulmonary nodules. Since the growth of endometrial tissue depends on the presence of estrogen, thoracic endometriosis usually occurs in menstruating women between 25 and 35 years of age. Menstrual disturbances are common in women with chronic kidney disease (CKD). However, they could be reversed after kidney transplantation. Therefore, previously asymptomatic endometriosis may become symptomatic after kidney transplantation. A 49-year-old woman with CKD underwent kidney transplantation. A month later, she experienced dyspnea, and hemothorax in her right hemithorax. However, there was no evidence of infectious diseases and malignancy in thoracentesis, pleural biopsy, and computed chest tomography (CT). The serum and pleural fluid levels of his carbohydrate antigen 125 were elevated. Hemothorax secondary to pleural endometriosis was suspected. We tried hormonal therapy, and the hemothorax disappeared. At the sixth-month follow-up, there was no recurrence of hemothorax.