1.Safety and durable patency of tunneled hemodialysis catheter inserted without fluoroscopy
Do Hyoung KIM ; Sojung YOUN ; Tae Hyun BAN ; Bum Soon CHOI ; Byung Soo KIM ; Cheol Whee PARK ; Chul Woo YANG ; Hoon Suk PARK
Kidney Research and Clinical Practice 2023;42(6):723-730
		                        		
		                        			
		                        			 A tunneled hemodialysis (HD) catheter is preferred due to its lower incidence of infection and malfunction than non-tunneled ones. For safer insertion, fluoroscopic guidance is desirable. However, if the patient is unstable, transfer to the fluoroscopy may be impossible or inappropriate. Methods: From June 2019 to September 2022, 81 tunneled HD catheter insertion cases performed under ultrasound guidance without fluoroscopy and 474 cases with fluoroscopy in our institutional HD catheter cohort were retrospectively compared. Results: Immediate complications, later catheter-associated problems, including infections and catheter dysfunction, were comparable between the two groups (p = 0.20 and p = 0.37, respectively). The patency of tunneled catheters inserted without fluoroscopy was comparable to the patency of tunneled catheters inserted with fluoroscopic guidance (p = 0.90). Conclusion: Tunneled HD catheter insertion without fluoroscopy can be performed safely and has durable patency compared to the insertion with fluoroscopy. Therefore, this method can be considered for the selected unstable patients (e.g., ventilator care) in the intensive care unit. 
		                        		
		                        		
		                        		
		                        	
2.Crohn’s Disease Identified as Granulomatous Tubulointerstitial Nephritis
Jung Suk HAN ; Bum Soon CHOI ; Cheol Whee PARK ; Yeong Jin CHOI ; Chul Woo YANG ; Han Hee LEE ; Tae Hyun BAN
Korean Journal of Medicine 2022;97(3):186-190
		                        		
		                        			
		                        			 Crohn’s disease is usually diagnosed according to intestinal symptoms, but extra-intestinal manifestations are important in approximately one-third of cases. Although several extra-intestinal symptoms associated with various organs have been reported, renal involvement is uncommon in patients with Crohn’s disease. Tubulointerstitial nephritis in a patient with Crohn’s disease is usually caused by infection, sarcoidosis, or medications. However, primary tubulointerstitial nephritis caused by Crohn’s disease alone is extremely rare. A 19-year-old male patient was referred to our hospital because of an increase in serum creatinine level. He underwent a kidney biopsy with renal insufficiency. Renal histological findings revealed granulomatous tubulointerstitial nephritis. Thereafter, a colonoscopy was performed with suspicion of Crohn’s disease. Ultimately, he was diagnosed with granulomatous tubulointerstitial nephritis based on Crohn’s disease. The patient had improved gastrointestinal symptoms after the last treatment. This case report presents a rare case of primary tubulointerstitial nephritis caused by Crohn’s disease. 
		                        		
		                        		
		                        		
		                        	
3.Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death
Yu Ji JIANG ; Sheng CUI ; Kang LUO ; Jun DING ; Qi Yan NAN ; Shang Guo PIAO ; Mei Ying XUAN ; Hai Lan ZHENG ; Yong Jie JIN ; Ji Zhe JIN ; Jung Pyo LEE ; Byung Ha CHUNG ; Bum Soon CHOI ; Chul Woo YANG ; Can LI
The Korean Journal of Internal Medicine 2021;36(6):1437-1449
		                        		
		                        			 Background/Aims:
		                        			Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. 
		                        		
		                        			Methods:
		                        			Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). 
		                        		
		                        			Results:
		                        			Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. 
		                        		
		                        			Conclusions
		                        			Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC. 
		                        		
		                        		
		                        		
		                        	
4.L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction
Hai Yan ZHAO ; Hui Ying LI ; Jian JIN ; Ji Zhe JIN ; Long Ye ZHANG ; Mei Ying XUAN ; Xue Mei JIN ; Yu Ji JIANG ; Hai Lan ZHENG ; Ying Shun JIN ; Yong Jie JIN ; Bum Soon CHOI ; Chul Woo YANG ; Shang Guo PIAO ; Can LI
The Korean Journal of Internal Medicine 2021;36(Suppl 1):S180-S195
		                        		
		                        			 Background/Aims:
		                        			Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. 
		                        		
		                        			Methods:
		                        			Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. 
		                        		
		                        			Results:
		                        			LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. 
		                        		
		                        			Conclusions
		                        			LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney. 
		                        		
		                        		
		                        		
		                        	
5.Mesenchymal Stem Cell-Mediated Therapy of Peripheral Artery Disease Is Stimulated by a Lamin A-Progerin Binding Inhibitor
Soon Chul HEO ; Yang Woo KWON ; Gyu Tae PARK ; Sang Mo KWON ; Sun Sik BAE ; Bum-Joon PARK ; Jae Ho KIM
Journal of Lipid and Atherosclerosis 2020;9(3):460-473
		                        		
		                        			 Objective:
		                        			Human adipose tissue-derived mesenchymal stem cells (ASCs) have been reported to promote angiogenesis and tissue repair. However, poor survival and engraftment efficiency of transplanted ASCs are the major bottlenecks for therapeutic application. The present study aims to improve the therapeutic efficacy of ASCs for peripheral artery diseases. 
		                        		
		                        			Methods:
		                        			Hydrogen peroxide (H2O2) was used to induce apoptotic cell death in ASCs.To measure apoptosis, we used flow cytometry-based apoptosis analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. A murine hindlimb ischemia model was established to measure the ASC-mediated therapeutic angiogenesis and in vivo survival ability of ASCs. 
		                        		
		                        			Results:
		                        			We identified that the inhibitor of lamin A-progerin binding, JH4, protects ASCs against H2O2-induced oxidative stress and apoptosis. Co-administration of ASCs with JH4 improved ASC-mediated blood reperfusion recovery and limb salvage compared to that of the control group in a mouse hind limb ischemia model. Immunofluorescence showed that JH4 treatment potentiated ASC-mediated vascular regeneration via reducing ASC apoptosis post transplantation. 
		                        		
		                        			Conclusion
		                        			JH4 exerts anti-apoptotic effects in ASCs in conditions of oxidative stress, and contributes to the repair of ischemic hind limb injury by improving cell survival. 
		                        		
		                        		
		                        		
		                        	
6.Clinical outcomes and effects of treatment in older patients with idiopathic membranous nephropathy
Yaeni KIM ; Hye Eun YOON ; Byung Ha CHUNG ; Bum Soon CHOI ; Cheol Whee PARK ; Chul Woo YANG ; Yong Soo KIM ; Yu Ah HONG ; Suk Young KIM ; Yoon Kyung CHANG ; Hyeon Seok HWANG
The Korean Journal of Internal Medicine 2019;34(5):1091-1099
		                        		
		                        			 BACKGROUND/AIMS:
		                        			Membranous nephropathy (MN) is the most common primary glomerular disease diagnosed in older patients. Few reports describe the clinical outcomes in older patients with idiopathic MN.
		                        		
		                        			METHODS:
		                        			The outcomes of 135 patients with histologically proven MN were analyzed. ‘Older’ was defined as 60 years of age or older at the time of the renal biopsy. The rates of complete remission (CR), progression to end-stage renal disease (ESRD) and infection were compared between older and younger patients.
		                        		
		                        			RESULTS:
		                        			The cumulative event rate for achieving CR was inferior (p = 0.012) and that for requiring renal replacement was higher (p = 0.015) in older patients, and they had a greater risk of infection (p = 0.005). Older age was a significant predictor of a lower rate of CR (adjusted odds ratio [OR], 0.51; 95% confidence interval [CI], 0.26 to 0.98), and was a robust predictor of infection (adjusted OR, 5.27; 95% CI, 1.31 to 21.20). Conservative treatment was associated with a lower remission rate (p = 0.036) and corticosteroid treatment was less effective in achieving CR (p = 0.014), in preventing progression to ESRD (p = 0.013) and in reducing infection (p = 0.033) in older patients. Cyclosporine treatment had similar clinical outcomes with regard to CR, ESRD progression, and infection in older patients.
		                        		
		                        			CONCLUSIONS
		                        			Older age was independently associated with inferior rates of CR and greater risk of infection. Treatment modalities affected the outcomes of older patients differently in that cyclosporine treatment is predicted to be more useful than corticosteroids. 
		                        		
		                        		
		                        		
		                        	
7.Shen-Kang protects against tacrolimus-induced renal injury
Long Ye ZHANG ; Jian JIN ; Kang LUO ; Shang Guo PIAO ; Hai Lan ZHENG ; Ji Zhe JIN ; Sun Woo LIM ; Bum Soon CHOI ; Chul Woo YANG ; Can LI
The Korean Journal of Internal Medicine 2019;34(5):1078-1090
		                        		
		                        			 BACKGROUND/AIMS:
		                        			Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy.
		                        		
		                        			METHODS:
		                        			Rats were treated daily with TAC (1.5mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor β1 [TGF-β1] and TGF-β inducible gene-h3 [βig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death.
		                        		
		                        			RESULTS:
		                        			Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-β1/Smad2/3, βig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/Bcl2-associated X [Bcl-2/Bax] ratio).
		                        		
		                        			CONCLUSIONS
		                        			SK protects against TAC-induced renal injury. 
		                        		
		                        		
		                        		
		                        	
8.Changing pattern and safety of pretransplant malignancy in kidney transplant recipients
Tae Hyun BAN ; Woo Yeong PARK ; Kyubok JIN ; Seungyeup HAN ; Byung Ha CHUNG ; Sun Cheol PARK ; Bum Soon CHOI ; Cheol Whee PARK ; Sang Seob YUN ; Yong Soo KIM ; Chul Woo YANG
Kidney Research and Clinical Practice 2019;38(4):509-516
		                        		
		                        			
		                        			BACKGROUND: Cancer rates are increasing not only in the general population but also in patients with end-stage renal disease. We investigated the changing pattern of pretransplant malignancy in kidney transplant recipients over 5 decades.METHODS: We reviewed 3,748 kidney transplant recipients between 1969 and 2016. We divided patients into three groups (1969–1998, 1999–2006, 2007–2016) based on the era of the cancer screening system used throughout the nation. We analyzed the incidence and pattern of pretransplant malignancy among the three groups. We also evaluated recurrent and de novo malignancy in these patients compared to patients without pretransplant malignancy.RESULTS: A total of 72 patients exhibited pretransplant malignancy (1.9%). There were no cases of pretransplant cancer until 1998, but the rate of pretransplant malignancy gradually increased to 1.1% during 1999–2006 and further increased to 4.3% thereafter. The most frequent types of pretransplant malignancy changed from the bladder, liver, and stomach cancers to thyroid cancer and renal cell carcinoma. There were no de novo cases, but there were three cases of recurrent cancer in patients with pretransplant malignancy; the recurrence rate among kidney transplant recipients with pretransplant malignancy was not significantly different from the incidence rate of de novo malignancy among kidney transplant recipients without pretransplant malignancy (4.2% vs. 6.9%, P = 0.48).CONCLUSION: The incidence of pretransplant malignancy in kidney transplantation candidates is gradually increasing, and recent increases were accompanied by changes in cancer types. Pretransplant malignancy may not be a hindrance to kidney transplantation because of the low incidence of posttransplant recurrence and de novo malignancy.
		                        		
		                        		
		                        		
		                        			Carcinoma, Renal Cell
		                        			;
		                        		
		                        			Early Detection of Cancer
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Incidence
		                        			;
		                        		
		                        			Kidney Failure, Chronic
		                        			;
		                        		
		                        			Kidney Transplantation
		                        			;
		                        		
		                        			Kidney
		                        			;
		                        		
		                        			Liver
		                        			;
		                        		
		                        			Recurrence
		                        			;
		                        		
		                        			Stomach Neoplasms
		                        			;
		                        		
		                        			Thyroid Neoplasms
		                        			;
		                        		
		                        			Transplant Recipients
		                        			;
		                        		
		                        			Urinary Bladder
		                        			
		                        		
		                        	
9.Clinical significance of the presence of anti-human leukocyte antigen-donor specific antibody in kidney transplant recipients with allograft dysfunction
Byung Ha CHUNG ; Jeong Ho KIM ; Bum Soon CHOI ; Cheol Whee PARK ; Ji Il KIM ; In Sung MOON ; Yong Soo KIM ; Yeong Jin CHOI ; Eun Jee OH ; Chul Woo YANG
The Korean Journal of Internal Medicine 2018;33(1):157-167
		                        		
		                        			 BACKGROUND/AIMS:
		                        			This study investigated the clinical significance of detecting anti-human leukocyte antigen-donor specific antibody (HLA-DSA) in kidney transplant recipients (KTRs) requiring indication biopsy owing to allograft dysfunction.
		                        		
		                        			METHODS:
		                        			We analyzed the presence of HLA-DSA in 210 KTRs who took indication biopsy. We divided these cases into two groups, HLA-DSA (+) (n = 52) and HLA-DSA (–) (n = 158) group, and compared the clinical characteristics, pathological findings, and clinical outcomes of the two groups.
		                        		
		                        			RESULTS:
		                        			The rates of retransplant, pretransplant sensitization, and HLA-mismatch were significantly higher in HLA-DSA (+) group than in HLA-DSA (–) group (p < 0.05 for each comparison). In histologic finding, all types of rejections were more frequent in the former group. Besides, scores of both the T-cell injury markers such as tubulitis, interstitial inf lammation, and vasculitis and antibody-mediated injury markers such as peritubular C4d deposition and microvascular inflammation (glomerulitis plus peritubular capillaritis) were higher in HLA-DSA (+) group (p < 0.05 for each). Notably, allograft outcomes were worse in HLA-DSA (+) group. Further, multivariate analysis showed that presence of HLA-DSA, advanced interstitial fibrosis/tubular atrophy (interstitial fibrosis plus tubular atrophy ≥ 2), and allograft rejection in biopsy were independent risk factors for allograft failure.
		                        		
		                        			CONCLUSIONS
		                        			The results of this study showed that presence of HLA-DSA in a case of allograft dysfunction adversely influences allograft outcome, and its detection, irrespective of the result of the allograft biopsy, necessitates intensive monitoring and treatment. 
		                        		
		                        		
		                        		
		                        	
10.Stabilization of serum alkaline phosphatase in hemodialysis patients by implementation of local chronic kidney disease-mineral bone disorder management strategy: A quality improvement study.
Kyubok JIN ; Tae Hyun BAN ; Ji Yong JUNG ; Ae Jin KIM ; Yaerim KIM ; So Young LEE ; Dong Ho YANG ; Bum Soon CHOI ; Kook Hwan OH ; Jieun KIM ; Young Joo KWON ; Jong Wook CHOI ; Gheun Ho KIM
Kidney Research and Clinical Practice 2018;37(2):157-166
		                        		
		                        			
		                        			BACKGROUND: The aim of this study is to narrow the gap between global guidelines and local practices, we recently established domestic recommendations by adapting the international guidelines for management of chronic kidney disease-mineral bone disorder (CKD-MBD) in patients on maintenance hemodialysis (MHD). This study was undertaken to determine whether application of this guideline adaptation was associated with improved serum mineral profiles in patients with CKD-MBD. METHODS: A total of 355 patients on MHD were enrolled from seven dialysis units. After adhering to our strategy for one year, serum phosphorus, calcium, intact parathyroid hormone (iPTH), and alkaline phosphatase (AP) levels were compared with the baseline. The endpoint was improvement in the proportion of patients with serum mineral levels at target recommendations. RESULTS: The median serum phosphorus level and proportion of patients with serum phosphorus within the target range were not changed. Although the median serum calcium level was significantly increased, the proportion of patients with serum calcium within the target range was not significantly affected. The proportion of patients with serum iPTH at the target level was not altered, although the median serum iPTH was significantly decreased. However, both median serum AP and the proportion of patients with serum AP at the target level (70.4% vs. 89.6%, P < 0.001) were improved. CONCLUSION: In our patients with MHD, serum mineral profiles were altered and the serum AP level stabilized after implementing our recommendations. Long-term follow-up evaluations are necessary to determine whether uremic bone disease and cardiovascular calcifications are affected by these recommendations.
		                        		
		                        		
		                        		
		                        			Alkaline Phosphatase*
		                        			;
		                        		
		                        			Bone Diseases
		                        			;
		                        		
		                        			Calcium
		                        			;
		                        		
		                        			Dialysis
		                        			;
		                        		
		                        			Follow-Up Studies
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hyperparathyroidism, Secondary
		                        			;
		                        		
		                        			Kidney*
		                        			;
		                        		
		                        			Miners
		                        			;
		                        		
		                        			Parathyroid Hormone
		                        			;
		                        		
		                        			Phosphorus
		                        			;
		                        		
		                        			Quality Improvement*
		                        			;
		                        		
		                        			Renal Dialysis*
		                        			
		                        		
		                        	
            
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