Furosemide에 의한 소디움 운반체 발현의 변화

오윤규 ( Yoon Kyu Oh ),나기영 ( Ki Young Na ),이재욱 ( Jay Wook Lee ),장혜련 ( Hye Ryun Chang ),박영선 ( Young Sun Park ),박정환 ( Jung Hwan Park ),주권욱 ( Kwon Wook Joo ),김근호 ( Gheun Ho Kim ),이정상 ( Jung Sang Lee ),한진석 ( 대한신장학회 2003 Kidney Research and Clinical Practice Vol.22 No.2

배경 : 임상에서 흔히 사용하는 이뇨제 furosemide는 비후상행각에서 Na+-K+-2CI- cotranspoter (NKCC2)를 억제하여 NaCl 재흡수를 차단하여 이뇨작용을 나타낸다. Furosemide를 장기간 투여하면 내성과 대사성 알카리증의 부작용이 발생할 수 있는데, 이는 집합관에 도달하는 소디움 증가와 관련 있을 가능성이 있다. 방법 : 저자들은 furosemide의 내성이나 부작용이 집합관 상피 소디움 통로 (ENaC) 단백발현의 변화와 관련이 있는지를 확인하고자, Sprague-Dawley rat에서 farosemide (12 mg/day)을 7일간 지속적 피하 주입한 후 반정량적 immunoblotting과 면역조직화학법을 이용하여 NKCC2, Na +-CL- cotransporter (NCC), ENaC 단백의 발현을 관찰하였다. 실험기간 동안 수분과 전해질 용액 (0.8% NaCl & 0.1% KCl)을 자유롭게 섭취하도록 하여 체액 감소를 방지하였다. 결과 : 부형약 (vehicle)을 투여한 대조군에 비하여, furosemide를 투여한 군에서 각각 요량과 요 소디움 배설이 증가하였으나, 체중, 혈청 알도스테론치 및 크레아티닌 청소율은 차이가 없었다. Furosemid 투여 후 NKCC2 단백은 피질 (151±10 vs. 100±10%, p<0.05)과 외수질 (122±5 vs. 100±3%, p<0.01)에서 증가해 있었다. ENaC 단백은 세 가지 subunit 모두 furosemide 투여 후 대조군에 비하여 피질 (α:187±25 vs. 100±22%, p<0.05; β:155±8 vs. 100±15%, p<0.05; γ:168±16 vs. 100±9%, p<0.05)과 외수질 (α:171±27 vs. 100±17%, p<0.05; β :986±91 vs. 100±33%, p<0.01; γ :242±24 vs. 100±22%, p<0.01)에서 증 가하였다. 면역조직화학법에서도 furosemide를 투여한 군의 집합관 주세포에서 ENaC β-subunit가 더 강하게 염색되었다. 결론 : 이상에서 장기간 furosemide 투여시 집합관 ENaC 발현이 증가하며, 이러한 원위부네프론의 적응 반응이 이뇨제 내성을 유발하는데 기여할 것으로 생각한다. Background : Furosemide inhibit NaCl absorption in the thick ascending limb and produce an increase in distal delivery of Na+. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic furosemide infusion is associated with compensatory increases in the abundance of Na+ transporters in distal nephron. Methods : Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day of furosemide(n=6) with simultaneous administration of 0.8% NaCl and 0.1% KCl in drinking water for 7days. Results : Compared with vehicle infused controls, urine volume and urine sodium amount were increased. However, there were no differences in body weight, serum aldosterone, and creatinine clearance. The abundance of Na+-K+-2CI - cotransporter after furosemide infusion was increased in cortex (151±10 vs. 100±10%, p<0.05) and outer medulla (122±5 vs. 100±3%, p<0.01). In furosemide infusion group, the abundance of all three subunits of epithelial sodium channel (ENaC) was increased both in cortex (α:187±25 vs. 100±17%, p<0.05; β:155±8 vs. 100±15%, p<0.05; γ :168±16 vs. 100±9%, p<0.05) and outer medulla (α:171±27 vs. 100±17%, p<0.05; β :986±91 vs. 100±33%, p<0.01; γ :242±24 vs. 100±22%, p<0.01). Consistent with these results, ENaC β-subunit immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with furosemide treatment. Conclusion : These increases in the abundance of ENaC protein may account for the generation of diuretic tolerance.

Gitelman 증후군 환자에서 면역조직화학법으로 확인한 원위세관 sodium-chloride cotransporter (NCCT)의 결손

장혜련 ( Hye Ryoun Jang ),허남주 ( Nam Ju Heo ),손민정 ( Min Jung Son ),이재욱 ( Jay Wook Lee ),이정환 ( Jeong Hwan Lee ),전은실 ( Un Sil Jeon ),신성준 ( Sung Jun Shin ),나기영 ( Ki Young Na ),주권욱 ( Kwon Wook Joo ),이정상 ( Jun 대한내과학회 2005 대한내과학회지 Vol.69 No.6

목적 : Gitelman 증후군은 저포타시움혈증, 대사성 알칼리증, 고레닌혈증, 고알도스테론혈증, 요 중 칼슘 배설의 저하 및 저마그네슘혈증을 특징으로 하는 유전성 질환이다. 이는 원위세관 sodium-chloride cotransporter (NCCT)의 유전자 돌연변이에 의하여 발생하는 것으로 알려져 있으나 사람의 신조직에서 NCCT 결손이 증명된 바는 없었다. 방법 : 저자들은 임상적으로 Gitelman 증후군이 의심되는 환자에서 이뇨제를 이용한 신청소율 검사와 유전자 검사를 시행하였고, 이를 통하여 감별진단한 Gitelman 증후군 환자의 신조직에서 인간 NCCT에 대한 토끼 다클론 항체를 이용한 면역조직화학법을 시행하였다. 신세포암으로 신적출술을 시행 받은 환자의 정상 신조직과 전해질 이상이 없었던 사구체신염 환자의 신조직을 각각 정상 대조군과 질환 대조군으로 하였다. 결과 : 대상 환자는 저포타시움혈증과 대사성 알칼리증, 저마그네슘혈증 및 요 중 칼슘 배설의 저하를 보였다. Bartter 증후군과 감별을 위하여 furosemide 및 hydrochlorothiazide를 이용한 신청소율 검사를 시행하였다. 수분 부하를 시행한 기저치(86.1%)에 비해서 furosemide를 투여한 후 distal fractional chloride reabsorption이 감소하였으나(9.7%) hydrochlorothiazide 투여 후에는 변화가 없었다(81.4%). 유전자 검사 결과 SLC12A3 유전자의 돌연변이(S967F)가 발견되었다. 신조직에서 면역조직화학법을 시행한 결과 정상 및 질환 대조군에서는 원위세관 세포의 내강 막 쪽에 NCCT가 뚜렷이 염색되었으나, Gitelman 증후군에서는 원위세관 세포의 NCCT에 대한 면역 반응성이 관찰되지 않았다. 반면에 Na/K-ATPase, Na-K-2Cl cotransporter, calbindin-D28K는 대조군과 대상 환자의 신조직에서 모두 관찰되었다. 결론 : 기능적 검사로 진단된 Gitelman 증후군 환자의 신조직에서 NCCT의 결함을 면역조직화학법으로 확인하였다. Background : Gitelman`s syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is known to be caused by a mutation of SLC12A3 gene coding the sodium-chloride cotransporter (NCCT) in the distal tubule. The defect of NCCT in human renal tissues has not been investigated, and we tested whether the defect of NCCT can be detected in renal tissue of a patient with Gitelman`s syndrome by using immunohistochemistry. Methods : In an adult patient with Gitelman`s syndrome, blood and urine samples were collected for measurement of biochemical parameters. Renal clearance study and gene analysis were performed. Immunohistochemistry was performed on the renal tissue of the patient using a rabbit polyclonal antibody directed against a synthetic peptide corresponding to a portion in the amino terminal tail for human NCCT. Normal human renal tissues from surgical nephrectomy due to renal cell carcinoma and renal biopsy tissues from patients with glomerulonephritis but without any electrolyte disturbance were used as controls. Results : The patient had hypokalemic metabolic alkalosis, hypocalciuria and hypomagnesemia. Renal clearance study revealed a decrease in distal fractional chloride reabsorption after the administration of furosemide. SLC12A3 gene mutation (S967F) was found by direct sequencing method. Immunohistochemistry showed the absence of NCCT staining in the renal tissue of the patient. On the other hand, the immunostaining of other transporters was all positive in renal tissues from both Gitelman`s syndrome patients and controls. Conclusions : We report the absence of intact NCCT in the renal tissue of a Gitelman`s syndrome patient.(Korean J Med 69:642-650, 2005)

급성신손상 : 관상동맥우회수술 환자에서 에리쓰로포이에틴의 급성신손상 예방효과

송영림 ( Young Rim Song ),이태우 ( Tae Woo Lee ),진호준 ( Ho Jun Chin ),채동완 ( Dong Wan Chae ),나기영 ( Ki Young Na ) 대한신장학회 2008 춘계학술대회 초록집 Vol.28 No.1

인산염(phosphate)을 함유한 완하제 사용 후 고인산혈증을 보인 환자의 임상적 특징

성은영 ( Eun Young Seong ),신성준 ( Sung Joon Shin ),박정환 ( Jung Hwan Park ),이정표 ( Jung Pyo Lee ),박동준 ( Dong Jun Park ),조영민 ( Young Min Cho ),나기영 ( Ki Young Na ),김연수 ( Yon Su Kim ),안규리 ( Cu Rie Ahn ),한진석 ( J 대한내과학회 2005 대한내과학회지 Vol.68 No.1

신장에서 V2 - 수용체를 통한 옥시토신의 aquaporin - 2 발현 조절

전은실(Un Sil Jeon),나기영(Ki Young Na),오윤규(Yoon Kyu Oh),한진석(Jin Suk Han),이정상(Jung Sang Lee),주권욱(Kwon Wook Joo),김진(Jin Kim),김근호(Gheun Ho Kim) 대한내과학회 2002 대한내과학회지 Vol.62 No.3

N/A Background: Oxytocin is a nonapeptide hormone secreted from posterior pituitary gland and has a very similar structure to vasopressin. The aquaporin-2 (AQP2) water channel is predominantly expressed in the kidney and plays a key role in regulation of water permeability of mammalian collecting duct, exerted by both short-term and long-term vasopressin action. We speculated that oxytocin may be involved in some part of vasopressin-independent urinary concentrating mechanism by regulating AQP2 trafficking in the kidney. Methods: This study was undertaken to investigate whether and how the acute stimulation of oxytocin induces changes in AQP2 localization in the kidney. Immunohistochemistry and semiquantitative immunoblotting of AQP2 were carried out from Sprague-Dawley rat kidneys after a single intraperitoneal injection of oxytocin with or without pretreatment of a vasopressin-2 receptor (V2R) antagonist. Results: Urinary cAMP excretion was increased by oxytocin administration. Immuno- histochemistry of inner medullary collecting duct (IMCD) revealed that AQP2 was shifted from diffuse cytoplasmic localization in controls to the apical and basolateral membrane domains in oxytocin-treated rats. This pattern of AQP2 redistribution was noted in connecting tubule, cortical collecting duct and outer medullary collecting duct as in IMCD, although the tendency to basolateral localization was somewhat less. Semiquantitative immunoblotting of membrane fractions of whole kidney homogenates was also used t o assess redistribution of AQP2. The band density ratio of theplasma membrane-rich fraction over cyoplasmic vesicle- rich fraction was higher in oxytocin- treated rat s than in controls (3.64 ±0.60 vs. 1.09 ±0.14, p<0.05>. Regarding the receptor pathway of oxytocin action in the kidney, we found that pretreatment with a V2 R ant antagonist (OPC- 31260) blocked redistribution of AQP2 which was induced by oxytocin. Conclusion: In conclusion, oxytocin induces a V2 R- mediated redistribution of AQP2- containing cytoplasmic vesicles t o both apical and basolateral plasma membrane domains in r at kidney. Oxytocin may be one of the facts or that accounts for vasopressin - independent AQP2 t argeting in the kidney.(Korean J Med 62:268-277, 2002)

혈중 요산 농도가 IgA 신병증의 진행에 미치는 연구

진호준 ( Ho Jun Chin ),나기영 ( Ki Young Na ),정해일 ( Hae Il Cheong ),김연수 ( Yon Su Kim ),김성권 ( Suhng Gwon Kim ),채동완 ( Dong Wan Chae ) 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.2

목적: 요산은 고혈압의 발병원인으로 거론되고 있으며 신질환에서 고혈압과 신 동맥 병변을 유발하여 신기능 악화에 관여하는 것으로 보고되고 있다. 본 연구에서는 IgA 신병증에서 가능한 교란 변수 효과를 배제하여 요산의 신기능 악화인자 역할을 조사하고 그 병리 기전으로 요산과 고혈압 및 신동맥 병변과의 관련성을 조사하였다. 방법: 신조직 검사에서 확진을 받은 서울대학교 병원의 IgA 신병증 환자 172명을 대상으로 하였다. 신기능 악화 기준은 추적 도중 혈청 크레아티닌이 신 조직 검사 당시 혈청 크레아티닌의 2배 이상 증가하는 경우로 정하였다. 고요산군은 정상인 혈청 요산 수치의 4사분위에 해당되는 요산 수치를 가진 환자군으로 정하였다. 결과: IgA 신병증에서 혈중 요산 수치는 간질 섬유화, 세뇨관 위축, 세동맥 경화의 존재와 관련이 있었고, 추적 전후 혈압의 변동과는 무관하였다. 고요산군은 다변량 분석에서 IgA 신병증의 신기능 악화에 대한 위험인자 이었다. 고혈압, 사구체 여과율, 병리 소견으로 세분하여 분석한 결과 고요산군은 고혈압 유무와 세동맥 경화 유무에 관련없이 신병증의 예후를 결정하는 독립적인 인자이었고, 사구체 여과율이 60mL/min/1.73m2 이상인 환자군에서도 예후 인자로 분석되었다. 결론: IgA 신병증에서 고요산혈증은 신 동맥 병변과 신기능 악화와 관련이 있었다. Purpose: Many evidences about hyperuricemia as a risk factor to hypertension and renal progression in kidney diseases have been reported. We have analyzed the impact of uric acid on renal progression of IgA nephropathy while getting rid of possible confounding variables and revealed the possible pathophysiology of uric acid in terms of hypertension or renal vasculopathy provoked by uric acid. Methods: We selected 172 patients with IgA nephropathy diagnosed by renal biopsy at Seoul National University Hospital. We adapted the criteria of renal progression as the final value of serum creatinine increased more then twice compared to the value at renal biopsy. Results: Serum uric acid was correlated with the severity of interstitial fibrosis and tubular atrophy and the presence of artherosclerosis. The incidence of hypertension during follow-up period was not different between low uric acid group and high uric acid group. The high uric acid level was an independent risk factor to renal progression in IgA nephropathy with multivariate analysis regardless of the presence of hypertension or artherosclerosis of renal pathologic finding. The high uric acid level was also a risk factor to renal progression in patients with estimated GFR more than 60 mL/min/1.73m2. Conclusion: Serum uric acid was related to the presence of artherosclerosis and the renal progression of IgA nephropathy.

전자의무기록 팝업차트를 활용한 CRRT 관리의 질향상 활동

고수령,이안나,김기표,진호준,나기영,채동완,김세중,Go, Su-Ryeong,Lee, An-Na,Kim, Ki-Pyo,Chin, Ho-Jun,Na, Ki-Young,Chae, Dong-Wan,Kim, Se-Joong 한국의료질향상학회 2019 한국의료질향상학회지 Vol.25 No.1

Purpose: The time lag between the decision to initiate continuous renal replacement therapy (CRRT) and its actual initiation remains a major barrier in our intensive care units. We developed a CRRT pop-up chart on EMR for managing CRRT machines. Methods: This study measured time interval between the decision to prepare the CRRT machine and the actual use of the machine before and after using a CRRT pop-up chart. This study conducted a questionnaire of the medical staff to assess the changes in the quality of CRRT preparation. Results: A total of 95 patients on CRRT is analyzed. The time to find an available CRRT machine is decreased by 24.6%. The time to move a CRRT machine to the patient's bedside is decreased by 55.8%. Medical surveys of 44 nurses gave the following results. 1) The time to apprehend machines for 1 to 3 minutes is improved from 29.5% to 81.8%, and the time to apprehend machines over 3 minutes is decreased from 70.5% to 18.2%. 2) The number (6-all) of known machine locations is improved from 22.7% to 63.4%. 3) Interruption of a nurse's work due to telephone calls asking for the possession of movable CRRT equipment also is improved. Scores of 1-4 are improved from 15.9% to 41%. Scores of 5-7 are reduced from 52% to 15.9%. Conclusions: CRRT pop-up chart is shortened the time lag of CRRT machine preparation, reduced the nurse's phone workload and helped to improve the quality of CRRT care.

한국인에서 고요산혈증 및 대사 증후군이 고혈압의 발생에 미치는 영향

진호준 ( Ho Jun Chin ),나기영 ( Ki Young Na ),김연수 ( Yon Su Kim ),채동완 ( Dong Wan Chae ),김성권 ( Suhng Gwon Kim ) 대한내과학회 2007 대한내과학회지 Vol.73 No.1

요산은 건강 검진을 받은 대상군에서 성별 및 대사 증후군과 무관하게 고혈압 발병의 위험인자이었으며, 대사증후군 역시 고혈압 발병에 중요한 위험인자이었다. Backgrouds: Uric acid has been proposed as an important risk factor for the development of primry hypertension. Many factors related to the serum uric acid level also influence the prevalence and incidence of hypertension. Especially, hyperuricemia is considered a secondary phenomena of metabolic syndrome. We evaluated the impact of uric acid and metabolic syndrome on the development of hypertension, with exclusion of the possible effects of confounding factors on both the uric acid level and the incidence of hypertension. Methods: We included 2,390 subjects without hypertension who had undergone multiple health check-ups at the Seoul National University Hospital during the last 10 years. We selected the JNC VII criteria for hypertension and the modified ATP III criteria for metabolic syndrome. Results: During the mean follow-up period of 54.3 months, hypertension was developed in 32.2% of the subjects. The incidence of hypertension in the high uric acid group was higher than that in the low uric acid group. Metabolic syndrome was an independent risk factor for hypertension and it was closely related to the prevalence of high uric acid level. Uric acid was also an independent risk factor for hypertension in each gender. The relationship between uric acid and hypertension was evident for the subjects without metabolic syndrome. Conclusions: Serum uric acid was a risk factor for hypertension in each gender regardless of the absence of metabolic syndrome. Metabolic syndorme also contributed to the development of hypertension.(Korean J Med 73:58-66, 2007)

UltraTEV를 이용한 변전소 부분방전 진단의 실제

김대복(Dae-Bok Kim),나기영(Ki-Young Na) 대한전기학회 2012 대한전기학회 학술대회 논문집 Vol.2012 No.4

UltraTEV 활용 부분 방전 진단

김대복(Dae-Bok Kim),나기영(Ki-Young Na),윤성수(Sung-Soo Yoon) 대한전기학회 2011 대한전기학회 학술대회 논문집 Vol.2011 No.11