원위부 신세뇨관성 산증에서 산-염기 운반체의 결손

김혜영,한진석,전은실,진호준,주권욱,나기영,정우경,오지은,김현리,이서진,이중건,김근호,엄재호,궁성수,김진,이정상 대한신장학회 2000 대한신장학회잡지 Vol.19 No.5

장기간 이뇨제 투여에 따른 요 산성화 능력과 집합관 H^(+)-ATPase 발현의 변화

김근호,나기영,한진석,오윤규,이정상,주권욱,엄재호 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2

목 적 : 저자들은 임상에서 흔히 사용하면서 대사성 알칼리증을 유발할 수 있는 furosemide와 hydrochlorothiazide를 장기간 투여할 때 발생하는 요 산성화능의 변화를 관찰하고, 이에 동반하여 근위세관 및 헨리고리관의 NHE3와 집합관의 H^(+)-ATPase 단백 발현에 변화가 있는지 조사하고자 하였다. 방 법 : Sprague-Dawley rat에서 수분과 전해질 용액을 자유롭게 섭취시키면서 furosemide12 mg/day/rat 혹은 hydrochlorothiazide 7.5 mg/day/rat을 각각 7일간 지속적 피하 주입시킨 후 신장에서 반정량적 immunoblot 분석을 시행하여 대조군과 비교하였다. 결 과 : Furosemide 투여 후 대조군과 실험군 사이에 체중, 혈청 알도스테론 및 크레아티닌청소율은 차이가 없었다. 요량 및 요 소디움 배설은 furosemide 투여 후 현저하게 증가하였다. 요 pH가 furosemide 투여 후 감소하였고, 요 암모늄 배설은 furosemide 투여 후 증가하였다. 반정량적 immunoblot 분석 결과 furosemide 투여 후 신 피질의 NHE3 발현에 유의한 변화는없었으나, 신 외수질의 NHE3 발현은 실험군(182±25%)에서 대조군(100±25%)에 비해 증가하였다(p<0.05). 또한, H^(+)-ATPase B1 subunit 발현은 furosemide 투여 후 신 피질(대조군100±13%, 실험군 178±11%, p<0.01)과 신 외수질(대조군 100±29%, 실험군 239±24%, p<0.05)에서 모두 증가하였다. Hydrochlorothiazide 투여 실험에서도 요량 및 요 소디움 배설의 증가와 요 pH의 감소를 확인하였다. 신 피질과 외수질의 NHE3 발현은 hydrochlorothiazide투여 후 변화 없었으나, H^(+)-ATPase B1 subunit 발현은 신 피질(대조군 100±24%, 실험군212±27%, p<0.05)과 신 외수질(대조군 100±13%, 실험군 194±13%, p<0.01)에서 모두 증가하였다. 결 론 : 장기간 furosemide 혹은 hydrochlorothiazide 투여에 의해 원위 요 산성화 능력의 항진을 확인하였고, 이는 집합관 H^(+)-ATPase 단백 발현이 증가하여 발생한 결과로 설명할 수 있을 것으로 생각한다. Purpose : Commonly used diuretics such as furosemide and hydrochlorothiazide may cause metabolic alkalosis by increasing proton secretion from distal nephron. We evaluated changes in urinary acidification and abundance of proton-secreting transporters in response to chronic subcutaneous infusion of diuretics. Methods : Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day furoemide or hydrochlorothiazide 7.5 mg/day for 7 days. All animals were offered tap water and a solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. Results : Compared with vehicle-infused controls, diuretic and natriuretic responses were evident from furosemide or hydrochlorothiazide infusion. However, there were no changes in body weight, serum aldosterone and creatinine clearance between diureticinfused( n=6) and control(n=6) rats. In both furosemide- infused and hydrochlorothiazide-infused rats, urine pH was significantly lowered compared with controls. Furosemide-infused rats showed significantly larger excretion of urinary ammonium. Semiquantitative immunoblotting was carried out from rat kidneys to investigate abundance of proximal tubule or medullary thick ascending limb Na^(+)/H^(+) exchanger type 3(NHE3) and collecting duct H^(+)- ATPase using specific polyclonal antibodies to NHE3 and H^(+)-ATPase B1 subunit, respectively. The abundance of NHE3 from cortical homogenates was not changed by either furosemide or hydrochlorothiazide infusion. However, the abundance of NHE3 from outer medullary homogenates was increased by furosemide infusion. The H^(+)-ATPase B1 subunit abundance was increased by furosemide or hydrochlorothiazide infusion in both cortical and outer medullary homogenates. Conculsion : These increases in the abundance of proton-secreting transporters may account for the enhanced distal urinary acidification in response to chronic diuretic administration. (Korean J Nephrol 2002;21(2):222-231)

이뇨제의 저항성과 내성 기전

오윤규,나기영,김근호,김소영,한진석 대한신장학회 2001 대한신장학회잡지 Vol.20 No.5

정상인에서 옥시토신의 항이뇨 작용

주권욱,전은실,오윤규,김근호,한진석,김성권,이정상 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2

배 경 : 옥시토신은 바소프레신과 매우 유사한 구조의 호르몬으로서, 과거부터 항이뇨 효과가 있을 것으로 생각하였으나, 최근에야 체외실험을 통하여 옥시토신의 항이뇨 작용이 증명되었다. 인체에서도 옥시토신이 항이뇨 호르몬으로 작용할 가능성이 있지만 아직 분명하지 않다. 저자들은 정상인에게 옥시토신 또는 desmopressin(dDAVP)을 투여하여 인체에서 옥시토신의 항이뇨 효과를 직접적으로 검증하고자 하였다. 방 법: 신기능 장애의 증거가 없는 건강한 성인 남자 10명을 대상으로 기저상태와 옥시토신(20 mU/hour로 정주) 또는 dDAVP(2 μg을 피하 주사)를 투여한 후 2시간 동안 수집한 요에서 요량, 요 삼투질농도, 자유수분 청소율 등을 측정하였고, 요 전해질 배설의 변화를 함께 관찰하였다. 결 과 : 혈청 전해질이나 삼투질농도는 옥시토신 또는 dDAVP 투여 후에 기저상태에 비해 유의한 변화가 없었다. 2시간 요량은 기저상태 446±75 mL로부터, dDAVP 투여 후 92±9 mL로 감소하였고(p<0.05), 옥시토신 투여 후에는 289±53 mL로 변화하였다. 요 삼투질농도는 기저상태 223±25.0 mOsm/kg에서, dDAVP 투여 후 936±34 mOsm/kg 및 옥시토신 투여 후427±63 mOsm/kg로 모두 증가하였다(p<0.05). 자유수분 청소율은 기저상태 110±51 mL/2hour로부터, dDAVP 투여 후 -218±28 mL/2 hour, 옥시토신 투여 후 -57±51 mL/2 hour로 각각 감소하였다(p<0.05). 요나트륨분획배설율(FENa)을 포함한 다른 요 전해질 배설의 유의한 변화는 없었다. 결 론 : 옥시토신이 정상 성인 남자에서 요 삼투질농도의 증가 및 자유수분 청소율의 저하를유발함을 확인하였으며, 이는 옥시토신이 인체에서도 항이뇨 작용이 있음을 시사하는 결과이다. 그러나 생리적인 농도에서 옥시토신이 어떤 역할을 할 것인가와 그 작용기전은 앞으로 규명되어야 할 과제이다. Background : The antidiuretic action of oxytocin in human has been controversial. To investigate whether oxytocin directly acts on water balance in human, we evaluated the parameters of urinary concentration in response to administration of oxytocin in ten healthy male volunteers. Methods : Oxytocin was infused intravenously at a rate of 20 mU/hour for 2.5 hours and urine was collected during the last 2 hours of oxytocin infusion. Changes in urine volume, urine osmolality, excretions of urine electrolytes and free water clearance after the administrartion of oxytocin were compared with the baseline data. Results : The changes in the levels of serum electrolytes and osmolality after the administration of oxytocin were not significant compared with the baseline data. The volume of 2 hours' urine were 446±75 mL and 289±53 mL in the basal state and after the administration of oxytocin, respectively. The urine osmolality was increased significantly by the infusion of oxytocin(427±63 mOsm/kg) compared with that in the basal state(223±25 mOsm/kg)(p< 0.05). The free water clearance was 110±51 mL/2 hours in the basal state and decreased significantly to -57±51 mL/2 hours(p<0.05). Conclusion : We conclude that administration of oxytocin to normal men enhances urinary concentration, evidenced by increased urinary osmolality and decreased free water clearance. In human, oxytocin may play an important role in the regulation of renal water excretion as an antidiuretic hormone. (Korean J Nephrol 2002;21(2):251-258)

Pseudohyponatremia : Does It Matter in Current Clinical Practice?

Gheun Ho Kim 대한전해질·혈압학회 2006 Electrolytes & Blood Pressure Vol.4 No.2

Review : Gaps between Global Guidelines and Local Practices in CKD-MBD

( Gheun Ho Kim ) 대한전해질학회 2014 Electrolytes & Blood Pressure Vol.12 No.2

The term ‘chronic kidney disease-mineral bone disorder’ (CKD-MBD) is a new term that, in contrast to the old term ‘renal osteodystrophy’, implies a systemic syndrome associated with cardiovascular morbidity and mortality. This new terminology is in line with previous studies that show elevated serum calcium, phosphorus, and parathyroid hormone (PTH) levels associated with increased cardiovascular and all-cause mortality. In order to improve outcomes in patients with CKD-MBD, many countries have developed clinical practice guidelines. Globally, the Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines are the most commonly used. However, whether these global guidelines can be successfully implemented on a local level needs to be studied. Differences in medical care and social factors between countries may limit the generalizability of global guidelines. Reports from the Korean registry and the Dialysis Outcomes and Practice Patterns Study (DOPPS) suggest that many dialysis patients are not within the target ranges recommended by the KDOQI and KDIGO guidelines for serum calcium, phosphorus, and PTH, suggesting gaps between global guidelines and local practices. Clinical studies with Korean CKD-MBD patients are necessary to compare Korean practices and outcomes to those suggested by global guidelines and to determine the target serum mineral levels associated with the best local outcomes.

Primary cilia of the kidney: from ciliopathy to urinary concentration

( Gheun-ho Kim ) 대한신장학회 2023 Kidney Research and Clinical Practice Vol.42 No.3

부종 질환에서 Oxytocin이 수분대사에 미치는 영향

김혜영,이종호,한진석,이정상,전은실,김근호,안규리,이서진,주권욱,허우성,김성권 대한신장학회 1998 Kidney Research and Clinical Practice Vol.17 No.4

Antidiuretic action of oxytocin is confirmed by in vitro study using with rat IMCD. Vasopressin is elevated in edematous disorders and may play a pathogenetic role in the formation of edema. If oxytocin plays a sirnilar role to vasopressin in water disturbances in human, oxytocin may change as the same way as vasopressin. To verify a role of oxytocin in the regulation of water balance in human, we measured plasma and urine oxytocin with vasopressin by radioimmunoassay in thirteen patients with generalized edema(8 nephrotic syndrome, 3 liver cirrhosis, 2 acute renal failure) before and after control of edema. And they were compared them with those of seven normal controls. As a result,plasma oxytocin and vasopressin Levels of patients with edematous state were higher than those of normal controls(p$lt;0.01).Plasma oxytocin of patients decreased after control of edema(table,P$lt;0.05), but was still higher than of normal controls(table, P$lt;0.01). Plasma vasopressin did not change after control of edema and sustained at elevated level(Table) Plasma oxytocin level correlated with plasma vasopressin level(r=0.543: P$lt;0.05) and urinary oxytocin level correlated linearly with urinary vaso-pressin(r=0.983, P$lt;0.01). After control of edema, body weight of patients decreased from 65±2 to 58±2kg and fractional excretion of sodium decreased from 3.3±1.1 to 1.2±0.696(P$lt;0.05). There were no significant changes in serum and urine Na, osmolality, free water clearance, plasma renin activity, aldosterone and norepinephrine. In conclusion, oxytocin was elevated in edematous disorders, and may participate in formation of edema similar to vasopressin.

Becoming a high impact journal

( Gheun-ho Kim ) 대한신장학회 2020 Kidney Research and Clinical Practice Vol.39 No.4

Treating lithium-induced nephrogenic diabetes insipidus with a COX-2 inhibitor improves polyuria via upregulation of AQP2 and NKCC2.

Kim, Gheun-Ho,Choi, Nak Won,Jung, Ju-Young,Song, Ji-Hyun,Lee, Chang Hwa,Kang, Chong Myung,Knepper, Mark A American Physiological Society 2008 American Journal of Physiology Vol.294 No.4

<P>Prostaglandin E(2) may antagonize vasopressin-stimulated salt absorption in the thick ascending limb and water absorption in the collecting duct. Blockade of prostaglandin E(2) synthesis by nonsteroidal anti-inflammatory drugs (NSAIDs) enhances urinary concentration, and these agents have antidiuretic effects in patients with nephrogenic diabetes insipidus (NDI) of different etiologies. Because renal prostaglandins are derived largely from cyclooxygenase-2 (COX-2), we hypothesized that treatment of NDI with a COX-2 inhibitor may relieve polyuria through increased expression of Na-K-2Cl cotransporter type 2 (NKCC2) in the thick ascending limb and aquaporin-2 (AQP2) in the collecting duct. To test this hypothesis, semiquantitative immunoblotting and immunohistochemistry were carried out from the kidneys of lithium-induced NDI rats with and without COX-2 inhibition. After male Sprague-Dawley rats were fed an LiCl-containing rat diet for 3 wk, the rats were randomly divided into control and experimental groups. The COX-2 inhibitor DFU (40 mg.kg(-1).day(-1)) was orally administered to the experimental rats for an additional week. Treatment with the COX-2 inhibitor significantly relieved polyuria and raised urine osmolality. Semiquantitative immunoblotting using whole-kidney homogenates revealed that COX-2 inhibition caused significant increases in the abundance of AQP2 and NKCC2. Immunohistochemistry for AQP2 and NKCC2 confirmed the effects of COX-2 inhibition in lithium-induced NDI rats. The upregulation of AQP2 and NKCC2 in response to the COX-2 inhibitor may underlie the therapeutic mechanisms by which NSAIDs enhance antidiuresis in patients with NDI.</P>