콩팥의 요세관은 발생학적 기원이 서로 다른 콩팥단위(nephron)와 집합관(collecting duct)로 구성되어 있으며, nephron의 각 부위를 구성하고 있는 상피세포의 경우 발생학적으로 기원이 같음에도 불구하고 그 형태학적 특징과 기능이 서로 다르다. 최근 분자생물학적 연구기법의 발달로 인하여 새로운 운반체들이 밝혀지고, 이들의 분포와 기능에 대한 연구가 활발히 진행되고 있다. 특히 원위세관과 집합관으로 구성된 distal nephron의 상피는 다향한 세포들로 구성되어 있으며, 그 기능 또한 다양하여, 각 부위에 대한 명칭의 정확한 이해와 각 부위의 세포들의 분포와 형태학적 및 기능을 이해할 필요가 있다. 또한 요농축기전에 관여하는 곧은혈관, 헨레고리, 집합관의 구조적 특징 그리고 이들 구조에서 요소운반체(urea transporter), 수분통로(aquaporin), Na-K-2C1 cotransporter 등의 분포에 대하여 알아보고자 하였다.

Water is the most abundant component of all living organisms, however cells and tissues are remarkably different in their ability to absorb or release water. Water selective channels (aquaporins) had long been suspected to provide rapid water permeation of certain tissues including kidney, however the molecular identity of these membrane proteins remained unknown until the serendipitous discovery of aquaporin-1 by Peter Agre and his colleagues. The subsequent identification of several renal aquaporins provided insight into the fundamental physiology of water balance and the pathophysiology of water balance disorders.

• Aquaporin
• Urine concentration
• Membrane protein

1981년 atrial natriuretic peptide(ANP)가 처음 발견된 이래 이와 비슷한 기능을 하는 natriuretic peptide (NP) 족으로서 brain natriuretic peptide (BNP), C-type NP (CNP), Dendroaspis NP (DNP) 등이 알려지게 되었다. 또한 지난 수년간의 연구결과는 혈장 ANP 농도는 나트륨 이뇨 및 수분 이뇨 증가와 직접 상관관계가 없을 뿐더러, 신장은 직접 ANP, BNP 및 CNP 등을 생산, 분비함을 보이고 있다. 이러한 소견은 신장의 국소 NP가 수분 및 전해질 대사 조절에 순환 NP보다 더 중요한 인자임을 시사한다. 따라서 NP에 대한 폭넓은 이해는 체액 항상성 유지에 대한 우리의 이해를 증진시킬 뿐 아니라 체액 균형 장애를 일으키는 각종 질환의 기전을 탐구하고 그 치료 방침을 세우는 데 공헌할 것이다.

신 세관에서의 이온 이동은 통로(channel)를 통한 단순 확산과 운반체(transporter 혹은 carrier)를 통한 촉진확산 혹은 능동적 운반 과정에 의한다. 단백 수준에서 확인된 이온 통로에는 epithelial Na channel (ENaC), ROMK potassium channel, CLC chloride channel 및 epithelial Ca channel (ECaC)이 있다. 주요 이온 운반체로는 Na+/H+ Exchanger (NHE), Type IIa NaPi cotransporter (NPT2a), Na+-HCO3- cotransporter (NBC), Na+-C1- cotransporter (NCC), Na+-K+-2Cl- cotransporter (NKCC)가 있다.

Urinary pH is lower than the arterial pH in normal subjects, which means the urine excretes acids. The daily amount of acids excretion are 50-100 mM, and which mostly come from the metabolism of the protein we take in. We can measure the amounts of urinary acids by using net acid excretion formula that is titratable acidity plus ammonium minus bicarbonate with the collection of 24-hour specimen of urine. The net acid excretion has the same value with the regenerated bicarbonate in the renal tubules in the steady state, since a bicarbonate is formed with the secretion of a proton for the titratable acidity and with the production of the ammonium ion that contains the proton. Proximal urinary acidification is mainly associated with the reclamation of the filtered bicarbonate and 80-90% of it takes place in the proximal tubule. The main mechanism of the H+ secretion is performed by Na+-H+ antiporter in the luminal membrane. The remainders are reclaimed in the thick ascending limb of Henle and outer medullary collecting tubules where carbonic anhydrase type IV is present on the luminal membrane. The reclaimed and regenerated bicarbonates enter the blood via Na+-3HCO3- cotransporter in the proximal tubule. Distal nephron is the main site of the urinary acidification. H+-ATPase pump in the luminal membrane of the cortical and medullary collecting tubules plays exclusive role. It works with epithelial sodium channel, H+-K+-ATPase, and Na+-K+-ATPase under influence of aldosterone in the cortical collecting tubules and is a major mechanism of the urinary acidification in the medullary collecting tubules with minor contribution of H+-K+-ATPase. The bicarbonates are regenerated in simultaneous with the secretion of H+ on molar base. The regenerated bicarbonates enter the blood via Cl-/HCO3- exchanger in the basolateral membrane in the collecting tubule. To test the proximal acidification defects, the fractional excretion of the bicarbonate with the normalization of the blood bicarbonates level is useful. There are several methods to test distal acidification defects including ammonium chloride loading test, sodium sulfate infusion test, sodium phosphate infusion test, sodium bicarbonate infusion with measurement of urine to blood total carbon dioxide gradient, and furosemide/fludrocortisone test.

Chinese herbs nephropathy (CHN)는 1992년 Vanherweghem에 의해 벨기에의 몇몇 여성에서 빠르게 말기 신부전에 이르는 간질성신염으로 보고되었다. 모든 환자들은 체중감량을 위해 동일한 약제를 복용하였는데 후에 원인으로 aristolochic acid (AA)와의 상관성이 밝혀져 aristolochic acid nephropathy (AAN)로 불려진다. 이르게 발생하는 심한 빈혈, 경도의 신세관성 단백뇨, 초기 정상 혈압 등의 임상소견을 보인다. 조직소견으로 광범위한 신피질의 저세포성 간질 섬유화, 세관 위축, 바깥 피질에서 안피질로 감소하는 경향을 보이는 사구체의 전반적인 경화 등이 특징적이다. 약 반수의 환자에서 이후 요로상피세포암이 발생하였다. 이러한 전형적인 임상소견외에 동양에서는 많은 환자에서 광범위한 근위세관 손상의 결과인 Fanconi 증후군의 임상소견을 보인다.

Gitelman syndrome (GS) and Bartter syndrome have in common the cardinal symptoms of renal salt wasting, hypokalemic metabolic alkalosis, and elevated plasma renin and aldosterone levels but normal blood pressure. On the basis of clinical presentation, additional symptoms, and the biochemical profile, especially with repect to calcium and magnesium handling, these two syndromes can be discerned. It is well known that chronic intake of furosemide or thiazide cause phenotypic features of Bartter syndrome or Gitelman syndrome, repectively. Long-term abuse of furosemide can cause medullary nephrocalcinisis and chronic interstitial nephritis. We describe a case showing features of both GS and Bartter syndrome with a review of literature. A 39 year old woman presented with muscle weakness for 1 year. Her laboratory results showed hypokalemia (K+ 2.0 mEq/L), meatbolic alkalosis (pH 7.51, PCO2 51.4 mmHg, HCO3- 39.9 meq/L), and hypermagnesiuria (FEMg=14.5%) and hypocalciuria (urinary calcium/creatinine mmol/mmol=0.04), which are typical features of GS. She also revealed severe dehydration and medullary nephrocalcinosis on her KUB, which are features of Bartter syndrome. After long denial, she admitted that she had taken furosemide 160 mg/day for 4 years and then has been taking thiazide 100 mg/day since one year ago. It is thought that thiazide makes features of GS on chronic interstitial nephritis which may be caused by furosemide.

• Gitelman syndrome
• Furosemide
• Bartter syndrome
• Thiazide

Distal RT A has manifeatations of hyperchloremic acidosis, hypokalemia, interstitial nephritis, renal calcinosis etc and may be associated with Sjogren syndrome. We experienced two cases of hypokalemic paralysis in Sjogren syndrome complicated with distal RTA. By immunohistochemistry, we confirmed the defect of H+-ATPase and Cl(-)-HCO3- exchanger in collecting duct.

• Hypokalemic paralysis
• Renal tubular acidosis
• Sjogren syndrome
• H+-ATPase
• Cl(-)-HCO3- exchanger

Gitelman`s syndrome (GS) (also called tubular hypomagnesemia-hypokalemia with hypocalciuria), an autosomal recessive disorder, is often not diagnosed until late childhood or even adulthood. GS is a more benign condition than Batter`s syndrome. However, the syndrome is usually symptomatic and can be associated with serious clinical manifestations such as cramps, severe fatigue, polyuria, and nocturia. Patients with GS have mutations in the gene coding for the thiazide-sensitive Na-Cl cotransporter in the distal tubule. A defect in this transporter can account for both the magnesium wasting and the often marked decrease in calcium excretion (the opposite of the hypercalciuria seen in classic Bartter`s syndrome). There is no direct correlation between the clinical phenotype and the underlying genotypic abnormality. A 37-year-old man was admitted with complaints of intemittent chest tightness and generalized weakness. He had no history of laxative or diuretic abuse or of vomiting, and he was taking no medications. Physical examination revealed a well-developed. His blood pressure was 124/80 mmHg. On admssion, laboratory values were: hemoglobin 17.0 g/dl, hematocrit 48.9%, white blood cell count 11,500/mm3, platelet 424,000/mm3, BUN 18 mg/dl, serum creatinine 1.20 mg/dl, AST 27 IU/L, ALT 29 IU/L, serum sodium 137 mEq/L, potassium 2.5 mEq/L, calcium 10 mg/dl, magnesium 1.2 mg/dl, TTKG 5.0, supine PRA 32.1 ng/ml/hr, supine aldosterone, 218.9 pg/ml, pH 7.44, PCO2 40.5 mmHg, HCO3- 26.9 mEq/L. Follow-up laboratory values revealed: serum sodium 133 mEq/L, potassium 2.2 mEq/L, calcium 9.8 mg/dl, magnesium 1.4 mg/dl, TTKG 5.3, supine PRA 48.2 ng/ml/hr, supine aldosterone 402.9 pg/ml, pH 7.45 PCO2 39 mmHg HCO3- 27.4 mEq/L, 24 hours urine calcium/creatinine ratio 0.09, fractional excretion of magnesium (FEMg) 56.5%. The patient was discharged on spirolactone 100 mg. Three monthe later, he remained asymptomatic and near normal serum potassium level.

• Gitelman`s syndrome
• Hypokalemia
• Alkalosis

증례: 지난 10년간 Type II 당뇨병 환자인 58세 남자가 최근 발견된 고혈압 때문에 개인 병원에서 지난 한달 동안 치료 받던중 감기약 복용으로도 없어지지 않는다고 주장하는 기침의 호소와 함께 동시에 조절되지 않는 혈압과 신부전을 걱정하여 대학 병원 선장내과 외래를 찾아왔다. 혈압 약제는 enalapril을 복용중이었으며 혈압은 160/110 mmHg 이외 다른 선체 검사상 특이 사항은 없었다. 초기 검사 결과에서 혈청 Na 140 mEq/L, Cl 110 mEq/L, HCO3 20 mEq/L, K 5.5 mEq/L, Glucose 156 mg/dL, Cr 2.1 mg/dL, BUN 26 mg/dL 그리고 소변 검사상 단백뇨 2 (+)와 점적뇨의 단백/크레아티닌 비는 2.0이었다. 문제: 이 환자에서 enalapril을 중지하고 angiotensin receptor blocker로 대치 사용할 경우 그 정당성과 사용시 주의할 점은 무엇인가?