Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder characterized by inability to concentrate the urine in spite of the presence of vasopressin. Most of the patients, if early diagnosis and proper management are delayed, suffer from recurrent episodes of hypernatremic dehydration in neonatal or early infant period, which result in growth and developmental retardations. The mode of transmission is X-linked recessive in about 90% of the patients [arginine vasopressin V2 receptor gene (AVPR2) mutation] and autosomal recessive or dominant in less than 10% of the patients [aquaporin 2 (AQP2) gene mutation]. Part of AVPR2 missense mutations are known to translate mutant receptors which can not be translocated to the cell membrane normally (intracellular mistrafficking) and retained in the endoplasmic reticulum (ER) due to misfolding. These mutant proteins can be functionally rescued by using so-called chemical chaperones. In this study, the genetic analysis of the AVPR2 and AQP2 genes were performed in patients with clinical diagnosis of NDI. In addition, the functional rescue of the some mutant AVPR2 molecules using chemical chaperones was tried. Considering the limited effectiveness of the current pharmacological management of NDI and the practical difficulties in applying gene therapies, chemical chaperones can provide a novel and more easily applicable therapeutic strategy.

• Congenital nephrogenic diabetes insipidus
• NDI
• Arginine vasopressin V2 receptor
• Arginine vasopressin V2 receptor gene
• AVPR2
• Aquaporin 2
• Aquaporin 2 gene
• AQP2
• Chemical chaperone
• Protein misfolding
• Functional rescue of mutant protein

뼈와 연골에 무기질침착이 제대로 이루어지기 위해서는 적절한 칼슘과 인이 공급되어야 한다. 적절한 공급이 이루어지지 않으면, 뼈에 무기질침착이 제대로 이루어지지 않아 골연화증(osteomalacia)이 초래된다. 성장하고 있는 아이들에서는 성장판 연골에도 무기질침착의 결핍이 초래되어 구루병(rickets)이 발생하게 된다. 골연화증 혹은 구루병을 초래하는 대표적인 예의 하나로 신성 저인산혈증성 골연화증을 들 수 있다. 과거 저인산혈증 보다는 일반적인 비타민 D의 치료로 질병이 호전되지 않는 점이 강조되어 비타민 D 저항성 구루병이라고 불렸으나, 이후 가족성 저인산혈증 그리고, 최근에는 원인들이 밝혀지면서 원인에 따라 각각 새로이 명명되었다.

Bartter`s syndrome is a group of rare autosomal-recessive disorders with a unifying pathophysiology consisting of severe reductions in, or losses of, salt absorption by the thick ascending limb of Henle (TAL). The characteristic phenotype of Bartter`s syndrome is renal salt wasting, hypokalemic metabolic alkalosis, hypercalciuria with a variable risk of renal stones and elevated renin and aldosterone levels, with normal or low blood pressure. Recent advances in the field of molecular genetics have demonstrated that there are five genetically distinct abnormalities, which result from mutations in renal electrolyte transporters and channels. Previously, three genes (SLC12A1, the sodium-potassium-chloride co-transporter; KCNJ1, the ROMK potassium ion channel; ClC-Kb, the basolateral chloride ion channel) had been identified as causing antenatal and `classic` Bartter`s syndrome. Two additional genes have now been identified. Barttin is a β-subunit that is required for the trafficking of CLC-K (both ClC-Ka and ClC-Kb) channels to the plasma membrane in both the thick ascending limb and the marginal cells in the scala media of the inner ear that secrete potassium ion-rich endolymph. Loss-of-function mutations in barttin thus cause Bartter`s syndrome with sensorineural deafness. In addition, severe gain-of-function mutations in the extracellular calcium ion-sensing receptor can result in a Bartter`s phenotype because activation of this G protein-coupled receptor inhibits salt transport in the thick ascending limb. Gitelman`s syndrome shares similar clinical characteristics with Bartter`s syndrome but, is distinguished from Bartter`s syndrome by hypomagnesemia and hypocalciuria. Gitelman`s syndrome is due to mutations in the gene encoding the Na-Cl cotransporter (NCCT).

• Bartter`s syndrome
• Gitelman`s syndrome

Oxidative stress implies an increased production of reactive oxygen species (ROS) or a decreased capacity to metabolize them. Recent studies suggested that oxidative stress is implicated in the pathogenesis of tissue injury and dysfunction in diabetes and hypertension, which are two major causes of ESRD. In these diseases, oxygen radicals are increased and contribute to diabetic nephropathy and hypertension by enhancing renal vascular tone, sensitivity to vasoconstrictors, inflammatory cell infiltration and tubuloglomerular feedback. ROS induced nitric oxide inactivation and induction of stress activated signaling pathways are main underlying mechanisms for ROS induced tissue injury and dysfunction. Treatment with pharmacological antioxidant agents such as TEMPOL (superoxide disqmutase mimetic) reverses many of these injury and dysfunction underlying the role of oxidative stress in the pathogenesis of diabetic nephropathy and hypertension.

• Reactive oxygen species
• Pathogenesis
• Diabetes mellitus
• Hypertension

헴(heme)은 여러 가지 신장 질환에서 중요한 병인이 된다. 세포의 헴은 헴 단백으로부터 유도되며 heme oxygenase (HO) 효소체계를 통해 조절된다. HO는 헴 분해의 율속 단계에 작용하여 철, 일산화탄소와 빌리버딘을 형성하며, 빌리버딘은 빌리버딘 환원효소에 의해 빌리루빈으로 전환된다. 최근 연구들은 HO 생산물들의 생물학적 효과인 항산화, 항염증 및 세포보호 기능에 초점을 두고 있다. HO 효소에는 유도형인 HO-1, 구조형인 HO-2와 HO-3 세 가지 동위형이 있다. HO-1은 여러 가지 해로운 자극에 유익하게 반응하고, 동맥경화, 이식 거부, 내독성 쇼크, 고혈압, 급성 폐손상 및 급성 신손상 등 다양한 질환에도 영향을 미친다.

TonEBP는 NFAT나 NFκB와 마찬가지로 Rel family에 속하는 전사조절인자(transcriptional activator)이지만 아미노산 서열이나 구조상으로 이들과 구별되며 5개의 transactivation 도메인을 통하여 더 정교하게 target 유전자의 전사를 조절한다. 포유류 신장에서 TonEBP는 compatible osmolyte 축적에 관여하는 유전자를 자극하여 세포내 이온 농도를 떨어뜨림으로써 hypertonicity의 유해한 자극으로부터 세포를 보호한다. TonEBP 활성은 단백 발현 증가, 인산화, transactivation, 세포내 위치 이동 등을 통하여 조절된다. TonEBP는 신장 이외에도 뇌, 심장, 간, T 임파구 등 여러 장기에 널리 분포하고 있고 면역반응, 당뇨, 암 등에도 관여하리라는 증거들이 제시되되 있다. RNA 간섭과 같은 기술을 이용하여 TonEBP의 loss-of-function을 연구하면 향후 더 다양한 생물학적 기능을 밝힐 수 있을 것이다.

Diverse control systems are involved in the regulation of blood pressure, including renal, vascular, cardiogenic, neurogenic, and endocrine mechanisms. Among them, the kidney plays the dominant role in the long-term regulation of arterial pressure, in which the volume of extracellular fluid is regulated primarily by excreting or retaining sodium. Therefore, hypertension is usually associated with an altered renal sodium handling. There are mediators between increased renal perfusion pressure and decreased tubular reabsorption of sodium in the kidney. Although a dysfunction of nitric oxide system in the kidney appears to play a major role in the development of salt-sensitive hypertension, the regulation of atrial natriuretic peptide (ANP) may also be altered in hypertension. This review will discuss the altered regulation of ANP system in the kidney in different models of hypertension.

• Atrial natriuretic peptide
• Natriuretic peptide receptor
• Kidney
• Hypertension

식이장애가 동반된 환자의 전해질 이상을 분석하였는데 그중 저칼륨혈증에 중점을 두었다. 식이장애 진단명은 각각 신경성 식욕부진 6명, 신경성 대식증 2명, 그리고 반추장애 1명이었다. 환자들의 체질량지수(Body mass index)는 17±2.5 kg/m2로 낮았고, 이중 아주 낮은 환자(17.5 kg/m2 이하)는 5명이었다(56%). 9명 중 6명(66%)의 환자가 약물을 사용 하였는데 이뇨제와 하제를 동시에 복용한 환자가 3명이었다. 1명은 이뇨제 복용력을 숨겨 약물 선별검사에서 확인되었다. 병적인 식이장애는 사춘기 여성이 아닌 장년 연령과 심지어 남성에서도 관찰되었고 2/3 이상에서 저칼륨혈증과 대사성 알칼리혈증의 부작용을 보였다. 원인이 뚜렷하지 않은 저칼륨혈증과 함께 특히 체질량지수 감소가 동반된 때에는 약물남용의 추적과 함께 그 원인질환으로 심각한 식이장애 이환 여부를 고려해야 할 것이다.

The most common causes of clinically significant hypernatremia occur as a consequence of three pathologic mechanisms: impaired thirst, solute or osmotic diuresis, and excessive losses of water (either through the kidneys or extrarenally), or in combination of these derangements. Any condition that increases insensible fluid loss such as severe exercise, exposure to high temperatures, high fever, respiratory infections, or burns predisposes toward the development of severe hypernatremia. Severe hypernatremic dehydration may be associated with coagulopathy and rhabdomyolysis. We report that a case of severe exercise-induced hypernatremic dehydration, disseminated intravascular coagulation, and rhabdomyolysis in a 15-year-old boy associated with weight loss.

• Hypernatremia
• Dehydration
• Severe exercise

Significant disturbances of potassium homeostasis may cause considerable morbidity and mortality and the prompt recognition and appropriate treatment of these disturbances after drinking inorganic acid could be life-saving. The administration of the mineral acid HCl to experimental animals causes an elevation in the plasma potassium concentration, which has been attributed to shift of the potassium from the intracellular to the extracellular space. The authors report upon a case of hyperkalemia due to the drinking inorganic acid (0.4N HCl) in 51 years-old male, and provide a literature review of hyperpotassemia in inorganic acid-related acidosis.

• Hyperkalemia
• HCl drinking