巴特综合征的诊断和治疗（Bartter syndrome, emdedicine）...

Laboratory Studies

实验室检查

• Consider possible renal tubular disorder if patients, especially dehydrated infants and young children, are found to have hypokalemia and a high serum bicarbonate concentration that do not correct with potassium and chloride replacement treatment.
• 如果患者尤其是婴幼儿出现脱水、低血钾、高血清碳酸氢根浓度，且难以用钾和氯替代治疗所纠正，应考虑肾小管疾病可的能。
• Initiate timed urine collection to determine potassium levels.
• 收集一定时间段的尿液，以确定钾的水平。
  • In hypokalemia, normal kidneys retain potassium.[14]  
  • 在低血钾状态下，正常的肾脏具有保钾功能。[14]
  • Elevated urinary potassium levels with low blood potassium levels suggest the kidneys are having problems retaining potassium.
  • 血钾水平降低的同时尿钾水平升高提示肾脏保钾异常。
• Next, initiate timed urine collection to determine aldosterone levels.
• 下一步，收集一定时间段的尿液测定醛固酮水平。
  • Aldosterone levels should be low in volume-replete patients.
  • 在液体容量不足的患者，醛固酮水平应该降低。
  • If urinary aldosterone levels are high despite volume replacement, there is an abnormal stimulation of aldosterone.
  • 如果经过容量替代治疗，患者尿液醛固酮水平仍高，那么就存在醛固酮的异常刺激。
  • Patients with primary hyperaldosteronism in a volume-replete state usually have normal-to-high blood pressure.
  • 在血容量不足的原发性醛固酮增多症患者，血压通常正常或升高。
  • Low or low-normal blood pressure with high aldosterone excretion suggests the primary problem is something else, and the aldosterone response is secondary to the undiagnosed primary abnormality.
  • 如果醛固酮分泌增高，但血压正常或正常偏低，提示存在其他疾病，醛固酮应答是继发于其他尚未诊断的其他疾病。
• Then, initiate a timed urine collection to determine chloride levels.
• 然后，收集一段时间的尿液，以确定氯化物水平。
  • Extrarenal volume depletion is a possible reason for low blood pressure, high aldosterone excretion, and potassium loss. In this case, the kidneys retain sodium and chloride, and urinary chloride concentrations should be low.
  • 肾外血容量减少是低血压、高醛固酮排泄、血钾丢失的一个可能原因。在这种情况下，肾脏保留钠和氯，尿氯浓度应偏低。
  • High urine chloride levels with low blood pressure, high aldosterone secretion, and high urinary potassium levels are found only with long-term diuretic use and Bartter or Gitelman syndrome.
  • 如果低血压、高醛固酮分泌、尿钾水平升高时如果氯离子水平也升高，这种情况仅见于长期使用利尿剂和Bartter或Gitelman综合征。
  • If diuretic abuse is suspected, a urine screen for diuretics can be ordered. Otherwise, the diagnosis is Bartter or Gitelman syndrome.
  • 如果怀疑患者滥用利尿剂，可以测定尿液中的利尿剂。否则，应诊断为Bartter或Gitelman综合征。
• Mutations in the different transporters cause Bartter syndrome. Mutations can be determined in the following ways:
• 多种不同的转运子突变导致巴特综合征。突变可以通过以下方式确定：
  • The older methods require more detailed physiologic investigations, including determination of serum magnesium levels and further urine collections to assess calcium, magnesium, and PGE2 levels.
  • 较古老的方法需要更详细的生理方面的检测，包括测定血清镁的水平，并进一步收集尿液，测定尿钙、镁和PGE2的水平。
  • In Bartter syndrome, urine calcium excretion is high, leading to nephrocalcinosis, while serum magnesium levels are normal.
  • 在Bartter综合征，尿钙排泄升高，导致肾结石，而血清镁水平是正常的。
  • With the transporter mutations that cause Gitelman syndrome, hypomagnesemia is common and is accompanied by hypocalciuria.
  • 在转运子突变导致Gitelman综合征的患者，常见低镁血症，并伴有低钙血症。
  • Genetic analysis has become the preferred methodology for determining if a mutation in one of the transporters has occurred. Some mutations lead to marked loss of function, while others do not.[15, 16]
  • 遗传分析已经成为确诊转运子突变的的首选方法。一些突变导致明显的功能丧失，而有的则不会。[15，16]

Imaging Studies海南医学院第一附属医院内分泌科王新军

影像学检查

• Antenatal Bartter syndrome can be diagnosed best by ultrasonography. The fetus may have polyhydramnios and intrauterine growth retardation. Amniotic chloride levels may be elevated.[17]
• 巴特综合征的产前诊断超声是最好的检查。胎儿可能有羊水过多和胎儿宫内发育迟缓。羊水中氯水平可能会升高。[17]
• After birth, especially if the disease is diagnosed in older patients who have hypercalciuria, consider a renal ultrasound or flat plate of the abdomen for nephrocalcinosis.
• 出生后，特别是如果这种疾病在老年人才得到诊断并伴有高钙尿症，考虑进行肾脏超声或腹部平片检查，以确定是否有肾结石。
  • Sonographic findings include diffusely increased echogenicity, hyperechoic pyramids, and interstitial calcium deposition.
  • 超声可发现弥漫性回声增加、金字塔高回声以及间质钙沉积。
  • Because continued calcium loss may affect bones, dual-energy radiographic absorptiometry scans to determine bone mineral density may be advisable in older patients.
  • 由于持续钙质流失可影响骨骼，建议老年患者进行双能X线骨密度仪扫描，以确定骨密度。
• Nephrocalcinosis can occur and is often associated with hypercalciuria. It can be diagnosed with abdominal radiographs, intravenous pyelograms (IVPs), renal ultrasonograms, or spiral computed tomography (CT) scans.

可能发生肾结石，并往往与高尿钙症有关。可以通过腹部X光片、静脉肾盂造影（IVPs）、肾声像或螺旋CT扫描（CT）扫描诊断。

Other Tests

其他检查

• An analysis of the genes for the transporters shows multiple problems leading to abnormal gene function, including missense, frame-shift, loss-of-function, and large deletion mutations.[2, 3, 4, 5]
• 对转运子进行基因分析常可发现多种导致基因功能异常的病变，包括错义突变、移码突变、功能缺失和大片段丢失等。

Medical Care

治疗

Medical Care Since first described in 1962, several types of medical treatment have been used.

自从1962年认识到本病以来，已经研究出多种治疗药物。

Sodium and potassium supplements are used for the electrolyte imbalances, and aldosterone antagonists and diuretic spironolactone are mainstays of therapy.

补充钠钾以纠正酸碱平衡，醛固酮拮抗剂和利尿剂螺内酯是主要的治疗药物。

ACE inhibitors are used to counteract the effects of ANG II and aldosterone.

ACE抑制剂用来抵消血管紧张素和醛固酮的作用。

Indomethacin is used to decrease prostaglandin excretion.

吲哚美辛用来减少前列腺素的排泄。

Growth hormone (GH) is used to treat short stature.

如果身材矮小，可用 生长激素来治疗。

Calcium or magnesium supplements may occasionally be needed if tetany or muscle spasms are present.

如果存在肌肉痉挛的症状，有时需要补充钙镁。

Surgical Care

外科治疗

• Bartter and Gitelman syndromes, by themselves, do not lead to chronic renal insufficiency; however, in patients with these syndromes who develop end-stage renal disease (ESRD) for other reasons, transplants from living relatives are an option and result in normal urinary handling of sodium, potassium, calcium, and magnesium.
• Bartter和Gitelman综合征本身不会导致慢性肾功能不全；然而患本综合征的患者可因其他原因导致终末期肾脏疾病（ESRD），可进行活体亲属肾移植使尿钠、钾、钙、镁保持正常。
  • Reports of renal transplants from living relatives in ESRD patients with Bartter syndrome suggest that many endocrinologic abnormalities in Bartter syndrome improve or normalize after transplantation.
  • 伴有终末期肾病的Bartter综合征患者活体亲属肾移植的报告提示，Bartter综合征的许多内分泌异常移植后可改善或恢复正常。
  • Because the genetic abnormality in Bartter syndrome may be found only in the kidneys (which is certain in Na-K-Cl cotransporter but may not be the case for some of the other mutations), transplantation corrects the problem by replacing unhealthy kidneys with normal ones.
  • 因为巴特综合征的基因异常可能只存在于肾脏（钠钾氯转运子基因异常，但其他一些突变可能并不如此），移植可通过用健康的肾脏纠正这些异常。
  • Bartter syndrome is an autosomal recessive disorder. Both parents carry at least 1 gene for the disorder. Statistically, only 1 of 4 siblings is completely healthy.
  • Bartter综合征是一种常染色体隐性遗传疾病。父母双方至少携带1个异常基因。据统计，每4个兄弟姐妹中仅有1个是完全健康的。
  • Whether carrying 1 gene for this abnormality leads to long-term problems late in life if 1 kidney is removed is unknown.
  • 携带1个这种异常基因是否在切除1个肾脏后会在晚年出现长期问题，仍不清楚。
• Transplants from living unrelated persons or cadavers are options for patients with ESRD.
• 也可用非亲属或尸体肾移植手术治疗终末期肾病患者。

Diet

饮食

• Adequate salt and water intake are necessary to prevent hypovolemia.
• 必须保证足够的盐和水的摄入量，以防止低血容量。
• Adequate potassium intake is essential to replace urinary potassium losses.
• 充足的钾摄入是必不可少的，以弥补尿钾的损失。
• With growth retardation, adequate overall nutritional balance (protein-calorie intake) is important. Whether other diet supplements (eg, citrate, magnesium, vitamins) are helpful is not clear.
• 发育迟缓的患者，保证充足的全面营养平衡（蛋白质热量摄入）是重要的。其他饮食补充剂（如柠檬酸、镁维生素）是否有益尚不清楚。

Medication Summary

药物治疗概述

Salt and water depletion due to inability to conserve sodium in the TALH or DCT leads to activation of the RAAS and high aldosterone levels. This helps the kidneys retain sodium distal to the site of the mutation but at the expense of losing potassium.

由于TALH或DCT不能保钠，因而会出现盐和水的丢失，继而会激活RAAS，使醛固酮水平升高。这有助于肾脏突变的远端保钠，但会以失钾为代价。

Aldosterone inhibitors and ACE inhibitors help block the RAAS and help prevent potassium loss in the distal tubules. The body conserves potassium, and less oral potassium supplementation is needed.

醛固酮抑制剂和血管紧张素转换酶抑制剂可辅助阻断RAAS，并有助于防止远端肾小管钾的损失。身体保钾，这样可减少口服补钾量。

Short stature and growth failure are common in Bartter syndrome. Exogenous GH increases the growth rate and helps patients with GH deficiency attain normal height. Although not well studied, at least 1 report describes a patient with low GH levels and Gitelman syndrome who was below the third percentile for height and whose growth rate improved 4-fold during GH treatment. Dose depends on brand used. Somatropin (up to 0.3 mg/kg/wk SC) and somatropin (rDNA origin, 0.1 mg/kg/d SC) have been used.

身材矮小和生长障碍在Bartter综合征是常见的。外源生长激素可增加生长速度，并有助于生长激素缺乏症患者达到正常的身高。虽然没有良好的研究，但至少有1项报告描述了身高低于第三百分位的低GH水平Gitelman综合征患者，在用生长激素治疗期间其增长速度提高了4倍。应用剂量取决于所用的品牌。生长激素Somatropin（0.3毫克/公斤/周SC）和生长激素somatropin（rDNA来源，0.1毫克/公斤/天SC）的已被批准使用。

Potassium supplements

补钾药

Class Summary

类别概述

Used to treat the hypokalemia associated with the syndrome.

用于治疗与本综合征相关的低钾血症。

Potassium chloride (K-Dur, Gen-K, Klor-Con)

 氯化钾

Depends on degree of receptor dysfunction and hypokalemia. Serum potassium levels often run in the range of 2-3 mEq/L, which may require several hundred milliequivalents of potassium per day.

依赖于受体异常和低钾血症的程度。血钾水平常在2~3 mEq/L之间，可能每天需要补充大约几百毫当量的钾。

Potassium sparing diuretics

保钾利尿剂

Class Summary

类别概述

These agents can increase potassium blood levels.

这类药物可以升高血钾水平。

Spironolactone (Aldactone)

 螺内酯

Aldosterone antagonist that competitively inhibits binding to the aldosterone receptor. It competes for receptor sites in the distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.

醛固酮拮抗剂可以竞争性抑制醛固酮受体。它可竞争远端肾小管受体结合位点，增加水的排泄，同时保钾和氢离子。

Angiotensin-converting enzyme inhibitors

血管紧张素转换酶抑制剂

Class Summary

类别概述

Block the conversion of ANG I to ANG II and prevent the secretion of aldosterone from the adrenal cortex.

阻断血管紧张素I向血管紧张素II的转化，防止肾上腺皮质分泌醛固酮。

Captopril (Capoten)

 卡托普利

Prevents conversion of ANG I to ANG II, a potent vasoconstrictor, resulting in lower aldosterone secretion. Also helpful in preventing potassium loss.

防止血管紧张素转换I转化为血管紧张素Ⅱ，血管紧张素Ⅱ是一种有效的血管收缩剂，从而降低醛固酮分泌。也有利于防止钾流失。

Enalapril (Vasotec)

 依那普利

Competitive inhibitor of ACE. Reduces ANG II levels, decreasing aldosterone secretion.

ACE的竞争性抑制剂。降低血管紧张素Ⅱ水平，减少醛固酮的分泌。

Lisinopril (Prinivil, Zestril)

 赖诺普利

Prevents conversion of ANG I to ANG II, a potent vasoconstrictor, resulting in lower aldosterone secretion. 
防止血管紧张素I转换为血管紧张素Ⅱ，血管紧张素Ⅱ是一种有效的血管收缩剂，从而降低醛固酮分泌。

Prostaglandin inhibitors

前列腺素抑制剂

Class Summary

类别概述

Vascular action of ANG II also activates the phosphatidylinositol pathway, increasing release of diacylglycerol, which leads to the release of arachidonic acid and can increase the production of prostaglandins. Bartter syndrome is associated with an increase in the renal excretion of vasodilating PGE2, which may help mediate the vasoconstrictive effects of ANG II. Hypokalemia also induces prostaglandin production.

血管紧张素Ⅱ的血管作用也可激活磷脂途径，增加甘油二酯的释放，从而导致花生四烯酸的释放，并可增加前列腺素的产生。 Bartter综合征与前列腺素E2的肾脏排泄增加相关，前列腺素E2可能有助于介导血管紧张素Ⅱ的血管收缩作用。低钾血症也会引起前列腺素的产生。

Indomethacin (Indocin)

 吲哚美辛

NSAID used in Bartter syndrome to help improve growth and decrease urinary potassium excretion.

Bartter综合征应用NSAID有助于促进生长，减少尿钾排泄。