Chronic renal failure in a boy with classic Bartter’s syndrome due to a novel mutation in CLCNKB coding for the chloride channel

详细信息    查看全文

• 作者：Chien-Ming Lin (1)
  Jeng-Daw Tsai (2)
  Yi-Fen Lo (3)
  Ming-Tso Yan (3)
  Sung-Sen Yang (3)
  Shih-Hua Lin (3)
  
• 关键词：Classic Bartter’s syndrome ; Renal failure ; NSAIDs ; Hypokalemia
• 刊名：European Journal of Pediatrics
• 出版年：2009
• 出版时间：September 2009
• 年：2009
• 卷：168
• 期：9
• 页码：1129-1133
• 全文大小：158KB
• 参考文献：1. Bettinelli A, Borsa N, Bellantuono R, Syrèn ML, Calabrese R, Edefonti A, Komninos J, Santostefano M, Beccaria L, Pela I, Bianchetti MG, Tedeschi S (2007) Patients with biallelic mutations in the chloride channel gene CLCNKB: long-term management and outcome. Am J Kidney Dis 49:91-8 doi:10.1053/j.ajkd.2006.10.001 CrossRef
  2. Birkenhager R, Otto E, Schurmann MJ, Vollmer M, Ruf EM, Maier-Lutz I, Beekmann F, Fekete A, Omran H, Feldmann D, Milford DV, Jeck N, Konrad M, Landau D, Knoers NV, Antignac C, Sudbrak R, Kispert A, Hildebrandt F (2001) Mutation of BSND causes Bartter’s syndrome with sensorineural deafness and kidney failure. Nat Genet 29:310-14 doi:10.1038/ng752 CrossRef
  3. Cremer W, Bock CW (1977) Symptoms and course of chronic hypokalemic nephropathy in man. Clin Nephrol 17:654-57
  4. Fukuyama S, Hiramatsu M, Akagi M, Higa M, Ohta T (2004) Novel mutations of the chloride channel Kb gene in two Japanese patients clinically diagnosed as Bartter syndrome with hypocalciuria. J Clin Endocrinol Metab 89:5847-850 doi:10.1210/jc.2004-0775 CrossRef
  5. Huang Y, Noble NA, Zhang J, Xu C, Border WA (2007) Renin-stimulated TGF-β1 expression is regulated by a mitogen-activated protein kinase in mesangial cells. Kidney Int 72:45-2 doi:10.1038/sj.ki.5002243 CrossRef
  6. Jeck N, Schlingmann KP, Reinalter SC, K?mhoff M, Peters M, Waldegger S, Seyberth HW (2005) Salt handling in the distal nephron: lessons learned from inherited human disorders. Am J Physiol Regul Integr Comp Physiol 288:R782–R795 doi:10.1152/ajpregu.00600.2004
  7. Konrad M, Leonhardt A, Hensen P, Seyberth HW, Kockerling A (1998) Prenatal and postnatal management of hyperprostaglandin E syndrome after genetic diagnosis from amniocytes. Pediatrics 103:678-83 doi:10.1542/peds.103.3.678 CrossRef
  8. Konrad M, Vollmer M, Lemmink HH, Jeck N, Vargas-Poussou R, Lakings A (2000) Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome. J Am Soc Nephrol 11:1449-459
  9. Nath KA, Hostetter MK, Hostetter TH (1991) Increased ammoniagenesis as a determinant of progressive renal injury. Am J Kidney Dis 17:654-57
  10. Nozu K, Fu XJ, Nakanishi K, Yoshikawa N, Kaito H, Kanda K, Krol RP, Miyashita R, Kamitsuji H, Kanda S, Hayashi Y, Satomura K, Shimizu N, Iijima K, Matsuo M (2007) Molecular analysis of patients with type III Bartter syndrome: picking up large heterozygous deletions with semiquantitative PCR. Pediatr Res 62:364-69 doi:10.1203/PDR.0b013e318123?fb90 CrossRef
  11. Palmer BF, Henrich WL (1995) Clinical acute renal failure with nonsteroidal anti-inflammatory drugs. Semin Nephrol 15:214-27
  12. Peters M, Jeck N, Reinalter S, Leonhardt A, T?nshoff B, Klaus GG, Konrad M, Seyberth HW (2002) Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies. Am J Med 112:183-90 doi:10.1016/S0002-9343(01)01086-5 CrossRef
  13. Reinalter SC, Grone HJ, Konrad M, Seyberth HW, Klaus G (2001) Evaluation of long-term treatment with indomethacin in hereditary hypokalemic salt-losing tubulopathies. J Pediatr 139:398-06 doi:10.1067/mpd.2001.117007 CrossRef
  14. Schachter AD, Arbus GS, Alexander RJ, Balfe JW (1998) Non-steroidal anti-inflammatory drug-associated nephrotoxicity in Bartter syndrome. Pediatr Nephrol 12:775-77 doi:10.1007/s004670050545 CrossRef
  15. Schlingmann KP, Konrad M, Jeck N, Waldegger P, Reinalter SC, Holder M, Seyberth HW, Waldegger S (2004) Salt wasting and deafness resulting from mutations in two chloride channels. N Engl J Med 350:1314-319 doi:10.1056/NEJMoa032843 CrossRef
  16. Seidel C, Reinalter S, Seyberth HW, Sch?rer K (1995) Prepubertal growth in the hyperprostaglandin E syndrome. Pediatr Nephrol 9:723-28 doi:10.1007/BF00868723 CrossRef
  17. Shaer AJ (2001) Inherited primary renal tubular hypokalemic alkalosis: a review of Gitelman and Bartter syndromes. Am J Med Sci 322:316-32 doi:10.1097/00000441-200112000-00004 CrossRef
  18. Simon DB, Bindra RS, Mansfield TA, Nelson-Williams C, Mendonca E, Stone R, Schurman S, Nayir A, Alpay H, Bakkaloglu A, Rodriguez-Soriano J, Morales JM, Sanjad SA, Taylor CM, Pilz D, Brem A, Trachtman H, Griswold W, Richard GA, John E, Lifton RP (1997) Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III. Nat Genet 17:171-78 doi:10.1038/ng1097-171 CrossRef
  19. Simon DB, Karet FE, Hamdan JM, DiPietro A, Sanjad SA, Lifton RP (1996) Bartter’s syndrome, hypokalemic alkalosis with hypercalciuria, is caused by mutations in the Na–K-Cl cotransporter NKCC2. Nat Genet 13:183-88 doi:10.1038/ng0696-183 CrossRef
  20. Simon DB, Karet FE, Rodriguez-Soriano J, Hamdan JH, DiPietro A, Trachtman H, Sanjad SA, Lifton RP (1996) Genetic heterogeneity of Bartter’s syndrome revealed by mutations in the K channel, ROMK. Nat Genet 14:152-56 doi:10.1038/ng1096-152 CrossRef
  21. Su IH, Frank R, Gauthier BG, Valderrama E, Simon DB, Lifton RP, Trachtman H (2000) Bartter syndrome and focal segmental glomerulosclerosis: a possible link between two diseases. Pediatr Nephrol 14:970-72 doi:10.1007/s004670050054 CrossRef
  22. Sun Y, Zhang JQ, Ramires FJ (2000) Local angiotensin II and transforming growth factor-beta 1 in renal fibrosis in rats. Hypertension 35:1078-084
  23. Tajima T, Nawate M, Takahashi Y, Mizoguchi Y (2006) Molecular analysis of the CLCNKB gene in Japanese patients with classic Bartter syndrome. Endocr J 53:647-52 doi:10.1507/endocrj.K06-034 CrossRef
  24. Tolins JP, Hostetter MK, Hostetter TH (1987) Hypokalemic nephropathy in the rat: role of ammonia in chronic tubular injury. J Clin Invest 79:1447-458 doi:10.1172/JCI112973 CrossRef
  25. Watanabe S, Fukumoto S, Chang H, Takeuchi Y, Hasegawa Y, Okazaki R, Chikatsu N, Fujita T (2002) Association between activating mutations of calcium-sensing receptor and Bartter’s syndrome. Lancet 360:692-94 doi:10.1016/S0140-6736(02)09842-2 CrossRef
  26. Zelikovic I, Szargel R, Hawash A, Labay V, Hatib I, Cohen N, Nakhoul F (2003) A novel mutation in the chloride channel gene, CLCNKB, as a cause of Gitelman and Bartter syndromes. Kidney Int 63:24-2 doi:10.1046/j.1523-1755.2003.00730.x CrossRef
  
• 作者单位：Chien-Ming Lin (1)
  Jeng-Daw Tsai (2)
  Yi-Fen Lo (3)
  Ming-Tso Yan (3)
  Sung-Sen Yang (3)
  Shih-Hua Lin (3)
  
  1. Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
  2. Department of Pediatrics, Mackay Memorial Hospital and Taipei Medical University, Taipei, Taiwan
  3. Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Road, Section 2, Neihu 114, Taipei, Taiwan, Repub, lic of China
  

文摘

Background Progressive renal failure in patients with classic Bartter’s syndrome (cBS) due to inactivating mutations in CLCNKB gene is extraordinarily rare. Discussion We describe a 17-year-old Chinese boy who presented with progressive muscle weakness and renal failure. He was diagnosed as BS of unknown type at the age of 9?months and treated with indomethacin (2?mg/kg/day) and potassium chloride (KCl) supplementation (1.5?mEq/kg/day) for hypokalemia (2.5?mmol/l). At the age of 12?years, serum K+ was 3.0?mmol/l and creatinine reached 2.0?mg/dl. On admission, his blood pressure was normal but volume status was depleted. Urinalysis was essentially normal. Biochemical studies showed hypokalemia (K+ 2.4?mmol/l) with a high transtubular K+ gradient (TTKG) 9.6, metabolic alkalosis (HCO3 ?/sup> 28.4?mmol/l), normomagnesemia (2.0?mg/dl), severe renal failure (BUN 94?mg/dl, Cr 6.3?mg/dl), and hypocalciuria (urine calcium/creatinine ratio 0.02?mg/mg). Abdominal sonography revealed bilateral small size kidneys without nephrocalcinosis or renal stones. After the withdrawal of indomethacin with regular KCl and adequate fluid supplementation for 1?year, serum creatinine and K+ levels have been maintained at 4.0?mg/dl and 3.3?mmol/l, respectively. Direct sequencing of NKCC2, ROMK, ClC-Kb, and NCCT in this patient disclosed a novel homozygous missense mutation (GGG to GAG, G470E) in CLCNKB. This G470E mutation was not identified in 100 healthy Chinese subjects. Long-term therapy of non-steroidal anti-inflammatory drugs (NSAIDs), prolonged hypokalemia, chronic volume depletion, and underlying genetic variety may contribute to the deterioration of his renal function. The cautious use of NSAIDs, aggressive correction of hypokalemia, and avoidance of severe volume depletion may prevent the irreversible renal damage in patients with BS due to a Cl?/sup> channel defect.