Evidence for a tubular defect in the loop of Henle

Early clearance studies suggested a defect in chloride transport in the TALH to be the proximal event in BS. [9] [10] In later studies, however, the combined use of clearance methods and diuretics revealed an impaired thiazide-sensitive salt reabsorption, suggesting that the distal convoluted tubule is the segment primarily affected in GS [13] and BS. [12] [15] Recently mutations in the thiazide-sensitive NaCl-cotransporter gene were detected in patients with GS. [49] Chaimovitz et al. [50] described a boy with “Bartter syndrome” who had a normal response to thiazides. This observation was probably the result of an incomplete characterization of the patient, who had typical features of HPS such as isosthenuria and severe failure to thrive. [50] Unfortunately no data referring to calcium and magnesium excretion were given in this case. Two of our children with HPS did show a normal response to hydrochlorothiazide (l mg/kg per day) during a treatment period of 1 week (unpublished observations).

In summary the classification of inborn hypokalemic tubular disorders into distinct entities could be confirmed by the use of furosemide administration. In HPS the markedly impaired response to furosemide revealed a tubular defect in the TALH. The beneficial effect of indomethacin treatment underscores the important pathophysiologic role of concomitant PGE2 overproduction in HPS. In contrast, patients with BS or GS had normal sensitivity to furosemide, indicating an intact function of the TALH in these disorders.

We thank Dr. Klaus Ehlenz for performing plasma renin activity and aldosterone assays, Dr. Horst Schweer for mass spectrometric analysis of urinary prostaglandins, and Bernhard Watzer for measuring the drug levels. We thank the nursing staff for their assistance in urine collections.

Supported by grant No. Se 263/11-1 from the Deutsche Forschungsgemeinschaft.

Presented in part at the International Congress of Nephrology, Madrid, Spain, July 2-6, 1995.

Submitted for publication Jan. 29, 1996; accepted May 23, 1996.Copyright ? 1996 by Mosby-Year Book, Inc.

REFERENCES

1. Stein JH. The pathogenetic spectrum of Bartter’s syndrome. Kidney Int 1985;28:85-93.

2. Clive DM. Bartter’s syndrome: the unsolved puzzle. Am J Kidney Dis 1995;25:813-23.

3. Bartter FS, Pronove O, Gill JR, MacCardle RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. Am J Med 1962;33:811-28.

4. Gitelman HJ, Graham JB, Welt LG. A new familial disorder characterized by hypokalemia and hypomagnesemia. Trans Assoc Am Physicians 1966;79:221-35.

5. Fanconi A, Schachenmann G, Nussli R, Prader A. Chronic hypokalaemia with growth retardation, normotensive hyperrenin-hyperaldosteronism (“Bartter’s syndrome”), and hypercalciuria. Helv Paediatr Acta 1971;2:144-63.

6. McCredie DA, Rotenberg E, Williams AL. Hypercalciuria in potassium-losing nephropathy: a variant of Bartter’s syndrome. Aust Paediatr J 1974;10:286-95.

7. Seyberth HW, Rascher W, Schweer H, Kuhl PG, Mehls O, Scharer K. Congenital hypokalemia with hypercalciuria in preterm infants: a hyperprostaglandinuric tubular syndrome different from Bartter syndrome. J Pediatr 1985;107:694-701.

8. Boer WH, Hene RJ, Koomans HA, Dorhout Mees EJ. Discrepancy between lithium and free water clearance in patients with Bartter’s syndrome. Nephron 1994;67:82-7.

9. Fujita T, Sakaguchi H, Shibagaki M, Fukui T, Nomura M, Sekiguchi S. The pathogenesis of Bartter’s syndrome. Am J Med 1977;63:467-74.

10. Gill JR, Bartter FC. Evidence for a prostaglandin-independent defect in chloride reabsorption in the loop of Henle as a proximal cause of Bartter’s syndrome. Am J Med 1978;65:766-72.

11. Zoccali C, Bartoll E, Curatola G, Maggiore Q. The renal tubular defect of Bartter’s syndrome. Nephron 1982;32:140-8.

12. Uribarri J, Alveranga D, Oh MS, Kukar NM, Del Monte ML, Carroll HJ. Bartter’s syndrome due to a defect in salt reabsorption in the distal convoluted tubule. Nephron 1985;40:52-6.

13. Sutton RAL, Mavichak V, Halabe A, Wilkins GE. Bartter’s syndrome: evidence suggesting a distal tubular defect in a hypocalciuric variant of the syndrome. Miner Electrolyte Metab 1992;18:43-51.

14. Colussi G, Rornbolh G, Verde G, Airaghi C, Loli P, Minetti L. Distal nephron function in Bartter’s syndrome: Abnormal conductance to chloride in the cortical collecting tubule? Am J Nephrol 1992;12:229-39.

15. Puschett JB, Greenberg A, Mitro R, Piraino B, Wailia R. Variant of Bartter’s syndrome with a distal tubular rather than loop of Henle defect. Nephron 1988;50:205-11.

16. Schroter J, Timmermans G, Seyberth HW, Greven J, Bachmann S. Marked reduction of Tamm-Horsfall protein synthesis in hyperprostaglandin-E-syndrome. Kidney Int 1993;44: 401-10.

17. Skellern G, Salole EG. High-speed liquid chromatographic analysis of indomethacin in plasma. J Chromatogr 1975;114: 483-5.

18. Radeck W, Heller M. Improved method for determination of furosemide in plasma by high-performance liquid chromatography. J Chromatogr 1989;497:367-70.

19. Schweer H, Watzer B, Seyberth HW. Determination of seven prostanoids in 1 ml of urine by gas chromatography-negative ion chemical ionization triple stage quatropole mass spectrometry. J Chromatogr 1994;B652:221-7.

20. Frolich JC, Wilson TW, Sweetman BJ, et al. Urinary prostaglandins: identification and origin. J Clin Invest 1975;55:763-9.

21. Seyberth HW, Sweetman BJ, Frolich JC, Oates JA. Quantification of the major urinary metabolite of the E prostaglandins by mass spectrometry: evaluation of the method’s application to clinical studies. Prostaglandins 1976;11:381-97.

22. Fichman MP, Telfer N, Zia PK, Speckart P, Golub M, Rude R. Role of prostaglandins in the pathogenesis of Bartter’s syndrome. Am J Med 1976;60:785-97.

23. Gill JR, Fro1ich JC, Bowden RE, et al. Bartter’s syndrome: a disorder characterized by high urinary prostaglandins and a dependence of hyperreninemia on prostaglandin synthesis. Am J Med 1976;61:43-51.

24. Verberckmoes R, van Damme B, Clement J, Amery A, Michielsen P. Bartter’s syndrome with hyperplasia of reno-medullary cells: successful treatment with indomethacin. Kidney Int 1976;9:302-7.

25. Seyberth HW, Leonhardt A, Tonshoff B, Gordjani N. Prostanoids in pediatric kidney diseases. Pediatr Nephrol 1991;5: 639-49.

26. Yoshida H, Kakuchi J, Yoshikawa N, et al. Angiotensin II type 1 receptor gene abnormality in a patient with Bartter’s syndrome. Kidney Int 1994;46:1505-9.

27. Hufnagle KG, Khan SN, Penn D, Cacciarelli A, Williams P. Renal calcifications: a complication of long-term furosemide therapy in preterm infants. Pediatrics 1982;70:360-3.

28. Venkataraman PS, Han BK, Tsang R, Daugerthy CC. Secondary hyperparathyroidism and bone disease in infants receiving long-term furosemide therapy. J Pediatr Adolesc Med [Am J Dis Child] 1983;137:1157-61.

29. Greger R, Heldland A. Action and clinical use of diuretics. In: Cameron S, Davison AM, Grnfeld JP, editors. Textbook of clinical nephrology. London: Oxford University Press, 1991: 197-223.

30. Bonilla-Felix M, Villegas-Medina O, Vehaskari VM. Renal acidification in children with idiopathic hypercalciuria. J Pediatr 1994;124:529-34.

31. Hammarlund MM, Odlind B, Paalzow LK. Acute tolerance to furosemide diuresis in humans: pharmacokinetic-pharmacodynamic modeling. J Pharmacol Exp Ther 1985;233:447-53.

32. Shoemaker L, Welch TR, Bergstrom W, Abrams SA, Yergey AL, Vieira N. Calcium kinetics in the hyperprostaglandin E syndrome. Pediatr Res 1993;33:92-6.

33. Knepper MA, Rector FC Jr. Urinary concentration and dilution. In: Brenner BM, Rector FC Jr, editors. The kidney. 4th ed. Philadelphia: WB Saunders, 1991:445-82.

34. Leonhardt A, Timmermanns G, Roth B, Seyberth HW. Calcium homeostasis and hypercalciuria in hyperprostaglandin E syndrome. J Pediatr 1992;120:546-54.

35. Bushinsky DA, Favus MG, Langman CB, Coe FL. Mechanism of chronic hypercalciuria with furosemide: increased calcium absorption. Am J Physiol 1986;251:F17-24.

36. Stokes JB. Effect of prostaglandin E2 on chloride transport across the rabbit thick ascending limb of Henle. J Clin Invest 1979;64:495-502.

37. Culpepper RM, Andreoli TE. Interactions among prostaglandin E2 , antidiuretic hormone and cyclic adenosine monophosphate in modulating C1 absorption in single mouse medullary thick ascending limbs of Henle. J Clin Invest 1983;71:1588-91.

38. Nivet H, Grenier B, Rolland JC, Lebranchu Y, Dray F. Raised urinary prostaglandins in patient without Bartter’s syndrome. Lancet 1978;1:333-4.

39. Mayatepek E, Seyberth HW, Nutzenadel W. Effects of indomethacin in congenital chloride diarrhea. J Pediatr Gastroenterol Nutr 1992;14:319-22.

40. Halushka PV, Margolius HS, Allen H, Conradi EC. Urinary excretion of prostaglandin E-like material and kallikrein: effects of furosemide. Prostaglandins 1979;18:359-68.

41. Patak RV, Fadem SZ, Rosenblatt SG, Lifschitz MD, Stein JH. Diuretic-induced changes in renal blood flow and prosta-glandin E excretion in the dog. Am J Physiol 1979;236:F494-500.

42. Katayama S, Attallah AA, Stahl RA, Bloch DL, Lee JB. Mechanism of furosemide-induced natriuresis by direct stimulation of renal prostaglandin E2 . Am J Physiol 1984;247:F555-61.

43. Gerber JG, Nies AS. Furosemide-induced vasodilation: importance of the state of hydration and filtration. Kidney Int 1980; 18:454-9.

44. Levenson DJ, Simmons CE, Brenner BM. Arachidonic acid metabolism, prostaglandins and the kidney. Am J Med 1982; 72:354-74.

45. Schlondorff D, Ardaillou R. Prostaglandins and other arachidonic acid metabolites in the kidney. Kidney Int 1986;29:108-19.

46. Aurell M, Rudin A. Effect of captopril on blood pressure, renal function, the electrolyte balance and the renin-angiotensin system in Bartter’s syndrome. Nephron 1983;33:274-8.

47. Bonvalet JP, Pradelles P, Farman N. Segmental synthesis and actions of prostaglandins along the nephron. Am J Physiol 1987;253:F377-87.

48. Hebert RL, Jacobson HR, Breyer MD. Prostaglandin E2 inhibits sodium transport in rabbit cortical collecting duct by increasing intracellular calcium. J Clin Invest 1991;87:1992-8.

49. Simon DB, Nelson-Williams C, Johnson Bia M, et al. Gitelman’s variant of Bartter’s syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nature Genet 1996;12:24-30.

50. Chaimovitz C, Levi J, Better OS, Oslander L, Benderli A. Studies on the site of renal salt loss in a patient with Bartter’s syndrome. Pediatr Res 1973;7:89-91.

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