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. 1967 Mar;46(3):336–345. doi: 10.1172/JCI105535

Nature of the Renal Concentrating Defect in Sickle Cell Disease*

Fred E Hatch 1,†, James W Culbertson 1, Lemuel W Diggs 1
PMCID: PMC297054  PMID: 6023770

Abstract

Free water reabsorption (TcH2O) measured during 10% mannitol diuresis and subsequently during 3% saline diuresis was compared in patients with sickle cell anemia and in normal subjects. During mannitol infusion, TcH2O progressively rose with increasing osmolar clearance (Cosm) and reached a maximal level in both groups studied. During hypertonic saline diuresis, TcH2O progressively rose in the normal subjects and exceeded the maximal levels attained during mannitol diuresis, with no evidence of a maximal TcH2O level appearing. In contrast, none of the saline curves significantly exceeded the mannitol curves in the sickle cell patients but tended to parallel the mannitol curves at comparable rates of solute clearance.

Since TcH2O is an index of both solute (sodium) transport from the loop of Henle and solute accumulation in the hypertonic medullary interstitium, tubular sodium handling was examined in both sickle cell patients and control subjects alike. No difference in the tubular transport of sodium could be demonstrated either under conditions of sodium loading or under conditions in which the tubular sodium load was low (water diuresis).

These data support the conclusion that the defect in urinary concentration in sickle cell patients is caused by a limitation in maintaining a high concentration of solute in the medullary interstitium, thus limiting the rate of TcH2O from the collecting duct.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALLEN T. D. SICKLE CELL DISEASE AND HEMATURIA: REPORT OF 29 CASES. J Urol. 1964 Feb;91:177–183. doi: 10.1016/S0022-5347(17)64084-9. [DOI] [PubMed] [Google Scholar]
  2. BERLINER R. W., DAVIDSON D. G. Production of hypertonic urine in the absence of pituitary antidiuretic hormone. J Clin Invest. 1957 Oct;36(10):1416–1427. doi: 10.1172/JCI103541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BERNSTEIN J., WHITTEN C. F. A histologic appraisal of the kidney in sickle cell anemia. Arch Pathol. 1960 Oct;70:407–418. [PubMed] [Google Scholar]
  4. ETTELDORF J. N., SMITH J. D., TUTTLE A. H., DIGGS L. W. Renal hemodynamic studies in adults with sickle cell anemia. Am J Med. 1955 Feb;18(2):243–248. doi: 10.1016/0002-9343(55)90239-4. [DOI] [PubMed] [Google Scholar]
  5. GIEBISCH G., KLOSE R. M., WINDHAGER E. E. MICROPUNCTURE STUDY OF HYPERTONIC SODIUM CHLORIDE LOADING IN THE RAT. Am J Physiol. 1964 Apr;206:687–693. doi: 10.1152/ajplegacy.1964.206.4.687. [DOI] [PubMed] [Google Scholar]
  6. GOLDBERG M., MCCURDY D. K., RAMIREZ M. A. DIFFERENCES BETWEEN SALINE AND MANNITOL DIURESIS IN HYDROPENIC MAN. J Clin Invest. 1965 Feb;44:182–192. doi: 10.1172/JCI105133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GOTTSCHALK C. W., MYLLE M. Micropuncture study of the mammalian urinary concentrating mechanism: evidence for the countercurrent hypothesis. Am J Physiol. 1959 Apr;196(4):927–936. doi: 10.1152/ajplegacy.1959.196.4.927. [DOI] [PubMed] [Google Scholar]
  8. GOTTSCHALK C. W. OSMOTIC CONCENTRATION AND DILUTION OF THE URINE. Am J Med. 1964 May;36:670–685. doi: 10.1016/0002-9343(64)90179-2. [DOI] [PubMed] [Google Scholar]
  9. HATCH F. E., DIGGS L. W. FLUID BALANCE IN SICKLE-CELL DISEASE. Arch Intern Med. 1965 Jul;116:10–17. doi: 10.1001/archinte.1965.03870010012003. [DOI] [PubMed] [Google Scholar]
  10. HEINEMANN H. O., CHEUNG M. W. Renal concentrating mechanism in sickle-cell anemia. J Lab Clin Med. 1957 Jun;49(6):923–927. [PubMed] [Google Scholar]
  11. ITANO H. A., KEITEL H. G., THOMPSON D. Hyposthenuria in sickle cell anemia: a reversible renal defect. J Clin Invest. 1956 Sep;35(9):998–1007. doi: 10.1172/JCI103360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LASSITER W. E., MYLLE M., GOTTSCHALK C. W. NET TRANSTUBULAR MOVEMENT OF WATER AND UREA IN SALINE DIURESIS. Am J Physiol. 1964 Apr;206:669–673. doi: 10.1152/ajplegacy.1964.206.4.669. [DOI] [PubMed] [Google Scholar]
  13. LEVITT M. F., HAUSER A. D., LEVY M. S., POLIMEROS D. The renal concentrating defect in sickle cell disease. Am J Med. 1960 Oct;29:611–622. doi: 10.1016/0002-9343(60)90094-2. [DOI] [PubMed] [Google Scholar]
  14. LUCAS W. M., BULLOCK W. H. Hematuria in sickie cell disease. J Urol. 1960 May;83:733–741. doi: 10.1016/S0022-5347(17)65789-6. [DOI] [PubMed] [Google Scholar]
  15. MOSTOFI F. K., VORDER BRUEGGE C. F., DIGGS L. W. Lesions in kidneys removed for unilateral hematuria in sickle-cell disease. AMA Arch Pathol. 1957 Apr;63(4):336–351. [PubMed] [Google Scholar]
  16. PERILLIE P. E., EPSTEIN F. H. Sickling phenomenon produced by hypertonic solutions: a possible explanation for the hyposthenuria of sicklemia. J Clin Invest. 1963 Apr;42:570–580. doi: 10.1172/JCI104746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. SCHLITT L., KEITEL H. G. Pathogenesis of hyposthenuria in persons with sickle cell anemia or the sickle cell trait. Pediatrics. 1960 Aug;26:249–254. [PubMed] [Google Scholar]
  18. TELLEM M., RUBENSTONE A. I., FRUMIN A. M. Renal failure and other unusual manifestations in sickle-cell trait. AMA Arch Pathol. 1957 May;63(5):508–512. [PubMed] [Google Scholar]
  19. WALSER M., DAVIDSON D. G., ORLOFF J. The renal clearance of alkali-stable inulin. J Clin Invest. 1955 Oct;34(10):1520–1523. doi: 10.1172/JCI103204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. WHITTEN C. F., YOUNES A. A. A comparative study of renal concentrating ability in children with sickel cell anemia and in normal children. J Lab Clin Med. 1960 Mar;55:400–415. [PubMed] [Google Scholar]
  21. WINDHAGER E. E., GIEBISCH G. Micropuncture study of renal tubular transfer of sodium chloride in the rat. Am J Physiol. 1961 Mar;200:581–590. doi: 10.1152/ajplegacy.1961.200.3.581. [DOI] [PubMed] [Google Scholar]
  22. ZAK G. A., BRUN C., SMITH H. W. The mechanism of formation of osmotically concentrated urine during the antidiuretic state. J Clin Invest. 1954 Jul;33(7):1064–1074. doi: 10.1172/JCI102974. [DOI] [PMC free article] [PubMed] [Google Scholar]

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