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. 1970 Jul;49(7):1447–1457. doi: 10.1172/JCI106362

Urine concentration and dilution in hypokalemic and hypercalcemic dogs

Cleaves M Bennett 1
PMCID: PMC322618  PMID: 5432374

Abstract

The urine-concentrating mechanism was studied in chronic hypokalemia (seven dogs given a low K+, high NaCl diet plus injections of deoxycorticosterone acetate [DOCA]) and chronic hypercalcemia (seven dogs given vitamin D). In the potassium-depleted dogs, muscle, serum, and urine K+ fell markedly, but glomerular filtration rate (GFR) and body weight varied little. Maximum urine osmolality fell in all dogs (mean decrease = 45%); however, solute-free water reabsorption (TCH2O) at high rates of solute excretion remained normal in three of four dogs. Free water excretion (CH2O) increased normally or supranormally as a function of increasing Na+ delivery to Henle's loop in six dogs so tested.

Hypercalcemia of several weeks duration caused a decrease in both GFR (mean 36%) as well as in maximum urine osmolality (mean 57%). Maximum TCH2O was not invariably depressed; in fact, when the values were adjusted for the reduced number of functioning nephrons (TCH2O/CIn), four of seven studies were normal. CH20/CIn increased normally (or supranormally) with increasing fractional Na delivery to Henle's loop in four of five dogs.

I conclude that the lowered maximum urine osmolality in these hypokalemic and hypercalcemic dogs was not related to abnormal water reabsorption from the collecting ducts. Although not specifically measured in this study, it is very likely that solute accumulation in the renal medulla was reduced. This probably was not caused by abnormal delivery of sodium to, nor reabsorption of sodium from Henle's loop. It is likely that a more subtle defect exists in the countercurrent mechanisms for establishing a steep concentration gradient in the renal medulla. In the few hypercalcemic dogs in whom GFR was very low, I believe that injury to, and blockage of medullary tubules could account for most of the reduction in maximum UOsm. Although not specifically ruled out, there is no evidence here to suggest that high serum Ca+ or low serum K+ per se causes a defect in sodium and water reabsorption in the mammalian nephron.

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Selected References

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

  1. BANK N., AYNEDJIAN H. S. A MICROPUNCTURE STUDY OF THE RENAL CONCENTRATING DEFECT OF POTASSIUM DEPLETION. Am J Physiol. 1964 Jun;206:1347–1354. doi: 10.1152/ajplegacy.1964.206.6.1347. [DOI] [PubMed] [Google Scholar]
  2. BANK N., AYNEDJIAN H. S. ON THE MECHANISM OF HYPOSTHENURIA IN HYPERCALCEMIA. J Clin Invest. 1965 Apr;44:681–693. doi: 10.1172/JCI105180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berliner R. W., Bennett C. M. Concentration of urine in the mammalian kidney. Am J Med. 1967 May;42(5):777–789. doi: 10.1016/0002-9343(67)90095-2. [DOI] [PubMed] [Google Scholar]
  4. Brunner F. P., Rector F. C., Jr, Seldin D. W. The mechanism of the urinary concentrating defect in potassium deficient rats. Pflugers Arch Gesamte Physiol Menschen Tiere. 1966;290(3):202–210. doi: 10.1007/BF00363123. [DOI] [PubMed] [Google Scholar]
  5. CARONE F. A., EPSTEIN F. H., BECK D., LEVITIN The effects upon the kidney of transienthypercalcemia induced by parathyroid extract. Am J Pathol. 1960 Jan;36:77–103. [PMC free article] [PubMed] [Google Scholar]
  6. COBURN J. W., GONICK H. C., RUBINI M. E., KLEEMAN C. R. STUDIES OF EXPERIMENTAL RENAL FAILURE IN DOGS. I. EFFECT OF 5-6 NEPHRECTOMY ON CONCENTRATING AND DILUTING CAPACITY OF RESIDUAL NEPHRONS. J Clin Invest. 1965 Apr;44:603–614. doi: 10.1172/JCI105173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. EARLEY L. E., KAHN M., ORLOFF J. The effects of infusions of chlorothiazide on urinary dilution and concentration in the dog. J Clin Invest. 1961 May;40:857–866. doi: 10.1172/JCI104320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. EIGLER J. O., SALASSA R. M., BAHN R. C., OWEN C. A., Jr Renal distribution of sodium in potassium-depleted and vitamin D-intoxicated rats. Am J Physiol. 1962 Jun;202:1115–1120. doi: 10.1152/ajplegacy.1962.202.6.1115. [DOI] [PubMed] [Google Scholar]
  9. EPSTEIN F. H., BECK D., CARONE F. A., LEVITIN H., MANITIUS A. Changes in renal concentrating ability produced by parathyroid extract. J Clin Invest. 1959 Jul;38(7):1214–1221. doi: 10.1172/JCI103896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GIEBISCH G., LOZANO R. The effects of adrenal steroids and potassium depletion on the elaboration of an osmotically concentrated urine. J Clin Invest. 1959 May;38(5):843–853. doi: 10.1172/JCI103866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. GOLDSMITH C., BEASLEY H. K., WHALLEY P. J., RECTOR F. C., Jr, SELDIN D. W. The effect of salt deprivation on the urinary concentrating mechanism in the dog. J Clin Invest. 1961 Nov;40:2043–2052. doi: 10.1172/JCI104430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. GOODMAN B., COHEN J. A., LEVITT M. F., KAHN M. RENAL CONCENTRATION IN THE NORMAL DOG: EFFECT OF AN ACUTE REDUCTION IN SALT EXCRETION. Am J Physiol. 1964 May;206:1123–1130. doi: 10.1152/ajplegacy.1964.206.5.1123. [DOI] [PubMed] [Google Scholar]
  13. Goldberg M., Ramirez M. A. Effects of saline and mannitol diuresis on the renal concentrating mechanism in dogs: alterations in renal tissue solutes and water. Clin Sci. 1967 Jun;32(3):475–493. [PubMed] [Google Scholar]
  14. Gottschalk C. W., Mylle M., Jones N. F., Winters R. W., Welt L. G. Osmolality of renal tubular fluids in potassium-depleted rodents. Clin Sci. 1965 Oct;29(2):249–260. [PubMed] [Google Scholar]
  15. Horster M., Thurau K. Micropuncture studies on the filtration rate of single superficial and juxtamedullary glomeruli in the rat kidney. Pflugers Arch Gesamte Physiol Menschen Tiere. 1968;301(2):162–181. doi: 10.1007/BF00362733. [DOI] [PubMed] [Google Scholar]
  16. IACOBELLIS M., MUNTWYLER E., GRIFFIN G. E. Kidney glutaminase and carbonic anhydrase activity and tissue electrolyte composition in potassium-deficient dogs. Am J Physiol. 1955 Dec;183(3):395–400. doi: 10.1152/ajplegacy.1955.183.3.395. [DOI] [PubMed] [Google Scholar]
  17. LEVINSKY N. G., BERLINER R. W. The role of urea in the urine concentrating mechanism. J Clin Invest. 1959 May;38(5):741–748. doi: 10.1172/JCI103854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MANITIUS A., LEVITIN H., BECK D., EPSTEIN F. H. On the mechanism of impairment of renal concentrating ability in hypercalcemia. J Clin Invest. 1960 Apr;39:693–697. doi: 10.1172/JCI104085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MANITIUS A., LEVITIN H., BECK D., EPSTEIN F. H. On the mechanism of impairment of renal concentrating ability in potassium deficiency. J Clin Invest. 1960 Apr;39:684–692. doi: 10.1172/JCI104084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. RUBINI M. E. Water excrtion in potassium-deficient man. J Clin Invest. 1961 Dec;40:2215–2224. doi: 10.1172/JCI104448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schwartz W. B., Relman A. S. Effects of electrolyte disorders on renal structure and function. N Engl J Med. 1967 Feb 16;276(7):383–contd. doi: 10.1056/NEJM196702162760705. [DOI] [PubMed] [Google Scholar]
  22. Schwartz W. B., Relman A. S. Effects of electrolyte disorders on renal structure and function. N Engl J Med. 1967 Feb 23;276(8):452–concl. doi: 10.1056/NEJM196702232760807. [DOI] [PubMed] [Google Scholar]
  23. Stein R. M., Abramson R. G., Kahn T., Levitt M. F. Effects of hypotonic saline loading in hydrated dog: evidence for a saline-induced limit on distal tubular sodium transport. J Clin Invest. 1967 Jul;46(7):1205–1214. doi: 10.1172/JCI105614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. WELT L. G., HOLLANDER W., Jr, BLYTHE W. B. The consequences of potassium depletion. J Chronic Dis. 1960 Mar;11:213–254. doi: 10.1016/0021-9681(60)90038-2. [DOI] [PubMed] [Google Scholar]

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