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UP FRONT MATTERSScience in Renal Medicine
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Mechanisms in Hyperkalemic Renal Tubular Acidosis

Fiona E. Karet
JASN February 2009, 20 (2) 251-254; DOI: https://doi.org/10.1681/ASN.2008020166
Fiona E. Karet
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Abstract

The form of renal tubular acidosis associated with hyperkalemia is usually attributable to real or apparent hypoaldosteronism. It is therefore a common feature in diabetes and a number of other conditions associated with underproduction of renin or aldosterone. In addition, the close relationship between potassium levels and ammonia production dictates that hyperkalemia per se can lead to acidosis. Here I describe the modern relationship between molecular function of the distal portion of the nephron, pathways of ammoniagenesis, and hyperkalemia.

To begin, we need a definition and differential diagnosis for hyperkalemic (type IV) renal tubular acidosis (RTA). Inability of the kidney either to excrete sufficient net acid or to retain sufficient bicarbonate results in a group of disorders known as RTAs.1 These all are normal anion gap hyperchloremic acidoses; in their traditional classification, type IV refers to the only variant associated with hyperkalemia. Unlike other distal RTAs, the collecting duct here fails to excrete both protons and potassium. Such a situation arises when aldosterone is insufficient in either quantity or activity and/or because of some intrinsic (genetic) or acquired molecular defect in relevant transporters. Sufficiency of aldosterone is both quantitatively and functionally necessary for adequate sodium reabsorption by the epithelial sodium channel (ENaC) located on the luminal surface of principal cells in the terminal portions of the nephron, which under normal conditions leads to the lumen-negative potential essential for potassium and proton secretion (Figure 1A). In addition, aldosterone has a direct, Na-independent, nongenomic effect on proton secretion through upregulation of apical proton pumps on intercalated cells, in rodents at least.2,3

Figure 1.
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Figure 1.

Factors involved in hyperkalemic acidosis. (A) Proper function of the ENaC at the apical surface of principal cells is necessary for K+ secretion by ROMK in these same cells and H+ secretion by adjacent intercalated cells. Inherited or acquired loss of ENaC function or its regulation by aldosterone via the mineralocorticoid receptor (MR) gives rise to hyperkalemic acidosis. (B) Hyperkalemia raises intracellular pH by exchange with protons, impairing enzymes involved in ammoniagenesis. (C) Ammoniagenesis in the proximal tubule is chiefly by deamidation of filtered or secreted glutamine (Gln). Ammonia (NH3) diffusing into the nascent urine assists in buffering H+; both NH3 and NH4+ undergo further reabsorption in the medullary loop followed by distal nephron movement into the final urine. Glu, glutamate; aKG, α-ketoglutarate.

TRUE HYPOALDOSTERONISM

Low levels of aldosterone or tubular unresponsiveness to this hormone are present in the majority of patients with hyperkalemia and impaired renal function before end stage.4,5 The most common medical conditions associated with hyporeninemic hypoaldosteronism include diabetes and various forms of interstitial disease, including amyloid, monoclonal gammopathies, and particularly the interstitial nephritis associated with nonsteroidal anti-inflammatory agents. In the last case, renin levels may be normal, and some patients with diabetes fail to respond with aldosterone synthesis or release despite hyperkalemia. Other situations in which hypoaldosteronism is present but not matched by hyporeninism include adrenal destruction (whether surgical, malignant, or hemorrhagic), Addison disease, angiotensin-converting enzyme inhibitor therapy or angiotensin receptor blockade, critical illness (because of direct adrenal suppression), and inhibition of aldosterone synthesis by heparin.6,7 Hyporeninemic hypoaldosteronism is also predictable with β blockade.8

APPARENT OR FUNCTIONAL HYPOALDOSTERONISM

Functional hypoaldosteronism occurs in the context either of various inherited disorders (see next section) or of a number of drugs that affect aldosterone activity, either directly by interference with its receptor or by affecting its target pathway.9 For example, mineralocorticoid receptors on the basolateral surface of distal nephron epithelia (Figure 1A) are antagonized by spironolactone and eplerenone, whereas the ENaC itself is blocked not only by amiloride and triamterene but also by trimethoprim and pentamidine.10,11 Cyclosporine therapy interferes with the sodium gradient in the collecting duct by interference with the basolateral Na/K-ATPase and possibly NKCC2 and/or distal K+ channels.12

WHAT CAN WE LEARN FROM MENDELIAN DISORDERS?

Single-gene disorders that affect the renal transporters mentioned in the previous section also contribute to knowledge of the complex interplay between salt handling and acid-base balance. A good example is pseudohypoaldosteronism type 1 (OMIM 264350, 177735). Here, despite activation of the renin-aldosterone axis, renal salt wasting is accompanied by hyperkalemia and hyperchloremic metabolic acidosis, all of which are due either to loss of function of ENaC because of mutations in one of the three genes encoding its subunits in the severe, recessive form of the disease13,14 or to abnormalities in the mineralocorticoid receptor in the milder, dominant form.15 These phenotypes are recapitulated in mouse models.16,17

Pseudohypoaldosteronism type 2 (OMIM 145260), also known as Gordon syndrome, represents a different problem: that of dominantly inherited hyperkalemic hypertension with an associated (usually mild) acidosis, in which either removal of the distal NaCl co-transporter from the distal convoluted tubule apical surface or insertion of ROMK into the collecting duct membrane is impaired because of mutation in one of their regulators, the WNK (with no lysine [K] kinases.18 Both of these defects have the effect of impairing distal K+ secretion—the former because distal sodium delivery falls and the latter because K+ secretion fails.19 In either case, the renin-aldosterone axis fails to compensate. Whether WNK kinases also regulate proton pumps in the collecting duct is unknown.

Rare nonrenal conditions that impair mineralocorticoid synthesis include inherited enzyme defects such as 21-hydroxylase, 3β-hydroxysteroid dehydrogenase, and corticosterone methyloxidase deficiency (OMIM 201910, 201810, 203400, 610600).

HOW DOES HYPERKALEMIA CAUSE ACIDOSIS?

Thirty-five years ago, normal men who were fed a high-K+ diet were observed to decrease their urine pH, ammonium, and net acid excretion. This was interpreted as being due to decreased renal ammonia production.20,21 In the presence of normal aldosterone production, however, a high intake of K+ does not commonly lead to metabolic acidosis per se in humans compared with rodents, in which dietary manipulation results in a much bigger K+ load. Reduction in ammonia production in humans is offset by an increase in distal sodium delivery and aldosterone upregulation, which promote K+ and H+ excretion as discussed already.

The roles of aldosterone and hyperkalemia in the physiology of human hyperkalemic acidosis were considered in a case report in the New England Journal of Medicine.22 The case concerned a patient with hyperkalemic hypoaldosteronism but only moderate renal impairment. The authors demonstrated reduced urinary ammonium excretion that resolved with the use of ion exchange resins to correct the hyperkalemia, whereas replacing the mineralocorticoid only partly corrected the biochemical and acid-base disturbance. This finding implicated hyperkalemia itself in the pathophysiology.

The mechanism of this observation was not addressed in the article, and the vast majority both of in vivo and in vitro studies from which conventional wisdom is extracted concern the kidneys of experimental animals. Experiments in dogs were probably the first to reveal that mineralocorticoid deficiency led not only to hyperkalemia but also to diminished ammonia production and proton secretion23,24 and revealed a species difference in that dogs are unable to lower urine pH in this context, whereas humans do. Kamm reported to the American Society of Nephrology in a 1971 abstract that chronic K+ loading in rats reduced ammonium excretion.25 A variety of studies thereafter agreed, albeit with differing percentage falls, DuBose and Good26 reporting a 40% drop in urinary ammonium excretion with 50% fall in whole-kidney ammonium production; however, the fine details of how this happens mechanistically are still to some extent unclear, in part because of methodologic as well as species differences between studies. For example, rats fed a high-K+ diet for 1 wk showed diminished distal nephron ammonium secretion in the isolated perfused kidney, although this was not significantly different from control animals, whereas perfusing individual kidney tubules with K+ led to a 30% fall in ammoniagenesis.27 The finding was amiloride independent,28 but the role of aldosterone was not addressed at that point.

Looking at the role of the proximal tubule at the level of the single nephron, both acute and chronic K+ loading in rats diminishes proximal ammonia generation but does not affect the rate of its transport in easily accessible cortical nephrons,26,29 leading to the suggestion that deeper nephrons contribute a greater net effect on ammonia physiology. Isolated perfused mouse nephrons yielded similar findings: a significant fall in proximal tubular ammonia production without affecting the rate of secretion.30

Despite agreement that proximal production is affected, how this is achieved is unclear. It probably involves potassium entry into cells, displacing protons and thereby raising intracellular pH,31,32 which by extrapolation from the opposite effects of acidosis likely leads to reduced enzyme function (Figure 1B); however, a number of unresolved issues remain. First, it is not clear whether this would be an acute or a chronic adaptation: In an early study, long-term K+ loading of rats led to drops in ammonia levels in kidney slices of 5% in cortex and 36% in medulla, whereas acutely treating kidney slices with K+ solution ex vivo did not have the same effect33 Conversely, another study showed rat cortical slices acutely exposed to K+ up to 10 mmol/L inhibited ammonia formation.34

Second, there has been controversy as to the actual mechanism modulating ammonia production, a large proportion of which normally takes place through deamidation of glutamine within mitochondria in proximal tubular cells (Figure 1C). Although there is support in the literature for lower levels of glutamate deamination in cortical tissue in hyperkalemic rat and dog,35 a study of isolated mitochondrial function in vitro concluded that overall glutamine metabolism was not greatly affected by high potassium.36 These differing observations are in contrast to increased mitochondrial activity repeatedly observed in K+ depletion. The differences may be accountable by in vitro experimental variations and/or effects of build-up of intermediate metabolites,37 and it is notable that assessments of changes in systemic and/or intracellular pH have not in general been reported in dietary K+ studies.

In addition, the reported effects of direct pH change on isolated mitochondria do not necessarily mirror those on intact cells, as exemplified by Tannen and Kunin's36 finding that lowering medium pH seems to inhibit isolated mitochondrial ammonia production in rats, whereas, contrary to expectation, it was alkalosis that had this effect in a dog study.38 Again, most studies are concerned with metabolic acidosis as the primary insult rather than hyperkalemia. Overall, however, there is agreement that ammonia production in the proximal tubule is indeed decreased by hyperkalemia, with the caveat that many studies have focused more on states of K+ depletion.

Further down the nephron, interstitial accumulation of both ammonia and ammonium by their movement out of the loop of Henle and their subsequent reappearance in the final urine play important roles in normal acid-base and fluid balance that may be disturbed in hyperkalemia and therefore contribute to the acidosis. Because a proportion of proximally produced ammonia is protonated by the extruded H+ ions exchanged for Na+ by NHE3 (Figure 1C), both nonionic diffusion of ammonia and ionic transport of ammonium are required for transport from lumen to interstitium and back again. These have been the subject of large bodies of work that in normal animals together demonstrate relative predominance of ammonium transport in the loop but ammonia diffusion in the collecting duct, both of which are subject to alterations that depend on pH, lumen voltage, and electrolyte concentrations.

The transport of ammonium in both loop and collecting duct has been implicated in the acidosis of hyperkalemia.39 In the loop, ammonium reabsorption is furosemide sensitive, suggesting a role for the apical Na/K/2Cl co-transporter.40 Hyperkalemia diminishes this transcellular transport, probably by direct competition between elevated luminal K+ and ammonium for the K+ binding site on the co-transporter.41,42 Similarly, in the inner medulla, failure of normal, transcellular ammonium secretion into urine in the context of hyperkalemia has been linked to impaired capacity of the collecting duct's basolateral sodium pump to carry the NH4+ ion.43 In addition, reduced availability in the collecting duct lumen of ammonia will preclude buffering of directly secreted protons (Figure 1A).

Thus, interplay between renal potassium and acid-base homeostatic function is complex,44 involving direct effects of one on the other through modulation of ion transport by aldosterone, lowering of ammonia formation, and defective medullary ammonium handling. In the clinical context, hypoaldosteronism is the dominant factor in human hyperkalemic RTA, and rodent studies of hyperkalemic metabolic alterations must be extrapolated with caution.

Disclosures

None.

Acknowledgments

F.E.K. is a Senior Clinical Research Fellow of the Wellcome Trust. With thanks to Tom DuBose and Kevin O'Shaughnessy for helpful discussion and Andy Fry for editorial assistance.

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

  • Copyright © 2009 by the American Society of Nephrology

REFERENCES

  1. ↵
    DuBose TD Jr: Acid-base disorders. In: Brenner and Rector's The Kidney, Vol. 1 , edited by Brenner BM, Philadelphia, W.B. Saunders Co., 2000 , pp 948– 962
    OpenUrl
  2. ↵
    Stone DK, Seldin DW, Kokko JP, Jacobson HR: Mineralocorticoid modulation of rabbit medullary collecting duct acidification: A sodium-independent effect. J Clin Invest 72 : 77– 83, 1983
    OpenUrlCrossRefPubMed
  3. ↵
    Winter C, Schulz N, Giebisch G, Geibel JP, Wagner CA: Nongenomic stimulation of vacuolar H+-ATPases in intercalated renal tubule cells by aldosterone. Proc Natl Acad Sci U S A 101 : 2636– 2641, 2004
    OpenUrlAbstract/FREE Full Text
  4. ↵
    Schambelan M, Sebastian A, Biglieri EG: Prevalence, pathogenesis, and functional significance of aldosterone deficiency in hyperkalemic patients with chronic renal insufficiency. Kidney Int 17 : 89– 101, 1980
    OpenUrlCrossRefPubMed
  5. ↵
    Arruda JA, Batlle DC, Sehy JT, Roseman MK, Baronowski RL, Kurtzman NA: Hyperkalemia and renal insufficiency: Role of selective aldosterone deficiency and tubular unresponsiveness to aldosterone. Am J Nephrol 1 : 160– 167, 1981
    OpenUrlPubMed
  6. ↵
    Abbott EC, Gornall AG, Sutherland DJ, Laidlaw JC, Stiefel M: The influence of a heparin-like compound on hypertension, electrolytes and aldosterone in man. CMAJ 94 : 1155– 1164, 1966
    OpenUrlPubMed
  7. ↵
    Kutyrina IM, Nikishova TA, Tareyeva IE: Effects of heparin-induced aldosterone deficiency on renal function in patients with chronic glomerulonephritis. Nephrol Dial Transplant 2 : 219– 223, 1987
    OpenUrlPubMed
  8. ↵
    Johnson JA, Davis JO, Gotshall RW, Lohmeier TE, Davis JL, Braverman B, Tempel GE: Evidence for an intrarenal beta receptor in control of renin release. Am J Physiol 230 : 410– 418, 1976
    OpenUrlPubMed
  9. ↵
    Perazella MA: Trimethoprim-induced hyperkalaemia: Clinical data, mechanism, prevention and management. Drug Saf 22 : 227– 236, 2000
    OpenUrlCrossRefPubMed
  10. ↵
    Velazquez H, Perazella MA, Wright FS, Ellison DH: Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med 119 : 296– 301, 1993
    OpenUrlCrossRefPubMed
  11. ↵
    Kleyman TR, Roberts C, Ling BN: A mechanism for pentamidine-induced hyperkalemia: Inhibition of distal nephron sodium transport. Ann Intern Med 122 : 103– 106, 1995
    OpenUrlCrossRefPubMed
  12. ↵
    Aker S, Heering P, Kinne-Saffran E, Deppe C, Grabensee B, Kinne RK: Different effects of cyclosporine a and FK506 on potassium transport systems in MDCK cells. Exp Nephrol 9 : 332– 340, 2001
    OpenUrlCrossRefPubMed
  13. ↵
    Chang SS, Grunder S, Hanukoglu A, Rosler A, Mathew PM, Hanukoglu I, Schild L, Lu Y, Shimkets RA, Nelson-Williams C, Rossier BC, Lifton RP: Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet 12 : 248– 253, 1996
    OpenUrlCrossRefPubMed
  14. ↵
    Strautnieks SS, Thompson RJ, Gardiner RM, Chung E: A novel splice-site mutation in the gamma subunit of the epithelial sodium channel gene in three pseudohypoaldosteronism type 1 families. Nat Genet 13 : 248– 250, 1996
    OpenUrlCrossRefPubMed
  15. ↵
    Geller DS, Rodriguez-Soriano J, Vallo Boado A, Schifter S, Bayer M, Chang SS, Lifton RP: Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. Nat Genet 19 : 279– 281, 1998
    OpenUrlCrossRefPubMed
  16. ↵
    Hummler E, Barker P, Talbot C, Wang Q, Verdumo C, Grubb B, Gatzy J, Burnier M, Horisberger JD, Beermann F, Boucher R, Rossier BC: A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism. Proc Natl Acad Sci U S A 94 : 11710– 11715, 1997
    OpenUrlAbstract/FREE Full Text
  17. ↵
    Berger S, Bleich M, Schmid W, Cole TJ, Peters J, Watanabe H, Kriz W, Warth R, Greger R, Schutz G: Mineralocorticoid receptor knockout mice: Pathophysiology of Na+ metabolism. Proc Natl Acad Sci U S A 95 : 9424– 9429, 1998
    OpenUrlAbstract/FREE Full Text
  18. ↵
    Wilson FH, Disse-Nicodeme S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP: Human hypertension caused by mutations in WNK kinases. Science 293 : 1107– 1112, 2001
    OpenUrlAbstract/FREE Full Text
  19. ↵
    Subramanya AR, Yang CL, McCormick JA, Ellison DH: WNK kinases regulate sodium chloride and potassium transport by the aldosterone-sensitive distal nephron. Kidney Int 70 : 630– 634, 2006
    OpenUrlCrossRefPubMed
  20. ↵
    Tannen RL, Wedell E, Moore R: Renal adaptation to a high potassium intake: The role of hydrogen ion. J Clin Invest 52 : 2089– 2101, 1973
    OpenUrlCrossRefPubMed
  21. ↵
    Tannen RL: Relationship of renal ammonia production and potassium homeostasis. Kidney Int 11 : 453– 465, 1977
    OpenUrlCrossRefPubMed
  22. ↵
    Szylman P, Better OS, Chaimowitz C, Rosler A: Role of hyperkalemia in the metabolic acidosis of isolated hypoaldosteronism. N Engl J Med 294 : 361– 365, 1976
    OpenUrlCrossRefPubMed
  23. ↵
    Kurtzman NA, White MG, Rogers PW: Aldosterone deficiency and renal bicarbonate reabsorption. J Lab Clin Med 77 : 931– 940, 1971
    OpenUrlPubMed
  24. ↵
    Hulter HN, Ilnicki LP, Harbottle JA, Sebastian A: Impaired renal H+ secretion and NH3 production in mineralocorticoid-deficient glucocorticoid-replete dogs. Am J Physiol 232 : F136– F146, 1977
    OpenUrlPubMed
  25. ↵
    Kamm DE: Dissociation of urine pH and NH3 excretion during KCl and NaCl loading (Abstract). Proc Annu. Meeting Am Soc Nephrol., 5th, Washington, DC, 1971 , p 36 .
  26. ↵
    DuBose TD Jr, Good DW: Effects of chronic hyperkalemia on renal production and proximal tubule transport of ammonium in rats. Am J Physiol 260 : F680– F687, 1991
    OpenUrlPubMed
  27. ↵
    Sastrasinh S, Tannen RL: Effect of potassium on renal NH3 production. Am J Physiol 244 : F383– F391, 1983
    OpenUrlPubMed
  28. ↵
    Kornandakieti C, Tannen RL: Hydrogen ion secretion by the distal nephron in the rat: Effect of potassium. J Lab Clin Med 104 : 293– 303, 1984
    OpenUrlPubMed
  29. ↵
    Jaeger P, Karlmark B, Giebisch G: Ammonium transport in rat cortical tubule: Relationship to potassium metabolism. Am J Physiol 245 : F593– F600, 1983
    OpenUrlPubMed
  30. ↵
    Nagami GT: Effect of bath and luminal potassium concentration on ammonia production and secretion by mouse proximal tubules perfused in vitro. J Clin Invest 86 : 32– 39, 1990
    OpenUrlCrossRefPubMed
  31. ↵
    Altenberg GA: Intracellular alkalosis induced by increasing extracellular potassium: Ionic dependence and effects of amiloride and DIDS. Miner Electrolyte Metab 16 : 197– 201, 1990
    OpenUrlPubMed
  32. ↵
    Wang WH, Wang Y, Silbernagl S, Oberleithner H: Fused cells of frog proximal tubule: II. Voltage-dependent intracellular pH. J Membr Biol 101 : 259– 265, 1988
    OpenUrlCrossRefPubMed
  33. ↵
    Tannen RL, McGill J: Influence of potassium on renal ammonia production. Am J Physiol 231 : 1178– 1184, 1976
    OpenUrlPubMed
  34. ↵
    Chester A, Eastman S, Preuss H: Direct effects of K+ on renal slice ammoniagenesis [Abstract]. Clin Res 26 : 459A , 1978
    OpenUrl
  35. ↵
    Sleeper RS, Belanger P, Lemieux G, Preuss HG: Effects of in vitro potassium on ammoniagenesis in rat and canine kidney tissue. Kidney Int 21 : 345– 353, 1982
    OpenUrlCrossRefPubMed
  36. ↵
    Tannen RL, Kunin AS: Effect of potassium on ammoniagenesis by renal mitochondria. Am J Physiol 231 : 44– 51, 1976
    OpenUrlPubMed
  37. ↵
    Goldstein L: Relation of glutamate to ammonia production in the rat kidney. Am J Physiol 210 : 661– 666, 1966
    OpenUrlPubMed
  38. ↵
    Simpson DP, Adam W: Glutamine transport and metabolism by mitochondria from dog renal cortex: General properties and response to acidosis and alkalosis. J Biol Chem 250 : 8148– 8158, 1975
    OpenUrlAbstract/FREE Full Text
  39. ↵
    DuBose TD Jr, Good DW: Chronic hyperkalemia impairs ammonium transport and accumulation in the inner medulla of the rat. J Clin Invest 90 : 1443– 1449, 1992
    OpenUrlCrossRefPubMed
  40. ↵
    Good DW, Knepper MA, Burg MB: Ammonia and bicarbonate transport by thick ascending limb of rat kidney. Am J Physiol 247 : F35– F44, 1984
    OpenUrlPubMed
  41. ↵
    Good DW: Ammonium transport by the thick ascending limb of Henle's loop. Annu Rev Physiol 56 : 623– 647, 1994
    OpenUrlCrossRefPubMed
  42. ↵
    Watts BA 3rd, Good DW: Effects of ammonium on intracellular pH in rat medullary thick ascending limb: Mechanisms of apical membrane NH4+ transport. J Gen Physiol 103 : 917– 936, 1994
    OpenUrlAbstract/FREE Full Text
  43. ↵
    Wall SM: NH4+ augments net acid secretion by a ouabain-sensitive mechanism in isolated perfused inner medullary collecting ducts. Am J Physiol 270 : F432– F439, 1996
    OpenUrlPubMed
  44. ↵
    DuBose TD Jr: Molecular and pathophysiologic mechanisms of hyperkalemic metabolic acidosis. Trans Am Clin Climatol Assoc 111 : 122– 133, discussion 133–124, 2000
    OpenUrlPubMed
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Mechanisms in Hyperkalemic Renal Tubular Acidosis
Fiona E. Karet
JASN Feb 2009, 20 (2) 251-254; DOI: 10.1681/ASN.2008020166

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Mechanisms in Hyperkalemic Renal Tubular Acidosis
Fiona E. Karet
JASN Feb 2009, 20 (2) 251-254; DOI: 10.1681/ASN.2008020166
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  • Article
    • Abstract
    • TRUE HYPOALDOSTERONISM
    • APPARENT OR FUNCTIONAL HYPOALDOSTERONISM
    • WHAT CAN WE LEARN FROM MENDELIAN DISORDERS?
    • HOW DOES HYPERKALEMIA CAUSE ACIDOSIS?
    • Disclosures
    • Acknowledgments
    • Footnotes
    • REFERENCES
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