The Various Etiologies Met in the United States With Emphasis on That Resulting From a Specific Form of Renal Acidosis, the Therapeutic Indications for Each Etiological Sub-Group, and the Relationship Between Osteomalacia and Milkmanʼs Syndrome

Albright, Fuller; Burnett, Charles H.; Parson, Walther; Reifenstein, Edward C.; Roos, Albert de

doi:10.1097/00005792-194612000-00002

Cited by 277 publications

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“…This inference constitutes the basis for the widely accepted conclusion that in classic RTA impaired renal conservation of potassium and sodium is exclusively a reversible consequence of the renal acidification defect (5, 10-13). But the validity of this inference can be questioned, since it cannot be ascertained from the results of published studies whether renal conservation of potassium and sodium is unimpaired when dietary intake of these ions is restricted and correction of acidosis is sustained (1)(2)(3)(4)(5)(6)(7)(8)(9) In the present investigation of children and adult patients with classic RTA, we have evaluated renal conservation of sodium when dietary intake of sodium was restricted and correction of systemic acidosis was sustained with potassium bicarbonate. Renal conservation of sodium and chloride was impaired in 5 of 10 patients studied and was not unequivocally unimpaired in the remaining patients.…”

Section: Introductionmentioning

confidence: 99%

“…In patients with classic renal tubular acidosis (type 1, "distal" RTA)V, irrespective of the presence or absence of nephrocalcinosis, correction of systemic acidosis with alkali therapy can result in a reduction of the urinary excretion rate of potassium, sodium, and aldosterone (1)(2)(3)(4)(5)(6)(7)(8)(9); when correction of acidosis is sustained and dietary intake of sodium and potassium is not restricted, the external balance of potassium and sodium can become sufficiently positive to correct hypokalemia and secondary hyperaldosteronism (4,5). It has been inferred from these observations that the impairment in renal conservation of potassium and sodium demonstrable in untreated, acidotic patients with classic RTA is fully corrected when acidosis is corrected with alkali therapy (5).…”

Section: Introductionmentioning

confidence: 99%

“…This inference constitutes the basis for the widely accepted conclusion that in classic RTA impaired renal conservation of potassium and sodium is exclusively a reversible consequence of the renal acidification defect (5,(10)(11)(12)(13). But the validity of this inference can be questioned, since it cannot be ascertained from the results of published studies whether renal conservation of potassium and sodium is unimpaired when dietary intake of these ions is restricted and correction of acidosis is sustained (1)(2)(3)(4)(5)(6)(7)(8)(9). In some patients with classic RTA, renal potassium wasting and hyperaldosteronism persist during sustained correction of acidosis with alkali therapy, despite provision of even supernormal amounts of dietary sodium (6).…”

Section: Introductionmentioning

confidence: 99%

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Impaired renal conservation of sodium and chloride during sustained correction of systemic acidosis in patients with type 1, classic renal tubular acidosis.

Sebastián¹,

McSherry²,

Morris³

1976

J. Clin. Invest.

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A B S T R A C T in 10 patients with classic renal tubular acidosis in whom correction of acidosis was sustained with orally administered potassium bicarbonate, renal conservation of sodium was evaluated when dietary intake of sodium was restricted to 9-13 meq/day. In five patients, renal conservation of sodium was impaired by at least one criterion of impairment. In the remaining patients, renal conservation of sodium appeared to be relatively well-maintained, but an impairment could not be excluded. In each of six patients studied during induced water diuresis, including two in whom renal conservation of sodium was not unequivocally impaired, the minimal urinary concentrations of sodium were inappropriately high and the urinary excretion rates of sodium were flow-dependent. These results provide direct evidence that an abnormality in renal transport of sodium can occur in classic renal tubular acidosis, and compel a reconsideration of the pathophysiology of disordered renal transport of sodium in this disorder. The results indicate that in at least some patients with classic renal tubular acidosis impaired renal conservation of sodium is not exclusively a reversible consequence of the renal acidification defect. These findings raise the question whether renal transport of sodium is unimpaired in any patients with classic renal tubular acidosis. In the presently studied patients, the impairment in renal conservation of sodium appeared to be in part the consequence of an impaired ability of the vasopressinresponsive segments of the distal nephron to generate and maintain appropriately steep transepithelial sodium concentration gradients. INTRODUCTIONIn patients with classic renal tubular acidosis (type 1, "distal" RTA)V, irrespective of the presence or absence of nephrocalcinosis, correction of systemic acidosis with alkali therapy can result in a reduction of the urinary excretion rate of potassium, sodium, and aldosterone (1-9); when correction of acidosis is sustained and dietary intake of sodium and potassium is not restricted, the external balance of potassium and sodium can become sufficiently positive to correct hypokalemia and secondary hyperaldosteronism (4, 5). It has been inferred from these observations that the impairment in renal conservation of potassium and sodium demonstrable in untreated, acidotic patients with classic RTA is fully corrected when acidosis is corrected with alkali therapy (5). This inference constitutes the basis for the widely accepted conclusion that in classic RTA impaired renal conservation of potassium and sodium is exclusively a reversible consequence of the renal acidification defect (5, 10-13). But the validity of this inference can be questioned, since it cannot be ascertained from the results of published studies whether renal conservation of potassium and sodium is unimpaired when dietary intake of these ions is restricted and correction of acidosis is sustained (1)(2)(3)(4)(5)(6)(7)(8)(9) In the present investigation of children and adult patients with classic RTA, w...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…This inference constitutes the basis for the widely accepted conclusion that in classic RTA impaired renal conservation of potassium and sodium is exclusively a reversible consequence of the renal acidification defect (5,(10)(11)(12)(13). But the validity of this inference can be questioned, since it cannot be ascertained from the results of published studies whether renal conservation of potassium and sodium is unimpaired when dietary intake of these ions is restricted and correction of acidosis is sustained (1)(2)(3)(4)(5)(6)(7)(8)(9). In some patients with classic RTA, renal potassium wasting and hyperaldosteronism persist during sustained correction of acidosis with alkali therapy, despite provision of even supernormal amounts of dietary sodium (6).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impaired renal conservation of sodium and chloride during sustained correction of systemic acidosis in patients with type 1, classic renal tubular acidosis.

Sebastián¹,

McSherry²,

Morris³

1976

J. Clin. Invest.

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“…It may be predicted with assurance that such subjects would be harmed by therapy with potassium cycle exchanger, since toxic levels of this cation would be reached that much sooner. This danger of course would not be present in patients with normal or even an increased ability to excrete potassium (23)(24)(25). From the practical point of view, however, it would be well not to use the potassium cycle exchanger in any patient with renal failure until the adequacy of the renal mechanisms for the disposal of excesses of this cation has been established.…”

Section: Discussionmentioning

confidence: 99%

Acidifying and Non-Acidifying Carboxylic Resin Mixtures Used Alone and With Acth or Cortisone

Peters¹,

Danowski²,

Greenman³

et al. 1951

J. Clin. Invest.

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Evidence has been presented indicating that a sufficient intake of a carboxylic cation exchanger in the potassium cycle increases the stool output of sodium in absolute as well as in relative terms (1)(2)(3)(4). Two other findings accompanying the use of this form of the resin are noteworthy: a) a significant proportion of the potassium taken with or as part of the resin can be retained in the body and b) ingestion of this particular resin does not produce acidosis. Its efficiency in removing sodium is probably not as great, however, as that of either the hydrogen or the ammonium forms of the resin, each of which interferes with potassium absorption and induces a metabolic acidosis. The first half of this paper deals with findings observed during the simultaneous administration of the two types of resin in equal proportions, i.e., potassium cycle mixed with either the hydrogen or the ammonium cycle, as well as in mixtures in which the acidifying resin predominated.The second half of this report describes results obtained during the use of resin mixtures with ACTH or cortisone or both. The expanding recourse to adrenal cortical effects in the therapy of a wide variety of disease states (5-7) has further emphasized that prolonged therapy is frequently not possible because of two particularly undesirable concomitants, i.e., sodium retention and potassium depletion. It seems probable that these side effects by necessitating interruption or intermittency of treatment deprive patients of benefits which might be otherwise obtainable. The combined resin and steroid or hormone studies herein presented describe attempts at prevention or deferment of such deviations in cation metabolism. MATERIALS AND METHODSEqual parts of the acidifying and non-acidifying exchange resins were administered in capsules for a daily total of 24 to 60 g. to hospitalized children or adults during 16 periods three to seven days in length. Mixtures preponderating in the acidifying resin, i.e., 75 to 80% in the ammonium or hydrogen cycle, were given in eight subsequent studies in four patients. In the final group of experiments four parts of ammonium or hydrogen form resin and one part of the potassium resin were administered to patients undergoing treatment with adrenocorticotrophic hormone or cortisone. In all three groups of studies control periods were included when possible. The experimental procedures and other pertinent information have been described earlier (1, 2). The dietary regimens employed, the results of blood and serum analyses, and the available balance data are presented in tabular form. To assist interpretation the findings have been expressed statistically wherever possible and presented in graphic form. RESULTS

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“…In extensive earlier studies of this "specific form of renal acidosis," which is now termed "classic" or "type I RTA," Albright et al (2) demonstrated that metabolic acidosis induces hypercalciuria and consequent negative calcium balance and recognized that over time these are critical and alkali-reversible pathogenic determinants of nephrocalcinosis and nephrolithiasis and of "osteomalacia and late rickets." The acidosis of type I RTA may also give rise to osteoporosis (3) and to other disorders of bone demineralization (4).…”

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confidence: 99%

Alkali Therapy In Renal Tubular Acidosis

Morris¹,

Sebastián²

2002

Journal of the American Society of Nephrology

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Pines and Mudge (1) coined the term "renal tubular acidosis" (RTA) to denote a renal tubular disorder that causes acidosis by restricting the reduction of urinary pH and thereby the titration of urinary buffers and excretion of acid. In extensive earlier studies of this "specific form of renal acidosis," which is now termed "classic" or "type I RTA," Albright et al. (2) demonstrated that metabolic acidosis induces hypercalciuria and consequent negative calcium balance and recognized that over time these are critical and alkali-reversible pathogenic determinants of nephrocalcinosis and nephrolithiasis and of "osteomalacia and late rickets." The acidosis of type I RTA may also give rise to osteoporosis (3) and to other disorders of bone demineralization (4). In children with classic RTA, alkali therapy can heal osteopenia and induce normal somatic growth, even after severe stunting (5-7), but apparently only when given in amounts that sustain full correction of acidosis. These amounts must be great enough not only to titrate endogenously produced nonvolatile acid but also to offset renal bicarbonate wasting that characterizes the classic RTA of children in whom bicarbonate therapy has induced rapid growth (6,8). Lesser amounts of alkali and the consequent plasma bicarbonate concentrations of low-grade metabolic acidosis have been found to be unavailing with respect both to the attainment of normal growth and the correction of hypercalciuria (5).These observations prompt a series of questions about the pathogenic potential of chronic low-grade metabolic acidosis in adults, their possible benefit from its treatment with alkali, and the kind of alkali that is most availing. In adults with type I RTA that is not fully expressed, can low-grade metabolic acidosis be a pathogenic determinant of clinically important metabolic disease? Nonvolatile acid is endogenously produced at a rate that can exceed the capacity of the normal kidney to excrete it (9,10), and such excessive acid is buffered by bone at the cost of its resorption and demineralization (11,12); can alkali therapy therefore prevent, delay, or reverse either metabolic bone disease or calcium-containing kidney stone formation in those with diet-induced, low-grade metabolic acidosis but neither a recognized form of RTA nor renal failure? If so is alkali therapy best provided to these patients as KHCO 3 because it: induces in normal humans a hypocalciuric effect greater than that induced by NaHCO 3 (13) and one that more than offsets the hypercalciuric effect of dietary NaCl (14); induces an improved external calcium balance in normal men (13) and women (15); occurs naturally and plentifully in precursory form in fruits and vegetables, e.g., as potassium citrate in which organate in vivo is completely converted to bicarbonate? Can realization of the therapeutic potential of alkali therapy depend on the attaining of a metabolically optimal range of plasma bicarbonate that is higher than that comprising its lower "normal" range (5,15,16)?Metabolic bone disease and ...

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The Various Etiologies Met in the United States With Emphasis on That Resulting From a Specific Form of Renal Acidosis, the Therapeutic Indications for Each Etiological Sub-Group, and the Relationship Between Osteomalacia and Milkmanʼs Syndrome

Cited by 277 publications

References 0 publications

Impaired renal conservation of sodium and chloride during sustained correction of systemic acidosis in patients with type 1, classic renal tubular acidosis.

Impaired renal conservation of sodium and chloride during sustained correction of systemic acidosis in patients with type 1, classic renal tubular acidosis.

Acidifying and Non-Acidifying Carboxylic Resin Mixtures Used Alone and With Acth or Cortisone

Alkali Therapy In Renal Tubular Acidosis

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