Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism

Osther, Palle Jørn Sloth; Bollerslev, Jens; Hansen, Annebirthe Bo; Engel, K.; Kildeberg, Poul

doi:10.1007/bf00590032

Cited by 38 publications

(22 citation statements)

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“…"Incomplete" dRTA is used as a diagnostic term when urine citrate excretion rate is low despite high urinary pH (pH >6.5) and blood chemistries are normal; given an oral acid load, such patients may fail to lower urinary pH below 5.5 (104,105). Treatment of the low urine citrate is as already described for CaOx and CaP SFs.…”

Section: Management Of Cap Sfsmentioning

confidence: 99%

Kidney stone disease

Coe

Evan

Worcester

2005

Journal of Clinical Investigation

676

527

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About 5% of American women and 12% of men will develop a kidney stone at some time in their life, and prevalence has been rising in both sexes. Approximately 80% of stones are composed of calcium oxalate (CaOx) and calcium phosphate (CaP); 10% of struvite (magnesium ammonium phosphate produced during infection with bacteria that possess the enzyme urease), 9% of uric acid (UA); and the remaining 1% are composed of cystine or ammonium acid urate or are diagnosed as drug-related stones. Stones ultimately arise because of an unwanted phase change of these substances from liquid to solid state. Here we focus on the mechanisms of pathogenesis involved in CaOx, CaP, UA, and cystine stone formation, including recent developments in our understanding of related changes in human kidney tissue and of underlying genetic causes, in addition to current therapeutics.

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Section: Management Of Cap Sfsmentioning

confidence: 99%

Kidney stone disease

Coe

Evan

Worcester

2005

Journal of Clinical Investigation

676

527

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“…We would have liked to perform a case-control study including patients with high and low bone densities, but unfortunately we were able to obtain informed consent for the unpleasant ammonium chloride test only in patients with osteoporosis (in whom the test may have therapeutic implications) and not in patients with normal bone density. It should be considered whether the measurement of urinary citrate could serve as a surrogate for ammonium chloride loading [14]. We also plan to evaluate whether the administration of furosemide could replace the ammonium chloride test [15].…”

Section: Discussionmentioning

confidence: 99%

Incomplete Renal Tubular Acidosis in 'Primary' Osteoporosis

Weger

Deutschmann

Weger

et al. 1999

Osteoporosis International

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Chronic metabolic acidosis may increase alkali mobilization from bone and thus promote the development of osteoporosis. While it is undisputed that overt metabolic acidosis is associated with metabolic bone disease, renal acidification in patients with idiopathic osteoporosis has not been studied systematically. The purpose of this study was to investigate the prevalence of renal acidification defects in patients with 'primary' osteoporosis. Thirty-two women (including 10 premenopausal women) and 16 men who were referred to our department for investigation of osteoporosis were enrolled in this study. Patients with obvious or possible secondary osteoporosis were excluded. None of the patients had overt metabolic acidosis. In random urine samples 12 of the 48 patients had pH levels below 5.5 and were therefore considered to have normal renal acidification. The remaining 36 patients underwent further testing by a short-course oral ammonium chloride load. In this test nine of these 36 patients (7 men and 2 premenopausal women) failed to lower urinary pH below 5.5 despite the induction of systemic metabolic acidosis. In these patients, therefore, the diagnosis of incomplete distal renal tubular acidosis was made (RTA I). Patients with incomplete RTA I had significantly lower spontaneous plasma pH (7.38 +/- 0.0081 vs 7.41 +/- 0.004, mean +/- SEM, p = 0.002), a lower serum bicarbonate concentration (21.9 +/- 0.49 mmol/l vs 23.1 +/- 0.24 mmol/l, p = 0.034), a lower base excess (-2.33 +/- 0.42 mmol/l vs -0.55 +/- 0.21 mmol/l, p = 0.001) and lower Z-scores in bone densitometry (-2.18 +/- 0.27 vs -1.40 +/- 0.15, p = 0.028) than patients with normal renal acidification. In conclusion, a high prevalence of incomplete RTA I (in 44% of the male patients, 20% of the premenopausal female patients and 6% of all female patients) was found in patients with osteoporosis who, without testing, would have been diagnosed as having 'primary' osteoporosis. The mild metabolic acidosis observed in these patients may have contributed to loss of bone mass by a compensatory mobilization of alkali and calcium from bone. Because of possible therapeutic consequences (e.g., administration of alkali salts and high doses of vitamin D) we propose that measurements of urinary pH and, if necessary, ammonium chloride testing should be included in the diagnostic investigation especially of male and of premenopausal female patients with osteoporosis. Since referral bias, although unlikely, cannot be excluded in our study, the prevalence of RTA I in unselected patients with osteoporosis needs to be determined at primary screening institutions.

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“…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 hypercalciuric nephrolithiasis would seem to occur frequently in adults with the incomplete syndrome of RTA (iRTA) (17,18), in which a modest impairment of renal acidification like that of type I RTA does not cause frank metabolic acidosis but can give rise to chronic low-grade metabolic acidosis (19,20). The severity and even the occurrence of that acidosis presumably depend not only on the extent to which renal excretion of acid is impaired but also on the rate at which nonvolatile acid is (or is not) generated from the diet.…”

mentioning

confidence: 99%

“…Metabolic bone disease and hypercalciuric nephrolithiasis would seem to occur frequently in adults with the incomplete syndrome of RTA (iRTA) (17,18), in which a modest impairment of renal acidification like that of type I RTA does not cause frank metabolic acidosis but can give rise to chronic low-grade metabolic acidosis (19,20). The severity and even the occurrence of that acidosis presumably depend not only on the extent to which renal excretion of acid is impaired but also on the rate at which nonvolatile acid is (or is not) generated from the diet.…”

mentioning

confidence: 99%

“…In adult patients with iRTA in whom acidosis was demonstrably absent, Pak et al (21,22) found that alkali therapy with potassium citrate that increased plasma bicarbonate only slightly still corrected hypercalciuria and hypocitraturia, reduced the rate at which kidney stones were formed, increased fractional intestinal calcium absorption, and increased mineral density in the radius. Subsequently, Osther et al (19) reported that biochemical markers of bone formation (serum osteocalcin) and bone resorption (urinary hydroxyproline) were significantly decreased and increased, respectively, in ten kidney stone formers with iRTA but not in 10 without. More recently, Weger et al (20) reported the occurrence of iRTA in 20 or 48 patients referred for evaluation of DXAdocumented osteoporosis, only two of whom had either kidney stones or nephrocalcinosis.…”

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confidence: 99%

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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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Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism

Cited by 38 publications

References 27 publications

Kidney stone disease

Kidney stone disease

Incomplete Renal Tubular Acidosis in 'Primary' Osteoporosis

Alkali Therapy In Renal Tubular Acidosis

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