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Importance of Mild Hyperoxaluria in the Pathogenesis of Urolithiasis - New Evidence from Studies in the Arabian Peninsula

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Importance of Mild Hyperoxaluria in the Pathogenesis of Urolithiasis - New Evidence from Studies in the Arabian Peninsula Scanning Microscopy Volume 7 Number 1 Article 42 10-23-1992 Importance of Mild Hyperoxaluria in the Pathogenesis of Urolithiasis - New Evidence from Studies in the Arabian Peninsula W. G. Robertson King Faisal Specialist Hospital and Research Centre H. Hughes King Faisal Specialist Hospital and Research Centre Follow this and additional works at: https://digitalcommons.usu.edu/microscopy Part of the Biology Commons Recommended Citation Robertson, W. G. and Hughes, H. (1992) "Importance of Mild Hyperoxaluria in the Pathogenesis of Urolithiasis - New Evidence from Studies in the Arabian Peninsula," Scanning Microscopy: Vol. 7 : No. 1 , Article 42. Available at: https://digitalcommons.usu.edu/microscopy/vol7/iss1/42 This Article is brought to you for free and open access by the Western Dairy Center at DigitalCommons@USU. It has been accepted for inclusion in Scanning Microscopy by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. Scanning Microscopy, Vol. 7, No. 1, 1993 (Pages 391-402) 0891-7035/93$5.00+ .00 Scanning Microscopy International, Chicago (AMF O'Hare), IL 60666 USA IMPORTANCEOF MILDHYPEROXALURIA IN THE PATHOGENESISOF UROLITHIASIS- NEWEVIDENCE FROM STUDIES IN THEARABIAN PENINSULA W.G. Robertson* and H. Hughes King Faisal Specialist Hospital and Research Centre Department of Biological and Medical Research Riyadh 11211, Kingdom of Saudi Arabia (Received for publication May 12, 1992, and in revised form October 23, 1992) Abstract Introduction The hypothesis that mild hyperoxa l uri a is For over half a century, hypercalciuria has more important than hyperca l ci uri a in the been considered by the majority of researchers pathogenesis of urolithiasis is re-examined in in the kidney stone field to be the main risk the light of new evidence. Small increments in factor for primary (idiopathic) and secondary urinary oxalate in the normal to high-normal calcium urol ithiasis (Flocks, 1939; Albright et range are much more critical than similar rises al., 1953; Hodgkinson and Pyrah, 1958; Pak et in urinary calcium for increasing the relative al., 1975; Coe and Favus, 1980; Hal abe and supersaturation of urine with respect to calcium Sutton, 1987). The main evidence cited in oxalate, the oxalate/calcium ratio in urine, the support of this hypothesis is that most we11- total volume of calcium oxalate crystals control led studies which have compared the excreted, the proportion of abnormally large urinary excretions of minerals by stone-formers crystals and aggregates of calcium oxalate and and normals have shown that the patients tend to the severity of the disorder as defined by the excrete more calcium although there is recurrence rate of stone-formation. Data from invariably a large degree of overlap between the the Arabian Peninsula, where the prevalence of two groups. This overlap is so considerable calcium-containing stones is considerably higher that, once allowance is made for the true than in the West, have shown that this occurs in prevalence of urinary stone-formation in the spite of the almost complete absence of population, the urinary calcium excretions of hyperca lei uri a. On the other hand, there is a stone-formers all lie within the projected range strong association between stone-formation and for the normal population, albeit within the the occurrence of mild hyperoxaluria. The life­ upper half of that range (Robertson et al., time expectancy of stone-formation in men from 1978; Bataille et al., 1983; Robertson and various countries is strongly correlated with Peacock, 1985a). There is certainly not the the average daily excretion of oxalate in the clear-cut separation between the urinary calcium urine of the normal men in these countries. excretions of calcium stone-formers and their This relationship extends to include patients controls that exists between the cystine with enteric and hereditary hyperoxaluria. excretions of cystinuric stone-formers and their There is no such relationship, however, between controls (Robertson and Peacock, 1985b). the life-time expectancy of stones and urinary If the hypothesis that hypercalciuria is calcium excretion in the same populations. the main risk factor for calcium stone-formation Studies on the regulation of urinary is correct, then therapeutic measures designed oxalate indicate that it is largely controlled to decrease urinary calcium excretion would be by the quantity of "free" dietary oxalate expected to reduce the rate of recurrence of available for absorption in the lower intestine calcium stone-formation in patients affected This can be calculated from the intakes of with the disorder. Although many of these calcium and oxalate and the urinary excretion of modalities, such as thiazide diuretics (Yendt, calcium. 1970; Coe and Kavalich, 1974), cellulose phosphate (Pak et al., 1974) and a low calcium KEY WORDS: Oxalate, Calcium Urolithiasis, diet (Nordin et al., 1973), have been claimed to Crystallization, Prevalence, Mild Hyperoxaluria, have a benefi ci a 1 effect on stone recurrence, Hyperca lei uri a. more recent reports have cast doubt on their efficacy. Such doubts have arisen (a) because of faults in the design of the studies concerned *Address for correspondence: ( Churchi 11 , 1987), ( b) because the effect of a W.G. Robertson, King Faisal Specialist Hospital particular form of treatment in long-term and Research Centre, Office of Chief Executive studies seems to be minimal (Marickar and Rose, Director, P.O. Box 3354, MBC-31, Riyadh 11211, 1985), or (c) because the treatment concerned Saudi Arabia. Phone No. (966)-1-442-7857 leads to adverse changes in urine biochemistry, 391 W.G. Robertson and H. Hughes such as an increase in urinary oxalate or pH, stone-formers and normals. In this respect mild which may more than offset the beneficial effect hyperoxal uri a does not appear to be different of reducing urinary calcium (Marshall and Barry, from hypercalciuria. More in-depth studies have 1973; Hall son and Rose, 1978; Hall son, 1988). shown, however, that, when stone-formers are There are growing doubts, therefore, about the studied when they first present with stones, importance of hyperca lei uri a ~ as a major their mild hyperoxaluria is much more marked risk factor for calcium stone-formation. This than after they consult their urologist or has led some of the former protagonists of the physician (Robertson and Peacock, 1980). The "hypercalciuria theory" to turn their attention overlap between the oxalate excretions of stone­ to other possible urinary risk factors, such as formers and normals when they first present is hypocitraturia (Pak et al., 1985) and defective much less than it is when they are referred inhibitors of crystallization such as later to the specialist Stone Clinic. This "nephrocalcin" (Coe and Parks, 1990). reduction following hospitalization or out­ One important factor which these and many patient consultation is now a recognised feature other workers continue to overlook, however, is of the so-called "stone clinic effect" (Hoskin the importance of mild hyperoxaluria in calcium et al., 1983; Norman et al., 1984) and should stone-formation. Calcium oxalate, after all, is not be discounted in the assessment of patients consistently the most common constituent of presenting with stones. calcium-containing calculi in stone series It would seem from the above evidence that reported from all parts of the world and mild hypercalciuria and mild hyperoxaluria are both hyperoxa1 uri a should deserve at 1east as much commonfindings among stone-forming populations, attention as hyperca 1c i uri a as a factor in the so why then has doubt been cast on the formation of such calculi. importance of hypercalciuria in the pathogenesis The main problem for most potential of stones and what new evidence is there to researchers in this area has been the difficulty support the hypothesis that mi1 d hyperoxal uri a in measuring oxalate reliably in biological is a much more significant risk factor than fluids. Unlike the situation with respect to hypercalciuria for stone-formation? the measurement of urinary calcium, the accurate determination of oxalate in urine has only Relative Importance of Hypercalciuria and Mild become possible in recent years with the Hyperoxaluria for Urolithiasis application of the modern techniques of high performance liquid chromatography (HPLC)(Hughes The relative effects of hypercalciuria and et al., 1982), ion-chromatography (Menon and mild hyperoxaluria on the risk of calcium Mahle, 1983; Robertson et al., 1982, Robertson oxalate stone-formation were first investigated and Scurr, 1984) and gas chromatography by Robertson and his co 11eagues ( Robertson and (Yanagawa et al., 1983). In general, however, Nordin, 1969; Robertson et al., 1971; Robertson urinary oxalate (where measured at all) is still and Peacock, 1980). Their initial findings in assayed badly (Samuell, 1988), particularly when this respect have since been largely confirmed using techniques other than those described by others (Bataille et al., 1983; Hallson, 1988; above. The reasons for the unre l i abi 1 ity of Lindsjo, 1989). The hypothesis that mild most methods are multifactorial but are most hyperoxaluria is much more critical than frequently due to inadequate handling and work­ hypercalciuria in the pathogenesis of calcium up of urine prior to the actua 1 measurement, oxalate stone-formation was developed based on particularly in the case of urines which contain findings obtained from both
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