SP771HISTORY OF RENAL AND OCULAR FINDINGS IN PRIMARY HYPEROXALURIA: FROM OXALIS ACETOSELLA TO THE MULBERRY CALCULUS, CKD, RETINOPATHY AND SYSTEMIC OXALOSIS

Abstract

INTRODUCTION AND AIMS: Primary hyperoxaluria (PRIOX) is a rare hereditary disease of glyoxylate metabolism with excessive calcium oxalate in urines. The term 'oxalosis' is referred to the deposition of oxalate in various organs. Its history includes the discovery of oxalic acid, its presence in renal stones, the emergence of primary oxaluria. The term Oxys in Classical Greek means acid and is used to name the plant Oxalis Acetosella (the wood sorrel), whose leaves have an acidic taste. In 1745, the Dutch Herman Boerhaave (1668-1738) isolated from that plant a salt, afterward called oxalic acid. Carl Scheele (1742-1785) synthesized in 1784 oxalic acid from the sugar of rhubarb. Oxalic acid played an important role in the development of chemical theories by Thomas Thomson in 1808. METHOD(S): In that period the work of Scheele and Antoine Francois de Fourcroy (1668-1738) led to the interest for the chemical composition of kidney stones. Therefore, in 1797, Willian H. Wollaston (1766-1829) found the 'oxalate of lime' in a urinary stone which he named 'mulberry calculus'. Alfred Donne (1801-1878) in 1838 first identified oxalate crystals in the urine. Golding Bird (1814-1854), a UK Physician, in 1842 described the excess of oxalate of lime in urine, now called Bird's disease. William Prout, in 1840, Begbie J in 1848 and the Neapolitan Cantani in 1856 coined the term "oxalic diathesis". In 1925 Carlos Lepoutre (1882-1950), professor of Surgery at the University of Lille, described multiple calculi in a newborn, with kidney infiltration by crystal deposits (J Urol 1925;20:424), which is recognized as the first report of primary hyperoxaluria.MLoeper in 1931 further investigated the metabolic origins of oxalemia, although the existence of the syndrome (oxalic diathesis) was challenged by Smoler in 1861 and other authors, who found oxalate crystals in the urine of normal subjects. The heredity in primary hyperoxaluria was first disclosed by HC Gram (Acta Med Scand 1932; 78:36) and confirmed later in 1957 by Archer et al (Lancet). 1986 Welt describes a second form of primary hyperoxaluria, much rarer. The familial form is thus divided into two types. In 1987 Wise et al described an idiopathic enteric form. RESULT(S): "The earliest symptoms are urolithiasis and nephrocalcinosis which lead to progressive renal involvement and chronic kidney disease. Renal damage is ultimately caused by a combination of tubular toxicity form oxalate, nephrocalcinosis and renal obstruction by stones often with superimposed infection" (Cochat/Rumsby N Engl J Med 2013). CONCLUSION(S): Retinal lesions in PRIOX were summarized in 1993 by Capone and Meredith in Diseases affecting the eye and the kidney. It emerged a continuum of lesions consisting of bilateral symmetrical yellow and yellow-white crystals within the inner retina throughout the posterior pole.When GFR drops to 45-30ml/min plasma oxalate levels arise and systemic oxalosis ensues and affects, in addition to retina, the joints, bones, heart, muscles, nerves and central nervous system.Therapy adopts hydration, potassium citrate, vitamin B12 and dialysis (which is not enough to remove the generated oxalate). The golden standard remains the combined liver-kidney transplantation. The history of PRIOX will be illustrated utilizing 15 patients of three family aggregates described by the Danish HC Gram, who described them in 1932 in Acta Medica Scandinavica.