Renal Fanconi Syndrome


Renal Fanconi syndrome is a tubular dysfunction increasing the urinary excretion of glucose, amino acids, phosphate and bicarbonate and inducing rickets in children and osteomalacia in adults.

Keywords: aminoaciduria; cadmium; cystinosis; glucosuria; maleate; megalin; phosphaturia; renal tubular acidosis; rickets; osteomalacia

Figure 1.

Schematic view of the cells of kidney tubules. The tubules form the renal functional unit, known as the nephron. Immediately after being filtered through the glomerulus, molecules (e.g. amino acids, glucose, sodium) and water are reabsorbed by the early part of the tubule, defined as the proximal nephron. The last part of the nephron is known as the distal and is comprised of tubular cells with different properties. In normal individuals, amino acids gain access to the proximal nephron cells (wide blue arrow) through the apical microvilli or through the infoldings of the antiluminal membrane. Intracellular accumulation of amino acids (∗) can occur against a concentration gradient. At the luminal border, uptake is a carrier‐mediated process and, when coupled to a sodium gradient (Na+ out > Na+ in), is ‘secondary active’ transport. Exit can occur at all membranes. Amino acids (AA) can also be metabolized (metab) in the renal tubular cells. In the distal nephron (thin blue arrows), similar amino acid movements occur except that there is no luminal entry of amino acids and little, if any, luminal entry of glucose and phosphate. (b) In the maleate model of Fanconi syndrome, there is a marked backleak of amino acids and sugar into the tubular lumen. As a consequence, intracellular amino acid levels fall significantly (pool). In proximal tubular cells, luminal amino acid uptake mechanisms are also disturbed, but residual luminal uptake still exceed backleak, allowing at least some net amino acid reabsorption. However, in the distal tubule where luminal uptake systems are absent, maleate‐induced exit of amino acids into the lumen is completely uncompensated, allowing net amino acid ‘secretion’ into the urine. Other forms of renal Fanconi syndrome have been ascribed to numerous complex mechanisms which might disturb luminal membrane function. These include: (1) a defect in some aspect of transport critical to all luminal carrier mechanisms (of note, most solutes lost in urine are coupled to luminal reabsorption of sodium); (2) a disturbance of luminal membrane organization affecting both uptake and backleak of solutes as in the maleate model above; (3) impaired production of metabolic energy or adenosine triphosphate (ATP) as in the example of human cytochrome c oxidase deficiency; (4) defective Na+–K+ ATPase activity at basolateral membranes, affecting the sodium gradient at the luminal membrane; (5) reduced H+ ATPase activity affecting the endocytotic recycling apparatus; (6) structural disorganization and dysfunction of organelles such as the endoplasmic reticulum or mitochondria; (7) defective megalin‐dependent recycling of transport proteins and transporters from endocytotic compartments to the luminal membrane. An integrative hypothesis that might link many forms of Fanconi syndrome is that they have in common a toxic effect or a primary cellular dysfunction that disrupts some critical element of endocytotic membrane recycling. Blockade at any point along the recycling pathway will modify luminal membrane function by trapping membrane transport proteins and other constituents in endosomes; depletion of these elements from the luminal membrane may limit reabsorptive transport and allow increased backleak of organic solutes.



Angielski S and Rogulski J (1962) Effect of maleic acid on the kidney. I. Oxidation of Krebs cycle intermediates by various tissues of maleate intoxicated rats. Acta Biochimica Polonica 9: 357–364.

Bergeron M and Laporte P (1973) Effet membranaire du maléate au niveau du néphron proximal et distal. Revue Canadienne de Biologie. 32: 275–279.

Bergeron M, Dubord L and Hausser C (1976) Membrane permeability as a cause of transport defects in experimental Fanconi syndrome: a new hypothesis. Journal of Clinical Investigation 57: 1181–1189.

Bergeron M, Gougoux A and Vinay P (1995) The renal Fanconi syndrome. In: Scriver CR, Beaudet AL, Sly WS and Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, 7th ed. pp. 3691–3704. New York: McGraw‐Hill

Bergeron M, Mayers P and Brown D (1996) Specific effect of maleate on an apical membrane glycoprotein (gp330) in proximal tubule of rat kidneys. American Journal of Physiology 271: F908–F916.

Berliner RW, Kennedy TJ and Hilton JG (1950) Effect of maleic acid on renal function. Proceedings of the Society for Experimental Biology and Medicine 75: 791–794.

Chesney RW, Kaplan BS, Colle E et al. (1980) Abnormalities of carbohydrate metabolism in idiopathic Fanconi syndrome. Pediatric Research 14: 209–215.

Coor C, Salmon RF, Quigley R et al. (1991) Role of adenosine triphosphate (ATP) and Na,K ATPase in the inhibition of proximal tubule transport with intracellular cystine loading. Journal of Clinical Investigation 87: 955–961.

Easley JR and Breitschwerdt EB (1976) Glycosuria associated with renal tubular dysfunction in three Basenji dogs. Journal of the American Veterinary Medical Association 168: 938–943.

Fanconi G (1936) Der nephrotisch‐glykosurische Zwergwuchs mit hypophosphatämischer Rachitis. Deutsche Medizinische Wochenschrift 62: 1169–1171.

Foreman JW, Roth KS (1989) Human renal Fanconi syndrome – then and now. Nephron 51: 301–306.

Frymoyer PA, Scheinman SJ, Dunham PB et al. (1991) X‐linked recessive nephrolithiasis with renal failure. New England Journal of Medicine 325: 681–686.

Gonick HC and Kramer HJ (1985) Pathogenesis of the Fanconi syndrome. In: Gonick HC and Buckalew VM Jr (eds): Renal Tubular Disorders. Pathophysiology, Diagnosis and Management, pp. 545–607. New York: Marcel Dekker

Gougoux A, Lemieux G and Lavoie N (1976) Maleate‐induced bicarbonaturia in the dog: a carbonic anhydrase‐independent effect. American Journal of Physiology 231: 1010–1017.

Gougoux A, Vinay P and Duplain M (1985) Maleate‐induced stimulation of glutamine metabolism in the intact dog kidney. American Journal of Physiology 248: F585–593.

Gougoux A, Zan N, Dansereau D and Vinay P (1989) Experimental Fanconi's syndrome resulting from 4‐pentenoate infusion in the dog. American Journal of Physiology 257: F959–966.

Gougoux A, Zan N, Dansereau D and Vinay P (1992) Metabolic effects of 4‐pentenoate on isolated dog kidney tubules. Kidney International 42: 586–594.

Harrison HE and Harrison HC (1954) Experimental production of renal glycosuria, phosphaturia, and aminoaciduria by infection of maleic acid. Science 120: 606–608.

Lowe CU, Terrey M and MacLachlan AE (1952) Organic‐aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation. American Journal of Diseases of Children 83: 164–184.

Morris RC Jr (1968) An experimental renal acidification defect in patients with hereditary fructose intolerance. II. Its distinction from classic renal tubular acidosis; its resemblance to the renal acidification defect associated with the Fanconi syndrome of children with cystinosis. Journal of Clinical Investigation 47: 1648–1663.

Nissim I, Weinberg JM (1996) Glycine attenuates Fanconi syndrome induced by maleate or ifosfamide in rats. Kidney International 49: 684–695.

Obaid AL, Rega AF and Garrahan PJ (1972) The effects of maleic anhydride on the ionic permeability of red cells. Journal of Membrane Biology 9: 385–401.

Rosen VJ, Kramer HJ and Gonick HC (1973) Experimental Fanconi syndrome. II. Effect of maleic acid on renal tubular ultrastructure. Laboratory Investigation 28: 446–455.

Rosenberg LE and Segal S (1964) Maleic acid‐induced inhibition of amino acid transport in rat kidney. Biochemical Journal 92: 345–352.

Szczepanska M and Angielski S (1980) Prevention of maleate‐induced tubular dysfunction by acetoacetate. American Journal of Physiology 239: F50–F56.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Bergeron, Michel, and Gougoux, André(Apr 2001) Renal Fanconi Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0002284]