Aminoglycoside-Associated Fanconi’s Syndrome: An Underrecognized Entity

Abstract

The Fanconi syndrome is an array of multiple proximal renal tubular dysfunctions occurring in association with several exogenous toxins, such as aminoglycosides. These antibiotics remain the drugs of choice in most gram-negative infections, but nephrotoxicity is the main drawback for them. Furthermore, the nephrotoxic effects may be overlooked with routine analyses. With the purpose of making physicians aware of this underrecognized complication, we are reporting here 3 cases of Fanconi’s syndrome related to the administration of high-dose aminoglycosides (ranging from 3.6 to 15 g) with normal serum urea nitrogen and creatinine levels. The pattern of aminoaciduria demonstrated high increases in neutral amino acids, followed by dibasic and near-normal acidic amino acids. We also report the urinary excretion rates of total protein and β₂-microglobulin and protein electrophoresis results. We compared these cases with others reported in the literature.

Renal function and effect of aminoglycoside therapy during the first ten days of life

“…In preterm infants, gentamicin administration appears to result in an increase in magnesium loss. Several tubular disorders with hypomagnesemia and other electrolyte disturbances have been reported in children and adults after long-term gentamicin administration [30,31,32]. Studies in rats have shown that gentamicin administration causes dose-related Mg and Ca renal wasting, days before any evidence of renal injury [33].…”

Aminoglycoside-Induced Reversible Tubular Dysfunction

“…In fact, the patient presented with renal glucosuria, phosphaturia, uricosuria, and metabolic hyperchloremic acidosis, features of a proximal tubular dysfunction. Even though the Fanconi syndrome has been associated with the administration of a number of antibiotics, an aminoglycoside-induced Fanconi syndrome is rare [2,[5][6][7][8]. Advanced age and longterm drug administration may predispose to the renal tubular damages observed [3,9,10,13,15].…”

“…The extent of the tubular dysfunction ranges from clinically undetectable enzymuria to substantial wasting of electrolytes and minerals [3]. Two types of renal tubular damage have been reported: a Fanconi-like syndrome of a rather generalized proximal tubular damage and a syndrome of hypokalemic metabolic alkalosis associated with hypomagnesemia [4][5][6][7][8][9][10][11][12][13][14][15][16]. We report 2 representative cases of a reversible tubular damage related to chronic aminoglycoside administration.…”

Decreased Expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy

“…However, gentamicin may cause a dose-dependent nephrotoxicity (Bennett, 1997). Previous studies have shown that gentamicin is mainly concentrated in the proximal tubular cells, and the resultant renal dysfunction may be recognized as Fanconi-like syndrome of a proximal tubular damage (Pastoriza-Munoz et al, 1979;Gainza et al, 1997).…”