Renal tubular dysfunction in schizophrenic patients treated with antipsychotic drugs.
Several factors have been considered in relation to the free radical formation in schizophrenia, such as the disease itself, drug treatment and smoking. Several chemicals and drugs may cause damage to the renal tubules by different subcellular mechanisms including oxidative stress, and the aim of our study was the investigation of tubular dysfunction in schizophrenic patients. The urinary excretion of beta-N-acetylhexosaminidase (Hex) and its isoenzymes Hex A and Hex B, alpha1-microglobulin, albumin, total proteins and fractionated porphyrins were determined in 45 schizophrenic patients treated with first- and second-generation antipsychotics. In 7 patients, an increase in proteinuria of tubular origin was found, and in one as a result of mixed glomerular/tubular origin. The group of patients had a significantly higher level of excretion than the control group (n = 54) of total Hex (p < 0.001), Hex A (p < 0.05), Hex B (p < 0.001) and the relative proportion of this isoenzyme (p < 0.001). In some cases with normal levels of total Hex and urinary alpha1-microglobulin, the proportion of Hex B was already increased. Significant correlations were found for total Hex and its isoenzymes with alpha1-microglobulin (p < 0.001). Also, the porphyrins had significant correlations with total Hex (p < 0.001), Hex A (p < 0.05), Hex B (p < 0.005) and alpha1-microglobulin (p < 0.001). In the group of patients studied, it was possible to reveal early tubular cell damage (affected structural integrity) with increased excretion of Hex B, possibly mediated by free radicals, previous to the decrease in tubular reabsorption of proteins with low molecular mass filtered by the glomerulus (affected functional integrity).
Tutor-Crespo
Maria J
MJ
Unidad Monitorización Fármacos, Laboratorio Central, Hospital Clinico Universitario, Santiago de Compostela, Spain.
Paz
Eduardo
E
Hermida
Jesús
J
Tutor
J Carlos
JC
D000328:Adult; D000368:Aged; D000510:Alpha-Globulins / Q000652:urine*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D005198:Fanconi Syndrome / Q000150:complications*; D005260:Female; D054818:Hexosaminidase A; D054819:Hexosaminidase B; D006801:Humans; D007527:Isoenzymes / Q000652:urine; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011166:Porphyrins / Q000652:urine*; D011507:Proteinuria / Q000175:diagnosis / Q000209:etiology / Q000652:urine; D012016:Reference Values; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy; D001619:beta-N-Acetylhexosaminidases / Q000652:urine*