The nephropathy of cystic fibrosis: a human model of chronic nephrotoxicity.
Patients with cystic fibrosis are chronically exposed to several potentially nephrotoxic factors. These include bacterial infections with their associated immune complexes and the antibiotics (aminoglycosides) used in their treatment. In addition, diabetes mellitus, liver disease, and cor pulmonale, commonly seen in these patients, may produce renal injury. To assess the extent of this injury, we performed morphologic and immunopathologic studies of the kidneys of 34 patients at autopsy. The group included 23 female and 11 male patients; their ages ranged from 4 months to 35 years and their disease was diagnosed one month to 22 years prior to death. The histological changes included glomerulomegaly, a mesangiopathic lesion, and tubulointerstitial disease frequently associated with acute and chronic tubular injury. The last was characterized by abundant tubular lysosomal proliferation and tubular atrophy suggestive of chronic amino-glycoside injury. Diagnostic diabetic lesions were not seen. Immunofluorescence studies predominantly revealed deposits of IgM or C3, or both, in glomeruli and arterioles in 18 patients. Although an anti-Pseudomonas antiserum did not show bacterial antigens in the tissues, elution studies in two specimens demonstrated antibacterial antibodies. These observations, coupled with the finding of ultrastructural glomerular deposits, suggest immune complex-mediated injury. No correlation was found between the severity or type of renal histologic lesion and patient age or duration of cystic fibrosis. Despite the occurrence of renal failure in six patients, renal involvement is currently of limited clinical concern in cystic fibrosis. Nevertheless, continued exposure to bacterial immune complexes and aminoglycosides, among other factors, can result in potentially serious renal disease.
D000293:Adolescent; D000328:Adult; D000936:Antigen-Antibody Complex / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003176:Complement C3 / Q000032:analysis; D003550:Cystic Fibrosis / Q000473:pathology*; D048909:Diabetes Complications; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D007223:Infant; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male
D000936:Antigen-Antibody Complex; D003176:Complement C3; D007075:Immunoglobulin M