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Over the past 20 years, there has been an increase in chronic interstitial nephritis in agricultural communities (CINAC) not associated with traditional risk factors. This disease has become an important public health problem and is observed in several countries in Central America and Asia. CINAC predominantly affects young male farmers between the third and fifth decades of life with women, children, and adolescents less often affected. Clinically, CINAC behaves like a chronic tubulointerstitial nephropathy but with systemic manifestations not attributable to kidney disease. Kidney biopsy reveals chronic tubulointerstitial nephritis with variable glomerulosclerosis and mild chronic vascular damage, with the severity depending on sex, occupation, and CKD stage. The presence of toxicological, occupational, and environmental risk factors within these communities suggests a multifactorial etiology for CINAC. This may include exposure to agrochemicals, a contaminated environment, repeated episodes of dehydration with heat stress, and an underlying genetic predisposition. An understanding of these interacting factors using a multidisciplinary approach with international cooperation and the formulation of a comprehensive hypothesis are essential for the development of public health programs to prevent this devastating epidemic.

To study the effects of relatively long-term interaction of antibodies with surface antigens of lung endothelium, rabbits were intravenously injected for a maximum of 4 d with goat anti-rabbit lung angiotensin-converting enzyme (Gt anti-RbACE) antibodies. On day 1 69%, on day 2 13%, and on days 3 and 4 of injection none of the rabbits developed lethal pulmonary edema. By immunofluorescence microscopy, deposits of GtIgG, frequently in association with RbC3, were found along the endothelium of alveolar capillary walls in all rabbits studied on day 1, in 57% on day 2, in 33% on day 3, and in none of them on day 4. While in vitro anti-ACE antibodies bound in a linear pattern to the lung endothelium, the binding pattern in vivo was distinctly granular. The in vivo interaction of antibodies with ACE also redistributed ACE in a granular pattern along capillary walls. In contrast to the granular deposition of injected anti-ACE IgG and F(ab')2 fragments of anti-ACE IgG, Fab fragments of anti-ACE IgG localized, without fixing C3, in a linear pattern along the endothelium of lung capillaries and did not modify the normal distribution of ACE. However, when the injection of Fab fragments of Gt anti-RbACE IgG was followed by an injection of Rb anti-GtIgG serum, granular deposits of Gt Fab fragments, RbIgG and RbC3 were seen along alveolar capillary walls. Biochemical measurement of ACE activity in lung homogenates provided data in agreement with those obtained by immunofluorescence microscopy, showing diminished activity to none on day 4, with some return of ACE activity on day 5, 24 h after the last injection of antibody, and normal values on day 21. The results obtained indicate that divalent antibodies to an antigen expressed on the plasma membrane of rabbit lung endothelial cells promotes a rapid redistribution of antigenic receptors, fixation of complement and, in surviving rabbits, disappearance of the antigen from the endothelial cells that are no longer susceptible to immune injury. In vivo "immunologic enzymectomy" induced by a ligand-surface antigen interaction is an example of antigenic modulation. These events may have an important role in the pathogenesis of inflammatory lesions induced by antibodies reacting with antigens expressed on the plasma membrane of cells in the lung and in other organs.

Nephropathies found in systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, and mixed connective tissue disease are discussed. Pathogenetic insights derived from the study of kidney tissue are highlighted and clinicopathologic correlations indicated. The question of whether to perform kidney biopsy in lupus patients is also addressed.