Dilationorcontractionoftubules,withatrophyoftheepitheliallining.Manyofthedilatedtubulescontainpinktoblue,glassy-appearingPAS-positivecasts,knownascolloid casts, thatsuggesttheappearanceofthyroidtissue—hencethedescriptivetermthyroidization.Often,neutrophilsareseenwithinthetubules
Many patients with chronic pyelonephritis come to medical attention relatively late in the course of the disease, because of the gradual onset of renal insufficiency or because signs of kidney disease are noticed on routine laboratory tests. In other cases, the renal disease is heralded by the development of hypertension. The radiologic image is characteristic: affected kidneys are asymmetrically contracted, with some degree of blunting and deformity of the calyceal system (caliectasis). The presence or absence of significant bacteriuria is not particularly helpful, as its absence does not rule out chronic pyelonephritis. If the disease is bilateral and progressive, tubular dysfunction leads to an inability to concentrate the urine (hyposthenuria), manifested by polyuria and nocturia.
Fig. 14.14 Typicalcoarsescarsofchronicpyelonephritisassociatedwithvesicoureteralreflux.Thescarsareusuallylocatedattheupperorlowerpolesofthekidneyandareassociatedwithunderlyingbluntedcalyces.
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As noted earlier, some individuals with chronic pyelonephritis or reflux nephropathy ultimately develop secondary glomerulosclerosis, associated with proteinuria; eventually, these injuries all contribute to progressive chronic kidney disease.
Acute drug-induced TIN occurs as an adverse reaction to any one of an increasing number of drugs. It is associated most frequently with penicillins (methicillin, ampicillin), other antibiotics (rifampin), diuretics (furosemide), proton pump inhibitors (omeprazole), nonsteroidal anti-inflammatory agents, and numerous other drugs (phenindione, cimetidine, immune checkpoint inhibitors).
Many features of the disease suggest an immune mechanism. Clinical features consistent with a hypersensitivity reaction include latent period between drug exposure and development of lesions, eosinophilia and rash, the idiosyncratic nature of the drug reaction (i.e., the lack of dose dependence), and the recurrence of the reaction following reexposure to the same drug or others of similar structure. Serum IgE levels are increased in some individuals, suggesting immediate (type I) hypersensitivity. In other cases, the nature of the inflammatory infiltrate and the presence of positive skin tests to drugs suggest a T cell–mediated (type IV) hypersensitivity reaction.
The most likely sequence of pathogenic events is that the drugs act as haptens that, during secretion by tubules, covalently bind to some cytoplasmic or extracellular component of tubular cells and become immunogenic. The resultant tubulointerstitial injury is then caused by IgEor T cell–mediated immune reactions to tubular cells or their basement membranes.
MORPHOLOGYTheabnormalitiesinacutedrug-inducednephritisareintheinterstitium,whichshowspronouncededemaandinfiltrationbymononuclearcells,principallylymphocytesandmacrophages(
Fig.14.15 ).Eosinophilsandneutrophilsmaybepresent,ofteninlargenumbers.Withsomedrugs(e.g.,methicillin,thiazides,rifampin),Tcellmediatedreactionmaygiverisetointerstitialnonnecrotizinggranulomaswithgiantcells.Theglomeruliarenormalexceptinsomecasescausedbynonsteroidalanti-inflammatoryagents,inwhichthehypersensitivityreactionalsoleadstopodocytefootprocesseffacementandthenephroticsyndrome.