The inflammatory response and tissue damage

Abstract

Most clinical and experimental evidence suggests that renal scarring occurs following urinary tract infections in those patients with an abnormality of the urinary tract or kidney function. Experimentally, bacterial multiplication within the kidney occurs only in the presence of obstruction, leading rapidly to acute exudative pyelonephritis and invariably to kidney scars within weeks. Various manipulations of the bacterial load and/or of the inflammatory response during acute pyelonephritis have demonstrated that the inflammatory processes, not the bacterial component of pyelonephritis, are responsible for permanent renal tissue damage. Polymorphonuclear leucocytes (PMNLs) infiltrating the kidney tissue during acute pyelonephritis appear to release metabolites that are toxic to the parenchyma. Indeed, both the prevention of PMNL influx into renal tissue, by means of colchicine or cyclophosphamide, and the inactivation of some of their toxic metabolites, by means of dapsone, have led to the prevention of tissue damage and kidney scars. However, the most potent protective activity was observed with early antibiotic treatment, which stopped bacterial multiplication and prevented the early influx of PMNLs, thus preventing tissue damage and scar formation. Similar observations have been made in children with acute pyelonephritic episodes, in whom early and aggressive antibiotic treatment prevented subsequent kidney scars, while delayed treatment did not.

Evaluation of acute pyelonephritis with DMSA scans in children presenting after the age of 5 years

“…Experimental investigations have shown that inflammation has an important role in the pathogenesis of renal damage in pyelonephritis, which involves the local infiltration of polymorphonuclear leukocyte and the extracellular release of cytotoxic metabolites [24,25,26]. DMSA scintigraphy is currently considered the imaging agent of choice for estimating the presence and extension of acute parenchymal changes as well as the development of permanent renal scarring.…”

Regeneration Processes in the Kidney after Acute Injury: Role of Infiltrating Cells

“…In contrast to other models of ARF, including I/R injury, where only scarce numbers of polymorphonuclear cells are observed, ARF resulting from bacterial infection (pyelonephritis) appears to be the only condition in which these cells accumulate in large numbers [18]. Nevertheless, numerous researchers ascribed (and still do) a key role to PMN, particularly neutrophils, in I/R injury in the kidney as well as in other organs (heart, lung, liver, etc.).…”

Blockade of Rennin-Angiotensin system blunts the fibrotic response in experimental acute pyelonephritis

“…It is accepted universally that antibiotic treatment after 72 hours does not prevent significant renal scarring. [1][2][3][4] This protocol closely imitates the clinical situation in pediatric UTI as most of the time diagnosis is made late.…”

“…It has been shown that late institution (> 72 hours) of antibiotic therapy may not prevent the scar formation effectively as the inflammatory response has already set in. [1][2][3][4] It is in this scenario that the role of adjunctive drugs to reduce the severity of scarring has been a topic of intense research. Experimental studies have examined the effect of addition of allopurinol, [2] corticosteroids, [3,5] anti-oxidants, [6] vitamins, [7,8] anti-inflammatory drugs, [9] angiotensin receptor blocker [10] and pentoxiphylline [4] to the antibiotic regimen with some success.…”