Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis

Abstract

We studied the possibility that tubule fluid iron could be involved in the pathogenesis of the tubulo-interstitial injury associated with primary glomerular disease. Tubule fluid iron is determined by the magnitude of the glomerular leak for transferrin and the iron saturation of transferrin. To minimize tubule fluid iron in an experimental model of glomerulonephritis, iron deficiency was induced in rats prior to the induction of nephrotoxic serum nephritis. Iron deficiency did not effect the development of glomerular disease as determined by proteinuria, but had a marked effect on preventing the development of tubulo-interstitial disease and renal functional deterioration. There was also a strong correlation between the amount of functional deterioration and extent of tubulo-interstitial disease and urinary iron excretion in both the control and iron deficient animals. It is proposed that injury results from iron being dissociated from transferrin at the more acid pH of the tubule fluid. Iron, a transition element, is able to catalyze the Haber-Weiss reaction with the formation of free hydroxyl radicals which causes renal tubule cell injury. This tubulo-interstitial injury is the major determinate of progressive renal functional deterioration in this experimental model of glomerulonephritis.

A Low-Iron-Available, Polyphenol-Enriched, Carbohydrate-Restricted Diet to Slow Progression of Diabetic Nephropathy

“…The aim of the current study was to identify a dietary pattern capable of slowing the progression of diabetic nephropathy more effectively than a low-protein diet. Because CHO restriction, polyphenol intake, and iron lowering delayed ESRD in animal models of chronic renal failure (10,11,20,23,24), all were combined and simultaneously implemented in a cohort of patients affected by diabetic nephropathy. When compared with standard protein restriction, ad-libitum intake of CR-LIPE significantly reduced all-cause mortality and rate of renal function loss and delayed ESRD and RRT.…”

“…Third, iron was an important factor in the progression of experimental nephropathy after the initial offending agent was removed (21). Iron promoted acute tissue damage during ischemia reperfusion (22) and chronic interstitial inflammation and fibrosis in animal models of renal failure associated with chronic proteinuria (23,24). Conversely, iron deficiency or chelation with deferoxamine prevented renal histological and functional deterioration (23,24).…”

“…Iron promoted acute tissue damage during ischemia reperfusion (22) and chronic interstitial inflammation and fibrosis in animal models of renal failure associated with chronic proteinuria (23,24). Conversely, iron deficiency or chelation with deferoxamine prevented renal histological and functional deterioration (23,24). Reduction of body iron can be induced by use of a low-iron available diet, i.e., a diet where iron absorption inhibitors (dairies, phytates, and polyphenols) prevail on enhancers (red meat, ascorbate, and citrate) (25).…”

Uric Acid as a Potential Cue to Screen for Iron Overload

“…14,25 Although there is significantly less information about iron overload and renal function, there is some evidence that excessive iron may be nephrotoxic. 26,27 The urinary albumin-to-creatinine ratio was used to classify persons as normal (Ͻ30 mg/g) or as having proteinuria (Ն30 mg/g).…”

Abnormal Iron Deposition in Renal Cells in the Rat with Chronic Angiotensin II Administration

“…Although the underlying mechanism of iron overload-associated renal injury has not been fully elucidated, iron accumulation is postulated to induce renal injury, at least in part, by increasing the production of reactive oxygen species (Zainal et al, 1999;Zhou et al, 2000). Accumulation of iron has also been suggested to play a role in the renal injury in rhabdomyolysis (Nath et al, 1992), ischemic renal disease (Paller and Hedlund, 1988), and glomerulonephritis (Alfrey et al, 1989).…”