Interstitial nephritis mechanisms

Adverse reactions may include the following Fever porphyria dysuria gout hepatic reaction nausea vomiting anorexia thrombocytopenia and sideroblastic anemia with erythroid hyperplasia vacuolation of erythrocytes increased serum iron concentration adverse effects on blood clotting mechanisms mild arthralgia and myalgia hypersensitivity reactions including rashes, urticaria, pruritus fever acne photosensitivity porphyria dysuria interstitial nephritis. 

The authors postulated that iodide toxicity had resulted in hemolysis and hemoglobinuria, which, together with acute interstitial nephritis secondary to inhibition of prostaglandin synthesis from mefenamic acid ingestion, had resulted in acute renal insufficiency. The mechanism of hemolysis resulting from toxic doses of iodine is not clear, although it may reflect inhibition of various red cell enzymes. 

The underlying mechanism of a series of clinical entities associated with beta-lactams, such as maculopapular rash, drug fever, eosinophilia, serum sickness-like disease, vesicular and bullous skin reactions, erythema nodosum, and acute interstitial nephritis, is suspected to be immunological but is still largely unknown. 

Impairment of renal function and even acute renal insufficiency can follow sulfinpyrazone treatment, by various mechanisms immunoallergic-induced acute interstitial nephritis, inhibition of renal prostaglandins, and precipitation of uric acid stones. These changes are probably reversible, since there have been cases in which renal impairment spontaneously normalized on withdrawal (5). 

Ravnskov U Glomerular, tubular and interstitial nephritis associated with non- steroidal anti-inflammatory drugs. Evidence of a common mechanism. Br Clin Pharmacol 1999 47 203-10. 

In this chapter we first will discuss the undesirable aspects of these effects of ACEI and will show how most of these effects may be prevented by cautious use of the agents. Since the mechanisms of the ACEI-induced membranous glomerulopathy and interstitial nephritis are different from those causing the fall in GFR, we will discuss each separately. 

Mechanisms of drug-induced kidney disease include immune-mediated toxicities (e.g., glomerulonephritis and allergic interstitial nephritis) and nonimmunologic-mediated toxicities which effect specialized characteristics of normal renal physiology. 

At least one case of acute interstitial nephritis has been attributed to amphetamine use [163]. This amphetamine abuser presented with acute nonoliguiic renal failure, large kidneys by ultrasonography, and microhematuria. The biopsy revealed interstitial edema and focal infiltrates of mononuclear cells and eosinophils with only patchy tubular degeneration. There was no evidence for rhabdomyolysis and the urine was negative for myoglobin. Although he required temporary hemodialytic support, renal function returned to normal after treatment with intravenous corticosteroids. The mechanism of this reaction remains unclear and its true relation to amphetamine abuse remains unproven. 

The mechanism differs from that underlying the sulfamethoxazole/trimethoprim interaction. Sulphonamides such as co-trimoxazole and sulfadiazine are known to cause renal dysfunction - interstitial nephritis and renal failure, which may -L excretion of methotrexate. Sulphonamides are also known to compete with methotrexate for renal elimination. Displacement from protein-binding sites of methotrexate is a minor contribution to the interaction... 

Patients with chronic parenchymal renal disease show a fall in RBF and GFR during treatment with NSAID, including aspirin . In chronic glomerulonephritis, afferent arteriolar dilatation may be a compensatory mechanism in the maintenance of filtration. A study of patients with systemic lupus erythematosus revealed an abnormal increase in basal PGE2 excretion consistent with the postulated means of compensation. In other aetiologies of renal insufficiency, including diabetes, hypertension and interstitial nephritis, there is acute worsening of renal function with NSAID " ... 

---