Glomerular, tubular and interstitial nephritis associated with non-steroidal antiinflammatory drugs. Evidence of a common mechanism

AIMS: To study the mechanisms behind NSAID-associated nephropathy. METHODS: Analysis of published case reports satisfying strict criteria for NSAID nephropathy. RESULTS: Ninety-seven cases with acute nephritis (AN; 19 patients), minimal change nephropathy (MC; 38 patients), membranous glomerulonephritis (MGN; 19 patients), focal sclerosis (FS; 13 patients) and other glomerulonephritis subgroups (8 patients) were identified. Hypersensitivity reactions were seen in all groups, most often in AN. Proteinuria was more severe in MC and FS than in MGN and unrelated to amount of glomerular deposits. The mean NSAID treatment time was 1.7 months in AN, 8.2 months in MC and 39 months in MGN and associated with amount of glomerular deposits, fusion of podocytes and proteinuria, and inversely associated with hypersensitivity, interstitial damage and renal failure. Rheumatic diseases were common in MGN. At follow-up 68 of 72 patients who had discontinued NSAID treatment had improved, 57 with normal renal function. CONCLUSIONS: NSAID nephropathy may be caused by hypersensitivity. The reaction is milder than in drug-induced acute tubulointerstitial nephritis, probably because the offending drug inhibits the inflammatory reaction it has started itself. Heavy proteinuria is probably due to lymphokines produced as a result of the immunological response. If the allergic reaction is strong, AN is produced rapidly with severe renal failure but little proteinuria; if it is less violent, immunocompetent cells may develop to produce lymphokines and proteinuria. Immune complexes may be formed eventually, secondary to the increased glomerular permeability, more easily in patients with a hyperactive immune system and with little consequence for renal function.     

Influence of hydrocarbon exposure on the course of glomerulonephritis

Seventy-one patients with nonsystemic, nonacute glomerulonephritis were included in a follow-up study on the influence of hydrocarbon exposure on the course of their disease. A possible exposure was ruled out by interview performed by occupational hygienists unaware of the outcome of the disease. The patients were allocated to three groups according to their hydrocarbon exposure. One group consisted of patients who had never been exposed; the second of patients who were exposed during follow-up and the third of patients who had discontinued their previous exposure. Each group was subdivided into one group with a glomerular filtration rate (GFR) that remained normal, and one group with a GFR that was, or became, subnormal. Patients with a subnormal GFR who discontinued their exposure had a more favorable course than those who continued to be exposed in spite of an initially lower mean GFR and an initially higher frequency of hypertension. No significant difference was seen between the groups with a normal GFR.     

The fallacies of the lipid hypothesis

Most researchers to-day consider that a high intake of saturated fat and elevated LDL cholesterol are the most important causes of atherosclerosis and coronary heart disease. The lipid hypothesis has dominated cardiovascular research and prevention for almost half a century although the number of contradictory studies may exceed those that are supportive. The harmful influence of a campaign that ignores much of the science extends to medical research, health care, food production and human life. There is an urgent need to draw attention to the most striking contradictions, many of which may be unknown to most doctors and researchers.     

A hypothesis out-of-date. the diet-heart idea

An almost endless number of observations and experiments have effectively falsified the hypothesis that dietary cholesterol and fats, and a high cholesterol level play a role in the causation of atherosclerosis and cardiovascular disease. The hypothesis is maintained because allegedly supportive, but insignificant findings, are inflated, and because most contradictory results are misinterpreted, misquoted or ignored.