Sulphasalazine induced renal failure.

Abstract

Two men with longstanding ulcerative colitis who were treated with sulphasalazine for several years and who developed chronic renal failure are reported. Renal biopsy specimens showed histological changes consistent with drug induced chronic intestinal nephritis. Extensive investigation made other causes of chronic renal failure unlikely. One of these patients underwent renal transplantation, the other has impaired but stable renal function.Case 1 A 53 year old man with total ulcerative colitis had been maintained on sulphasalazine 1 g twice a day, and was well apart from several exacerbations that required treatment with short courses of oral corticosteroids. He was not taking any other regular medication. Twenty years after onset of his colitis he complained, at routine follow up, of lethargy, nausea and anorexia, and a 2 kg weight loss. Apart from pallor, physical examination was unremarkable.Investigations showed a haemoglobin of 6.6 g/dl with a normocytic and normochromic picture and normal serum vitamin B 12, folate, and ferritin concentrations. His serum urea value was high at 29-9 mmol/l and the serum creatinine concentration was 750 ,tmol/l. A 24 hour urinary protein excretion was 0.4 g/l. Ultrasound scan showed two small kidneys with no obstructive features. Antinuclear antibody and immunoelectrophoresis were negative and serum C3, C4 values were normal.A renal biopsy specimen showed changes consistent with a drug induced intestinal nephritis. The histological changes included global sclerosis of the glomeruli, fibrosis of the interstitium, and tubular atrophy with a marked lymphocytic infiltrate.In view of the active lymphocytic infiltration he was treated with oral prednisolone and a low protein diet. The sulphasalazine was stopped.His serum creatinine fell rapidly to 320 [tmol/l from a peak level of 800 ,umol/l. His renal function is still impaired but stable.Case 2 A 61 year old man with a seven year history of total ulcerative colitis treated with sulphasalazine 1 g twice a day and intermittent corticosteroids presented with lethargy, nausea, anorexia, and weight loss. On examination he was pale and unwell.Investigations included serum sodium 139 mmol/l, potassium 4 6 mmol/l, urea 35.7 mmol/l, creatinine 973 ,umol/1, and haemoglobin 6.4 g/dl (normocytic, normochromic).

Sulfasalazine induces mitochondrial dysfunction and renal injury

“…Some investigations mentioned that the obstructive nephropathy induced by sulfasalazine might be associated with sulfonamide crystals in the kidney [39]. It has also been found that sulfasalazine nephrotoxicity might be attributed to the intratubular precipitation of sulfapyridine crystals [3]. Hence, sulfapyridine-induced renal injury might play a role in sulfasalazine-induced renal injury and mitochondrial dysfunction.…”

“…Although sulfasalazine is generally considered as a safe medication [2], several cases of renal injury have been reported with sulfasalazine administration [3][4][5][6][7].…”

Drug-Induced Nephrotoxicity in Inflammatory Bowel Disease

“…Renal toxicity due to 5-ASA may present as GN, minimal-change nephropathy with nephrotic syndrome and interstitial nephritis, which may be associated with nephrogenic diabetes insipidus [10,11,12,13,14,15,16,17]. In many cases, it remains unclear whether renal impairment emerges as an extraintestinal manifestation or as an adverse drug effect.…”

“…The injury is usually reversible, but when diagnosis is delayed, it may be permanent [9,13,15]. Steroid or immunosuppressive therapy may improve renal dysfunction [9,13,14].…”

Sulfasalazine-induced renal injury in rats and the protective role of thiol-reductants

“…2 On the other hand, some investigations indicate decrease in renal function in sulfasalazine-treated patients. 3,4 Sulfasalazine-induced renal injury has typically been presented as interstitial nephritis, glomerulonephritis, nephritic syndrome and acute renal failure. [5][6][7] Sulfasalazine-induced renal injury, might be potentially irreversible.…”