Effect of oral cyclosporin on renal function in Crohn's disease

Abstract

Twenty-one patients with Crohn's disease were followed prospectively for 24 weeks to examine the effect of a low-dose cyclosporin regime on renal function (initial dose 5 mg/kg reduced by 1 mg/kg every two months to a maintenance of 2 mg/kg). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by radioisotope clearance at 0, 6 and 24 weeks. GFR and ERPF fell significantly (mean GFR at baseline: 120.9 ml/min/1.73 m2; at six weeks: 100.9 ml/min/1.73 m2; mean ERPF at baseline: 497.3 ml/min/1.73 m2; at six weeks: 398.5 ml/min/1.73 m2). Following dose reduction, the ERPF remained lower than baseline (mean 408.6 ml/min/1.73 m2), and there was a trend towards the GFR remaining low (mean 111.8 ml/min/1.73 m2). Serum creatinine rose significantly (median pretreatment 72 mumol/liter; median at four weeks 86 mumol/liter) but returned to baseline after dose reduction. Plasma cyclosporin levels and serum creatinine did not help predict the extent of changes in renal function. At low doses, cyclosporin causes changes in renal hemodynamics that may not be reversed by dose reduction.

Oral cyclosporin in refractory inflammatory bowel disease

“…Irreversible reduction of glomerular filtration may be associated with its chronic use and interstitial fibrosis is reported in 20% of patients with normal preexisting renal function treated for autoimmune disease. [12][13][14] The development of opportunistic infections, including Pneumocystis carinii, may be related to the degree of immunosuppression, especially when corticosteroids are used concurrently.I5 Neurological disturbances including paraesthesia and tremor are common, and grand ma1 seizures are reported in 1 5 5 . 5 % of transplant recipients.I6 Mild reversible impairment of liver function, hypertension, hyperlipidaemia, hyperkalaemia and hyperuricaemia are less common.1o In our experience, adverse effects were frequent, though most of these were mild and transient.…”

Cyclosporine and inflammatory bowel disease: buying time

“…27 A few case reports dealing w ith severe and sometimes fatal opportunistic infections have been reported. [23][24][25][26] Importantly, these infections occurre d during high-dose cyclosporine treatme nt in combination with corticoste roids.…”

“…Being a powerful immunosuppressant, cyclosporine also has potential side effects including: renal insufficiency (6%), hyperte nsion (11%), infectious complications (3%), severe neurological disorders including epilepsy (1%), paresthesias (26-70%), tre mor (7%), headache (5%), hypertrichosis (13%), gingival hyperplasia (2%), and anaphylax is (0.3%) [23][24][25][26] (Table 1).…”

The renal and urologic complications of inflammatory bowel disease

“…This is thought to be related to vasoconstriction and a decrease in afferent arteriolar blood flow. Nephrotoxicity may present as reversible dysfunction, irreversible acute renal failure, chronic renal insufficiency, hyperchloremic hyperkalemic acidosis, and thrombotic microangiopathy (55). Almost all patients with IBD receiving chronic cyclosporine therapy demonstrate a 20% decline in their effective renal plasma flow and glomerular filtration rate, which is reversible within 2 weeks of discontinuation of therapy.…”

“…However, patients with CD treated with lowdose (4 mg/kg/day) cyclosporine given orally do not experience major changes in renal hemodynamics. Serum levels of BUN and creatinine may increase, although often within the normal range (55). However, a recent study of renal biopsy data suggested that histopathologic evidence of nephropathy is found in 21% of patients and includes arteriolopathy (2%), interstitial fibrosis (5%) and tubular atrophy (1.5%) (56).…”