Immunoglobulin as a risk factor for contrast media nephrotoxicity

Nader Bassilios, Lucile Mercadal and Gilbert Deray

Nephrology Department, CHU Pitié-Salpêtrière, Paris, France

Sir,

Nephrotoxicity of iodinated radiographic agents remains frequent [1,2]. The incidence of radiocontrast nephropathy varies from 0 to 90%, depending on a number of risk factors such as: renal insufficiency, diabetes mellitus, congestive heart failure, dehydration volume of the contrast agent administered and the use of other nephrotoxic drugs [1,3,4].

Intravenous immunoglobulins (IVIG) are used for a variety of disorders such as: chronic lymphocytic leukaemia, idiopathic thrombocytopenic purpura, Kawasaki's syndrome and Guillain-Barré syndrome [5]. IVIG have well known side-effects including: hypertension, chest pain, myalgia, fever and chills [6]. Acute renal failure (ARF) is a known but less frequent side-effect of IVIG [6].

We describe two patients who developed ARF after IVIG therapy in association with the injection of iodinated radio-contrast agent.

Case 1.

A 51-year-old woman was hospitalized for haemolytic anaemia and thrombocytopenic purpura after failure of a variety of immunosuppressive therapies to control her hepatitis C. The patient had a past history for hypertension, unstable angina controlled with medical treatment, adult onset diabetes actually treated by insulin and hepatitis C-positive liver cirrhosis without ascites.

On admission the patient's medication included trimetazidine 20 mg three times daily, molsidomine 2 mg three times daily, acebutolol 100 mg three times daily, amlodipine 5 mg/day and human insulin 2 injections/day. The initial blood urea nitrogen and serum creatinine were 5 mmol/l and 80 µmol/l respectively. Urine analysis showed microalbuminuria (150 mg/day).

A 2-day course of IVIG therapy was started at a dose of 0.60 g/kg/day over 12 h (Tégéline® 10 g/200 ml, Laboratoire Français du Fractionnement et des Biotechnologies, LFB). On the first day of IVIG therapy the patient had an abdominal CT scan with injection of 60 ml of iodinated radiocontrast agent which eliminated a liver tumour. Twenty-four hours prior to the CT scan the patient received 1000 ml of isotonic serum saline i.v. Two days later serum creatinine increased to 125 µmol/l, and then to 250 µmol/l the following day and up to 450 µmol/l at day 5. Urine output decreased to 200 ml/day. Renal ultrasound was normal and urine analysis revealed neither proteinuria nor hematuria. Urine output improved on day 6 with furosemide 250 mg/day. Serum creatinine started to decrease on day 8 without haemodialysis and returned to baseline on day 12. Renal biopsy was not performed due to the severe thrombocytopenia and the rapidly favourable evolution of renal function. Two months later the patient received a 5-day course of IVIG therapy for her idiopathic thrombocytopenic purpura at a dose of 0.2 g/kg/day (Octagam® 50 mg/ml, Octapharma Pharmazeutika, Austria) without iodinated radiocontrast agent injection. Renal function remained unchanged.

Case 2.

A 77-year-old woman was hospitalized for dermatopolymyositis of unknown aetiology. The patient had a past history of myocardial infarction, Raynaud syndrome, and deep lower limb vein thrombosis. On admission the patient's medication included acetylosalicylic acid 100 mg/day, fluindione 20 mg/day, molsidomine 2 mg three times daily, and prednisone 70 mg/day. Initial blood urea nitrogen and serum creatinine were 6 mmol/l and 90 µmol/l respectively. Urine analysis was negative for protein, and the microscopic sediment was benign. A 2-day course of IVIG therapy was started at a dose of 0.85 g/kg/day over 4 h (Tégéline® 10 g/200 ml, Laboratoire Français du Fractionnement et des Biotechnologies, LFB) over 4 h. On the second day of the IVIG therapy the patient had a thoracic spiral CT scan angiography with 130 ml iodinated radiocontrast agent which eliminated pulmonary embolism. Two days later serum creatinine increased to 300 µmol/l and urine output decreased to 300 ml/day. Renal ultrasound was normal and urine analysis revealed neither proteinuria nor haematuria. The patient became anuric and volume overloaded, and serum creatinine increased to 550 µmol/l. The patient required one haemodialysis session on day 4 for symptomatic uraemia and volume overload. The patient's urine output improved with 500 mg/day of furosemide and serum creatinine normalized by day 10. A renal biopsy was not performed due to the oral anticoagulant therapy taken by the patient and the rapidly favourable evolution of renal function.

Comment.

IVIG nephrotoxicity is a rare complication that was first reported by Barton et al. [9] in 1987. Many potential mechanisms of IVIG-associated ARF were suggested such as proximal renal tubular cell swelling. The expected risk of osmotic-induced changes is probably higher with sucrose and maltose-containing products because of their relatively high molecular weights (sucrose 232, maltose 232, and glucose 180) [9]. Obstructive ischaemia secondary to renal artery vasoconstriction and alterations in glomerular haemodynamics due to an elevated plasma oncotic pressure can also be responsible of this type of ARF [10]. Hansen-Schmidt et al. [11] found that glycine-containing immunoglobulin could be less nephrotoxic than IVIG containing sucrose. This could be explained by the fact that glycine is an intracellular product and various pathways are available for its metabolic degradation. Our two patients received IVIG fixed by sucrose and maltose which are the largely most frequently used types in France.

We suggest that IVIG may be a risk factor for contrast media nephrotoxicity. Our first case where the patient was rechallenged with IVIG without contrast media and without renal toxicity, strongly support our suggestion. Both drugs are responsible for osmotic nephrosis. This common toxic effect on renal cells may explain a synergistic effect on renal function. Therefore, we recommend avoiding the usage of iodinated radiocontrast agents in patients treated with IVIG.

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