Immunoglobulin M ‘Flare’ after rituximab-associated acute tubular necrosis in Waldenstr?m’s macroglobulinemia

Waldenström’s macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma characterized by a circulating monoclonal IgM. Renal involvement in classical cases of WM is rare, and the pathological hallmark finding in the renal biopsy specimen is a thrombotic microangiopathy. We report the case of a 69-year-old man with the diagnosis of WM for 3 months before he presented with acute renal failure (ARF). A renal biopsy performed suggested the diagnosis of acute tubular necrosis. The diagnosis of ARF related to IgM flare after Rituximab therapy was made.     

Néphropathie induite par les produits de contraste iodés,l’épuration extrarénale est-elle efficace en prevention ?

A FREQUENT AND EXPENSIVE PROBLEM: Ninety percent of contrast media nephrotoxicity (CMN) occur in patients with pre-existing kidney failure. Its aggravation may require early chronic dialysis. PREVENTIVE MEASURES: CMN prophylaxis is important in these patients. Pre- and post-hydration, with infusion of isotonic saline solution or sodium bicarbonate, and reduction of contrast medium (CM) volume to the strict minimum are essential for preventing CM-induced kidney failure. THE INTEREST OF PROPHYLACTIC HEMODIALYSIS AND HEMOFILTRATION: An interesting approach in preventing CMN is the early elimination of the CM with dialysis techniques. Preventive hemodialysis does not reduce the risk of CMN, but hemofiltration has shown significant efficacy in a population of patients with kidney failure. THE INTEREST OF IMMEDIATE HEMODIALYSIS IN CHRONIC HEMODIALYSIS PATIENTS: Although nephrotoxicity is no longer a problem in patients undergoing chronic hemodialysis, CM, especially in high-dose injections, may be responsible for fluid and electrolyte abnormalities and/or volemic expansion. No data yet justify a conclusion that a hemodialysis session immediately after injection of a CM in chronic dialysis patients might be helpful.     

COX-2 inhibitors and acute interstitial nephritis: case report and review of the literature

We report a case of biopsy-proven acute interstitial nephritis (AIN) in a 50-year-old diabetic woman, who had been treated with celecoxib for 4 weeks before presentation. She presented with clinical findings of renal proximal tubulopathy, aseptic leukocyturia and acute renal failure. A kidney biopsy specimen showed AIN with intense tubuli and eosinophilic infiltrate in the interstitium. She recovered normal renal function two weeks after cessation of celecoxib and use of a corticosteroid. A review of the literature yielded eight cases of COX-2 inhibitor-associated AIN with a biopsy-proven diagnosis. Among the reported cases, AIN was diagnosed after an average of 8.3 months of therapy (SD 12 months, range 3 days - 3 years) with 25 mg rofecoxib or 200 mg celecoxib daily. Common symptoms included asthenia, anorexia, nausea and vomiting. The classic triad of fever, rash and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, eosinophilia. Renal failure was common at the time of diagnosis. Mean serum creatinine levels were 0.86 +/- 0.11 mg/dl, 5.66 +/- 3.50 mg/dl and 1.15 +/- 0.24 before treatment, at time of diagnosis and 1 - 2 months after COX-2 inhibitor withdrawal, respectively. Three patients required emergency hemodialysis. After cessation of COX-2 inhibitor treatment, patients recovered completely with a normalized serum creatinine level after one to two months. Management consisted of withdrawal of the COX-2 inhibitor drug and in four patients, corticosteroid therapy was well-tolerated and may have been beneficial.     

Pharmacokinetic changes in renal failure

DRUG PHARMACOKINETICS: One of the first steps in the clinical development of drugs consists in studies of their pharmacokinetics. Dosage and administration interval necessary to ensure secure and efficient plasma levels are derived from the values of pharmacokinetic parameters. Renal disease usually implies multiple pathophysiological modifications that generate alteration in drugs pharmacokinetic profile. Those modifications mainly occur on elimination phase but also to a significant extent on absorption and distribution. PATHOPHYSIOLOGICAL CHANGES: In this article we describe potential alteration in drugs absorption, distribution (volume of distribution, binding to plasma proteins), hepatic or renal metabolism, and parent compound and/or metabolites elimination in patients with renal insufficiency. Furthermore, in patients with end-stage renal disease treated by dialysis, drugs are likely to be removed by extracorporal epuration and dosage and/or interval modifications should thus be applied to treatments in those patients. CLINICAL ASSESSMENT: Pharmacokinetics of drugs should be evaluated in patients with renal failure to determine whereas dosage and/or administration interval should thus be modified to enhance tolerance and pharmacological efficacy. Such studies are obviously necessary for drugs that are mainly excreted unchanged in urine. They should also be performed for drugs that are mainly degraded in the liver with emphasis on metabolites pharmacokinetics.