title: Altered clearance of N-1 methylnicotinamide associated with the use of low doses of cyclosporine.
abstract: To improve the monitoring of patients on low doses of cyclosporine there is a need for new tests of tubular function. N-1 methylnicotinamide (NMM) is an endogenous organic cation that is secreted by the proximal tubule and its clearance can be measured. In 27 patients with psoriasis, serial measurements of NMN clearance, plasma aldosterone, plasma chloride, bicarbonate, and magnesium were compared with changes in the radionuclide measurement of glomerular filtration rate and renal blood flow before, during, and after a 3-month course of low-dose cyclosporine (< 5 mg/kg/d). N-1 methylnicotinamide clearance decreased significantly with cyclosporine only (2.5 mg/kg/d, n = 10, P < 0.01). Recovery of NMN clearance lagged behind that of glomerular filtration rate and renal blood flow. Serum magnesium decreased significantly on cyclosporine (2.5 mg/kg, n = 10, P < 0.01; 5 mg/kg, n = 9, P < 0.0001). In the whole group, plasma potassium increased significantly (n = 27, P < 0.02) and plasma aldosterone was inappropriately low. Low doses of cyclosporine in psoriasis cause a reduced clearance of NMN, hypomagnesemia, and a variable hyperchloremic acidosis. Nifedipine may alter these biochemical variables without necessarily improving renal hemodynamics. The delayed recovery of NMN clearance in comparison with renal haemodynamic measurements following cyclosporine therapy suggests that this noninvasive test of tubular function may be a marker of persisting cyclosporine nephrotoxicity and that it should be evaluated further.
authors.affiliation: Department of Medicine, Manchester Royal Infirmary, UK.
authors.forename: B D
authors.initials: BD
authors.lastname: Edwards
authors.forename: A
authors.initials: A
authors.lastname: Maiza
authors.forename: P T
authors.initials: PT
authors.lastname: Daley-Yates
authors.forename: R J
authors.initials: RJ
authors.lastname: Chalmers
authors.forename: J B
authors.initials: JB
authors.lastname: O'Driscoll
authors.forename: R S
authors.initials: RS
authors.lastname: Lawson
authors.forename: H J
authors.initials: HJ
authors.lastname: Testa
authors.forename: F W
authors.initials: FW
authors.lastname: Ballardie
mesh_terms: D000704:Analysis of Variance; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006801:Humans; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D012079:Renal Circulation
chemical_list: D009536:Niacinamide; D016572:Cyclosporine; D009543:Nifedipine; C024058:N(1)-methylnicotinamide