TY - JOUR
T1 - Levamisole causes a transient increase in plasma creatinine levels but does not affect kidney function based on cystatin C
AU - Veltkamp, Floor
AU - Bökenkamp, Arend
AU - Slaats, Jeroen
AU - Hamer, Henrike
AU - Bouts, Antonia H. M.
N1 - Funding Information: F.V. and A.H.M. are supported by a consortium grant from the Dutch Kidney Foundation (CP16.03). Funding Information: The authors would like to thank G.H. Khan for preparing and providing the levamisole stock solution. The LEARNS study is an interuniversity collaboration in the Netherlands that is established to perform a double blind, placebo-controlled randomized clinical trial on the efficacy of levamisole on relapses in children with a first episode of steroid-sensitive nephrotic syndrome, and to study basic mechanisms underlying nephrotic syndrome and the mode of action of levamisole. Principal investigators are (in alphabetical order): A.H.M. Bouts (Department of Pediatric Nephrology, Amsterdam UMC, location AMC, Amsterdam, the Netherlands), S. Florquin (Department of Pathology, Amsterdam UMC, location AMC, Amsterdam, the Netherlands), J.E. Guikema (Amsterdam UMC, location AMC, Amsterdam, the Netherlands), L. Haverman (Psychosocial Department, Amsterdam UMC, location AMC, Amsterdam, the Netherlands), L.P.W.J. van den Heuvel (Radboud Institute for Molecular Sciences, Radboud University Medical Center, Nijmegen, the Netherlands), E. Levtchenko (Department of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium), R.A.A. Mathôt (Department of Hospital Pharmacy, Amsterdam UMC, location AMC, Amsterdam, the Netherlands), M.F. Schreuder (Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, the Netherlands), B. Smeets (Radboud Institute for Molecular Sciences, Radboud University Medical Center, Nijmegen, the Netherlands ), and J.A.E. van Wijk (Department of Pediatric Nephrology, Amsterdam UMC, location AMC, Amsterdam, the Netherlands). Publisher Copyright: © 2022, The Author(s).
PY - 2022/10
Y1 - 2022/10
N2 - Background: In pediatric patients treated with levamisole to prevent relapses of idiopathic nephrotic syndrome (INS), a transient and non-progressive rise in creatinine levels has been observed. It has been suggested that levamisole affects tubular secretion of creatinine. However, other potential mechanisms — nephrotoxicity and interference with the analytical assay for creatinine — have never been thoroughly investigated. Methods: In three steroid-sensitive nephrotic syndrome (SSNS) patients with elevated plasma creatinine levels, treated with levamisole 2.5 mg/kg every other day, serum cystatin C was determined. The glomerular filtration rate (GFR) was estimated using the full age spectrum for creatinine and the full age spectrum for cystatin C equations. Interference of levamisole with the enzymatic creatinine assay was tested using spare human plasma of different creatinine concentrations spiked with levamisole (4, 20, and 100 µM). Results: Three patients who received levamisole with elevated plasma creatinine levels had normal serum cystatin C levels and corresponding estimated GFR. There was no assay interference. Conclusion: Levamisole increases plasma creatinine levels, which is most probably due to impaired tubular secretion of creatinine since there was no assay interference and patients had normal eGFR based on serum cystatin C. However, interference of metabolites of levamisole could not be excluded. To monitor GFR, cystatin C in addition to creatinine should be used and be measured before and during levamisole use.
AB - Background: In pediatric patients treated with levamisole to prevent relapses of idiopathic nephrotic syndrome (INS), a transient and non-progressive rise in creatinine levels has been observed. It has been suggested that levamisole affects tubular secretion of creatinine. However, other potential mechanisms — nephrotoxicity and interference with the analytical assay for creatinine — have never been thoroughly investigated. Methods: In three steroid-sensitive nephrotic syndrome (SSNS) patients with elevated plasma creatinine levels, treated with levamisole 2.5 mg/kg every other day, serum cystatin C was determined. The glomerular filtration rate (GFR) was estimated using the full age spectrum for creatinine and the full age spectrum for cystatin C equations. Interference of levamisole with the enzymatic creatinine assay was tested using spare human plasma of different creatinine concentrations spiked with levamisole (4, 20, and 100 µM). Results: Three patients who received levamisole with elevated plasma creatinine levels had normal serum cystatin C levels and corresponding estimated GFR. There was no assay interference. Conclusion: Levamisole increases plasma creatinine levels, which is most probably due to impaired tubular secretion of creatinine since there was no assay interference and patients had normal eGFR based on serum cystatin C. However, interference of metabolites of levamisole could not be excluded. To monitor GFR, cystatin C in addition to creatinine should be used and be measured before and during levamisole use.
KW - Creatinine
KW - Cystatin C
KW - Estimated glomerular filtration rate
KW - Levamisole
UR - http://www.scopus.com/inward/record.url?scp=85128204120&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00467-022-05547-9
DO - https://doi.org/10.1007/s00467-022-05547-9
M3 - Article
C2 - 35416496
SN - 0931-041X
VL - 37
SP - 2515
EP - 2519
JO - Pediatric nephrology (Berlin, Germany)
JF - Pediatric nephrology (Berlin, Germany)
IS - 10
ER -