Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Mar;34(3):389-403.
doi: 10.1007/s00467-018-3929-z. Epub 2018 Mar 16.

Pharmacology and pharmacogenetics of prednisone and prednisolone in patients with nephrotic syndrome

Anne M Schijvens  1 , Rob Ter Heine  2 , Saskia N de Wildt  3   4 , Michiel F Schreuder  5
Affiliations
Review

Pharmacology and pharmacogenetics of prednisone and prednisolone in patients with nephrotic syndrome

Anne M Schijvens et al. Pediatr Nephrol. 2019 Mar.

Abstract

Nephrotic syndrome is one of the most common glomerular disorders in childhood. Glucocorticoids have been the cornerstone of the treatment of childhood nephrotic syndrome for several decades, as the majority of children achieves complete remission after prednisone or prednisolone treatment. Currently, treatment guidelines for the first manifestation and relapse of nephrotic syndrome are mostly standardized, while large inter-individual variation is present in the clinical course of disease and side effects of glucocorticoid treatment. This review describes the mechanisms of glucocorticoid action and clinical pharmacokinetics and pharmacodynamics of prednisone and prednisolone in nephrotic syndrome patients. However, these mechanisms do not account for the large inter-individual variability in the response to glucocorticoid treatment. Previous research has shown that genetic factors can have a major influence on the pharmacokinetic and dynamic profile of the individual patient. Therefore, pharmacogenetics may have a promising role in personalized medicine for patients with nephrotic syndrome. Currently, little is known about the impact of genetic polymorphisms on glucocorticoid response and steroid-related toxicities in children with nephrotic syndrome. Although the evidence is limited, the data summarized in this study do suggest a role for pharmacogenetics to improve individualization of glucocorticoid therapy. Therefore, studies in larger cohorts with nephrotic syndrome patients are necessary to draw final conclusions about the influence of genetic polymorphisms on the glucocorticoid response and steroid-related toxicities to ultimately implement pharmacogenetics in clinical practice.

Keywords: Glucocorticoids; Nephrotic syndrome; Pharmacogenetics; Pharmacology; Prednisolone; Prednisone.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Molecular mechanisms of glucocorticoid action. AP-1, activator protein 1; IκB, inhibitor of kappa B; IPO-13, importin-13; NF-κB, nuclear factor κB; GRE, glucocorticoid response elements
Fig. 2
Fig. 2
ADME prednisone/prednisolone in patients with nephrotic syndrome
Fig. 3
Fig. 3
Unchanged unbound (free) concentration in patients with nephrotic syndrome
See this image and copyright information in PMC

References

    1. El Bakkali L, Rodrigues Pereira R, Kuik DJ, Ket JC, van Wijk JA. Nephrotic syndrome in the Netherlands: a population-based cohort study and a review of the literature. Pediatr Nephrol. 2011;26:1241–1246. - PMC - PubMed
    1. Tarshish P, Tobin JN, Bernstein J, Edelmann CM., Jr Prognostic significance of the early course of minimal change nephrotic syndrome: report of the international study of kidney disease in children. J Am Soc Nephrol. 1997;8:769–776. - PubMed
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group (2012) KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl 2:139–274
    1. Samuel SM, Flynn R, Zappitelli M, Dart A, Parekh R, Pinsk M, Mammen C, Wade A, Scott SD, Canadian Childhood Nephrotic Syndrome Project T Factors influencing practice variation in the management of nephrotic syndrome: a qualitative study of pediatric nephrology care providers. CMAJ Open. 2017;5:E424–E430. - PMC - PubMed
    1. Teeninga N, Kist-van Holthe JE, van Rijswijk N, de Mos NI, Hop WC, Wetzels JF, van der Heijden AJ, Nauta J. Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. J Am Soc Nephrol. 2013;24:149–159. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources