Effects of Glucocorticoid Immunosuppression on Serum Cystatin C Concentrations in Renal Transplant Patients

Risch, Lorenz; Herklotz, Roberto; Blumberg, A; Huber, Andreas

doi:10.1093/clinchem/47.11.2055

Cited by 272 publications

(123 citation statements)

References 25 publications

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“…1). These results parallel those of Risch et al 16 who demonstrated that in humans subjected to kidney transplantation sCysC was higher in patients treated with corticosteroids and raised with increasing glucocorticoid doses. Similar results were reported by P€ oge et al 36 who described that, in patients subjected to kidney transplantation treated with 500 mg of methylprednisolone, sCysC peaked after 24 hours and that this rise was dose-dependent.…”

Section: Discussionsupporting

confidence: 90%

“…[7][8][9] Nevertheless, as its clinical application was initiated in human medicine, it has been reported that several conditions unrelated to renal failure such as thyroid dysfunction, chronic liver disease, malignancies, or asthma among others can alter sCysC. [10][11][12][13][14][15][16][17][18][19][20][21] However, it has to be noted that the treatment of choice for all these conditions include exogenous glucocorticoid administration and that methylprednisolone or prednisone administration deeply influence sCysC in humans. 10,15,22 In veterinary medicine, reference values for sCysC canvary with age and body weight (<15 kg), 23 these results are controversial.…”

mentioning

confidence: 99%

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Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs

Múñoz

Soblechero

Duque

et al. 2017

Veterinary Internal Medicne

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BackgroundOral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans.ObjectiveTo determine if oral administration of prednisone alters sCysC in dogs without pre‐existing renal disease.AnimalsForty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary‐dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C).MethodsRetrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21).ResultsIn group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P < 0.01); sCysC values decreased to basal at day 14 when the dose was decreased and after 1 week of withdrawal of prednisone (0.27 ± 0.03 mg/L for group A at day 14 and 0.15 ± 0.02 mg/L at day 21; P > 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05).Conclusions and Clinical ImportanceOral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose‐dependent fashion.

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs

Múñoz

Soblechero

Duque

et al. 2017

Veterinary Internal Medicne

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“…Immunosuppressive therapy may have a significant impact on CysC concentration. Glucocorticoid therapy was shown to have an influence on the CysC production rate and consequently on its serum level (22). Interestingly, we found no difference when comparing patients with and without steroid therapy.…”

Section: Discussioncontrasting

confidence: 58%

Intra‐individual variation of cystatin C and creatinine in pediatric solid organ transplant recipients

Podracká

Feber

Lepage

et al. 2005

Pediatric Transplantation

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There is controversy about the feasibility of cystatin C (CysC) as a marker of glomerular filtration rate (GFR) post-transplant (Tx). We studied intra-patient variability of CysC in comparison with serum creatinine (SCr) in 20 children (11 males, mean age 11.5 +/- 6.4 yr) with solid organ transplants (14 kidney, four liver, and two combined liver + kidney transplants). The mean age at Tx was 7.0 +/- 5.6 yr. A total of 178 simultaneous SCr and CysC measurements (median 8 per patient) were analyzed. In addition, GFR was calculated using the Schwartz and a novel CysC-based formula. Intra-individual coefficient of variations (CV) was calculated as ratio of standard deviation over mean. The mean CV was significantly lower for SCr (7.71 +/- 4.16%) when compared with CysC (10.27 +/- 4.87, p = 0.04), but was no longer significantly different when excluding patients with a bladder augment. The CV of the GFR estimated by Schwartz formula (7.44 +/- 3.77) was significantly lower than GFR calculated from CysC (12.52 +/- 7.37), p = 0.001. The mean ratio between the Schwartz GFR and the GFR calculated from CysC was 102.6 +/- 12.8%, not significantly different from 100% (p = 0.3796). The only potential confounding factors to explain increased CV after Tx were gender and bladder augmentation, whereas calcineurin inhibitors or steroids did not influence CV. With the limitation of a small number of subjects, our data suggest that the CysC and the CysC-calculated GFR is equivalent but not better than SCr and Schwartz formula. We therefore conclude that measurement of CysC can be used for longitudinal intra-individual follow-up of renal function post-Tx.

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“…45,46 In addition, body mass index and inflammation may affect cystatin C concentrations independent of kidney function and these factors must be considered when evaluating cystatin C levels in clinical practice. 47 Indeed, a positive association between proinflammatory C-reactive protein and cystatin C levels was observed, however, this study used creatine clearance to compare cystatin C and creatinine, which may have biased results against cystatin C. 48,49 Nonetheless, the list of confounding diseases or conditions modifying cystatin C is relatively small compared with creatinine. 8 Another limitation of cystatin C is related to its application in eGFR equations.…”

Section: Limitations Of Cystatin C As a Gfr Biomarkermentioning

confidence: 96%

Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies

Kar

Paglialunga

Islam

2018

The Journal of Clinical Pharma

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Glomerular filtration rate (GFR) is routinely used as a surrogate endpoint for the development of investigational drugs in clinical trials. GFR and staging of chronic kidney disease are typically assessed by measuring the concentration of endogenous serum biomarkers such as albumin and creatinine. However, creatinine is subject to high biological variability, and levels of creatinine do not rise until nearly 50% of kidney function is damaged, leading to inaccurate chronic kidney disease staging and false negatives. A newer biomarker for GFR, cystatin C, has been shown to be subject to less biological interference and more sensitive to early declines in kidney function. Cystatin C has also been shown to outperform creatinine as an indicator of true GFR and to add information about the occurrence of acute kidney injury. Comparison studies of cystatin C and creatinine continue to demonstrate its increased accuracy and sensitivity for changes in true GFR. While challenges remain for use of cystatin C, international agencies and working groups continue to validate cystatin C as a biomarker and accompanying GFR estimating equations for diagnostic and drug development use. In this review, we summarize these comparison studies, regulatory and industry guidelines, and clinical trial case studies for use of cystatin C in drug development.

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Effects of Glucocorticoid Immunosuppression on Serum Cystatin C Concentrations in Renal Transplant Patients

Cited by 272 publications

References 25 publications

Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs

Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs

Intra‐individual variation of cystatin C and creatinine in pediatric solid organ transplant recipients

Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies

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