Addition of cystatin C predicts cardiovascular death better than creatinine in intensive care

Helmersson‐Karlqvist, Johanna; Lipcsey, Miklós; Ärnlöv, Johan; Bell, Max; Ravn, Bo; Dardashti, Alain; Larsson, Anders

doi:10.1136/heartjnl-2020-318860

Cited by 10 publications

(7 citation statements)

References 32 publications

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“…In addition, we found that eGFR discrepancy is associated with significantly higher 30-day mortality even after adjustment for demographics, comorbidities, baseline laboratory studies, and medication use. Although higher serum creatinine and cystatin C have each been shown to be associated with increased mortality in multiple clinical settings, [49][50][51][52][53][54] our finding suggests that discrepancy between creatinine and cystatin C, in addition to the absolute values of either marker, adds further information and potentially serves as an independent predictor of death.…”

Section: Discussionmentioning

confidence: 70%

Medication-related adverse events in patients with cancer and discrepancies in cystatin C- versus creatinine-based eGFR

Sise

2023

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Background: Creatinine-based estimated glomerular filtration rate (eGFRCRE) may overestimate kidney function in patients with cancer. Cystatin C-based eGFR (eGFRCYS) is an alternative marker of kidney function. We investigated whether patients with an eGFR discrepancy, defined as eGFRCYS >30% lower than the concurrent eGFRCRE, had an increased risk of adverse events resulting from renally-cleared medications. Patients and Methods: We conducted a cohort study of adult patients with cancer who had serum creatinine and cystatin C measured on the same day between May 2010 and January 2022 at two academic cancer centers in Boston, MA. The primary outcome was the incidence of each of the following medication-related adverse events: 1) supratherapeutic vancomycin levels (>30ug/mL); 2) trimethoprim-sulfamethoxazole-related hyperkalemia (>5.5mEq/L); 3) baclofen-induced neurotoxicity; and 4) supratherapeutic digoxin levels (>2.0ng/mL). Results: 1988 patients with cancer had simultaneous eGFRCYS and eGFRCRE. The mean age was 66 years (SD +/- 14), 965 (49%) were female, and 1555 (78%) were non-Hispanic white. eGFR discrepancy occurred in 579 patients (29%). Patients with eGFR discrepancy were more likely to experience medication-related adverse events compared to those without eGFR discrepancy: vancomycin levels >30ug/mL (24% vs. 10%, p=0.004), trimethoprim- sulfamethoxazole-related hyperkalemia (24% vs. 12%, p=0.013), baclofen-induced neurotoxicity (25% vs. 0%, p=0.13), and supratherapeutic digoxin levels (38% vs. 0%, p=0.03). The adjusted OR for vancomycin levels >30ug/mL was 2.30 (95% CI 1.05 - 5.51, p = 0.047). Conclusion: Among patients with cancer with simultaneous assessment of eGFRCYS and eGFRCRE, medication-related adverse events occur more commonly in those with eGFR discrepancy. These findings underscore the importance of accurate assessment of kidney function and appropriate dosing of renally-cleared medications in patients with cancer.

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Section: Discussionmentioning

confidence: 70%

Medication-related adverse events in patients with cancer and discrepancies in cystatin C- versus creatinine-based eGFR

Sise

2023

Preprint

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“…It is worth highlighting that SEM 2 and eGFRcys outperformed eGFRcrecys in CVD risk prediction. A previous study reported that a combination of eGFRcre- and eGFRcys-based categories could improve prediction of CVD mortality in intensive care [ 37 ], but this may be a very different context compared to a general population situation, where most individuals are healthy or have a low burden of disease. The question remains as to why the performance of a single biomarker, eGFRcys, was not much inferior to SEM.…”

Section: Discussionmentioning

confidence: 99%

Structural equation modeling (SEM) of kidney function markers and longitudinal CVD risk assessment

et al. 2023

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Lower kidney function is known to enhance cardiovascular disease (CVD) risk. It is unclear which estimated glomerular filtration rate (eGFR) equation best predict an increased CVD risk and if prediction can be improved by integration of multiple kidney function markers. We performed structural equation modeling (SEM) of kidney markers and compared the performance of the resulting pooled indexes with established eGFR equations to predict CVD risk in a 10-year longitudinal population-based design. We split the study sample into a set of participants with only baseline data (n = 647; model-building set) and a set with longitudinal data (n = 670; longitudinal set). In the model-building set, we fitted five SEM models based on serum creatinine or creatinine-based eGFR (eGFRcre), cystatin C or cystatin-based eGFR (eGFRcys), uric acid (UA), and blood urea nitrogen (BUN). In the longitudinal set, 10-year incident CVD risk was defined as a Framingham risk score (FRS)>5% and a pooled cohort equation (PCE)>5%. Predictive performances of the different kidney function indexes were compared using the C-statistic and the DeLong test. In the longitudinal set, a SEM-based estimate of latent kidney function based on eGFRcre, eGFRcys, UA, and BUN showed better prediction performance for both FRS>5% (C-statistic: 0.70; 95% CI: 0.65–0.74) and PCE>5% (C-statistic: 0.75; 95%CI: 0.71–0.79) than other SEM models and different eGFR formulas (DeLong test p-values<3.21×10−6 for FRS>5% and <1.49×10−9 for PCE>5%, respectively). However, the new derived marker could not outperform eGFRcys (DeLong test p-values = 0.88 for FRS>5% and 0.20 for PCE>5%, respectively). SEM is a promising approach to identify latent kidney function signatures. However, for incident CVD risk prediction, eGFRcys could still be preferrable given its simpler derivation.

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“…Cystatine C has a predictive value in COVID-19 [ 13 , 34 , 65 , 66 ] and also in ICU patients in general [ 14 , 21 , 67 ]. Cystatin C has the drawback of being affected by corticosteroids [ 15 , 16 , 17 ], but not by CRP [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

“…In 2020, dexamethasone was identified as being able to improve outcomes in hospitalized COVID-19 patients needing supplemental oxygen [ 19 , 20 ]. This implies a potential for underestimating eGFR when using the cystatine C CAPA (Caucasian, Asian, Pediatric, and Adult) equation [ 21 ] in the COVID-19 cohort. The effect of dexamethasone on eGFR CAPA in COVID-19 has, to the best of our knowledge, not previously been evaluated.…”

Section: Introductionmentioning

confidence: 99%

Differential Bias for Creatinine- and Cystatin C- Derived Estimated Glomerular Filtration Rate in Critical COVID-19

et al. 2022

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COVID-19 is a systemic disease, frequently affecting kidney function. Dexamethasone is standard treatment in severe COVID-19 cases, and is considered to increase plasma levels of cystatin C. However, this has not been studied in COVID-19. Glomerular filtration rate (GFR) is a clinically important indicator of renal function, but often estimated using equations (eGFR) based on filtered metabolites. This study focuses on sources of bias for eGFRs (mL/min) using a creatinine-based equation (eGFRLMR) and a cystatin C-based equation (eGFRCAPA) in intensive-care-treated patients with COVID-19. This study was performed on 351 patients aged 18 years old or above with severe COVID-19 infections, admitted to the intensive care unit (ICU) in Uppsala University Hospital, a tertiary care hospital in Uppsala, Sweden, between 14 March 2020 and 10 March 2021. Dexamethasone treatment (6 mg for up to 10 days) was introduced 22 June 2020 (n = 232). Values are presented as medians (IQR). eGFRCAPA in dexamethasone-treated patients was 69 (37), and 74 (46) in patients not given dexamethasone (p = 0.01). eGFRLMR was not affected by dexamethasone. eGFRLMR in females was 94 (20), and 75 (38) in males (p = 0.00001). Age and maximal CRP correlated negatively to eGFRCAPA and eGFRLMR, whereas both eGFR equations correlated positively to BMI. In ICU patients with COVID-19, dexamethasone treatment was associated with reduced eGFRCAPA. This finding may be explained by corticosteroid-induced increases in plasma cystatin C. This observation is important from a clinical perspective since adequate interpretation of laboratory results is crucial.

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Addition of cystatin C predicts cardiovascular death better than creatinine in intensive care

Cited by 10 publications

References 32 publications

Medication-related adverse events in patients with cancer and discrepancies in cystatin C- versus creatinine-based eGFR

Medication-related adverse events in patients with cancer and discrepancies in cystatin C- versus creatinine-based eGFR

Structural equation modeling (SEM) of kidney function markers and longitudinal CVD risk assessment

Differential Bias for Creatinine- and Cystatin C- Derived Estimated Glomerular Filtration Rate in Critical COVID-19

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