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Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine
Örebro universitet, Institutionen för medicinska vetenskaper.ORCID-id: 0000-0001-8128-732X
School of Medical Sciences, Örebro University, Örebro, Sweden.
School of Medical Sciences, Örebro University, Örebro, Sweden.
School of Medical Sciences, Örebro University, Örebro, Sweden.
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2017 (Engelska)Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 32, nr 4, s. 663-670Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk.

Methods: Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol.

Results: Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2  = 0.61). Addition of mGFR did not improve the model.

Conclusions: Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined.

Ort, förlag, år, upplaga, sidor
Oxford University Press, 2017. Vol. 32, nr 4, s. 663-670
Nyckelord [en]
GFR, creatinine, cystatin C, epidemiology, prognosis
Nationell ämneskategori
Urologi och njurmedicin
Identifikatorer
URN: urn:nbn:se:oru:diva-57361DOI: 10.1093/ndt/gfx004ISI: 000401057000013PubMedID: 28340079Scopus ID: 2-s2.0-85019091905OAI: oai:DiVA.org:oru-57361DiVA, id: diva2:1097005
Anmärkning

Funding agencies:

Research Committee of the Örebro County Council (OLL-330601, OLL-408481 and OLL-506561)

Tillgänglig från: 2017-05-21 Skapad: 2017-05-21 Senast uppdaterad: 2019-09-19Bibliografiskt granskad
Ingår i avhandling
1. A life-course approach to chronic kidney disease: risks and consequences
Öppna denna publikation i ny flik eller fönster >>A life-course approach to chronic kidney disease: risks and consequences
2019 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Successful primary prevention of chronic kidney disease (CKD) relies on understanding the pathways leading to established disease, including how they extend over the life-course. Projects in this thesis examine risk factors for CKD and consequences of impaired kidney function from a life-course perspective using routinely collected health-data in Swedish registers and research cohort data from the United Kingdom.

The main findings regarding risk factors for CKD are, that markers of health and development determined at conscription assessment in adolescence, independently predict diagnosis of end-stage renal disease in middle age. We also identified a persistent increased risk of CKD following hospital admission with pneumonia in adulthood with highest magnitude risks in years immediately following infection, but still statistically significantly raised more than 15 years after the pneumonia episode. Our main findings relevant to predicting the consequences of impaired kidney function are that creatinine and cystatin C used clinically to estimate kidney function (estimated glomerular filtration rate, eGFR) have associations with increased mortality risk independent of GFR measured with an exogenous filtration marker (mGFR). If cystatin C and creatinine are combined, adding mGFR does not improve mortality risk prediction. Another important finding is that moderately reduced eGFR is only associated with a statistically significant increased mortality risk among individuals in the lowest third of the distribution of grip strength in a general population sample followed for 4-5 years, after adjustment for potential confounding factors.

These results highlight the importance of adopting a life-course perspective when studying risk factors for CKD, since these associations can extend over different stages in the life-course. When assessing increased mortality risk associated with measures of GFR, combining cystatin and creatinine improves risk prediction. Potential effect modification across subgroups, including by grip strength, should be considered.

Ort, förlag, år, upplaga, sidor
Örebro: Örebro University, 2019. s. 89
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 196
Nyckelord
Chronic kidney disease, pneumonia, grip strength, creatinine, cystatin C, adolescence, life-course epidemiology, risk factor, mortality
Nationell ämneskategori
Allmänmedicin Urologi och njurmedicin Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
Identifikatorer
urn:nbn:se:oru:diva-74659 (URN)978-91-7529-290-8 (ISBN)
Disputation
2019-09-06, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2019-06-11 Skapad: 2019-06-11 Senast uppdaterad: 2019-09-19Bibliografiskt granskad

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