Ratio of cystatin C and creatinine-based estimates of the glomerular filtration rate predicts mortality in healthy seniors independent of kidney function

Purde, Mette-Triin; Nock, Stefan; Risch, Lorenz; Escobar, Pedro Medina; Grebhardt, Chris; Nydegger, Urs E.; Stanga, Zeno; Risch, Martin

doi:10.3109/00365513.2016.1149882

Cited by 22 publications

(26 citation statements)

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“…Because GFR generally is measured using molecules less than 5 kDa, measured GFR could be normal in the situation described above with selectively lowered sieving coefficients for molecules between 5 and 40 kDa, even in the presence of an abnormal ultrafiltrate and specific changes in the plasma levels of certain proteins indicating impaired filtration quality. As SPS is connected to a strong increase in mortality and morbidity, even in the absence of reduced GFR,6, 7, 8, 9 it may be important to measure “filtration quality” 32 in addition to GFR when screening for kidney disease. Present screening for CKD includes eGFR, based on creatinine, cystatin C, or both, as well as the urinary albumin-to-creatinine ratio.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that an eGFR cystatin C /eGFR creatinine ratio ≤0.60 represents a new syndrome, called shrunken pore syndrome (SPS), 5 as the glomerular filtration of 12- to 29-kDa molecules seemed to be selectively impaired 4, 5. The long-term mortality6, 7, 8 and morbidity8, 9 of patients with SPS have been shown to be strongly increased in several cohorts, even in the absence of reduced GFR. Moreover, cardiovascular manifestations have represented a major part of the mortality 6, 7, 8, 9, 10.…”

mentioning

confidence: 99%

“…The long-term mortality6, 7, 8 and morbidity8, 9 of patients with SPS have been shown to be strongly increased in several cohorts, even in the absence of reduced GFR. Moreover, cardiovascular manifestations have represented a major part of the mortality 6, 7, 8, 9, 10. All of these studies have used cystatin C−based and/or creatinine-based GFR estimating equations to estimate GFR, but in an ongoing investigation of 2805 patients with measured GFR, SPS is also associated with a markedly shortened survival (A. Grubb, J. Björk, unpublished data).…”

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confidence: 99%

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Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins

Almén

Björk

Nyman

et al. 2019

Kidney International Reports

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IntroductionShrunken pore syndrome (SPS), originally defined by cystatin C−based estimated glomerular filtration rate (eGFRcystatin C) being less than 60% of creatinine-based estimated glomerular filtration rate (eGFRcreatinine) in the absence of extrarenal influences on the plasma levels of cystatin C or creatinine, is associated with a high increase in mortality, even in the absence of reduced glomerular filtration rate (GFR). The objective of the present study was to determine whether the proteome of patients with SPS shows differences from that of patients with normal or reduced measured GFR (mGFR) without SPS.MethodsFour patient cohorts were included: 1 cohort with normal mGFR without SPS, 1 with normal mGFR with SPS, 1 with reduced mGFR without SPS, and 1 with reduced mGFR with SPS. The plasma levels of 177 selected proteins were analyzed.ResultsDifferences in the levels of 30 proteins were specific for SPS; 31 differences were specific for patients with both SPS and reduced mGFR; and 27 were specific for reduced mGFR. Eighteen of the differences specific for SPS concerned proteins described as promoting, or being associated with, atherosclerosis. Twelve of the differences specific for patients with both SPS and reduced mGFR and 10 of the differences specific for reduced mGFR also concerned proteins described as promoting, or being associated with, atherosclerosis. Almost all (82 of 88) of the concentration differences represented increased levels. For SPS, but not for reduced mGFR, a correlation between protein size and increase in level was observed, with smaller proteins being associated with higher levels.ConclusionThe high mortality in shrunken pore syndrome might be caused by the accumulation of atherosclerosis-promoting proteins in this condition.

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confidence: 99%

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Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins

Almén

Björk

Nyman

et al. 2019

Kidney International Reports

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“…Recent studies in select adult populations have shown that close to 10% of patients studied display a ratio of eGFR cys to eGFR creat less than or equal to 0.6, which has been defined by researchers as indicative of shrunken pore syndrome [ 49 ]. These patients are at generally increased risk for morbidity and mortality, and at higher risk for right ventricular dysfunction and for death after coronary artery bypass grafting [ 11 – 13 ]. It is unknown to what extent the hypothesized shrunken pore syndrome may explain differences in GFR estimates in elderly populations compared to other non-GFR determinants of cystatin C and creatinine that were found to be correlated to differences in eGFR in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…Better understanding of affected subgroups could lead to recommendations on which biomarker to favor when choosing an equation for a patient in a particular subgroup, or could lead to development of additional correction coefficients for non-GFR determinants of biomarker concentrations. Some recent studies have also indicated that a large difference between cystatin C based and creatinine based eGFR can be a marker for increased risk for morbidity and mortality [ 11 – 13 ]. The pathophysiology of this association has not been determined although glomerular pore size has been hypothesized to play a role.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and determinants of differences in cystatin C and creatinine-based estimated glomerular filtration rate in community-dwelling older adults: a cross-sectional study

et al. 2017

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BackgroundDifferences in cystatin C and creatinine-based estimated glomerular filtration rate (eGFR) can lead to clinical uncertainty. Existing eGFR equations perform poorly in a subset of individuals. This study aims to describe the prevalence of differences between cystatin C-based (eGFRcys) and creatinine-based (eGFRcreat) eGFR in older adults and to explore which subsets of individuals may be most affected by differing estimations.MethodsIn this cross-sectional study, participants from a cohort of community-dwelling older adults were examined at a baseline visit in 2001-2004 as part of the larger “Good Aging in Skåne” study. Exposure variables were obtained from questionnaires, interviews, examinations, and medical records. Blood samples were taken during the baseline visit, cryopreserved, and analyzed at a later time for biomarkers. The CKD-EPI equations were used to estimate GFR. Initial descriptive analyses were performed on 2931 individuals. A total of 2532 participants were included in the final multiple linear regression.ResultsNearly two-thirds of participants had eGFR differences exceeding 10%, with nearly 20 % of participants having eGFR differences exceeding 30%. Smoking, age, body mass index (BMI), C-reactive protein (CRP), glucocorticoid use, and mean eGFR were correlated with differences between eGFRcreat and eGFRcys.ConclusionsDifferences between eGFRcreat and eGFRcys are common and often of large magnitude in this community-dwelling population of older adults. The finding of multiple non-GFR determinants correlated to differences in GFR estimations can help direct future research to improve eGFR equations for subgroups prone to conflicting GFR estimations or to guide choice of biomarker for GFR estimation in these subgroups.Electronic supplementary materialThe online version of this article (10.1186/s12882-017-0759-3) contains supplementary material, which is available to authorized users.

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The Shrunken pore syndrome is associated with poor prognosis and lower quality of life in heart failure patients: the HARVEST‐Malmö study

et al. 2021

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Aims This study aimed to investigate the association between the 'Shrunken pore syndrome' (SPS) and risk of death, 30 day rehospitalization, and health-related quality of life (QoL) in heart failure (HF) patients. SPS is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFR cystatin C /eGFR creatinine ratio. Methods and results A total of 373 patients hospitalized for HF [mean age 74.8 (±12.1) years; 118 (31.6%) women] were retrieved from the HeARt and brain failure inVESTigation trial (HARVEST-Malmö). Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were used for estimation of glomerular filtration rate (eGFR). Presence of SPS was defined as eGFR cystatin C ≤ 60% of eGFR creatinine . In Cox regression multivariate models, associations between SPS, risk of death (median follow-up time 1.8 years), and risk of 30 day rehospitalization were studied. Associations between SPS and impaired QoL were studied using multivariate logistic regressions. In multivariate models, SPS was associated with all-cause mortality [124 events; hazard ratio (HR) 1.99; 95% confidence interval (95% CI) 1.23-3.21; P = 0.005] and with 30 day rehospitalization (70 events; HR 1.82; CI 95% 1.04-3.18; P = 0.036). Analyses of QoL, based on a Kansas City Cardiomyopathy Questionnaire overall score < 50, revealed that SPS was associated with higher risk of low health-related QoL (odds ratios 2.15; CI 95% 1.03-4.49; P = 0.042). Conclusions The results of this observational study show for the first time an association between SPS and poor prognosis in HF. Further studies are needed to confirm the results in HF cohorts and experimental settings to identify pathophysiological mechanisms.

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Ratio of cystatin C and creatinine-based estimates of the glomerular filtration rate predicts mortality in healthy seniors independent of kidney function

Cited by 22 publications

References 9 publications

Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins

Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins

Prevalence and determinants of differences in cystatin C and creatinine-based estimated glomerular filtration rate in community-dwelling older adults: a cross-sectional study

The Shrunken pore syndrome is associated with poor prognosis and lower quality of life in heart failure patients: the HARVEST‐Malmö study

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