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The cardiorenal syndrome: Structural and functional aspects including associations with the shrunken pore syndrome

Xhakollari, Liana LU (2021) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Mild to moderate renal impairment affects 10% of the general population. Renal impairment is difficult to detect because of the lack of symptoms, but it can be estimated by calculating the estimated glomerular filtration rate (eGFR) on the basis of plasma creatinine and/or cystatin C concentrations. Chronic kidney disease (CKD) is associated with an increased risk of development of cardiovascular disease and an increase in the mortality rate. As kidney function decreases, structural and functional changes in the heart increase. Cardiovascular disease also affects renal function, leading to CKD. This pathophysiological association between the two organs is referred to as cardiorenal syndrome (CRS). Mortality and morbidity rates are... (More)
Mild to moderate renal impairment affects 10% of the general population. Renal impairment is difficult to detect because of the lack of symptoms, but it can be estimated by calculating the estimated glomerular filtration rate (eGFR) on the basis of plasma creatinine and/or cystatin C concentrations. Chronic kidney disease (CKD) is associated with an increased risk of development of cardiovascular disease and an increase in the mortality rate. As kidney function decreases, structural and functional changes in the heart increase. Cardiovascular disease also affects renal function, leading to CKD. This pathophysiological association between the two organs is referred to as cardiorenal syndrome (CRS). Mortality and morbidity rates are increased in patients with CRS, and early detection of this syndrome can lead to a reduction in the disease burden. To more accurately stage CKD and calculate the mortality risk, the eGFR based on creatinine (eGFRCR) and cystatin C (eGFRCYS) is recommended for use in clinical practice. The eGFRCYS and eGFRCR usually correspond well with each other. In some individuals, the eGFRCYS/eGFRCR ratio is < 0.7, and it is associated with increased morbidity and mortality. A selective decrease in renal filtration of cystatin C is thought to cause the difference between eGFRCYS and eGFRCR, and this condition is called shrunken pore syndrome (SPS). This thesis presents studies on the early detection of CRS and the association of SPS with mortality and morbidity in patients with heart failure (HF) and in individuals who were randomly chosen from a population-based cohort. In Paper I, data from 1504 individuals without HF from the Malmö Prevention Project, which is a population-based cohort, showed significant associations between mild to moderate impairment of renal function and echocardiographic markers of cardiac structure and diastolic function. These findings support the hypothesis that there is an interaction between the kidney and heart, even at eGFR 45–60 mL/min/1.73 m2. In Papers II and III, data from approximately 300 hospitalized patients with HF from the HeARt and brain failure inVESTigation trial showed an association between SPS and a doubled risk of all-cause mortality, higher risk of 30-day rehospitalization, and impaired quality of life. Proteomic analyses showed that in patients with HF, SPS was associated with proteins related to atherosclerosis and cell proliferation. These findings may help identify pathophysiological pathways involved in the known adverse effects of SPS. In Paper IV, data from 5061 individuals from the Malmö Diet and Cancer cardiovascular cohort, which is a population-based cohort, showed that SPS affected as much as 8% of the general middle-aged population, and that individuals with SPS had a 38% higher risk of all-cause mortality. In conclusion, structural changes in the heart can develop already at mild to moderate impairment of renal function. SPS is an important predictor of mortality in patients with HF and in individuals in the general population. Further studies are required to investigate the pathophysiology of SPS and the mechanism behind the association between SPS and mortality. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Senior Professor Stegmayr, Bernd, Umeå University
organization
alternative title
Det kardiorenala syndromet: strukturella och funktionella aspekter inklusive associationer med Krympt por-syndrom
publishing date
type
Thesis
publication status
published
subject
keywords
cardiorenal syndrome, Shrunken Pore Syndrome, mortality, cystatin C, eGFR, cardiovascular disease, chronical kidney disease
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2021:135
pages
68 pages
publisher
Lund University, Faculty of Medicine
defense location
Wroblevskisalen, Ruth Lundskogsgatan 5, 5th floor, Skånes Universitetssjukhus i Malmö. Join by Zoom: https://lu-se.zoom.us/j/64598586669
defense date
2021-12-09 13:00:00
ISSN
1652-8220
ISBN
978-91-8021-142-0
language
English
LU publication?
yes
id
81c858e6-0d9a-423d-9885-2f3aa2123bd8
date added to LUP
2021-11-15 13:32:26
date last changed
2021-11-20 10:45:58
@phdthesis{81c858e6-0d9a-423d-9885-2f3aa2123bd8,
  abstract     = {{Mild to moderate renal impairment affects 10% of the general population. Renal impairment is difficult to detect because of the lack of symptoms, but it can be estimated by calculating the estimated glomerular filtration rate (eGFR) on the basis of plasma creatinine and/or cystatin C concentrations. Chronic kidney disease (CKD) is associated with an increased risk of development of cardiovascular disease and an increase in the mortality rate. As kidney function decreases, structural and functional changes in the heart increase. Cardiovascular disease also affects renal function, leading to CKD. This pathophysiological association between the two organs is referred to as cardiorenal syndrome (CRS). Mortality and morbidity rates are increased in patients with CRS, and early detection of this syndrome can lead to a reduction in the disease burden. To more accurately stage CKD and calculate the mortality risk, the eGFR based on creatinine (eGFRCR) and cystatin C (eGFRCYS) is recommended for use in clinical practice. The eGFRCYS and eGFRCR usually correspond well with each other. In some individuals, the eGFRCYS/eGFRCR ratio is &lt; 0.7, and it is associated with increased morbidity and mortality. A selective decrease in renal filtration of cystatin C is thought to cause the difference between eGFRCYS and eGFRCR, and this condition is called shrunken pore syndrome (SPS). This thesis presents studies on the early detection of CRS and the association of SPS with mortality and morbidity in patients with heart failure (HF) and in individuals who were randomly chosen from a population-based cohort. In Paper I, data from 1504 individuals without HF from the Malmö Prevention Project, which is a population-based cohort, showed significant associations between mild to moderate impairment of renal function and echocardiographic markers of cardiac structure and diastolic function. These findings support the hypothesis that there is an interaction between the kidney and heart, even at eGFR 45–60 mL/min/1.73 m2. In Papers II and III, data from approximately 300 hospitalized patients with HF from the HeARt and brain failure inVESTigation trial showed an association between SPS and a doubled risk of all-cause mortality, higher risk of 30-day rehospitalization, and impaired quality of life. Proteomic analyses showed that in patients with HF, SPS was associated with proteins related to atherosclerosis and cell proliferation. These findings may help identify pathophysiological pathways involved in the known adverse effects of SPS. In Paper IV, data from 5061 individuals from the Malmö Diet and Cancer cardiovascular cohort, which is a population-based cohort, showed that SPS affected as much as 8% of the general middle-aged population, and that individuals with SPS had a 38% higher risk of all-cause mortality. In conclusion, structural changes in the heart can develop already at mild to moderate impairment of renal function. SPS is an important predictor of mortality in patients with HF and in individuals in the general population. Further studies are required to investigate the pathophysiology of SPS and the mechanism behind the association between SPS and mortality.}},
  author       = {{Xhakollari, Liana}},
  isbn         = {{978-91-8021-142-0}},
  issn         = {{1652-8220}},
  keywords     = {{cardiorenal syndrome; Shrunken Pore Syndrome; mortality; cystatin C; eGFR; cardiovascular disease; chronical kidney disease}},
  language     = {{eng}},
  number       = {{2021:135}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{The cardiorenal syndrome: Structural and functional aspects including associations with the shrunken pore syndrome}},
  url          = {{https://lup.lub.lu.se/search/files/109755281/Liana_Xhakollari_WEBB.pdf}},
  year         = {{2021}},
}