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

Abstract

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.

Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis

“…endothelial dysfunction. Endothelial dysfunction is an early indicator of cardiovascular disease and renal dysfunction [23], and our findings of the predictive value of a decreased ratio 10 years before AVR suggest that the process leading to AVR starts early, that is supported by recent observations on the accumulation of atherosclerosispromoting proteins in shrunken pore syndrome [21]. Microalbuminuria has been found to be associated with cardiovascular disease and endothelial dysfunction, e.g.…”

“…A low ratio between eGFR cystatin C and eGFR creatinine has recently been suggested as representing a new syndrome, named shrunken pore syndrome [5], and has been shown to be a risk marker for cardiovascular disease and mortality [6,7,21,22], including subjectively healthy elderly [8]. An increased retention of 5-40 kDa molecules compared to small molecules, like creatinine and water, has been described in this condition.…”

“…An increased retention of 5-40 kDa molecules compared to small molecules, like creatinine and water, has been described in this condition. These larger molecules include atherosclerosis-promoting proteins [5,21]. A recent study showed that the lower the ratio between the eGFR cystatin C and eGFR creatinine used to identify the syndrome, the higher was the mortality associated with it [22].…”

Proteins linked to atherosclerosis and cell proliferation are associated with the shrunken pore syndrome in heart failure patients

“…Only three of the proteins used in these two panels overlap (monocyte chemotactic protein 1 (MCP-1), osteoprotegerin (OPG) and urokinasetype plasminogen activator (uPA) and we were able to confirm the association between SPS and OPG but not with MCP-1. No associa-tions between uPA and SPS were seen in neither the study by Almen et al, nor our study) [13].…”

Cystatin C and α-1-Microglobulin Predict Severe Acute Kidney Injury in Patients with Hemorrhagic Fever with Renal Syndrome

“…In another study, patients in need of cardiac surgery had higher 1-and 3-year mortality if they had SPS at the time of operation [41]. The underlying mechanism for the observed increased long-term mortality and morbidity has been proposed to be due to increased levels of proteins that facilitate atherosclerosis [42]. Our study is a short-term study, where transient increase of kidney damage markers during an acute viral infection are investigated.…”