Purpose:The "Shrunken pore syndrome" (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFR cystatinC /eGFR creatinine -ratio. Studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure. Experimental Design: Plasma samples from 300 individuals in HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 74.9 ± 11.5 years; 30.0% female), were analyzed with a proximity extension assay consisting of 92 proteins. A Bonferroni-corrected p-value of 0.05/92 = 5.4 × 10 −4 was considered significant in the initial age and sex-adjusted analyses. Presence of SPS was defined as eGFR cystatinC ≤ 60% of eGFR creatinine .Results: SPS presented with significant associations (p < 5.4 × 10 −4 ) in age and sexadjusted logistic regressions with elevated levels of six proteins; scavenger receptor cysteine rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosineprotein kinase receptor UFO. All proteins remained associated (p < 0.05) with SPS after multivariate adjustments. Conclusions and clinical relevance:In heart failure patients, SPS was associated with proteins linked to atherosclerosis and cell proliferation.

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endoge-nous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, # Linnea Malmgren and Carl Öberg contributed equally as first authors.

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.