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Background: In 2015, a selective decrease in the glomerular filtration of middle‐sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed "Shrunken pore syndrome." Numerous studies have thereafter found an association between this syndrome (defined by a low eGFRcystatin C to eGFRcreatinine ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFRcystatin C and eGFRcreatinine to describe a similar disorder, and this investigation compares the two measures. Methods: Using a cohort of 2781 adults with a median follow‐up of 5.6 years, referred for determination of glomerular filtration rate (GFR), estimated GFR (eGFR) was determined using four equations. SGHS was defined using the eGFRdifference and the eGFRratio and association to mortality investigated through adjusted Cox proportional hazard models. From each adjusted regression model, Harrell's C‐index and 95% confidence intervals were calculated. Results: Both measures were associated with mortality. No significant differences concerning hazard ratios or Harrell's C‐index were found between the two measures to estimate mortality, and both identified SGHS and increased mortality in a subpopulation of 567 "healthy" individuals with no prior diagnosis and with no kidney disorder according to the kidney disease improving global outcomes‐criteria. Conclusion: The eGFRdifference is not superior to the eGFRratio in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Shrunken pore syndrome (SPS) is defined as eGFRcystatin C/eGFRcreatinine ratio <0.70 and predicts high CVD mortality. The Framingham Risk Score (FRS) is used to estimate an individual’s 10-year CVD risk. This study investigated the association between FRS and eGFRcystatin C/eGFRcreatinine ratio in T2DM patients. Patients aged 18-80 years who were newly diagnosed with T2DM were included in this retrospective study. Ordinal logistic regression analysis was used to investigate the association between risk factors of T2DM and FRS. A Generalized Linear Model was used to calculate odds ratios (OR) and 95% confidence intervals (CI). There were 270 patients included in the study. Only 27 patients (10%) met the diagnostic criteria of SPS. Ordinal logistic regression analysis showed that SPS was not correlated with FRS risk (OR = 1.99, 95%CI = 0.94–4.23, p = 0.07), whereas eGFRcystatin C/eGFRcreatinine (OR = 0.86, 95%CI = 0.77–0.97, p = 0.01) showed a significant negative association with FRS risk. Compared with eGFRcystatin C/eGFRcreatinine>0.85, eGFRcystatin C/eGFRcreatinine≤0.85 increased FRS risk (OR = 1.95, 95%CI = 1.18–3.21, p < 0.01). After adjustment for confounding factors, increased eGFRcystatin C/eGFRcreatinine ratio was associated with decreased FRS risk when considered as a continuous variable (OR = 0.87, 95%CI = 0.77–0.99, p = 0.03). The FRS risk in patients with eGFRcystatin C/eGFRcreatinine≤0.85 is 1.86 times higher than that in patients with eGFRcystatin C/eGFRcreatinine>0.85 (OR = 1.86, 95%CI = 1.08–3.21, p = 0.03). In the current study, no significant association between SPS and FRS was identified. However, lower eGFRcystatin C/eGFRcreatinine and eGFRcystatin C/eGFRcreatinine≤0.85 were associated with a significantly increased CVD risk in T2DM. [ABSTRACT FROM AUTHOR]

A low eGFRcystatin C/eGFRcreatinine-ratio is characteristic of a group of serious kidney disorders called 'Selective Glomerular Hypofiltration Syndromes'. This study examines if such a low ratio can also be used to evaluate the risk for women with hypertensive disorders in pregnancy to develop severe maternal morbidity. All women discharged from the perinatal ward at the Skåne University Hospital in Lund during the period of 1-9-2016 to 31-8-2017 under one of the diagnoses within hypertensive disorders in pregnancy were considered for inclusion in the study. After delivery and discharge from the hospital, records from included patients were reviewed and all registered measures of renal function were analysed. An eGFRcystatin C/eGFRcreatinine-ratio ≤0.60 in a sample drawn not earlier than three days before delivery was considered as defining a high risk for severe maternal morbidity. A strong association (p-value: 0.035) between severe maternal morbidity and an eGFRcystatin C/eGFRcreatinine-ratio ≤0.60 was found in a subgroup of 32 women diagnosed with 'preeclampsia with severe features'. A total of 69 women were included in the study. Fifty were defined as high-risk and seventeen of them (34%) developed severe maternal morbidity. Among the nineteen women defined as low-risk only two (10.5%) developed severe maternal morbidity (p-value: 0.051). A low eGFRcystatin C/eGFRcreatinine-ratio seems promising as a predictive marker for maternal morbidity in hypertension in pregnancy. Its performance as a tool in the monitoring of progressing disease should be evaluated further in larger cohorts. Delivery before the eGFRcystatin C/eGFRcreatinine-ratio decreases to, or below, 0.60 might help avoid maternal complications. [ABSTRACT FROM AUTHOR]

The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, β2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was −0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes. [ABSTRACT FROM AUTHOR]

Abstract Background Shrunken Pore Syndrome (SPS), defined as a reduced ratio between two estimated filtration rates (based on cystatin C and creatinine) is an increasingly recognized risk factor for long-term mortality. Although some patients with other conditions might be erroneously identified as SPS. Our aim was to bring the focus on possible pathophysiologic mechanisms influencing the ratio in the setting of SARS-CoV-2 pneumonia and acute kidney injury. Methods A single-centered prospective cohort study was conducted to investigate biomarkers in symptomatic COVID-19 pneumonia patients admitted to a hospital in Latvia. Nineteen biomarkers were measured in blood and three in urine samples. Associations were sought between these biomarkers, chronic diseases and the estimated GFRcystatinC/eGFRcreatinine ratio

Background: Shrunken pore syndrome (SPS) is defined as cystatin C‐based‐eGFR (eGFRcys)/creatinine‐based‐eGFR (eGFRcreat) <0.6 or 0.7 and is associated with an increased cardiovascular risk. SPS has been described in children, but no link to increased morbi‐mortality was demonstrated. Objectives: Study the prevalence of SPS in a pediatric population using several glomerular filtration rate (GFR) estimating formulas and measured GFR and evaluate the potential link with cardiovascular risk. Methods: In 307 renal risk pediatric patients, we studied prevalence of SPS either with CKiDU25creat and cyst or with FAScreat and cyst and EKFCcreat. The characteristics of patients with SPS (defined with Full‐age spectrum equation (FAS) and/or European Kidney Function Consortium equation (EKFC)) were compared. Results and conclusion: The prevalence of SPS varies widely depending on the threshold and the formulas used. Higher C‐reactive protein (CRP) and phosphate levels and smaller size are observed in children with SPS defined with FAS and/or EKFC and might be associated with long‐term increased cardiovascular risk. Further studies in wider general pediatric populations are warranted. [ABSTRACT FROM AUTHOR]

Background: Shrunken Pore Syndrome (SPS), defined as a reduced ratio between two estimated filtration rates (based on cystatin C and creatinine) is an increasingly recognized risk factor for long-term mortality. Although some patients with other conditions might be erroneously identified as SPS. Our aim was to bring the focus on possible pathophysiologic mechanisms influencing the ratio in the setting of SARS-CoV-2 pneumonia and acute kidney injury. Methods: A single-centered prospective cohort study was conducted to investigate biomarkers in symptomatic COVID-19 pneumonia patients admitted to a hospital in Latvia. Nineteen biomarkers were measured in blood and three in urine samples. Associations were sought between these biomarkers, chronic diseases and the estimated GFRcystatinC/eGFRcreatinine ratio < 0.6, mortality rates, and acute kidney injury development. Data analysis was performed using SPSS Statistics, with significance set at p < 0.05. Results: We included 59 patients (average age 65.5 years, 45.8% female) admitted with COVID-19. Acute kidney injury occurred in 27.1%, and 25.4% died. Ratio < 0.6 was seen in 38.6%, associated with female sex, diabetes, hypothyroidism, and higher age. Ratio < 0.6 group had mortality notably higher − 40.9% vs. 16.2% and more cases of acute kidney injury (40.9% vs. 18.9%). Cystatin C showed strong associations with the ratio < 0.6 compared to creatinine. Urea levels and urea/creatinine ratio were higher in the ratio < 0.6 group. After excluding acute kidney injury patients, ratio < 0.6 remained associated with higher cystatin C and urea levels. Other biomarkers linked to a kidney injury as NGAL, and proteinuria did not differ. Conclusion: We prove that reduced ratio is common in hospitalized patients with SARS-CoV-2 pneumonia and is associated with increased mortality during hospitalization. Factors that influence this ratio are complex and, in addition to the possible shrinkage of pores, other conditions such as thickening of glomerular basal membrane, comorbidities, prerenal kidney failure and others may play an important role and should be addressed when diagnosing SPS. We highlight the need for additional diagnostic criteria for SPS and larger studies to better understand its implications in acute COVID-19 settings. [ABSTRACT FROM AUTHOR]

In this issue of Clinical Kidney Journal , Stehlé and colleagues demonstrate that estimation of glomerular filtration rate (GFR) by use of creatinine and a measure, total lumbar muscle cross-sectional area, reflecting the total muscle mass of an individual, is superior to GFR-estimating equations based upon creatinine and demographic variables. The report by Stehlé et al. demonstrates one solution to the interference of muscle mass in the use of creatinine to estimate GFR. This interference was identified already at the start, in 1959, of using creatinine for estimation of GFR. Different ways of taking the muscle mass into account when creatinine-based estimations of GFR have been used generally include use of controversial race and sex coefficients. A new marker of GFR, cystatin C, introduced in 1979, has been shown to be virtually uninfluenced by muscle mass. In this editorial, the simultaneous use of creatinine and cystatin C to estimate GFR, muscle mass and selective glomerular hypofiltration syndromes is described. [ABSTRACT FROM AUTHOR]

A selective decrease in the renal filtration of larger molecules is attributed to the shrinkage of glomerular pores, a condition termed Shrunken Pore Syndrome (SPS). SPS is associated with poor long-term prognosis. We studied SPS as a risk marker in a cohort of patients with COVID-19 treated in an intensive care unit. SPS was defined as a ratio < 0.7 when the estimated glomerular filtration rate (eGFR), determined by cystatin C, calculated by the Cystatin C Caucasian-Asian-Pediatric-Adult equation (CAPA), was divided by the eGFR determined by creatinine, calculated by the revised Lund–Malmö creatinine equation (LMR). Clinical data were prospectively collected. In total, SPS was present in 86 (24%) of 352 patients with COVID-19 on ICU admission. Patients with SPS had a higher BMI, Simplified Physiology Score (SAPS3), and had diabetes and/or hypertension more frequently than patients without SPS. Ninety-nine patients in the total cohort were women, 50 of whom had SPS. In dexamethasone-naïve patients, C-reactive protein (CRP), TNF-alpha, and interleukin-6 did not differ between SPS and non-SPS patients. Demographic factors (gender, BMI) and illness severity (SAPS3) were independent predictors of SPS. Age and dexamethasone treatment did not affect the frequency of SPS after adjustments for age, sex, BMI, and acute severity. SPS is frequent in severely ill COVID-19 patients. Female gender was associated with a higher proportion of SPS. Demographic factors and illness severity were independent predictors of SPS. [ABSTRACT FROM AUTHOR]

Background Shrunken pore syndrome (SPS) as a novel phenotype of renal dysfunction is characterized by a difference in renal filtration between cystatin C and creatinine. The manifestation of SPS was defined as a cystatin C–based estimated glomerular filtration rate (eGFR)

Childhood cancer survivors (CCS) are at risk of kidney dysfunction. Recently, the shrunken pore syndrome (SPS) has been described, which is characterized by selectively impaired filtration of larger molecules like cystatin C, while filtration of smaller molecules like creatinine is unaltered. It has been associated with increased mortality, even in the presence of a normal estimated glomerular filtration rate (eGFR). The aim of this study was to evaluate the prevalence of SPS in CCS exposed to potentially nephrotoxic therapy. In the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 Renal study, a nationwide cross-sectional cohort study, 1024 CCS ≥5 years after diagnosis, aged ≥18 years at study, treated between 1963-2001 with nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide or hematopoietic stem cell transplantation participated, and 500 age- and sex-matched controls form Lifelines. SPS was defined as an eGFRcys/eGFRcr ratio <0.6 in the absence of non-GFR determinants of cystatin C and creatinine metabolism (i.e. hyperthyroidism, corticosteroids, underweight). Three pairs of eGFR-equations were used; CKD-EPIcys/CKD-EPIcr, CAPA/LMR, and FAScys/FASage. Median age was 32 years. Although an eGFRcys/eGFRcr ratio <0.6 was more common in CCS (1.0%) than controls (0%) based on the CKD-EPI equations, most cases were explained by non-GFR determinants. The prevalence of SPS in CCS was 0.3% (CKD-EPI equations), 0.2% (CAPA/LMR) and 0.1% (FAS equations), and not increased compared to controls. CCS treated with nephrotoxic therapy are not at increased risk for SPS compared to controls. Yet, non-GFR determinants are more common and should be taken into account when estimating GFR. [ABSTRACT FROM AUTHOR]

Impaired renal function is associated both with the development of cardiovascular disease and its prognosis. A new syndrome called ′Shrunken Pore Syndrome′ has been suggested, as the estimated glomerular filtration rate for cystatin C (eGFRcystatin C) is affected earlier due to differences in molecular size compared to eGFRcreatinine. The aim was to investigate if a lower eGFRcystatin C/eGFRcreatinine ratio in a prospective setting increases the risk of later developing a first-ever myocardial infarction (MI) independently of other cardiovascular risk factors. We used a nested case-referent study design within the Northern Sweden Health and Disease Study, and 545 subjects (29.0% women) were identified who prospectively developed a first-ever MI, and their 1054 matched referents. For women, but not for men, one standard deviation (SD) increase of ln z-scores of eGFRcystatin C/eGFRcreatinine ratio was associated with a lower risk of a future MI: odds ratio [95% confidence interval] 0.58 [0.34–0.99], adjusted for apolipoprotein B/A1 ratio, CRP, homocysteine, systolic blood pressure, body mass index, and diabetes. Furthermore, a high eGFRcreatinine associated independently with an increased risk of future MI in men only: OR 1.25 [1.05–1.48]. Thus, for women, a lower eGFRcystatin C/eGFRcreatinine ratio is associated with a higher risk of having a future first-ever MI, and it may be a valuable, easily implemented biomarker for risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

A major function of the kidney is to, by glomerular filtration, maintain the overall steady‐state of 5–30 kDa proteins, many of which are signalling molecules. This function of the kidney has been overlooked, since predominantly low‐molecular‐mass substances <1 kDa have been used to measure or estimate glomerular filtration rate (GFR). The use of cystatin C (13 kDa) as a marker of GFR has allowed the discovery that the filtration of 5–30 kDa molecules can be selectively impaired defining the shrunken pore syndrome. The discovery, pathophysiology, morbidity (mainly cardiovascular manifestations) and mortality of this syndrome are described. [ABSTRACT FROM AUTHOR]

GİRİŞ: Sistatin C bazlı tahmini Glomerüler filtrasyon hızı (GFR) ölçümleri son dönem böbrek yetmezliği, kardiyovasküler bulgular ve mortaliteyi öngörmede kreatinin bazlı ölçümlerden üstün olup; cinsiyet, yaş ve kas kitlesinden bağımsızdır. Bazı olgularda sistatin C’nin filtrasyonunun, kreatinine göre daha az olduğu gözlemlenmiş ve bunun porların daralmasından kaynaklandığı kanıtlanmıştır. Sistatin C bazlı tahmini GFR (eGFRsistatin C), kreatinin bazlı tahmini GFR’nin (eGFRkreatinin) %60’ına eşit veya bunun altında olması patofizyolojik olarak ‘Shrunken Pore Sendromu’ olarak tanımlanmıştır. Bu yazıda Shrunlen Pore sendromlu bir kız olgudan bahsedildi. OLGU: 16 aylık kız hastanın meningomiyelosel ve nörojenik mesane ile Ege Üniversitesi Çocuk Nefroloji polikliniğine başvurdu. Özgeçmişinde antenatal meningomyelosel ve hidrosefali nedeniyle Arnold Chiari tip 2 tanısı, postnatal 1. günde meningomyelosel kesesi eksizyonu ve ventriküloperitoneal şant operasyonu mevcuttu. Piyelonefrit öyküsü yoktu. Fizik bakısında; dismorfik yüz görünümü, parapleji, belde operasyon skarı, ayak parmaklarında sindaktili mevcuttu. Laboratuvar incelemesinde; üre:24 mg/dL, kreatinin: 0,3 mg/dL, parathormon: 47 ng/mL, Sistatin C 1,4 mg/L (RA:0.53-0.95), kan beta 2 mikroglobulin: 2716 ng/mL idi. Hastanın eGFRsistatin C: 107 ml/ dk/1.73m2 ve eGFRkreatinin: 188 ml/dk/1,73m2 idi. Hastada eGFR sistatin C değeri ile eGFRkreatinin değeri arasındaki farktan dolayı Shrunken Pore Sendromu düşünüldü. SONUÇ: Shrunken Pore Sendromlu hastalarda artmış kardiyak mortalite riski belirtildiğinden; GFR belirteci olarak sistatin C‘nin kullanılması, hem kardiyak riskli hastaları hem de hastalığın gerçek prevalansını belirlemeyi sağlamakta önem taşımaktadır.

INTRODUCTION: Creatinine was started to be used as a marker of glomerular filtration rate (GFR) in 1920’s. Later in the 1990s, cystatin C was shown to be superior to creatinine in assessing GFR. In some patients, glomerular filtration of cystatin C was found to be low compared to creatinine, and it was hypothesized that glomerular pores may have been shrunken in these patients. For the group of patients having a cystatin C based estimation of GFR (eGFR cystatin C) to creatinine-based estimation of GFR (eGFR creatinine) ratio of ≤60%, the pathophysiological classification is defined as Shrunken Pore Syndrome. CASE: A 16-month-old female patient was admitted to Ege University Pediatric nephrology clinic with the diagnosis of neurogenic bladder secondary to meningomyelocele. She had a history of antenatal meningomyelocele, and hydrocephalus diagnosed as Arnold Chiari type 2. On postnatal day 1, she had undergone meningomyelocele sac excision and ventriculoperitoneal shunt operation. There was no history of pyelonephritis. Systemic examination revealed a dysmorphic facial appearance, operation scar on her back and syndactyly of the toes, and paraplegia on neurological examination. In laboratory examination; urea: 24 mg/dL, creatinine: 0.3 mg/dL, parathormone: 47 ng/mL, cystatin C: 1.4 mg/L (RR: 0.53-0.95), blood β2 microglobulin: 2716 ng/mL. Patient’s eGFRcystatin C: 107 ml/min/1.73m2 and eGFRcreatinine: 188 ml/min/1.73m2. Shrunken Pore Syndrome was considered due to the difference between the patient's eGFRcystatin C value and eGFRcreatinine value. CONCLUSION: Shrunken Pore Syndrome has no known treatment; however, it is important to diagnose these patients because of accompanying risks such as increased cardiac mortality. With the usage of cystatin C as a marker of GFR, possible mortality risks can be predictable and preventive measures can be taken early on.

INTRODUCTION: Creatinine was started to be used as a marker of glomerular filtration rate (GFR) in 1920’s. Later in the 1990s, cystatin C was shown to be superior to creatinine in assessing GFR. In some patients, glomerular filtration of cystatin C was found to be low compared to creatinine, and it was hypothesized that glomerular pores may have been shrunken in these patients. For the group of patients having a cystatin C based estimation of GFR (eGFR cystatin C) to creatinine-based estimation of GFR (eGFR creatinine) ratio of ≤60%, the pathophysiological classification is defined as Shrunken Pore Syndrome. CASE: A 16-month-old female patient was admitted to Ege University Pediatric nephrology clinic with the diagnosis of neurogenic bladder secondary to meningomyelocele. She had a history of antenatal meningomyelocele, and hydrocephalus diagnosed as Arnold Chiari type 2. On postnatal day 1, she had undergone meningomyelocele sac excision and ventriculoperitoneal shunt operation. There was no history of pyelonephritis. Systemic examination revealed a dysmorphic facial appearance, operation scar on her back and syndactyly of the toes, and paraplegia on neurological examination. In laboratory examination; urea: 24 mg/dL, creatinine: 0.3 mg/dL, parathormone: 47 ng/mL, cystatin C: 1.4 mg/L (RR: 0.53-0.95), blood β2 microglobulin: 2716 ng/mL. Patient’s eGFRcystatin C: 107 ml/min/1.73m2 and eGFRcreatinine: 188 ml/min/1.73m2. Shrunken Pore Syndrome was considered due to the difference between the patient's eGFRcystatin C value and eGFRcreatinine value. CONCLUSION: Shrunken Pore Syndrome has no known treatment; however, it is important to diagnose these patients because of accompanying risks such as increased cardiac mortality. With the usage of cystatin C as a marker of GFR, possible mortality risks can be predictable and preventive measures can be taken early on.

Plasma cystatin C and shrunken pore syndrome (SPS) are associated with increased mortality in older adults. The objective was to assess the association between these markers of kidney function at admission and mortality in hip fracture patients. Hip fracture patients presenting at Lund University Hospital were eligible for inclusion. Cox regression was used to assess association between plasma cystatin C, creatinine, cystatin C- or creatinine-based estimations of glomerular filtration rate (eGFRCYS and eGFRCREA), or SPS (defined as eGFRCYS/eGFRCREA < 0.7) and mortality during one year follow up. Improvement in discrimination relative to the Nottingham Hip fracture score was assessed by Receiver Operational Characteristics (ROC) analysis and calculation of Net Reclassification Index (NRI). 996 patients were included in the study. Cystatin C, creatinine, eGFRCYS and eGFRCREA were associated with one-year mortality in both unadjusted and adjusted analyses. The association with mortality was stronger for cystatin C and for eGFRCYS than for creatinine and eGFRCREA. Patients with SPS had doubled mortality compared with patients without SPS (43.7 and 20.2%, respectively, p <.001). Hazard ratio for SPS in the adjusted analysis was 1.66 (95%CI; 1.16–2.39, p =.006). None of the markers improved discrimination compared to the Nottingham Hip Fracture Score using ROC analysis whereas eGFRCYS and eGFRCREA improved NRI. Our conclusion is that plasma concentrations of creatinine or cystatin C, eGFRCYS or eGFRCREA or SPS at admission in hip fracture patients are associated with mortality when known risk factors are accounted for. Identification of high risk patients may be improved by eGFRCYS or eGFRCREA. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the influence of shrunken pore syndrome (SPS), defined as a cystatin C (CysC)-based estimated glomerular filtration rate (eGFRCysC) <60% of the creatinine (Cr)-based eGFR (eGFRCr), on bone mineral density (BMD) in patients with rheumatic diseases. A total of 831 patients with rheumatic diseases were enrolled in the study. Patients were classified into the SPS group (G-SPS) and non-SPS group (G-nSPS). The correlation between the presence of SPS and BMD of the lumbar spine (BMD_LS), BMD of the femoral neck (BMD_FN), serum parathyroid hormone (PTH) level, chronic kidney dysfunction (CKD), and parameters were evaluated statistically. The prevalence of SPS was 4.0%. Serum PTH level, tartrate-resistant acid phosphatase-5b (TRACP-5b), and eGFRCr in the G-SPS were significantly higher than in the G-nSPS, whereas BMD_LS and BMD_FN in the G-SPS were significantly lower than in the G-nSPS. Serum PTH level was significantly correlated with CysC. BMD_LS had no significant correlation with BMD_FN. The presence of SPS was the only factor that demonstrated significant negative correlation with both BMD_LS and BMD_FN. Relationship between BMD_LS and the presence of SPS was present regardless of CKD stage; however, the negative relationship between BMD_LS and serum PTH was observed only in CKD stage 1 and 2 patients. BMD_FN demonstrated significant negative correlation with serum PTH in the group with progression of CKD. These results suggest that there is a serious potential risk of osteoporosis in patients with SPS and increased PTH, and BMD_LS poses a higher risk in CKD stage 1 and 2. [ABSTRACT FROM AUTHOR]

• Shrunken pore syndrome (SPS) is a newly identified kidney disorder. • SPS is diagnosed by an eGFR cystatin C /eGFR creatinine -ratio below 0.60 in a patient. • The mortality of SPS is high (up to 62%) in many common patient cohorts. • The prevalence of SPS is high (up to 36%) in many relevant patient cohorts. • SPS cannot be diagnosed using the criteria in the KDIGO 2012 guide. Invasive studies show that the glomerular sieving coefficients for 5–30 kDa plasma proteins in the human kidney may be selectively reduced compared to those for small molecules < 0.9 kDa, commonly used to measure glomerular filtration rate (GFR). Identification of this pathophysiological state, called shrunken pore syndrome (SPS), can easily and non-invasively be done by comparing estimations of GFR using cystatin C (13.3 kDa) and creatinine (0.113 kDa). SPS is present if the estimate of GFR using cystatin C is lower than 60 or 70% of the estimate using creatinine in the absence of non-renal influences on cystatin C or creatinine. All studies of SPS show that the 3- or 5-year mortality is strongly increased and high hazard ratios for mortality associated with SPS have been observed for many different patient cohorts, including cohorts with normal measured GFR, no albuminuria and no diagnosis. The prevalence of SPS in the cohorts so far investigated is between 0.2 and 36%. Proteome studies of SPS demonstrate that the high mortality associated with the syndrome might be caused by the accumulation of 10–30 kDa signalling proteins promoting development of atherosclerosis and thus suggesting use of monoclonal antibodies to reduce the levels of the most detrimental signalling proteins as a treatment option. The KDIGO recommendations for classification of chronic kidney disease (CKD) comprise determination, or estimation, of GFR and analysis of albuminuria and therefore cannot identify a large fraction of the patients with SPS. The high prevalence and mortality of SPS and the possible treatment options strongly suggest that the KDIGO recommendations should be expanded to include determination of cystatin C to be able to identify all patients with SPS. [ABSTRACT FROM AUTHOR]

The link between cystatin C and mortality independent of glomerular filtration rate (GFR) in adults has prompted the "Shrunken Pore Syndrome" (SPS) hypothesis, where high serum cystatin C with normal creatinine is explained by smaller glomerular pores, through which creatinine can pass freely, while the larger cystatin C, beta-trace protein (BTP) and pro-inflammatory molecules are retained. This study set out to apply the definition of SPS to children. In 294 children who underwent inulin clearance (Cin) test, serum creatinine, cystatin C and BTP were measured. For all three markers eGFRx was calculated using the full age spectrum equations. The ratio eGFRcys/eGFRcrea was plotted against the error of eGFRBTP(%) (i.e. eGFRBTP-Cin)/Cin*100%). Patients with and without SPS according to different cut-off points of eGFRcys/eGFRcrea and eGFRcys/Cin (i.e. ≤0.6,0.7,0.8) were compared in terms of eGFRx, Cin, error of eGFRx(%) and eGFRBTP/eGFRcrea-ratio. The ratio eGFRcys/eGFRcrea and error of eGFRBTP(%) were positively correlated. The prevalence of SPS by eGFRcys/eGFRcrea with a cut-off of 0.6 was 4.8%. Patients with SPS had a more negative error of eGFRcys(%) and eGFRBTP(%) and higher Cin regardless of the definition. Overestimation of eGFRcrea in patients with SPS was only present when using the eGFRcys/eGFRcrea rather than the eGFRcys/Cin definition. Cystatin C and BTP are related independent of creatinine, suggesting glomerular pore size as a common denominator. The prevalence of SPS in children is comparable to adults. For research in SPS, a definition based on eGFRcys/exogenous clearance study may be useful to study the effect of SPS on creatinine metabolism. [ABSTRACT FROM AUTHOR]

Shrunken pore syndrome (SPS) is a condition in which the estimated glomerular filtration rate (eGFR) based on serum/plasma cystatin C concentration is significantly lower than the eGFR based on creatinine. According to the literatures, the diagnosis of SPS could be defined when the eGFR cystatin C is <70% of eGFR creatinine. Although the incidence of SPS varies in different patient populations and healthy seniors, it has been demonstrated that patients with SPS have poor prognosis. The present review has summarized its diagnosis, epidemiology, prognosis and possible pathophysiology basis. Moreover, we discuss the prevention and treatment of SPS in clinical practice as future challenges. • Shrunken pore syndrome was defined by eGFR cystatin C /eGFR creatinine -ratio < 0.70. • This phenomenon is due to a reduction in pore diameter of the glomerular filtration barrier. • Shrunken pore syndrome was associated with a strong increase in mortality. [ABSTRACT FROM AUTHOR]

Shrunken pore syndrome (SPS) is a condition in which estimated glomerular filtration rate (eGFR) based upon cystatin C is lower than eGFR based upon creatinine. It has been associated with increased mortality even in the presence of normal GFR in both a cardiac surgical population and a general population. No systematic studies of the variation in eGFRcystatin C/eGFRcreatinine-ratio used for SPS diagnosis have been published. This study aims to evaluate whether early and midterm mortality following elective cardiac surgery varies with the ratio used to identify SPS. Preoperative levels of cystatin C and creatinine were analysed in 4007 patients undergoing elective coronary artery bypass grafting (CABG) and/or surgical aortic valve replacement (sAVR). The eGFRcystatin C/eGFRcreatinine-ratio was calculated based on the equation pairs CKD-EPIcystatin C/CKD-EPIcreatinine and CAPA/LMrev. The overall 1- and 3-year all-cause mortality was 2.9 and 6.8%, respectively. Mean follow-up time was 3.6 years. Mortality markedly and progressively increased with a decrease in the eGFRcystatin C/eGFRcreatinine-ratio for both equation pairs. An increase in mortality was noted already when the ratio decreased from 1.0 to 0.90. To facilitate the clinical decisions based upon the SPS-defining eGFRcystatin C/eGFRcreatinine-ratio, we calculated both the ratios defining the highest combined sensitivity and specificity and the ratios producing a high specificity of 95%, finding different cut-off for these scenarios. [ABSTRACT FROM AUTHOR]

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 sex-adjusted 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 tyrosine-protein 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., (© 2021 The Authors. Proteomics - Clinical Applications published by Wiley-VCH GmbH.)