Shrunken pore syndrome - a common kidney disorder with high mortality. Diagnosis, prevalence, pathophysiology and treatment options

作者：Anders Grubb · 发表于：Clinical Biochemistry · 年份：2020 · DOI：10.1016/j.clinbiochem.2020.06.002 · 被引用次数：83 · 研究领域：Chronic Kidney Disease and Diabetes、Dialysis and Renal Disease Management、Renal Diseases and Glomerulopathies

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 ident...