Shrunken Pore Syndrome

Shrunken Pore Syndrome (SPS) is a recently identified kidney condition characterized by a disparity in the glomerular filtration rate (GFR) for different sized molecules, specifically affecting the filtration of medium-sized molecules like cystatin C compared to smaller molecules like creatinine. This difference is often observed when comparing cystatin C-based estimated GFR (eGFR) to creatinine-based eGFR, with SPS defined as eGFR(cystatin C) being significantly lower than eGFR(creatinine). SPS has been associated with increased mortality and morbidity, particularly in patients with cardiovascular and kidney diseases.

[Schematic view of possible pathophysiology of Shrunken Pore Syndrome]

Your kidneys filter blood through tiny structures called glomeruli, which have pores that allow small molecules to pass through while retaining larger ones. Think of it as a sieve.

Normally, both small molecules like creatinine and slightly larger molecules like cystatin C are filtered efficiently.

However, in Shrunken Pore Syndrome, the pores in the glomeruli are thought to be narrowed or 'shrunken', selectively impacting the filtration of medium-sized molecules like cystatin C, while smaller molecules like creatinine are still filtered relatively well.

This leads to a lower eGFR calculated based on cystatin C levels compared to creatinine-based eGFR, indicating a selective impairment in the kidney's ability to filter larger molecules.

Is this bad, you might ask. The answer is: very bad. Shrunken Pore Syndrome is associated with increased mortality and morbidity, especially in individuals with diabetes type-2 and kidney diseases[1]. Shrunken Pore Syndrome has also been linked to the progression of atherosclerosis and poor outcomes in patients with cardiovascular disease[2]. Shrunken Pore Syndrome has been observed in severe cases of COVID-19, potentially contributing to poorer outcomes[3].

While the exact cause of Shrunken Pore Syndrome is still being investigated, it is hypothesized that changes in the glomerular filtration barrier, such as narrowing of the pores, contribute to the syndrome. Other factors like thickening of the glomerular basement membrane may also play a role. Inflammatory and neurohormonal mechanisms are also implicated in the progression of Shrunken Pore Syndrome.

[1] Bruce et al: The relationship between shrunken pore syndrome and all-cause mortality in people with type 2 diabetes and normal renal function: the Fremantle Diabetes Study Phase II in Diabetologica – 2025
[2] Xhakollari et al: The Shrunken pore syndrome is associated with poor prognosis and lower quality of life in heart failure patients: the HARVEST-Malmö study in ESC Heart Failure - 2021
[3] Larsson et al: Shrunken Pore Syndrome Is Frequently Occurring in Severe COVID-19 in International Journal of Molecular Science - 2022