To better identify and treat patients with shrunken pore syndrome (SPS), a common kidney disorder associated with a high mortality rate, one researcher recommends an update to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines to include determination of cystatin C as part of the workup for chronic kidney disease (CKD). The existing KDIGO guidelines, which classify CKD based on determining (or estimating) glomerular filtration rate (GFR) and albuminuria, miss “a significant number of patients with SPS,” according to Anders Grubb, MD, PhD, professor of clinical chemistry at Lund University’s Departments of Clinical Chemistry and Pharmacology and Laboratory Medicine in Lund, Sweden.

SPS occurs when patients have decreased renal clearance of low molecular weight proteins or peptides (5-30 kDa) but normal clearance of creatinine. Cystatin C measurements, Lund contends in a review, better identify disruptions in the kidney filtration process that cause poorer filtration of these proteins.

KDIGO currently estimates glomerular filtration rate (GFR) using small molecules and looks for albuminuria. “This cannot identify a kidney disorder comprising a selective decrease in the filtration of molecules >10 kDa. This selective reduction might occur, and often occurs, in kidneys with normal filtration of low molecular mass substances e.g. creatinine and water, and in patients without albuminuria,” explained Grubb.

The bottom line is clinicians need to know more about SPS to effectively treat or cure this disorder in the future, said Grubb. “Although we cannot cure patients with the syndrome, we can consider the diagnosis when we try to decide the suitable treatment intensity of other disorders or risk factors of a patient,” he added.

SPS is diagnosed by an estimated GFR (eGFR) eGFRcystatin C/eGFRcreatinine-ratio <0.60. The disorder increases mortality risk by threefold over a period of 5 years. Studies have suggested that the accumulation of 10–30 kDa signaling proteins leads to atherosclerosis and may explain the high death rate in SPS patients. This suggests that monoclonal antibodies may be an optimal treatment option for reducing detrimental signaling proteins, Grubb summarized in his paper.

In his review of SPS, Grubb explored why a reduction in GFR estimated by a cystatin C-based equation—eGFRcystatin C, (or by the level of cystatin C)—did a better job of predicting end-stage renal disease, cardiovascular events, hospitalization, and death in SPS patients than another formula—a reduction in GFR estimated by a creatinine-based equation, eGFRcreatinine, (or by the level of creatinine).

Two current hypotheses: that eGFRcystatin C is a much better estimate of measured GFR than eGFRcreatinine, or that inflammation increases the cystatin C level, probably aren’t correct, Grubb said. In his paper, he noted that cystatin C is a preferred option because muscle mass changes don’t affect this marker as much as creatinine.

“Since muscle mass only marginally influences cystatin C, several cystatin C-based equations work for both children and adults,” observed Grubb.

Diagnosing SPS, however, calls for both eGFRcystatin C and eGFRcreatinine, Grubb wrote in his paper. These estimates usually agree within about 20%. However, if eGFRcystatin C is only 60% or 70% of eGFRcreatinine , kidney filtration of molecules >10 kDa like cystatin C is selectively reduced compared to small molecules like creatinine.

“This means that you need both cystatin C and creatinine to diagnose SPS,” noted Grubb.

Grubb recommended adding a determination of plasma/serum cystatin C in the KDIGO guidelines. KDIGO previously didn’t include this because SPS wasn’t known when the guidelines were developed in 2012, he said. Grubb and colleagues first described SPS in a 2015 article published in the Scandinavian Journal of Clinical and Laboratory Investigation.