TOPLINE:

Shrunken pore syndrome — a discrepancy between cystatin C-based and creatinine‑based estimated glomerular filtration rates (eGFRs), thought to reflect a reduced filtration of mid‑sized molecules — was associated with markedly higher risks for heart failure (HF), peripheral artery disease, and all‑cause mortality in patients with type 1 diabetes (T1D) who had not yet developed albuminuria.

METHODOLOGY:

• Researchers analysed data of 3769 patients with T1D (median age, 36.6 years; 51.8% men) to examine whether shrunken pore syndrome was associated with cardiovascular outcomes and all‑cause mortality and whether these associations differed by albuminuria status.
• Patients had both serum creatinine and serum cystatin C data available and had not developed kidney failure at baseline.
• Serum cystatin C and serum creatinine were used to calculate cystatin C-based and creatinine‑based eGFRs; shrunken pore syndrome was defined as a cystatin C-based eGFR/creatinine‑based eGFR ratio < 0.7.
• Patients with either moderate or severe albuminuria were classified as having albuminuria; those with normal urinary albumin excretion were classified as having no albuminuria.
• Outcomes were incident coronary artery disease, stroke, peripheral artery disease, and HF and all-cause mortality, identified from national health registries over a median follow-up duration of 19.7 years; the cystatin C-based eGFR/creatinine-based eGFR ratio was evaluated both categorically and continuously, and cystatin C-based eGFR and creatinine-based eGFR were analysed separately.

TAKEAWAY:

• Among patients without albuminuria, shrunken pore syndrome was associated with higher risks for HF (hazard ratio [HR], 3.07; 95% CI, 1.47-6.69), peripheral artery disease (HR, 3.64; 95% CI, 1.75-7.57), and all-cause mortality (HR, 3.08; 95% CI, 1.86-5.11).
• In patients with albuminuria, shrunken pore syndrome was significantly associated with only HF (HR, 1.54; 95% CI, 1.02-2.33).
• When analysed continuously, a lower cystatin C-based eGFR/creatinine‑based eGFR ratio showed a non-linear association with higher risks for peripheral artery disease, HF, and all‑cause mortality — with risks rising once cystatin C-based eGFR fell below creatinine‑based eGFR — but the ratio showed no associations in patients with albuminuria.
• When analysed separately, cystatin C-based eGFR alone was linked to peripheral artery disease, and both measures were linked to HF and all-cause mortality in patients without albuminuria.

IN PRACTICE:

"Our study suggests that monitoring of eGFRcys [cystatin C-based eGFR] provides clinically relevant and useful additional information about individuals without albuminuria, because evaluating both eGFRcys and eGFRcr [creatinine-based eGFR], and their differences, can help assess future risk of HF, PAD [peripheral artery disease], and premature death at an early stage," the authors wrote.

SOURCE:

This study was led by Valma Harjutsalo, Folkhälsan Research Centre, Biomedicum Helsinki, Helsinki, Finland. It was published online on March 17, 2026, in Diabetes Care.

LIMITATIONS:

The study lacked measured GFRs and repeat cystatin C-based eGFR measurements, so it could not directly track changes in kidney function over time. The cystatin C assay was not yet standardised to the International Federation of Clinical Chemistry and Laboratory Medicine reference material as standardisation was implemented after the measurements were taken.

DISCLOSURES:

The study received support from multiple sources, including Folkhälsan Research Foundation, Wilhelm and Else Stockmann Foundation, Liv och Hälsa Society, and Medical Society of Finland. One author reported receiving investigator-initiated research grants, serving on advisory boards, and receiving lecture fees from various organisations, including Medscape.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.