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Tuesday Nov 24th 9 pm EDT, 6 pm PST

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N Engl J Med. Nov 12;373(20):1916-25. doi: 10.1056/NEJMoa1506362. Epub 2015 Nov 5.

Soluble Urokinase Receptor and Chronic Kidney Disease.

Hayek SS, Sever S, Ko YA, Trachtman H, Awad M, Wadhwani S, Altintas MM, Wei C, Hotton AL, French AL, Sperling LS, Lerakis S, Quyyumi AA, Reiser J.

PMID: 26539835

Preamble

In 2011 suPAR, the soluble urokinase-type plasminogen activation receptor (free PMC pdf review), arrived in the literature on a wave of hype. Serum suPAR levels were elevated in two thirds of patients with FSGS. More significantly, this was purported to be specific for FSGS. A pathogenic role for suPAR was supported by three mouse models. Since the 2011 paper, as to often occurs, the hype was replaced by controversy as verification of these findings was difficult.

At #KidneyWk 2015, suPAR shed its FSGS etiology origin story and was reborn as a CKD biomarker.

Methods

This was a prospective study that measured plasma suPAR in 3,683 patients enrolled in a biobank. They followed renal function at subsequent visits in 2,292 and used diverse analytical techniques to assess the relationship between suPAR, baseline eGFR, change in eGFR, and the development of CKD.

Results

  • Splitting serum suPAR into two groups showed that higher suPAR at baseline was associated with numerous traditional CKD risk factors

  • Decline in eGFR was greater in patients with higher suPAR and this was independent of race and diabetes but not of baseline eGFR

  • Patients with a normal eGFR at baseline had the largest suPAR related decline in renal function

  • 24% of the cohort developed CKD and this incidence of CKD was associated with a higher suPAR level at baseline almost in a “dose dependent” manner

Conclusion & Discussion

“elevated plasma suPAR levels were associated with incident chronic kidney disease and a more rapid decline in the eGFR in persons with normal kidney function at baseline.”

Questions:

Did the study’s lack of a decent quantification of proteinuria mean that suPAR is just a novel replacement for albuminuria measurement?

Why were there no calculations of positive and negative predictive values or repeat suPAR measurements?

Hopefully, we can answer all these questions in this week’s #NephJC

Summary by Tom Oates

#NephJC chat

Tuesday Nov 24th 9 pm EDT, 6 pm PST

Wednesday Nov 25th 8 pm BST, 12 noon PST, 3 pm EDT