| Project outline

RENUM – Renal Function Assessment by Nuclear Magnetic Resonance based Metabolomics

Objective:
Development and validation of an NMR based metabolic constellation determining glomerular filtration rate for a more accurate picture of the underlying kidney function.

 

“A diagnostic test as precise as mGFR, as simple as eGFR, and fit for clinical routine“,
Dr. Eric Schiffer, Head of Clinical Development, numares AG

The glomerular filtration rate (GFR) is the most important parameter in assessing kidney function. The gold standard to determine GFR is inulin clearance [1, 2], but other substances have been explored for measuring GFR (mGFR) as well [3]. Although very precise, mGFR methods are expensive, time-consuming and therefore impractical in routine. Therefore, GFR is mostly estimated by a simple serum creatinine analysis (eGFR) [4]. However, serum creatinine levels strongly depend on patient’s individual features, i.e. muscle mass, age or physical activity level. Thus, this approach is associated with a distinct imprecision. There exist more than 50 eGFR equations illustrating the degree of uncertainty associated with the approach [5]. Based on these facts, there is a clinical need for a test system that combines precision of mGFR approaches with the easy accessibility of eGFR.

Study design:
RENUM is a retrospective multi-center observational study

Material:
Biobanked serum samples of patients with broad spectrum of primary renal diseases and degrees of renal impairment

Reference standard:
mGFR

Approach:
The scientific literature indicates that there is a connection between increasing/ decreasing concentrations of endogenous blood metabolites and the GFR. To establish a combination of endogenous metabolites with creatinine to a metabolic constellation reflecting GFR, numares uses its precise, fast and flexible analytical AXINON® System, which allows simultaneous detection of metabolites in a highly reproducible single analytical step.

Phase 1:
The association of endogenous serum metabolites with GFR will be tested. Quantitative NMR signals of both, literature reported candidates and proprietary metabolic markers, will be correlated with mGFR reference data. Candidates significantly associated with GFR will be used to model renal clearance based mGFR. 

Phase 2:
The diagnostic performance (trueness and precision) of the obtained model(s) will be tested in a further, independent sample set (not used for discovery or modelling).

Success:
Our efforts will result in a novel, simple blood test that will be available for clinical routine in early 2019: AXINON® Clearance Check.

References: 
1. Smith, H.W., The kidney: Structure and function in health and disease. Oxford University Press Inc, New York, 1951.
2. National Kidney, F., K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis, 2002. 39(2 Suppl 1): p. S1-266.
3. Stevens, L.A. and A.S. Levey, Measured GFR as a confirmatory test for estimated GFR. J Am Soc Nephrol, 2009. 20(11): p. 2305-13.
4. Kemperman, F.A., R.T. Krediet, and L. Arisz, Formula-derived prediction of the glomerular filtration rate from plasma creatinine concentration. Nephron, 2002. 91(4): p. 547-58.
5. Johnson, D. and I. Caring for Australians with Renal, The CARI guidelines. Evaluation of renal function. Nephrology (Carlton), 2005. 10 Suppl 4: p. S133-76.

*numares’ products are not yet available for sale within the United States; they have not yet been approved or cleared by the U.S. Food and Drug Administration.