Use of 1,25-Dihydroxyvitamin D Values in Ratio with PTH as a Prognostic Biomarker

a technology of dihydroxyvitamin d and pth, which is applied in the direction of disease diagnosis, instruments, biological material analysis, etc., can solve the problems of increasing burden on health care systems, unfavorable outcomes, and progressing deterioration of renal function, so as to improve renal function in patients

Pending Publication Date: 2021-03-11
DIASORIN ITALIA SPA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016]The present invention provides a method for predicting or stratifying the risk of worsening renal function (WRF) in a patient at risk of renal injury or in a patient affected by renal injury, using the level of 1,25(OH)2D in conjunction with the level of parathyroid hormone (PTH) to determine the ratio of 1,25(OH)2D to PTH. The ratio value allows for risk prediction or stratification of worsening renal function in the patient.
[0019]The measurement of the ratio of 1,25(OH)2D to PTH in patients at risk of renal injury or in patients affected by renal injury offers several advantages, such as improvement of the area under the receiver operating curve, translating added clinical value, integration of more than one physiopathologicaly interrelated biomarker and modulation of two different hormones to increase the significance of the ratio.

Problems solved by technology

Progressive deterioration of renal function is common in patients with different diseases such as chronic heart failure (HF), chronic kidney disease (CKD) and metabolic syndrome, and is associated with unfavorable outcomes, which can be improved by timely interventions.
The cross talk between the diseased heart and kidney is a growing burden for health care systems as the incidence of HF and chronic kidney disease (CKD) has been steadily increasing and will further increase due to ageing of the general population and better treatment of acute cardiac and renal diseases.
It has also been realized that the progressive development of worsening renal function (WRF) over time carries an increased risk of death and hospitalizations.
To the inventors' knowledge, there are, however, scant reports on the ability of circulating markers of bone mineral metabolism to predict deterioration of renal function over time.
Lack of reliable automated testing of 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active metabolite of vitamin D, has in the past precluded evaluation of the prognostic value of this measurement.

Method used

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  • Use of 1,25-Dihydroxyvitamin D Values in Ratio with PTH as a Prognostic Biomarker
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  • Use of 1,25-Dihydroxyvitamin D Values in Ratio with PTH as a Prognostic Biomarker

Examples

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Effect test

example 1

sub>2D assay

[0134]One of the preferred embodiment of the assay of the invention is described in in PCT Patent Publication WO 2014 / 114780 and in US Patent Publication No. 2015-0361178. In brief, paramagnetic microparticles (PMPs) (Dynal, Norway) were coated with a conformation-specific monoclonal antibody capable of recognizing the VDR-LBD / 1,25(OH)2D complex antibody following the supplier instructions. The recombinant VDR-LBD that was used in the assay was prepared as described in Example 1, and was coupled to an affinity tag (designated in the following as “TAG”). The 11B4H11H10 monoclonal antibody, described above, was used for this purpose. A mouse monoclonal anti-TAG antibody was conjugated with cyclic AminoButhylEthylisoluminol (cABEI) in PBS buffer pH 7.4. The calculated cABEI incorporation was from 2-3 molecules per antibody molecule. Calibrators were prepared by adding different concentrations of an ethanolic solution of 1,25(OH)2D into a steroid-free, charcoal-stripped huma...

example 2

OH)2D / PTH Ratio as Biomarker of Renal Injury

[0137]Materials and Methods

[0138]The cohort studied consisted of 1083 patients enrolled in a biomarker substudy of a randomized, double-blind, placebo controlled, multicenter study that enrolled 6975 patients with clinical evidence of chronic and stable HF (NYHA II-IV), irrespective of the cause and the level of left ventricular ejection fraction (LVEF). In relation to renal function, 180 patients of the cohort were normal (i.e., eGFR (mL / min / 1.73 m2)≥90) and the remainder had eGFR below 90. Venous blood samples were drawn on EDTA at randomization and after three months of follow-up. Patients rested supine for at least 15 min before blood sampling. Blood was centrifuged at 4° C. within 10 minutes of draw and plasma aliquots were shipped on dry ice to a central laboratory. Samples were stored at −70° C. until assayed. In the analysis, worsening of renal function (WRF) was employed as the endpoint.

[0139]The plasma concentrations of 1,25-dihy...

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Abstract

The present invention relates to the use of 1,25-dihydroxyvitamin D values in ratio with PTH as a prognostic biomarker. More particularly, the present invention relates to a method for predicting or stratifying the risk of worsening renal function (WRF) in a patient at risk of renal injury or affected by renal injury. Levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) are measured in a biological sample and taken together with parathyroid hormone (PTH) levels to provide a ratio indicative of the risk of worsening renal function.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application is:[0002](A) a divisional application of U.S. patent application Ser. No. 15 / 651,517 (filed on Jul. 17, 2017; pending), which application is:[0003](1) a continuation-in-part of U.S. Patent Appln. Serial No. PCT / IB2016 / 050230 (filed on Jan. 18, 2016; expired), which claims priority to U.S. Patent Appln. Ser. No. 62 / 104,802 (filed on Jan. 18, 2015, expired); and[0004](2) a continuation-in-part of U.S. patent application Ser. No. 15 / 606,284 (filed on May 26, 2017; issued Dec. 10, 2019 as U.S. Pat. No. 10,501,548), which application is a division of U.S. patent application Ser. No. 14 / 763,264 (filed Jul. 24, 2015; issued Feb. 5, 2019 as U.S. Pat. No. 10,196,449), which application is a § 371 Application of PCT / EP2014 / 051482 (filed on Jan. 27, 2014; now lapsed), which claims priority to European Patent Application EP 13152851.5 (filed on Jan. 28, 2013); and[0005](B) a continuation-in-part of U.S. patent application Ser....

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/82G01N33/50G01N33/68G01N33/78G01N33/74
CPCG01N33/82G01N33/5005G01N33/5091G01N33/6893G01N2333/635G01N33/74G01N2800/347G01N2800/60G01N33/78
Inventor COLOTTA, FRANCESCOBONELLI, FABRIZIOBLOCKI, FRANKZIEROLD, CLAUDIA
Owner DIASORIN ITALIA SPA
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