ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO843

Glucocorticoid Metabolism in ADPKD Patients and the Effect of Treatment with a Vasopressin V2 Receptor Antagonist

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Heida, Judith E., University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Minovic, Isidor, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Boertien, Wendy Ellen, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Bakker, Stephan J.L., University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Gansevoort, Ron T., University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Van beek, André, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Background

Vasopressin concentration is increased in Autosomal Dominant Polycystic Kidney Disease (ADPKD), and increases even further when a vasopressin V2 receptor antagonist (V2RA) is used as renoprotective treatment. We investigated the stimulatory function of these elevated vasopressin levels on the hypothalamic-pituitary-adrenal axis.

Methods

24-hour urinary excretion of total cortisol, cortisone, THE, THF and aTHF were measured in 27 ADPKD patients using a validated high-performance LC-MS/MS assay. Results were compared to those in healthy controls (HC, n=81) and in IgA nephropathy patients (IgAN, n=27) that were matched for sex, age and kidney function. Next, in the ADPKD patients the effect of the V2RA tolvaptan (3 weeks of 90/30 mg split dose) was investigated on both urine and plasma glucocorticoid levels.

Results

In comparison to HC, ADPKD patients demonstrated lower 24 hour urinary excretion of total cortisol (p=0.001), cortisone ( p<0.001) and cortisone break-down product THE (p<0.02), whereas in comparison to IgAN patients no differences were found (Table). Treatment with the V2RA increased urinary cortisone (p<0.001) and decreased aTHF excretion (p<0.001), without changing the urinary excretion of other glucocorticoid compounds or plasma levels.

Conclusion

ADPKD patients demonstrated a decreased urinary excretion of glucocorticoids compared to HC, both of biologically active and inactive compounds. This is not disease specific, but likely caused by their impaired kidney function. The V2RA increased excretion of glucocorticoids in the form of the inactive glucocorticoid cortisone, but without increasing active cortisol, neither in urine nor in plasma. Overall, renal function appears to have a stronger effect on glucocorticoid metabolism than vasopressin.

 Healthy controlsADPKD
baseline
ADPKD + VR2AIgA Nephropathy
Number8127-27
eGFR
(ml/min/1.73m2)
96 ± 1457 ± 33*-54 ± 20
Cortisol
(µmol/24hr)
0.34
[0.26 -0.45]
0.23*
[0.19 – 0.30]
0.24*
[0.17 – 0.35]
0.26*
[0.20 – 0.33]
Cortisone
(µmol/24hr)
0.52
[0.42 – 0.67]
0.29*
[0.22 – 0.42]
0.44#
[0.35 – 0.61]
0.34*
[0.26 – 0.43]
THE
(µmol/24hr)
12.5
[8.0 – 16.6]
9.27*
[6.14 – 14.6]
9.24*
[4.54 – 12.5]
10.2*
[7.42 – 15.0]
THF
(µmol/24hr)
6.95
[5.13 – 9.10]
5.91
[4.07 – 7.88]
5.54*
[4.07 – 8.00]
5.81
[4.07 – 8.91]
aTHF
(µmol/24hr)
3.87
[2.33 – 7.12]
4.16
[1.94 – 6.31]
3.54#
[0.76 – 5.16]
5.29
[3.34 – 8.35]
Total glucocorticoid
(µmol/24hr)
25.1
[17.1 – 34.0]
21.7
[14.2 – 28.4]
18.3*
[13.8 – 24.8]
22.7
[16.9 – 31.6]

mean ± SD or median [IQR], * p<0.05 vs healthy controls, # p<0.05 vs ADPKD baseline