P0219INFLUENCE OF UNDERLYING RENAL DISEASE AND IMMUNOSUPPRESSIVE REGIMEN ON PREMATURE OVARIAN FAILURE IN PREMENOPAUSAL RENAL PATIENTS
Authors: Julia Rasała , Anna Ciszewska , Małgorzata Król , Mariusz Kusztal , Marcelina Żabińska , Katarzyna Kościelska-Kasprzak , Maciej Kanafa , Hanna Augustyniak-Bartosik , Mazanowska Oktawia , Magdalena Krajewska 
Published: June 2020

Abstract

Background and Aims
Aging, renal pathology (eg SLE, ADPKD), X-ray exposition and pharmacological treatments, especially previous immunosuppressives, may negatively influence the ovarian reserve in childbearing age women. Anti-Müllerian hormone (AMH) is regarded as biomarker for ovarian reserve. The aim was to assess influence of immunosuppressive therapy, X-ray exposition and renal pathology on ovarian in female patients with normal menstrual cycle and chronic kidney disease, including kidney transplant recipients.

Method
Consecutive premenopausal females visiting renal outpatient setting at university hospital who gave informed consent and met exclusion criteria (past ovarian surgical procedure, PCOS, eGFR &lt;30ml/min, diabetes) were enrolled in cross-sectional study. Clinical (renal pathology, smoking, X-rays exposition, eGFR standardized MDRD4, contraceptives) and demographic characteristics, as well as previous and current therapies were recorded. Serum AMH levels were measured by enzyme-linked immunosorbent assay; AMH levels were classified as low or normal/above age-adjusted reference levels (published norms).

Results
In cohort of consecutive 153 premenopausal females (mean age 32,2 y.,range 18-45), 83 (54,2%) were treated recently with antiproliferation immunosuppressive regimen (mycophenolate/azathioprine/methotrexate) and 39 (25,5%) had received cyclophosphamide (CYC) in the past. Median eGFR was 68,5 (IQR 54, 82) ml/min/1.73m2 and renal pathology were as follows glomerulonephritis (n=75), lupus nephritis (n=42), ADPKD (n=6), interstitial (n=5), vasculitis (n=7), other/unknown (n=18). 55 patients were kidney transplant recipients.
Median AMH concentration was 2,9 ng/ml (IQR 1,0 ; 5,2); AMH levels were classified in 45 females as low (median 0,64 IQR 0,05; 1,84) and in 108 as normal/above age-adjusted reference (median 4 IQR 2,1; 5,9). AMH levels did not differ between patients treated with or without antiproliferation immunosuppressives (2.6 IQR 0,9; 5,0  vs. 3.2  IQR 1,1; 5,2 ng/ml, p=0.33) or as well as between being kidney transplant recipients or not (2.72  IQR 0,8; 4,0 vs. 3,0 IQR 1,15; 5,0 ng/ml, p=0.08).
Referring to CYC exposition, AMH levels were lower in females treated with CYC regardless of reason (1.1 ± 1.4 ng/ml vs. 3.2 ± 2 ng/ml, p=0.003). Linking AHA level with renal disease, only lupus patients showed low age-adjusted AMH levels ( 18/42 – 43%), especially with history of CYC exposition (11 of 18 with low level). Significant negative correlation was found between AMH level and age (r -0,45, p&lt; 0,0001), and very weak with eGFR (r 0,2, p=0,005).

Conclusion
Almost 1/3 of studied childbearing age women with chronic kidney disease (eGFR &gt;30) showed a reduction of the ovarian reserve. It was associated with underlying disease (lupus), cyclophosphamide treatment but not with cumulative X-ray exposition, contraceptives or smoking. Further studies on biomarkers of ovarian reserve in renal patients are still needed for better therapeutic strategy and family planning.