{"id":7979,"date":"2024-02-08T08:56:24","date_gmt":"2024-02-08T08:56:24","guid":{"rendered":"https:\/\/www.kauveryhospital.com\/ima-journal\/?p=7979"},"modified":"2025-04-09T10:59:27","modified_gmt":"2025-04-09T10:59:27","slug":"association-of-cyp3a5-genotyping-and-c0-d-levels-in-post-renal-transplant-diabetes-mellitus","status":"publish","type":"post","link":"https:\/\/www.kauveryhospital.com\/ima-journal\/ima-journal-february-2024\/association-of-cyp3a5-genotyping-and-c0-d-levels-in-post-renal-transplant-diabetes-mellitus\/","title":{"rendered":"ASSOCIATION OF CYP3A5 GENOTYPING AND C0\/D LEVELS IN POST RENAL TRANSPLANT DIABETES MELLITUS"},"content":{"rendered":"

[vc_row][vc_column][vc_column_text]<\/p>\n

INTRODUCTION:<\/b><\/strong><\/h2>\n

Post transplant diabetes mellitus (PTDM) is known to occur in 4-25% of renal transplant patients, with 34.7% occurring in the first year, 46.9% and 56.2% in the 3rd<\/sup>\u00a0and 5th<\/sup>\u00a0year follow ups, respectively. Various factors contribute to the development of PTDM including the diabetogenic immunosuppressive medications (Corticosteroids, tacrolimus, etc), Hepatitis C virus infection, etc. PTDM has been shown to be a very strong independent predictor of mortality and graft failure.<\/p>\n

Tacrolimus is metabolised by CYP3A5 enzyme and contributes to its bioavailabilty. They are categorised based on the allele being carried and are called expressers (CYP3A5 1\/3, 1\/1) or non- expressers (CYP3A5 3\/3), with the latter being more common. Expressers tend to require higher tacrolimus dose, in view of the fast metabolism. C0\/D ratio is the concentration to dose ratio of tacrolimus and is found to be low in expressers, thereby demanding a higher dose in them.<\/p>\n

Previous studies elaborate on the association of CYP3A5 genotyping and C0\/D ratio, whereas, further research is needed on the risk stratification of development of PTDM based on CYP3A5 and C0\/D ratio associations, especially in Indian settings, which we aim to do through this study.<\/p>\n

AIM:<\/b><\/strong><\/h2>\n

To study the onset of PTDM and association of CYP3A5 genotyping and C0\/D levels in the development of post transplant diabetes mellitus.<\/p>\n

METHODS:<\/b><\/strong><\/h2>\n
    \n
  • A retrospective study including all renal transplant recipients at our centre from 2019-2023, who developed post transplant diabetes mellitus, defined by random glucose levels more than 200mg\/dl and fasting glucose levels more than 140mg\/dl, along with the need to use anti-diabetic agents in the post transplant period, excluding post transplant hyperglycemia.<\/li>\n
  • Recipients with good HLA match and negative DSA profile, did not receive induction agents.<\/li>\n
  • High risk recipients received ATG as induction agent.<\/li>\n
  • All the recipients, irrespective of their risk status received triple immunosuppression including steroid, MMF and tacrolimus, post transplant.<\/li>\n
  • Data including the CYP3A5 levels (calculated by real time PCR assay) and tacrolimus trough level at day 3 were collected.<\/li>\n
  • C0\/D ratio calculated as the trough level of tacrolimus in ng\/ml \/ the daily dose (mg).<\/li>\n<\/ul>\n

    The data was analysed for the development of PTDM, including the following outcomes:<\/em><\/strong><\/p>\n

      \n
    • Time of onset of PTDM<\/li>\n
    • Association of CYP3A5 genotyping and development of PTDM<\/li>\n
    • Association of C0\/D levels at day 3 with the development of PTDM<\/li>\n<\/ul>\n

      Statistical analysis was done using SPSS software version 25.0.<\/p>\n

      RESULTS:<\/b><\/strong><\/h2>\n

      Among a total of 110 patients, who underwent renal transplant, from 2019-2023, 14 patients were found to develop PTDM (12.7%).<\/p>\n

      Among them, 11 were males (78.5%) and 3 were females (21.5%).<\/p>\n

      The age distribution ranged from 31years to 54 years with a mean of 41.07years<\/p>\n

      PTDM was found to develop in the first year in 85.7% patients (n=12), which includes 64.1% patients who developed the same in the first month itself.<\/p>\n

      The tacrolimus trough levels measured at day 3, ranged from 4.2ng\/ml to >30ng\/ml with a mean of 11.7ng\/ml.<\/p>\n

      C0\/D ratio at day 3 ranged from 0.6 to 6.925 per mg of daily tacrolimus dose with a mean of 2.0025.<\/p>\n

      C0\/D ratio at the time of onset of PTDM was ranging from 0.4 to 5.82 per mg of daily tacrolimus dose with a mean of 1.70.<\/p>\n

      The C0\/D ratio at post op day 3 was categorized further as \u00a31.5 and >1.5 (based on study by Teun van Gelder,et.al).<\/p>\n

      Among them, 6 patients had C0\/D ratio \u00a31.5 (42.8%) and 8 patients with >1.5 (57.14%).<\/p>\n

      Among the patients with C0\/D ratio \u00a31.5, 100% of patients were having CYP3A5 genotype of 1\/3(expressers), whereas, among those with C0\/D ratio >1.5, 62.5% of patients had CYP3A5 genotyping of 1\/3 (expressers) and 37.5% of 3\/3 (non-expressers).<\/p>\n

      PTDM was reported in 37.93% of the 1\/3 genotype cases and 15.15% of the 3\/3 genotype cases (P = 0.058), showing statistical significance.<\/p>\n

      Two patients had developed Acute cell mediated rejection prior to the development of PTDM which could have confounded the development of PTDM.<\/p>\n

      With regards to PTDM, C0\/D demonstrated significant differences (p = 0.023 and p=0.008 respectively) among genotypes, with median values of 1.19(0.847-1.818) and 1.14(0.74-1.225) for 1\/3 which was significantly lower than 3\/3 genotype (2.04(1.87-3.185) and 2.62(2.04-3.75).<\/p>\n

      CONCLUSION: <\/b><\/strong><\/h2>\n
        \n
      • The onset of PTDM among our population was more within the first year post transplant, especially within the first month.<\/li>\n
      • The CYP3A5 genotypic polymorphism plays a major role in predicting the risk of development of PTDM with expressers (1\/3), being more prone.<\/li>\n
      • The C0\/D ratio \u00a35 at day 3 post operatively, is an independent predictor of development of PTDM, especially in those with CYP3A5 of 1\/3 genotype.<\/li>\n<\/ul>\n

         <\/p>\n

        \"\"Dr. Rashmi Shivram<\/strong>
        \nResident \u2013 Nephrology<\/em>
        \nKauvery Hospital, Chennai<\/p>\n

         <\/p>\n

         <\/p>\n

        \"Dr.Dr. R. Balasubramaniyam<\/strong>
        \nChief Nephrologist<\/em>
        \nKauvery Hospital, Chennai<\/p>\n

         <\/p>\n

         <\/p>\n

        \"\"Dr. Balaji Kirushnan<\/strong>
        \nNephrologist<\/em>
        \nKauvery Hospital, Chennai[\/vc_column_text][\/vc_column][\/vc_row]<\/p>\n","protected":false},"excerpt":{"rendered":"

        [vc_row][vc_column][vc_column_text] INTRODUCTION: Post transplant diabetes mellitus (PTDM) is known to occur in 4-25% of renal transplant patients, with 34.7% occurring in the first year, 46.9% and 56.2% in the 3rd\u00a0and<\/p>\n","protected":false},"author":2,"featured_media":7980,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[62],"tags":[],"class_list":["post-7979","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-ima-journal-february-2024"],"yoast_head":"\nASSOCIATION OF CYP3A5 GENOTYPING AND C0\/D LEVELS IN POST RENAL TRANSPLANT DIABETES MELLITUS<\/title>\n<meta name=\"description\" content=\"Post transplant diabetes mellitus (PTDM) is known to occur in 4-25% of renal transplant patients, with 34.7% occurring in the first year, 46.9% and 56.2% in the 3rd and 5th year follow ups, respectively.\" \/>\n<meta name=\"robots\" content=\"index, follow, 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