High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft Loss
Background. High calcineurin inhibitor (CNI) intrapatient variability (IPV) has been associated with poor kidney allograft outcomes. However, the relationship between early allograft histological changes, their progression, and CNI-IPV is less well studied. Hence, we evaluated effect of CNI-IPV defi...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2019-02-01
|
| Series: | Transplantation Direct |
| Online Access: | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000000862 |
| _version_ | 1819066891980767232 |
|---|---|
| author | Akhil Sharma, MD Aravind Cherukuri, MD, PhD Rajil B. Mehta, MD Puneet Sood, MD Sundaram Hariharan, MD |
| author_facet | Akhil Sharma, MD Aravind Cherukuri, MD, PhD Rajil B. Mehta, MD Puneet Sood, MD Sundaram Hariharan, MD |
| author_sort | Akhil Sharma, MD |
| collection | DOAJ |
| description | Background. High calcineurin inhibitor (CNI) intrapatient variability (IPV) has been associated with poor kidney allograft outcomes. However, the relationship between early allograft histological changes, their progression, and CNI-IPV is less well studied. Hence, we evaluated effect of CNI-IPV defined by the degree of fluctuation of CNI levels in all kidney transplant patients over 2 to 12 months posttransplant on early allograft inflammation, subsequent chronicity, and later clinical outcomes.
Methods. Two hundred eighty-six patients transplanted from January 2013 to November 2014 were enrolled with protocol and indication biopsies. The mean CNI-IPV was 28.5% and a quarter of our cohort had IPV of 35% or greater (high CNI IPV). Baseline demographic differences were similar between high and low CNI IPV groups.
Results. High CNI-IPV was associated with a higher incidence of acute rejection (AR) within 1 year (52% vs 31% P < 0.001), more persistent/recurrent AR by 1 year (18.2% vs 6.2%, P = 0.002), higher-grade AR (≥Banff 1B, 27.5% vs 7.3%, P < 0.001), and worse interstitial fibrosis/tubular atrophy (P = 0.005). High CNI-IPV was associated with increased graft loss (GL) and impending graft loss (iGL, defined as eGFR<30 ml/min and >30% decline in eGFR from baseline), regardless of donor-specific antibody, delayed graft function, rejection, or race. In a multivariate Cox Proportional Hazards Model, high CNI-IPV was independently associated with GL + iGL (hazard ratio, 3.1; 95% confidence interval, 1.6–5.9, P < 0.001).
Conclusions. High CNI-IPV within 1 year posttransplant is associated with higher incidence of AR, severe AR, allograft chronicity, GL, and iGL. This represents a subset of patients who are at risk for poor kidney transplant outcomes and potentially a modifiable risk factor for late allograft loss. |
| first_indexed | 2024-12-21T16:09:34Z |
| format | Article |
| id | doaj.art-f44e078390ee43f1b6f9cbaa22ac8e8b |
| institution | Directory Open Access Journal |
| issn | 2373-8731 |
| language | English |
| last_indexed | 2024-12-21T16:09:34Z |
| publishDate | 2019-02-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Transplantation Direct |
| spelling | doaj.art-f44e078390ee43f1b6f9cbaa22ac8e8b2022-12-21T18:57:50ZengWolters KluwerTransplantation Direct2373-87312019-02-0152e42410.1097/TXD.0000000000000862201902000-0003High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft LossAkhil Sharma, MD0Aravind Cherukuri, MD, PhD1Rajil B. Mehta, MD2Puneet Sood, MD3Sundaram Hariharan, MD41 Department of Medicine and Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.1 Department of Medicine and Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.1 Department of Medicine and Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.1 Department of Medicine and Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.1 Department of Medicine and Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.Background. High calcineurin inhibitor (CNI) intrapatient variability (IPV) has been associated with poor kidney allograft outcomes. However, the relationship between early allograft histological changes, their progression, and CNI-IPV is less well studied. Hence, we evaluated effect of CNI-IPV defined by the degree of fluctuation of CNI levels in all kidney transplant patients over 2 to 12 months posttransplant on early allograft inflammation, subsequent chronicity, and later clinical outcomes. Methods. Two hundred eighty-six patients transplanted from January 2013 to November 2014 were enrolled with protocol and indication biopsies. The mean CNI-IPV was 28.5% and a quarter of our cohort had IPV of 35% or greater (high CNI IPV). Baseline demographic differences were similar between high and low CNI IPV groups. Results. High CNI-IPV was associated with a higher incidence of acute rejection (AR) within 1 year (52% vs 31% P < 0.001), more persistent/recurrent AR by 1 year (18.2% vs 6.2%, P = 0.002), higher-grade AR (≥Banff 1B, 27.5% vs 7.3%, P < 0.001), and worse interstitial fibrosis/tubular atrophy (P = 0.005). High CNI-IPV was associated with increased graft loss (GL) and impending graft loss (iGL, defined as eGFR<30 ml/min and >30% decline in eGFR from baseline), regardless of donor-specific antibody, delayed graft function, rejection, or race. In a multivariate Cox Proportional Hazards Model, high CNI-IPV was independently associated with GL + iGL (hazard ratio, 3.1; 95% confidence interval, 1.6–5.9, P < 0.001). Conclusions. High CNI-IPV within 1 year posttransplant is associated with higher incidence of AR, severe AR, allograft chronicity, GL, and iGL. This represents a subset of patients who are at risk for poor kidney transplant outcomes and potentially a modifiable risk factor for late allograft loss.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000000862 |
| spellingShingle | Akhil Sharma, MD Aravind Cherukuri, MD, PhD Rajil B. Mehta, MD Puneet Sood, MD Sundaram Hariharan, MD High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft Loss Transplantation Direct |
| title | High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft Loss |
| title_full | High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft Loss |
| title_fullStr | High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft Loss |
| title_full_unstemmed | High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft Loss |
| title_short | High Calcineurin Inhibitor Intrapatient Variability Is Associated With Renal Allograft Inflammation, Chronicity, and Graft Loss |
| title_sort | high calcineurin inhibitor intrapatient variability is associated with renal allograft inflammation chronicity and graft loss |
| url | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000000862 |
| work_keys_str_mv | AT akhilsharmamd highcalcineurininhibitorintrapatientvariabilityisassociatedwithrenalallograftinflammationchronicityandgraftloss AT aravindcherukurimdphd highcalcineurininhibitorintrapatientvariabilityisassociatedwithrenalallograftinflammationchronicityandgraftloss AT rajilbmehtamd highcalcineurininhibitorintrapatientvariabilityisassociatedwithrenalallograftinflammationchronicityandgraftloss AT puneetsoodmd highcalcineurininhibitorintrapatientvariabilityisassociatedwithrenalallograftinflammationchronicityandgraftloss AT sundaramhariharanmd highcalcineurininhibitorintrapatientvariabilityisassociatedwithrenalallograftinflammationchronicityandgraftloss |