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Warfarin Related Nephropathy:  Evidence Based Medicine Wisit Cheungpasitporn, MD. PGY -2, Internal  Medicine
<ul><li>How can warfarin cause nephropathy? </li></ul>
<ul><li>Abt AB, Carroll LE, Mohler JH.  </li></ul><ul><li>Department of Pathology, Milton S. Hershey Medical Center, Penn ...
 
 
<ul><li>Warfarin may induce AKI by causing  glomerular hemorrhage  and  renal tubular obstruction   by  RBC casts .  </li>...
Warfarin and AIN <ul><li>Nephron .  1989;52(2):196. </li></ul><ul><li>Acute renal failure due to hypersensitivity intersti...
<ul><li>Intern Med J.  2008 Apr;38(4):281-3. </li></ul><ul><li>Warfarin-induced allergic interstitial nephritis and leucoc...
CONCLUSIONS: Overanticoagulation is  associated  with faster  progression  of CKD in a high percentage of patients.  Our r...
<ul><li>“ The authors have termed the  unexplained increase in Cr  associated with  INR >3.0 , warfarin-related nephropath...
 
Objective <ul><li>To investigate further the prevalence, risk factors, and consequence of WRN, with emphasis on the extent...
Methods <ul><li>Analyzing the de-identified data of consecutive patients who had initiated warfarin therapy during the per...
Methods <ul><li>A multistep algorithm was utilized to identify patients with  presumptive WRN.  </li></ul><ul><li>The anal...
<ul><li>Cohort 1  ( N = 15,258 ): All patients who had  warfarin  between January 2005 and December 2009 </li></ul>Methods
<ul><li>Cohort 2  ( N = 6019 ). Pts who had at least one episode of INR >3.0 recorded. </li></ul><ul><li>(If multiple epis...
<ul><li>Cohort 4  ( N = 4816 ). Pts who had Cr within 3 mths before the 1st abnormal INR >3.0.  </li></ul><ul><ul><li>Excl...
Methods <ul><li>Cohort 5  (final cohort;  N = 4006 ).  </li></ul><ul><ul><li>This cohort was stratified into  CKD or no CK...
Statistical Methods <ul><li>The authors checked for the significance of group as a predictor of survival,  controlling for...
Statistical Methods <ul><li>The  χ  2- tests  were used to assess differences in categorical variables between groups; a t...
Results <ul><li>Identification of the Study Patients  in the Ohio State University Medical Center Information Warehouse Da...
Results <ul><li>Cohort 5  ( N = 4006 ) </li></ul><ul><ul><li>821 pts with presumptive WRN (increase in Cr ≥0.3 mg/dl withi...
Results <ul><li>INR  and Sequential Changes in  Cr  and Estimated  GFR  in WRN Patients Compared With No-WRN Patients </li...
Figure 1 4.44 4.15 4.57 4.13 4.22 4.22 2.75±1.65 1.17±0.71 1.80±1.24 1.13±0.67 P <0.0001 2.45±1.57 1.01±0.49 P <0.0001 1.5...
Figure 2
Figure 3 eGFR calculated by CKD-EPI Creatinine Equation
Results <ul><li>Baseline Clinical  Characteristics  of the WRN Patients and the No-WRN Patients </li></ul>
 
 
Hematuria and WRN Figure 4
Results <ul><li>Concurrent Medication and WRN </li></ul>
 
<ul><li>Survival Rate and WRN </li></ul>Results
Figure 5 73% 58% P<0.001 81.1% 68.9% P= 0.049 P=0.064 3.65,  95% CI 2.81-4.75 Non-significant levels 6months Controlling f...
<ul><li>Of the 4006 patients who experienced an INR >3.0,  20.5%  developed presumptive WRN  </li></ul><ul><li>Among the C...
<ul><li>Why such a common complication of warfarin therapy has been unrecognized until just recently?   </li></ul><ul><li>...
<ul><li>Why such a common complication of warfarin therapy has been unrecognized until just recently? </li></ul><ul><li>Th...
Limitation <ul><li>A retrospective study in which the testing protocol was not prespecified. Thus, this work suffers from ...
Summary <ul><li>To clearly establish the risk factors for WRN and its consequences will require a prospective study.   The...
Implications for practice  <ul><li>Warfarin may induce AKI  </li></ul><ul><ul><li>glomerular hemorrhage  and  renal tubula...
Implications for research <ul><li>Prospective study </li></ul><ul><li>Retrospective study </li></ul><ul><ul><li>Control gr...
RIFLE vs. AKIN criteria <ul><li>The  RIFLE  criteria was put forward by the Acute Dialysis Quality Initiative (ADQI) in 20...
AKIN Criteria
 
Special Thanks to: <ul><li>Dr. Zoltick ; my EBM preceptor </li></ul><ul><li>Dr. Knight  ; my statistic teacher and fly fis...
eGFR calculated by CKD-EPI Creatinine Equation
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Evidence base in Warfarin related nephropathy

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Warfarin related nephropathy; Evidence Based Medicine

  1. 1. Warfarin Related Nephropathy: Evidence Based Medicine Wisit Cheungpasitporn, MD. PGY -2, Internal Medicine
  2. 2. <ul><li>How can warfarin cause nephropathy? </li></ul>
  3. 3. <ul><li>Abt AB, Carroll LE, Mohler JH. </li></ul><ul><li>Department of Pathology, Milton S. Hershey Medical Center, Penn </li></ul><ul><li>State Geisinger Health System, Hershey, PA 17033, USA. </li></ul><ul><li>Glomerular hematuria in a pt with excessive warfarin anticoagulation from with underlying structural abnormality of glomerular basement membrane, suspected warfarin-induced glomerular hematuria. </li></ul>Thin basement membrane disease and acute renal failure secondary to gross hematuria and tubular necrosis Am J Kidney Dis. 2000 Mar;35(3):533-6.
  4. 6. <ul><li>Warfarin may induce AKI by causing  glomerular hemorrhage  and  renal tubular obstruction   by RBC casts . </li></ul>Warfarin Related Nephropathy?
  5. 7. Warfarin and AIN <ul><li>Nephron .  1989;52(2):196. </li></ul><ul><li>Acute renal failure due to hypersensitivity interstitial nephritis induced by warfarin sodium. </li></ul><ul><li>Volpi A ,  Ferrario GM ,  Giordano F ,  Antiga G ,  Battini G ,  Fabbri C ,  Meroni M ,  Sessa A . </li></ul><ul><li>Source </li></ul><ul><li>Unità Operativa di Nefrologia e Dialisi. Servizio di Anatomia Patologica. Ospedale di Vimercate, Italia. </li></ul>
  6. 8. <ul><li>Intern Med J.  2008 Apr;38(4):281-3. </li></ul><ul><li>Warfarin-induced allergic interstitial nephritis and leucocytoclastic vasculitis. </li></ul><ul><li>Kapoor KG ,  Bekaii -Saab T . </li></ul><ul><li>Source </li></ul><ul><li>The Ohio State University College of Medicine, Columbus, Ohio , USA. </li></ul>Warfarin and AIN
  7. 9. CONCLUSIONS: Overanticoagulation is  associated  with faster  progression  of CKD in a high percentage of patients. Our results indicate the need for prospective trials. Nevertheless, we suggest that our findings are sufficiently compelling at this point to justify extra caution in  warfarin -treated CKD patients to avoid overanticoagulation. 37% of CKD pts with elevated INR developed elevated Cr
  8. 10. <ul><li>“ The authors have termed the unexplained increase in Cr associated with INR >3.0 , warfarin-related nephropathy (WRN).” </li></ul>
  9. 12. Objective <ul><li>To investigate further the prevalence, risk factors, and consequence of WRN, with emphasis on the extent to which WRN develops in CKD compared with no-CKD patients.  </li></ul>
  10. 13. Methods <ul><li>Analyzing the de-identified data of consecutive patients who had initiated warfarin therapy during the period of January 2005 to December 2009 at the OSUMC. </li></ul>
  11. 14. Methods <ul><li>A multistep algorithm was utilized to identify patients with presumptive WRN. </li></ul><ul><li>The analysis reported here was performed on cohort 5 (the final cohort). </li></ul>
  12. 15. <ul><li>Cohort 1 ( N = 15,258 ): All patients who had warfarin between January 2005 and December 2009 </li></ul>Methods
  13. 16. <ul><li>Cohort 2 ( N = 6019 ). Pts who had at least one episode of INR >3.0 recorded. </li></ul><ul><li>(If multiple episodes occurred, used the 1st one for the present analysis) </li></ul><ul><li>Cohort 3 ( N = 4848 ). Pts who had Cr within 1 week after the first INR > 3.0. </li></ul>Methods
  14. 17. <ul><li>Cohort 4 ( N = 4816 ). Pts who had Cr within 3 mths before the 1st abnormal INR >3.0. </li></ul><ul><ul><li>Excluded those who had, based on ICD-9 codes, end-stage renal disease or evidence of clinically relevant hemorrhage within the first week after INR >3.0 </li></ul></ul>Methods
  15. 18. Methods <ul><li>Cohort 5 (final cohort;  N = 4006 ). </li></ul><ul><ul><li>This cohort was stratified into CKD or no CKD using the ICD-9 codes. </li></ul></ul>
  16. 19. Statistical Methods <ul><li>The authors checked for the significance of group as a predictor of survival, controlling for the following covariates: </li></ul><ul><ul><li>Age at INR spike </li></ul></ul><ul><ul><li>CKD </li></ul></ul><ul><ul><li>DM and DN </li></ul></ul><ul><ul><li>Heart failure </li></ul></ul><ul><ul><li>Atrial fibrillation </li></ul></ul><ul><ul><li>Glomerulonephritis </li></ul></ul>
  17. 20. Statistical Methods <ul><li>The  χ  2- tests were used to assess differences in categorical variables between groups; a two-sample  t -test was used for age. </li></ul><ul><li>Two-sample  t -tests were performed to compare INR between WRN and no WRN as explorative analyses for the overall sample and CKD/non-CKD subgroups. </li></ul>
  18. 21. Results <ul><li>Identification of the Study Patients in the Ohio State University Medical Center Information Warehouse Database </li></ul>
  19. 22. Results <ul><li>Cohort 5 ( N = 4006 ) </li></ul><ul><ul><li>821 pts with presumptive WRN (increase in Cr ≥0.3 mg/dl within 1 week of INR >3.0, 20.5% of cohort 5) </li></ul></ul><ul><ul><li>3185 pts with no WRN (no increase in Cr≥0.3 mg/dl within 1 week of INR >3.0, 79.5% of cohort 5). </li></ul></ul>
  20. 23. Results <ul><li>INR and Sequential Changes in Cr and Estimated GFR in WRN Patients Compared With No-WRN Patients </li></ul>
  21. 24. Figure 1 4.44 4.15 4.57 4.13 4.22 4.22 2.75±1.65 1.17±0.71 1.80±1.24 1.13±0.67 P <0.0001 2.45±1.57 1.01±0.49 P <0.0001 1.52±1.08 1.00±0.51 3.25±1.67 1.79±1.09 P <0.0001 2.29±1.33 1.65±0.94
  22. 25. Figure 2
  23. 26. Figure 3 eGFR calculated by CKD-EPI Creatinine Equation
  24. 27. Results <ul><li>Baseline Clinical Characteristics of the WRN Patients and the No-WRN Patients </li></ul>
  25. 30. Hematuria and WRN Figure 4
  26. 31. Results <ul><li>Concurrent Medication and WRN </li></ul>
  27. 33. <ul><li>Survival Rate and WRN </li></ul>Results
  28. 34. Figure 5 73% 58% P<0.001 81.1% 68.9% P= 0.049 P=0.064 3.65, 95% CI 2.81-4.75 Non-significant levels 6months Controlling for covariates; age, CKD, DM, heart falure, GN 3.19, 95% CI 2.45-4.15 Hazard ratio for death
  29. 35. <ul><li>Of the 4006 patients who experienced an INR >3.0, 20.5% developed presumptive WRN </li></ul><ul><li>Among the CKD patients , the incidence of presumptive WRN was 33% , which is comparable to the 37% incidence of WRN that previously reported in warfarin-treated CKD patients. </li></ul><ul><li>Among the no-CKD patients , the incidence of presumptive WRN was 16.5%. </li></ul>Discussion
  30. 36. <ul><li>Why such a common complication of warfarin therapy has been unrecognized until just recently? </li></ul><ul><li>Before this study, there was no compelling reason to believe that lesser degrees of warfarin coagulopathy could cause AKI. </li></ul><ul><li>WRN usually occurs early in the course of warfarin therapy. Thus, at any given time, the prevalence of acute WRN among all warfarin-treated patients is relatively low. </li></ul>Discussion
  31. 37. <ul><li>Why such a common complication of warfarin therapy has been unrecognized until just recently? </li></ul><ul><li>The risk of WRN is particularly great in high-risk patients who have multiple risk factors for AKI. </li></ul><ul><li>Nephrologists might be reluctant to perform a kidney biopsy in patients receiving warfarin. </li></ul>Discussion
  32. 38. Limitation <ul><li>A retrospective study in which the testing protocol was not prespecified. Thus, this work suffers from ascertainment bias. </li></ul><ul><li>Study required Cr by 1 week after the onset of INR >3.0. Frequent measurement of Cr is more likely in sicker patients. Thus, this study may have identified the sickest patients with INR >3.0. </li></ul><ul><li>No consistent testing of proteinuria around the time of the INR spike. ?proteinuria itself was a risk factor for WRN. </li></ul>
  33. 39. Summary <ul><li>To clearly establish the risk factors for WRN and its consequences will require a prospective study. The authors suggest that the present work provides compelling reasons to proceed with the prospective study. </li></ul>
  34. 40. Implications for practice <ul><li>Warfarin may induce AKI </li></ul><ul><ul><li>glomerular hemorrhage  and  renal tubular obstruction   by RBC casts </li></ul></ul><ul><ul><li>?AIN (2 case reports) </li></ul></ul><ul><li>Watch more carefully in INR>3.0 pts. </li></ul><ul><ul><li>?Mechanical valve replacement pts. </li></ul></ul><ul><li>?WRN and mortality rate </li></ul>
  35. 41. Implications for research <ul><li>Prospective study </li></ul><ul><li>Retrospective study </li></ul><ul><ul><li>Control group (patients who are not on warfarin) </li></ul></ul><ul><ul><li>Confounding factors </li></ul></ul><ul><ul><li>Definition of AKI; RIFLE vs. AKIN criteria </li></ul></ul><ul><ul><li>Drugs interaction with warfarin </li></ul></ul>
  36. 42. RIFLE vs. AKIN criteria <ul><li>The RIFLE criteria was put forward by the Acute Dialysis Quality Initiative (ADQI) in 2005.  </li></ul><ul><li>The AKIN &quot;Acute Kidney Injury Network&quot; criteria were published in 2007 after a meeting in the Netherlands comprised of multiple experts on AKI. </li></ul>
  37. 43. AKIN Criteria
  38. 45. Special Thanks to: <ul><li>Dr. Zoltick ; my EBM preceptor </li></ul><ul><li>Dr. Knight ; my statistic teacher and fly fishing master </li></ul>
  39. 46. eGFR calculated by CKD-EPI Creatinine Equation
  • RahmaMahmoud3

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  • ScientiaMedicina

    Jan. 4, 2015
  • NegarMortazavi

    Nov. 26, 2014
  • HammadQadir

    May. 14, 2013

Evidence base in Warfarin related nephropathy

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