Raj Kiran Medapalli, MD, MPH.  Nephrology Fellow January 5 th  2011 Mount Sinai School of Medicine Division of Nephrology ...
Transplant Nephrectomy Improves Survival following a Failed Renal Allograft . JASN 21: 374–380, 2010. Journal Club  Januar...
Failed renal allograft - Disease burden <ul><li>Each year approximately 2000 patients enter dialysis in the US after allog...
Prognosis after failed primary renal allograft <ul><li>19208 pts with primary renal allograft failure between 1985 & 1995(...
Death after primary renal allograft loss 78564 pts who underwent primary renal transplant  between 1988-1998; 10 yr follow...
Source: Kaplan and Meier-Kriesche. AJT 2002; 2: 970-74
Potential explanations for high mortality in patients with allograft failure <ul><li>Chronically rejected renal allograft ...
Allograft nephrectomy after transplant failure <ul><li>19107 pts with allograft failure who initiated dialysis between 199...
<ul><li>Peri-operative mortality rate (within 90 days of nephrectomy): 5% </li></ul><ul><li>Median length of hospitalizati...
Allograft nephrectomy & repeat transplantation <ul><li>Nephrectomy and sensitization prior to repeat transplantation </li>...
Usual indications for transplant nephrectomy <ul><li>Hyperacute allograft rejection (ABO incomp,  anti-HLA abs, anti-endot...
Withdrawal of immunosuppression after allograft failure <ul><li>No data from controlled prospective studies to guide us.  ...
 
Study Design - 1 <ul><li>Source database : USRDS. </li></ul><ul><li>Inclusion Criteria : </li></ul><ul><li>Age > 18 years ...
 
 
Study Design - 2 <ul><li>Follow-up period : </li></ul><ul><li>From return to dialysis to study end (12/31/04) or death or ...
Study outcomes & Statistical analysis <ul><li>Groups being compared: Nephrectomy vs. Non-nephrectomy. </li></ul><ul><li>Al...
Propensity Scores <ul><li>The propensity score is the  conditional probability of receiving the treatment given measured c...
Propensity Scores <ul><li>For e.g. each subject has a set of measured covariates (X) and an indicator of treatment (Z = 1 ...
Propensity Scores <ul><li>The propensity score e(X) = prob(Z = 1|X) was  estimated using logistic regression  to predict t...
Results <ul><li>Mean f/u time: 2.93 ± 2.26 years. </li></ul><ul><li>Only 124 pts out of 10,951 pts (1.1%) were lost to f/u...
 
 
b Defined as need for dialysis before hospital discharge after transplantation.
 
d Coded during any hospitalization occurring after return to dialysis after failed kidney transplant.
 
Unadjusted Rates (1994-2004) All-cause mortality Total N=10,951 32 vs. 36 per 100 Person Years (p=0.0324) Repeat transplan...
Adjusted for : <ul><li>Quartile of propensity score. </li></ul><ul><li>Subject age, race, gender, lack of insurance. </li>...
Adjusted rates + Sensitivity Analysis
Results summary <ul><li>Allograft nephrectomy vs. no-nephrectomy </li></ul><ul><li>26-37% reduction in mortality in patien...
Study strengths <ul><li>USRDS - nationally representative sample.  </li></ul><ul><li>When compared to the previous study b...
Study weaknesses <ul><li>Registry data: susceptible to effects of missing data, misclassification and residual confounding...
My Conclusions - 1 <ul><li>Considering the following:  </li></ul><ul><ul><li>high overall annual mortality in patients wit...
<ul><li>Black race, cadaveric donor, receipt of OKT3/Thymo, episodes of rejection,  DGF, etc, are more commonly seen  in p...
My conclusions - 3 <ul><li>Routine allograft nephrectomy in stable dialysis patients with a failed renal allograft should ...
<ul><li>Thank you. </li></ul>
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Transplant Nephrectomy Improves Survival following a Failed Renal Allograft (Journal Club)

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Transplant Nephrectomy Improves Survival following a Failed Renal Allograft (Journal Club)

  1. 1. Raj Kiran Medapalli, MD, MPH. Nephrology Fellow January 5 th 2011 Mount Sinai School of Medicine Division of Nephrology Journal Club
  2. 2. Transplant Nephrectomy Improves Survival following a Failed Renal Allograft . JASN 21: 374–380, 2010. Journal Club January 5 th 2011 Raj Kiran Medapalli, MD, MPH.
  3. 3. Failed renal allograft - Disease burden <ul><li>Each year approximately 2000 patients enter dialysis in the US after allograft failure. </li></ul><ul><li>Approximately 20% of all patients on the renal transplant waiting list in the US (16,000 out of 80,000 listed) have had a previously failed allograft. </li></ul><ul><li>Source: Perl et al. Semin Dial 21:239–244, 2008 </li></ul>
  4. 4. Prognosis after failed primary renal allograft <ul><li>19208 pts with primary renal allograft failure between 1985 & 1995(USRDS). F/u until death, transplantation or 12/31/96. Mean f/u: 3.8 years. </li></ul><ul><li>Total mortality during f/u : </li></ul><ul><ul><li>34.5% </li></ul></ul><ul><li>5-yr patient survival before re-transplantation : </li></ul><ul><ul><li>DM-Type1: 36%, DM-Type2: 49%, Non-diabetic ESRD: 65% </li></ul></ul><ul><li>5-yr repeat transplantation rates : </li></ul><ul><ul><li>DM-Type1: 29%, DM-Type2: 15%, Non-diabetic ESRD: 19% </li></ul></ul><ul><li>Repeat transplantation was associated with reduction in 5-yr mortality compared to waitlisted dialysis pts with prior allograft failure : </li></ul><ul><ul><li>DM-Type1: 45% reduction </li></ul></ul><ul><ul><li>Non-diabetic ESRD: 23% reduction. </li></ul></ul><ul><li>Most common causes of death : </li></ul><ul><ul><li>Unknown (33%), heart disease (22.7%), cardiac arrest (18.4%), sepsis (15.5%), CVA (4.8%), GI/liver disease (3.8%), & malignancy (1.8%). </li></ul></ul><ul><li>Source: Ojo et al. Transplantation. 1998: 66(12), 1651-59. </li></ul>
  5. 5. Death after primary renal allograft loss 78564 pts who underwent primary renal transplant between 1988-1998; 10 yr follow-up. USRDS In comparison, annual death rate on renal transplant waiting list is 6.33% per 100-pt-years (9.27% for diabetics) Annual adjusted death rates per 100 pt-years Death with functioning transplant Death after graft loss N Annual rate % N Annual rate % Overall 10816 2.81 4712 9.42 Cardio-vasc 3402 0.69 2252 4.31 Infectious 1856 0.37 879 1.63 Malignancy 808 0.19 122 0.11
  6. 6. Source: Kaplan and Meier-Kriesche. AJT 2002; 2: 970-74
  7. 7. Potential explanations for high mortality in patients with allograft failure <ul><li>Chronically rejected renal allograft serves as a nidus for immunoreactivity. </li></ul><ul><li>Analogous to clotted grafts with subclinical infection in patients on hemodialysis, the failed graft may contribute to a chronic inflammatory state characterized by hypoalbuminemia, elevated CRP & anemia. </li></ul><ul><li>Continued use of low-dosage immunosuppression increases risk of CV and infectious complications. </li></ul>
  8. 8. Allograft nephrectomy after transplant failure <ul><li>19107 pts with allograft failure who initiated dialysis between 1995 and 2003 (USRDS). F/u until death, re-transplantation or 12/31/04 (mean f/u 2.4 yrs). </li></ul><ul><li>Patients categorized as having early graft failure (graft survival <12 months) & late graft failure (>= 12 months) based on initial exploratory analysis which suggested that the nephrectomy rates differed in these pts. </li></ul><ul><li>In 3707 patients with early transplant failaure: </li></ul><ul><ul><li>Nephrectomy rate: 56% </li></ul></ul><ul><ul><li>Higher risk of death (HR: 1.13, 1.01-1.26) </li></ul></ul><ul><li>In 15400 patients with late transplant failure : </li></ul><ul><ul><li>Nephrectomy rate: 27% </li></ul></ul><ul><ul><li>Lower risk of death (HR: 0.88, 0.83-0.95) </li></ul></ul><ul><li>Cumulative probability of nephrectomy at 1 week, 2 weeks, 3 months, 6 months and 1 year after transplant failure: </li></ul><ul><ul><li>5.3%, 7.9%, 17.6%, 25%, 30.9%. </li></ul></ul><ul><ul><li>89% of the nephrectomies were performed within 1 yr of graft failure </li></ul></ul><ul><ul><li>Source: Johnston et al. AJT 2007. 7:1961-67. </li></ul></ul>
  9. 9. <ul><li>Peri-operative mortality rate (within 90 days of nephrectomy): 5% </li></ul><ul><li>Median length of hospitalization: 6 days. (IQR: 4-12) </li></ul><ul><li>Sepsis was the most frequent non-fatal short term complication, followed by CHF. </li></ul><ul><li>Factors consistently associated with nephrectomy : </li></ul><ul><ul><li>Age < 40 years at allograft failure </li></ul></ul><ul><ul><li>HLA mismatch > 3 </li></ul></ul><ul><ul><li>Wait listing for repeat transplantation within 1 yr. </li></ul></ul><ul><li>Factors uniquely associated Nx in patients with early graft failure : </li></ul><ul><ul><li>Delayed graft function </li></ul></ul><ul><li>Factors uniquely associated Nx in patients with late graft failure : </li></ul><ul><ul><li>Female gender, Black race, absence of diabetes </li></ul></ul><ul><ul><li>Decreased donor transplant, induction with non-depleting antibody. </li></ul></ul><ul><ul><li>HD after transplant failure between 1995-97 compared with 2001-03. Source: Johnston et al. AJT 2007. 7:1961-67 </li></ul></ul>Allograft nephrectomy after transplant failure (US)
  10. 10. Allograft nephrectomy & repeat transplantation <ul><li>Nephrectomy and sensitization prior to repeat transplantation </li></ul><ul><ul><li>18% (3496) patients received a second transplant </li></ul></ul><ul><ul><li>37% percent of these patients had a allograft nephrectomy prior to the 2 nd Tx. </li></ul></ul><ul><ul><li>In patients who had PRA levels of 0-10% or 11-30% prior to the 1 st transplant, the PRA levels prior to repeat transplantation were significantly higher in patients who had a transplant nephrectomy (p<0.0001) </li></ul></ul><ul><ul><li>No difference in patients who had PRA levels of > 31%. </li></ul></ul><ul><li>Nephrectomy and 2 nd allograft survival after repeat transplantation </li></ul><ul><ul><li>In patients with early graft failure : </li></ul></ul><ul><ul><ul><li>Decreased risk of allograft failure after adjusting for multiple covariates (HR: 0.72, 0.56 to 0.94) </li></ul></ul></ul><ul><ul><li>In patients with delayed graft failure : </li></ul></ul><ul><ul><ul><li>Increased risk of allograft failure (HR: 1.20, 1.02 – 1.41) </li></ul></ul></ul><ul><ul><ul><li>Source: Johnston et al. AJT 2007. 7:1961-67 </li></ul></ul></ul>
  11. 11. Usual indications for transplant nephrectomy <ul><li>Hyperacute allograft rejection (ABO incomp, anti-HLA abs, anti-endothelial abs) </li></ul><ul><li>Graft thrombosis (with/without rejection) – accounts for 45% of graft loss before 90d </li></ul><ul><li>Onset of symptoms and/or complications related to rejection and necrosis after withdrawal of immunosuppression </li></ul><ul><ul><li>Graft tenderness, fever, hematuria, localized edema, and occasionally infection </li></ul></ul><ul><li>History of early graft failure (with or without symptoms and/or complications) </li></ul><ul><ul><li>These patients are at much high risk of graft complications independent of whether immunosuppressive medications are withdrawn or not. </li></ul></ul><ul><ul><li>Abrupt withdrawal of immunosuppression increases risk. </li></ul></ul><ul><li>Signs and symptoms of a chronic inflammatory state with no other cause </li></ul><ul><ul><li>Anemia, hypoalbuminemia, elevated CRP </li></ul></ul><ul><li>Usual arguments against nephrectomy </li></ul><ul><li>Reported peri-operative complication rate: 6 to 37% </li></ul><ul><li>Concern that increased recipient immunoreactivity due to exposure to foreign antigens during nephrectomy operation can lead to reduced rates of repeat transplantation and possibly increased risk of subsequent allograft failure. </li></ul>
  12. 12. Withdrawal of immunosuppression after allograft failure <ul><li>No data from controlled prospective studies to guide us. </li></ul><ul><li>Usual practice : </li></ul><ul><li>For patients with early graft failure (< 1 year) : </li></ul><ul><ul><li>Immediate withdrawal combined with preemptive nephrectomy </li></ul></ul><ul><li>For patients with late allograft failure (>=1 year) : </li></ul><ul><ul><li>CNI and anti-metabolite are withdrawn immediately. </li></ul></ul><ul><ul><li>Prednisone tapered by 1mg/month until the drug is discontinued. </li></ul></ul><ul><ul><li>Monitor for symptoms of adrenal insufficiency. </li></ul></ul><ul><li>For patients with residual renal function : </li></ul><ul><ul><li>Anti-metabolite is withdrawn immediately. </li></ul></ul><ul><ul><li>Initially CNI reduced to once daily in the morning. </li></ul></ul><ul><ul><li>Initially prednisone reduced to 5mg/d. </li></ul></ul><ul><ul><li>CNI & prednisone tapered slowly over 3-6 months. </li></ul></ul><ul><ul><li>Slow taper may preserve residual renal function longer. </li></ul></ul><ul><li>For patients who develop symptoms of allograft rejection with withdrawal : </li></ul><ul><ul><li>Administer 5-7 day course of prednisone (0.3-1.0 mg/kg/d) </li></ul></ul><ul><ul><li>Refer to surgery for nephrectomy. </li></ul></ul>
  13. 14. Study Design - 1 <ul><li>Source database : USRDS. </li></ul><ul><li>Inclusion Criteria : </li></ul><ul><li>Age > 18 years </li></ul><ul><li>Returned to dialysis after allograft failure between Jan 1 st 1994 & December 31, 2004. </li></ul><ul><li>Single kidney transplant or 2 non-sequential kidney transplants. </li></ul><ul><li>Exclusion Criteria : </li></ul><ul><li>Renal allograft failed within 90 d of transplantation (because many of them will be 2/2 hyperacute rejection or graft thrombosis which are classical and accepted indications for nephrectomy). </li></ul><ul><li>Death within < 1 day after allograft failure (allograft failure 2/2 to death? Potential for misclassification in a retrospective database). </li></ul><ul><li>Did not have Medicare within 90 days of returning to dialysis (used medicare claims data used to define many variables). </li></ul><ul><li>Those without confirmed sequential transplants. </li></ul>
  14. 17. Study Design - 2 <ul><li>Follow-up period : </li></ul><ul><li>From return to dialysis to study end (12/31/04) or death or lost-to-f/u. </li></ul><ul><li>Patients were considered lost-to-f/u if no evidence of dialysis billing for 12 consecutive months in the absence of an identified death date. </li></ul><ul><li>Variable definitions : </li></ul><ul><li>Receipt of transplant nephrectomy was ascertained using Medicare claims data (CPT codes). </li></ul><ul><li>Info on demographics, co-morbidities and baseline labs was obtained from the USRDS 2728 form that was completed closest to the start of dialysis. </li></ul><ul><li>Info on transplant variables, donor characteristics, immunological risk, and immunosuppression and delayed graft fxn obtained from USRDS UNOS registration forms. </li></ul><ul><li>Hospitalization for conditions associated with transplant nephrectomy (fever, anemia, hematuria, abd pian, urinary obstruction, sepsis, UTI, cachexia, malnutrition and rejection) during the f/u period identified using primary or secondary ICD-9 codes </li></ul>
  15. 18. Study outcomes & Statistical analysis <ul><li>Groups being compared: Nephrectomy vs. Non-nephrectomy. </li></ul><ul><li>All cause mortality (primary outcome) </li></ul><ul><li>Unadjusted mortality rates (per 100 p-yrs) </li></ul><ul><li>Adjusted mortality rate using Cox-regression analysis (hazard ratio): </li></ul><ul><ul><ul><li>Quartile of propensity score for likelihood of receiving allograft nephrectomy during follow-up (c-statistic: 0.76). </li></ul></ul></ul><ul><ul><ul><li>Variables known to be associated with mortality after failed transplant. </li></ul></ul></ul><ul><ul><ul><li>Other variables that differed between those who died and those who did not die during f/u. </li></ul></ul></ul><ul><li>6 Sensitivity analyses (to test the impact of including each sub-group of patients who were excluded because of the exclusion criteria & establish robustness of the findings) </li></ul><ul><li>Likelihood of receiving 2 nd transplant during follow-up period. </li></ul><ul><li>Unadjusted rate of death within 30 days of Tx nephrectomy. </li></ul>
  16. 19. Propensity Scores <ul><li>The propensity score is the conditional probability of receiving the treatment given measured covariates . </li></ul><ul><li>In the absence of random assignment, adjustment for an estimated propensity score tends to balance the measured covariates that were used to construct the score among the treatment groups. </li></ul><ul><li>However, unlike random assignment of treatments, the propensity score does not balance covariates that were not measured . </li></ul><ul><li>The propensity score complements model-based procedures and is not a substitute for them . It is often used in conjunction with further model-based adjustments using regression or log-linear models. </li></ul>
  17. 20. Propensity Scores <ul><li>For e.g. each subject has a set of measured covariates (X) and an indicator of treatment (Z = 1 if treated and Z = 0 if control). </li></ul><ul><li>The propensity score, e(X), is the chance that a person with covariates X will receive treatment, that is, e(X) =prob(Z = 1|X). </li></ul><ul><li>What it means in the context of current study </li></ul><ul><li>Current retrospective study compares nephrectomy (Z = 1) with no-nephrectomy (Z= 0). </li></ul><ul><li>A propensity score was formulated from more than 50 covariates that characterized patient health at return to dialysis. </li></ul><ul><li>The covariates included, age, sex, race, smoking status, CAD, living donor vs. deceased donor kidney among other characteristics. </li></ul><ul><li>At baseline (return to dialysis) the two groups differed significantly in terms of many of these covariates. </li></ul>
  18. 21. Propensity Scores <ul><li>The propensity score e(X) = prob(Z = 1|X) was estimated using logistic regression to predict the probability of nephrectomy (Z) based on the covariates (X). </li></ul><ul><li>Patients were then divided into four strata according to their propensity score ; each stratum contained 25 percent of the patients. </li></ul><ul><li>Within each strata , the patients who did and did not undergo nephrectomy will have similar distributions of the covariates . </li></ul><ul><li>Patient outcomes were then compared among the two groups using Cox-regression analysis relating all-cause mortality to nephrectomy, multiple covariates and the four propensity score strata. </li></ul><ul><li>Accounting for the propensity score strata hence is an attempt to address and reduce the effect of possible treatment selection bias . </li></ul>
  19. 22. Results <ul><li>Mean f/u time: 2.93 ± 2.26 years. </li></ul><ul><li>Only 124 pts out of 10,951 pts (1.1%) were lost to f/u. </li></ul><ul><li>3785 pts out of 10,951 pts (34.56%) died by the end of follow-up. </li></ul><ul><li>3451 pts out of 10,951 pts (31.5%) had a transplant nephrectomy. </li></ul><ul><li>53 patients died within 30 days of transplant nephrectomy (i.e., rate of death at 30 days of transplant nephrectomy is 1.5%) </li></ul><ul><li>Median time between return to dialysis and nephrectomy: 1.66 yrs (IQR: 0.73 - 3.02). </li></ul>
  20. 25. b Defined as need for dialysis before hospital discharge after transplantation.
  21. 27. d Coded during any hospitalization occurring after return to dialysis after failed kidney transplant.
  22. 29. Unadjusted Rates (1994-2004) All-cause mortality Total N=10,951 32 vs. 36 per 100 Person Years (p=0.0324) Repeat transplantation Total N=10,951 10% vs. 4.1% (p<0.001)
  23. 30. Adjusted for : <ul><li>Quartile of propensity score. </li></ul><ul><li>Subject age, race, gender, lack of insurance. </li></ul><ul><li>CAD, MI, cardiac arrest, CHF, CVA. </li></ul><ul><li>Diabetes, HTN, COPD, Cancer. </li></ul><ul><li>Inability to ambulate/transfer. </li></ul><ul><li>Obesity. </li></ul><ul><li>Serum creatinine, albumin, hemoglobin. </li></ul><ul><li>Year of transplantation. </li></ul><ul><li>Donor age, donor race, donor cause of death, cold-ischemia time and anoxia. </li></ul><ul><li>Interim hospitalizations for any of the following: anemia, abdominal pain, urinary obstruction, sepsis, UTI, malnutrition, or complication of transplanted kidney. </li></ul>
  24. 31. Adjusted rates + Sensitivity Analysis
  25. 32. Results summary <ul><li>Allograft nephrectomy vs. no-nephrectomy </li></ul><ul><li>26-37% reduction in mortality in patients who underwent allograft nephrectomy after adjustment for potential confounders and likelihood of receiving nephrectomy (HR: 0.68, 95%CI: 0.63-0.74). </li></ul><ul><li>Beneficial effect on mortality is present regardless of timing of allograft failure and more pronounced in patients who experienced late allograft failure (HR: 0.65 vs. 0.76). </li></ul><ul><li>Patients who underwent allograft nephrectomy were 2.4 times more likely to undergo repeat transplantation (10% vs 4%, p < 0.001, unadjusted estimate). </li></ul><ul><li>Low risk of death from nephrectomy itself: Rate of death within 30 days of transplant nephrectomy was 1.5% (53 out of 3451 pts). </li></ul>
  26. 33. Study strengths <ul><li>USRDS - nationally representative sample. </li></ul><ul><li>When compared to the previous study by Johnston et al: </li></ul><ul><ul><li>Excluded patients whose graft failed within 90days of transplantation (N=13K). Graft failure in many of these pts is likely secondary to hyperacute rejection or graft thrombosis - which are classical and accepted indications for nephrectomy. </li></ul></ul><ul><ul><li>Excluded pts who died < 1 day after allograft failure (N=7K). Allograft failure 2/2 to death? Potential for misclassification in a retrospective database. </li></ul></ul><ul><ul><li>Included a larger set of potential confounders. </li></ul></ul><ul><ul><li>Accounted for clinical events (hospitalizations) during f/u. </li></ul></ul><ul><li>Also attempted to control for potential biases using propensity score method and adjusting for all relevant measured confounders which was no done in earlier studies. </li></ul><ul><li>Performed several sensitivity analyses to demonstrate robustness of the findings and examined the effect of some of the inclusion and exclusion criteria used. </li></ul>
  27. 34. Study weaknesses <ul><li>Registry data: susceptible to effects of missing data, misclassification and residual confounding from unmeasured variables </li></ul><ul><li>Treatment selection bias: the two groups had major differences at baseline with respect to many important co-morbidities which will impact the decision to perform the nephrectomy as well as mortality. </li></ul><ul><li>Propensity scoring mitigates the treatment selection bias to some extent but does not account for unmeasured variables. </li></ul><ul><li>No information on cause of graft failure and cause of death. </li></ul><ul><li>No information on timing of withdrawal of immunosuppression and immunosuppression at the time of nephrectomy. </li></ul><ul><li>Did not look at non-fatal complications of nephrectomy (need for transfusions, sepsis, etc) </li></ul><ul><li>Did not report morality rates by primary dz (diabetic, non-diabetic) </li></ul><ul><li>Did not look at wait listing rates. </li></ul><ul><li>Did not look at graft and patient survival in pts who underwent re-transplantation . </li></ul>
  28. 35. My Conclusions - 1 <ul><li>Considering the following: </li></ul><ul><ul><li>high overall annual mortality in patients with a failed transplant (10% per 100-pt yrs) </li></ul></ul><ul><ul><li>low peri-operative mortality associated with allograft nephrectomy (1.5%) </li></ul></ul><ul><ul><li>potential mortality benefit associated with it (26-37%) and </li></ul></ul><ul><ul><li>improved chances of receiving a 2 nd transplant (10% vs. 4%), </li></ul></ul><ul><li>elective allograft nephrectomy should be discussed as an option and offered to stable dialysis patients with a failed renal allograft, especially to those patients who are good surgical candidates in general and to all patients with symptoms suggestive of rejection after withdrawal of immunosuppression. </li></ul>
  29. 36. <ul><li>Black race, cadaveric donor, receipt of OKT3/Thymo, episodes of rejection, DGF, etc, are more commonly seen in patients who underwent allograft nephrectomy in this study. </li></ul><ul><li>However, because this is a retrospective study we cannot conclude that there is relationship between these variables and nephrectomy. For e.g. we cannot use them to predict who will need or benefit more from a nephrectomy in the future. </li></ul><ul><li>Utility of such results technically limited to hypothesis generation. </li></ul>My Conclusions - 2
  30. 37. My conclusions - 3 <ul><li>Routine allograft nephrectomy in stable dialysis patients with a failed renal allograft should be evaluated against current management strategies in a prospective setting. </li></ul><ul><li>A RCT trial may be difficult to do as recruitment will be difficult and drop out rate may be high (especially in the nephrectomy arm). </li></ul><ul><li>A multi-center prospective cohort study would also allow for more robust evaluation of this hypothesis: </li></ul><ul><ul><li>Offer nephrectomy to all stable dialysis pts (>=90 days after re-initiation of dialysis) who meet preset eligibility criteria (to exclude high surgical risk pts) and follow patients who did and did not undergo nephrectomy for 5 years . </li></ul></ul><ul><ul><li>Examine mortality and its causes/predictors, timing of immunosuppresion withdrawal, early vs. late graft failure, immunogenecity, re-transplantation rates & graft survival. </li></ul></ul><ul><ul><li>Also examine histology , especially in asymptomatic patients to see if there was any sub-clinical inflammation. </li></ul></ul>
  31. 38. <ul><li>Thank you. </li></ul>

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