Utility of mammography for chronic kidney disease patients undergoing kidney transplant evaluation.

UNLABELLED: Transplant centers typically require screening mammography (MMG) for women ≥40 during evaluation. American Cancer Society recommends starting annual MMG at 40, while USPSTF recommends biennial MMG at 50. We sought to determine the effect of age and other breast malignancy risk factors on screening MMG in the pre-transplant renal failure population undergoing transplant evaluation. METHODS: We retrospectively examined women ≥40 undergoing kidney transplant evaluation from 2006 to 2012 (n = 541). RESULTS: Patients aged 40.0-49.9 and ≥50 had similar rates of breast biopsy and breast malignancy. African Americans underwent a higher rate of biopsies (OR 2.391, 95%CI 1.111-5.019, p = 0.026), with a lower rate of biopsy in those already on dialysis at presentation (OR 0.434, 95%CI 0.212-0.888, p = 0.022). Higher breast density (>50% fibroglandular tissue) increased both rate of biopsy (OR 2.876, 95%CI 1.377-6.010, p = 0.005) and malignancy (OR 5.061, 95%CI 1.012-25.315, p = 0.048). CONCLUSIONS: As we found no independent differences in biopsy or malignancy between age groups, it is reasonable for transplant centers to use the same evaluation MMG screening policy for all women ≥40. However, as malignancy risk increased with higher breast density, a lower threshold for additional workup may be warranted in patients with dense breasts or an indeterminate lesion on MMG.

Enhancing kidney function with thrombolytic therapy following donation after cardiac death: a multicenter quasi-blinded prospective randomized trial.

Kidneys from donors after cardiac death (DCD) are at risk for inferior outcomes, possibly due to microthrombi and additional warm ischemia. We describe an organ procurement organization-wide trial utilizing thrombolytic tissue plasminogen activator (tPA) during machine pulsatile perfusion (MPP). A kidney from each recovered kidney pair was prospectively randomized to receive tPA (50 mg Alteplase) or no tPA (control) in the MPP perfusate. From 2011 to 2013, 24 kidneys were placed with enrolled recipients from 19 DCD kidney donors. There were no significant differences for absolute values of flow or resistance while undergoing MPP between the groups, nor rates of achieving discrete flow and resistance targets. While there was a trend toward lower creatinine and higher glomerular filtration rates in the tPA group at 3, 6, 9, and 12 months, these differences were not significant. Delayed graft function (DGF) rates were 41.7% in the tPA group vs. 58.4% in the control group (OR 0.51, 95%CI 0.10-2.59, p = 0.68). Death-censored graft survival was similar between the groups. In this pilot study, encouraging trends are seen in kidney allograft function independent of MPP parameters following DCD kidney transplantation for those kidneys receiving thrombolytic tPA and MPP, compared with standard MPP.

Pancreatic resection in octogenarians.

BACKGROUND: Few studies exist that evaluate outcomes of pancreatectomy in patients > or =80 y of age, an age group increasing in size in the United States. This study analyzes the outcomes of pancreatectomy in patients > or =80 y of age. METHODS: The medical records of 32 patients > or =80 y of age undergoing pancreatectomy at our institution from April 1995 through October 2008 were reviewed, and outcomes were analyzed. RESULTS: The median patient age was 82 y, and 75% were ASA Class 3. Eighty-one percent of the resections were pancreaticoduodenectomies. There were no operative deaths. Sixty-six percent of patients suffered at least one complication. The median length of stay was 11 d. Eighty-one percent of the resections were performed for cancer. Median survival for all patients was 14.4 mo. Median survival for patients with cancer was 12 mo versus 103 mo for patients without cancer, P = 0.017. CONCLUSIONS: Pancreatectomy in patients > or =80 y of age can be performed with a low risk of mortality but with significant morbidity.

Long-term graft outcomes after steroid withdrawal in African American kidney transplant recipients receiving sirolimus and tacrolimus.

BACKGROUND: We previously reported excellent short-term outcomes in African American kidney transplant patients receiving tacrolimus/sirolimus and withdrawn from corticosteroid therapy three months after transplantation. We now report the long-term outcomes of patients subjected to this protocol. METHODS: In all, 47 African American kidney transplant recipients were enrolled in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids, without antibody induction therapy. Eligible patients were withdrawn from prednisone between three and five months posttransplant, and followed for acute rejection and changes in renal function. Outcomes (group 1, n=32) were compared to those of patients deemed not to be candidates for steroid withdrawal (group 2, n=15). RESULTS: After a mean follow-up of 48.5 months, 13 of 32 patients (41%) in group 1 developed acute rejection; only 13 patients (41%) remain steroid-free. Nine of 13 rejection episodes were associated with noncompliance. Graft loss occurred in 8 of 32 patients (25%) in group 1 and in 5 of 15 patients (33%) in group 2 (P=NS). Serum creatinine rose from 1.4+/-0.41 to 2.45+/-1.7 mg/dL in group 1 (P=0.004) and from 2.1+/-0.45 to 2.62+/-1.2 mg/dL (P=NS) in group 2. Among 13 patients in group 1 who remain steroid-free, creatinine concentration has risen from 1.28+/-.0.37 prior to steroid withdrawal to 1.64+0.54 at last follow-up (P=0.027). CONCLUSIONS: Late noncompliance and/or rejection in African Americans withdrawn from steroids have a negative impact on long-term graft function and survival. Steroid withdrawal may be associated with long-term deterioration of renal function, even in the absence of overt acute rejection.

The Utility of Screening Colonoscopy During Kidney Transplant Evaluation.

OBJECTIVES: Transplant centers often recommend, but not necessarily require, screening colonoscopies for people over 50 years of age in accordance with the US Preventative Services Task Force guidelines for the general population. We sought to identify risk factors affecting colonoscopy results in renal failure patients undergoing kidney transplant evaluation. MATERIALS AND METHODS: We retrospectively examined patients undergoing kidney transplant evaluation from 2009 to 2012 (n = 469 patients). Comparisons were made between colonoscopy reports categorized as normal (no finding or hyperplastic polyp) or abnormal (adenomatous polyp or carcinoma). RESULTS: Of 469 patients who met the study criteria, 303 (64.6%) had normal colonoscopies and 166 (35.4%) had abnormal colonoscopies. Logistic regression analysis showed that male sex (odds ratio = 2.09; 95% confidence interval, 1.37-3.20; P = .001) and increasing age (odds ratio = 1.04; 95% confidence interval, 1.01-1.08; P = .019) were more likely to correspond to abnormal findings. Those with dialysis vintage (length of time on dialysis) up to 3 years (odds ratio = 2.10; 95% confidence interval, 1.09-4.06; P = .027) and hypertension as the cause of renal failure (odds ratio = 1.79; 95% confidence interval, 1.05-2.87; P = .002) had more abnormal findings. No differences in length of evaluation, rate of being listed for transplant, and rate of transplant were shown. CONCLUSIONS: The overall rate of adenomatous findings on colonoscopy was higher among patients with pretransplant end-stage renal disease than in the general population, as shown in other studies. Age, sex, dialysis vintage up to 3 years, and hypertensive renal failure were associated with adenomatous polyps of the colon in this study population. Because adenomatous polyp rates are high in patients with chronic kidney disease who are undergoing transplant evaluation and colonoscopic findings do not appear to delay transplant evaluations or listing rates, screening colonoscopies should be encouraged.

Improved renal function after conversion from tacrolimus/sirolimus to tacrolimus/mycophenolate mofetil in kidney transplant recipients.

BACKGROUND: There is limited data on the potential nephrotoxicity of sirolimus (SRL) and tacrolimus (TAC) in combination. METHODS: We reviewed the course of 97 kidney transplant patients treated with SRL and reduced-dose TAC. Conversion from SRL to mycophenolate mofetil (MMF) was prescribed in a minority (n = 19) for various nonrenal side effects. We compared outcomes of converted patients to those remaining on TAC/SRL (n = 78). RESULTS: TAC levels were increased in converters (P = 0.009). Rejection rates were similar between groups over 18 months (21% vs. 16%, p = ns). Serum creatinine (Cr) and MDRD glomerular filtration rate (GFR) were similar between groups at nadir and six-months, but at 18 months the percent change from six-month Cr was +17% in non-converters vs. -10% in converters (P = 0.004 for the difference). The difference in GFR between groups at 18 months was also significant (P = 0.01). By multivariate analysis, only conversion to MMF was associated with a greater percent change in Cr from 6 to 18 months (P = 0.015). Conversion to MMF also correlated with higher GFR at 18 months independent of rejection, delayed graft function, and ethnicity. CONCLUSIONS: Conversion from TAC/SRL to TAC/MMF led to improved renal function despite increased TAC exposure after conversion.

Outcome differences between young children and adolescents undergoing kidney transplantation.

BACKGROUND/PURPOSE: Although graft loss remains the biggest challenge for all pediatric kidney transplant (KT) recipients, unique challenges exist within different age groups. We aim to evaluate the different characteristics and graft survival outcomes of young children and adolescents undergoing KT. METHODS: Children who underwent isolated KT between 2000 and 2013 at our institution were included in this retrospective analysis. Patient characteristics and outcomes were compared using student's t-test, chi-square test, Kaplan-Meier curve and Cox proportional hazards model. RESULTS: Of 73 children who underwent KT, 31 were <12 (young children), and 42 were ≥ 12 years old (adolescents). Overall patient survival was 100%. The younger group had superior 5-year (100% vs. 75.5%) and 10-year (94.4% vs. 43.8%) graft survival (p=0.008). Factors predictive of poor graft survival on multivariate analysis were older age at transplantation (HR 1.2, CI 1-1.4, p=0.047), female gender (HR 9.0, CI 1.9-43, p=0.006), and acute rejection episodes (HR 13, CI 2-90, p=0.008). The most common causes of graft loss were acute and chronic rejection episodes and immunosuppression nonadherence. CONCLUSION: Adolescents undergoing KT have inferior graft survival compared to younger children. In adjusted modeling, children with older age, female gender, and acute rejection episodes have inferior graft survival.

Inhibition of endothelin-1 improves survival and vasculopathy in rat cardiac transplants treated with cyclosporine.

BACKGROUND: In animal models, endothelin-1 (ET-1) blockade attenuates transplant vasculopathy and chronic allograft dysfunction even in the absence of cyclosporine (CsA). As CsA has side effects and ET-1 antagonism alone has significant benefits, we postulated that allograft survival could be significantly improved by combining an endothelin-converting enzyme inhibitor with low-dose CsA. METHODS: Survival of Lewis to Fisher 344 rat heterotopic cardiac allografts was determined in untreated animals and compared with those treated with high-dose CsA (62 mg/kg i.m. on day 2), low-dose CsA (25 mg/kg), an endothelin-converting enzyme inhibitor, phosphoramidon (PA, 10 mg/kg/day), or low-dose CsA + PA. RESULTS: Untreated allografts had a median survival of 16 days compared with 20 days for low-dose CsA. Grafts treated with PA survived for 28 days, and combination of PA and low-dose CsA improved median survival to 47 days (P<0.01). Median survival with combination therapy was similar to that for high-dose CsA (42 days). To explore mechanisms underlying the benefits of combination therapy, cardiac allografts treated as above (n=4 each group) were explanted at 20 d and analyzed for parenchymal rejection, neointimal vasculopathy, myocardial fibrosis, and macrophage infiltration. Low-dose CsA alone but not PA improved parenchymal rejection; in contrast, PA alone but not low-dose CsA improved vasculopathy. Both parenchymal rejection and vasculopathy were improved by combination therapy with low-dose CsA and PA. Unlike CsA, inhibition of ET-1 biosynthesis significantly reduced myocardial fibrosis in allografts. CONCLUSIONS: These results suggest that the combination of low-dose CsA and endothelin-converting enzyme inhibition may prove useful to improve long-term graft survival while minimizing potential side effects of CsA.

Withdrawal of steroid therapy in African American kidney transplant recipients receiving sirolimus and tacrolimus.

BACKGROUND: Withdrawal of corticosteroids from the immunosuppressive regimens of kidney transplant recipients has been associated with an increased risk of acute and chronic allograft rejection. Previous studies indicate that the risk of rejection is particularly high in African Americans. METHODS: We prospectively enrolled 44 African American kidney transplant recipients to participate in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids. No patient received antibody induction therapy. Prednisone was withdrawn from eligible patients free of acute rejection beginning as early as 3 months posttransplant, and followed for a minimum of 9 months posttransplant. Patients were followed for acute rejection and for changes in blood pressure, body weight, and serum creatinine concentrations before and after withdrawal of steroids. RESULTS: Thirty of 44 patients (68%) were weaned off of prednisone. Follow-up after withdrawal of prednisone ranged from 3 to 26 months (mean, 14.3+/-7.7 months). Two of 30 patients (6.7%) developed acute rejection. At last follow-up, 27 of 30 patients (90%) remain steroid-free. Steroid withdrawal was associated with significant reductions in blood pressure. CONCLUSIONS: Use of sirolimus and tacrolimus, without the use of induction antibody therapy, allows withdrawal of prednisone as early as 3 months posttransplant with low rates of subsequent acute rejection in African American kidney transplant recipients. Withdrawal of prednisone was associated with lower blood pressures and the need for fewer antihypertensive medications.

Outcomes of African American kidney transplant recipients treated with sirolimus, tacrolimus, and corticosteroids.

BACKGROUND: African American kidney transplant recipients generally exhibit poor long-term graft survival compared with other ethnic groups. The combination of sirolimus, tacrolimus, and corticosteroids has proven to be effective in reducing rejection episodes in high-risk organ and islet cell transplant recipients but has not yet been tested in a large number of African American patients. METHODS: The outcomes of 56 African American adult, primary kidney transplant recipients treated with corticosteroids, sirolimus, and tacrolimus targeted to relatively low trough blood levels were compared with those of a concurrent group of 65 white patients treated with steroids, mycophenolate mofetil, and tacrolimus targeted to relatively high blood levels. Induction antibody therapy was not routinely used in either group. RESULTS: The incidence of acute rejection in the first 3 posttransplantation months was 7.1% in African Americans and 16.9% in whites (P=NS). Actuarial 2-year patient, graft, and rejection-free graft survival rates were equivalent in the two groups. Posttransplantation diabetes mellitus occurred in 36% of the African American patients, despite similar doses of corticosteroids and lower trough levels of tacrolimus, compared with 15% of white patients (P=0.024). CONCLUSIONS: The combination of corticosteroids, sirolimus, and relatively low doses of tacrolimus results in acute rejection, graft survival, and patient survival rates equivalent to those achieved in white patients receiving steroids, mycophenolate mofetil, and relatively high doses of tacrolimus, even without the routine use of induction antibody therapy. Posttransplantation diabetes mellitus remains a problem for African Americans receiving this combination of immunosuppressants, despite relatively low tacrolimus blood levels.

Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: three-year results.

BACKGROUND: Historically, antibody induction has been used because of the higher immunologic risk of graft loss or rejection observed in simultaneous pancreas and kidney (SPK) transplantation compared with kidney transplantation alone. This trial was designed to assess the effect of antibody induction in SPK transplant recipients receiving tacrolimus, mycophenolate mofetil, and corticosteroids. Induction agents included T-cell-depleting and interleukin-2 receptor antibodies. METHODS: A total of 174 SPK transplant recipients were enrolled in a prospective, open-label, multi-center study. They were randomized to induction (n=87) or non-induction (n=87) groups and followed for 3 years. RESULTS: At 3 years, actual patient (94.3% and 89.7%) and pancreas (75.9% and 75.9%) survivals were similar between the induction and non-induction groups, respectively. Actual kidney survival was similar at 1 and 2 years, but at 3 years, it was significantly better in the induction group compared with the non-induction group (92% vs. 81.6%; P =0.04). At 3 years, median serum creatinine and hemoglobin A1C were similar between the induction and non-induction groups (1.35 mg/dL and 1.20 mg/dL, 5.4% and 5.5%, respectively). Three-year cumulative incidence of biopsy-confirmed, treated acute kidney rejection in the induction and non-induction groups was 19.5% and 27.5% (P =0.14), respectively, with odds 4.6 times greater in African Americans regardless of treatment (P =0.004). Significantly higher rates of cytomegalovirus (CMV) viremia and CMV syndrome occurred in those receiving T-cell-depleting antibody induction (36.1%) when compared with those receiving anti-interleukin-2 receptor antibodies (2%) and non-induction (8.1%) (P <0.0001). CONCLUSIONS: Tacrolimus, mycophenolate mofetil, and corticosteroids resulted in excellent safety and efficacy in SPK transplant recipients. Actual 3-year kidney survival was significantly better in the induction group; however, CMV viremia and CMV syndrome rates were significantly higher in the T-cell-depleting antibody group. African Americans demonstrated a significantly greater risk of acute rejection despite antibody induction. Decisions regarding the use of induction therapy must weigh the risk of kidney graft loss or rejection against the risk of infection.

Abdominal catastrophe revisited: the risk and outcome of enteric peritoneal contamination.

OBJECTIVE: Peritonitis from a visceral source is associated with striking morbidity and mortality in patients treated with peritoneal dialysis (PD). Surgical intervention for both diagnosis and repair is definitive. However, because the antecedents of enteric injury leading to peritonitis are unpredictable, no preventive strategy has been proposed or adopted. The goal of this study was to examine risk factors influencing the occurrence and outcome of anatomically documented peritonitis of enteric origin. DESIGN: Retrospective chart and database review. SETTING: Peritoneal dialysis unit in tertiary-care referral hospital. PATIENTS: 330 patients treated with PD for end-stage renal disease between 1988 and 2000. MAIN OUTCOME MEASURES: Prevalence of peritonitis of anatomically documented enteric origin over two consecutive time periods within the study interval: period 1, from 1 January 1988 through 30 June 1996; period 2, from 1 July 1996 through 30 June 2000. RESULTS: At least 1 episode of peritonitis occurred in 202 of 330 patients during the entire study period of 12.5 years (600.74 patient-years of care). There were 543 episodes of peritonitis. Anatomically documented visceral Injury caused bacterial peritonitis in 41 patients with a total of 63 discrete episodes, an incidence rate of 0.1048 per patient-year. Peritonitis-free survival was compared between the two periods using Kaplan-Meier analysis. The curve representing risk distribution for anatomically documented visceral peritonitis remained constant over the two periods, in contrast to improvements found in all other types of peritonitis, taken as a group (p= 0.044). Logistic regression modeling showed that the only risk factor associated with development of anatomically documented visceral peritonitis was older age. There was no influence of race, sex, time on PD, and underlying disease etiology. 31 deaths were attributed to peritonitis during the study period. The mortality rate from enteric peritonitis due to visceral injury was 46.3% (19/41 cases), compared to 7.5% for all other peritonitis taken as a group (12/161 cases, p < 0.0001). CONCLUSIONS: The experience at University Hospitals of Cleveland suggests that abdominal catastrophe occurs in approximately 10% of all patients treated with PD, and is associated with high mortality, which has not changed over time. Therefore, peritonitis due to spontaneous visceral injury presents a great diagnostic and therapeutic challenge. It is important to develop a research strategy to understand this devastating complication.

Arteriovenous grafts have higher secondary patency in the short term compared with autologous fistulae.

BACKGROUND: To estimate patency of arteriovenous fistulas (AVFs) and grafts (AVGs) for dialysis access. METHODS: Records of all adult patients who had a dialysis access placed from January 2008 to June 2011 were retrospectively reviewed. RESULTS: A total of 494 patients with 655 accesses (390 AVFs, 265 AVGs) were examined. We found that AVG fared worse in assisted primary patency. But AVG had superior secondary patency up to 1.2 years (hazard ratio [HR] .6, confidence interval [CI]: [.4 to .8]) and was no different than AVF after 1.2 years. (HR 1.6, CI: [.9 to 3.1]). On univariate analysis, dialysis catheters negatively impacted assisted primary patency (HR 1.4, CI: [1.09 to 1.77]). CONCLUSIONS: AVG can be maintained with higher rates of secondary patency in the short term and are no different in the long term. This result suggests that in patients with limited life expectancy an AVG may be an effective alternative to an AVF to reduce both catheter time and associated complications.

Fever, infection, and rejection after kidney transplant failure.

BACKGROUND: Patients returning to dialysis therapy after renal transplant failure have high morbidity and retransplant rates. After observing frequent hospitalizations with fever after failure, it was hypothesized that maintaining immunosuppression for the failed allograft increases the risk of infection, while weaning immunosuppression can lead to symptomatic rejection mimicking infection. METHODS: One hundred eighty-six patients with failed kidney transplants were analyzed for rates of hospitalization with fever within 6 months of allograft failure. Patients were stratified by the presence of full immunosuppression versus minimal (low-dose prednisone) or no immunosuppression, before hospital admission. Subsequent rates of documented infection and nephrectomy, as well as patient survival, were ascertained. RESULTS: Hospitalization with fever within 6 months of allograft failure was common, occurring in 44% of patients overall. However, among febrile hospitalized patients who had been weaned off of immunosuppression before admission, only 38% had documented infection. In contrast, 88% of patients maintained on immunosuppression had documented infection (P<0.001). In both groups, dialysis catheter-related infections were the most common infection source. Allograft nephrectomy was performed in 81% of hospitalized patients with no infection, compared to 30% of patients with documented infection (P<0.001). Mortality risk was significantly higher in patients with concurrent pancreas transplants or who were hospitalized with documented infection. CONCLUSIONS: Maintenance immunosuppression after kidney allograft failure was associated with a greater incidence of infection, while weaning of immunosuppression commonly resulted in symptomatic rejection with fever mimicking infection on presentation. Management of the failed allograft should include planning to avoid both infection and sensitizing events.

Effects of cellular sensitization and donor age on acute rejection and graft function after deceased-donor kidney transplantation.

BACKGROUND: Allografts from older donors may be more immunogenic than those from younger donors. Pretransplantation cellular sensitization may interact with advanced donor age to increase the risk of immune injury after deceased-donor kidney transplantation. METHODS: The outcomes of 118 consecutive deceased-donor kidney transplant recipients with available pretransplantation donor-stimulated enzyme-linked immunosorbent spot (ELISPOT) assays for interferon gamma were analyzed retrospectively to determine the impact of cellular sensitization and other clinical variables, including donor age, on the incidence of acute rejection (AR) in the first year after deceased-donor transplantation and on estimated glomerular filtration rate 12 months after transplantation. RESULTS: The incidence of AR was higher in patients with positive pretransplantation ELISPOT assays versus those with negative assays (36% vs. 14%, P=0.009). Logistic regression indicated that the combination of donor age 50 years or older and a positive pretransplantation ELISPOT assay was more strongly associated with AR (odds ratio, 12.1; confidence interval, 1.1-133) than either variable alone. Estimated glomerular filtration 12 months after transplantation was highest in ELISPOT-negative patients receiving kidneys from donors younger than 50 years and lowest in ELISPOT-positive recipients with donors 50 years or older. CONCLUSION: The combination of advanced donor age and pretransplantation cellular sensitization increases the risk of AR and poor graft function after deceased-donor kidney transplantation beyond the risk associated with each factor alone.

Independent of nephrectomy, weaning immunosuppression leads to late sensitization after kidney transplant failure.

BACKGROUND: Patients returning to dialysis therapy after renal transplant failure have a high rate of human leukocyte antigen antibody sensitization, and sensitization has been linked to allograft nephrectomy. We hypothesized that nephrectomy for cause is a consequence of weaning immunosuppression and that weaning leads to sensitization even in the absence of nephrectomy. METHODS: We examined outcomes in 300 consecutive patients with kidney allograft failure and survival of more than 30 days after failure. We analyzed a subset of 119 patients with a low panel reactive antibody (PRA) before transplantation and follow-up PRA testing at 6 to 24 months after failure (late PRA). RESULTS: By late PRA testing, 56% of patients were highly sensitized (class I or II PRA ≥80%). On multivariate analysis controlling for human leukocyte antigen matching, allograft nephrectomy, and other variables, weaning of immunosuppression predicted high sensitization (odds ratio, 14.34; P=0.004). In a subset of patients, the percentage of those who were highly sensitized increased from 21% at the time of failure on immunosuppressive therapy to 68% by late PRA after weaning (P<0.001). Conversely, patients who maintained immunosuppression showed minimal sensitization after failure. Transplant nephrectomy was required in 41% of patients who weaned immunosuppression versus 0% of the 24 patients who maintained immunosuppression with calcineurin inhibitor therapy after failure (P<0.001). CONCLUSIONS: Weaning immunosuppression was a triggering event leading to late rejection and allograft nephrectomy and was an independent predictor of alloantibody sensitization after kidney allograft failure.

Effect of parathyroidectomy on anemia and erythropoietin dosing in end-stage renal disease patients with hyperparathyroidism.

BACKGROUND: It has been suggested that parathyroidectomy for hyperparathyroidism (HPT) in end-stage renal disease (ESRD) may result in improvement in anemia and the response to erythropoiesis-stimulating drugs. This study examines the effect parathyroidectomy had on erythropoietin (EPO) dosing requirements and anemia in ESRD. METHODS: A retrospective review was conducted. Patients were included if pre-operative and 12 month postoperative hemoglobin (Hg) and hematocrit (Hct) levels were available and they did not receive a kidney transplant or have failure of parathyroidectomy during the follow-up. Erythropoietin (EPO) dose and serum levels of calcium, phosphorus, alkaline phosphatase, albumin, and parathyroid hormone (PTH) were also obtained. Other data collections were at 1 and 2 mos. postoperatively. RESULTS: Thirty-seven patients met inclusion criteria. Parathyroidectomy resulted in decreased PTH from 1,871 +/- 236 (mean +/- SEM) to 172 +/- 29 pg/mL (P < .001) at 1 year. EPO dosing requirement showed a profound decrease from 10,086 +/- 1,721 to 3,514 +/- 620 units/week (P < .05). Hb and Hct levels followed an upward trend at 12 mos (11.4 +/- 0.3 to 12.1 +/- 0.2 g/dL and 35.7 +/- 1.0 to 37.1 +/- 0.6%, respectively). CONCLUSION: In ESRD, parathyroidectomy for HPT improves anemia and decreases requirements for exogenous erythropoietin suggesting either increased endogenous EPO production or improved response. As a result, we propose refractory ESRD-associated anemia as a secondary indication for parathyroidectomy resection in this population.

Reduction in erythropoietin resistance after conversion from sirolimus to enteric coated mycophenolate sodium.

BACKGROUND: Anemia is a known adverse effect of sirolimus (SRL) therapy. Sirolimus may contribute to anemia by a direct antiproliferative effect or by increasing inflammation, worsening kidney function, or decreasing iron utilization. After observing the need for high dose exogenous erythropoietin dosage in some patients on SRL, we hypothesized that SRL therapy may influence anemia by inducing a state of erythropoietin resistance. METHODS: Twenty-five stable renal transplant patients on maintenance tacrolimus and SRL therapy were enrolled in a prospective trial with conversion from SRL to enteric coated mycophenolate sodium. Measurement of plasma erythropoietin and red cell indices were performed pre- and postconversion. RESULTS: Renal function remained unchanged after conversion. Serum hemoglobin (Hb) increased in 18/21 (86%) of patients after conversion. Endogenous erythropoietin level decreased from a median of 28.3 (11.5-374) to 16.6 (3.1-78.8) mIU/mL, (P<0.001); and the erythropoietin:Hb ratio dropped from 2.7 (0.7-34.3) to 1.2 (0.2-6.7), (P<0.001); indicating less erythropoietin resistance after conversion. Mean corpuscular volume increased after conversion, but transferrin saturation and ferritin did not change. Conversion was complicated by posttransplant erythrocytosis in two patients. DISCUSSION: Conversion from SRL to enteric coated mycophenolate sodium led to an increase in Hb and a decrease in erythropoietin resistance in stable kidney transplant recipients. Increase in Hb seemed to be independent of renal functional changes or changes in iron sequestration.

Early experience with intraoperative radiotherapy in patients with resected pancreatic adenocarcinoma.

BACKGROUND: The use of intraoperative radiotherapy (IORT) in patients with resected pancreatic adenocarcinoma has not been clearly defined. METHODS: The medical records of our first 22 patients receiving IORT for resected pancreatic adenocarcinoma (2001 to 2006) were reviewed and compared with the records of 27 consecutive patients not receiving IORT for resected pancreatic adenocarcinoma (2004 to 2006). RESULTS: There were no 30-day mortalities in either group, and complication rates were similar. Local recurrence occurred in 18% in the IORT group (median 14 months) and 12% in the no-IORT group (median 7 months). Distant recurrence occurred in 47% in the IORT group (median 11 months) and 32% in the no-IORT group (median 6.5 months). Median overall, stage-specific, and location-specific survival did not differ between the groups. CONCLUSIONS: Although limited in size and follow-up, our experience showed that complications, recurrence, and survival were not affected by IORT, but time to recurrence may be longer with IORT.