Outcomes of Early Steroid Withdrawal in Recipients of Deceased-Donor Expanded Criteria Kidney Transplants in the Era of Induction Therapy.

OBJECTIVES: This study explored the safety of early steroid withdrawal in recipients of expanded criteria deceased-donor kidney transplants. MATERIALS AND METHODS: Using the Organ Procurement and Transplant Network-United Network of Organ Sharing database, we identified patients who underwent expanded criteria deceased-donor kidney transplant between January 2000 and December 2008 after receiving induction with rabbit-antithymocyte globulin (n = 3717), alemtuzumab (n = 763), or interleukin 2 blocking agent (n = 2600) followed by calcineurin inhibitor and mycophenolate mofetil-based maintenance with and without steroid therapy. RESULTS: Adjusted overall graft survival (hazard ratio 1.32; 95% confidence interval, 1.1-1.56; P = .002) and patient survival (hazard ratio 1.46, 95% confidence interval, 1.16-1.83, P = .001) were inferior, whereas death-censored graft survival (hazard ratio 1.13; 95% confidence interval, 0.87-1.47; P = .35) was similar for chronic steroid maintenance versus early steroid withdrawal groups in rabbit-antithymocyte globulin-induced patients. Graft and patient outcomes were similar for chronic steroid maintenance versus early steroid withdrawal groups among alemtuzumab and interleukin 2 blocking agent-induced patients. Among rabbit-antithymocyte globulin-induced patients, adjusted overall graft survival (hazard ratio 1.57; 95% confidence interval, 1.2-2.0; P < .001) and patient survival (hazard ratio 1.5; 95% CI, 1.15-2.1; P = .004) were inferior, whereas death-censored graft survival (hazard ratio 1.5; 95% confidence interval, 0.97-2.43; P = .07) trended inferior for chronic steroid maintenance versus early steroid withdrawal groups in recipients > 60 years old (n = 1729). CONCLUSIONS: Our study showed safety of early steroid withdrawal in recipients of expanded criteria deceased-donor kidney transplants who underwent perioperative induction followed by calcineurin inhibitor and mycophenolate mofetil maintenance. Among rabbit-antithymocyte globulin-induced patients, chronic steroid maintenance was associated with inferior graft and patient outcomes, an effect limited to older recipients.

Role of steroid maintenance in sensitized kidney transplant recipients.

AIM: To evaluate whether there is a threshold sensitization level beyond which benefits of chronic steroid maintenance (CSM) emerge. METHODS: Using Organ Procurement and Transplant Network/United Network of Organ Sharing database, we compared the adjusted graft and patient survivals for CSM vs early steroid withdrawal (ESW) among patients who underwent deceased-donor kidney (DDK) transplantation from 2000 to 2008 who were stratified by peak-panel reactive antibody (peak-PRA) titers (0%-30%, 31%-60% and > 60%). All patients received perioperative induction therapy and maintenance immunosuppression based on calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF). RESULTS: The study included 42851 patients. In the 0%-30% peak-PRA class, adjusted over-all graft-failure (HR 1.11, 95%CI: 1.03-1.20, P = 0.009) and patient-death (HR 1.29, 95%CI: 1.16-1.43, P < 0.001) risks were higher and death-censored graft-failure risk (HR 1.06, 95%CI: 0.98-1.14, P = 0.16) similar for CSM (n = 25218) vs ESW (n = 7399). Over-all (HR 1.04, 95%CI: 0.85-1.28, P = 0.70) and death-censored (HR 0.97, 95%CI: 0.78-1.21, P = 0.81) graft-failure risks were similar and patient-death risk (HR 1.39, 95%CI: 1.03-1.87, P = 0.03) higher for CSM (n = 3495) vs ESW (n = 850) groups for 31%-60% peak-PRA class. In the > 60% peak-PRA class, adjusted overall graft-failure (HR 0.90, 95%CI: 0.76-1.08, P = 0.25) and patient-death (HR 0.92, 95%CI: 0.71-1.17, P = 0.47) risks were similar and death-censored graft-failure risk lower (HR 0.84, 95%CI: 0.71-0.99, P = 0.04) for CSM (n = 4966) vs ESW (n = 923). CONCLUSION: In DDK transplant recipients who underwent perioperative induction and CNI/MMF maintenance, CSM appears to be associated with increased risk for death with functioning graft in minimally-sensitized patients and improved death-censored graft survival in highly-sensitized patients.

Inpatient venous access practices: PICC culture and the kidney patient.

PURPOSE: Depleted venous access is frequently cited as a reason for low fistula achievement. These quality assurance studies were designed to clarify the interactions between kidney disease, acuity of care and vascular access practices, and define the impact of nephrology intervention. METHODS: The inpatient population at an urban teaching hospital was surveyed three times between May 2010 and May 2012. Data were collected on limb protection and vascular access practices, as well as level of kidney function and level of care. RESULTS: Peripherally inserted central catheter (PICC) insertion consistently exceeded 30% in patients with chronic kidney disease; reasons for insertion were often poorly defined. More than 50% of patients had devices in the nondominant arm; use of limb protection bracelets was rare. An educational intervention designed to increase nephrologist awareness increased limb protection slightly, but did not affect the distribution of vascular access devices. CONCLUSIONS: PICC placement and invasion of the nondominant arm are both frequent in patients with abnormal kidney function, in spite of guidelines discouraging their use. The rate of PICC is higher than that of patients with normal kidney function. Current vascular access practices have substantial potential to affect future fistula rates. Effective vein protection may require participation of the entire medical community.

Impact of steroid maintenance on the outcomes in first-time deceased donor kidney transplant recipients: Analysis by induction type.

AIM: To analyze the impact of steroid maintenance on the outcomes in kidney transplant recipients stratified by induction agent received. METHODS: Patients who underwent first-time deceased donor kidney transplantation between 2000 and 2008 after receiving induction therapy with rabbit-antithymocyte globulin (r-ATG), alemtuzumab or an interleukin-2 receptor blocker (IL-2B) and discharged on a calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF)-regimen along with or without steroids were identified from the Organ Procurement and Transplant Network/United Network of Organ Sharing database. For each induction type, adjusted overall and death-censored graft as well as patient survivals were compared between patients discharged on steroid vs no steroid. Among r-ATG induced patients, analysis was repeated after splitting the group into low and high immune risk groups. RESULTS: Among the 37217 patients included in the analysis, 17863 received r-ATG (steroid = 13001, no-steroid = 4862), 3028 alemtuzumab (steroid = 852, no-steroid = 2176) and 16326 IL-2B (steroid = 15008, no-steroid = 1318). Adjusted overall graft survival was inferior (HR = 1.16, 95%CI: 1.06-1.27, P = 0.002) with similar death-censored graft survival (HR = 0.99, 95%CI: 0.86-1.14, P = 0.86) for steroid vs no-steroid groups in r-ATG induced patients. Both adjusted overall and death-censored graft survivals for steroid vs no-steroid groups were similar in alemtuzumab (HR = 0.92, 95%CI: 0.73-1.15, P = 0.47 and HR = 0.87, 95%CI: 0.62-1.22, P = 0.43 respectively) and IL-2B (HR = 1.05, 95%CI: 0.91-1.21, P = 0.48 and HR = 0.94, 95%CI: 0.75-1.18, P = 0.60 respectively) induced groups. Adjusted patient survivals were inferior for steroid vs no-steroid groups in r-ATG induced (HR = 1.31, 95%CI: 1.15-1.49, P < 0.001) but similar in alemtuzumab (HR = 1.02, 95%CI: 0.75-1.38, P = 0.92) and IL-2B (HR = 1.17, 95%CI: 0.97-1.40, P = 0.10) induced patients. Among the r-ATG induced group there were 4346 patients in the low immune risk and 13517 patients in the high immune risk group. Adjusted overall graft survivals were inferior for steroid vs no steroid groups in both low immune (HR = 1.34, 95%CI: 1.09-1.64, P = 0.001) and high immune (HR = 1.18, 95%CI: 1.07-1.30, P = 0.005) risk groups. Adjusted death-censored graft survivals for steroid vs no steroid groups were similar in both low (HR = 1.06, 95%CI: 0.78-1.45, P = 0.70) and high (HR = 1.04, 95%CI: 0.98-1.20, P = 0.60) immune risk groups. Adjusted patient survivals were inferior for steroid vs no steroid groups in both low immune (HR = 1.54, 95%CI: 1.18-2.02, P < 0.001) and high immune (HR = 1.32, 95%CI: 1.16-1.51, P = 0.002) risk groups. Overall, there were significantly higher deaths from infections and cardiovascular causes in patients maintained on steroids. CONCLUSION: Our study showed an association between steroid addition to a CNI/MMF-maintenance regimen and increased death with functioning graft in patients receiving r-ATG induction for first-time deceased donor kidney transplantation.

Effect of allopurinol on slowing allograft functional decline in kidney transplant recipients.

OBJECTIVES: Hyperuricemia may be a risk factor for graft loss in kidney transplant recipients. The purpose of this study was to evaluate the effects of allopurinol in kidney transplant recipients. MATERIALS AND METHODS: A single center retrospective case-control study was performed with kidney transplant recipients who were treated with allopurinol (54 patients) and a control group matched for time of transplant (± 3 months) and estimated glomerular filtration rate (54 patients). We evaluated the relation between allopurinol use and estimated glomerular filtration rate, graft survival, blood pressure, and number of anti-hypertensive drugs used. RESULTS: At the start of allopurinol therapy, mean serum uric acid level was greater in the allopurinol (476 ± 119 µmol/L) than control group (404 ± 125 µmol/L; P ≤ .001) and estimated glomerular filtration rate was similar between the 2 groups (allopurinol, 39 ± 16 mL/min; control, 38 ± 16 mL/min; not significant). At 1 year, mean estimated glomerular filtration rate was greater in the allopurinol than control group (allopurinol, 41 ± 15 mL/min; control, 36 ± 13 mL/min; P ≤ .04). At 2 years, mean serum uric acid level was significantly lower in the allopurinol (399 ± 101 µmol/L) than control group (452 ± 95 µmol/L; P ≤ .02). Graft survival, blood pressure, and antihypertensive requirements were similar between the groups. CONCLUSIONS: Allopurinol use is associated with preservation of estimated glomerular filtration rate in kidney transplant recipients. There may be potential benefit in treating asymptomatic hyperuricemia in kidney transplant recipients.

Steroid maintenance in repeat kidney transplantation: influence of induction agents on outcomes.

The influence of steroid maintenance on the outcomes of repeat kidney transplant (RKT) recipients with respect to induction type is unclear. Using the Organ Procurement and Transplant Network/United Network of Organ Sharing (OPTN/UNOS) database, we identified patients (≥ 18 years) who underwent deceased donor RKT from January 2000 to December 2008 after receiving induction with rabbit-antithymocyte globulin (r-ATG), alemtuzumab or an IL-2 receptor blocker (IL-2B) and were discharged on a calcineurin inhibitor/mycophenolate mofetil regimen with or without steroids. Of 5634 patients, 3643 received r-ATG (steroid = 3157, no-steroid = 486), 448 alemtuzumab (steroid = 196, no-steroid = 252) and 1543 an IL-2B (steroid = 1465, no-steroid = 78). Unadjusted graft survivals were similar for the no-steroid versus steroid groups for induction with r-ATG [hazard ratio (HR) 0.85 and 95% confidence interval (95% CI) 0.70-1.03, P = 0.10], alemtuzumab (HR 0.76, 95% CI 0.51-1.14, P = 0.18) and IL-2B (HR 0.77, 95% CI 0.56-1.70, P = 0.23). In the adjusted model, steroid use improved graft survival in alemtuzumab (HR 0.44, 95% CI 0.25-0.76, P = 0.003) but not in the r-ATG (HR 0.86, 95% CI 0.68-1.09, P = 0.21) or IL-2B (HR 0.98, 95% CI 0.56-1.70, P = 0.94) groups. Steroid use was associated with inferior patient survival in unadjusted (HR 1.30, 95% CI 1.17-1.44, P <0.001) and adjusted (HR 1.29, 95% CI 1.14-1.45, P <0.001) models for r-ATG induction, whereas this was not observed with alemtuzumab (unadjusted HR 1.11, 95% CI 0.89-1.37, P = 0.36; adjusted HR 0.90, 95% CI 0.68-1.20, P = 0.49) or IL-2B (unadjusted HR 1.01, 95% CI 0.87-1.18, P = 0.87; adjusted HR 1.15, 95% CI 0.97-1.38, P = 0.12) inductions. Our study showed a graft survival benefit in the alemtuzumab- and patient death risk in the r-ATG-induced RKT recipients discharged on steroids.

Treatment of antibody-mediated rejection in kidney transplant recipients: a single-center experience with a bortezomib-based regimen.

OBJECTIVES: Antibody-mediated rejection after kidney transplant is less responsive to conventional antirejection therapies. The proteasome inhibitor bortezomib has activity against mature plasma cells that produce damaging donor-specific antibodies. We present our experience of using a bortezomib-based regimen in patients with severe antibody-mediated rejection. MATERIALS AND METHODS: A retrospective chart review was performed on patients with biopsy-proven antibody-mediated rejection after kidney transplant at our institution over 12 months. Diagnosis of antibody-mediated rejection was made on the basis of positive peritubular capillary C4d staining along with either histologic evidence of acute rejection or positive donor-specific antibody titers. Treatment for antibody-mediated rejection included plasmapheresis, intravenous immunoglobulin, steroids, single-dose rituximab (375 mg/m²) along with bortezomib (1.3 mg/m²) on days 1, 4, 8, and 11. Antibody-mediated rejection was diagnosed in 6 patients. Patients received induction with either alemtuzumab (n=4) or rabbit-antithymocyte globulin (n=2) and were maintained on a tacrolimus/mycophenolate mofetil/early steroid withdrawal protocol. RESULTS: Four of 6 patients responded to treatment. Patients had stable kidney function during followup (median 14 months) after bortezomib therapy. CONCLUSIONS: In this series, we demonstrated the effectiveness of a bortezomib-based treatment regimen in achieving reduction of donor-specific antibody titers and stable renal function in patients experiencing severe antibody-mediated rejection.

Effect of high-dose erythropoietin on graft function after kidney transplantation: a randomized, double-blind clinical trial.

BACKGROUND AND OBJECTIVES: Delayed graft function (DGF) is associated with adverse long-term outcomes after deceased-donor kidney (DDK) transplantation. Ischemia-reperfusion injury plays a crucial role in the development of DGF. On the basis of promising animal data, this study evaluated any potential benefits of erythropoietin-alfa (EPO-α) given intra-arterially at the time of reperfusion of renal allograft on the degree of allograft function, as well as tubular cell injury measured by urinary biomarkers in the early post-transplant period. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the influence of EPO-α administered intraoperatively on the outcomes of DDK transplantations performed at the study center between March 2007 and July 2009. RESULTS: Seventy-two patients were randomly assigned to EPO-α (n=36) or placebo (n=36). The incidences of DGF, slow graft function, and immediate graft function did not significantly differ between the treatment and control groups (41.7% versus 47.2%, 25.0% versus 36.1%, and 33.3% versus 16.7%, respectively; P=0.24). The groups had similar levels of urinary biomarkers, including neutrophil gelatinase-associated lipocalin and IL-18 at multiple times points soon after transplantation; urinary output during the first 3 postoperative days; 1-month renal function; and BP readings, hemoglobin, and adverse effects during the first month. CONCLUSIONS: This study did not show any clinically demonstrable beneficial effects of high-dose EPO-α given intra-arterially during the early reperfusion phase in DDK transplant recipients in terms of reducing the incidence of DGF or improving short-term allograft function.

Association between peritransplant kidney injury biomarkers and 1-year allograft outcomes.

BACKGROUND AND OBJECTIVES: Current tools to predict outcomes after kidney transplantation are inadequate. The objective of this study was to determine the association of perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 with poor 1-year allograft function (return to dialysis or estimated GFR<30 ml/min per 1.73 m(2)). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Neutrophil gelatinase-associated lipocalin and IL-18 from early post-transplant urine was measured in this prospective, multicenter study of deceased-donor kidney transplant recipients. The outcome of poor allograft function at 1 year relative to these biomarkers using multivariable logistic regression and net reclassification improvement was examined. Also, the interaction between delayed graft function and the biomarkers on the outcome were evaluated, and the change in biomarkers over consecutive days related to the outcome using trend tests was examined. RESULTS: Mean age for the 153 recipients was 54 ± 13 years. Delayed graft function occurred in 42%, and 24 (16%) recipients had the 1-year outcome. Upper median values for neutrophil gelatinase-associated lipocalin and IL-18 on the first postoperative day had adjusted odds ratios (95% confidence interval) of 6.0 (1.5-24.0) and 5.5 (1.4-21.5), respectively. Net reclassification improvement (95% confidence interval) was significant for neutrophil gelatinase-associated lipocalin and IL-18 at 36% (1%-71%) and 45% (8%-83%), respectively. There was no significant interaction between biomarkers and delayed graft function on the outcome. Change in biomarkers moderately trended with the outcome. CONCLUSIONS: Perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 are associated with poor 1-year allograft function, suggesting their potential for identifying patients for therapies that minimize the risk of additional injury.

Proteasome inhibition with bortezomib: an effective therapy for severe antibody mediated rejection after renal transplantation.

Antibody-mediated rejection (AMR) following renal transplantation is less responsive to conventional anti-rejection therapies. Plasmapheresis (PP), intravenous immunoglobulin (IVIg), rabbit antithymocyte globulin (rATG) and rituximab deplete immature B-cells but not mature plasma cells. The proteasome inhibitor bortezomib has activity against mature plasma cell, the source of damaging donor-specific antibody (DSA).We present the successful use of bortezomib in 2 patients who developed AMR following kidney transplantation. The first patient was a 54-year-old white female who received living-unrelated kidney transplantation from her husband. She developed severe AMR early after transplantation with rising DSA titers consistent with an anamnestic immune response by memory cells to the donor antigens. Renal function deteriorated despite treatment with pulse methylprednisolone (MP), PP and IVIg. After initiation of therapy with bortezomib, DSA titers became negative and serum creatinine returned to baseline with histological resolution of AMR. The second patient was a 19-year-old white male who received deceased donor kidney transplantation and developed AMR within 2 weeks, refractory to therapy with pulse MP, PP and IVIg with rising DSA. Bortezomib use resulted in disappearance of DSA and renal function improvement. Both patients tolerated the treatment well with stable renal function at last follow-up. The novel mechanisms of action and preliminary results with bortezomib are encouraging, but require larger studies and longer follow-up.

Influence of induction modality on the outcome of deceased donor kidney transplant recipients discharged on steroid-free maintenance immunosuppression.

BACKGROUND: Over last several years, alemtuzumab induction has been increasingly used in kidney transplantation especially in patients maintained on steroid-free immunosuppression. It is unclear which induction agent is associated with better graft and patient outcomes in these patients. METHODS: Using Organ Procurement and Transplant Network/United Network of Organ Sharing database, graft and patient survivals were compared with multivariate analysis for deceased donor kidney transplant recipients from January 2000 to December 2008 who received induction with rabbit-antithymocyte globulin (r-ATG), alemtuzumab, or an interleukin-2 (IL-2) receptor blocker and were discharged on a calcineurin inhibitor/mycophenolate mofetil/steroid-free immunosuppression. RESULTS: When compared with r-ATG (n=5348), adjusted graft survival was inferior with alemtuzumab (n=2428, hazards ratio [HR] 1.26, 95% confidence interval [CI] 1.10-1.43, P=0.001) and IL-2 receptor blocker (n=1396, HR 1.19, 95% CI 1.01-1.39, P=0.04) inductions and patient survival was inferior with alemtuzumab (HR 1.29, 95% CI 1.08-1.55, P=0.006). Alemtuzumab induction was associated with higher adjusted graft failure risks in patients with panel reactive antibody more than 20% (HR 1.30, 95% CI 1.01-1.68, P=0.04), recipients of expanded criteria donor kidneys (HR 1.58, 95% CI 1.23-2.02, P<0.001), and kidneys with cold ischemia time more than 24 hr (HR 1.31, 95% CI 1.04-1.65, P=0.02) and higher patient death risks in recipients of expanded criteria donor kidney (HR 1.66, 95% CI 1.20-1.30, P=0.002) and kidneys with cold ischemia time more than 24 hr (HR 1.44, 95% CI 1.04-2.00, P=0.03). Adjusted graft survival rates were similar for different induction agents in the low-immune risk group. CONCLUSIONS: When compared with alemtuzumab and IL-2 receptor blocker, r-ATG induction seems to be associated with superior outcomes in deceased donor kidney transplant recipients maintained on calcineurin inhibitor/mycophenolate mofetil/steroid-free regimen.

Urine cystatin C as a biomarker of proximal tubular function immediately after kidney transplantation.

BACKGROUND/AIMS: Clinical methods to predict allograft function soon after kidney transplantation are ineffective. METHODS: We analyzed urine cystatin C (CyC) in a prospective multicenter observational cohort study of deceased-donor kidney transplants to determine its peritransplant excretion pattern, utility for predicting delayed graft function (DGF) and association with 3-month graft function. Serial urine samples were collected for 2 days following transplant and analyzed blindly for CyC. We defined DGF as any hemodialysis in the first week after transplant, slow graft function (SGF) as a serum creatinine reduction < 70% by the first week and immediate graft function (IGF) as a reduction ≥ 70%. RESULTS: Of 91 recipients, 33 had DGF, 34 had SGF and 24 had IGF. Urine CyC/urine creatinine was highest in DGF for all time-points. The area under the curve (95% CI) for predicting DGF at 6 h was 0.69 (0.57-0.81) for urine CyC, 0.74 (0.62-0.86) for urine CyC/urine creatinine and 0.60 (0.45-0.75) for percent change in urine CyC. On the first postoperative day, urine CyC/urine creatinine and percent change in urine CyC were associated with 3-month graft function. CONCLUSION: Urine CyC on the day after transplant differs between degrees of perioperative graft function and modestly corresponds with 3-month function.

IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation.

Current methods for predicting graft recovery after kidney transplantation are not reliable. We performed a prospective, multicenter, observational cohort study of deceased-donor kidney transplant patients to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, and kidney injury molecule-1 (KIM-1) as biomarkers for predicting dialysis within 1 wk of transplant and subsequent graft recovery. We collected serial urine samples for 3 d after transplant and analyzed levels of these putative biomarkers. We classified graft recovery as delayed graft function (DGF), slow graft function (SGF), or immediate graft function (IGF). Of the 91 patients in the cohort, 34 had DGF, 33 had SGF, and 24 had IGF. Median NGAL and IL-18 levels, but not KIM-1 levels, were statistically different among these three groups at all time points. ROC curve analysis suggested that the abilities of NGAL or IL-18 to predict dialysis within 1 wk were moderately accurate when measured on the first postoperative day, whereas the fall in serum creatinine (Scr) was not predictive. In multivariate analysis, elevated levels of NGAL or IL-18 predicted the need for dialysis after adjusting for recipient and donor age, cold ischemia time, urine output, and Scr. NGAL and IL-18 quantiles also predicted graft recovery up to 3 mo later. In summary, urinary NGAL and IL-18 are early, noninvasive, accurate predictors of both the need for dialysis within the first week of kidney transplantation and 3-mo recovery of graft function.

Impact of the addition of maintenance steroids to a rapid steroid discontinuation immunosuppressive protocol following acute renal transplant rejection.

OBJECTIVES: Rapid steroid discontinuation immunosuppressive protocols are increasingly used in renal transplant. The optimal immunosuppressive regimen in patients who develop acute rejection while on a rapid steroid discontinuation protocol is less clear. We examined our experience of adding maintenance steroid therapy in renal transplant recipients who developed 1 or more acute rejection episode while on a rapid steroid discontinuation protocol. MATERIALS AND METHODS: The outcome of 145 patients who underwent renal transplant from 2002 to 2007 and initiated a rapid steroid discontinuation protocol was analyzed. Patients were divided into the following 5 groups: (i): acute rejection X 1 and no maintenance steroids, (ii): acute rejection X 1 and started on maintenance steroids, (iii): acute rejection X 2 and no maintenance steroids (iv): acute rejection X 2 and started on maintenance steroids, and (v): no acute rejection RESULTS: Compared with patients with no acute rejection, graft survival was significantly inferior in patients who experienced 2 or more acute rejection episodes-whether they were started on maintenance steroids (P = .003) or not (P = .006) - but was similar in patients who experienced only 1 episode of acute rejection, and were started either on maintenance steroids (P = .87) or were continued on the rapid steroid discontinuation protocol (P = .69). In patients who sustained 2 episodes of acute rejection, addition of maintenance steroids had no impact on graft survival (P = .97). CONCLUSIONS: More than 1 episode of acute rejection in renal transplant recipients on rapid steroid discontinuation protocol is associated with poor, long-term, graft survival, which remains unchanged despite starting maintenance steroids. The use of maintenance steroids may not have a positive impact on graft survival after acute rejection.

Sorbent hemodialysis: clinical experience with new sorbent cartridges and hemodialyzers.

To recycle spent dialysate, a sorbent hemodialyzer uses a purification cartridge, adapted from water reclamation systems originally designed for the aerospace program. Increasing interest in home hemodialysis has driven a renewed examination of sorbent dialyzer technology, resulting in the development of a modern sorbent hemodialyzer and an array of new sorbent cartridges. Initial clinical experience with the Allient Hemodialysis System and the new sorbent cartridges is presented, with an emphasis on achievable clearances and ultrafiltration, as well as information about symptom profile and electrolyte balance.

Emerging role of Alemtuzumab in renal and renal-pancreas transplantation.

BACKGROUND: Alemtuzumab is a humanized anti-CD52 monoclonal antibody that is increasingly used in solid organ transplantation. OBJECTIVE: The novel mechanism by which alemtuzumab works was used to provide an understanding of its clinical efficacy and adverse effects. METHODS: Human studies of alemtuzumab in adult renal and pancreas transplantation were reviewed. These studies looked at the role of alemtuzumab as a tolerogenic and induction agent as well as its role in the treatment of acute rejection. RESULTS/CONCLUSIONS: Overall, alemtuzumab induction resulted in patient and graft outcomes comparable to other induction strategies but studies failed to show development of true tolerance. Economic benefit is a major attraction for alemtuzumab use. Future studies will further identify the optimal use of alemtuzumab.

Biofilms in nephrology.

BACKGROUND: Biofilms are bacterial communities ubiquitous to moist environments. Biofilm formation is a factor in the development and persistence of infectious diseases. In clinical nephrology, biofilms influence the development of kidney stones and affect dialysis systems, including peritoneal and central venous catheters. Biofilms also play critical roles in persistent and resistant renal and urinary tract infections. OBJECTIVE: To describe the physiology of biofilms and potential effects of biofilms upon infectious diseases, focusing on the role of biofilms in kidney stones, indwelling catheters and dialysis equipment. METHODS: A literature search with Medline to identify pertinent English language articles published up to early 2008 using the keywords biofilm, nephrology, renal, calculi and infection. RESULTS/CONCLUSION: Biofilms are ubiquitous in clinical nephrology and play a role in the pathogenesis of resistant infections. Strategies for reducing the effects of biofilms in nephrology are described.

Tissue plasminogen activator as a hemodialysis catheter locking solution.

Tunneled hemodialysis catheters require a "locking solution" between treatments to prevent catheter thrombosis. Heparin locks can be unsafe in patients with life-threatening bleeding diathesis because of unintentional anticoagulation. This study was designed to define the hematologic consequences of using tissue plasminogen activator (t-PA) as an alternative locking solution after heparin-free hemodialysis (HF-HD). Following HF-HD, t-PA 2 mg was instilled into each lumen of the dialysis catheter in 10 patients. Euglobulin clot lysis time (ECLT), fibrinogen, D-dimer, and fibrin degradation products were measured during the last hour of dialysis, and repeated 15 and 30 minutes after catheter locking. Dialysis catheter performance was reassessed at the time of the next hemodialysis. Fibrinogen, D-dimer, and fibrin degradation products were elevated at all time points, but did not change after t-PA. ECLT decreased significantly from baseline 15 minutes after catheter locking (217+/-64 vs. 132+/-75 min, p=0.016). ECLT values had returned to baseline (202+/-56 minutes) by 30 minutes. No episodes of bleeding or catheter thrombosis occurred, and catheter performance did not deteriorate. A 2 mg t-PA locking solution preserved dialysis catheter performance. ECLT decreased at 15 minutes, but normalized by 30 minutes, and did not enter the range in which bleeding would be likely. No clinical events were seen during this transient increase in systemic fibrinolysis.