Graft-versus-Host Disease after Living-Unrelated Kidney Transplantation.

Graft-versus-host disease (GVHD) is a rare complication after solid organ transplantation and consists of a reaction of donor derived immune cells directed against host tissues. The vast majority of cases reported in the literature involve liver, small intestine and pancreas transplantation. We report a case of GVHD in a 48-year-old man after living-unrelated kidney transplantation at another center. Six months postoperatively he developed a skin rash, anorexia, and diarrhea that resulted in malnutrition and a 90 pound weight loss. At this point he was transferred to our center with a BMI of 16 and severe cachexia. Intravenous hyperalimentation was initiated and an extensive work-up for an infectious etiology was performed and was negative. An esophagogastroduodenoscopy was performed and revealed nodularity of the gastric mucosa, atrophy, and edema in the first and second portion of his duodenum. Biopsy findings were consistent with GVHD. Aggressive immunosuppressive therapy was instituted with a good response. The anorexia and diarrhea resolved, and he was discharged on hospital day 20. Three months later, there had been no recurrence of the diarrhea, the patient had gained an additional 40 pounds, BMI of 25, and a repeat upper endoscopy revealed complete resolution of the initial endoscopic abnormalities.

Long-term quality of life after living kidney donation.

BACKGROUND: The supply of deceased donor kidneys available for transplantation is not sufficient to meet the demand. Despite a low rate of complications for donors and superior outcomes for recipients, living kidney donation (LKD) is on the decline for reasons that remain unclear. METHODS: We performed a retrospective review and analysis of living kidney donors (LDs) who underwent donor nephrectomy between January 1, 2000 and December 31, 2010. Candidates who were excluded from LKD were identified as control subjects (CSs). LDs and CSs were invited to voluntarily undergo a quality of life assessment using Short Form 12 v1.0 Questionnaire (SF-12) and an addendum questionnaire (AQ). The SF-12 and AQ were administered by telephone. Statistical analysis of the results was performed to obtain the SF-12 physical component score (PCS), SF-12 mental component score (MCS), and the AQ score. PCS and MCS for the general population were obtained from the 1998 National Survey of Functional Health Status. RESULTS: During the study period, 83 LDs and 116 CSs were interviewed. LDs were noted to have higher PCS (54.1 vs 49.6) and MCS (55.7 vs 49.4) compared with the general population. Ninety-nine percent of LDs believed that their quality of life did not decrease after LKD; 21.7% reported experiencing complications. Half of the LDs (48%) reported missing 1 day of work for evaluation; 71% of LDs reported missing at least 4 weeks of work after LKD. Nearly all LDs (99%) would undergo donation again. Fifty-two percent of LDs reported adhering to the recommended 2-year follow-up schedule with the transplantation team; 87% of LDs reported seeing their primary care physician. CONCLUSION: LDs are physically and mentally healthier after LKD compared to the general population. Most donors miss at least 1 month of work for LKD and undergo some form of post-donation monitoring. Despite this commitment, LKD is a very satisfying experience.

Antithymocyte antibody-induced coagulopathy in renal transplant recipients.

BACKGROUND: Antithymocyte antibody (ATA) remains the most commonly used induction immunosuppressive agent in renal transplantation (RT). To date, few case reports of ATA-induced coagulopathy exist. METHODS: We performed a single-center, retrospective analysis of renal transplant recipients (RTRs) who underwent RT followed by ATA therapy between 2007 and 2011. The protocol used for deceased donor and unrelated living donor recipient immunosuppression was Thymoglobulin (TMG), methylprednisolone, Cellcept, Prograf, and Rapamune. In related living donor recipients, Simulect (SIM) was substituted for TMG. The international normalized ratio (INR) was routinely checked on days 0 and 2, and thereafter at the discretion of the surgeon. RTRs were transfused packed red blood cells (PRBCs) or fresh frozen plasma (FFP) at the discretion of the surgeon. RESULTS: During the study period, 257 RTs were performed at our institution. The following 18 RTR were excluded: simultaneous kidney and pancreas transplant recipients (4), RTRs on warfarin at the time of admission (2), RTRs who received OKT3 (2), and RTRs with INR ≥ 1.2 at the time of admission (10). Of the remaining 239 RTR, 208 (87%) underwent TMG induction therapy; 31 RTR (13%) underwent SIM induction therapy. The mean INR peaked in both groups on day 4 but was higher in TMG recipients (TMG 1.35, SIM 1.20). FFP was transfused in 65 TMG (31%) and 3 SIM (10%) recipients (P = .01); PRBCs were transfused in 88 TMG (44%) and 6 SIM (19%) recipients (P = .02). No patients returned to the operating room for bleeding complications within 7 days of RT. Patient age, gender, ethnicity, and diabetes status were not statistically significant factors in the development of coagulopathy. CONCLUSION: TMG administration is associated with coagulopathy. Using an INR screening protocol and an aggressive transfusion protocol, bleeding complications associated with coagulopathy can be avoided in this higher-risk group.

Ureteral stents: a risk factor for polyomavirus BK viremia in kidney transplant recipients undergoing protocol screening.

BACKGROUND: Polyomavirus BK nephropathy (BKN) remains a common cause of early renal transplant dysfunction and graft loss. To date, little has been reported on the role, if any, of transplant ureteral stents in the development of polyomavirus BK viremia (BVK) and BKN. METHODS: We performed a single-center, retrospective analysis of renal transplant recipients who underwent renal transplantation followed by monthly BKV screening at Albany Medical Center between January 1, 2006, and December 31, 2009. A transplant ureteral stent was placed at the discretion of the surgeon. The immunosuppression protocol employed for deceased donor and unrelated living -donor recipients was antithymocyte antibody induction with methylprednisolone, mycophenolate mofetil, tacrolimus, and sirolimus. RESULTS: During the study period, 186 recipients were identified; 124 (67%) underwent intraoperative transplant ureteral stent placement, while 62 patients (33%) did not undergo stent placement. With our monthly screening protocol, we detected BKV in 32 of the 186 recipients (17%) following transplantation; 27 of the 32 (84%) viremic patients were stent recipients. In all patients who developed BKV, an immunosuppression dose reduction protocol was employed. Ureteral stent placement conferred a statistically significant elevated risk of developing BKV (odds ratio = 3.17, 95% confidence interval 1.16-8.70). Patient gender, age, ethnicity, diabetes status, and retransplant status were not statistically significant factors in the development of BKV. CONCLUSION: Our study demonstrated the elevated risk of BKV in recipients who undergo transplant ureteral stenting. Monthly BK polymerase chain reaction screening appears to be a useful tool for the early detection of BKV in this higher-risk group.

Initiation of a screening protocol for polyoma virus results in a decreased rate of opportunistic non-BK viral disease after renal transplantation.

BACKGROUND: Polyoma BK virus nephropathy (PVN) is a leading cause of renal allograft injury and loss. The mainstay of treatment, as there are no target therapies approved by the US Food & Drug Administration, is reduction in immunosuppression. However, current approaches are shifting to screening for viremia as an indicator of oncoming nephropathy, with subsequent reduction in immunotherapy. We attempted not only to replicate these data but also to evaluate the utility of polyoma viremia as a surrogate marker for overimmunosuppression in general, thus allowing prevention not only of PVN but also of other viral opportunistic infections such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV) disease. PATIENTS AND METHODS: We conducted a retrospective cohort analysis of renal transplant recipients at our center. The historical controls (2003-2005, n = 134) had received their allograft before the institution of a monthly serum polymerase chain reaction (PCR) polyoma screening protocol. The screened cohort received their allograft afterwards (2006-2008, n=134). Screening was performed using PCR techniques with prompt reduction in immunosuppression for viremic patients. The patients were followed for the development of PVN, acute rejection, renal allograft function, and survival. RESULTS: Polyoma viremia was noted in 16% of the screened population, with none developing PVN after prompt reduction of immunosuppression. Clearance of the viremia occurred by 6 months in 95% of the patients after reduction of immunotherapy. No patient in the screened group developed CMV or EBV disease. Of the controls, 7 (5%) developed PVN and 12 (9%) developed CMV or EBV disease, compared with none of the screened patients (P<0.05). The incidence of acute rejection was comparable between the groups (4% controls, 5% screened). No deleterious effects were noted on patient or allograft survival, allograft function (measured by serum creatinine), rates of fungal infection, or the rate of post-transplant lymphoproliferative disorder in the screened patients. CONCLUSIONS: Monthly PCR monitoring for BK viremia, together with a modest decrease in immunotherapy, is not only safe but also effectively prevents PVN and is associated with a significantly decreased rate of CMV and EBV disease in renal transplant patients. BK viremia may also serve as a surrogate marker for overimmunosuppression.

A case of Campylobacter jejuni bacteremia in a renal transplant patient.

Only 2 cases of Campylobacter bacteremia have been reported in renal transplant recipients, to our knowledge, with both resulting in significant morbidity and mortality. We present a case of a 56-year-old renal transplant recipient who presented with brief diarrheal illness followed by Campylobacter jejuni bacteremia. She remained asymptomatic for 5 days after initial presentation despite positive blood cultures. She was treated with levofloxacin for a total of 4 weeks and, fortunately, did not develop any complications. C. jejuni should be considered in the differential diagnosis as a potential cause of bacteremia in immunosuppressed renal transplant patients presenting with diarrheal illness.

Effect of preoperative sonographic mapping on vascular access outcomes in hemodialysis patients.

BACKGROUND: Current DOQI guidelines encourage placing arteriovenous (AV) fistulas in more hemodialysis patients. However, many new fistulas fail to mature sufficiently to be usable for hemodialysis. Preoperative vascular mapping to identify suitable vessels may improve vascular access outcomes. The present study prospectively evaluated the effect of routine preoperative vascular mapping on the type of vascular accesses placed and their outcomes. METHODS: During a 17-month period, preoperative sonographic evaluation of the upper extremity arteries and veins was obtained routinely. The surgeons used the information obtained to plan the vascular access procedure. The types of access placed, their initial adequacy for dialysis, and their long-term outcomes were compared to institutional historical controls placed on the basis of physical examination alone. RESULTS: The proportion of fistulas placed increased from 34% during the historical control period to 64% with preoperative vascular mapping (P < 0.001). When all fistulas were assessed, the initial adequacy rate for dialysis increased mildly from 46 to 54% (P = 0.34). For the subset of forearm fistulas, the initial adequacy increased substantially from 34 to 54% (P = 0.06); the greatest improvement occurred among women (from 7 to 36%, P = 0.06) and diabetic patients (from 21 to 50%, P = 0.055). In contrast, the initial adequacy rate of upper arm fistulas was not improved by preoperative vascular mapping (59 vs. 56%, P = 0.75). Primary access failure was higher for fistulas than grafts (46.4 vs. 20.6%, P = 0.001), but the subsequent long-term failure rate was higher for grafts than fistulas (P < 0.05). Moreover, grafts required a threefold higher intervention rate (1.67 vs. 0.57 per year, P < 0.001) to maintain their patency. The overall effect of this strategy was to double the proportion of patients dialyzing with a fistula in our population from 16 to 34% (P < 0.001). CONCLUSIONS: Routine preoperative vascular mapping results in a marked increase in placement of AV fistulas, as well as an improvement in the adequacy of forearm fistulas for dialysis. This approach resulted in a substantial increase in the proportion of patients dialyzing with a fistula in our patient population. Fistulas have a higher primary failure rate than grafts, but have a lower subsequent failure rate and require fewer procedures to maintain their long-term patency.

Risk and benefit of coronary revascularization in renal transplant candidates.

The field of transplantation along with all of medicine has made tremendous progress in the past 30 years. Patients with end-stage renal disease are managed more effectively despite increasing chronic multisystemic comorbidities, particularly involving their cardiovascular system. These same patients are also undergoing renal transplant surgery with better short- and long-term results than any era previous. We will present some of the changing demographics encountered in today's renal transplant candidates along with the processes our institution is undertaking to optimize the patient's success with the renal allograft, particularly with respect to the diagnosis and therapeutics used to manage coronary artery disease.

US vascular mapping before hemodialysis access placement.

PURPOSE: To prospectively assess the effect of preoperative ultrasonographic (US) mapping on surgical selection, placement of arteriovenous fistulas (AVFs) and grafts, and negative surgical exploration rates. MATERIALS AND METHODS: US assessment of the upper extremity arterial and venous anatomy was performed in 70 patients with chronic renal failure before surgical evaluation. The surgeon documented the planned access procedure, which was based on physical examination results, and then reviewed the US preoperative mapping report. The surgical procedure and outcome were recorded. RESULTS: Fifty-two of the 70 patients who underwent mapping had vascular access placement. Preoperative US mapping resulted in a change in the planned surgical procedure in 16 (31%) of the 52 patients. An AVF rather than the planned graft was placed in eight (15%) patients. The AVF placement rate increased from 32% (126 of 395 patients) to 58% (30 of 52 patients). Unsuccessful surgical explorations decreased from 11% (28 of 256) to 0%. CONCLUSION: Preoperative US mapping before hemodialysis access placement can result in a change in surgical management, with an increased number of AVFs placed and an improved likelihood of selecting the most functional vessels preoperatively. Further study is needed to determine longer term outcomes.

Improved outcomes in cadaveric renal allografts with pulsatile preservation.

BACKGROUND: Early immunologic and non-immunologic injury of renal allografts adversely affects long-term graft survival. Some degree of preservation injury is inevitable in cadaveric renal transplantation, and, with the reduction in early acute rejection, this non-immunologic injury has assumed a greater relative importance. Optimal graft preservation will maximize the chances of early graft function and long-term graft survival, but the best method of preservation pulsatile perfusion (PP) versus cold storage (CS) is debated. METHODS: Primary cadaveric kidney recipients from January 1990 through December 1995 were evaluated. The effects of implantation warm ischemic time (WIT) ( < or = 20 min, 21-40 min, or > 40 min) and total ischemic time (TIT) ( < or > or = 20 h) on death-censored graft survival were compared between kidneys preserved by PP versus those preserved by CS. The effect of preservation method on delayed graft function (DGF) was also examined. RESULTS: There were 568 PP kidneys and 268 CS kidneys. Overall death-censored graft survival was not significantly different between groups, despite worse donor and recipient characteristics in the PP group. CS kidneys with an implantation WIT > 40 min had worse graft survival than those with < 40 min (p = 0.0004). Survival of PP kidneys and those transplanted into 2 DR-matched recipients was not affected by longer implantation WIT. Longer TIT did not impact survival. DGF was more likely after CS preservation (20.2% versus 8.8%, p = 0.001). CONCLUSIONS: Preservation with PP improves early graft function and lessens the adverse effect of increased warm ischemia in cadaveric renal transplantation. This method is likely associated with less preservation injury and/or increases the threshold for injury from other sources and is superior to CS.

Renal retransplantation at the University of Alabama at Birmingham: incidence and outcome.

Only half the patients who lost a renal allograft either returned to the waiting list (32%) or were retransplanted (17%). One fifth died soon after allograft loss. Patients did not return to the waiting list for multiple reasons including patient choice, worsened medical condition and most commonly, interest but non-referral. Diabetics had a significantly diminished chance for survival on dialysis after graft loss. African-Americans had a better chance of survival after graft loss but a much worse opportunity to be retransplanted. The use of CellCept in triple immunosuppressive therapy, along with a flow cytometry crossmatch, has improved retransplant allograft survival commensurate with primary graft outcome. The incidence of retransplantation is decreasing at our institution even though the number of potential candidates for retransplantation remains stable.

Comparative pharmacokinetics and renal effects of cyclosporin A and cyclosporin G in renal allograft recipients.

Cyclosporin G (CSG) has produced less nephrotoxicity than cyclosporin A (CSA) at equivalent doses in animal models. Conflicting results have been reported concerning differences in the pharmacokinetics of CSA and CSG in preclinical studies, and no data exist regarding the effect of steady-state oral administration of CSG on renal function in transplant patients or CSG-induced release of endothelin and nitric oxide (NO) in vivo. The objective of the study was to examine steady-state pharmacokinetic profiles of adult renal allograft recipients receiving CSA and CSG in relation to concentrations of endothelin-1 and NO2/NO3 in urine and plasma, creatinine clearance (Clcr), and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) 9 months after transplantation. Concentrations of CSA and CSG were measured in whole blood over a 12-hour dose interval by both a monoclonal and polyclonal fluorescence polarization radioimmunoassay for CSA. A metabolite fraction was defined as the numerical difference between the levels obtained at each time point by both assays. Patient groups were defined as follows: group 1: initial CSA (n = 6); group 2: initial CSG (n = 7); group 3: five of the seven patients in group 2 taking CSG subsequently undergoing conversion to CSA; group 4: the same five patients in group 3 restudied 1 month after 1:1 dosage conversion to CSA; and group 5: CSA groups 1 and 4 combined (n = 11). In group 1, the metabolite fraction accounted for 32% to 54% of the total measurable drug concentration at each time point, whereas in group 2, the metabolite fraction accounted for at most 10% to 15% of the total drug levels measurable by polyclonal fluorescence polarization radioimmunoassay. Although there were no significant differences in any of the mean pharmacokinetic parameters between groups using monoclonal fluorescence polarization radioimmunoassay, the normalized area under the concentration-time curve (NAUC) value was less in four of five patients after conversion from CSG to CSA, with a more variable and delayed time to reach peak concentration (tmax) but equivalent apparent oral clearance (Clpa) values. Clcr was found to change significantly with time in groups 1 and 5 but not in group 2, with CSA producing a more profound and sustained decrease than CSG. Endothelin-1 and NO2/NO3 levels in plasma and urine remained relatively constant after administration of both CSA and CSG, and there were no significant differences between groups 3 and 4 regarding mean endothelin-1 and NO2/NO3 concentrations in plasma, urinary release of endothelin-1 and NO2/NO3, and mean AUC of endothelin-1 and AUC of NO2/NO3. However, monoclonal NAUC correlated significantly with total urinary endothelin-1 within CSA groups 1 and 5 but not within CSG group 2. Metabolite NAUC correlated significantly with total urinary NAG within CSA group 1. Although limited by the small number of patients, this study suggests that 1) CSG may produce less of a reduction in Clcr over time after oral administration at steady state than does CSA, and 2) this beneficial effect of CSG may be in part due to decreased intrarenal release of endothelin-1, as urinary excretion of endothelin-1 seemed to correlate better with CSA than with CSG exposure.

Preemptive ganciclovir therapy in cytomegalovirus-seropositive renal transplants recipients.

OBJECTIVE: To evaluate the efficacy, safety, and cost of preemptive ganciclovir therapy in cytomegalovirus (CMV)-seropositive renal transplant recipients treated with antilymphocyte antibody (ALA) preparations. DESIGN AND SETTING: A prospective, randomized trial at a 650-bed tertiary medical center hospital. PATIENTS: Forty consecutive CMV-seropositive renal allograft recipients who underwent transplantation between January 1992 and January 1994 and were treated with ALA for induction immunosuppression or acute rejection therapy. MAIN OUTCOME MEASURES: The incidence and severity of CMV disease, length of hospitalization, and patient and allograft survival. INTERVENTION: Cytomegalovirus infection prophylaxis by use of intravenous ganciclovir during ALA therapy was administered to 22 patients (group 1) and the results were compared with those obtained in 18 control patients who did not receive prophylaxis for CMV disease (group 2). RESULTS: Preemptive ganciclovir therapy significantly reduced the incidence of CMV disease (P < .05) in CMV-seropositive renal transplant patients who were treated with ALA and was well tolerated. In addition, the cost of prophylactic therapy was offset by the decreased length of hospitalization observed in patients in group 1. CONCLUSION: Preemptive ganciclovir therapy provides a cost-effective approach toward significantly improving the outcome of renal transplantation in CMV-seropositive patients treated with ALA.

Placement of a double lumen silastic catheter for hemodialysis access through the cephalic vein.

The cephalic vein within the deltopectoral groove provides adequate access to the central venous system for the PermCath hemodialysis catheter. Unlike EJV techniques, which are successful in few instances, the cephalic vein approach was successful in approximately 75 percent of instances. In addition, the rate of complications secondary to bleeding or catheter kinking are decreased with the cephalic vein technique as compared with insertion through the EJV or IJV. We conclude that the cephalic vein is a dependable and functional approach to the central venous system for the PermCath hemodialysis catheter.

Macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor stimulate the synthesis of plasminogen-activator inhibitors by human monocytes.

Macrophage colony-stimulating factor (M-CSF or CSF-1) and granulocyte-macrophage CSF (GM-CSF) have been shown to increase human monocyte urokinase-type plasminogen-activator (u-PA) activity with possible consequences for cell migration and tissue remodeling; because monocyte u-PA activity is likely to be controlled in part also by the PA inhibitors (PAIs) made by the cell, the effect of M-CSF and GM-CSF on human monocyte PAI-2 and PAI-1 synthesis was investigated. To this end, elutriation-purified human monocytes were treated in vitro with purified recombinant human M-CSF and GM-CSF, and PAI-2 and PAI-1 antigen and mRNA levels measured by specific enzyme-linked immunosorbent assays and Northern blot, respectively. Each CSF could enhance the protein and mRNA levels of PAI-2 and PAI-1 at similar concentrations for each product. This similar regulation of monocyte PAI expression in response to the CSFs contrasted with that found for the effects of lipopolysaccharide, transforming growth factor-beta and a glucocorticoid. Therefore, PAIs may be modulating the effects of the CSFs on monocyte u-PA activity at sites of inflammation and tissue remodeling.

Regulation of plasminogen activator inhibitor-1 levels in human monocytes.

The regulation of PAI-1 synthesis by elutriation-purified human monocytes was studied in vitro and compared to that for PAI-2. PAI-1 formation, as measured by ELISA, was upregulated by TGF-beta (> or = 1 ng/ml) and surprisingly down-regulated by LPS (100 ng/ml), particularly in the presence of TGF-beta; LPS elevated PAI-2 levels (ELISA) while TGF-beta reduced its basal levels and those in LPS-treated cultures. Concomitant changes in mRNA expression occurred. The glucocorticoid dexamethasone (10(-7) M) elevated PAI-1 and acted in concert with TGF-beta in this regard at both the antigen and mRNA levels; interleukin-4 (IL-4) (250 pM) failed to mimic the steroid in its regulation of PAI-1 formation. Since monocyte/macrophage PA activity is likely to be important in tissue remodeling and cell migration at sites of inflammation and in fibrinolysis, it is proposed from these studies that PAI-1, as well as the usually considered PAI-2, may be involved in the negative control of PA activity in this cell type. The synthesis of each PAI appears to be independently regulated.