Outcomes of kidney transplant (KT) in multiple myeloma (MM) were investigated using the OPTON/UNOS database. Two hundred and eighteen MM KT patients were compared to 490,089 general KT patients. KT MM patients had equivalent graft and age-matched overall survival compared to the general population. Therefore select patients with MM renal failure should be considered for transplantation and have potential for excellent KT outcomes. Introduction: Describe graft and overall survival outcomes in multiple myeloma (MM) patients who underwent kidney transplant (KT) compared to the general KT population. Patients and Methods: The Organ Procurement and Transplantation Network/National United Network for Organ Sharing (OPTON/UNOS) database was analyzed from 1988 to 2019 with R 4.00 and the 2013-2017 United States Renal Data System (USRDS) was surveyed for incidence and mortality of MM ESRD. Results: USRDS analysis revealed 961 patients diagnosed with ESRD due to MM on average annually, accounting for 0.8% of the ESRD population. Without KT, 44.4% of MM patients died in the first year of renal replacement initiation. OPTON/UNOS analysis identified 218 MM KT patients, compared to 490,089 patients without MM. There was no difference in graft survival between MM KT and the general population (P-value =.13, HR = 1.19 [0.95, 1.49], 95% CI). Median graft survival in MM KT was 2683 days (7.4 years). KT patients with MM had a higher risk for death (P-value = <.0001, HR = 1.83 [1.41, 2.37], 95% CI), and median overall survival was 3076 days (8.4 years). Survival difference was lost when comparing patients >= 50 years (P-value =.42, HR = 1.14 [0.83, 1.56], 95% CI). Conclusion: Patients with MM renal failure who underwent KT had equivalent graft and age-matched overall survival compared to the general KT population. Therefore select patients with MM renal failure have potential for excellent KT outcomes, should be considered for transplantation when feasible, and should not be excluded from KT based on a history of MM.

Polyomavirus nephropathy (PVN) is a major complication of kidney transplantation. Most reports describe polyomavirus viremia either precedes or is detectable at the time of diagnosis of PVN. This association is the basis of current screening recommendations. We retrospectively reviewed the PCR results of blood and urine samples from 29 kidney transplant recipients with biopsy-proven PVN. Biopsies were performed for a rise in serum creatinine or persistent high-level BK viruria. All biopsies showed polyoma virus large T-antigen expression in tubular epithelium using immunohistochemistry. All had viruria preceding or at the time of biopsy (range, 5.2 × 104 to >25 × 106 BKV DNA copies/ml). Twenty (69%) had viremia ranging from 2.5 × 103 to 4.3 × 106 copies/ml at the time of the biopsy. Via blood BK PCR assay, nine (31%) had no BK viremia detected either preceding or at the time of the biopsy. In five recipients where sufficient specimen permitted, additional plasma BK assessment revealed positive detection of viremia. A comparative analysis of assays from two centres was performed with spiked samples. BK DNA may not be detected in the blood of some kidney transplant recipients with histologically confirmed PVN. This may reflect limitation of whole blood as opposed to plasma-based BK DNA assessment.

Antibody-mediated rejection (AMR) remains a problem without a reliable treatment in the care of kidney transplant patients. We proposed and tested a program of screening for donor specific antibodies (DSA) to initiate treatment of patients before AMR was detected and to prevent its occurrence. Starting in April 2012, we stratified patients into high-, medium-, and low-risk groups for the development of DSA and instituted a program of screening for and treatment of these antibodies. We used a historic control group of patients transplanted at our center as a comparator and looked at rates of DSA testing and development as well as rates of development of AMR, cell-mediated rejection, and graft loss. 614 patients were transplanted under the protocol compared with 266 patients in the control group. Length of follow-up was similar in both groups. The group undergoing DSA screening had lower rates of DSA development (17.6% versus 24.8%, p=0.016) and that DSA was found at a significantly earlier time post-transplant (147 versus 248 days, p=0.02). Incidence of AMR was dramatically lower in the screened group (1.3% versus 8.6%, p<0.0001) with no grafts lost due to AMR. AMR was found to occur at an average of 181 days post-transplant. Rates of acute cellular rejection did not decrease in a manner similar to AMR rates. In conclusion, a program of universal risk-stratified DSA testing in kidney transplant patients can dramatically reduce rates of AMR and virtually eliminate graft loss due to AMR.

IMPORTANCE Despite the potential for altruistic nondirected donors (NDDs) to trigger multiple transplants through nonsimultaneous transplant chains, concerns exist that these chains siphon NDDs from the deceased donor wait list and that donors within chains might not donate after their partner receives a transplant. OBJECTIVE To determine the number of transplantations NDDs trigger through chains. DESIGN Retrospective review of large, multicenter living donor-recipient database. SETTING Fifty-seven US transplant centers contributing donor-recipient pairs to the database. PARTICIPANTS The NDDs initiating chain transplantation. MAIN OUTCOMES MEASURE Number of transplants per NDD. RESULTS Seventy-seven NDDs enabled 373 transplantations during 46 months starting February 2008. Mean chain length initiated by NDDs was 4.8 transplants (median, 3; range, 1-30). The 40 blood type O NDDs triggered a mean chain length of 6.0 (median, 4; range, 2-30). During the interval, 66 of 77 chains were closed to the wait list, 4 of 77 were ongoing, and 7 of 77 were broken because bridge donors became unavailable. No chains were broken in the last 15 months, and every recipient whose incompatible donor donated received a kidney. One hundred thirty-three blood type O recipients were transplanted. CONCLUSION AND RELEVANCE This large series demonstrates that NDDs trigger almost 5 transplants on average, more if the NDD is blood type O. There were more blood type O recipients than blood type O NDDs participating. The benefits of transplanting 373 patients and enabling others without living donors to advance outweigh the risk of broken chains that is decreasing with experience. Even 66 patients on the wait list without living donors underwent transplantation with living-donor grafts at the end of these chains.

Renal transplant recipients continue to have progressive kidney dysfunction and renal graft loss has been attributed to emerging opportunistic infections, specifically BK virus (BKV). BKV is postulated to be selected by the new potent immunosuppressive medications and to be an important factor in graft failure. The prevalence of BKV nephropathy (BKVN) is estimated to be 1% to 10% and renal allograft loss from BKVN has been estimated to occur in up to 50% of affected recipients. With the increasing recognition of BKV infection using PCR assays coupled with the immediate reduction in immunosuppression for BKVN, the incidence of graft failure secondary to BKVN may be decreasing.

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BACKGROUND AND OBJECTIVESGlomerular lesions in allografts in recipients with end-stage nephritis resulting from systemic lupus erythematosus (SLE) were examined to determine the spectrum of glomerular pathology in recurrent glomerulonephritis (GN).DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSA total of 156 biopsy samples, from 49 serial allografts in 43 recipients with end-stage lupus nephritis, were examined by light microscopy, and by immunofluorescence and electron microscopy in selected cases. These were compared with control allografts (n = 35).RESULTSGlomerular lesions best explained by recurrent lupus nephritis were observed in 19 of 49 allografts (38.8%) in lupus recipients. Three categories of glomerulopathies were identified: 1) immune complex glomerulopathies, including mesangial GN (28%) and membranous GN (4%); 2) atypical glomerulopathies, including acute proliferative GN (32%) and focal segmental glomerulosclerosis (12%), with scant immune deposits in glomerular capillaries, frequent endothelial tubuloreticular inclusions, and thrombotic microangiopathy; and 3) transplant-associated glomerulopathies (24%).CONCLUSIONSAllografts from recipients with SLE had typical immune complex-mediated GN and atypical pauci-immune, proliferative GN and segmental glomerular sclerosis. Atypical glomerulopathies like these suggest a role for nonimmune complex-mediated glomerular injury in recurrent lupus GN.

BACKGROUND:Clinical outcome of renal transplantation among systemic lupus erythematosus (SLE) patients remains a topic of controversy. Most of the previous reports were based upon small single-centre studies that were not always well-designed.METHODS:We conducted the retrospective analysis using data from USRDS and UNOS databases. Patients were divided into five groups based on the cause of end-stage renal disease (ESRD): diabetes mellitus (DM), SLE, glomerulonephritis, hypertension and other causes. Between 1990 and 1999, 2886 renal transplantation recipients with ESRD due to SLE were identified from a total of 92 844 patients.RESULTS:The mean follow-up period of this study was 4.7 +/- 2.4 years. While unadjusted analysis using Kaplan-Meier curves demonstrated an association between SLE and improved allograft survival compared with DM, in multivariate analysis the SLE group had worse allograft [hazard ratio (HR) 1.09, P < 0.05] and recipient (HR 1.19, P < 0.05) survival compared with the DM group. Subgroup analysis based on the type of donor showed that SLE patients who received deceased donor allograft had worse allograft and recipient survival (HR 1.14, P = 0.002 and HR 1.30, P = 0.001, respectively) compared with non-SLE deceased donor allograft recipients. Among living allograft recipients, there were no significant differences in either allograft or recipient survival compared with non-SLE recipients.CONCLUSIONS:SLE as a cause of ESRD in renal transplant recipients is associated with worse allograft and recipient survival compared with DM; this association is true for the entire population and for the recipients of deceased donor (but not living donor) transplant. Deceased donor allograft recipients have worse outcomes compared with living allograft recipients.

Leflunomide, trade name Arava (R) (Aventis Pharmaceuticals Incorporation, Bridgewater, New Jersey, U.S.A.), belongs to a family of drugs called the malonitrilamides. Some, like leflunomide, have substantial immune suppressive activity in experimental allo models. In addition to experimental data suggesting leflunomides value in preventing and reversing acure(1,5) and chronic rejection,(6,7) it has been shown to inhibit human cytomegalovirus (CMV) and herpes simplex virus (HSV) in vitro.(8-10) Because it is a drug with a variety of biologic activities, it has been investigated for diseases as disparate as cancer and autoimmunity. Leflunomide was approved for the treatment of rheumatoid arthritis and has been used in more than 300,000 patients worldwide with efficacy and a favorable side effect profile. In this chapter, we will discuss the immunemodulatory effects of leflunomide and its metabolite A77 1726 that prevent organ rejection. We will also share our experience in the treatment of polyomavirus infections.

Background. Polyoma BK virus produces an aggressively destructive nephropathy in approximately 3% to 8% of renal allografts, is associated with graft loss within one year in 35% to 67% of those infected and there is no therapy of proven efficacy. Leflunomide is an immune suppressive drug with anti viral activity in vitro and in animals.Methods. We treated twenty-six patients with biopsy proven NK virus nephropathy (BKN) with either leflunomide alone (n=17) or leflunomide plus a course of cidofovir (n=9) and followed them for six to forty months. Leflunomide was dosed to a targeted blood level of active metabolite, A77 1726, of 50 mu g/ml to 100 mu g/ml (150 mu M to 300 mu M). Response to treatment was gauged by serial determinations of viral load in blood and urine (PCR), serum creatinine, and repeat allograft biopsy.Results. In the 22 patients consistently sustaining the targeted blood levels of active drug, blood and urine viral load levels uniformly decreased over time (P <.001). Mean serum creatinine levels stabilized over the first six months of treatment, and with 12 months or more of follow-up in 16 patients the mean serum creatinine has not changed significantly from base line. Four patients who did not consistently have blood levels of active drug (A77 1726) above 40 mu g/ml did not clear the virus until these levels were attained or cidofovir was added.Conclusions. Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.