Characterizing the risk of human leukocyte antigen-incompatible living donor kidney transplantation in older recipients.

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.45 2.093.02 ; PFNC = 1.67 2.403.46 ; PCC = 1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.34 1.621.95 ) than CLDKT (aHR = 1.96 2.292.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors.

BACKGROUND: A report from a high-volume single center indicated a survival benefit of receiving a kidney transplant from an HLA-incompatible live donor as compared with remaining on the waiting list, whether or not a kidney from a deceased donor was received. The generalizability of that finding is unclear. METHODS: In a 22-center study, we estimated the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting-list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group). We analyzed the data with and without patients from the highest-volume center in the study. RESULTS: Recipients of kidney transplants from incompatible live donors had a higher survival rate than either control group at 1 year (95.0%, vs. 94.0% for the waiting-list-or-transplant control group and 89.6% for the waiting-list-only control group), 3 years (91.7% vs. 83.6% and 72.7%, respectively), 5 years (86.0% vs. 74.4% and 59.2%), and 8 years (76.5% vs. 62.9% and 43.9%) (P<0.001 for all comparisons with the two control groups). The survival benefit was significant at 8 years across all levels of donor-specific antibody: 89.2% for recipients of kidney transplants from incompatible live donors who had a positive Luminex assay for anti-HLA antibody but a negative flow-cytometric cross-match versus 65.0% for the waiting-list-or-transplant control group and 47.1% for the waiting-list-only control group; 76.3% for recipients with a positive flow-cytometric cross-match but a negative cytotoxic cross-match versus 63.3% and 43.0% in the two control groups, respectively; and 71.0% for recipients with a positive cytotoxic cross-match versus 61.5% and 43.7%, respectively. The findings did not change when patients from the highest-volume center were excluded. CONCLUSIONS: This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

Hospital readmissions following HLA-incompatible live donor kidney transplantation: A multi-center study.

Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant-matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed-effects Poisson regression. In the first month, ILDKTs had a 1.28-fold higher readmission risk than compatible controls (95% confidence interval [CI] 1.13-1.46; P < .001). Risk peaked at 6-12 months (relative risk [RR] 1.67, 95% CI 1.49-1.87; P < .001), attenuating by 24-36 months (RR 1.24, 95% CI 1.10-1.40; P < .001). ILDKTs had a 5.86-fold higher readmission risk (95% CI 4.96-6.92; P < .001) in the first month compared to waitlist-only controls. At 12-24 (RR 0.85, 95% CI 0.77-0.95; P = .002) and 24-36 months (RR 0.74, 95% CI 0.66-0.84; P < .001), ILDKTs had a lower risk than waitlist-only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist-only controls should be considered in regulatory/payment schemas and planning clinical care.

Laparoendoscopic single-site (LESS) vs laparoscopic living-donor nephrectomy: a systematic review and meta-analysis.

The aim of this study was to provide a systematic review and meta-analysis of reports comparing laparoendoscopic single-site (LESS) living-donor nephrectomy (LDN) vs standard laparoscopic LDN (LLDN). A systematic review of the literature was performed in September 2013 using PubMed, Scopus, Ovid and The Cochrane library databases. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Weighted mean differences (WMDs) were used to measure continuous variables and odds ratios (ORs) to measure categorical ones. Nine publications meeting eligibility criteria were identified, including 461 LESS LDN and 1006 LLDN cases. There were more left-side cases in the LESS LDN group (96.5% vs 88.6%, P < 0.001). Meta-analysis of extractable data showed that LLDN had a shorter operative time (WMD 15.06 min, 95% confidence interval [CI] 4.9-25.1; P = 0.003), without a significant difference in warm ischaemia time (WMD 0.41 min, 95% CI -0.02 to 0.84; P = 0.06). Estimated blood loss was lower for LESS LDN (WMD -22.09 mL, 95% CI -29.5 to -14.6; P < 0.001); however, this difference was not clinically significant. There was a greater likelihood of conversion for LESS LDN (OR 13.21, 95% CI 4.65-37.53; P < 0.001). Hospital stay was similar (WMD -0.11 days, 95% CI -0.33 to 0.12; P = 0.35), as well as the visual analogue pain score at discharge (WMD -0.31, 95% CI -0.96 to 0.35; P = 0.36), but the analgesic requirement was lower for LESS LDN (WMD -2.58 mg, 95% CI -5.01 to -0.15; P = 0.04). Moreover, there was no difference in the postoperative complication rate (OR 1.00, 95% CI 0.65-1.54; P = 0.99). Renal function of the recipient, as based on creatinine levels at 1 month, showed similar outcomes between groups (WMD 0.10 mg/dL, -0.09 to 0.29; P = 0.29). In conclusion, LESS LDN represents an emerging option for living kidney donation. This procedure offers comparable surgical and early functional outcomes to the conventional LLDN, with a lower analgesic requirement. However, it is more technically challenging than LLDN, as shown by a greater likelihood of conversion. The role of LESS LDN remains to be defined.

Does reduction in mycophenolic acid dose compromise efficacy regardless of tacrolimus exposure level? An analysis of prospective data from the Mycophenolic Renal Transplant (MORE) Registry.

Prospective data are lacking concerning the effect of reduced mycophenolic acid (MPA) dosing on efficacy and the influence of concomitant tacrolimus exposure. The Mycophenolic Renal Transplant (MORE) Registry is a prospective, observational study of de novo kidney transplant patients receiving MPA therapy under routine management. The effect of MPA dose reduction, interruption, or discontinuation (dose changes) was assessed in 870 tacrolimus-treated patients: 375 (43.1%) reduced tacrolimus (≤ 7 ng/mL at baseline) and 495 (56.9%) standard tacrolimus (>7 ng/mL); enteric-coated mycophenolate sodium 589 (67.7%) and mycophenolate mofetil 281 (32.3%). During baseline to month 1, months 1-3, months 3-6, and months 6-12, 9.3% (78/838), 16.6% (132/794), 20.7% (145/701), and 13.1% (70/535) patients, respectively, required MPA dose changes. These patients experienced an increased risk of biopsy-proven acute rejection at one yr with tacrolimus exposure either included in the model (hazard ratio [HR] 2.60, 95% CI 1.28-5.29, p = 0.008) or excluded (HR 2.58, 95% CI 1.28-5.23, p = 0.008). MPA dose changes were significantly associated with one yr graft failure when tacrolimus exposure was included (HR 2.23; 95% CI 1.01-4.89, p = 0.047) but not when tacrolimus exposure was excluded (HR 2.16; 95% CI 0.99-4.79; p = 0.054). These results suggest that reducing or discontinuing MPA can adversely affect graft outcomes regardless of tacrolimus trough levels.

Association of mycophenolic acid dose with efficacy and safety events in kidney transplant patients receiving tacrolimus: an analysis of the Mycophenolic acid Observational REnal transplant registry.

BACKGROUND: Dose-finding studies for mycophenolic acid (MPA) in tacrolimus-treated kidney transplant patients are lacking. METHODS: Data from 901 de novo kidney transplant recipients enrolled in the prospective, non-interventional Mycophenolic acid Observational REnal (MORE) transplant registry were analyzed according to baseline daily MPA dose (<2000, 2000 or >2000 mg). RESULTS: The proportion of patients receiving 2000 and <2000 mg was 77.6% and 19.9% at baseline, 74.5% and 23.3% at month 1, 62.4% and 35.5% at month 3, 48.5% and 50.2% at month 6, and 44.1% and 55.2% at month 12. More patients were maintained on 2000 mg with enteric-coated mycophenolate sodium (EC-MPS) vs. mycophenolate mofetil (month 6, 52.7% vs. 43.0% [p=0.02]; month 12, 47.3% vs. 39.4% [p=0.08]). Multivariate modeling showed no significant effect of baseline MPA dose on 12-month risk of biopsy-proven acute rejection, graft loss or estimated GFR, or on safety events including MPA discontinuation other than a higher rate of gastrointestinal adverse events in patients with an initial MPA dose>2000 mg (p=0.029) vs. 2000 mg. CONCLUSIONS: These findings suggest that an initial MPA dose of <2000 mg does not compromise 12-month efficacy in tacrolimus-treated kidney transplants, but controlled trials are required and the lower threshold for MPA dose remains to be defined.

Feasibility and safety of retroperitoneoscopic laparoendoscopic single-site nephrectomy: technique and early outcomes.

UNLABELLED: What's known on the subject? and What does the study add? Laparoendoscopic single-site (LESS) nephrectomy is feasible to remove diseased kidneys. Most of such procedures previously reported were performed through a transperitoneal (trans-abdominal) approach. We report the feasibility, safety, and techniques of performing such operations without disturbing the bowels (a retroperitoneal LESS approach). This approach provides acceptable operative outcomes, and is especially valuable for patients who need to have an intact peritoneal envelope, or those with potentially abnormal or obliterated peritoneal space. OBJECTIVES: • To retrospectively review our experience with respect to evaluating the feasibility and safety of retroperitoneoscopic laparoendoscopic single-site surgery (LESS) nephrectomy. • To present the technical details of such a procedure. PATIENTS AND METHODS: • In total, eight retroperitoneoscopic LESS nephrectomies (in seven patients) were completed for a variety of indications in a single centre. • The GelPOINT apparatus (Applied Medical, Rancho Santa Margarita, CA, USA) was used as an access platform through a flank incision (3-5 cm). • Except for a bendable grasper and flexible vascular staplers, all instruments used were conventional straight laparoscopic instruments. • Perioperative data were retrospectively obtained for all patients, including demographic data, operative indications, operative records, length of stay, complications, and pathological analysis. RESULTS: • All retroperitoneoscopic LESS nephrectomy procedures attempted were completed successfully without complications. No extra working port was required for any case. • Median (range) operating time was 164 (87-198) min and median (range) estimated blood loss was 50 (10-200) cm(3) . Median (range) length of hospital stay was 2 (1-3) days. • The median narcotic used was 34 mg of parental morphine sulphate equivalent. The median (range) visual analogue pain scale score at discharge was 2 (0-3) out of 10. • The present single arm observation study is limited by the small patient number and the absence of a control cohort. CONCLUSIONS: • Retroperitoneoscopic LESS nephrectomy using the GelPOINT apparatus as an access platform is feasible and safe. • It provides adequate flexibility and spacing of port placements as well as acceptable operative outcomes. • It is especially valuable for those patients who need to maintain peritoneal integrity or those with an abnormal or obliterated peritoneal space.

Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes.

BACKGROUND: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. METHODS: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSIONS: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.

Immunosuppression after kidney transplantation: current stragegies and drug interactions.

The success of kidney transplantation has improved over the last decade largely due to new immunosuppressive agents that resulted in decrease in incidence and severity of acute cellular rejection. Minimizing the adverse effects of immunosuppressive agents is essential to improving long-term survival. This article reviews the current immunosuppressive agents available to the clinician, their side effects and interaction with other medications. Current immunosuppressive protocols are also discussed including newer steroid avoidance protocols and calcineurin avoidance protocol.

The benefits of pulsatile machine perfusion of standard criteria deceased donor kidneys at a geographically remote transplant center.

Benefits of pulsatile machine perfusion (pumping) of standard criteria donor (SCD) kidneys are unclear. Our center is located 4½ hours from our Organ Procurement Organization. We evaluated outcomes of pumping SCD kidneys under such circumstances by conducting a retrospective examination of all SCD kidneys transplanted between January 2007 and March 2012, comparing kidneys pumped (28 [group 1]) versus standard cold storage (77 [group 2]). Group 1 had fewer delayed graft function (DGF, 3.57% vs. 23.38%, p = 0.02) and slow graft function (SGF, 7.14% vs. 24.68%; p = 0.047) and faster serum creatinine recovery curve (p < 0.001) than group 2. Having a kidney pumped decreases the incidence (odds ratio [OR], 0.059) of DGF, SGF, or primary nonfunction. Group 1 were quicker to reach an estimated glomerular filtration rate (eGFR) >30 ml/min (OR, 4.186; confidence interval [CI], [2.448-7.157]) or an eGFR >60 ml/min (OR, 2.669; CI [1.255-5.679]). Pumping the SCD kidneys in a geographically remote transplant center tended to be better than those preserved in cold storage. However, except recovery curve of serum creatinine during the first postoperative month, other parameters failed to reach statistical significance in the post hoc examination of the contemporary groups. Prospective paired kidney study is required to scrutinize this finding.

Safe initiation of a laparoendoscopic single site living donor nephrectomy program in a small-volume transplant center.

OBJECTIVE: To describe keys to successful programmatic implementation of laparoendoscopic single-site (LESS)-living donor nephrectomy (LDN) in a small-volume center. Laparoscopic LDN has become the standard of care. Technically challenging LESS-LDN has been limited to high-volume centers. However, approximately half of all U.S. transplant centers perform ≤15 LDNs/year, including our center. METHODS: A hand-assisted laparoscopy (HAL) device was used as the LESS platform at a periumbilical midline incision. We used an adhesive drape to cover the platform to prevent gas leakage. A 30° telescope and 3-4 instruments were inserted through its gel-cap. After careful dissection, the kidney was bagged into a recovery device with an external handle before its vessels were ligated with staples and was then removed immediately through the LESS wound. RESULTS: LESS-LDN was successful in all of 10 living donors without any multisite laparoscopic or open conversion and without any instruments inserted through extra wounds. No patient had perioperative complications or received transfusions. Median operative time was 271 minutes with a warm ischemia time (WIT) of 3.5 minutes. Hospital stay averaged 2 days with visual analog pain score 4 of 10 at discharge and 2 of 10 at 2 weeks. All recipients recuperated well with immediate graft function. CONCLUSION: Our LESS-LDN technique offers improved cosmesis, favorable perioperative outcomes, and versatile options for conversion, if necessary, making it a viable approach for small-volume centers.

Simultaneous laparoendoscopic single-site radical nephrectomy for native kidney and open nonischemic partial nephrectomy to treat concomitant renal cell carcinomas in native and transplant kidneys and to preserve allograft function.

OBJECTIVE: To report a technique of minimally invasive radical nephrectomy for a native renal cell carcinoma (RCC) and nonischemic open partial nephrectomy for a transplant kidney RCC with only a laparoendoscopic single-site (LESS) incision. Concomitant RCCs in a native and transplant kidneys are very rare. Conventional surgical approach requires a long incision. METHODS: A 50-year-old man 14 years after renal transplant was found incidentally to have concomitant RCCs in his native right kidney and transplant kidney. A right lower abdomen Gibson incision, along his transplant wound, was used initially for LESS right radical nephrectomy and lymphadenectomy, and that same wound was used for a nonischemic open partial nephrectomy in the transplant kidney. RESULTS: The LESS right radical nephrectomy took 3.25 hours with estimated blood loss (EBL) of 80 mL and the partial nephrectomy for the transplant kidney took 3 hours with EBL of 220 mL. No transfusion was required. Pathologic examination revealed both tumors to be RCC, clear cell type, and 6.5 cm in the right native kidney and 2.8 cm in the transplant kidney. The final wound measured 9 cm. Postoperative recovery was uneventful with inpatient narcotic requirement of 37 mg morphine sulfate equivalent, and oral intake of food resumed in 2.5 days. His allograft function was well preserved with a serum creatinine unchanged (1.4 mg/dL) at discharge. CONCLUSION: In a patient with concomitant tumors in a native kidney and a transplant kidney, this unique approach provides exceptional benefits of minimally invasive tumor excision for both tumors, and good preservation of renal function.