Temporal trends in kidney paired donation in the United States: 2006-2021 UNOS/OPTN database analysis.

Kidney paired donation (KPD) is a major innovation that is changing the landscape of kidney transplantation in the United States. We used the 2006-2021 United Network for Organ Sharing data to examine trends over time. KPD is increasing, with 1 in 5 living donor kidney transplants (LDKTs) in 2021 facilitated by KPD. The proportion of LDKT performed via KPD was comparable for non-Whites and Whites. An increasing proportion of KPD transplants are going to non-Whites. End-chain recipients are not identified in the database. To what extent these trends reflect how end-chain kidneys are allocated, as opposed to increase in living donation among minorities, remains unclear. Half the LDKT in 2021 in sensitized (panel reactive antibody ≥ 80%) and highly sensitized (panel reactive antibody ≥ 98%) groups occurred via KPD. Yet, the proportion of KPD transplants performed in sensitized recipients has declined since 2013, likely due to changes in the deceased donor allocation policies and newer KPD strategies such as compatible KPD. In 2021, 40% of the programs reported not performing any KPD transplants. Our study highlights the need for understanding barriers to pursuing and expanding KPD at the center level and the need for more detailed and accurate data collection at the national level.

Genetic evaluation of living kidney donor candidates: A review and recommendations for best practices.

The growing accessibility and falling costs of genetic sequencing techniques has expanded the utilization of genetic testing in clinical practice. For living kidney donation, genetic evaluation has been increasingly used to identify genetic kidney disease in potential candidates, especially in those of younger ages. However, genetic testing on asymptomatic living kidney donors remains fraught with many challenges and uncertainties. Not all transplant practitioners are aware of the limitations of genetic testing, are comfortable with selecting testing methods, comprehending test results, or providing counsel, and many do not have access to a renal genetic counselor or a clinical geneticist. Although genetic testing can be a valuable tool in living kidney donor evaluation, its overall benefit in donor evaluation has not been demonstrated and it can also lead to confusion, inappropriate donor exclusion, or misleading reassurance. Until more published data become available, this practice resource should provide guidance for centers and transplant practitioners on the responsible use of genetic testing in the evaluation of living kidney donor candidates.

Factors enabling transplant program participation in the Scientific Registry of Transplant Recipients (SRTR) Living Donor Collective: A national survey.

BACKGROUND: The Scientific Registry of Transplant Recipients (SRTR) Living Donor Collective (LDC), the first effort to create a lifetime registry for living donor candidates in the United States, requires transplant programs to register donor candidates while the SRTR conducts follow-up. METHODS: To better understand facilitators and barriers to program participation, we conducted a brief electronic survey of U.S. transplant program staff from October 26, 2021 to December 17, 2021. RESULTS: We received 132 responses, with at least one response from 87 living donor programs (46 kidney programs, 33 kidney and liver programs, and eight liver programs alone). We found 86% of program representatives strongly agreed or agreed that funding adequate to cover the cost of data collection would facilitate LDC participation, 92% agreed or strongly agreed with importance of electronic data submission options, and 74% reported that elimination of requirements to submit duplicative pre-operative information to the Organ Procurement and Transplantation Network (OPTN) would be helpful. Other potentially enabling factors include reduction in duration of OPTN postdonation follow-up requirements, ease-of-use, protection from data use for regulation, adequate data security, and equity in data access. CONCLUSION: This survey identifies potential targets to strengthen participation in the effort to create a national living donor registry in the United States. Collaboration and investment to overcome barriers to LDC participation among transplant programs are vital to generate long-term data on living donation for donor candidates, donors, and patients in need of transplant.

Telemedicine services for living kidney donation: A US survey of multidisciplinary providers.

Individuals considering living kidney donation face geographic, financial, and logistical challenges. Telemedicine can facilitate healthcare access/care coordination. Yet difficulties exist in telemedicine implementation and sustainability. We sought to examine centers' practices and providers' attitudes toward telemedicine to improve services for donors. We surveyed multidisciplinary providers from 194 active adult US living donor kidney transplant centers; 293 providers from 128 unique centers responded to the survey (center representation rate = 66.0%), reflecting 83.9% of practice by donor volume and 91.5% of US states/territories. Most centers (70.3%) plan to continue using telemedicine beyond the pandemic for donor evaluation/follow-up. Video was mostly used by nephrologists, surgeons, and psychiatrists/psychologists. Telephone and video were mostly used by social workers, while video or telephone was equally used by coordinators. Half of respondent nephrologists and surgeons were willing to accept a remote completion of physical exam; 68.3% of respondent psychiatrists/psychologists and social workers were willing to accept a remote completion of mental status exam. Providers strongly agreed that telemedicine was convenient for donors and would improve the likelihood of completing donor evaluation. However, providers (65.5%) perceived out-of-state licensing as a key policy/regulatory barrier. These findings help inform practice and underscore the instigation of policies to remove barriers using telemedicine to increase living kidney donation.

Operational challenges in the COVID-19 era: Asymptomatic infections and vaccination timing.

The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid testing (NAT) for SARS-CoV-2 is unclear, as this result may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of robust outcomes data, transplant professionals at US adult kidney transplant centers were surveyed (February 13, 2021 to April 29, 2021) to determine community practice (N: 92 centers, capturing 41% of centers and 57% of transplants performed). The majority (97%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 32% of centers proceed with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with kidney transplant in patients with positive SARS-CoV-2 NAT results due to presumed viral shedding. Furthermore, few centers are requiring COVID-19 vaccination prior to transplantation at this time.

Late pancreatic panniculitis in a simultaneous pancreas kidney transplant patient with failed allografts.

We present a rare case of pancreatic panniculitis in a 59-year-old male simultaneous pancreas-kidney (SPK) recipient with failed allografts. The patient presented with fever and painful erythematous nodules on his leg 1 month after stopping all immunosuppression. A thorough infectious and rheumatological workup was negative. He had pancreas rejection 4 years after SKP transplant and was restarted on dialysis after 14 years when his renal allograft failed due to chronic allograft nephropathy. His chronic immunosuppression (tacrolimus, azathioprine) was stopped and prednisone was weaned over 3 months at that time. A skin biopsy revealed saponification of the subcutaneous fat with inflammation pathognomonic of pancreatic panniculitis. Concurrent allograft pancreatitis confirmed with elevated lipase and a computed tomography scan finding of peripancreatic graft stranding and atrophic native pancreas. He was started on pulse steroid therapy for 3 days followed by oral taper. This resulted in dramatic resolution of all skin lesions and normalization of lipase levels within 1 week, followed by resumption of low-dose tacrolimus and azathioprine. This is an extremely rare occurrence of panniculitis in pancreas allograft after 10 years of pancreatic failure associated with stopping immunosuppression.

Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience.

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.

Steroid-free three-drug maintenance regimen for pancreas transplant alone: Comparison of induction with rabbit antithymocyte globulin +/- rituximab.

Graft survival following pancreas transplant alone (PTA) is inferior to other pancreas transplants. Steroid elimination is appealing, but a two-drug maintenance strategy may be inadequate. Additionally, recipients tend to have diabetic nephropathy and do not tolerate nephrotoxic medications. A three-drug maintenance strategy permits immunosuppression through different mechanisms as well as an opportunity to use lower doses of the individual medications. Induction consisted of five doses of rabbit antithymocyte globulin (1 mg/kg/dose). As of October 2007, a single dose of rituximab (150 mg/m2 ) was added. Maintenance consisted of tacrolimus, sirolimus and mycophenolate mofetil. From 2004 to 2017, 166 PTA were performed. Graft loss at 7 and 90 days were 4% and 5%, and 1-year patient and graft survival were 97% and 91%. Comparing induction without and with rituximab, there was no significant difference in 7- or 90-day graft loss, 1-year patient or graft survival, or in the rate of rejection or infection. Rabbit antithymocyte globulin induction and steroid withdrawal followed by a three-drug immunosuppression regimen is an excellent strategy for PTA recipients.

Kidney allograft survival outcomes in combined intestinal-kidney transplant: An analysis of the UNOS/OPTN database 2000-2014.

BACKGROUND AND OBJECTIVES: Intestinal transplants carry a high morbidity/mortality. Kidney allograft outcomes after combined intestinal (IT) with kidney transplant (CIKT) remain largely uninvestigated. MATERIALS AND METHODS: The UNOS STAR database was queried to identify all such combined organ transplants from 2000 to 2015. RESULTS: Out of a total 2215 (51.4% peds vs 48.6% adults) intestinal transplants, 111 (5.0%) CIKT were identified (32.4% peds vs 67.6% adults). Over the study period of CIKT, a total of 45.9% of these cases died with a functioning kidney graft. DGF rate was 9.0%. The 1-year reported kidney acute rejection rate was 6.3%. For the entire CIKT population over the entire study era, the 1-, 3-, and 5-year unadjusted kidney graft survival was 57%, 39%, and 34%, while death-censored kidney graft survival was 93%, 90%, and 86%, respectively. Overall conditional 5-year kidney graft survival (defined as 1-year kidney graft survival) was 58%. Overall, patient survival was significantly lower in recipients of CIKT compared to intestinal transplant (IT) (P < .005); However, the 5-year conditional (1 year kidney graft) patient survival in adults was not significantly different between IT and CIKT overall (P = .194). CONCLUSIONS: Kidney allograft survival is primarily dependent on 1-year patient survival. Guidelines regarding allocation of kidney allografts in CIKT need to take into consideration utility and urgency.

Cell-Free DNA and Active Rejection in Kidney Allografts.

Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls (P=0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.

Native Nephrectomy with Renal Transplantation is Associated with a Decrease in Hypertension Medication Requirements for Autosomal Dominant Polycystic Kidney Disease.

PURPOSE: We assessed hypertensive control after native nephrectomy and renal transplantation in patients with autosomal dominant polycystic kidney disease. MATERIALS AND METHODS: Blood pressure control was studied retrospectively in 118 patients with autosomal dominant polycystic kidney disease who underwent renal transplantation between 2003 and 2013. Overall 54 patients underwent transplantation alone (group 1) and 64 underwent transplantation with concurrent ipsilateral nephrectomy (group 2). Of these 64 patients 32 underwent ipsilateral nephrectomy only (group 2a) and 32 underwent eventual delayed contralateral native nephrectomy (group 2b). The number of antihypertensive drugs and defined daily dose of each antihypertensive was recorded at transplantation and up to 36-month followup. RESULTS: Comparing preoperative to postoperative medications at 12, 24 and 36-month followup, transplantation with concurrent ipsilateral nephrectomy had a greater decrease in quantity (-1.2 vs -0.5 medications, p=0.008; -1.1 vs -0.3, p=0.007 and -1.2 vs -0.4, p=0.03, respectively) and defined daily dose of antihypertensive drug (-3.3 vs -1.0, p=0.0008; -2.9 vs -1.0, p=0.006 and -2.7 vs -0.6, p=0.007, respectively) than transplantation alone at each point. Native nephrectomy continued to be a predictor of hypertensive requirements on multivariable analysis (p <0.0001). The mean decrease in number of medications in group 2b from after ipsilateral nephrectomy to 12 months after contralateral nephrectomy was -0.6 (p=0.0005) and the mean decrease in defined daily dose was -0.6 (p=0.009). CONCLUSIONS: In patients with autosomal dominant polycystic kidney disease undergoing renal transplantation, concurrent ipsilateral native nephrectomy is associated with a significant decrease in the quantity and defined daily dose of antihypertensive drugs needed for hypertension control. Delayed contralateral native nephrectomy is associated with improved control of blood pressure to an even greater degree.

Trends and outcomes in right vs. left living donor nephrectomy: an analysis of the OPTN/UNOS database of donor and recipient outcomes--should we be doing more right-sided nephrectomies?

BACKGROUND: Discussion continues about right vs. left donor nephrectomy (LDN). Left side is preferred due to longer renal vein while right side has been associated with renal vein thrombosis and shorter vessels. METHODS: A retrospective analysis of UNOS database for adult living donor transplants between 1 January 2000 and 31 December 2009. RESULTS: We identified 58 599 living donor transplants, of which 86.1% were LDN. There were no significant differences between the recipients or donors demographics. There were higher rates of delayed graft function in right donor nephrectomy (RDN) recipients with a hazard risk of 1.38 (95% CI 1.24-1.53; p < 0.0001). Primary failure rates were similar. In the RDN group, graft thrombosis as cause of graft failure was statistically higher with a hazard ratio of 1.48 (95% CI 1.18-1.86, p = 0.0004), and graft survival was significantly inferior (p = 0.006 log-rank test). For living donors outcomes, the conversion from laparoscopic to open was higher in the RDN group with an odds ratio of 2.02 (95% CI 1.61-2.52; p < 0.00001). There was no significant difference in vascular complications or re-operation required due to bleeding. Re-operations and re-admissions were higher in the LDN group. CONCLUSION: There are statistical differences between left and right kidney donor nephrectomies on recipient outcomes, but the difference is extremely small. The choice and laterality should be based on center and surgeon preference and experience.

Re-transplants compared to primary kidney transplants recipients: a mate kidney paired analysis of the OPTN/UNOS database.

Outcomes of kidney re-transplant recipients (RTR) were compared to primary recipients (FTR) from paired donor kidneys. Organ Procurement and Transplantation Network (OPTN) database was used to identify deceased donors (n = 6266) who donated one kidney to an RTR and the mate kidney to an FTR between January 2000 to December 2010. As compared to FTR, RTR were younger (45 vs. 52 yr, p < 0.001) and had higher proportion of plasma reactive antibody >80 (25% vs 7%, p < 0.001). There were higher 0 mismatches in RTR (19% vs. 16%, p < 0.001). There were more pre-emptive transplants in RTR (24% vs. 21%, p = 0.002). Delayed graft function (28% vs. 25%, p = 0.007) was higher in RTR. Patient survival was similar in FTR and RTR groups at one, three, and five yr (95.7%, 90.2%, and 82.5% vs. 95.2%, 89.8% and 82.7%). Allograft survival rates were higher in FTR group compared to RTR group at one, three, and five yr (91.1%, 82.4%, and 70.9% vs. 87.8%, 77.4%, and 66.1% p < 0.001). Death-censored allograft survival rates were higher in FTR group at one, three, and five yr (91.3%, 82.7% and 71.4% vs. 88%, 77.7% and 66.5% p < 0.001). In today's era of modern immunosuppression, graft survival in RTR has improved but remains inferior to FTR when controlling for donor factors.

Long-term outcomes of transplant recipients referred for angiography for suspected transplant renal artery stenosis.

Our aim was to study the long-term outcomes of all transplant recipients who underwent angiography for suspected TRAS at our institution. The patients were divided into TRAS+ve and TRAS-ve groups based upon angiographically confirmed results. TRAS was confirmed in 58.1% of 74 patients with median time of 8.9 months. Primary angioplasty alone was performed in 56% of patients with TRAS, while the remaining had PTA with stent (PTAS). There was reduction in systolic and diastolic BP (165 ± 19-136 ± 15 mmHg and 82 ± 14 mmHg to 68 ± 12 mmHg; p < 0.05) and number of antihypertensive drugs (3.5 ± 0.9-2.7 ± 1.0; p < 0.05). Overall, graft survival and patient survival from time of transplant were similar in both groups. Graft function was similar for the patients with treated TRAS+ve as compared to TRAS-ve over time. Graft survival and patient survival when compared to an age- and year of transplant-matched cohort control group were also similar. In conclusion, angiography for suspected TRAS is more likely to yield a confirmatory result early in the transplant course as compared to late. Treatment of TRAS in these patients had sustained long-term graft function. Alternative etiologies of HTN and graft dysfunction should be sought for recipients further out from transplant.

Re-exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies.

Re-exposure to beta cell autoantigens and its relevance in the presence of donor-specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty-three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2), insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8). Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA-2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post-transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p < 0.0001), 12 months (p < 0.0001), and from post-6 to post-12 months (p = 0.0002) was seen. No new BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow-up (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.

Pre-transplant angiotensin receptor II type 1 antibodies and risk of post-transplant focal segmental glomerulosclerosis recurrence.

Post-kidney transplant recurrence of focal segmental glomerulosclerosis (FSGS) is a major problem. AT1R is expressed on podocyte; its expression is elevated in the proteinuric state. Using an ELISA, we tested pre-transplant sera of 28 patients with history of idiopathic FSGS for anti-AT1R levels and serum soluble urokinase-type plasminogen activator receptor (suPAR) as a biomarker for risk of recurrence of FSGS. Sera from 11 patients with polycystic kidney disease (PKD) were used as controls. Twelve patients had biopsy proven post-transplant FSGS recurrence at 1.5 months. No difference was found in the pre-transplant suPAR levels of FSGS patients (5993 ± 2292 pg/mL) vs. PKD (7334 ± 4538 pg/mL) (p = 0.23). Serum suPAR levels in patients with FSGS recurrence (5786 ± 1899 pg/mL) vs. no FSGS recurrence (6149 ± 2598 pg/mL) (p = 0.69) were not different. Anti-AT1R levels in patients with FSGS were 12.66 ± 11.85 U/mL vs. 8.69 ± 6.52 U/mL in PKD (p = 0.32); however, a difference was found in patients with and without FSGS recurrence 20.41 ± 14.36 U/mL 6.84 ± 4.181 U/mL, respectively (p < 0.01). Area under curve for suPAR and anti-AT1R to predict post-transplant FSGS recurrence was 0.51 and 0.84, respectively. Pre-transplant anti-AT1R levels appear to be a helpful biomarker in identifying patients at high risk of post-transplant FSGS recurrence.

Correlation between CT-based measured renal volumes and nuclear-renography-based split renal function in living kidney donors. Clinical diagnostic utility and practice patterns.

INTRODUCTION: Living donor evaluation involves imaging to determine the choice of kidney for nephrectomy. Our aim was to study the diagnostic accuracy and correlation between CT-based volume measurements and split renal function (SRF) as measured by nuclear renography in potential living donors and its impact on kidney selection decision. METHODS: We analyzed 190 CT-based volume measurements in healthy donors, of which 65 donors had a radionuclide study performed to determine SRF. RESULTS: There were no differences in demographics, anthropometric measurements, total volumes, eGFR, creatinine clearances between those who required a nuclear scan and those who did not. There was a significant correlation between CT-volume-measurement-based SRF and nuclear-scan-based SRF (Pearson coefficient r 0.59; p < 0.001). Furthermore, selective nuclear-based SRF allowed careful selection of donor nephrectomy, leaving the donor with the higher functioning kidney in most cases. There was also a significantly higher number of right-sided nephrectomies selected after nuclear-based SRF studies. CONCLUSION: CT-based volume measurements in living donor imaging have sufficient correlation with nuclear-based SRF. Selective use of nuclear-scan-based SRF allows careful selection for donor nephrectomy.