Single center results of simultaneous pancreas-kidney transplantation in patients with type 2 diabetes.

Studies have found similar outcomes of Simultaneous Pancreas-Kidney transplantation (SPKT) in patients with Type 2 (T2D) and Type 1 diabetes (T1D). However, there are scarce data evaluating the association of recipient factors such as age, BMI, or pretransplant insulin requirements with outcomes, thus the criteria for the optimal recipient selection remains unclear. In this study, 284 T1D and 39 T2D patients, who underwent SPKT between 2006 and 2017 with 1 year of follow-up at minimum, were assessed for potential relationship of pretransplant BMI and insulin requirements with posttransplant diabetes and pancreatic graft failure. Kaplan-Meier analysis showed similar rates of freedom from posttransplant diabetes (94.7% T2D vs. 92.3% T1D at 1 yr, and 88.1% T2D vs. 81.1% T1D at 5 yrs) and graft survival (89.7% T2D vs. 90.4% T1D at 1 yr, and 89.7% T2D vs. 81.2% T1D at 5 yrs). There was no significant association between BMI or pretransplant insulin requirements with posttransplant diabetes occurrence in either T1D (p = .10, .43, respectively) or T2D (p = .12, .63) patients in the cohort; or with graft failure (T1D: p = .40, .09; T2D: p = .71, .28). These observations suggest a less restricted approach to selective use of SPKT in patients with T2D.

Association of human leukocyte antigen mismatches between donor-recipient and donor-donor in pancreas after kidney transplant recipients.

The effects of HLA mismatching on pancreas outcomes among pancreas after kidney (PAK) recipients are undefined. Outcomes might potentially differ depending on whether there is a mismatch between pancreas donor and recipient (PD-R) or pancreas donor and kidney donor(PD-KD). All primary PAK at our centre were included in this study. Patients were divided into two groups based on the degree of HLA mismatching: low (L-MM) as 0-4 and high (H-MM) as 5-6. We analysed all (N = 73) PAK for PD-R mismatch and the subset of PAK for PD-KD mismatch (N = 71). Comparing PD-R L-MM (n = 39) and H-MM (n = 34) PAKs, we observed no difference in the rate of pancreas graft failure. There was also no difference in the rate of rejection (L-MM 33% vs. H-MM 41%) or the severity of rejection. However, we observed a significantly (P < 0.01) shorter time to acute pancreas rejection in the H-MM group (6.8 ± 8.7 mo) versus the L-MM cohort (29.0 ± 36.2 mo) (P < 0.001). Similar to the PD-R mismatched cohort, we did not observe a detrimental effect of HLA mismatching on graft outcomes in the PD-KD cohort; time to rejection was again shorter in the H-MM subset. In this study, we found no impact of HLA mismatch on either pancreas graft survival or rejection rates, though rejection occurred earlier in high mismatched PAK transplants.

Pancreas transplants from small donors: are the outcomes acceptable? A retrospective study.

Despite good organ quality, pancreata from extremely small pediatric donors (<30 kg) are generally avoided by many centers because of concerns of reduced islet cell mass and early technical failure. Therefore, we sought to compare the outcomes of small pancreas grafts (<30 kg) to those from higher weight donors from transplants performed between 1994 and 2015 (n = 1183). A total of 33 pancreata were from donors' ≤30 kg (3%), with a mean weight of 23.8 kg and mean age of 7.8 years. Patient survival was similar at 1, 5, and 10 years between recipients of ≤30 and >30 kg donors (≤30 kg: 96.8%, 86.8%, and 78.1% vs. >30 kg: 96.8%, 89.5%, and 79.1%, P = 0.5). Pancreas graft survival at 1, 5, and 10 years was also similar, ≤30 kg: 93.9%, 73.2%, and 61.0% vs. >30 kg: 87%, 73.3%, and 58.3% (P = 0.7). This graft survival pattern was also seen when comparing pancreata from ≤20 kg donors to those from >20 to 30 kg. Cause of graft loss, and metabolic and physiologic outcomes did not differ between the groups. After assessing the impact of donor weight as a continuous variable and calculating recipient-to-donor weight ratio (RDWR), we observed no effect of donor weight on patient and graft outcomes.

Polyomavirus and cytomegalovirus infections are risk factors for grafts loss in simultaneous pancreas and kidney transplant.

BACKGROUND: Published literature on predictors of polyomavirus (BKV) and cytomegalovirus (CMV) infections in simultaneous pancreas and kidney (SPK) transplant and their impact on allograft outcomes remain sparse. We hypothesize that BKV and CMV viremia infections decrease allograft survival in SPK. Identifying modifiable predictors of BKV and CMV may help tailor immunosuppression and improve allograft survival. METHODS: All SPK recipients at our institution between January 2000 and April 2016 were included (n = 757). Thirty-nine recipients had BKV only and 25 had CMV only, and infection occurred at median follow-up times of 217 and 163 days, respectively. Event density sampling was used to match recipients with BKV or CMV to up to 10 recipients without infection by age, sex, and HLA mismatch status, and these were followed for a median of 4.3 years after infection. RESULTS: Older age (HR 1.49 for each decade; 95% CI: 0.95, 2.35; P = .083) and tacrolimus use (HR 20.6; 95% CI: 2.37, 179.53; P = .006) were associated with increased incidence of BKV, but not CMV, infection. Both BKV and CMV infections were associated with increased risk of allograft failure for both pancreas (BKV [HR 2.17; 95% CI 1.47, 3.208; P = .000], CMV [HR 1.7; 95% CI 1.077, 2.687; P = .023]) and kidney (BKV [HR 2.65; 95% CI 1.765, 3.984; P = .000], CMV [HR 2.07; 95% CI 1.295, 3.308; P = .002]). CONCLUSION: Older age at time of transplant and tacrolimus may help predict BKV infection in SPK recipients.

Enteric conversion after bladder-drained pancreas transplantation is not associated with worse allograft survival.

In the early experience of pancreas transplantation, bladder drainage was favored, but it often caused urologic, metabolic, and infectious complications that necessitated conversion to enteric drainage. Long-term graft survival after enteric conversion and the impact of time interval from transplantation to enteric conversion on graft survival is poorly understood. We studied all bladder-drained first-time pancreas transplantations performed at the University of Wisconsin from 1985 to 2000. Time to conversion was estimated with the Kaplan-Meier technique, whereas risk factors associated with conversion were estimated via a time-varying Cox proportional hazards model. Of 386 bladder-drained pancreata, 162 (41.9%) eventually required enteric conversion, 29 (17.9%) within the first year. Median time to conversion varied by indication: 0.68 years for surgical, 3.1 years for urologic, and 2.7 years for metabolic disorders. In a time-varying Cox model adjusting for donor and recipient factors, enteric conversion did not affect the risk of pancreas graft loss (hazard ratio [HR] 0.86, P = .26). Kidney survival was not associated with enteric conversion. When necessary due to symptoms or complications, enteric conversion of bladder-drained pancreata is safe and does not affect overall graft survival. This relationship appears to be true no matter when the conversion is performed.

Prevalence and outcomes of cystic lesions of the transplant pancreas: The University of Wisconsin Experience.

Literature on the behavior of cystic lesions in pancreas transplants is scarce, and hence a better understanding is warranted. Data on recipients and their respective donors that underwent simultaneous kidney and pancreas, pancreas transplant alone, and pancreas after kidney between 1994 and 2015 were reviewed (n = 1185). Cystic lesions of the transplant pancreas developed in 22 patients (1.8%): 12 pseudocysts, 2 cysts/remnants, 4 intraductal papillary mucinous neoplasms (IPMN), 2 adenocarcinomas, 1 low-grade intraepithelial pancreatic neoplasia, and 1 case of polycystic kidney disease. The median size was 3.6 cm (1.6-5.5 cm), and occurred at a median time of 65.5 months (2-183 months) posttransplant. The median age of the graft at time of diagnosis was 42 years (25.7-54.5), with 17 of 22 grafts (77%) functioning at time of diagnosis. Triggers for investigation were elevations in pancreatic enzymes, re-admissions for abdominal pain, and incidentalomas. High-resolution imaging and diagnostic biopsy/aspiration with ancillary tests were the main diagnostic tests. Most pseudocysts were managed by percutaneous drainage, and although no firm inference can be made from such a small series, we have observed that the behavior and management of IPMN and adenocarcinoma in the pancreas graft appears congruent to that of the native pancreas.

Ipsilateral versus contralateral placement of the pancreas allograft in pancreas after kidney transplant recipients.

BACKGROUND: In a diabetic, uremic kidney transplant recipient that may receive a future pancreas after kidney (PAK) transplant, the kidney is typically implanted on the left side in anticipation of the subsequent pancreas transplant on the right side. In this study, we sought to determine if ipsilateral PAK (iPAK) is as safe as contralateral PAK (cPAK). METHODS: The 115 PAK transplants (iPAK n = 57, cPAK n = 58) were performed from 1997-2010 and results were compared between the groups. RESULTS: Kidney graft survival and pancreas graft survival was similar between the two groups. Kidney graft function according to serum creatinine and eGFR was not different between the cPAK and the iPAK groups and there were no episodes of kidney graft thrombosis in either group. Subgroup analyses focusing on donor source also did not show worse outcomes for graft survivals in iPAK group when compared to cPAK group. CONCLUSIONS: Pancreas and kidney graft survival in PAK transplants is unaffected by the surgical procedure and iPAK is safe.

Concurrent biopsies of both grafts in recipients of simultaneous pancreas and kidney demonstrate high rates of discordance for rejection as well as discordance in type of rejection - a retrospective study.

It is commonly assumed that in simultaneous pancreas and kidney (SPK) recipients, rejection of the two organs is concordant. As a result, concurrent biopsies of both organs are rarely performed and there are limited histological data on how often rejection is in fact discordant. We reviewed all SPK recipients transplanted at the University of Wisconsin between January 01, 2001, and December 31, 2016, that underwent biopsy of both organs. We included all patients whose biopsies were within 30 days. If patients were treated for rejection between biopsies, they were excluded if the biopsies were more than 4 days apart. Ninety-one simultaneous biopsies were performed within 30 days of each other, and 40 met our inclusion criteria. A total of 25 (62.5%) patients had concordance of biopsy findings: 11 had rejection of both organs, and 14 had no rejection of either organ. The other 15 (37.5%) were discordant for rejection, with 10 having pancreas-only rejection and five kidney-only rejection. It was striking to find that four of the 11 patients with concordance for rejection (36%) had different types (AMR, ACR, or mixed) of rejection in the two organs. This large series of simultaneous pancreas and kidney biopsies demonstrates the continued utility of performing biopsies of both organs.

When Do DCD Donors Die?: Outcomes and Implications of DCD at a High-volume, Single-center OPO in the United States.

OBJECTIVE: The objective of this study was to determine the fate of patients who attempted to donate organs after circulatory death (DCD) using a standardized DCD protocol. BACKGROUND: Successful donation is not always possible after attempted DCD. METHODS: Data were collected for all DCD donors between 1/2011 and 9/2014. DCDs were carried out using a uniform protocol at a single-center organ procurement organization. RESULTS: During the timeframe considered, DCD donation was attempted in 169 patients. In 46 patients (27.2%), no organs were recovered because the patients did not die within 2 hours. Successful donation was more likely if withdrawal of support occurred in the operating room versus the intensive care unit (P = 0.006). Time from extubation to death was available for 161/169 donors (95.3%). Of 161 donors, 111 (66.9%) died in under 1 hour. The mean time from withdrawal of support to patient death for unsuccessful donations was 33 hours, 37 minutes (range, 24 minutes-242 hours) versus 29 minutes (range, 5 minutes-2 hours, 4 minutes) for successful donations. Twenty-seven patients who unsuccessfully donated (67.5%) died within 24 hours. Were unsuccessful donations converted to successful donations, as many as 837 abdominal transplants could have been carried out in the United States, during the study period. CONCLUSIONS: DCD is an important form of organ donation. A large number of abdominal transplants are not possible due to unsuccessful DCD organ donation. It may be useful to explore DCD donor family satisfaction to identify other options for improving DCD donation.

Pancreas transplantation in older patients is safe, but patient selection is paramount.

Pancreas transplant outcomes have progressively improved. Despite this, some centers have continued to employ historical age limits for pancreas transplant candidates. We sought to determine the importance of chronological age in determining patient and graft survival rates after pancreas transplantation. A single-center, retrospective study of adult, deceased donor simultaneous pancreas and kidney (SPK) and solitary pancreas transplants (SP, including pancreas transplant alone and pancreas after kidney transplants) in recipients ≥ 55 years (55 + ), occurring between July 1, 1999, and June 30, 2012, was performed. Seven-hundred and forty patients underwent pancreas transplantation, of which 28 patients were 55 + . Patient survival was comparable for younger and older pancreas transplant recipients. Both non-death-censored and death-censored pancreatic graft survival rates were similar in younger and in older patients. Patients aged 45-54 and those aged 55 +  had more frequent cardiovascular events than younger pancreas transplant recipients. There was no difference in renal graft survival for SPK patients when compared with diabetic kidney transplant alone recipients aged 55 years and older. Older pancreas transplant recipients had acceptable long-term patient and graft survival rates, although complications may occur. Chronological age alone should not exclude a patient for pancreas transplant candidacy.

Loin pain hematuria syndrome.

Loin pain hematuria syndrome is a rare disease with a prevalence of ∼0.012%. The most prominent clinical features include periods of severe intermittent or persistent unilateral or bilateral loin pain accompanied by either microscopic or gross hematuria. Patients with loin pain hematuria syndrome initially present with hematuria, flank pain, or most often both hematuria and flank pain. Kidney biopsies from patients with loin pain hematuria typically reveal only minor pathologic abnormalities. Further, loin pain hematuria syndrome is not associated with loss of kidney function or urinary tract infections. Loin pain hematuria syndrome-associated hematuria and pain are postulated to be linked to vascular disease of the kidney, coagulopathy, renal vasospasm with microinfarction, hypersensitivity, complement activation on arterioles, venocalyceal fistula, abnormal ureteral peristalsis, and intratubular deposition of calcium or uric acid microcrystals. Many patients with loin pain hematuria syndrome also meet criteria for a somatoform disorder, and analgesic medications, including narcotics, commonly are used to treat loin pain hematuria syndrome-associated pain. Interventional treatments include renal denervation, kidney autotransplantation, and nephrectomy; however, these methods should be used only as a last resort when less invasive measures have been tried unsuccessfully. In this review article, we discuss and critique current clinical practices related to loin pain hematuria syndrome pathophysiology, diagnosis, treatment, and prognosis.

Incentives for organ donation: proposed standards for an internationally acceptable system.

Incentives for organ donation, currently prohibited in most countries, may increase donation and save lives. Discussion of incentives has focused on two areas: (1) whether or not there are ethical principles that justify the current prohibition and (2) whether incentives would do more good than harm. We herein address the second concern and propose for discussion standards and guidelines for an acceptable system of incentives for donation. We believe that if systems based on these guidelines were developed, harms would be no greater than those to today's conventional donors. Ultimately, until there are trials of incentives, the question of benefits and harms cannot be satisfactorily answered.

The impact of hepatitis C virus donor and recipient status on long-term kidney transplant outcomes: University of Wisconsin experience.

The survival benefit of transplanting hepatitis C (HCV)-positive donor kidneys into HCV-positive recipients remains uncertain. The purpose of this study was to assess the effect of HCV-status of the donor (D) kidney on the long-term outcomes in kidney transplant recipients (R). We evaluated 2169 consecutive recipients of deceased-donor kidney transplants performed between 1991 and 2007. The following HCV cohorts were identified: D-/R- (n = 1897), D-/R+ (n = 59), D+/R- (n = 118), and D+/R+ (n = 95). Patients were followed for a mean of 6.02 (standard deviation = 4.26) yr. In a mulitvariable Cox-proportional hazards model, D+/R+ cohort had significantly lower patient survival (adjusted-hazard ratio [HR] 2.1, 95% CI [1.4-2.9]) with respect to the reference D-/R- group, whereas mortality was not increased in D-/R+ group. The rate of graft loss was increased in both D+/R+ and D-/R+ but was comparable with each other (adjusted-HR 1.8, 95% CI [1.4-2.5]) vs. adjusted-HR 2.0, 95% CI [1.4-2.8], respectively). D-/R+ cohort experienced significantly higher rate of rejection (adjusted-HR 1.7, 95% CI [1.2-2.5]) and chronic allograft nephropathy (adjusted-HR 2.1, 95% CI [1.2-3.7]). Neither donor nor recipient HCV-status impacted the risk of recurrent or de novo GN. Transplanting HCV-positive kidneys as opposed to HCV-negative kidneys into HCV-positive recipients provided similar graft survival but compromised patient survival in the long term.

Simultaneous pancreas and kidney (SPK) retransplantation in prior SPK recipients.

INTRODUCTION: We have performed 113 renal and 28 isolated pancreas retransplants in our cohort of more than 1200 prior simultaneous pancreas and kidney (SPK) recipients. On the basis of these experiences, we began performing repeat SPK in prior SPK recipients (n = 9). METHODS: This retrospective review summarizes our experience with repeat SPK transplantation in prior SPK recipients. Mean age at retransplant was 39 yr; mean interval to retransplant was 7.8 yr. Thirty-three percent were pre-dialysis. Eighty-nine percent of patients underwent transplant nephrectomy (five during the repeat SPK and three prior to it), and 78% underwent transplant pancreatectomy (four during the repeat SPK and three prior to it). Enteric drainage was performed in all repeat SPKs. RESULTS: Median length of stay was 11 d. Perioperative complications included the following: renal artery thrombosis (1), pancreatic portal venous thrombosis (1), enteric leak (1), and hematoma (2). Overall pancreatic allograft survival was 78% at one yr and 67% at two yr. Overall renal allograft survival was 89% at one yr and 78% at two yr. Patient survival at one and three yr was 100%. CONCLUSIONS: Survival of repeat SPK allografts is acceptable despite the increased technical and immunologic demands of retransplantation. Graftectomy prior to or at the time of retransplantation is often necessary.

Alemtuzumab as compared to alternative contemporary induction regimens.

Between 1 January 2002 and 31 December 2007, our center performed 1687 adult renal transplants. A retrospective analysis was performed to compare outcomes between patients receiving alemtuzumab (n = 632) and those receiving either basiliximab (n = 690) or thymoglobulin (n = 125). Patients receiving alemtuzumab were younger (49 vs. 51 years, P = 0.02), had fewer HLA matches (1.7 vs. 2.0, P < 0.0001), were more likely to have a cytomegalovirus (CMV) donor(+)/recipient(-) transplant (22% vs. 17%, P = 0.03) and were less likely to receive a living donor allograft (32% vs. 37%, P = 0.04). Alemtuzumab recipients were less likely to receive tacrolimus (35% vs. 47%, P < 0.0001). The 1-, 3-, and 5-year cumulative incidence of antibody-mediated rejection (AMR) in alemtuzumab-treated patients was 19%, 24%, and 27%, vs. 11%, 15%, and 18% for the other group (P < 0.0001). The 1-, 3-, and 5-year allograft survival in the alemtuzumab group was 88%, 75%, and 67%, vs. 91%, 82%, and 74% for the other group (P < 0.0001). Patient survival was equivalent. Alemtuzumab was an independent risk factor for living donor allograft loss (HR 2.0, P = 0.004), opportunistic infections (HR 1.3, P = 0.01), CMV infections (HR 1.6, P = 0.001), and AMR (HR 1.5, P = 0.002). The significantly worse graft survival in the alemtuzumab cohort may be due to the increased rates of AMR and infectious complications.

Early Increases in Posttransplant Pancreatic Enzymes Are Associated With Surgical Complications But Not Graft Failure Among Pancreas Transplant Recipients.

OBJECTIVES: This study aimed to find the association between immediate postoperative increases in pancreatic enzymes and posttransplant complications among pancreas transplant recipients (PTRs). METHODS: We analyzed all PTRs transplanted at the University of Wisconsin between June 2009 and September 2018. Enzyme levels were presented as a ratio of absolute numbers to the upper limit of normal value, with value >1 considered as abnormal. We specifically evaluated bleeding, fluid collections, and thrombosis complications based on the amylase or lipase ratios on day 1 (Amylase1, Lipase1) and maximum ratios within 5 days of transplant (Amylasemax, Lipasemax). For early complications, we focused on technical complications that occurred within 90 days of transplant. For long-term outcomes, we assessed patient and graft survival, and rejections. RESULTS: There were a total of 443 PTRs, 287 were simultaneous pancreas and kidney recipients, and 156 were solitary pancreas recipients. Higher Amylase1, Liplase1, Amylasemax, and Lipasemax were associated with an increase in early complications, mainly need for pancreatectomy, fluid collections, bleeding complications, or graft thrombosis, particularly in the solitary pancreas group. CONCLUSIONS: Our finding suggests that cases of early perioperative enzyme increase merit consideration for early imaging investigation to mitigate detrimental outcomes.

Biliary complications after liver transplantation from donation after cardiac death donors: an analysis of risk factors and long-term outcomes from a single center.

OBJECTIVE: This study evaluates the long-term outcomes, biliary complication rates, and risk factors for biliary complications after liver transplantation from "donation after cardiac death" (DCD) donors. BACKGROUND: Recent enthusiasm toward increased use of DCD donors' livers is mitigated by high biliary complication rates. Predictive risk factors for the development of biliary complications after DCD liver transplantation remain incompletely defined. METHODS: We performed a retrospective review of 1157 "donation after brain death" (DBD) and 87 DCD liver transplants performed between January 1, 1993, and December 31, 2008. Patient and graft survivals and complication rates within the first year of transplantation were compared between DBD and DCD groups. Cox proportional hazards models were used to assess the influence of potential risk factors. RESULTS: Patient survival was significantly lower in the DCD group compared with the DBD group at 1, 5, 10, and 15 years (DCD: 84%, 68%, 54%, and 54% vs DBD: 91%, 81%, 67%, and 58%; P < 0.01). Graft survival was also significantly lower in the DCD group compared with the DBD group at 1, 5, 10, and 15 years (DCD: 69%, 56%, 43%, 43% vs DBD: 86%, 76%, 60%, 51%; P < 0.001). Rates of overall biliary complications (OBC) (DCD: 47% vs DBD: 26%; P < 0.01) and ischemic cholangiopathy (IC) (DCD: 34% vs DBD: 1%; P < 0.01) were significantly higher in the DCD group. Donor age [hazard ratio (HR): 1.04; P < 0.01] and donor age greater than 40 years (HR: 3.13; P < 0.01) were significant risk factors for the development of OBC. Multivariate analysis revealed that cold ischemic time (CIT) greater than 8 hours (HR: 2.46; P = 0.05) and donor age greater than 40 years (HR: 2.90; P < 0.01) significantly increased the risk of IC. CONCLUSIONS: Long-term patient and graft survival after DCD liver transplantation remain significantly lower but acceptable when compared with DBD liver transplantations. Donor age and CIT greater than 8 hours are the strongest predictors for the development of IC. Careful selection of younger DCD donors and minimization of CIT may limit the incidence of severe biliary complications and improve the successful utilization of DCD donors' livers.

Long-term outcomes after simultaneous pancreas-kidney transplant.

PURPOSE OF REVIEW: Simultaneous pancreas-kidney (SPK) transplantation represents the only proven long-term therapeutic approach for type 1 diabetic, dialysis-dependent patients. This procedure potentially liberates these patients from dialysis and the need for exogenous insulin replacement. For the first time, data on the long-term natural history of patients receiving SPK have recently been analyzed. In this review, we discuss the outcomes and complications for patients receiving SPK in the context of the current literature. RECENT FINDINGS: In our analysis of 1000 SPKs performed at our center, we demonstrated that SPK increases patient survival compared with live-donor kidney alone or deceased donor kidney alone transplantation. The 5-year, 10-year, and 20-year patient survival for SPK recipients was 89, 80, and 58%, respectively. Enteric drainage improves quality of life, but not allograft survival, when compared with bladder drainage. After transplantation, approximately 50% of bladder-drained transplants undergo enteric conversion and late conversion after transplantation is associated with a higher complication rate. Surgical complications are higher in enteric-drained compared with bladder-drained pancreas transplants. SUMMARY: Selecting the appropriate therapy for a type 1 diabetic recipient with renal failure continues to be a critical decision for programs offering pancreas transplantation. The principles and guidelines at our center are driven by the potential benefit of the SPK transplant needing to outweigh the increased morbidity of the surgical procedure and the use of lifelong immunosuppression. Results from long-term studies demonstrating improved patient survival suggest that the treatment of choice for an appropriate type 1 diabetic recipient is an SPK transplant.

FcER1: A Novel Molecule Implicated in the Progression of Human Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p < 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p < 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.

Complex Ureteral Reconstruction in Kidney Transplantation.

OBJECTIVES: Despite advances in surgical techniques and organ preservation, transplant ureteric strictures remain a common complication in kidney transplantation. A variety of endourological and surgical techniques have been utilized; however, there is a lack of consensus on the optimal modality in dealing with these complex cases. MATERIALS AND METHODS: We present challenging ureteral reconstruction cases after failed attempts at ureteral dilatation, failed conventional open repairs, and/or with bladder dysfunction. RESULTS: All renal allografts were salvaged by successful use of bladder Boari flap and intestinal segment interpositions/diversions. CONCLUSIONS: Operative repair remains the most durable and successful approach, and minimally invasive options should be reserved for nonsurgical candidates, with consideration of a single attempt in patients with early, distal, short (<2 cm), nonischemic strictures.