This multicenter trial showed that, despite immunologic challenges, recipients of kidney transplants from HLA-incompatible live donors had a survival benefit as compared with controls who remained on ...the waiting list or received transplants from deceased donors.
More than 32,000 patients awaiting kidney transplantation in the United States have anti-HLA antibodies.
1
The presence of anti-HLA antibodies makes it very difficult to find a match with a compatible donor, and these “sensitized” patients can remain on the waiting list for a kidney transplant for years without a suitable donor ever being identified.
2
,
3
Those fortunate enough to have a willing but incompatible live donor can either participate in paired kidney donation, for which the chance of a compatible match is also limited,
4
–
9
or undergo desensitization and subsequent transplantation with a kidney from an incompatible live donor.
10
– . . .
Autosomal dominant polycystic kidney disease (ADPKD) is a ciliopathy caused by mutations in
and
that is characterized by renal tubular epithelial cell proliferation and progressive CKD. Although the ...molecular mechanisms involved in cystogenesis are not established, concurrent inactivating constitutional and somatic mutations in ADPKD genes in cyst epithelium have been proposed as a cellular recessive mechanism.
We characterized, by whole-exome sequencing (WES) and long-range PCR techniques, the somatic mutations in
and
genes in renal epithelial cells from 83 kidney cysts obtained from nine patients with ADPKD, for whom a constitutional mutation in
or
was identified.
Complete sequencing data by long-range PCR and WES was available for 63 and 65 cysts, respectively. Private somatic mutations of
or
were identified in all patients and in 90% of the cysts analyzed; 90% of these mutations were truncating, splice site, or in-frame variations predicted to be pathogenic mutations. No
-heterozygous mutations of
or
genes were identified. Copy number changes of
ranging from 151 bp to 28 kb were observed in 12% of the cysts. WES also identified significant mutations in 53 non-
genes, including other ciliopathy genes and cancer-related genes.
These findings support a cellular recessive mechanism for cyst formation in ADPKD caused primarily by inactivating constitutional and somatic mutations of
or
in kidney cyst epithelium. The potential interactions of these genes with other ciliopathy- and cancer-related genes to influence ADPKD severity merits further evaluation.
BACKGROUNDCharacteristics of pretransplant antibodies directed at donor human leukocyte antigen (HLA) donor-specific antibodies (DSA) associated with adverse outcomes in kidney transplant recipients ...are being elucidated but uncertainties exist.
METHODSWe prospectively screened pretransplant sera from 543 kidney recipients using single antigen bead assays and identified 154 patients with and 389 without DSA. We investigated the association of DSA features to acute rejection and graft failure.
RESULTSOne-year acute rejection incidence was higher in DSA-positive group (P < 0.001), primarily due to antibody-mediated rejection (AMR, 13% vs. 1.8%, P < 0.001) and not T cell–mediated rejection (ACR, 5% vs.6%, P = 0.65). The sum of mean fluorescence intensity of DSA (DSA MFI-Sum) of 6,000 or higher (OR, 18; 95% CI, 7.0–47; P < 0.001) and the presence of DSA against both HLA class I and II (OR, 39; 95% CI, 14–106; P < 0.0001) predicted 1-year AMR, independent of other covariates. Calculated panel reactive antibody and a positive flow cytometry cross-match result were associated with AMR by bivariate analysis but neither was an independent predictor in a multivariable regression analysis that included DSA-MFI-Sum or HLA DSA class. In multivariable Cox proportional hazards models, the covariate-adjusted hazard ratio for graft failure was 2.03 (95%CI, 1.05–3.92; P = 0.04) for DSA MFI-Sum of 6,000 or higher and 2.23 (95% CI, 1.04–4.80; P = 0.04) for class I and II DSA. Prediction of graft failure was not independent of AMR.
CONCLUSIONOur study suggests that DSA MFI-Sum and HLA class of DSA are characteristics predictive of AMR and graft failure. The elevated risk of graft failure in those with the identified features of DSA is attributable to increased risk of AMR.
Objective To present a comparison of perioperative donor outcomes and recipient graft function in a series of patients undergoing laparoendoscopic single-site donor nephrectomy (LESS-DN) versus ...conventional laparoscopic donor nephrectomy (LDN). Methods Data were collected for 50 consecutive LESS-DN patients and a matched cohort of 50 LDN patients. The donor outcomes analyzed included operative time, estimated blood loss, complications, visual analog pain scores, and recovery time. The recipient outcomes analyzed included serum creatinine at discharge and follow-up and the incidence of delayed graft function. Results The mean total operative time was shorter in the LDN group than in the LESS-DN group ( P < .0001). Linear regression analysis of the LESS-DN operative times relative to case number showed a significant decrease in the operative time with increasing case number ( r = 0.19, P = .002). No statistically significant differences were found in estimated blood loss, warm ischemia time, length of stay, or visual analog pain scores between the 2 groups. However, the surgical incision was significantly smaller in the LESS-DN group ( P < .0001). After discharge, the patient-reported time to complete recovery was faster in the LESS-DN group ( P = .01). The incidence of complications was similar in both groups; however, major complications only occurred in the LDN group. No differences were found in the recipient serum creatinine values or the incidence of delayed graft function. Conclusion Our initial experience with LESS-DN is encouraging. This retrospective matched-pair comparison between LESS-DN and LDN suggests that the single-port approach might be associated with quicker convalescence. Longer operative times in the LESS-DN group could simply represent the learning curve of a novel procedure.
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This article updates the unique opportunities available to kidney transplant candidates through kidney paired donation (KPD). KPD enables kidney transplant candidates with willing but incompatible ...living donors to enroll in a registry of other incompatible pairs to find a compatible transplant. Because of the ongoing shortage of deceased donor organs, KPD represents the most promising opportunity to increase the number of kidneys available for transplantation.
Background
Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction ...in HIV-infected kidney transplant recipients has been associated with a lower risk of acute rejection, but data on the rates of
de novo
malignancy and BK viremia in these patients is lacking.
Methods
We performed a single-center retrospective cohort study of adult HIV-infected individuals who underwent kidney transplantation with rATG induction between January 2006 and December 2016. The primary outcome was the development of
de novo
malignancy. Secondary outcomes included the development of BK viremia, infections requiring hospitalization, HIV progression, biopsy-proven acute rejection, and patient and allograft survival.
Results
Twenty-seven HIV-infected individuals with end-stage kidney disease received deceased (n=23) or living (n=4) donor kidney transplants. The cumulative rate of malignancy at five years was 29%, of whom 29% died because of advanced malignancy. BK viremia was detected in six participants (22%), of whom one had biopsy-proven BK virus-associated nephropathy and all of whom cleared the BK viremia. Five-year acute rejection rates, patient survival and death-censored allograft survival were 17%, 85% and 80% respectively.
Conclusion
rATG induction in HIV-infected kidney transplant recipients was associated with a low risk of acute rejection, but a potentially higher risk of
de novo
malignancies and BK viremia in this cohort. Screening strategies to closely monitor for BK virus infection and malignancy post-transplantation may improve outcomes in HIV-infected kidney transplant recipients receiving rATG induction.
Despite significant accomplishments to date, kidney transplantation is a relatively young field in medicine. Due to the armamentarium of agents available to effectively suppress the immune system, ...the past decade has seen a shift in focus from prevention of rejection to a focus on extending the life of the allograft and novel strategies to increase the organ donor pool. This book covers basic concepts in kidney transplantation while also addressing ways to manage kidney transplant recipients in order to maximize patient and graft survival. In addition, novel concepts to increase organ availability are addressed, including kidney paired donation and single site laparoendoscopic donor nephrectomy for living donor kidney transplantation, and utilization of marginal, hepatitis C positive, and older donor organs to increase deceased donor transplant opportunities.
The COVID‐19 pandemic has brought unprecedented challenges to the transplant community. The reduction in transplantation volume during this time is partly due to concerns over potentially increased ...susceptibility and worsened outcomes of COVID‐19 in immunosuppressed recipients. The consequences of COVID‐19 on patients waitlisted for kidney transplantation, however, have not previously been characterized. We studied 56 waitlisted patients and 80 kidney transplant recipients diagnosed with COVID‐19 between March 13 and May 20, 2020. Despite similar demographics and burden of comorbidities between waitlisted and transplant patients, waitlisted patients were more likely to require hospitalization (82% vs. 65%, P = .03) and were at a higher risk of mortality (34% vs. 16%, P = .02). Intubation was required in one third of hospitalized patients in each group, and portended a very poor prognosis. The vast majority of patients who died were male (84% waitlist, 100% transplant). Multivariate analysis demonstrated waitlist status, age, and male sex were independently associated with mortality. COVID‐19 has had a dramatic impact on waitlisted patients, decreasing their opportunities for transplantation and posing significant mortality risk. Understanding the impact of COVID‐19 on waitlist patients in comparison to transplant recipients may aid centers in weighing the risks and benefits of transplantation in the setting of ongoing COVID‐19.
Comparisons of kidney waitlisted patients and transplant recipients show that waitlisted patients are more likely to require hospitalization and are at higher mortality risk, which is independently associated with waitlist status, age, male sex, and diabetes.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Solid organ transplant recipients may be at a high risk for SARS‐CoV‐2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with ...SARS‐CoV‐2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty‐six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual‐organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty‐two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non‐rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID‐19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID‐19 has the potential to severely impact solid organ transplant recipients.
In this multicenter study of 90 solid organ transplant recipients diagnosed with COVID‐19 during the first three weeks of the outbreak in New York City, the authors report on the clinical presentation, laboratory abnormalities, risk factors, disease severity, and outcomes.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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