De NovoDonor-Specific Antibody at the Time of Kidney Transplant Biopsy Associates with Microvascular Pathology and Late Graft Failure

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.

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Review of Outcomes after Diagnosis of Malignancy in Kidney Transplant Patients: UNOS Database

Transplantology ◽

10.3390/transplantology2030024 ◽

2021 ◽

Vol 2 (3) ◽

pp. 253-263

Author(s):

Het Patel ◽

Nikhil Agrawal ◽

Voravech Nissaisorakarn ◽

Ridhi Gupta ◽

Francesca Cardarelli

Keyword(s):

Kidney Transplant ◽

Graft Failure ◽

Event Analysis ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Time To Event ◽

Transplant Patients ◽

Kaplan Meier ◽

Lung Malignancy ◽

Kidney Transplant Patients

Malignancy is the third major cause of death among transplant recipients. Patient and kidney transplant outcomes after the diagnosis of malignancy are not well described. We reviewed incidences and outcomes of colorectal, lung, PTLD, and renal malignancy after transplant among patients who received a transplant from January 2000 to December 2018 using the UNOS/OPTN database. Incidence of each malignancy was measured at 5 years and 10 years of transplant. The Kaplan–Meier curve was used for time-to-event analysis (graft and patient outcomes). Additionally, we sought to identify the causes of graft failure among these recipients. We found that 12,764 (5.5%) patients suffered malignancy, excluding squamous and basal cell skin carcinoma after transplant. During the first 5 years of transplant, incidence of colorectal, lung, PTLD, and renal malignancies was 2.99, 9.21, 15.61, and 8.55 per 10,000 person-years, respectively. Rates of graft failure were 10.3%, 7.6%, 19.9%, and 18.8%, respectively, among these patients at 5 years. Mortality rate was highest among patients who suffered lung malignancy (84%), followed by colorectal (61.5%), PTLD (49.1%), and renal (35.5%) at 5 years after diagnosis of malignancy. In conclusion, kidney transplant recipients diagnosed with lung malignancy have the lowest graft survival, compared to PTLD, colorectal, and renal malignancy. PTLD has the highest incidence rate in the first 5 years of transplant.

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Clinical impact of serum bilirubin levels on kidney transplant outcomes

Scientific Reports ◽

10.1038/s41598-021-86330-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Juhan Lee ◽

Eun Jin Kim ◽

Jae Geun Lee ◽

Beom Seok Kim ◽

Kyu Ha Huh ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Failure ◽

Serum Bilirubin ◽

Graft Loss ◽

Multivariable Analysis ◽

Post Transplantation ◽

Transplant Outcomes ◽

Increased Risk ◽

All Cause Mortality ◽

Kidney Transplantations

AbstractSerum bilirubin, a potent endogenous antioxidant, has been associated with decreased risks of cardiovascular disease, diabetes, and kidney disease. However, the effects of serum bilirubin on kidney transplant outcomes remain undetermined. We analyzed 1628 patients who underwent kidney transplantations between 2003 and 2017. Patients were grouped into sex-specific quartiles according to mean serum bilirubin levels, 3–12 months post-transplantation. Median bilirubin levels were 0.66 mg/dL in males and 0.60 mg/dL in females. The intra-individual variability of serum bilirubin levels was low (9%). Serum bilirubin levels were inversely associated with graft loss, death-censored graft failure, and all-cause mortality, independent of renal function, donor status, and transplant characteristics. Multivariable analysis revealed that the lowest serum bilirubin quartile was associated with increased risk of graft loss (HR 2.64, 95% CI 1.67–4.18, P < 0.001), death-censored graft failure (HR 2.97, 95% CI 1.63–5.42, P < 0.001), and all-cause mortality (HR 2.07, 95% CI 1.01–4.22, P = 0.046). Patients with lower serum bilirubin were also at greater risk of rejection and exhibited consistently lower glomerular filtration rates than those with higher serum bilirubin. Serum bilirubin levels were significantly associated with transplantation outcomes, suggesting that bilirubin could represent a therapeutic target for improving long-term transplant outcomes.

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Outcomes of Kidney Transplantation in Fabry Disease: A Meta-Analysis

Diseases ◽

10.3390/diseases9010002 ◽

2020 ◽

Vol 9 (1) ◽

pp. 2

Author(s):

Maria L. Gonzalez Suarez ◽

Charat Thongprayoon ◽

Panupong Hansrivijit ◽

Juan Medaura ◽

Pradeep Vaitla ◽

...

Keyword(s):

Kidney Transplantation ◽

Fabry Disease ◽

Kidney Transplant ◽

Allograft Rejection ◽

Graft Failure ◽

Current Therapy ◽

Transplant Recipients ◽

Lysosomal Storage ◽

Kidney Transplant Recipients ◽

Enzyme Replacement

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%–42.5%), 14.5% (95%CI: 8.4%–23.7%), and 20.2% (95%CI: 15.4%–25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%–37.3%), 11.7% (95%CI: 8.4%–16.0%), and 20.2% (95%CI: 15.5%–26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%–29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.

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Net Endogenous Acid Excretion and Kidney Allograft Outcomes

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.00780121 ◽

2021 ◽

pp. CJN.00780121

Author(s):

Stanley Yeung ◽

Antonio Gomes-Neto ◽

Maryse Osté ◽

Else van den Berg ◽

Jenny Kootstra-Ros ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Failure ◽

Plasma Creatinine ◽

Transplant Recipients ◽

Acid Excretion ◽

Kidney Transplant Recipients ◽

Dietary Acid Load ◽

Dietary Acid ◽

Acid Load ◽

Net Acid Excretion

Background and objectives: High dietary acid load may accelerate kidney function decline. We prospectively investigated whether dietary acid load is associated with graft outcomes in kidney transplant recipients and whether venous bicarbonate (HCO3−) mediates this association. Design, setting, participants and measurements: We used data from 642 kidney transplant recipients with a functioning graft ≥1 year after transplantation. Net endogenous acid production (NEAP) was estimated using food frequency questionnaires (FFQ) and, alternatively, 24-hour urinary urea and potassium excretion to estimate NEAPUrine. We defined composite kidney endpoint as doubling of plasma creatinine or graft failure. Multivariable Cox regression analyses, adjusted for potential confounders, were used to study the associations of dietary acid load with kidney endpoint. We evaluated potential mediation effects of venous HCO3− , urinary HCO3− excretion, urinary ammonium (NH4+) excretion, titratable acid excretion, and net acid excretion on the association between NEAP and kidney endpoint. Results: Median NEAPFFQ and NEAPUrine were 40 (Interquartile range [IQR] 35-45) and 54 (IQR 44-66) mEq/day, respectively. During a median follow-up time of 5.3 (IQR 4.1-6.0) years, 121 (19%) participants reached kidney endpoint. After multivariable adjustment, NEAPFFQ and NEAPUrine (per SD higher) were independently associated with higher risk for kidney endpoint (hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.12-1.57, P=0.001 and HR 95%CI, 1.44 [1.24-1.69], P<0.001 resp.). Baseline venous HCO3− mediated 20% of the association between NEAPFFQ and kidney endpoint. Baseline venous HCO3−, urinary NH4+ excretion and net acid excretion mediated 25%, -14% and -18% resp. of the association between NEAPUrine and kidney endpoint. Conclusion: Higher dietary acid load was associated with a higher risk of doubling of plasma creatinine or graft failure, and this association was partly mediated by venous HCO3−, urinary NH4+ and net acid excretion.

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185 Low Serum Bicarbonate Is Associated With Graft Failure in Kidney Transplant Recipients

American Journal of Kidney Diseases ◽

10.1053/j.ajkd.2021.02.190 ◽

2021 ◽

Vol 77 (4) ◽

pp. 625

Keyword(s):

Kidney Transplant ◽

Graft Failure ◽

Serum Bicarbonate ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Low Serum

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Time-Varying Proteinuria and the Risk of Cardiovascular Disease and Graft Failure in Kidney Transplant Recipients

Progress in Transplantation ◽

10.1177/15269248211046011 ◽

2021 ◽

Vol 31 (4) ◽

pp. 288-297

Author(s):

Tanya Kuper ◽

Olusegun Famure ◽

Jamie Greenfield ◽

Yanhong Li ◽

Syed Ibrahim ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Failure ◽

Graft Loss ◽

Major Adverse Cardiac Events ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cardiac Events ◽

Urine Protein ◽

Hazard Ratios ◽

Adverse Cardiac Events

Introduction: Proteinuria is recognized as an independent risk factor for cardiovascular disease in kidney transplant recipients, but previous studies have not considered the impact of changes in urine protein over time. Research Question and Design: We used time-dependent, multivariable Cox proportional hazards models in this observational cohort study of adult kidney transplant recipients to evaluate whether proteinuria measured by dipstick on random spot urine samples starting from 1-month post-transplant was associated with the risk of major adverse cardiac events and graft loss. Results: A total of 144 major adverse cardiac events, defined as acute myocardial infarction, cerebrovascular accident, revascularization, or all-cause mortality, were observed in 1106 patients over 5728.7 person-years. Any level of proteinuria greater or equal to trace resulted in a two-fold increase in the risk of major adverse cardiac events (hazard ratio 2.00 [95% confidence interval 1.41, 2.84]). This relationship was not found to be dose-dependent (hazard ratios of 2.98, 1.76, 1.63, and 1.54 for trace, 1+, 2+, and 3+ urine protein, respectively). There was an increased risk of graft failure with greater urine protein concentration (hazard ratios 2.22, 2.85, 6.41, and 19.71 for trace, 1+, 2+, and 3+, respectively). Conclusion: Urine protein is associated with major adverse cardiac events and graft loss in kidney transplant recipients. The role of interventions to reduce proteinuria on decreasing the risk of adverse cardiovascular and graft outcomes in kidney transplant recipients requires further study.

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MO941CLINICAL OUTCOMES IN KIDNEY RE-TRANSPLANTATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab110.0020 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Clara Pardinhas ◽

Rita Leal ◽

Francisco Caramelo ◽

Teofilo Yan ◽

Carolina Figueiredo ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Graft Survival ◽

Graft Failure ◽

Graft Function ◽

Delayed Graft Function ◽

First Year ◽

Kidney Transplant Recipients ◽

Post Transplant

Abstract Background and Aims As kidney transplants are growing in absolute numbers, so are patients with failed allografts and thus potential candidates for re-transplantation. Re-transplantation is challenging due to immunological barriers, surgical difficulties and clinical complexities but it has been proven that successful second transplantation improves life expectancy over dialysis. It is important to evaluate re-transplantation outcomes since 20% of patients on the waiting list are waiting for a second graft. Our aim was to compare major clinical outcomes such as acute rejection, graft and patient survival, between patients receiving a first or a second kidney transplant. Method We performed a retrospective study, that included 1552 patients submitted to a first (N=1443, 93%) or a second kidney transplant (N=109, 7%), between January 2008 and December 2018. Patients with more than 2 grafts or multi-organ transplant were excluded. Demographic, clinical and histocompatibility characteristics of both groups were registered from our unit database and compared. Delayed graft function was defined has the need of dialysis in the first week post-transplant. All acute rejection episodes were biopsy proven, according to Banff 2017 criteria. Follow-up time was defined at 1st June 2020 for functioning grafts or at graft failure (including death with a functioning graft). Results Recipients of a second graft were significantly younger (43 ±12 vs 50 ± 13 years old, p<0.001) and there were significantly fewer expanded-criteria donors in the second transplant group (31.5% vs 57.5%, p<0.001). The waiting time for a second graft was longer (63±50 vs 48±29 months, p=0.011). HLA mismatch was similar for both groups but PRA was significantly higher for second KT patients (21.6±25% versus 3±9%; p<0.001). All patients submitted to a second KT had thymoglobulin as induction therapy compared to 16% of the first KT group (p<0.001). We found no difference in primary dysfunction or delayed graft function between groups. Acute rejection was significantly more frequent in second kidney transplant recipients (19% vs 5%, p<0.001), being 10 acute cellular rejections, 7 were antibody mediated and 3 were borderline changes. For the majority of the patients (85%), acute rejection occurred in the first-year post-transplant. Death censored graft failure occurred in 236 (16.4%) patients with first kidney transplant and 25 (23%) patients with a second graft, p=0.08. Survival analysis showed similar graft survival for both groups (log-rank p=0.392). We found no difference in patients’ mortality at follow up for both groups. Conclusion Although second graft patients presented more episodes of biopsy proven acute rejection, especially at the first-year post-transplant, we found no differences in death censored graft survival or patients’ mortality for patients with a second kidney transplant. Second transplants should be offered to patients whenever feasible.

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