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

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.

scholarly journals Mediterranean Style Diet and Kidney Function Loss in Kidney Transplant Recipients

2020 ◽  
Vol 15 (2) ◽  
pp. 238-246 ◽  
Author(s):  
António W. Gomes-Neto ◽  
Maryse C.J. Osté ◽  
Camilo G. Sotomayor ◽  
Else van den Berg ◽  
Johanna Marianna Geleijnse ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Mediterranean Diet ◽  
Kidney Function ◽  
Graft Failure ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Mediterranean Diet Score ◽  
The Mediterranean ◽  
Diet Score

Background and objectivesDespite improvement of short-term graft survival over recent years, long-term graft survival after kidney transplantation has not improved. Studies in the general population suggest the Mediterranean diet benefits kidney function preservation. We investigated whether adherence to the Mediterranean diet is associated with kidney outcomes in kidney transplant recipients.Design, setting, participants, & measurementsWe included 632 adult kidney transplant recipients with a functioning graft for ≥1 year. Dietary intake was inquired using a 177-item validated food frequency questionnaire. Adherence to the Mediterranean diet was assessed using a nine-point Mediterranean Diet Score. Primary end point of the study was graft failure and secondary end points included kidney function decline (doubling of serum creatinine or graft failure) and graft loss (graft failure or death with a functioning graft). Cox regression analyses were used to prospectively study the associations of the Mediterranean Diet Score with study end points.ResultsDuring median follow-up of 5.4 (interquartile range, 4.9–6.0) years, 76 participants developed graft failure, 119 developed kidney function decline, and 181 developed graft loss. The Mediterranean Diet Score was inversely associated with all study end points (graft failure: hazard ratio [HR], 0.68; 95% confidence interval [95% CI], 0.50 to 0.91; kidney function decline: HR, 0.68; 95% CI, 0.55 to 0.85; and graft loss: HR, 0.74; 95% CI, 0.63 to 0.88 per two-point increase in Mediterranean Diet Score) independent of potential confounders. We identified 24-hour urinary protein excretion and time since transplantation to be an effect modifier, with stronger inverse associations between the Mediterranean Diet Score and kidney outcomes observed in participants with higher urinary protein excretion and participants transplanted more recently.ConclusionsAdherence to the Mediterranean diet is associated with better kidney function outcomes in kidney transplant recipients.

scholarly journals Long-Term Outcomes among Kidney Transplant Recipients and after Graft Failure: A Single-Center Cohort Study in Brazil

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Paula Rebello Bicalho ◽  
Lúcio R. Requião-Moura ◽  
Érika Ferraz Arruda ◽  
Rogerio Chinen ◽  
Luciana Mello ◽  
...  
Keyword(s):  
Cohort Study ◽  
Kidney Transplantation ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
Cause Of Death ◽  
Chronic Rejection ◽  
Graft Failure ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background. The results of kidney transplantation are impacted by the categories of events responsible for patient death and graft failure. The objective of this study was to evaluate the causes of death and graft failure and outcomes after graft failure among kidney transplant recipients. Methodology. A retrospective cohort study was conducted with 944 patients who underwent kidney transplantation. Outcomes were categorized in a managed and hierarchical manner. Results. The crude mortality rate was 10.8% (n=102): in 35.3% cause of death was infection, in 30.4% cardiovascular disease, and in 15.7% neoplasia and in 6.8%, it was not possible to determine the cause of death. The rate of graft loss was 10.6%. The main causes of graft failure were chronic rejection (40%), acute rejection (18.3%), thrombosis (17.3%), and recurrence of primary disease (16.5%). Failures due to an acute rejection occurred earlier than those due to chronic rejection and recurrence (p<0.0001). As late causes of graft loss, death with the functioning kidney occurred earlier than recurrence and chronic rejection (p=0.008). The outcomes after graft failure were retransplantation in 26.1% and death in 21.4%, at a mean of 25.5 and 21.4 months, respectively. Conclusion. It was possible to identify more than 90% of the events responsible for the deaths of transplanted patients, predominantly infectious and cardiovascular diseases. Among the causes of graft failure, chronic and acute rejections and recurrence were the main causes of graft failure which were followed more frequently by retransplantation than by death on dialysis.

Immunosuppressive Management of Pediatric Kidney Transplant Recipients

2020 ◽  
Vol 26 (28) ◽  
pp. 3451-3459
Author(s):  
Tomáš Seeman
Keyword(s):  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Graft Loss ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Therapeutic Drug ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

: Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. : Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. : The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. : Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). : The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.

scholarly journals BK Polyomavirus Micro-RNAs: Time Course and Clinical Relevance in Kidney Transplant Recipients

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 351
Author(s):  
Baptiste Demey ◽  
Véronique Descamps ◽  
Claire Presne ◽  
Francois Helle ◽  
Catherine Francois ◽  
...  
Keyword(s):  
Viral Replication ◽  
Kidney Transplant ◽  
Clinical Relevance ◽  
Graft Loss ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Bk Polyomavirus ◽  
Micro Rnas

Background: Kidney transplant recipients (KTRs) are exposed to a high risk of BK polyomavirus (BKPyV) replication, which in turn may lead to graft loss. Although the microRNAs (miRNAs) bkv-miR-B1-3p and bkv-miR-B1-5p are produced during the viral cycle, their putative value as markers of viral replication has yet to be established. In KTRs, the clinical relevance of the changes over time in BKPyV miRNA levels has not been determined. Methods: In a retrospective study, we analyzed 186 urine samples and 120 plasma samples collected from 67 KTRs during the first year post-transplantation. Using a reproducible, standardized, quantitative RT-PCR assay, we measured the levels of bkv-miR-B1-3p and bkv-miR-B1-5p (relative to the BKPyV DNA load). Results: Detection of the two miRNAs had low diagnostic value for identifying patients with DNAemia or for predicting DNAuria during follow-up. Seven of the 14 KTRs with a sustained BKPyV infection within the first year post-transplantation showed a progressive reduction in the DNA load and then a rapid disappearance of the miRNAs. DNA and miRNA loads were stable in the other seven KTRs. Conclusions: After the DNA-based diagnosis of BKPyV infection in KTRs, bkv-miR-B1-3p and bkv-miR-B1-5p levels in the urine might be valuable markers for viral replication monitoring and thus might help physicians to avoid an excessive reduction in the immunosuppressive regimen.

scholarly journals Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1102
Author(s):  
Angelica Rodriguez-Niño ◽  
Diego O. Pastene ◽  
Adrian Post ◽  
M. Yusof Said ◽  
Antonio W. Gomes-Neto ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Cox Regression ◽  
Carbonyl Stress ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Increased Risk ◽  
High Concentrations ◽  
Kidney Function Decline

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.

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

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.

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

Diseases ◽  
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.

Net Endogenous Acid Excretion and Kidney Allograft Outcomes

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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