Survival after Kidney Transplantation during Childhood and Adolescence

Background and objectivesSurvival in pediatric kidney transplant recipients has improved over the past five decades, but changes in cause-specific mortality remain uncertain. The aim of this retrospective cohort study was to estimate the associations between transplant era and overall and cause-specific mortality for child and adolescent recipients of kidney transplants.Design, setting, participants, & measurementsData were obtained on all children and adolescents (aged <20 years) who received their first kidney transplant from 1970 to 2015 from the Australian and New Zealand Dialysis and Transplant Registry. Mortality rates were compared across eras using Cox regression, adjusted for confounders.ResultsA total of 1810 recipients (median age at transplantation 14 years, 58% male, 52% living donor) were followed for a median of 13.4 years. Of these, 431 (24%) died, 174 (40%) from cardiovascular causes, 74 (17%) from infection, 50 (12%) from cancer, and 133 (31%) from other causes. Survival rates improved over time, with 5-year survival rising from 85% for those first transplanted in 1970–1985 (95% confidence interval [95% CI], 81% to 88%) to 99% in 2005–2015 (95% CI, 98% to 100%). This was primarily because of reductions in deaths from cardiovascular causes (adjusted hazard ratio [aHR], 0.25; 95% CI, 0.08 to 0.68) and infections (aHR, 0.16; 95% CI, 0.04 to 0.70; both for 2005–2015 compared with 1970–1985). Compared with patients transplanted 1970–1985, mortality risk was 72% lower among those transplanted 2005–2015 (aHR, 0.28; 95% CI, 0.18 to 0.69), after adjusting for potential confounders.ConclusionsSurvival after pediatric kidney transplantation has improved considerably over the past four decades, predominantly because of marked reductions in cardiovascular- and infection-related deaths.

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Early-Onset Coronary Artery Disease after Pediatric Kidney Transplantation: Implicating the Angiogenesis Inhibitor, Endostatin

The American Surgeon ◽

10.1177/000313481107700629 ◽

2011 ◽

Vol 77 (6) ◽

pp. 731-735 ◽

Cited By ~ 1

Author(s):

Corey W. Iqbal ◽

Patrick G. Dean ◽

Michael B. Ishitani

Keyword(s):

Kidney Transplantation ◽

Liver Transplant ◽

Kidney Transplant ◽

Angiogenesis Inhibitor ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Pediatric Kidney Transplantation ◽

Control Subjects ◽

Artery Disease ◽

Liver Transplant Recipients

Pediatric kidney transplant recipients have a higher rate of coronary artery disease (CAD) as adults. The angiogenesis inhibitor, endostatin, has been implicated in the development of atherosclerosis. Endostatin levels will vary between adult patients who received a kidney transplant as a child. We conducted a study in young adult patients who had undergone pediatric kidney (n = 12) or liver transplantation (n = 8). Coronary arterial calcification was measured using electron beam CT. Values were compared with age-matched control subjects from an epidemiologic database. Serum endostatin levels were measured using enzyme-linked immunosorbent assay. Risk factors for atherosclerosis were assessed. Kidney transplant recipients had a higher rate of CAD compared with liver transplant recipients (33 vs 0%, P = 0.03). Mean (± standard error of mean) serum endostatin levels were higher in kidney transplant recipients compared with liver transplant recipients (26 ± 7 vs 14 ± 3 ng/mL, P = 0.04) and control subjects (26 ± 7 vs 11 ± 1 ng/ mL, P = 0.01). Pediatric kidney transplantation is associated with a higher rate of adult-onset CAD compared with liver transplantation. Endostatin levels were greater in kidney transplant recipients compared with liver transplant recipients and healthy control subjects. Endostatin may play a role in the development of atherosclerosis after kidney transplantation and may serve as a biomarker for atherosclerotic disease.

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P1706THE GRAFT SURVIVAL OF KIDNEY TRANSPLANTATION ACCORDING TO ETHNICITY IN KIDNEY TRANSPLANT RECIPIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1706 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Yeonsoon Jung ◽

Jisu Kim ◽

Haesu Jeon ◽

Ye Na Kim ◽

Ho Sik Shin ◽

...

Keyword(s):

African American ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Graft Survival ◽

Cox Regression ◽

Patient Survival ◽

Graft Loss ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Data Set

Abstract Background African American kidney transplant recipients experience disproportionately high rates of graft loss. The aim of this analysis was to use a UNOS data set that contains detailed baseline and longitudinal clinical data to establish and quantify the impact of the current overall graft loss definition on suppressing the true disparity magnitude in US AA kidney transplant outcomes. Methods Longitudinal cohort study of kidney transplant recipients using a data set created by United Network for Organ Sharing (UNOS), including 266,128 (African American 70,215, Non-African American 195,913) transplant patient between 1987 and December 2016. Multivariable analysis was conducted using 2-stage joint modeling of random and fixed effects of longitudinal data (linear mixed model) with time to event outcomes (Cox regression). Results 195,913 non-African American (AA) (73.6%) were compared with 70,215 AA (26.4%) recipients. 10-year-graft survival of AA in all era is lower than that of non-AA (31% in deceased kidney transplants (DKT) AA recipient and 42% in living kidney transplantation (LKT) non-AA recipient). 10-year-patient survival of AA with functioning graft in all era is similar that of non-AA. Multivariate Cox regression of factors associated with patient survival with functioning graft are acute rejection within 6 months, DM, hypertension and etc. Pre-transplant recipient BMI in AA show the trend as a protective factor in patient survival with functioning graft although not significantly in statistics Conclusions African American kidney transplant recipients experience a substantial disparity in graft loss, but not patient death with functioning graft.

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The NFKB1 Promoter Polymorphism (-94ins/delATTG) Is Associated with Susceptibility to Cytomegalovirus Infection after Kidney Transplantation and Should Have Implications on CMV Prophylaxis Regimens

Cells ◽

10.3390/cells10020380 ◽

2021 ◽

Vol 10 (2) ◽

pp. 380

Author(s):

Hartmuth Nowak ◽

Svenja Vornweg ◽

Katharina Rump ◽

Tim Rahmel ◽

Matthias Unterberg ◽

...

Keyword(s):

Kidney Transplantation ◽

Kidney Transplant ◽

Cox Regression ◽

Opportunistic Infections ◽

Late Onset ◽

Association Studies ◽

Promoter Polymorphism ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cmv Infection

Infections with cytomegalovirus (CMV) are one of the most frequent opportunistic infections in kidney transplant recipients. Current risk-adapted CMV chemoprophylaxis regimens are based almost solely on the donor and recipient CMV serostatus. Of note, the NFKB1 -94ins/delATTG promoter polymorphism was recently associated with a higher risk of CMV infection. Since single genetic association studies suffer from poor reliability for drawing therapeutic implications, we performed this confirmatory study and included 256 kidney transplant recipients from 2007 to 2014 in this retrospective study. Patients were genotyped for the -94ins/delATTG NFKB1 promoter polymorphism and followed up for 12 months. The incidence of CMV infection within 12 months after kidney transplantation was 37.5% (33/88) for the ins/ins, 21.5% (28/130) for the ins/del, and 23.7% (9/38) for the del/del genotypes (p = 0.023). Moreover, we evaluated the time of CMV infection onset. Ins/ins carriers had primarily late-onset CMV infection (median 194 days; interquartile range (IQR) 117–267 days) compared with heterozygous (ins/del; median 158 days; IQR 82–195 days) and homozygous deletion allele carriers (del/del; median 95 days; 84–123 days). Multivariate-restricted Cox regression model confirmed the ins/ins genotype to be an independent risk factor for the development of late-onset CMV infections. These findings should have an impact on post-kidney transplantation CMV chemoprophylaxis regimens.

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Current Pharmacological Intervention and Medical Management for Diabetic Kidney Transplant Recipients

Pharmaceutics ◽

10.3390/pharmaceutics13030413 ◽

2021 ◽

Vol 13 (3) ◽

pp. 413

Author(s):

Theerawut Klangjareonchai ◽

Natsuki Eguchi ◽

Ekamol Tantisattamo ◽

Antoney J. Ferrey ◽

Uttam Reddy ◽

...

Keyword(s):

Diabetes Mellitus ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Pharmacological Intervention ◽

Diabetic Patients ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Kidney Allograft ◽

Post Transplant ◽

Glucose Management

Hyperglycemia after kidney transplantation is common in both diabetic and non-diabetic patients. Both pretransplant and post-transplant diabetes mellitus are associated with increased kidney allograft failure and mortality. Glucose management may be challenging for kidney transplant recipients. The pathophysiology and pattern of hyperglycemia in patients following kidney transplantation is different from those with type 2 diabetes mellitus. In patients with pre-existing and post-transplant diabetes mellitus, there is limited data on the management of hyperglycemia after kidney transplantation. The following article discusses the nomenclature and diagnosis of pre- and post-transplant diabetes mellitus, the impact of transplant-related hyperglycemia on patient and kidney allograft outcomes, risk factors and potential pathogenic mechanisms of hyperglycemia after kidney transplantation, glucose management before and after transplantation, and modalities for prevention of post-transplant diabetes mellitus.

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Soluble urokinase-type plasminogen activator receptor (suPAR) is a risk indicator for eGFR loss in kidney transplant recipients

Scientific Reports ◽

10.1038/s41598-021-83333-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ulrich Jehn ◽

Katharina Schütte-Nütgen ◽

Ute Henke ◽

Hermann Pavenstädt ◽

Barbara Suwelack ◽

...

Keyword(s):

Kidney Transplantation ◽

Cox Regression ◽

Kidney Diseases ◽

Prognostic Significance ◽

Risk Indicator ◽

Kidney Transplant Recipients ◽

Supar Level ◽

Type Plasminogen Activator ◽

Urokinase Type Plasminogen Activator ◽

One Year

AbstractThe prognostic significance of suPAR in various kidney diseases has recently been demonstrated. Its role in transplantation-specific outcomes is still largely unknown. Therefore, we prospectively investigated the prognostic relevance of suPAR in patients before and one year after kidney transplantation (KTx). We included 100 patients who had received a kidney transplantation between 2013 and 2015. The plasma concentration of suPAR was measured by ELISA assay. In recipients of living donations (LD), pre-transplant suPAR levels were significantly lower than those of recipients of deceased donations (DD). After KTx, suPAR levels significantly declined in LD and DD recipients, without a detectable difference between both groups any more. Higher suPAR levels in recipients one year after KTx were associated with a more severe eGFR loss in the following three years in multivariable cox-regression (n = 82, p = 0.021). suPAR-levels above 6212 pg/ml one year after KTx are associated with eGFR loss > 30%, which occurred almost twice as fast as in patients with suPAR ≤ 6212 pg/ml (p < 0.001). Hence, suPAR level at one year mark might be a risk indicator of increased eGFR loss.

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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 ◽

10.3390/antiox10071102 ◽

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.

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Circulating endothelial cells transiently increase in peripheral blood after kidney transplantation

Scientific Reports ◽

10.1038/s41598-021-88411-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

H. Tejeda-Mora ◽

J. G. H. P. Verhoeven ◽

W. Verschoor ◽

K. Boer ◽

D. A. Hesselink ◽

...

Keyword(s):

Endothelial Cells ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Allograft Rejection ◽

Flow Cytometric Analysis ◽

Principal Component ◽

Circulating Endothelial Cells ◽

Clinical Markers ◽

Kidney Transplant Recipients ◽

Post Transplant

AbstractThe diagnosis of kidney allograft rejection is based on late histological and clinical markers. Early, specific and minimally-invasive biomarkers may improve rejection diagnosis. Endothelial cells (EC) are one of the earliest targets in kidney transplant rejection. We investigated whether circulating EC (cEC) could serve as an earlier and less invasive biomarker for allograft rejection. Blood was collected from a cohort of 51 kidney transplant recipients before and at multiple timepoints after transplantation, including during a for cause biopsy. The number and phenotype of EC was assessed by flow-cytometric analysis. Unbiased selection of EC was done using principal component (PCA) analysis. Paired analysis revealed a transient cEC increase of 2.1-fold on the third day post-transplant, recovering to preoperative levels at seventh day post-transplant and onwards. Analysis of HLA subtype demonstrated that cEC mainly originate from the recipient. cEC levels were not associated with allograft rejection, allograft function or other allograft pathologies. However, cEC in patients with allograft rejection and increased levels of cEC showed elevated levels of KIM-1 (kidney injury marker-1). These findings indicate that cEC numbers and phenotype are affected after kidney transplantation but may not improve rejection diagnosis.

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Trends in Kidney Transplantation Outcome: The Andalusian Kidney Transplant Registry, 1984–2007

Transplantation Proceedings ◽

10.1016/j.transproceed.2009.01.094 ◽

2009 ◽

Vol 41 (5) ◽

pp. 1583-1585 ◽

Cited By ~ 13

Author(s):

M.A. Gentil Govantes ◽

A. Rodriguez-Benot ◽

E. Sola ◽

A. Osuna ◽

A. Mazuecos ◽

...

Keyword(s):

Kidney Transplantation ◽

Kidney Transplant ◽

Transplant Registry

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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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FC 124PATTERNS OF RENAL OSTEODYSTROPHY ONE YEAR AFTER KIDNEY TRANSPLANTATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab147.003 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Hanne Skou Jørgensen ◽

Geert Behets ◽

Patrick D'Haese ◽

Pieter Evenepoel

Keyword(s):

Kidney Transplantation ◽

Bone Turnover ◽

Kidney Transplant ◽

Renal Osteodystrophy ◽

Bone Disease ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Transplant ◽

Steroid Dose ◽

Bone Biopsies

Abstract Background and Aims Bone disease after kidney transplantation is an issue of growing concern, as prolonged graft survival and older age of recipients necessitate focus on long-term health burdens such as osteoporosis and fractures. Pre-existing type of renal osteodystrophy, post-transplant immunosuppressive treatment, and de novo disturbances of mineral metabolism all contribute to bone disease in kidney transplant recipients. The current pattern of renal osteodystrophy after kidney transplantation is not well characterized. This study reports histomorphometric findings of protocolled bone biopsies in a large cohort of kidney transplant recipients 1 year post-transplant. Method Histomorphometric analysis of transiliac bone biopsies with prior tetracycline labelling was performed in 141 kidney transplant recipients. Biochemical measurements included bioactive parathyroid hormone (PTH), total calcium, phosphate, calcidiol, bicarbonate, and sclerostin. Kruskal-Wallis and Wilcoxon signed rank tests were used to evaluate differences across categories and between groups, respectively. Stepwise multivariate linear regression was performed to identify key demographic and biochemical determinants of bone turnover (bone formation rate, BFR), mineralization (mineralization lag time, Mlt), and volume (Bone area, BAr). Results Mean age was 57±11 years, 71% were men, and all were Caucasian. Mean eGFR was 49±16 (range 19 to 106) ml/min/1.73 m². Hyperparathyroidism (PTH > 1.5xUNL) was seen in 48%, hypercalcemia (>10.3 mg/dL) in 18%, hypophosphatemia (<2.3 mg/dl) in 12%, and vitamin D deficiency (<15 ng/mL) in 4% of patients. Categorization of bone turnover, mineralization, and volume is shown in Figure 1. Bone turnover was normal in the vast majority (71%). Patients with low turnover (26%) had received a higher cumulative steroid dose (2.78 vs 2.34g in low vs non-low turnover; p=0.02). Patients with delayed mineralization (16%) were younger (52 vs 58 yrs, p=0.02) and had received a higher cumulative steroid dose (2.85 vs 2.36g, p=0.003). They had higher levels of PTH (124 vs 53 ng/L, p<0.001), and lower levels of phosphate (2.68 vs 3.18 mg/dL, p<0.001), calcidiol (29 vs 37ug/L, p=0.02), bicarbonate (21.3 vs 23.3 mmol/L, p=0.004), and sclerostin (493 vs 594 pg/mL, p=0.03) compared to patients with normal mineralization. Patients with low bone volume tended to be older (61 vs 56 years, p=0.07). Independent determinants of BFR were PTH (β=0.68, p<0.001) and cumulative steroid dose (β = -0.22, p=0.02). Determinants of Mlt were phosphate (β=-0.48, p=0.001) and cumulative steroid dose (β=0.18, p=0.004), and determinants of BAr were age (β=-0.15, p=0.002), and BMI (β=0.33, p=0.002). Conclusion Bone turnover is normal in the majority of kidney transplant recipients at 1 year post-transplant, despite a high prevalence of hyperparathyroidism. Low levels of bicarbonate, phosphate, and calcidiol may contribute to delayed bone mineralization in kidney transplant recipients.

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