Effects of Aging on Kidney Graft Function, Oxidative Stress and Gene Expression after Kidney Transplantation

Background Reduced free thiols in plasma are indicative of oxidative stress, which is an important contributor to ischaemia-reperfusion injury (IRI) in kidney transplantation leading to kidney damage and possibly delayed graft function (DGF). In a post-hoc, exploratory analysis of the randomised controlled CONTEXT trial, we investigated whether higher (i.e. less oxidised) plasma levels of free thiols as a biomarker of reduced oxidative stress are associated with a better initial graft function or a higher GFR. Methods Free thiol levels were measured in plasma at baseline, 30 and 90 minutes after reperfusion of the kidney as well as at Day 1, Day 5 and twelve months after kidney transplantation in 217 patients from the CONTEXT study. Free thiol levels were compared to the kidney graft function measured as the estimated time to a 50% reduction in plasma creatinine (tCr50), the risk of DGF and measured GFR (mGFR) at Day 5 and twelve months after transplantation. Results Higher levels of free thiols at Day 1 and Day 5 are associated with higher mGFR at Day 5 (p<0.001, r2adj. = 0.16; p<0.001, r2adj. = 0.25), as well as with mGFR at twelve months (p<0.001, r2adj. = 0.20; p<0.001, r2adj. = 0.16). However, plasma levels of free thiols at 30 minutes and 90 minutes, but not Day 1, were significantly higher among patients experiencing DGF. Conclusion Higher levels of plasma free thiols at Day 1 and Day 5, which are reflective of lower levels of oxidative stress, are associated with better early and late graft function in recipients of a kidney graft from deceased donors. Trial registration ClinicalTrials.gov Identifier: NCT01395719.

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Gene Expression Profile in Delay Graft Function: Inflammatory Markers Are Associated with Recipient and Donor Risk Factors

Mediators of Inflammation ◽

10.1155/2014/167361 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Diego Guerrieri ◽

Luis Re ◽

Jorgelina Petroni ◽

Nella Ambrosi ◽

Roxana E. Pilotti ◽

...

Keyword(s):

Gene Expression ◽

Risk Factors ◽

Kidney Transplantation ◽

Inflammatory Markers ◽

Graft Function ◽

Deceased Donor ◽

Specific Pattern ◽

Inflammatory Gene Expression ◽

Inflammatory Gene ◽

Recipient Age

Background.Delayed graft function (DGF) remains an important problem after kidney transplantation and reduced long-term graft survival of the transplanted organ. The aim of the present study was to determine if the development of DGF was associated with a specific pattern of inflammatory gene expression in expanded criteria of deceased donor kidney transplantation. Also, we explored the presence of correlations between DGF risk factors and the profile that was found.Methods.Seven days after kidney transplant, a cDNA microarray was performed on biopsies of graft from patients with and without DGF. Data was confirmed by real-time PCR. Correlations were performed between inflammatory gene expression and clinical risk factors.Results.From a total of 84 genes analyzed, 58 genes were upregulated while only 1 gene was downregulated in patients with DGF compared with no DGF (P=0.01). The most relevant genes fold changes observed was IFNA1, IL-10, IL-1F7, IL-1R1, HMOX-1, and TGF-β. The results were confirmed for IFNA1, IL-1R1, HMOX-1 and TGF-β. A correlation was observed between TGF-β, donor age, and preablation creatinine, but not body mass index (BMI). Also, TGF-βshowed an association with recipient age, while IFNA1 correlated with recipient BMI. Furthermore, TGF-β, IFNA1 and HMOX-1 correlated with several posttransplant kidney function markers, such as diuresis, ultrasound Doppler, and glycemia.Conclusions.Overall, the present study shows that DGF is associated with inflammatory markers, which are correlated with donor and recipient DGF risk factors.

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LONG-TERM KIDNEY GRAFT FUNCTION AFTER COMBINED LIVER-KIDNEY TRANSPLANTATION

Transplantation Journal ◽

10.1097/01.tp.0000330829.25198.8f ◽

2008 ◽

Vol 86 (Supplement) ◽

pp. 696

Author(s):

R Ruiz ◽

B Fischbach ◽

N Onaca ◽

G McKenna ◽

H Randall ◽

...

Keyword(s):

Kidney Transplantation ◽

Graft Function ◽

Kidney Graft

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P1021MARKERS OF “METABOLIC MEMORY” AND KIDNEY GRAFT FUNCTION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1021 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Irina Larina ◽

Anastasia Severina ◽

Minara Shamhalova ◽

Marina Shestakova ◽

Larisa Nikankina ◽

...

Keyword(s):

Oxidative Stress ◽

Carbohydrate Metabolism ◽

Graft Function ◽

Metabolic Memory ◽

Kidney Graft ◽

Stress Markers ◽

Pancreas Kidney Transplantation ◽

Simultaneous Pancreas Kidney ◽

Simultaneous Pancreas Kidney Transplantation

Abstract Background and Aims To evaluate the relationship between oxidative stress markers and advanced glycation end products receptor (RAGE) with kidney graft function and complications of end-stage renal disease (ESRD) in patients with type 1 diabetes mellitus (T1DM), who reached stable euglycemia after simultaneous pancreas-kidney transplantation (SPKT). Method The study included 27 patients with T1DM duration for 21 [19; 28] years, diabetic nephropathy (DN) duration 7,0 [5,5; 13,5] years and duration of renal replacement therapy (dialysis) for 2 [1; 4] years after successful SPKT. The posttransplantation period at the time of inclusion was 61 [20; 90] months. Assessment included examination of oxidative stress markers (3-nitrothyrosine (3-NT), superoxide dismutase (SOD) and RAGE, analysis of the main kidney transplant dysfunction markers (KIM-1, NGAL, podocin, IL-18) and state of carbohydrate metabolism with monitoring for 1 year. All patients received three-component immunosuppressive therapy. Results SPKT allowed to achieve stable euglycemia (HbA1c 5.5 [5.1; 5.9] %, 5.5 [5.3; 5.7] % and С-peptide 2,9 [2,1; 3,6] ng/ml, 2,6 [2,0; 3,4] ng/ml at baseline and after 1 year of follow – up, respectively) and the restoration of graft function to the rate of estimated glomerular filtration rate (eGFR) CKD-EPI stage C2, albuminuria stage A1 of chronic kidney disease (CKD). However, 22% of patients experienced an increase of albumin-to-creatinine ratio to A2 at different times after surgical treatment. There was a statistically significant increase in SOD level (p=0.0005) and RAGE level (p=0.011) after 12 months of observation. Significant correlations of kidney transplant function parameters with “metabolic memory" markers (oxidative stress and RAGE) were also found: RAGE & creatinine (R=0.50, p=0.02), RAGE & KIM-1 (R=0.43, p=0.047), 3-NT& eGFR (R= - 0.40, p=0.046), IL-18 & SOD baseline (R=0.43, p=0.047). Attention is drawn to the correlations of RAGE & HbA1c+12 month (R=0.47, p=0.01), podocin with HbA1c (R=-0.46, p=0.03), which may probably reflect the direct influence of carbohydrate metabolism compensation to the kidney graft condition and also the correlation of SOD baseline & RAGE +12 month (R= - 0.70, p=0.0008), which may demonstrate the relative influence of components of "metabolic memory”. Conclusion SPKT as the way to achieve compensation of carbohydrate metabolism remains just one of factors of stable kidney graft function. The results of analysis of “metabolic memory” markers could indicate not only their direct contribution to the persistence of metabolic consequences of DM and DN, but also their possible participation in the development of recurrent nephropathy.

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Urinary Biomarkers α-GST and π-GST for Evaluation and Monitoring in Living and Deceased Donor Kidney Grafts

Journal of Clinical Medicine ◽

10.3390/jcm8111899 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1899 ◽

Cited By ~ 2

Author(s):

Shadi Katou ◽

Brigitta Globke ◽

M. Haluk Morgul ◽

Thomas Vogel ◽

Benjamin Struecker ◽

...

Keyword(s):

Kidney Transplantation ◽

Graft Function ◽

Rejection Sensitivity ◽

Deceased Donor ◽

Urine Samples ◽

Kidney Graft ◽

Donor Kidney ◽

Kidney Recipients ◽

Deceased Donor Kidney ◽

Brain Dead

The aim of this study was to analyze the value of urine α- and π-GST in monitoring and predicting kidney graft function following transplantation. In addition, urine samples from corresponding organ donors was analyzed and compared with graft function after organ donation from brain-dead and living donors. Urine samples from brain-dead (n = 30) and living related (n = 50) donors and their corresponding recipients were analyzed before and after kidney transplantation. Urine α- and π-GST values were measured. Kidney recipients were grouped into patients with acute graft rejection (AGR), calcineurin inhibitor toxicity (CNI), and delayed graft function (DGF), and compared to those with unimpaired graft function. Urinary π-GST revealed significant differences in deceased kidney donor recipients with episodes of AGR or DGF at day one after transplantation (p = 0.0023 and p = 0.036, respectively). High π-GST values at postoperative day 1 (cutoff: >21.4 ng/mg urine creatinine (uCrea) or >18.3 ng/mg uCrea for AGR or DGF, respectively) distinguished between rejection and no rejection (sensitivity, 100%; specificity, 66.6%) as well as between DGF and normal-functioning grafts (sensitivity, 100%; specificity, 62.6%). In living donor recipients, urine levels of α- and π-GST were about 10 times lower than in deceased donor recipients. In deceased donors with impaired graft function in corresponding recipients, urinary α- and π-GST were elevated. α-GST values >33.97 ng/mg uCrea were indicative of AGR with a sensitivity and specificity of 77.7% and 100%, respectively. In deceased donor kidney transplantation, evaluation of urinary α- and π-GST seems to predict different events that deteriorate graft function. To elucidate the potential advantages of such biomarkers, further analysis is warranted.

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Gene Expression Patterns in Deceased Donor Kidneys Developing Delayed Graft Function After Kidney Transplantation

Transplantation Journal ◽

10.1097/tp.0b013e318165491f ◽

2008 ◽

Vol 85 (4) ◽

pp. 626-635 ◽

Cited By ~ 25

Author(s):

Valeria R. Mas ◽

Kellie J. Archer ◽

Kenneth Yanek ◽

Catherine I. Dumur ◽

Maria I. Capparuccini ◽

...

Keyword(s):

Gene Expression ◽

Kidney Transplantation ◽

Expression Patterns ◽

Graft Function ◽

Deceased Donor ◽

Delayed Graft Function ◽

Gene Expression Patterns

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P1667ANALYSIS OF RISK FACTORS FOR CMV DISEASE IN KIDNEY TRANSPLANT PATIENTS - SINGLE CENTER STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1667 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Vladimir Hanzal ◽

Janka Slatinska ◽

Petra Hruba ◽

Ondrej Viklicky

Keyword(s):

Risk Factors ◽

Kidney Transplantation ◽

Multivariable Analysis ◽

Graft Function ◽

Kidney Graft ◽

Cmv Infection ◽

Post Transplantation ◽

Increased Risk ◽

Cmv Disease ◽

Cmv Prophylaxis

Abstract Background and Aims Cytomegalovirus (CMV) disease and infection negatively influence outcome of kidney transplantation. The aim of this retrospective study was to analyze risk factors for CMV disease and its influence on kidney graft function and survival. Method 1050 patients underwent kidney transplantation from January 2014 to December 2018 and received calcineurin inhibitor, mycophenolate mofetil and steroid-based immunosuppression. Recipients with PRA>20% received rATG while others had received basiliximab as induction. 825 out of 1050 patients (78.6%) received CMV prophylaxis (D+/R-, n=173; R+, n=652). Patients were followed up to 71 months /median 38 months/. Results CMV tissue invasive disease occurred in 49 out of 1050 patients (4.7%), while CMV infection in 87 patients (8.3%). CMV disease, but not CMV infection, had significant negative influence on graft survival at 5 years post transplantation (p=0.0029). Patients with CMV disease had significantly worse graft function at 4 years post transplantation (p<0.0001). CMV disease occurred in 31 out of 173 patients (17.9%) in D+/R- group vs. 18 out of 652 patients (2.8%) in R+ group. Incidence of CMV infection was 30/173 patients (17.3%) in D+/R- group vs. 57/652 patients (8.7%) with induction therapy. Shortening of CMV prophylaxis was found in 82 patients (9.9%). Leukopenia (≤ 2.0 x 109/L) was observed in 97 (11.7%) patients from those who received CMV prophylaxis, Its shortening significantly increased risk for both CMV infection (20,7% vs. 7.2%, p<0,0001) and CMV disease (8,5% vs. 4,2%, p=0,04). Among most significant risk factors for CMV disease in univariable analysis were CMV mismatch (OR 11, 95% CI: 5,9-20,4; p<0,0001), delayed graft function (OR 2,8, 95% CI: 1,6-5,1; p<0,0001, cadaveric donor (OR 6, 95% CI: 1,5-25,1; p=0,00013) and shortening of CMV prophylaxis (OR 2.1, 95% CI: 0,91-4,86; p=0,08). Multivariable analysis revealed as independent significant predictors of CMV disease DGF (OR 2,29, 95% CI: 1,2-4,3; p=0,01) and CMV mismatch (OR 10,8, 95% CI: 5,7-20,6; p<0.0001) in a model adjusted for type of donor, prophylaxis shortening and leukopenia. Conclusion CMV mismatch is the main independent predictor of CMV disease after kidney transplantation in multivariable analysis.

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Gene Expression Changes Are Associated With Loss of Kidney Graft Function and Interstitial Fibrosis and Tubular Atrophy: Diagnosis Versus Prediction

Transplantation Journal ◽

10.1097/tp.0b013e3182094a5a ◽

2011 ◽

Vol 91 (6) ◽

pp. 657-665 ◽

Cited By ~ 25

Author(s):

Mariano J. Scian ◽

Daniel G. Maluf ◽

Kellie J. Archer ◽

Jihee L. Suh ◽

David Massey ◽

...

Keyword(s):

Gene Expression ◽

Interstitial Fibrosis ◽

Graft Function ◽

Kidney Graft ◽

Tubular Atrophy

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Surgical and Medical Management of Tertiary Hyperparathyroidism

World Journal of Endocrine Surgery ◽

10.5005/jp-journals-10002-1033 ◽

2010 ◽

Vol 2 (3) ◽

pp. 105-109 ◽

Cited By ~ 1

Author(s):

Yoshihiro Tominaga

Keyword(s):

Clinical Trial ◽

Kidney Transplantation ◽

Cardiovascular Events ◽

Graft Function ◽

Controlled Clinical Trial ◽

Kidney Graft ◽

Common Complication ◽

Surgical Indications ◽

Tertiary Hyperparathyroidism ◽

Persistent Hyperparathyroidism

ABSTRACT Persistent hyperparathyroidism (HPT) after successful kidney transplantation (RTx) (tertiary HPT; THPT) is a common complication in patients with RTx and may affect bone disease, deterioration of graft function and cardiovascular events. Parathyroidectomy (PTx) is the most successful treatment for resolving advanced HPT in patients with THPT. However, the surgical indications for THPT and timing of the operation are problematic because hypercalcemia can be resolved spontaneously. Subtotal and total PTx with autotransplantaion are widely accepted for THPT. The evidence to know which procedure is more appropriated could not be found. Recently the deterioration of kidney graft function after PTx for THPT has been reported and hypoparathyroidism after PTx may be avoided. Recently cinacalcet has been applied for patients with THPT and the medicine can dramaticaly control HPT and hypercalcemia. Possible risks of cinacalcet are hypocalcemia and increased calciuria and the approval for THPT remains highly controversial. A large number of prospective controlled clinical trial should be required.

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