Journal of Clinical Medicine

Research

14 pages, 1434 KiB

Open AccessArticle

Aorto-Iliac Artery Calcification and Graft Outcomes in Kidney Transplant Recipients

by Stan Benjamens, Saleh Z. Alghamdi, Elsaline Rijkse, Charlotte A. te Velde-Keyzer, Stefan P. Berger, Cyril Moers, Martin H. de Borst, Riemer H. J. A. Slart, Frank J. M. F. Dor, Robert C. Minnee and Robert A. Pol

J. Clin. Med. 2021, 10(2), 325; https://doi.org/10.3390/jcm10020325 - 17 Jan 2021

Cited by 5 | Viewed by 1949

Abstract

While the association of vascular calcification with inferior patient outcomes in kidney transplant recipients is well-established, the association with graft outcomes has received less attention. With this dual-centre cohort study, we aimed to determine the clinical impact of recipient pre-transplant aorto-iliac calcification, measured [...] Read more.

While the association of vascular calcification with inferior patient outcomes in kidney transplant recipients is well-established, the association with graft outcomes has received less attention. With this dual-centre cohort study, we aimed to determine the clinical impact of recipient pre-transplant aorto-iliac calcification, measured on non-contrast enhanced computed tomography (CT)-imaging within three years prior to transplantation (2005–2018). We included 547 patients (61.4% male, age 60 (interquartile range 51–68) years), with a median follow-up of 3.1 (1.4–5.2) years after transplantation. The aorto-iliac calcification score (CaScore) was inversely associated with one-year estimated-glomerular filtration rate (eGFR) in univariate linear regression analysis (standard β −3.3 (95% CI −5.1 to −1.5, p < 0.0001), but not after adjustment for potential confounders, including donor and recipient age (p = 0.077). In multivariable Cox regression analyses, a high CaScore was associated with overall graft failure (p = 0.004) and death with a functioning graft (p = 0.002), but not with death-censored graft failure and graft function decline. This study demonstrated that pre-transplant aorto-iliac calcification is associated with one-year eGFR in univariate, but not in multivariable linear regression analyses. Moreover, this study underlines that transplantation in patients with a high CaScore does not result in earlier transplant function decline or worse death censored graft survival, although ongoing efforts for the prevention of death with a functioning graft remain essential. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

14 pages, 1068 KiB

Open AccessArticle

Progression of Interstitial Fibrosis and Tubular Atrophy in Low Immunological Risk Renal Transplants Monitored by Sequential Surveillance Biopsies: The Influence of TAC Exposure and Metabolism

by Betty Chamoun, Irina B. Torres, Alejandra Gabaldón, Joana Sellarés, Manel Perelló, Eva Castellá, Xavier Guri, Maite Salcedo, Nestor G. Toapanta, Ignacio Cidraque, Francesc Moreso and Daniel Seron

J. Clin. Med. 2021, 10(1), 141; https://doi.org/10.3390/jcm10010141 - 04 Jan 2021

Cited by 7 | Viewed by 2604

Abstract

The combination of tacrolimus (TAC) and mycophenolate is the most widely employed maintenance immunosuppression in renal transplants. Different surrogates of tacrolimus exposure or metabolism such as tacrolimus trough levels (TAC-C₀), coefficient of variation of tacrolimus (CV-TAC-C₀), time in therapeutic [...] Read more.

The combination of tacrolimus (TAC) and mycophenolate is the most widely employed maintenance immunosuppression in renal transplants. Different surrogates of tacrolimus exposure or metabolism such as tacrolimus trough levels (TAC-C₀), coefficient of variation of tacrolimus (CV-TAC-C₀), time in therapeutic range (TTR), and tacrolimus concentration dose ratio (C/D) have been associated with graft outcomes. We explore in a cohort of low immunological risk renal transplants (n = 85) treated with TAC, mycophenolate mofetil (MMF), and steroids and then monitored by paired surveillance biopsies the association between histological lesions and TAC-C₀ at the time of biopsy as well as CV-TAC-C₀, TTR, and C/D during follow up. Interstitial inflammation (i-Banff score ≥ 1) in the first surveillance biopsy was associated with TAC-C₀ (odds ratio (OR): 0.69, 95% confidence interval (CI): 0.50–0.96; p = 0.027). In the second surveillance biopsy, inflammation was associated with time below the therapeutic range (OR: 1.05 and 95% CI: 1.01–1.10; p = 0.023). Interstitial inflammation in scarred areas (i-IFTA score ≥ 1) was not associated with surrogates of TAC exposure/metabolism. Progression of interstitial fibrosis/tubular atrophy (IF/TA) was observed in 35 cases (41.2%). Multivariate regression logistic analysis showed that mean C/D (OR: 0.48; 95% CI: 0.25–0.92; p = 0.026) and IF/TA in the first biopsy (OR: 0.43, 95% CI: 0.24–0.77, p = 0.005) were associated with IF/TA progression between biopsies. A low C/D ratio is associated with IF/TA progression, suggesting that TAC nephrotoxicity may contribute to fibrosis progression in well immunosuppressed patients. Our data support that TAC exposure is associated with inflammation in healthy kidney areas but not in scarred tissue. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

14 pages, 1090 KiB

Open AccessArticle

Antihypertensive Treatment in Kidney Transplant Recipients—A Current Single Center Experience

by Ulrich Jehn, Katharina Schütte-Nütgen, Markus Strauss, Jan Kunert, Hermann Pavenstädt, Gerold Thölking, Barbara Suwelack and Stefan Reuter

J. Clin. Med. 2020, 9(12), 3969; https://doi.org/10.3390/jcm9123969 - 07 Dec 2020

Cited by 2 | Viewed by 1821

Abstract

Arterial hypertension affects the survival of the kidney graft and the cardiovascular morbidity and mortality of the recipient after kidney transplantation (KTx). Thus, antihypertensive treatment is necessary for a vast majority of these patients. Long-term data on antihypertensive drugs and their effects on [...] Read more.

Arterial hypertension affects the survival of the kidney graft and the cardiovascular morbidity and mortality of the recipient after kidney transplantation (KTx). Thus, antihypertensive treatment is necessary for a vast majority of these patients. Long-term data on antihypertensive drugs and their effects on allograft function after KTx is still limited, and further investigation is required. We retrospectively analyzed a cohort of 854 recipients who received a kidney transplant at our transplant center between 2007 and 2015 with regard to antihypertensive treatment and its influence on graft function and survival. 1-y after KTx, 95.3% patients were treated with antihypertensive therapy. Of these, 38.6% received mono- or dual-drug therapy, 38.0% received three to four drugs and 8.1% were on a regimen of ≥5 drugs. Beta-blockers were the most frequently used antihypertensive agents (68.1%). Neither the use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (51.9%) and calcium channel blockers (51.5%), nor the use the use of loop diuretics (38.7%) affected allograft survival. Arterial hypertension and the number of antihypertensive agents were associated with unfavorable allograft outcomes (each p < 0.001). In addition to the well-known risk factors of cold ischemic time and acute rejection episodes, the number of antihypertensive drugs after one year, which reflects the severity of hypertension, is a strong predictor of unfavorable allograft survival. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

12 pages, 1982 KiB

Open AccessArticle

Low Seroprevalence of SARS-CoV-2 Antibodies during Systematic Antibody Screening and Serum Responses in Patients after COVID-19 in a German Transplant Center

by Mira Choi, Friederike Bachmann, Marcel Ganesh Naik, Wiebke Duettmann, Michael Duerr, Bianca Zukunft, Tatjana Schwarz, Victor Max Corman, Lutz Liefeldt, Klemens Budde and Fabian Halleck

J. Clin. Med. 2020, 9(11), 3401; https://doi.org/10.3390/jcm9113401 - 23 Oct 2020

Cited by 11 | Viewed by 3002

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 denotes a global health issue. Data regarding COVID-19 incidence in kidney transplant recipients (KTR) are sparse. From 19 March to 19 May 2020, we performed a systematic screening for COVID-19 in KTR. Tests included [...] Read more.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 denotes a global health issue. Data regarding COVID-19 incidence in kidney transplant recipients (KTR) are sparse. From 19 March to 19 May 2020, we performed a systematic screening for COVID-19 in KTR. Tests included serum analysis for SARS-CoV-2 antibodies using S protein-based immunofluorescence, anti-SARS-CoV-2 S1 immunoglobulin G (IgG) and immunoglobulin A (IgA) enzyme-linked immunosorbent assays (ELISA), and/or quantitative reverse transcription polymerase chain reaction (qRT-PCR) from nasal-throat swabs. Outpatient serum samples from KTR with PCR confirmed COVID-19, and swab samples from recipients (+donors) undergoing kidney transplantation were analyzed. Out of 223 samples from outpatients, 13 patients were positive with solely anti-SARS-CoV-2-IgA and 3 with both anti-IgA and anti-IgG. In total, 53 patients were symptomatic in the past, but positive results could be found in both symptomatic and asymptomatic patients. After an in depth analysis using immunofluorescence and neutralization tests in 2 KTR, recent COVID-19 infection remained highly suspicious. Apart from outpatient visits, only 5 out of 2044 KTR were symptomatic and tested positive via PCR, of which 4 recovered and one died. All patients showed seroconversion during the course of the disease. This study demonstrated a low seroprevalence in a German KTR cohort, and seroconversion of IgA and IgG after COVID-19 could be demonstrated. Effective containment strategies enabled us to continue our transplant program. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

12 pages, 848 KiB

Open AccessArticle

Myocardial Infarction after Kidney Transplantation: A Risk and Specific Profile Analysis from a Nationwide French Medical Information Database

by Romain Didier, Hermann Yao, Mathieu Legendre, Jean Michel Halimi, Jean Michel Rebibou, Julien Herbert, Marianne Zeller, Laurent Fauchier and Yves Cottin

J. Clin. Med. 2020, 9(10), 3356; https://doi.org/10.3390/jcm9103356 - 19 Oct 2020

Cited by 10 | Viewed by 2106

Abstract

Introduction: Renal transplant recipients have a high peri-operative risk for cardiovascular events. The post-transplantation period also carries a risk of myocardial infarction (MI). Coronary artery disease (CAD) is a leading cause of death in these patients. We aimed to assess the risk of [...] Read more.

Introduction: Renal transplant recipients have a high peri-operative risk for cardiovascular events. The post-transplantation period also carries a risk of myocardial infarction (MI). Coronary artery disease (CAD) is a leading cause of death in these patients. We aimed to assess the risk of MI, the specific morbidity profile of MI after transplantation as well as the long-term prognosis after MI in renal transplantation (RT) patients regarding cardiovascular (CV) death and all-cause death. Methods: From a French national medical information database, all of the patients seen in French hospitals in 2013 with at least 5-years follow-up were retrospectively identified and patients without transplantation but with previous dialysis at baseline were excluded. There were 17,526 patients with RT and 3,288,857 with no RT. Results: Among these patients, 1020 in the RT group (5.8%), and 93,320 in the non-RT group (2.8%) suffered acute MI during a median follow-up of 5.4 years. After multivariable adjustment, risk of MI was higher in RT patients than in non-RT patients (HR 1.45, IC 95% 1.35–1.55). The mean age was 59.5 years for transplant patients with MI, and 70.6 years for the reference population with MI (p < 0.0001). MI patients with RT (vs. non RT patients) were more likely to have hypertension, diabetes dyslipidemia, and peripheral artery disease (76.0% vs. 48.1%, 38.7% vs. 25.2%, 33.2% vs. 23.2%, and 31.2% vs. 17.3%, respectively, p < 0.0001). Incidence of non ST-elevation MI (NSTEMI) was higher in RT patients while incidence of ST-elevation MI (STEMI) was higher in patients without RT. In unadjusted analysis, risk of all-cause death and CV death within the first month after MI were higher in patients without RT (18% vs. 11.1% p < 0.0001 and 12.3% vs. 7.8%, p < 0.0001, respectively). However, multivariable analysis indicated that risk of all-cause death was higher in patients with RT than in those with no RT (adjusted HR 1.15 IC 95% 1.03–1.28). Conclusions: MI is not an uncommon complication after RT (incidence of around 5.8% after 5 years). RT is independently associated with a 45% higher risk of MI than in patients without RT, with a predominance of NSTEMI. MI in patients with RT is independently associated with a 15% higher risk of all-cause death than that in patients with MI and no RT. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

13 pages, 1055 KiB

Open AccessArticle

Aorto-Iliac Artery Calcification Prior to Kidney Transplantation

by Stan Benjamens, Elsaline Rijkse, Charlotte A. te Velde-Keyzer, Stefan P. Berger, Cyril Moers, Martin H. de Borst, Derya Yakar, Riemer H. J. A. Slart, Frank J. M. F. Dor, Robert C. Minnee and Robert A. Pol

J. Clin. Med. 2020, 9(9), 2893; https://doi.org/10.3390/jcm9092893 - 07 Sep 2020

Cited by 14 | Viewed by 7535

Abstract

As vascular calcification is common in kidney transplant candidates, aorto-iliac vessel imaging is performed for surgical planning. The aim of the present study was to investigate whether a novel non-contrast enhanced computed tomography-based quantification technique for aorto-iliac calcification can be used for cardiovascular [...] Read more.

As vascular calcification is common in kidney transplant candidates, aorto-iliac vessel imaging is performed for surgical planning. The aim of the present study was to investigate whether a novel non-contrast enhanced computed tomography-based quantification technique for aorto-iliac calcification can be used for cardiovascular risk stratification prior to kidney transplantation. In this dual-center cohort study, we measured the aorto-iliac calcium score (CaScore) of 547 patients within three years prior to transplantation (2005–2018). During a median (interquartile range) follow-up of 3.1 (1.4, 5.2) years after transplantation, 80 (14.7%) patients died, of which 32 (40.0%) died due to cardiovascular causes, and 84 (15.5%) patients had a cardiovascular event. Kaplan-Meier survival curves showed significant differences between the CaScore tertiles for cumulative overall-survival (Log-rank test p < 0.0001), cardiovascular survival (p < 0.0001), and cardiovascular event-free survival (p < 0.001). In multivariable Cox regression, the aorto-iliac CaScore was associated with all-cause mortality (hazard ratio 1.53, 95%CI 1.14–2.06, p = 0.005), cardiovascular mortality (2.04, 1.20–3.45, p = 0.008), and cardiovascular events (1.35, 1.01–1.80, p = 0.042). These independent associations of the aorto-iliac CaScore with the outcome measures can improve the identification of patients at risk for (cardiovascular) death and those who could potentially benefit from stringent cardiovascular monitoring to improve their prognosis after transplantation. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Graphical abstract

15 pages, 1993 KiB

Open AccessArticle

Analysis of Risk Factors and Long-Term Outcomes in Kidney Transplant Patients with Identified Lymphoceles

by Lukas J. Lehner, Arnim Hohberger, Lisanne Marschke, Nils Lachmann, Robert Peters, Frank Friedersdorff, Dmytro Khadzhynov, Fabian Halleck, Klemens Budde, Oliver Staeck and Michael Duerr

J. Clin. Med. 2020, 9(9), 2841; https://doi.org/10.3390/jcm9092841 - 02 Sep 2020

Cited by 6 | Viewed by 2015

Abstract

The collection of lymphatic fluids (lymphoceles) is a frequent adverse event following renal transplantation. A variety of surgical and medical factors has been linked to this entity, but reliable data on risk factors and long-term outcomes are lacking. This retrospective single-center study included [...] Read more.

The collection of lymphatic fluids (lymphoceles) is a frequent adverse event following renal transplantation. A variety of surgical and medical factors has been linked to this entity, but reliable data on risk factors and long-term outcomes are lacking. This retrospective single-center study included 867 adult transplant recipients who received a kidney transplantation from 2006 to 2015. We evaluated for patient and graft survival, rejection episodes, or detectable donor-specific antibodies (dnDSA) in patients with identified lymphoceles in comparison to controls. We identified 305/867 (35.2%) patients with lymphocele formation, of whom 72/867 (8.3%) needed intervention. Multivariate analysis identified rejection episode as an independent risk factor (OR 1.61, CI 95% 1.17–2.21, p = 0.003) for lymphocele formation, while delayed graft function was independently associated with symptomatic lymphoceles (OR 1.9, CI 95% 1.16–3.12, p = 0.011). Interestingly, there was no difference in detectable dnDSA between groups with a similar graft and patient survival in all groups after 10 years. Lymphoceles frequently occur after transplantation and were found to be independently associated with rejection episodes, while symptomatic lymphoceles were associated with delayed graft function in our cohort. As both are inflammatory processes, they might play a causative role in the formation of lymphoceles. However, development or intervention of lymphoceles did not lead to impaired graft survival in the long-term. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

12 pages, 1941 KiB

Open AccessArticle

Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients

by Niamh Nolan, Katherine Valdivieso, Rekha Mani, Joshua Y. C. Yang, Reuben D. Sarwal, Phoebe Katzenbach, Kavita Chalasani, Donna Hongo, Gladys Lugtu, Corinne Mark, Edna Chen, Reggie Nijor, David Savoca, David S. Wexler, Todd Whitson, Shih-Jwo Huang, Lucy H. Lu, Robert J. X. Zawada, Evangelos Hytopoulos and Minnie M. Sarwal

J. Clin. Med. 2020, 9(8), 2325; https://doi.org/10.3390/jcm9082325 - 22 Jul 2020

Cited by 18 | Viewed by 2898

Abstract

In this clinical validation study, we developed and validated a urinary Q-Score generated from the quantitative test QSant, formerly known as QiSant, for the detection of biopsy-confirmed acute rejection in kidney transplants. Using a cohort of 223 distinct urine samples collected from three [...] Read more.

In this clinical validation study, we developed and validated a urinary Q-Score generated from the quantitative test QSant, formerly known as QiSant, for the detection of biopsy-confirmed acute rejection in kidney transplants. Using a cohort of 223 distinct urine samples collected from three independent sites and from both adult and pediatric renal transplant patients, we examined the diagnostic utility of the urinary Q-Score for detection of acute rejection in renal allografts. Statistical models based upon the measurements of the six QSant biomarkers (cell-free DNA, methylated-cell-free DNA, clusterin, CXCL10, creatinine, and total protein) generated a renal transplant Q-Score that reliably differentiated stable allografts from acute rejections in both adult and pediatric renal transplant patients. The composite Q-Score was able to detect both T cell-mediated rejection and antibody-mediated rejection patients and differentiate them from stable non-rejecting patients with a receiver–operator characteristic curve area under the curve of 99.8% and an accuracy of 98.2%. Q-Scores < 32 indicated the absence of active rejection and Q-Scores ≥ 32 indicated an increased risk of active rejection. At the Q-Score cutoff of 32, the overall sensitivity was 95.8% and specificity was 99.3%. At a prevalence of 25%, positive and negative predictive values for active rejection were 98.0% and 98.6%, respectively. The Q-Score also detected subclinical rejection in patients without an elevated serum creatinine level but identified by a protocol biopsy. This study confirms that QSant is an accurate and quantitative measurement suitable for routine monitoring of renal allograft status. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

10 pages, 1302 KiB

Open AccessArticle

Number of Regularly Prescribed Drugs and Intrapatient Tacrolimus Trough Levels Variability in Stable Kidney Transplant Recipients

by Piotr Giza, Rafał Ficek, Tomasz Dwulit, Jerzy Chudek, Iwona Woźniak, Andrzej Więcek and Aureliusz Kolonko

J. Clin. Med. 2020, 9(6), 1926; https://doi.org/10.3390/jcm9061926 - 19 Jun 2020

Cited by 5 | Viewed by 1974

Abstract

High intra-patient variability (IPV) of tacrolimus levels is associated with poor long-term outcome after transplantation. We aimed to evaluate whether the number of regularly prescribed medications is associated with the tacrolimus IPV. We have studied 152 kidney transplant recipients (KTRs) with mean post-transplant [...] Read more.

High intra-patient variability (IPV) of tacrolimus levels is associated with poor long-term outcome after transplantation. We aimed to evaluate whether the number of regularly prescribed medications is associated with the tacrolimus IPV. We have studied 152 kidney transplant recipients (KTRs) with mean post-transplant time of 6.0 ± 3.1 years. The coefficient of variation (CV) as a measure of IPV was calculated in each individual patient. Data concerning the type and number of currently prescribed medications were collected. The participants were divided into four groups, based on the number of regularly prescribed drugs (≤3, 4–6, 7–9, ≥10 drugs, respectively). There was an increasing trend for median CV, proportional to the increasing number of medications [group 1: 0.11 (interquartile range, 0.08–0.14), group 2: 0.14 (0.01–0.17), group 3: 0.17 (0.14–0.23), group 4: 0.17 (0.15–0.30); p value for trend = 0.001]. Stepwise backward multivariate regression analysis revealed that the number of medications [partial correlation coefficient (r_partial) = 0.503, p < 0.001] independently influenced the tacrolimus IPV. Concomitant steroid or diuretics use increased IPV only in Advagraf-treated KTRs, whereas proton-pump inhibitor or statin use increased IPV in the Prograf group but not in the Advagraf group. A large number of concomitant medications significantly increases the tacrolimus IPV in stable KTRs. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

13 pages, 1280 KiB

Open AccessArticle

The effect of Maintenance Treatment with Twice-daily or Prolonged Once-daily Tacrolimus Formulation on Visual Evoked Potentials in Stable Kidney Transplant Recipients

by Aureliusz Kolonko, Małgorzata Jurys, Sebastian Sirek, Tomasz Dwulit, Dorota Pojda-Wilczek and Andrzej Więcek

J. Clin. Med. 2020, 9(6), 1827; https://doi.org/10.3390/jcm9061827 - 11 Jun 2020

Cited by 3 | Viewed by 1991

Abstract

In kidney transplant recipients (KTRs), uraemia-induced central nervous system damage partly subsides, while the long-lasting exposure to tacrolimus may cause pathologic visual evoked potentials (VEP) findings, which have not been investigated yet. Thus, the aim of the present study was to assess the [...] Read more.

In kidney transplant recipients (KTRs), uraemia-induced central nervous system damage partly subsides, while the long-lasting exposure to tacrolimus may cause pathologic visual evoked potentials (VEP) findings, which have not been investigated yet. Thus, the aim of the present study was to assess the effect of tacrolimus maintenance treatment on bioelectrical function of optic nerves in stable KTRs. Sixty-five stable KTRs were enrolled, including 30 patients treated with twice-daily (Prograf) and 35 patients treated with prolonged once-daily (Advagraf) tacrolimus formulation. In all patients, pattern and flash VEP measurements were performed. Tacrolimus dosing and exposure were also analyzed. Overall, 129 eyes were analyzed. In pattern VEP, both (1°) and (15′) latencies of P100 waves were significantly longer, whereas (1°) and (15′) amplitudes were lower in the Advagraf group as compared with the Prograf group. Multivariate regression analyses revealed that the use of Advagraf (vs. Prograf) was independently associated with longer (1°) and (15′) P100 latencies and lower corresponding amplitudes, whereas log tacrolimus daily dose was only related to amplitudes in a whole study group. In flash VEP, log tacrolimus trough level was associated with negative changes in P2 wave amplitude irrespective of tacrolimus formulation, whereas its association with P2 latency was observed only in the Prograf group. Both the type of tacrolimus formulation and drug exposure influenced the VEP parameters in stable KTRs. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

16 pages, 1662 KiB

Open AccessArticle

Multiparametric Assessment of Changes in Renal Tissue after Kidney Transplantation with Quantitative MR Relaxometry and Diffusion-Tensor Imaging at 3 T

by Lisa C. Adams, Keno K. Bressem, Sonja Scheibl, Max Nunninger, Andre Gentsch, Ute L. Fahlenkamp, Kai-Uwe Eckardt, Bernd Hamm and Marcus R. Makowski

J. Clin. Med. 2020, 9(5), 1551; https://doi.org/10.3390/jcm9051551 - 21 May 2020

Cited by 17 | Viewed by 2868

Abstract

Background: Magnetic resonance relaxometry (MRR) offers highly reproducible pixel-wise parametric maps of T1 and T2 relaxation times, reflecting specific tissue properties, while diffusion-tensor imaging (DTI) is a promising technique for the characterization of microstructural changes, depending on the directionality of molecular motion. Both [...] Read more.

Background: Magnetic resonance relaxometry (MRR) offers highly reproducible pixel-wise parametric maps of T1 and T2 relaxation times, reflecting specific tissue properties, while diffusion-tensor imaging (DTI) is a promising technique for the characterization of microstructural changes, depending on the directionality of molecular motion. Both MMR and DTI may be used for non-invasive assessment of parenchymal changes caused by kidney injury or graft dysfunction. Methods: We examined 46 patients with kidney transplantation and 16 healthy controls, using T1/T2 relaxometry and DTI at 3 T. Twenty-two early transplants and 24 late transplants were included. Seven of the patients had prior renal biopsy (all of them dysfunctional allografts; 6/7 with tubular atrophy and 7/7 with interstitial fibrosis). Results: Compared to healthy controls, T1 and T2 relaxation times in the renal parenchyma were increased after transplantation, with the highest T1/T2 values in early transplants (T1: 1700 ± 53 ms/T2: 83 ± 6 ms compared to T1: 1514 ± 29 ms/T2: 78 ± 4 ms in controls). Medullary and cortical ADC/FA values were decreased in early transplants and highest in controls, with medullary FA values showing the most pronounced difference. Cortical renal T1, mean medullary FA and corticomedullary differentiation (CMD) values correlated best with renal function as measured by eGFR (cortical T1: r = −0.63, p < 0.001; medullary FA: r = 0.67, p < 0.001; FA CMD: r = 0.62, p < 0.001). Mean medullary FA proved to be a significant predictor for tubular atrophy (p < 0.001), while cortical T1 appeared as a significant predictor of interstitial fibrosis (p = 0.003). Conclusion: Cortical T1, medullary FA, and FA CMD might serve as new imaging biomarkers of renal function and histopathologic microstructure. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Graphical abstract

18 pages, 3666 KiB

Open AccessArticle

Prognostic Value of Growth Differentiation Factor 15 in Kidney Donors and Recipients

by Ulrich Jehn, Katharina Schütte-Nütgen, Ute Henke, Joachim Bautz, Hermann Pavenstädt, Barbara Suwelack and Stefan Reuter

J. Clin. Med. 2020, 9(5), 1333; https://doi.org/10.3390/jcm9051333 - 03 May 2020

Cited by 12 | Viewed by 2257

Abstract

Growth differentiation factor-15 (GDF15) is associated with inflammatory conditions, chronic kidney disease, cardiovascular disease and mortality. There is very limited data on GDF15 after kidney donation and transplantation. We analyzed serum samples of patients who donated a kidney (54 living donors) or who [...] Read more.

Growth differentiation factor-15 (GDF15) is associated with inflammatory conditions, chronic kidney disease, cardiovascular disease and mortality. There is very limited data on GDF15 after kidney donation and transplantation. We analyzed serum samples of patients who donated a kidney (54 living donors) or who underwent kidney transplantation (104 recipients) at the University Hospital of Münster (Germany) between 2013 and 2015, for GDF15 levels immediately prior and one year after surgery. GDF15 levels were significantly elevated in end-stage renal disease patients compared to healthy individuals (2844 (IQR 2087, 3361) pg/ml vs. 384 (IQR 307, 487) pg/ml, p < 0.001). GDF15 was strongly associated with the dialysis vintage. While kidney transplantation led to a significant decrease of GDF15 (913 (IQR 674, 1453) pg/ml, p < 0.001), kidney donation caused a moderate increase of GDF15 (510 (IQR 420, 626), p < 0.001) one year after surgery. GDF15 levels remained significantly higher in recipients and kidney donors than in healthy controls (735 (IQR 536, 1202) pg/ml vs. 384 (IQR 307, 487) pg/ml, p < 0.001). GDF15 is increased in patients with kidney disease and is associated with dialysis vintage. Given its decrease after transplantation and its increase after uni-nephrectomy, GDF15 might be a marker of kidney function. However, since it correlates only to the eGFR in transplanted patients it may indicate chronic kidney disease. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

16 pages, 1231 KiB

Open AccessArticle

Outcome Comparison between Low-Dose Rabbit Anti-Thymocyte Globulin and Basiliximab in Low-Risk Living Donor Kidney Transplantation

by Sang Jin Kim, Jinsoo Rhu, Heejin Yoo, Kyunga Kim, Kyo Won Lee and Jae Berm Park

J. Clin. Med. 2020, 9(5), 1320; https://doi.org/10.3390/jcm9051320 - 02 May 2020

Cited by 13 | Viewed by 3537

Abstract

The objective of this study was to compare outcomes between basiliximab and low-dose r-ATG in living donor kidney transplantation recipients with low immunological risk. Patients in the low-dose r-ATG group received 1.5 mg/kg of r-ATG for 3 days (total 4.5 mg/kg). Graft survival, [...] Read more.

The objective of this study was to compare outcomes between basiliximab and low-dose r-ATG in living donor kidney transplantation recipients with low immunological risk. Patients in the low-dose r-ATG group received 1.5 mg/kg of r-ATG for 3 days (total 4.5 mg/kg). Graft survival, patient survival, acute rejection, de novo donor specific antibody (DSA), estimated glomerular filtration rate (e-GFR) changes, and infection status were compared. Among 268 patients, 37 received r-ATG, and 231 received basiliximab. There was no noticeable difference in the graft failure rate (r-ATG vs. basiliximab: 2.7% vs. 4.8%) or rejection (51.4% vs. 45.9%). de novo DSA was more frequent in the r-ATG group (11.4% vs. 2.4%, p = 0.017). e-GFR changes did not differ noticeably between groups. Although most infections showed no noticeable differences between groups, more patients in the r-ATG group had cytomegalovirus (CMV) antigenemia and serum polyomavirus (BK virus) (73.0% vs. 51.9%, p = 0.032 in CMV; 37.8% vs. 15.6%, p = 0.002 in BK), which did not aggravate graft failure. Living donor kidney transplantation patients who received low-dose r-ATG and patients who received basiliximab showed comparable outcomes in terms of graft survival, function, and overall infections. Although CMV antigenemia, BK viremia were more frequent in the r-ATG group, those factors didn’t change the graft outcomes. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

14 pages, 1627 KiB

Open AccessArticle

Group IIA Secretory Phospholipase A₂ Predicts Graft Failure and Mortality in Renal Transplant Recipients by Mediating Decreased Kidney Function

by Wijtske Annema, Jan Freark de Boer, Arne Dikkers, Lidiya G. Dimova, Markus van der Giet, Stephan J.L. Bakker and Uwe J.F. Tietge

J. Clin. Med. 2020, 9(5), 1282; https://doi.org/10.3390/jcm9051282 - 29 Apr 2020

Cited by 3 | Viewed by 2135

Abstract

The acute phase protein group IIA secretory phospholipase A₂ (sPLA₂-IIA) has intrinsic proatherosclerotic properties. The present prospective cohort study investigated whether plasma sPLA₂-IIA associates with graft failure, cardiovascular, and all-cause mortality in renal transplant recipients (RTRs), patients with [...] Read more.

The acute phase protein group IIA secretory phospholipase A₂ (sPLA₂-IIA) has intrinsic proatherosclerotic properties. The present prospective cohort study investigated whether plasma sPLA₂-IIA associates with graft failure, cardiovascular, and all-cause mortality in renal transplant recipients (RTRs), patients with accelerated atherosclerosis formation both systemically and within the graft. In 511 RTRs from a single academic center with stable graft function >1 year, baseline plasma sPLA₂-IIA was determined by ELISA. Primary end points were death-censored graft failure and mortality (median follow-up, 7.0 years). Baseline sPLA₂-IIA was higher in RTRs than in healthy controls (median 384 ng/dL (range 86–6951) vs. 185 ng/dL (range 104–271), p < 0.001). Kaplan–Meier analysis demonstrated increased risk for graft failure (p = 0.002), as well as cardiovascular (p < 0.001) and all-cause mortality (p < 0.001), with increasing sPLA₂-IIA quartiles. Cox regression showed strong associations of sPLA₂-IIA with increased risks of graft failure (hazard ratio (HR) = 1.42 (1.11–1.83), p = 0.006), as well as cardiovascular (HR = 1.48 (1.18−1.85), p = 0.001) and all-cause mortality (HR = 1.39 (1.17−1.64), p < 0.001), dependent on parameters of kidney function. Renal function during follow-up declined faster in RTRs with higher baseline sPLA₂-IIA levels. In RTRs, sPLA₂-IIA is a significant predictive biomarker for chronic graft failure, as well as overall and cardiovascular disease mortality dependent on kidney function. This dependency is conceivably explained by sPLA₂-IIA impacting negatively on kidney function. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

17 pages, 3804 KiB

Open AccessArticle

Long-Term Redistribution of Peripheral Lymphocyte Subpopulations after Switching from Calcineurin to mTOR Inhibitors in Kidney Transplant Recipients

by Laura Llinàs-Mallol, Dolores Redondo-Pachón, Dàlia Raïch-Regué, María José Pérez-Sáez, José Yélamos, Xavier Duran, Anna Faura, Miguel López-Botet, Julio Pascual and Marta Crespo

J. Clin. Med. 2020, 9(4), 1088; https://doi.org/10.3390/jcm9041088 - 11 Apr 2020

Cited by 5 | Viewed by 2645

Abstract

Classical immunosuppression based on steroids, calcineurin inhibitors, and mycophenolate results in several unwanted effects and unsatisfactory long-term outcomes in kidney transplantation (KT). New immunosuppressors search for fewer adverse events and increased graft survival but may have a distinct impact on graft function and [...] Read more.

Classical immunosuppression based on steroids, calcineurin inhibitors, and mycophenolate results in several unwanted effects and unsatisfactory long-term outcomes in kidney transplantation (KT). New immunosuppressors search for fewer adverse events and increased graft survival but may have a distinct impact on graft function and immunological biomarkers according to their mechanism of action. This prospective study evaluates the immunological effect of tacrolimus to serine/threonine protein kinase mechanistic target of rapamycin inhibitors (mTORi) conversion in 29 KT recipients compared with 16 controls maintained on tacrolimus. We evaluated renal function, human leukocyte antigen (HLA) antibodies and peripheral blood lymphocyte subsets at inclusion and at 3, 12, and 24 months later. Twenty immunophenotyped healthy subjects served as reference. Renal function remained stable in both groups with no significant change in proteinuria. Two patients in the mTORi group developed HLA donor-specific antibodies and none in the control group (7% vs. 0%, p = 0.53). Both groups showed a progressive increase in regulatory T cells, more prominent in patients converted to mTORi within the first 18 months post-KT (p < 0.001). All patients showed a decrease in naïve B cells (p < 0.001), excepting those converted to mTORi without receiving steroids (p = 0.31). Transitional B cells significantly decreased in mTORi patients (p < 0.001), independently of concomitant steroid treatment. Finally, CD56^bright and CD94/NK group 2 member A receptor positive (NKG2A⁺) Natural Killer (NK) cell subsets increased in mTORi- compared to tacrolimus-treated patients (both p < 0.001). Patients switched to mTORi displayed a significant redistribution of peripheral blood lymphocyte subpopulations proposed to be associated with graft outcomes. The administration of steroids modified some of these changes. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

12 pages, 540 KiB

Open AccessArticle

Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients

by Anna van der Veen, Isidor Minović, Martijn van Faassen, Antόnio W. Gomes-Neto, Stefan P. Berger, Stephan J. L. Bakker and Ido P. Kema

J. Clin. Med. 2020, 9(2), 525; https://doi.org/10.3390/jcm9020525 - 14 Feb 2020

Cited by 2 | Viewed by 2688

Abstract

Melatonin is a multifaceted hormone which rises upon the onset of darkness. Pineal synthesis of melatonin is known to be disturbed in patients with end-stage renal disease, but it is not known if its production is restored to normal after successful renal transplantation. [...] Read more.

Melatonin is a multifaceted hormone which rises upon the onset of darkness. Pineal synthesis of melatonin is known to be disturbed in patients with end-stage renal disease, but it is not known if its production is restored to normal after successful renal transplantation. We hypothesized that urinary excretion of 6-sulfatoxymelatonin, the major metabolite of melatonin, is lower in renal transplant recipients (RTRs) compared to healthy controls and that this is associated with excess mortality. Urinary 6-sulfatoxymelatonin was measured via LC-MS/MS in 701 stable outpatient RTRs and 285 healthy controls. Median urinary 6-sulfatoxymelatonin in RTR was 13.2 nmol/24 h, which was 47% lower than in healthy controls. Urinary 6-sufatoxymelatonin appeared undetectable in the majority of 36 RTRs with diabetic nephropathy as primary renal disease. Therefore, this subgroup was excluded from further analyses. Of the remaining 665 RTRs, during 5.4 years of follow-up, 110 RTRs died, of whom 38 died due to a cardiovascular cause. In Cox-regression analyses, urinary 6-sulfatoxymelatonin was significantly associated with all-cause mortality (0.60 (0.44–0.81), p = 0.001) and cardiovascular mortality (0.49 (0.29–0.84), p = 0.009), independent of conventional risk factors and kidney function parameters. Based on these results, evaluation and management of melatonin metabolism could be considered for improvement of long-term outcomes in RTRs. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

16 pages, 3613 KiB

Open AccessArticle

Cytomegalovirus Viremia after Living and Deceased Donation in Kidney Transplantation

by Ulrich Jehn, Katharina Schütte-Nütgen, Joachim Bautz, Hermann Pavenstädt, Barbara Suwelack, Gerold Thölking, Hauke Heinzow and Stefan Reuter

J. Clin. Med. 2020, 9(1), 252; https://doi.org/10.3390/jcm9010252 - 17 Jan 2020

Cited by 9 | Viewed by 3373

Abstract

Despite screening, effective anti-viral drugs and risk-balanced prophylaxis, cytomegalovirus (CMV) remains a major cause of morbidity in transplant patients. The objective of this study was to retrospectively analyze the risk factors associated with CMV viremia after kidney transplantation in a large European cohort [...] Read more.

Despite screening, effective anti-viral drugs and risk-balanced prophylaxis, cytomegalovirus (CMV) remains a major cause of morbidity in transplant patients. The objective of this study was to retrospectively analyze the risk factors associated with CMV viremia after kidney transplantation in a large European cohort with standardized valganciclovir prophylaxis in the present era. A special focus was placed on the comparison of living and postmortal donation. We conducted a longitudinal observational study involving 723 adult patients with a total of 3292 patient-years who were transplanted at our center between 2007 and 2015. Valganciclovir prophylaxis was administered over 100 days for CMV+ donors (D) or recipients (R), over 200 days for D+/R−, and none in D−/R−. A CMV+ donor, rejection episodes, and deceased donor transplantation were identified to be associated with increased incidences of CMV viremia. Although we did not find a reduced overall survival rate for patients with CMV viremia, it was associated with worse graft function. Since we observed a relevant number of CMV infections despite prescribing valganciclovir prophylaxis, a pre-emptive strategy in patients with (suspected) adherence restrictions could be favored. Our data can help transplant physicians educate their patients about their individual CMV risk and choose the most appropriate CMV treatment approach. Full article

(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Clinical Complications after Kidney Transplantation

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issue

Published Papers (17 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI