The effect of kidney transplantation from living and deceased-donors to conventional and novel biomarkers of cardiovascular disease

Background. Cardiovascular disease remains the leading cause of death after kidney transplantation. Notably, cardiovascular risk is increased in the early post-transplant period, especially in kidney transplant recipients from deceased compared to those of living donors.Methods. In this prospective study we evaluated proprotein convertase subtilisin/kexin type 9 (PCSK9), a newly recognized biomarker of cardiovascular risk and interleukin (IL)-6, a biomarker of inflammation, in the early post-transplant period. A total of eighty-three (83) patients with end-stage renal disease (ESRD) were enrolled. Ten out of them remained on the waiting-list and served as control group. Seventy-three patients were transplanted, half of them from a living and the others from a deceased donor. PCSK9 and IL-6 were assessed pre-transplantation (day 0), at 1 month and at 6 months post-transplantation. Results. We observed an increase in PCSK9 levels after transplantation that persisted for 6 months (p<0.001). During the same period, IL-6 levels were significantly reduced. There was no correlation between PCSK9 and IL-6 levels during follow-up while differences were observed between living and deceased-donor recipients both in the levels of PCSK9 and in the other inflammatory biomarkers. Delayed graft function (DGF) was altered in relation to IL-6 levels in deceased-donor transplants. Conclusions. Notably, biomarkers of systemic inflammation are improved early after transplantation, especially in living-donor recipients, while PCSK9 still remains increased. The period after transplantation is crucial since any kidney injury during this time can affect long-term outcome. Early interventions could probably be beneficial for long-term transplant and recipient outcomes.Σκοπός: Τα καρδιαγγειακά νοσήματα αποτελούν την κύρια αιτία θνητότητας μετά από μεταμόσχευση νεφρού. Στην πρώιμη μεταμοσχευτική περίοδο ο κίνδυνος είναι μεγαλύτερος, ειδικά στους λήπτες μοσχευμάτων από αποβιώσαντα δότη συγκριτικά με αυτούς από ζώντα δότη. Υλικό & Μέθοδος: Πρόκειται για προοπτική μελέτη παρακολούθησης της Proprotein convertase subtilisin/kexintype 9 (PCSK9), ενός πρόσφατα αναγνωρισμένου βιοδείκτη καρδιαγγειακού κινδύνου και της Ιντερλευκίνης (IL)-6, ενός βιοδείκτη φλεγμονής, στην πρώιμη μεταμοσχευτική περίοδο. Συνολικά στη μελέτη συμπεριελήφθησαν 83 ασθενείς με χρόνια νεφρική νόσο τελικού σταδίου. Δέκα από αυτούς παρέμειναν στο μητρώο αναμονής για μεταμόσχευση και χρησίμευσαν σαν ομάδα ελέγχου, ενώ εβδομήντα τρεις ασθενείς υποβλήθηκαν σε μεταμόσχευση νεφρού, οι μισοί περίπου από ζώντα και οι υπόλοιποι από αποβιώσαντα δότη. Οι τιμές της PCSK9 και της IL-6 αξιολογήθηκαν πριν από τη μεταμόσχευση (ημέρα 0), 1 μήνα και 6 μήνες μετά τη μεταμόσχευση νεφρού. Αποτελέσματα: Υπήρξε σημαντική αύξηση των επιπέδων της PCSK9 μετά από τη μεταμόσχευση νεφρού που παρέμεινε αυξημένη τους πρώτους 6 μήνες (p <0,001). Κατά την ίδια χρονική περίοδο, τα επίπεδα της IL-6 μειώθηκαν σημαντικά. Δεν υπήρξε στατιστικά σημαντική συσχέτιση μεταξύ των επιπέδων PCSK9 και IL-6 κατά τη διάρκεια της παρακολούθησης, ενώ παρατηρήθηκαν διαφορές μεταξύ των μεταμοσχευμένων από ζώντα και αποβιώσαντα δότη, τόσο στα επίπεδα της PCSK9, όσο και στους άλλους φλεγμονώδεις βιοδείκτες. Η καθυστερημένη λειτουργία του μοσχεύματος (DGF) συσχετίστηκε με τα επίπεδα της IL-6 στους μεταμοσχευμένους από αποβιώσαντα δότη. Συμπέρασματα: Την άμεση μεταμοσχευτική περίοδο οι φλεγμονώδεις βιοδείκτες παρουσιάζουν μείωση, ειδικά στους μεταμοσχευμένους από ζώντα δότη, ενώ τα επίπεδα της PCSK9 παραμένουν υψηλά,. Η περίοδος αυτή είναι ιδιαίτερης σημασίας, αφού οι μεταβολές που συμβαίνουν στο νεφρό μπορεί να επηρεάσουν τα μακροχρόνια αποτελέσματα της μεταμόσχευσης. Πρώιμες θεραπευτικές φαρμακευτικές παρεμβάσεις πιθανόν να αποδειχθούν ωφέλιμες για τους ασθενείς αυτούς

Η επίδραση της μεταμόσχευσης νεφρού από ζώντες και αποβιώσαντες δότες σε καθιερωμένους και νεότερους βιοδείκτες καρδιαγγειακού κινδύνου

Σκοπός: Τα καρδιαγγειακά νοσήματα αποτελούν την κύρια αιτία θνητότητας μετά από μεταμόσχευση νεφρού. Στην πρώιμη μεταμοσχευτική περίοδο ο κίνδυνος είναι μεγαλύτερος, ειδικά στους λήπτες μοσχευμάτων από αποβιώσαντα δότη συγκριτικά με αυτούς από ζώντα δότη. Υλικό &amp; Μέθοδος: Πρόκειται για προοπτική μελέτη παρακολούθησης της Proprotein convertase subtilisin/kexintype 9 (PCSK9), ενός πρόσφατα αναγνωρισμένου βιοδείκτη καρδιαγγειακού κινδύνου και της Ιντερλευκίνης (IL)-6, ενός βιοδείκτη φλεγμονής, στην πρώιμη μεταμοσχευτική περίοδο. Συνολικά στη μελέτη συμπεριελήφθησαν 83 ασθενείς με χρόνια νεφρική νόσο τελικού σταδίου. Δέκα από αυτούς παρέμειναν στο μητρώο αναμονής για μεταμόσχευση και χρησίμευσαν σαν ομάδα ελέγχου, ενώ εβδομήντα τρείς ασθενείς υποβλήθηκαν σε μεταμόσχευση νεφρού, οι μισοί περίπου από ζώντα και οι υπόλοιποι από αποβιώσαντα δότη. Οι τιμές της PCSK9 και της IL-6 αξιολογήθηκαν πριν από τη μεταμόσχευση (ημέρα 0), 1 μήνα και 6 μήνες μετά τη μεταμόσχευση νεφρού. Αποτελέσματα: Υπήρξε σημαντική αύξηση των επιπέδων της PCSK9 μετά από τη μεταμόσχευση νεφρού που παρέμεινε αυξημένη τους πρώτους 6 μήνες (p &lt;0,001). Κατά την ίδια χρονική περίοδο, τα επίπεδα της IL-6 μειώθηκαν σημαντικά. Δεν υπήρξε στατιστικά σημαντική συσχέτιση μεταξύ των επιπέδων PCSK9 και IL-6 κατά τη διάρκεια της παρακολούθησης, ενώ παρατηρήθηκαν διαφορές μεταξύ των μεταμοσχευμένων από ζώντα και αποβιώσαντα δότη, τόσο στα επίπεδα της PCSK9, όσο και στους άλλους φλεγμονώδεις βιοδείκτες. Η καθυστερημένη λειτουργία του μοσχεύματος (DGF) συσχετίστηκε με τα επίπεδα της IL-6 στους μεταμοσχευμένους από αποβιώσαντα δότη. Συμπέρασματα: Την άμεση μεταμοσχευτική περίοδο οι φλεγμονώδεις βιοδείκτες παρουσιάζουν μείωση, ειδικά στους μεταμοσχευμένους από ζώντα δότη, ενώ τα επίπεδα της PCSK9 παραμένουν υψηλά,. Η περίοδος αυτή είναι ιδιαίτερης σημασίας, αφού οι μεταβολές που συμβαίνουν στο νεφρό μπορεί να επηρεάσουν τα μακροχρόνια αποτελέσματα της μεταμόσχευσης. Πρώιμες θεραπευτικές φαρμακευτικές παρεμβάσεις πιθανόν να αποδειχθούν ωφέλιμες για τους ασθενείς αυτούς.Background. Cardiovascular disease remains the leading cause of death after kidney transplantation. Notably, cardiovascular risk is increased in the early post-transplant period, especially in kidney transplant recipients from deceased compared to those of living donors. Methods. In this prospective study we evaluated proprotein convertase subtilisin/kexin type 9 (PCSK9), a newly recognized biomarker of cardiovascular risk and interleukin (IL)-6, a biomarker of inflammation, in the early post-transplant period. A total of eighty-three (83) patients with end-stage renal disease (ESRD) were enrolled. Ten out of them remained on the waiting-list and served as control group. Seventy-three patients were transplanted, half of them from a living and the others from a deceased donor. PCSK9 and IL-6 were assessed pre-transplantation (day 0), at 1 month and at 6 months post-transplantation. Results. We observed an increase in PCSK9 levels after transplantation that persisted for 6 months (p&lt;0.001). During the same period, IL-6 levels were significantly reduced. There was no correlation between PCSK9 and IL-6 levels during follow-up while differences were observed between living and deceased-donor recipients both in the levels of PCSK9 and in the other inflammatory biomarkers. Delayed graft function (DGF) was altered in relation to IL-6 levels in deceased-donor transplants. Conclusions. Notably, biomarkers of systemic inflammation are improved early after transplantation, especially in living-donor recipients, while PCSK9 still remains increased. The period after transplantation is crucial since any kidney injury during this time can affect long-term outcome. Early interventions could probably be beneficial for long-term transplant and recipient outcomes

Therapeutic Options for Recurrence of Primary Focal Segmental Glomerulonephritis (FSGS) in the Renal Allograft: Single-Center Experience

Focal Segmental Glomerulosclerosis (FSGS) recurrence after kidney transplantation (KTx) is relatively frequent and is associated with poor graft survival. The aim of this study was to investigate which management strategies were associated with better outcomes in our cohort of KTx recipients with primary FSGS. We retrospectively collected data on patients with primary FSGS who received a KTx between 1993 and 2019. A history of biopsy proven FSGS in native kidneys and new onset of significant proteinuria early post-KTx led to the diagnosis of recurrence, which was confirmed by graft biopsy. From 1993 to 2019 we performed 46 KTxs in patients with primary FSGS. We identified 26 episodes of recurrence in 25 patients, 67% of them occurring in males. They were younger at the time of KTx (33.8 vs. 41.1 years old, p = 0.067) and had progressed to end stage renal disease (ESRD) faster after FSGS diagnosis (61.4 vs. 111.2 months, p = 0.038), while they were less likely to have received prophylactic plasmapheresis (61.5% vs. 90%, p = 0.029). 76.7% of recurrences were found early, after a median of 0.5 months (IQR 0.1–1) with a median proteinuria was 8.5 (IQR 4.9–11.9) g/day. All patients with recurrence were treated with plasmapheresis, while 8 (30.7%) additionally received rituximab, 1 (3.8%) abatacept, and 4 (15.4%) ACTH. 7 (27%) patients experienced complete and 11 (42.3%) partial remission after a mean time of 3 (±1.79) and 4.4 (±2.25) months, respectively. Prognosis was worse for patients who experienced a recurrence. Eleven (42.3%) patients lost their graft from FSGS in a median time of 33 (IQR 17.5–43.3) months. In this series of patients, primary FSGS recurred frequently after KTx. Prophylacic plasmapheresis was shown efficacious in avoiding FSGS recurrence, while timely diagnosis and plasmapheresis-based regimens induced remission in more than half of the patients

The Changing Landscape of Pneumocystis Jiroveci Infection in Kidney Transplant Recipients: Single-Center Experience of Late-Onset Pneumocystis Pneumonia

Background. Pneumocystis jiroveci pneumonia (PCP) is a life-threatening pulmonary infection after kidney transplantation (KTx). Its onset in the current era of modern immunosuppression and of routine use of universal PCP prophylaxis seems to differ from its onset in previous decades in terms of late onset with subtle clinical presentation, indicating a need for increased vigilance. Methods. We retrospectively studied all KTx recipients from our center who underwent bronchoscopy and bronchoalveolar lavage (BAL) between 2009 and 2018. Of these, all cases with confirmed PCP any time after the first post-KTx year were included in the analysis. Results. Among 60 patients with KTx who had undergone bronchoscopy and BAL, 12 cases with late-onset PCP were identified. PCP appeared late at a median of 10.8 (interquartile range, 2.4-15.8) years after transplantation. Patients’ mean age was 59 years, and all were receiving stable low-dose immunosuppression. Most of the patients (67%) had received PCP prophylaxis after KTx. Five out of 12 patients (42%) had concomitant cytomegalovirus (CMV) reactivation at the time of PCP. In almost all cases, clinical presentation was mild. Treatment consisted of trimethoprim-sulfamethoxazole (TMP-SMX) and intravenous corticosteroid administration, and concomitant immunosuppression was temporarily reduced or withdrawn. Outcome was generally good. None of the patients developed respiratory insufficiency or required mechanical ventilation. One patient died as a result of sepsis, and 3 more with preexisting advanced chronic kidney disease subsequently lost their grafts. Conclusion. Renal transplant recipients are at risk of late-onset PCP, even at a steady state of low-dose maintenance immunosuppression. Because of its subtle clinical presentation, high suspicion of the disease is warranted. Its early recognition and proper management are essential for a successful outcome

Τhe Impact of Pre-Transplant Kidney Biopsy on the Evaluation of Prospective Living Kidney Donors

Living kidney donation contributes to increasing the donor pool. Since safety and excellent outcomes of living kidney donors (LKD) are essential, renal biopsy must be part of the pre-transplant evaluation in donors with isolated urine abnormalities or other risk factors. We retrospectively collected data on potential living donors evaluated in the pre-transplant outpatient clinic of Laiko General Hospital of Athens between 2007 and 2022, who underwent a pre-transplant biopsy. Biopsy indications included microscopic hematuria, borderline proteinuria and comorbidities suggestive of chronicity. Those with glomerular diseases or chronic lesions were excluded from donation. We identified 59 potential living donors who underwent renal biopsy. Of these, 10 (16.9%) were male. Median age was 58 (IQR 51–63) years, while 23 (39%) were older than 60 years. 49 out of 59 (83%) had glomerular hematuria, 10 (16.7%) had proteinuria (150–300 mg/d). Out of the 59 donors, 21 (35.6%) were hypertensive, three (5.1%) had impaired glucose tolerance and seven (11.9%) had a BMI > 30 kg/m2. A total of 32 (54.2%) potential donors were accepted for donation. Eight (13.6%) had IgA nephropathy, 10 (16.9%) TBMD and nine (15.3%) had increased chronicity including secondary FSGS. When compared with a control group of donors who did not need a pre-transplant biopsy, those 32 who donated were more frequently hypertensive (p = 0.003), but had similar eGFR [61.3 (±10.4) vs. 61.9 (±13.8), p = 0.866] after a follow-up of 79 (36–114) months. Renal biopsy is a useful tool in the evaluation of prospective LKD. Thorough assessment of donors with isolated urine abnormalities and marginal donors is critical to ensure good post-donation outcomes

Arteriovenous renal replacement therapy in end-stage left-sided heart failure patients has a detrimental effect on patients with impaired right ventricular function

Objective: Chronic intermittent renal replacement therapy(RRT) is an alternate method of decongestion for patients presenting with diuretic-resistant, end-stage heart failure( HF) and cardiorenal syndrome. The optimal method of vascular access has not been confirmed. This study investigated the 6-month outcomes of patients with end-stage HF after the creation of arteriovenous communications (AVC) compared with other means of RRT. Methods: We treated 40 patients with chronic, intermittent, ambulatory RRT, of whom 15 (37.5%; Group A) underwent creation of AVC, and 25 (62.5%; Group B) received intraperitoneal (n=6) or internal jugular catheters (n=19) with the goal of achieving body weight stabilization and relief from congestion. Results: The characteristics of the two groups were similar. According to Cox regression analysis, the 6-month rate of death or re-hospitalization for HF was significantly higher in Group A (73%) than in Group B (44%); hazard ratio (HR): 2.58; 95% confidence interval (CI) 1.2-6.2; P=0.02. Over a 6-month follow-up, the cumulative survival was significantly shorter (P=0.03) in Group A (13.8 +/- 10 weeks) than in Group B (20.7 +/- 7 weeks). In the 15 patients who received AVC, the only independent predictor of adverse outcome at 6 months was serum total bilirubin concentration (HR 2.5; 95% CI 1.1-5.7, p=0.02), whereas in the 25 patients who underwent other means of RRT, pulmonary vascular resistance (PVR) was identified as a risk factor for hospitalization or death at 1-year follow-up (HR 1.26; 95% CI 1.1-1.57, p=0.04). Conclusion: In patients with end-stage HF, the creation of AVC for intermittent RRT was followed by a significant increase in morbidity and mortality in comparison to the safe and effective placement of permanent central venous catheters. Patients with elevated PVR seem to comprise a group at high risk for adverse outcomes after central catheter insertion. (C) 2016 Hellenic Society of Cardiology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Arteriovenous renal replacement therapy in end-stage left-sided heart failure patients has a detrimental effect on patients with impaired right ventricular function

Objective: Chronic intermittent renal replacement therapy(RRT) is an alternate method of decongestion for patients presenting with diuretic-resistant, end-stage heart failure(HF) and cardiorenal syndrome. The optimal method of vascular access has not been confirmed. This study investigated the 6-month outcomes of patients with end-stage HF after the creation of arteriovenous communications (AVC) compared with other means of RRT. Methods: We treated 40 patients with chronic, intermittent, ambulatory RRT, of whom 15 (37.5%; Group A) underwent creation of AVC, and 25 (62.5%; Group B) received intraperitoneal (n=6) or internal jugular catheters (n=19) with the goal of achieving body weight stabilization and relief from congestion. Results: The characteristics of the two groups were similar. According to Cox regression analysis, the 6-month rate of death or re-hospitalization for HF was significantly higher in Group A (73%) than in Group B (44%); hazard ratio (HR): 2.58; 95% confidence interval (CI) 1.2-6.2; P=0.02. Over a 6-month follow-up, the cumulative survival was significantly shorter (P=0.03) in Group A (13.8±10 weeks) than in Group B (20.7±7 weeks). In the 15 patients who received AVC, the only independent predictor of adverse outcome at 6 months was serum total bilirubin concentration (HR 2.5; 95% CI 1.1-5.7, p=0.02), whereas in the 25 patients who underwent other means of RRT, pulmonary vascular resistance (PVR) was identified as a risk factor for hospitalization or death at 1-year follow-up (HR 1.26; 95% CI 1.1-1.57, p=0.04). Conclusion: In patients with end-stage HF, the creation of AVC for intermittent RRT was followed by a significant increase in morbidity and mortality in comparison to the safe and effective placement of permanent central venous catheters. Patients with elevated PVR seem to comprise a group at high risk for adverse outcomes after central catheter insertion

Diagnosis and management of asymptomatic bacteriuria in kidney transplant recipients: a survey of current practice in Europe

International audienceBackgroundAsymptomatic bacteriuria is frequent in kidney transplant recipients (KTRs). However, there is no consensus on diagnosis or management. We conducted a European survey to explore current practice related to the diagnosis and management of asymptomatic bacteriuria in adult KTRs.MethodsA panel of experts from the European Renal Association–European Dialysis Transplant Association/Developing Education Science and Care for Renal Transplantation in European States working group and the European Study Group for Infections in Compromised Hosts of the European Society of Clinical Microbiology and Infectious Diseases designed this cross-sectional, questionnaire-based, self-administered survey. Invitations to participate were e-mailed to European physicians involved in the care of KTRs.ResultsTwo hundred and forty-four participants from 138 institutions in 25 countries answered the survey (response rate 30%). Most participants [72% (176/244)] said they always screen for asymptomatic bacteriuria in KTRs. Six per cent (15/240) reported never treating asymptomatic bacteriuria with antibiotics. When antimicrobial treatment was used, 24% of the participants (53/224) said they would start with empirical antibiotics. For an episode of asymptomatic bacteriuria caused by a fully susceptible microorganism and despite no contraindications, a majority of participants (121/223) said they would use a fluoroquinolone (n = 56), amoxicillin/clavulanic acid (n = 38) or oral cephalosporins (n = 27).ConclusionsScreening for and treating asymptomatic bacteriuria are common in KTRs despite uncertainties around the benefits and harms. In an era of antimicrobial resistance, further studies are needed to address the diagnosis and management of asymptomatic bacteriuria in these patients