Μεταμόσχευση νεφρού υπερευαισθητοποιημένων ασθενών με το πρόγραμμα των αποδεκτών ασύμβατων αντιγόνων

Στην παρούσα μελέτη, αξιολογήσαμε τα αποτελέσματα της μεταμόσχευσης υπερευαισθητοποιημένων ασθενών (ΥΕΑ) οι οποίοι μεταμοσχεύθηκαν με το πρόγραμμα προτεραιότητας στην επιλογή των υποψήφιων ληπτών προς μεταμόσχευση από αποβιώσαντα δότη σε συνδυασμό με την εφαρμογή του πρωτοκόλλου των μη αποδεκτών ασυμβατοτήτων. Στη μελέτη, συμπεριλήφθηκαν 97 ΥΕΑ ασθενείς, με Panel Reactive Antibodies -PRA τάξης Ι ή τάξης ΙΙ > 70%, οι οποίοι υπεβλήθησαν σε μεταμόσχευση νεφρού στη Μονάδα Μεταμόσχευσης Νεφρού του ΓΝΑ «ΛΑΪΚΟ» τη χρονική περίοδο 1ος/2004 έως και 12ος/ 2016. Οι ασθενείς αυτοί συγκρίθηκαν με 96 ασθενείς με χαμηλή ή καθόλου ευαισθητοποίηση και PRA 0(0-5)%, διάμεσος (ενδοτ. εύρος) που μεταμοσχεύθηκαν την ίδια χρονική περίοδο και απετέλεσαν την ομάδα ελέγχου (OE). Σε δεύτερη ανάλυση της μελέτης, οι 97 ΥΕΑ χωρίστηκαν σε δύο υπο-ομάδες: 35 (36.08%) ασθενείς με παρουσία DSAs (ΥΕΑ/DSA+) με διάμεση MFI=3332 (IQR:1656-4842) την ημέρα της μεταμόσχευσης και σε 62 (63.9%) ασθενείς χωρίς DSA(YEA/DSA-) κατά τη μεταμόσχευση. Όλοι μεταμοσχεύθηκαν με αρνητικά CDC/ T/BFCXM. Στους ΥΕΑ DSA+ διενεργήθηκε επιπλέον, virtual crossmatch κατά την επιλογή. Όλοι οι ασθενείς έλαβαν θεραπεία επαγωγής με Basiliximab. Στην ομάδα των ΥΕΑ/DSA+ χορηγήθηκε Rituximab σε 18 ασθενείς και υπεβλήθησαν σε συνεδρίες πλασμαφαίρεσης 11 ασθενείς. Η επταετής επιβίωση των ασθενών ήταν 95.3% (SE=2,3%) στους ΥΕΑ και 91,7% (SD=3,0) στην ΟΕ, (p=0,274) και των μοσχευμάτων 90,1% (SE=3,2%) στους ΥΕΑ και 95,3% (SE=2,3%) στην ΟΕ (p=0,253). Παρατηρήθηκαν περισσότερα επεισόδια οξείας απόρριψης στους ΥΕΑ, αλλά χωρίς σημαντική διαφορά με τους ασθενείς της ΟΕ (p=0,523). Παρατηρήθηκε ωστόσο διαφορά στα επεισόδια απόρριψης μεταξύ των ΥΕΑ/DSA+ και YEA/DSA-, 22,9% έναντι 6,5%, αντίστοιχα (p=0,025). Δεν παρατηρήθηκε σημαντική διαφορά στα επεισόδια λοιμώξεων, νεοπλασιών και μειζόνων επιπλοκών, σε όλες τις ομάδες. Συμπερασματικά, η μεταμόσχευση των ΥΕΑ με το πρόγραμμα προτεραιότητας στην επιλογή σε συνδυασμό με την εφαρμογή του πρωτοκόλλου της μη αποδεκτής ασυμβατότητας είναι ασφαλής, με εξαιρετικά μακροπρόθεσμα αποτελέσματα, ισοδύναμα με αυτά των μη ευαισθητοποιημένων ασθενών.Highly sensitized patients (HSP) have a low chance to find a compatible kidney allograft. According to the kidney allocation program in Greece, HSP with panel reactive antibody -%PRA>70 enter a priority list and proceed to crossmatch if the donor does not express unacceptable HLA-A,-B,-C,-DR,-DQ molecules. Patients with negative CDC and T/B Flow cytometric crossmatch (T/B FCXM) with the donor receive the graft. This study discusses the long term outcome of 97 highly sensitized renal transplant recipients. Our high immunologic risk program included 97 HSP who received a graft between January 2004 and December 2016 in Laikon Hospital, Athens. Their characteristics were compared with a control group (CG) including 96 non sensitized patients, transplanted in the same period. The HSP were divided into 2 groups: group A- 35 patients (36.08%) transplanted with preformed donor specific antibodies (DSAs), (HSP/DSA+), with median MFI=3332 (IQR: 1656-4842) on day 0 and group B- 62 patients (63.9%) without DSAs (MFI<1000), (HSP/DSA-). All patients were transplanted with negative CDC and T/B FCXM and received induction therapy with Basiliximab. Additionally, Rituximab was given in 18 pts of HSP/DSA+ group. Eleven patients of HSP/DSA+ group also received 3 plasma exchanges with low dose IVIG. Τhe seven–year patient survival was 95.3% (SE=2.3%) in the HSP and 91.7% (SE=3.0) in the CG ( p=0.274). The seven-year graft survival was 90.1% (SE=3.2%) in the HSP and 95.3% (SE=2.3%) in the CG (p=0.253). The HSP experienced an increased risk of biopsy proven acute rejection episodes, as compared to CG. However, the difference did not reach statistical significance (p=0.523). There was a significant difference in the number of patients who experienced acute rejection episodes, especially cellular rejections, in the HSP/DSA+ group compared to those in HSP/DSA- group (p=0.025). Patient survival rates were similar in the two groups (p=0.496). No difference was observed in graft survival rates (p=0.924). No statistical difference was observed regarding infections, surgical complications and malignancies among all study groups. We conclude that renal transplantation in HSP with unacceptable mismatch antigen program and negative CDC and T/B FCXM is safe, with low immunological risk

Kidney transplantation of highly sensitized patients via the acceptable mismatch program

Highly sensitized patients (HSP) have a low chance to find a compatible kidney allograft. According to the kidney allocation program in Greece, HSP with panel reactive antibody -%PRA>70 enter a priority list and proceed to crossmatch if the donor does not express unacceptable HLA-A,-B,-C,-DR,-DQ molecules. Patients with negative CDC and T/B Flow cytometric crossmatch (T/B FCXM) with the donor receive the graft. This study discusses the long term outcome of 97 highly sensitized renal transplant recipients. Our high immunologic risk program included 97 HSP who received a graft between January 2004 and December 2016 in Laikon Hospital, Athens. Their characteristics were compared with a control group (CG) including 96 non sensitized patients, transplanted in the same period. The HSP were divided into 2 groups: group A- 35 patients (36.08%) transplanted with preformed donor specific antibodies (DSAs), (HSP/DSA+), with median MFI=3332 (IQR: 1656-4842) on day 0 and group B- 62 patients (63.9%) without DSAs (MFI 70%, οι οποίοι υπεβλήθησαν σε μεταμόσχευση νεφρού στη Μονάδα Μεταμόσχευσης Νεφρού του ΓΝΑ «ΛΑΪΚΟ» τη χρονική περίοδο 1ος/2004 έως και 12ος/ 2016. Οι ασθενείς αυτοί συγκρίθηκαν με 96 ασθενείς με χαμηλή ή καθόλου ευαισθητοποίηση και PRA 0(0-5)%, διάμεσος (ενδοτ. εύρος) που μεταμοσχεύθηκαν την ίδια χρονική περίοδο και απετέλεσαν την ομάδα ελέγχου (OE).Σε δεύτερη ανάλυση της μελέτης, οι 97 ΥΕΑ χωρίστηκαν σε δύο υπο-ομάδες: 35 (36.08%) ασθενείς με παρουσία DSAs (ΥΕΑ/DSA+) με διάμεση MFI=3332 (IQR:1656-4842) την ημέρα της μεταμόσχευσης και σε 62 (63.9%) ασθενείς χωρίς DSA(YEA/DSA-) κατά τη μεταμόσχευση. Όλοι μεταμοσχεύθηκαν με αρνητικά CDC/ T/BFCXM. Στους ΥΕΑ DSA+ διενεργήθηκε επιπλέον, virtual crossmatch κατά την επιλογή. Όλοι οι ασθενείς έλαβαν θεραπεία επαγωγής με Basiliximab. Στην ομάδα των ΥΕΑ/DSA+ χορηγήθηκε Rituximab σε 18 ασθενείς και υπεβλήθησαν σε συνεδρίες πλασμαφαίρεσης 11 ασθενείς. Η επταετής επιβίωση των ασθενών ήταν 95.3% (SE=2,3%) στους ΥΕΑ και 91,7% (SD=3,0) στην ΟΕ, (p=0,274) και των μοσχευμάτων 90,1% (SE=3,2%) στους ΥΕΑ και 95,3% (SE=2,3%) στην ΟΕ (p=0,253). Παρατηρήθηκαν περισσότερα επεισόδια οξείας απόρριψης στους ΥΕΑ, αλλά χωρίς σημαντική διαφορά με τους ασθενείς της ΟΕ (p=0,523). Παρατηρήθηκε ωστόσο διαφορά στα επεισόδια απόρριψης μεταξύ των ΥΕΑ/DSA+ και YEA/DSA-, 22,9% έναντι 6,5%, αντίστοιχα (p=0,025). Δεν παρατηρήθηκε σημαντική διαφορά στα επεισόδια λοιμώξεων, νεοπλασιών και μειζόνων επιπλοκών, σε όλες τις ομάδες. Συμπερασματικά, η μεταμόσχευση των ΥΕΑ με το πρόγραμμα προτεραιότητας στην επιλογή σε συνδυασμό με την εφαρμογή του πρωτοκόλλου της μη αποδεκτής ασυμβατότητας είναι ασφαλής, με εξαιρετικά μακροπρόθεσμα αποτελέσματα, ισοδύναμα με αυτά των μη ευαισθητοποιημένων ασθενών

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

The Evolution of Living Donor Nephrectomy Program at A Hellenic Transplant Center. Laparoscopic vs. Open Donor Nephrectomy: Single-Center Experience

Since its introduction in 1995, laparoscopic nephrectomy has emerged as the preferred surgical approach for living donor nephrectomy. Given the ubiquity of the surgical procedure and the need for favorable outcomes, as it is an elective operation on otherwise healthy individuals, it is imperative to ensure appropriate preoperative risk stratification and anticipate intraoperative challenges. The aim of the present study was to compare peri-and postoperative outcomes of living kidney donors (LD), who had undergone laparoscopic nephrectomy (LDN), with a control group of those who had undergone open nephrectomy (ODN). Health-related quality of life (QoL) was also assessed using the validated SF-36 questionnaire. Data from 252 LD from a single transplant center from March 2015 to December 2020 were analyzed retrospectively. In total, 117 donors in the LDN and 135 in the ODN groups were assessed. Demographics, type of transplantation, BMI, duration of surgery, length of hospital stay, peri- and postoperative complications, renal function at discharge and QoL were recorded and compared between the two groups using Stata 13.0 software. There was no difference in baseline characteristics, nor in the prevalence of peri-and postoperative complications, with a total complication rate of 16% (mostly minor, Clavien–Dindo grade II) in both groups, while a different pattern of surgical complications was noticed between them. Duration of surgery was significantly longer in the ODN group (median 240 min vs. 160 min in LDN, p < 0.01), warm ischemia time was longer in the LDN group (median 6 min vs.2 min in ODN, p < 0.01) and length of hospital stay shorter in the LDN group (median 3 days vs. 7 days in ODN). Conversion rate from laparoscopic to open surgery was 2.5%. There was a drop in estimated glomerular filtration rate (eGFR) at discharge of 36 mL/min in the LDN and 32 mL/min in the ODN groups, respectively (p = 0.03). No death, readmission or reoperation were recorded. There was a significant difference in favor of LDN group for each one of the eight items of the questionnaire (SF1–SF8). As for the two summary scores, while the total physical component summary (PCS) score was comparable between the two groups (57.87 in the LDN group and 57.07 in the ODN group), the mental component summary (MCS) score was significantly higher (62.14 vs. 45.22, p < 0.001) in the LDN group. This study provides evidence that minimally invasive surgery can be performed safely, with very good short-term outcomes, providing several benefits for the living kidney donor, thereby contributing to expanding the living donor pool, which is essential, especially in countries with deceased-donor organ shortage