There is no specific therapy for polyoma BK virus nephropathy (BKVN) in kidney transplant recipients, a condition associated with poor outcomes. Everolimus showed promising antiviral effects, but ...data from prospective studies are limited. Therefore, we converted ten consecutive kidney transplant recipients with biopsy-proven BKVN from standard exposure Calcineurin inhibitors and Mycophenolate to Everolimus and reduced exposure Calcineurin inhibitors. Ten patients not administered Everolimus, on reduced exposure Calcineurin inhibitor and halved MPA doses served as controls. All kidney transplant recipients continued steroid therapy. Each patient underwent kidney graft biopsy, BKV replication by PCR, and de novo DSA determination. During a 3-year follow-up no graft loss occurred in kidney transplant recipients on Everolimus but it was observed in 5/10 controls (P = 0.032). eGFR improved on Everolimus and worsened in controls (between group difference + 25.6 ml/min/1.73 m
2
, 95% CI 10.5–40.7, P = 0.002). BKV replication declined in the Everolimus group alone (from 6.4 ± 0.8 to 3.6 ± 1.6 Log 10 genomic copies, P = 0.0001), and we found a significant inverse relationship between eGFR and BKV genomic copy changes (P = 0.022). Average Calcineurin inhibitors trough levels did not differ between the two study groups during follow-up. By multivariable Cox regression analysis, Everolimus treatment resulted the only significant predictor of survival free of a combined endpoint of graft loss and 57% eGFR reduction (P = 0.02). Kidney transplant recipients on Everolimus had a higher survival free of adverse graft outcome (log-rank test, P = 0.009). In conclusion an Everolimus-based immunosuppressive protocol with minimization of Calcineurin inhibitors and antimetabolite discontinuation effectively treated BKVN in kidney transplant recipients.
Rare diseases are chronic and life-threatening disorders affecting < 1 person every 2,000. For most of them, clinical symptoms and signs can be observed at birth or childhood. Approximately 80% of ...all rare diseases have a genetic background and most of them are monogenic conditions. In addition, while the majority of these diseases is still incurable, early diagnosis and specific treatment can improve patients' quality of life. Transplantation is among the therapeutic options and represents the definitive treatment for end-stage organ failure, both in children and adults. The aim of this paper was to analyze, in a large cohort of Italian patients, the main rare genetic diseases that led to organ transplantation, specifically pointing the attention on the pediatric cohort. To the purpose of our analysis, we considered heart, lung, liver and kidney transplants included in the Transplant Registry (TR) of the Italian National Transplantation Center in the 2002-2019 timeframe. Overall, 49,404 recipients were enrolled in the cohort, 5.1% of whom in the pediatric age. For 40,909 (82.8%) transplant recipients, a disease diagnosis was available, of which 38,615 in the adult cohort, while 8,495 patients (17.2%) were undiagnosed. There were 128 disease categories, and of these, 117 were listed in the main rare disease databases. In the pediatric cohort, 2,294 (5.6%) patients had a disease diagnosis: of the 2,126 (92.7%) patients affected by a rare disease, 1,402 (61.1%) presented with a monogenic condition. As expected, the frequencies of pathologies leading to organ failure were different between the pediatric and the adult cohort. Moreover, the pediatric group was characterized, compared to the adult one, by an overall better survival of the graft at ten years after transplant, with the only exception of lung transplants. When comparing survival considering rare vs non-rare diseases or rare and monogenic vs rare non-monogenic conditions, no differences were highlighted for kidney and lung transplants, while rare diseases had a better survival in liver as opposed to heart transplants. This work represents the first national survey analyzing the main genetic causes and frequencies of rare and/or monogenic diseases leading to organ failure and requiring transplantation both in adults and children.
Introduction. Hepatitis C virus (HCV) infection continues to represent a poor prognostic factor in kidney transplant (KTx) patients. New direct-acting antiviral agents (DAA) have dramatically changed ...the therapy management for HCV, showing promising results in terms of sustained virologic response. Timing for DAA therapy in HCV positive kidney waitlist patients continues to be controversial, and caution is recommended due to the potential difficult immunosuppressant dose adjustments, particularly in the early posttransplant period. We report a case of a KTx performed during antiviral DAA therapy. Report of Case. Patient was a 44-year-old man suffering from chronic HCV hepatitis associated with end-stage kidney disease (ESRD), waitlisted for a second KTx as a sensitized patient (panel-reactive antibody peak 85%) in March 2019. Four months later, antiviral DAA therapy was started (glecaprevir/pibrentasvir 300 mg/120 mg daily, for 8 weeks). After 30 days, a left kidney was offered and, given the good compatibility, we decided to proceed with KTx without discontinuing the DAA therapy. A standard straightforward kidney transplant was performed. Immunosuppression included thymoglobulin and prednisone for induction and tacrolimus and mycophenolate for maintenance. After a transient delay graft function, creatinine levels progressively decreased. From postoperative day 3, tacrolimus reached target levels and remained stable. No episodes of acute rejection occurred. The 8-week DAA therapy was carried out without interruption. All HCV-RNA level controls resulted undetectable. On postoperative day 15, the patient was discharged and remains in healthy condition with normal renal function and HCV negative after 18 months of follow-up. Discussion. In this case, DAA therapy during the perioperative KTx period was well tolerated and effective. If confirmed, patients should not necessarily be suspended from the waiting list during DAA therapy for HCV eradication.
Dual kidney transplantation (DKT) was developed because allows the utilization of suboptimal kidneys procured from extended criteria donors. Compared to single kidney transplant, DKT is a demanding ...procedure, with higher risk of complications1–3.
In 2006, a mini-invasive technique has been introduced in single kidney transplant, using a minimal incision of 5-8 cm oflength4–7.
We describe a novel minimally invasive technique of ipsilateral dual kidney transplantation, using a 8 cm of length mini-incision.
The patient was a 67-year-old male, with an end-stage renal disease secondary to a glomerulonephritis, who received two kidneys from a 73-year-old woman, deceased for subarachnoid haemorrhage. Pre-transplant renal biopsies showed a Remuzzi–Karpinski score of 4 and 5.
Surgical time was 220 min. Warm ischemia times were of 33 min and 31 min, respectively. Post-operative course was uneventful and on POD 11, the patient was discharged in good condition with a normal renal function (creatinine level: 1.0 mg/dl).
He remains in healthy conditions with regular kidney function after eighteen months of follow-up.
Minimal incision ipsilateral dual kidney transplantation (MIDKT) seems technically feasible. Surgical time and warm ischemia times were comparable to those obtained using the conventional technique. Reduced post-operative pain, cosmetic result, absence of complications and good graft function seem promising.
MIDKT seems to add the positive aspects of a conventional surgery as the easy achievability and the low costs, to those of a mini-invasive surgery, such as reduced trauma, reduced pain, better cosmetic and faster recovery.
Immunity to Human leukocyte antigen (HLA) cannot explain all cases of ABMR, nor the differences observed in the outcome of kidney recipients with circulating DSAs endowed with similar biologic ...characteristics. Thus, increasing attention has recently been focused on the role of immunity to non-HLA antigenic targets.
We analyzed humoral auto- and alloimmune responses to the non-HLA antigen glutathione S-transferase theta 1 (GSTT1), along with development of
(
)HLA-DSAs, in a cohort of 146 pediatric non-sensitized recipients of first kidney allograft, to analyze its role in ABMR and graft loss. A multiplex bead assay was employed to assess GSTT1 antibodies (Abs).
We observed development of GSTT1 Abs in 71 recipients after transplantation, 16 with MFI > 8031 (4th quartile: Q4 group). In univariate analyses, we found an association between Q4-GSTT1Abs and ABMR and graft loss, suggesting a potential role in inducing graft damage, as GSTT1 Abs were identified within ABMR biopsies of patients with graft function deterioration in the absence of concomitant intragraft HLA-DSAs. HLA-DSAs and GSTT1 Abs were independent predictors of graft loss in our cohort. As GSTT1 Ab development preceded or coincided with the appearance of
HLA-DSAs, we tested and found that a model with the two combined parameters proved more fit to classify patients at risk of graft loss.
Our observations on the harmful effects of GSTT1Abs, alone or in combination with HLA-DSAs, add to the evidence pointing to a negative role of allo- and auto-non-HLA Abs on kidney graft outcome.
De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear ...whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24.6 months. In 15 patients, dnDSAs developed within 1 year (early-onset group), while the other 24 seroconverted after the first posttransplant year (late-onset group). The two groups were comparable when considering patient- and transplant-related factors, as well as DSA biological properties, including C1q and C3d complement-binding ability. Only recipient age at transplant significantly differed in the two cohorts, with younger patients showing earlier dnDSA development. Late AMR was diagnosed in 47% of the early group and in 58% of the late group. Graft loss occurred in 3/15 (20%) and 4/24 (17%) patients in early- and late-onset groups, respectively (p = ns). In our pediatric kidney recipients, dnDSAs predict AMR and graft loss irrespective of the time elapsed between transplantation and antibody occurrence.
Development of de novo donor-specific antibodies (dnDSA) is associated with late or chronic antibody-mediated rejection (CAMR) and poor graft outcome in low-risk kidney transplant recipients. ...High-level soluble B-cell activating factor (sBAFF) was observed in kidney recipients at higher risk of developing dnDSA.
We longitudinally analyzed sBAFF levels in 81 consecutive primary pediatric kidney recipients monitored for de novo human leukocyte antigen (HLA) antibody (Ab) occurrence to gain insight into the events conditioning B-cell activation posttransplant and to analyze the usefulness of paired DSA-sBAFF monitoring in this clinical setting.
At a median follow-up of 65 months, 23 patients (28%) developed dnDSA, with 13 of 23 developing CAMR. Irrespective of HLA Ab status, sBAFF levels progressively increased in all patients in the first posttransplant year, thereafter reaching a plateau. sBAFF levels were influenced by the degree of HLA class I antigen match and donor age. Despite higher levels of sBAFF in HLA Ab-positive patients (median and 95% confidence interval sBAFF in DSA+non-DSA patients: 568, 534-608 pg/mL vs. 502, 422-548 pg/mL in Ab-negative patients; P<0.05), we found that sBAFF monitoring could not predict DSA development by a time to event longitudinal analysis. Moreover, sBAFF kinetics up to CAMR onset could not anticipate CAMR development in the DSA cohort.
Our findings provide evidence of early posttransplant B-cell activation even in unsensitized recipients of first kidney allograft. The significance of this activation, likely induced by exposition to the allograft, is yet unclear.
Summary
This 5 year observational multicentre study conducted in the Nord Italian Transplant programme area evaluated outcomes in patients receiving kidneys from donors over 60 years allocated ...according to a combined clinical and histological algorithm. Low‐risk donors 60–69 years without risk factors were allocated to single kidney transplant (LR‐SKT) based on clinical criteria. Biopsy was performed in donors over 70 years or 60–69 years with risk factors, allocated to Single (HR‐SKT) or Dual kidney transplant (HR‐DKT) according to the severity of histological damage. Forty HR‐DKTs, 41 HR‐SKTs and 234 LR‐SKTs were evaluated. Baseline differences generally reflected stratification and allocation criteria. Patient and graft (death censored) survival were 90% and 92% for HR‐DKT, 85% and 89% for HR‐SKT, 88% and 87% for LR‐SKT. The algorithm appeared user‐friendly in daily practice and was safe and efficient, as demonstrated by satisfactory outcomes in all groups at 5 years. Clinical criteria performed well in low‐risk donors. The excellent outcomes observed in DKTs call for fine‐tuning of cut‐off scores for allocation to DKT or SKT in high‐risk patients.
Kidneys with more than 3 arteries are very rare and decision to use or not these organs can be difficult, because there is an increased risk of post-transplant vascular complications, with a higher ...risk of worse outcome.
Here we report a case of a successful transplant a deceased donor left kidney with 5 arteries, using 2 separate wide patches containing 3 and 2 arteries, respectively.
These kidneys should be considered as a source for maximize the number of organs available, but a careful selection of the recipient is also crucial for minimize the risk of complications.
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