Effect of Leflunomide on Treatment of Pediatric Renal Transplant Recipients With BK Virus Infection.

OBJECTIVES: Infection with the BK virus is a significant complication after renal transplant and can progress to BK virus nephropathy and graft dysfunction. There is no consensus on the management of BK virus infection in pediatric renal transplant recipients. The most common therapeutic option is immunosuppression reduction, which can increase rejection risk. We aimed to examine the effect of leflunomide, an agent with antiviral and immunosuppressive actions, in a case series of pediatric renal transplant recipients with BK virus infection. MATERIALS AND METHODS: Routine screening with blood BK virus DNA polymerase chain reaction was performed regularly in all of our renal transplant patients. When BK virus was detected, we reduced tacrolimus levels, discontinued mycophenolate mofetil, and started active treatment with leflunomide. Treatment with leflunomide was continued until BK virus was undetectable by polymerase chain reaction in at least 2 blood samples 2 weeks apart. RESULTS: All pediatric patients developed BK virus infection in a mean period of 3.9 months after transplant. Graft dysfunction was evident in all patients with 20% to 100% elevation of creatinine from baseline. Afterleflunomide initiation, all patients had undetectable levels of BK virus by plasma polymerase chain reaction in at least 2 different samples within a mean period of 3.4 months, and renal function had normalized back to the baseline. None of our patients had evidence of hepatotoxicity or anemia on regular monitoring, with no other adverse events. Renal function remained stable in the follow-up period with no reoccurrence of BK viremia up to the date of this writing. CONCLUSIONS: Treatment with leflunomide resulted in rapid BK virus clearance and preservation of renal function with no adverse effects.

Clinical Outcome of Kidney Transplant Recipients with C1q-Binding De Novo Donor Specific Antibodies: A Single-Center Experience.

Complement activation by HLA antibodies is a key component of immune-mediated graft injury. We examined the clinical outcomes of kidney transplant recipients with complement-fixing de novo donor-specific antibodies (dnDSA) who were followed in our center. The C1q-binding ability was retrospectively assessed in 69 patients with dnDSA and mean fluorescence intensity (MFI) values > 2000 out of the 1325 kidney transplant recipients who were screened for DSA between 2015 and 2019. Luminex IgG single antigen beads (SAB)and C1q-SAB assays (One Lambda) were used. C1q-binding dnDSA was identified in 32/69 (46.4%) of the patients. Significantly higher MFI values were observed in C1q-positive DSA (18,978 versus 5840, p < 0.001). Renal graft biopsies were performed in 43 of the kidney transplant recipients (62.3%) with allograft dysfunction. Antibody-mediated rejection (ABMR) was detected in 29/43 (67.4%) of the patients. The incidence of ABMR was similar among patients with C1q-binding and non-C1q-binding DSA (51.7% vs. 48.3%, p = 0.523). Graft loss occurred in 30/69 (43.5%) of the patients at a median time of 82.5 months (IQR 45-135) from DSA detection. C1q-binding DSA was present in more patients who experienced graft loss (53.1% vs. 35.1%, p = 0.152). Higher MFI values and inferior clinical outcomes occurred in most of the kidney transplant recipients with C1q-binding dnDSA.

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.

Evaluation of Kidney Donor Risk Index/Kidney Donor Profile Index as Predictor Tools of Deceased-Donor Kidney Transplant Outcomes in a Greek Cohort.

The Kidney Donor Risk Index (KDRI) and Kidney Donor Profile Index (KDPI) have been developed to assess deceased-donor graft quality, although validation of their utility outside the USA remains limited. This single-center retrospective cohort study evaluated the ability of KDRI and KDPI to predict transplant outcomes in a Greek cohort. The efficacy of KDRI, KDPI, and donor's age in predicting death-censored graft failure was primarily assessed. Overall, 394 donors and 456 recipients were included. Death-censored graft survival was significantly worse with increasing KDRI (hazard ratio-HR: 2.21, 95% confidence intervals-CI: 1.16-4.22), KDPI (HR: 1.01, 95% CI: 1.00-1.02), and donor's age (HR: 1.03, 95% CI: 1.00-1.05). The unadjusted discriminative ability was similar for KDPI (C-statistic: 0.54) and donor's age (C-statistic: 0.52). The KDPI threshold of 85 was not predictive of graft failure (p-value: 0.19). Higher KDPI was linked to delayed graft function and worse kidney function, but not among expanded-criteria donor transplantations. No significant association was found between KDRI, KDPI, and patient survival. In conclusion, increasing KDRI and KDPI are linked to worse graft function, although their ability to discriminate long-term graft failure remains limited.

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.

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.

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.

Bloodstream infections by gram-negative bacteria in kidney transplant patients: Incidence, risk factors, and outcome.

BACKGROUND: Kidney transplant recipients (KTRs) are at increased risk of infections. METHODS: The aims of this study were to describe the incidence of bloodstream infections (BSIs) by gram-negative bacteria in a cohort of KTRs, the risk factors for BSI due to multi-drug-resistant (MDR) gram-negative bacteria, and the predictors for unfavorable outcome, defined as death or nephrectomy or return to dialysis, within 30 days from BSI. We conducted a retrospective cohort study at the renal transplant unit of a tertiary care hospital in Athens, Greece. RESULTS: In a total of 1962 KTRs, we recorded 195 BSI episodes in 182 single patients (male/female = 97/85), with a median (interquartile range) age of 57.2 (44-64.9) years. The incidence was 1.393/100 patient-years. The most common source of infection was urinary tract (70.9%), and Escherichia coli (63.7%) was the most common pathogen. 19.2% of the infecting organisms were MDR; previous antibiotic use (OR 8.2; CI 2.1-32.9) and previous stay in the intensive care unit (OR 34.2; CI 1.6-730.2) were associated with MDR BSIs. 6% of patients died, and 2.2% underwent nephrectomy, while no patients had to return to dialysis. Diabetes mellitus (OR 8.1; 95% CI 1.3-50.3), Pseudomonas aeruginosa BSI (OR 46.1; 95% CI 3.9-552.3), and septic shock (OR 46.7; 95% CI 1.7-1304.9) were independent predictors of unfavorable outcome. CONCLUSION: Bloodstream infections in KTRs have a significant impact on allograft and patients outcome.

Efficacy and safety of new direct-acting antivirals in kidney transplant recipients with chronic hepatitis C: a single-center study.

BACKGROUND: The recent interferon-free direct-acting antiviral (DAA) regimens have very good safety and efficacy profiles and are highly recommended for kidney transplant (KT) recipients with chronic hepatitis C (CHC). METHODS: All KT recipients with CHC followed at our hospital and who received therapy with the current DAAs were included. At the baseline visit, demographic, clinical and laboratory variables before and after KT, as well as at the commencement of DAAs, at the end of antiviral therapy and the end of follow up, were recorded, including assessment of glomerular filtration rate (eGFR). The changes in eGFR (DGFR) between baseline and end of therapy (1st period), and between end of therapy and end of follow up (2nd period), were evaluated. RESULTS: Twelve KT recipients were retrospectively evaluated: 2 had received antiviral therapy in the past; 4 (33.3%) patients had genotype 1 and 3 (25%) genotype 4 CHC. The median stiffness was 11.9 kPa (range 5-16.8), while 5 patients, none with decompensated cirrhosis, had stiffness >12.5 kPa. Eight patients received a sofosbuvir-containing antiviral regimen (Group 1) and 4 patients received an antiviral regimen without sofosbuvir (Group 2). Eleven (91.7%) patients achieved a sustained virological response (SVR). One patient discontinued DAAs early after treatment and did not achieve SVR. Otherwise, DAAs were well tolerated and no rejection episode was recorded. The DGFRs in the 1st period and 2nd period did not differ significantly between Group 1 and Group 2 patients. CONCLUSION: In this real-world study of KT recipients with CHC, the high efficacy and clinically acceptable tolerability of DAAs were confirmed.

Coronary artery disease in renal transplant recipients: an angiographic study.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in renal transplant recipients (RT). Coronary artery disease (CAD) in such patients is poorly studied. METHODS: During 2012-2017, 50 patients with a renal graft (functioning for a minimum of 6 months) were subjected to coronary angiography in our institution. They were matched (for age, gender, diabetes, and indication for angiography) with 50 patients with end-stage renal disease (ESRD) undergoing chronic dialysis and 50 patients with normal renal function who were subjected to coronary angiography during the same period. The extent and severity of CAD were assessed by using the SYNTAX score. RESULTS: RT had a significantly longer duration of ESRD than patients on dialysis (17.5±7.1 vs. 8.5±8.7 years, p<0.01). Mean SYNTAX score was 13.3±12.0 in RT, 20.6±17.5 in patients on dialysis, and 9.4±9.2 in control patients (p<0.01). At least one significantly calcified lesion was present in 75.7% of RT recipients, 92.1% of patients on dialysis, and 15.8% of control patients (p<0.01). Percutaneous coronary intervention (PCI) was successful in 93.8% of the attempted cases in RT, 75% of patients on chronic dialysis, and 100% of control patients (p=0.04). In the RT group, SYNTAX score significantly correlated with smoking (p=0.02) and the total vintage of ESRD (p=0.04). CONCLUSIONS: In this angiographic study, CAD was less severe in RT than in patients on long-term dialysis despite a longer duration of ESRD. Coronary artery calcification was highly prevalent after renal transplantation. PCI in RT had a high rate of angiographic success.

Valproate-induced hyperammonemic encephalopathy in a renal transplanted patient.

Neurological complications after renal transplantation constitute an important cause of morbidity and mortality. Their differential diagnosis is difficult and essential for subsequent patient's management. Valproate-induced hyperammonemic encephalopathy is an uncommon but serious effect of valproate treatment. Here, we describe the case of a 15-year-old girl who was on a long-term therapy with valproate due to epilepsy and revealed impaired consciousness with hyperammonemia 12 days after renal transplantation. After withdraw of valproate, patients' symptoms resolved within 24 h. Clinicians should increase their awareness for potential complication of valproate, especially in transplanted patients.

Impact of donor and recipient age difference on long-term allograft survival after living donor renal transplantation: analysis of 478 cases.

INTRODUCTION: Either deceased or living-related renal transplantation constitutes the best therapeutic option for patients with end-stage renal disease. In this retrospective study, an attempt to identify parameters that affect allograft survival in living donor renal transplantation was made. METHODS: Between January 2000 and July 2012, 478 adult patients received a renal transplant from a living-related donor in our center and their records were retrospectively reviewed in November 2012. Data concerning donor age, recipient age, donor/recipient age difference, donor/recipient gender, and ABO compatibility/incompatibility were recorded and associated with renal allograft survival rate. RESULTS: Renal allograft survival rate was 96%, 89.5%, and 77.7% in the first, fifth, and 10th yr after transplantation, respectively. Only the difference between donor and recipient age was statistically significant in relation to graft survival. In cases with age difference >13 yr, graft survival rate was lower from the third yr onward. CONCLUSIONS: Only the age difference between donor and recipient exerts an adverse impact on graft outcome after living donor renal transplantation, whereas donor age, recipient age, donor/recipient gender, and ABO incompatibility do not significantly influence renal allograft survival.

Long-term follow up for anti-HLA donor specific antibodies postrenal transplantation: high immunogenicity of HLA class II graft molecules.

Τhe clinical significance of de novo post-transplant anti-HLA donor-specific antibodies (DSA) was evaluated using 4241 serum samples collected between 2000 and 2007 from 597 renal transplant recipients. Patients transplanted before December 1996 (n = 77) were included in the historic group and those transplanted thereafter (n = 520) were included in the study group. All recipients were negative for DSA before transplantation (Tx). Post-Tx, de novo DSA were detected in 92/597 (15.4%) patients, while 196 had third party anti-HLA antibodies (DSA-negative). DSA were more frequent in the historic group (33.8%) compared with the study group (12.7%) (P < 0.001). Anti-HLA class-II DSA predominated in both groups (84.6% vs. 69.7%). Recipients of HLA class II-incompatible grafts developed DSA more frequently than those receiving HLA class II-compatible grafts (17.9% vs.7.9%, P = 0.003), directed mainly against HLA-DQ graft molecules (64/446, 14.4%). DSA production was not different between presensitized and nonsensitized patients (P = 0.842). Graft survival was higher in patients without antibodies compared with DSA-positive (log-rank test, P = 0.002) and DSA-negative patients (log-rank test, P = 0.002). Univariate and multivariate analysis showed independent association for DSA class I (HR = 31.78), DSA class II (HR = 20.92) and non-DSA (HR = 5.94) and graft failure. We conclude that HLA class II incompatible graft transplantations need careful monitoring and should be avoided in high immunological risk cases.

IgM antibodies towards pre-endothelial cells: strong indication for an association with accelerated rejection. A case report.

A 27-year-old woman developed a graft loss due to an accelerated humoral rejection after receiving a blood group identical, human leucocyte antigens (HLA) haploidentical living-related kidney, despite the fact that she did not refer any sensitization event before transplantation. The complement-dependent cytotoxicity and flow cytometry crossmatches were negative for T and B cells. Retrospectively, IgM antibodies against donor precursor endothelial Tie-2(+) cells were detected using a commercially available assay and the pre-transplant serum sample. This case illustrates the necessity of detection of other than the classical HLA-directed antibodies prior organ grafting.