BACKGROUND:Real-world data on burden of refractory/resistant cytomegalovirus infection or intolerance to anti-cytomegalovirus (CMV) therapies (RRI CMV) among solid organ transplant (SOT) recipients are lacking. METHODS:Data from SOT recipients with RRI CMV aged ≥18 years were retrospectively collected from 13 centers (Europe, the United States) between 2014 and 2021. Anti-CMV treatment patterns, clinical outcomes, and hospitalization data were analyzed descriptively. RESULTS:Of 218 patients enrolled, 93.6% developed RRI CMV during their first CMV episode post-SOT. Valganciclovir was the most commonly used anti-CMV therapy for primary prophylaxis (97.1%), secondary prophylaxis (80.0%), and first-line treatment (90.1%). Most patients with data (59.6% [127/213]) received ≥2 anti-CMV therapies for treatment. Overall, 90.4% of patients experienced dose changes/treatment discontinuations during RRI CMV episodes. From RRI diagnosis, 50.0% of nephrotoxicity events occurred in patients receiving foscarnet and 61.3% of myelosuppression events in those receiving valganciclovir. CMV viremia cleared in 78.9% of patients during the first RRI CMV episode, and recurrent CMV episodes occurred in 21.6%. Graft loss occurred after the RRI CMV date in 8.4% (18/218) of patients. Overall mortality was 19.7%. Significantly more patients with RR CMV had CMV-related hospitalizations following SOT than those with intolerance to anti-CMV agents (58.2% vs 13.2%; P < .001). CONCLUSION:In this multinational real-world study of SOT recipients with RRI CMV infection, 21.1% did not achieve viremia clearance and 21.6% experienced recurrence, and a notable portion had unfavorable outcomes, such as adverse events, mortality, and hospitalizations. Results suggest that therapies that achieve and maintain CMV clearance without treatment-limiting toxicities are needed.
We present a modified dual kidney transplantation technique using a cold-preserved third-party donor iliac conduit fashioned into a Y-shaped graft, addressing the limitations of conventional approaches. Both kidneys were preserved with hypothermic machine perfusion and implanted unilaterally in the right iliac fossa. A cold-preserved third-party donor iliac artery was fashioned into a Y-shaped interposition graft, enabling a single arterial anastomosis to the internal iliac artery; both renal veins were anastomosed to the external iliac vein. Each ureter was implanted separately into the bladder. The warm ischemia time was 5 minutes, the cold ischemia time 14 hours, and the operative duration 186 minutes. The patient demonstrated immediate graft function without dialysis. The serum creatinine decreased to 153 µmol/L at discharge and stabilized around 210 µmol/L at follow-up. Color Doppler examination and magnetic resonance angiography confirmed good graft perfusion without stenosis, kinking, or thrombosis. This technique combines the efficiency of a single arterial anastomosis with the preservation of operative workspace, avoids dependence on quality of the index donor's iliac artery, and enables the reliable placement of both grafts in the right iliac fossa, providing a promising option for expanded-criteria donor utilization.
BACKGROUND:Lung transplant recipients (LuTRs) remain highly susceptible to severe COVID-19 due to chronic immunosuppression and graft vulnerability. Although early pandemic data described high morbidity and mortality, contemporary nationwide evidence from the post-acute pandemic period is limited. METHODS:Using ICD-10-CM codes, we identified 9,276 adult LuTR hospitalizations in NRD-2022, of which 12.8% (n = 1185) had COVID-19. Primary outcomes included in-hospital mortality, CLAD, and 90-day readmission. Secondary outcomes included ARDS, invasive mechanical ventilation (IMV), acute kidney injury (AKI), ICU admission, shock, thromboembolic events, and resource utilization (length of stay [LOS], total charges). Multivariable logistic and linear regression models adjusted for patient- and hospital-level covariates. RESULTS:COVID-19-positive LuTRs had significantly higher in-hospital mortality than non-COVID LuTRs (aOR 3.97; p < .001) and markedly increased odds of CLAD (aOR 10.55; p < .001). They also demonstrated higher odds of ARDS (aOR 9.36; p < .001), IMV (aOR 3.07; p < .001), ICU admission (aOR 2.82; p < .001), shock (aOR 1.85; p < .001), AKI (aOR 1.53; p < .001), and superimposed bacterial pneumonia (aOR 1.75; p < .001). Rates of tracheostomy, VV-ECMO use, pulmonary embolism, and deep venous thrombosis did not differ significantly. Ninety-day readmission rates were similar (aOR 1.06; p = .41). COVID-19 hospitalizations were associated with longer LOS (+3.72 days; p = .001) and higher total charges (+$59,350; p = .012). CONCLUSION:In the post-acute pandemic era, COVID-19 continues to impose a substantial clinical and economic burden on LuTRs, with elevated risks of mortality, CLAD, respiratory failure, multiorgan dysfunction, and greater resource utilization. Continued vigilance, preventive strategies, and tailored management remain essential for this high-risk population.
BACKGROUND:Kidney transplant recipients are at increased risk of severe varicella-zoster virus (VZV) infection due to chronic immunosuppression. While antiviral therapy is the mainstay of treatment, the role of adjunctive VZV-specific intravenous immunoglobulin (VZV-IVIG) in complicated disease remains insufficiently defined. METHODS:We present a case series of 3 kidney transplant recipients with complicated VZV infection treated with VZV-IVIG in addition to standard antiviral therapy at a tertiary transplant center between 2024 and 2025. Clinical presentation, virological course, immunosuppression management, graft function, and outcomes were analyzed. RESULTS:All patients were receiving maintenance immunosuppression and developed severe VZV manifestations, including disseminated primary infection with visceral and ocular involvement and herpes zoster with suspected ocular/visceral involvement. VZV-IVIG was administered as a single dose, short weekly course, or prolonged monthly therapy based on disease severity and virological response. Treatment was well tolerated, with no significant adverse events or deterioration in renal allograft function. Clinical stabilization and regression of cutaneous and systemic manifestations were observed in all cases. One patient with panuveitis and persistent viremia required repeated VZV-IVIG courses and achieved gradual virological suppression with prevention of further end-organ damage, although residual visual impairment remained. CONCLUSIONS:Adjunctive VZV-IVIG may be a useful and safe therapeutic option in selected kidney transplant recipients with severe, refractory, or organ-threatening VZV infection, particularly in cases of persistent viremia or ocular involvement. Larger studies are needed to define optimal patient selection, dosing strategies, and treatment duration.
INTRODUCTION:Calcineurin inhibitors (CNIs) such as tacrolimus remain essential for preventing réjection in kidney transplantation; however, their chronic use frequently causes nephrotoxicity and limits long-term graft survival. The molecular mechanisms underlying CNI-induced tubular injury remain incompletely understood and currently require invasive biopsy for confirmation. METHODS:Renal biopsies from 21 kidney transplant recipients under tacrolimus therapy were analyzed, including 10 patients with confirmed CNI toxicity (CNIT) and 11 controls without histological or clinical evidence of toxicity. Expression profiling of 96 apoptosis-related genes was performed using RT² Profiler PCR arrays, followed by validation of key targets (BAX, NOL3, XIAP) through quantitative RT-PCR and immunohistochemistry. RESULTS:Patients with CNIT showed significant overexpression of BAX, NOL3, and XIAP (P = .002, .001, and .022, respectively), indicating activation of the extrinsic apoptotic pathway. Immunohistochemical analysis confirmed BAX protein accumulation in tubular epithelial cells but not in the glomerular region, consistent with localized tubular injury. Control samples displayed only basal gene expression and no BAX staining. CONCLUSION:Dysregulation of the extrinsic apoptotic pathway-characterized by BAX upregulation and compensatory increases in antiapoptotic mediators NOL3 and XIAP-underlies the molecular pathology of CNIT. This consistent expression pattern provides mechanistic insight into CNI-induced nephrotoxicity and may support the development of molecular approaches for CNIT detection and monitoring, reducing reliance on invasive biopsy.
BACKGROUND:Graft-versus-host disease (GVHD) is a rare but highly lethal complication following liver transplantation (LT). Human Leukocyte Antigen one-way mismatch (HLAOWMM), defined as a donor possessing alleles entirely contained within the recipient's profile, is a known significant risk factor for GVHD. It is important to compare HLAOWMM with other known risk factors to contextualize its relative importance in clinical decision-making. The role of factors such as recipient age over 65 years, recipient-donor age difference of 22 years or more, and underlying conditions like autoimmune hepatitis and alcoholic liver disease has been explored in other studies. However, HLAOWMM appears to pose a definitive and critical risk when compared to these factors. Hypothesized immunological mechanisms suggest that HLAOWMM-induced GVHD results from donor T-cell activation against host antigens, leading to an aggressive immune response. This study examines a single-center series of liver transplantation cases to evaluate the association between HLAOWMM and the development of GVHD as well as patient mortality. PATIENTS AND METHODS:This was a retrospective analysis of 2398 LT procedures (2357 LDLT) performed at our institution between August 2006 and October 2018. Eight cases involving HLAOWMM were identified. HLAOWMM was defined as the situation in which all donor alleles are present in the recipient, whereas the reverse is not true. Clinical outcomes were analyzed, and a detailed Case 8 is presented to illustrate a recent HLAOWMM case resulting from the accidental omission of pre-transplant HLA testing. RESULTS:Eight patients underwent LT with HLAOWMM, giving an incidence of 3.3 per 1,000 LT procedures (8/2398). Five out of the 8 patients (62.5%) developed confirmed or highly suspected GVHD, resulting in a 100% mortality rate for the entire HLAOWMM cohort. The typical presentation was delayed (median onset 6 weeks post-LT) with cutaneous and mucosal symptoms. The detailed case demonstrated a classic histopathologic pattern of severe interface dermatitis with necrotic keratinocytes on skin biopsy, strongly supporting the diagnosis of acute GVHD. Diagnosis of GVHD was based on a combination of clinical presentations, including skin rash and oral ulcers, laboratory findings, including elevated liver enzymes and cytopenias, and histopathological examination showing interface dermatitis. The presence of apoptotic keratinocytes and basal-layer degeneration was a key histological criterion for diagnosing GVHD in these patients. CONCLUSION:HLAOWMM is a definitive and critical risk factor for GVHD in LDLT, associated with devastating outcomes and uniform mortality in this series. In response to the adverse outcome observed in Case 8, the policy of mandatory HLA matching was formally reinforced and reintroduced as a non-negotiable component of the evaluation protocol for all cases. The exclusion of such high-risk donor-recipient pairs should be established as the standard of care to prevent this fatal complication.
BACKGROUND:Renal transplant recipients are at increased risk of urothelial carcinoma (UC), with BK polyomavirus (BKPyV) increasingly implicated as a potential oncogenic driver in immunosuppressed patients. BKPyV-associated UC is rare, and carcinoma in situ (CIS) involving the renal allograft is exceptionally uncommon. Management is particularly challenging, as treatment must balance oncologic control against preservation of graft function and avoidance of return to dialysis, with limited evidence available to guide kidney-sparing approaches. METHODS:We present a case and updated literature review of BKPyV-associated urothelial CIS arising within a renal allograft in a female renal transplant recipient in her 60s with prior BKPyV nephropathy. Clinical, cytologic, radiologic, and histopathologic findings were reviewed alongside relevant literature describing BKPyV-associated urothelial malignancies in transplant recipients. Histopathology demonstrated high-grade atypia with diffuse SV40 and p53 positivity, supporting viral-associated oncogenesis. RESULTS:The patient presented with biopsy-proven urothelial CIS involving the renal medulla without visible upper tract lesions on imaging or endoscopy. Owing to the morbidity associated with radical urothelial clearance and the patient's desire to preserve graft function and avoid dialysis, a kidney-sparing approach using intrarenal gemcitabine instillation and intensive surveillance was undertaken. Initial surveillance demonstrated negative upper tract washings and no radiologic progression; however, a repeat transplant biopsy 2 years later demonstrated persistent CIS with ongoing BKPyV replication. A literature review identified more than 40 reported cases of BKPyV-associated UC in immunosuppressed patients, the majority demonstrating aggressive histologic features and poor oncologic outcomes. CONCLUSION:BKPyV-associated urothelial CIS of the renal allograft is an exceptionally rare but clinically significant entity. Management remains challenging, requiring a careful balance between oncologic control and allograft preservation. This case demonstrates a pragmatic kidney-sparing treatment strategy using localized therapy and close surveillance, although persistent disease remains a concern. Further research is required to guide the optimal management of BKPyV-associated urothelial malignancy in transplant recipients. This case is particularly relevant to the Australian transplant population given the high burden of renal transplantation, increasing long-term graft survival, and the growing recognition of BKPyV-associated malignancy in chronically immunosuppressed patients, for whom management decisions may directly impact graft preservation and dialysis dependence.
BACKGROUND:Acute renal allograft rejection remains a leading cause of graft loss despite advances in immunosuppressive therapy. Conventional predictors such as histopathology and immunologic markers have limitations in early detection. The C-reactive protein-albumin-lymphocyte (CALLY) index, Prognostic Nutritional Index (PNI) and Glasgow Prognostic Score (GPS) emerging inflammatory-nutritional markers, has shown prognostic value in oncology but has not been evaluated in renal transplantation. This study aimed to assess the predictive value of these indices for acute rejection after kidney transplantation. METHODS:This cohort included 59 adult renal transplant recipients between January 2015 and December 2024. Pretransplant laboratory parameters were used to calculate CALLY, PNI and Glasgow GPS. The primary endpoint was biopsy proven acute rejection within 12 months posttransplant. Logistic regression analyses identified independent predictors, and receiver operating characteristic (ROC) curves evaluated discriminative performance. RESULTS:Acute rejection occurred in 16 patients (27.1%). Compared with non-rejection cases, lower CALLY values were independently associated with acute rejection (OR = 0.083, 95% CI 0.010-0.650, P = .018) and showed superior discriminative performance (AUC = 0.968, 95% CI 0.925-1.000, P < .001) compared with PNI and GPS. CONCLUSIONS:Pretransplant CALLY index is a simple, inexpensive, and independent predictor of acute renal allograft rejection. Incorporating this immune-nutritional biomarker into pretransplant evaluation may improve early risk stratification and individualized management in kidney transplantation.
INTRODUCTION:Nontuberculous mycobacteria (NTM) disease is a significant morbidity in solid organ transplant recipients. Its management needs to be individualized based on factors including the potential drug-related adverse effects, which is a particular concern for liver transplant (LTx) recipients. We aim to investigate the incidence proportion, clinical presentation, management, and outcome of NTM isolation and NTM diseases in our LTx recipients. METHODS:We conducted a single-center retrospective study in Japan. We included all LTx recipients with age ≥ 18 who had posttransplant mycobacterial microbiological testing of any clinical specimens between April 2005 and March 2022. Participants with NTM isolation who satisfied the diagnostic criteria in American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) guidelines were defined as having NTM diseases. We collected demographic, clinical, microbiological, and radiographic data of participants through chart reviews. RESULTS:Of all 472 LTx recipients, 115 received at least one mycobacterial microbiological test, of whom 15 had positive test results. Six participants had an NTM disease, all of which were pulmonary infections (6/472: 1.3%). None of them received treatment for NTM diseases, even when alternative diagnoses were absent. Except for one patient who died of posttransplant lymphoproliferative disorder, five remained free of exacerbation of NTM disease and were alive at the end of the study period, with 1067-4825 days of follow-up periods. CONCLUSIONS:Late-onset pulmonary NTM diseases meeting ATS/IDSA criteria may be safely observed without treatment in selected LTx recipients. Diagnostic criteria may need to be tailored for immunocompromised patients including LTx recipients to help guide the management.
BACKGROUND:Sarcopenia, characterized by loss of muscle mass and strength, is a common condition in patients with cirrhosis and can influence outcomes after liver transplantation. This study aimed to compare the effects of sarcopenia on postoperative bacteremia, complications, and survival rates in living donor liver transplantation (LDLT) recipients in the Turkish population. METHODS:We conducted a retrospective analysis of 65 adult LDLT recipients from May 2021 to May 2023. Sarcopenia was diagnosed using preoperative abdominal CT by assessing psoas muscle area and psoas muscle index. Recipients were categorized into sarcopenic (Group 1) and nonsarcopenic (Group 2) groups. Demographic data, comorbidities, postoperative complications, and survival rates were analyzed. Statistical analyses included univariate and multivariate Cox regression for survival. RESULTS:The prevalence of sarcopenia was 55%. Major complications occurred in 44% of sarcopenic and 14% of nonsarcopenic recipients (P = .008). The 30-day and 3-month survival rates were significantly lower in sarcopenic recipients (83% versus 100%, P = .023). Although 1-year and overall survival rates showed no significant difference, sarcopenic recipients demonstrated a trend toward lower survival rates. Multivariate analysis revealed that sarcopenia and hypertension significantly impacted overall survival. CONCLUSIONS:Sarcopenia was associated with increased postoperative complications and a tendency for lower short-term survival in LDLT recipients. The findings underscore the clinical importance of early detection and management of sarcopenia in improving outcomes for liver transplant candidates. This study highlights the multifactorial nature of mortality risk in liver transplant recipients, with sarcopenia playing a crucial role.
