Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease worldwide and is a leading cause of chronic kidney disease. The current paradigm of IgAN risk stratification, the International IgAN Prediction Tool (IIgAN-PT), relies on clinical and histologic data collected at the time of biopsy. Clinical data includes variables such as estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure. Histologic data from the diagnostic kidney biopsy are assessed by the Oxford classification system; however, its reliability can be significantly affected by interobserver variability. The emergence of "pathomics," in which morphometric features are extracted from histologic objects, aims to address this issue and provides a more objective and reproducible assessment. In this study, we created a dataset of clinical variables and averaged pathomic features from non-globally sclerotic glomeruli, arteries/arterioles, and tubules. We used this data to train and test logistic regressions (LGs) to predict whether patients would experience kidney function decline (i.e., eGFR decline > 50% from baseline or dialysis initiation within 5 years post-biopsy). LGs on only glomerular pathomic features and clinical variables did not perform better than IIgAN-PT predictions, but there was some improvement in accuracy, balanced accuracy, precision, and recall when adding other histologic objects (i.e. tubules and arteries/arterioles) with the elastic net penalty. The greatest improvement in performance was derived from including pathomic features from non-glomerular histologic objects and removing MEST-C variables. This improved model accuracy, balanced accuracy, precision, and recall for LG with the ridge penalty from 0.714 to 0.929, 0.455 to 0.833, 0 to 1.000, and 0 to 0.667.

BACKGROUND:Kidney transplantation is the optimal renal replacement therapy, offering superior survival and quality of life compared with dialysis. Although outcomes after repeat transplantation may be inferior to those of first transplantation, retransplantation provides a survival benefit compared with remaining on dialysis. Living donor kidney transplantation (LDKT) offers advantages such as improved HLA matching and reduced cold ischemia time, potentially mitigating retransplantation-related risks. METHODS:We performed a retrospective single-center study including all LDKT performed at ULS Coimbra between 2009-2020, with a mean follow-up of 9 years. Clinical and immunological donor-recipient variables were collected. Death-censored graft survival was assessed using Kaplan-Meier analysis and univariable Cox regression was used to explore predictors of graft loss. Acute rejection was defined according to Banff 2019 criteria. RESULTS:Seventy-six patients were included: 63 underwent a first LDKT and 13 a second LDKT. Baseline characteristics were similar regarding gender, dialysis vintage, HLA mismatches, and cold ischemia time. Second LDKT recipients were older (42 vs 33 years, p = 0.025), had higher historical panel reactive antibody levels, and more frequently received thymoglobulin induction (69.2% vs 16.7%, p < 0.001). Serum creatinine at 1 year was associated with graft loss (p = 0.007). Acute rejection was rare (4% vs 0%). Five- and 10-year death-censored graft survival was comparable between first and second LDKT (88.9% and 87.3% vs 100% and 92.3%, respectively). CONCLUSIONS:Second living donor kidney transplantation achieved excellent long-term graft survival comparable to first transplantation, supporting its safety and efficacy.

The prevention of donor-transmitted diseases in solid organ transplantation depends on the thorough screening of donors while maintaining a high level of clinical suspicion. The evolution in these practices reduced the incidence of donor-transmitted tumors to minimal and unexpected events. Nevertheless, the recipients of these exceptional transmissions hold significant clinical consequences, challenging decisions, and poor outcomes. The intravascular large B-cell lymphoma (IVLBCL) is an extremely rare and aggressive tumor with almost exclusive intrasmall vessel growth. Its clinical and morphological features make diagnosing potential deceased donors virtually impossible. We report the case of the post-transplant diagnosis of the transmission of this cancer in a multiorgan kidney and liver transplantation. Following the IVLBCL diagnosis on a routine preimplantation kidney biopsy, the transplanted kidney grafts were removed, and a conservative management approach was adopted for the liver recipient. Histological examination of the kidney grafts revealed multifocal involvement by an IVLBCL neoplasm. Subsequent liver recipient biopsy showed no evidence of the known IVLBCL. After three years of follow-up, both kidney recipients have undergone a second kidney transplant, and the liver recipient continues to demonstrate no signs of the IVLBCL disease.

The diagnosis of new onset autoimmune diseases in kidney transplant patients is challenging with new onset SLE after kidney transplant being a rare condition, with very few cases reported. We describe a case of a kidney transplant patient who, after 9 years presented with intermittent fever and diarrhea, inflammatory migratory polyarthralgia, myalgias, cramps and an erythematous rash in the cleavage area. Immunological testing revealed positive antinuclear antibodies (ANA 1:640), anti-double-stranded DNA antibodies (53.2 IU/mL), and elevated beta-2 microglobulin (105.59 U/mL), leading to the diagnosis of de novo SLE according to EULAR/ACR 2019 criteria. Notably, the patient exhibited no evidence of renal involvement from the onset, with stable kidney function and normal urinary sediment throughout follow-up. Ten months after undergoing treatment with corticosteroids and belimumab there was partial clinical and serological improvement. This case highlights a rare presentation of post-transplant SLE without renal involvement, reinforcing the need for a high index of suspicion in transplant recipients presenting with non-specific inflammatory symptoms.

The limited availability of donor kidneys represents a major obstacle to accessing kidney transplantation. Procurement biopsies are frequently utilized to assess donor kidney quality, but they are associated with high discard rates, especially for marginal donors. This raises concerns that some potentially viable kidneys may be discarded due to limitations in current evaluation methods. We have developed ComPRePS (Computational Renal Pathology Suite), an open-source, end-to-end, cloud-based platform designed for AI/ML-driven analysis of kidney biopsies. Using this platform, we aimed to establish a computational model that integrates donor pathological and clinical data to enhance the prediction of post-transplant graft function and mitigate organ discard rates. Our analysis focused on 213 harvest core needle biopsies from kidneys of 152 deceased donors: 139 cases from 110 donors were allocated for single kidney transplantation, while 74 cases from 42 donors were discarded due to biopsy findings. The tissue samples were processed using a rapid Formalin-Fixed Paraffin-Embedded method, with tissue sections prepared at a thickness of 2–3 μm and stained with Periodic Acid–Schiff. The slides were then digitized using a brightfield microscopy whole-slide scanner at 40× magnification. We collected a complete set of clinical data for both donors and recipients, including the glomerular filtration rate at different time points. Our computational pipeline automatically segment glomeruli, tubules, arteries, and arterioles followed by a comprehensive extraction of 73 quantitative pathomic features from these regions: measures of distance, color, texture, morphology, and summary statistics. Additionally, separate pre-trained convolutional neural networks assessed the degree of arterial fibrointimal thickening, interstitial fibrosis, and tubular atrophy (IFTA). A penalized LASSO Cox regression machine learning model was employed to identify the most significant predictors of the 12-month post-transplant eGFR outcome. Finally, we developed a computational Remuzzi score using ComPRePS and compared it to the original on-call pathologist assessment to evaluate the potential reduction in organ discard rates. Our regression model included 24 variables to predict the 12-month eGFR: donor variables (age and last eGFR), arterial fibrointimal thickening, IFTA and 20 pathomic features. This model demonstrated excellent performance, with an area under the curve of 0.85 (95% CI, 0.78 to 0.91) for predicting an estimated glomerular filtration rate (eGFR) ≥55 ml/min/1.73 m2 at 12 months post-transplantation compared to 0.70 (95% CI, 0.61 to 0.79) of the Kidney Donor Profile Index, and 0.57 (95% CI, 0.47 to 0.67) for the initial on-call Pathologist Remuzzi score (Fig. 1). Additionally, our analysis revealed that the combined computational Remuzzi score would have deemed 42.4% of previously discarded kidneys as suitable for transplantation (Computational Remuzzi score <4). Based on our eGFR prediction model, 18.2% of these kidneys would have been expected to have an eGFR ≥55 mL/min/1.73 m2 or greater at 12 months post-transplantation. This study highlights the potential of integrating pathological and clinical data from deceased kidney donors using ML analysis. Our computational model outperformed existing methods in predicting post-transplant graft function and has demonstrated the potential to reduce organ discard rates.

Kidney graft survival is influenced by multiple factors. The estimated glomerular filtration rate (eGFR) at one year post-transplant is commonly used as a predictor of graft survival. However, the decline in eGFR over time is often overlooked. This study aimed to compare the impact of eGFR at one year (eGFR1) and eGFR decline over the subsequent 5 years to assess their relative influence on long-term graft survival. We conducted a retrospective observational cohort study using data from the Transplantation Network database of a kidney transplant center. We included adult recipients (≥18 years old) undergoing their first kidney transplant (KT) from a deceased donor aged >10 years between 2012 and 2019. Recipients who experienced graft loss within the first year were excluded. We analysed the impact of eGFR1 and eGFR decline from years 1 to 5 post-transplant (categorized as reductions >10, >20, and >30 mL/min/1.73 m²) on death-censored graft survival and recipient survival. A total of 753 kidney transplant recipients were included. The median donor and recipient ages were 54.0 years [IQR: 47.0–62.5] and 53.0 years [IQR: 44.0–61.0], respectively. The median donor eGFR was 101.3 mL/min/1.73 m² [IQR: 84.3–110.6]. The median eGFR1 was 57.6 mL/min/1.73 m² [IQR: 44.6–76.6], and the median eGFR at year 5 (eGFR5) was 60.3 mL/min/1.73 m² [IQR: 46.2–78.2]. The mean recipient survival was 11.5 ± 0.1 years, with a mortality rate of 13.9% (n = 105). The mean death-censored graft survival was 11.9 ± 0.1 years, with a death-censored graft loss of 9.8% (n = 65). Multivariate Cox regression analysis showed that both eGFR1 and eGFR decline between years 1 and 5 were significantly associated with death-censored graft survival. eGFR1 was associated with a hazard ratio (HR) of 0.93 (95% CI: 0.90–0.96, P < 0.001). In contrast, an eGFR decline >10, >20, and >30 mL/min/1.73 m² was associated with significantly higher risks of graft loss: HR 9.81 (95% CI: 3.85–24.93, P < 0.001), HR 19.17 (95% CI: 6.81–53.97, P < 0.001), and HR 25.43 (95% CI: 7.00–92.40, P < 0.001), respectively. Regarding recipient survival, significant risk factors included recipient age, donor eGFR, eGFR1, and eGFR decline from years 1 to 5. Notably, an eGFR decline >30 mL/min/1.73 m² was associated with the highest risk (HR 3.83, 95% CI: 1.45–10.13, P = 0.007). Both higher eGFR1 and a slower rate of eGFR decline were associated with better graft and recipient survival. While eGFR1 alone provides valuable prognostic information, the decline in eGFR between years 1 and 5 post-transplant was a more robust predictor of long-term adverse outcomes, with greater reductions in eGFR (>10, >20, and >30 mL/min/1.73 m²) showing a progressively higher risks of graft loss and mortality. These findings underscore the critical importance of monitoring eGFR trends during post-transplant follow-up. The rate of eGFR decline should be considered a key indicator for predicting long-term graft function and patient survival, guiding early intervention strategies aimed at improving long-term outcomes.

Kidney transplant (KT) recipients who return to dialysis face significant challenges in accessing a second transplant due to HLA sensitization. Although it is recognized that immunosuppression (IS) management after graft failure (KTF) can influence the sensitization status, there are no strong evidence-based guidelines, leading to widely variable clinical practices. This systematic review with meta-analysis aims to evaluate the impact of different IS withdrawal strategies after kidney transplant failure on HLA sensitization. We systematically reviewed prospective and retrospective cohort studies assessing the impact of prolonged or earlier IS withdrawal strategies on the following outcomes after graft failure: HLA sensitization (including the development of de novo DSA and average cPRA values or cPRA variation rate) and graft nephrectomy or embolization rates. We conducted a comprehensive search across Medline, Embase, and Cochrane Library and used the ROBINS-I scale to assess the risk of bias. The results were synthesized in a meta-analysis, and combined odds ratios and weighted mean differences were calculated using a random-effects model. The protocol for this meta-analysis was registered within PROSPERO (CRD42024496706). From 8008 citations, we identified 12 studies involving 1346 patients that fulfilled the eligibility criteria. Most of these studies were retrospective (n = 11), single-center (n = 10) cohorts and exhibited moderate to serious risk of bias. In all studies, the IS regimens in the prolonged withdrawal group involved maintaining more than one immunosuppressant for at least three months after graft failure. Five studies comprising 600 patients reported post-KTF cPRA absolute values; three studies comprising 316 patients reported cPRA variation rates; four studies comprising 498 patients reported de novo DSA occurrence, and nine studies comprising 1112 patients reported graft nephrectomy or embolization rates. Earlier IS withdrawal was significantly associated with decreased odds of cPRA maintenance (OR 0.22, 95% CI 0.05–0.96) and increased odds of graft nephrectomy or embolization (OR 2.13, 95% CI 1.39–3.26). While earlier IS withdrawal also favored a higher occurrence of de novo DSA (OR 2.41, 95% CI 0.43–13.46) and a higher absolute cPRA value (md +0.87, 95% CI −0.45–2.2), neither of these findings reached statistical significance. While prolonged IS withdrawal did not prevent the development of de novo DSA or lower cPRA values, it appeared to have a role in preserving the sensitization status of KT recipients returning to dialysis. Efforts were made to minimize heterogeneity among the included studies, particularly regarding the IS regimens compared and the methods and timing of HLA evaluation. Nonetheless, some heterogeneity remained, which may limit the generalizability of our findings. Importantly, the protective effect of prolonged IS withdrawal against graft intolerance syndrome was consistently observed across studies. This study also underscores the lack of multicenter and prospective research on this increasingly relevant topic, as the number of hypersensitized patients with previous graft failures on transplant waiting lists continues to grow.

Recent landmark studies such as CREDENCE, EMPA-REG, and DAPA-CKD have demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT2i) are relatively safe, with minimal side effects, and provide substantial benefits in diabetic patients with chronic kidney disease (CKD). These benefits include reduced proteinuria, slower decline in kidney function, and decreased cardiovascular events and mortality. However, data on the effects of SGLT2i in diabetic kidney transplant recipients remain scarce. This study aims to evaluate the safety and efficacy of SGLT2i by comparing two groups of diabetic kidney transplant patients: those receiving SGLT2i versus those not receiving SGLT2i. This was an observational retrospective single-center study including an initial cohort of 473 diabetic kidney transplant recipients. Of these, we identified 45 patients who had been taking SGLT2i for at least six months. These patients were matched with a control group of 45 diabetic kidney transplant recipients who were not taking SGLT2i. Matching criteria included age, gender, baseline serum creatinine at the time of SGLT2i initiation, and time since transplantation. Exclusion criteria were patients with type 1 diabetes or other diabetes mellitus modalities (LADA or MODY) (n = 41); patients with multiple organ transplant (n = 7); patients taking SGLT2i for less of six months (n = 19) and patients who lost of follow-up (n = 6). Primary outcomes were assessed at 6 months and 12 months and included: changes in proteinuria, kidney function (measured by serum creatinine), body mass index and glycated haemoglobin. Secondary outcomes included adverse events (genito-urinary infections, acute limb ischemia, euglycemic ketoacidosis), major cardiovascular events (stroke, myocardial infarction, cardiovascular death) and overall mortality. A 95% confidence interval was used for statistical analysis. The Mann-Whitney test was applied for comparisons between groups. A total of 90 patients were included and divided into two groups (45 patients per group). The demographic characteristics are detailed in Table 1. No significant differences were observed between the groups regarding HbA1c reduction (6 months: p = 0.373; 12 months: p = 0.278) and BMI changes (6 months: p = 1.0; 12 months: p = 0.755). Kidney function (serum creatinine) showed no significant differences at 6 months (p = 0.681) or 12 months (p = 0.908). Proteinuria showed a statistically significant reduction at 6 months in the SGLT2i group (median reduction of 13 mg/g, p = 0.04) compared to a median increase of 60 mg/g in the control group. This reduction was not observed at 12 months, likely due to the smaller follow-up sample size. No side effects were detected in the SGLT2i group. In the control group, one patient required hospitalization due to complicated pyelonephritis. The mortality rate was 2.2% (n = 1) in the SGLT2i group, with the patient experiencing multiorgan dysfunction following complications from coronary artery bypass surgery. These results supports the safety and potential efficacy of SGLT2i in kidney transplant patients. No significant adverse effects were observed in patients receiving SGLT2i, and a reduction in proteinuria was noted at 6 months. However, further larger-scale studies with longer follow-up periods are needed to confirm these findings and assess the long-term impact on allograft function, proteinuria, and cardiovascular outcomes.

A kidney transplant is the best option for patients with end-stage renal disease. The waiting list period can be long, especially for highly sensitized patients. We describe a 60-year-old woman who received a second transplant and was highly sensitized to vascular access exhaustion, anuric, and performing peritoneal dialysis. At 27 days post-transplant, the patient developed thrombosis of the allograft vein, oliguria, and elevated serum creatinine. Fibrinolysis was attempted, but the patient remained oliguric and with acute graft dysfunction. She had a suction thrombectomy using the Penumbra System, allowing the removal of all thrombi and repermeabilization of the vein graft, resolving the acute graft dysfunction.

BACKGROUND:Despite progressive improvements in graft and patient survival after kidney transplantation over the last decades, an increasing number of patients are waitlisted for retransplantation. Identifying the risk factors for second graft failure can help us improve management for such patients. The aim of this study was to compare the outcomes of kidney retransplantation with those of first transplantation.METHODS:This retrospective study included all the recipients of a second kidney transplant between January 2008 and December 2019. For each patient with a second kidney transplant, we selected the paired recipient from the same donor. We excluded recipients of donations from living donors, patient-and-donor pairs with more than 1 transplant, and patients without a pair. The follow-up took place December 31, 2020. We included 152 patients, corresponding to 76 pairs of recipients.RESULTS:Patients who underwent a second transplant had significantly higher panel reactive antibody values and longer waiting time for retransplantation. Biopsy-proven acute rejection episodes were doubled in patients undergoing a second transplant (P = .12). There was a lower survival of second grafts at the first, fifth, and 10th year (P < .05). The main factor influencing graft loss for both groups was acute rejection, and, in patients, with a second transplant, acute rejection increased the risk of graft loss by 17 times (odds ratio, 17.5; 95% confidence interval, 4.19-98).CONCLUSIONS:The clinical results of second kidney transplants still fall short of first transplants, with the main factor of poor prognosis being acute rejection. In young patients, allocation and immunosuppression management should consider this risk to improve long-term outcomes.

Patients with a failed kidney allograft have steadily increase in recent years and returning to dialysis after graft loss is one of the most difficult transitions for chronic kidney disease patients and their assistant physicians. The management of these patients is complex and encompasses the treatment of chronic kidney disease complications, dialysis restart and access planning, immunosuppression withdrawal, graft nephrectomy, and evaluation for a potential retransplant. In recent years, several groups have focused on the management of the patient with a failing renal graft and expert recommendations are arising. A review of Pubmed, ScienceDirect and the Cochrane Library was performed focusing on the specific care of these patients, from the management of low clearance complications to concerns with a subsequent kidney transplant. Conclusion: There is a growing interest in the failing renal graft and new approaches to improve these patients' outcomes are being defined including specific multidisciplinary programs, individualized immunosuppression withdrawal schemes, and strategies to prevent HLA sensitization and increase retransplant rates.

An increasing number of patients waitlisted for kidney transplantation have a previously failed graft. Retransplantation provides a significant improvement in morbidity, mortality, and quality of life when compared to dialysis. However, HLA sensitization is a major barrier to kidney retransplantation and the majority of the highly sensitized patients are waiting for a subsequent kidney transplant. A multidisciplinary team that includes immunogeneticists, transplant nephrologists and surgeons, and adequate allocation policies is fundamental to increase access to a kidney retransplant. A review of Pubmed, ScienceDirect, and the Cochrane Library was performed on the challenges of kidney retransplantation after graft loss, focusing on the HLA barrier and new strategies to overcome sensitization. Conclusion: Technical advances in immunogenetics, new desensitization protocols, and complex allocation programs have emerged in recent years to provide a new hope to kidney recipients with a previously failed graft.