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In recent years, advancements in immunosuppressive medications and post-transplant management have led to a significant decrease in acute rejection rates in renal allografts and consequent improvement in short-term graft survival. In contrast, recent data have shown an increased incidence of post-transplant glomerular diseases, which currently represent a leading cause of allograft loss. Although pathogenesis is not fully understood, growing evidence supports the role of inherited and immunological factors and has identified potential pre- and post-transplant predictors. In this review, we illustrate recent advancements in the pathogenesis of post-transplant glomerular disease and the role of risk factors and immunological triggers. In addition, we discuss potential prevention and management strategies. [ABSTRACT FROM AUTHOR]

We describe the epidemiology of cancer after kidney transplantation (KTx), investigating its risk factors and impact on therapeutic management and survival in KTx recipients (KTRs). The association between modification of immunosuppressive (IS) therapy after cancer and survival outcomes was analyzed. We collected data from 930 KTRs followed for 7 [1--19] years. The majority of KTRs received KTx from a deceased donor (84%). In total, 74% of patients received induction therapy with basiliximab and 26% with ATG. Maintenance therapy included steroids, calcineurin inhibitors, and mycophenolate. Patients with at least one cancer (CA+) amounted to 19%. NMSC was the most common tumor (55%). CA+ were older and had a higher BMI. Vasculitis and ADPKD were more prevalent in CA+. ATG was independently associated with CA+ and was related to earlier cancer development in survival and competing risk analyses (p = 0.01 and <0.0001; basiliximab 89 ± 4 vs. ATG 40 ± 4 months). After cancer diagnosis, a significant prognostic impact was derived from the shift to mTOR inhibitors compared to a definitive IS drug suspension (p = 0.004). Our data confirm the relevance of cancer as a complication in KTRs with ATG as an independent risk factor. An individualized choice of IS to be proposed at the time of KTx is crucial in the prevention of neoplastic risk. Finally, switching to mTORi could represent an important strategy to improve patient survival. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the prevalence and determinants of glucose metabolism abnormalities and their impact on long-term clinical outcomes in kidney transplant recipients (KTxps). A retrospective analysis of 832 KTxps (2004–2020) was performed. Patients were assessed at 1 (T1), 6 (T6), and 12 (T12) months post-transplantation and clinically followed for an average of 103 ± 60 months. At T6, 484 patients underwent an oral glucose tolerance test for the diagnosis of alterations in glucose metabolism (AMG+) or post-transplant diabetes mellitus (PTDM+). The prevalence of pre-transplant diabetes was 6.2%, with 22.4% of PTDM+ within the 1st year. Patients with AMG were older and exhibited altered lipid profiles, higher body mass index, and increased inflammatory indices. Age at transplantation, lipid profile, and inflammatory status were significant determinants of PTDM. Graft loss was unaffected by glucose metabolism alterations. Survival analysis demonstrated significantly worse long-term survival for KTxps with diabetes (pre- and PTDM+, p = 0.04). In a comparison of the ND and PTDM+ groups, no significant differences in death with a functioning graft were found. The AMG+ group exhibited worse survival (p < 0.001) than AMG−, even after excluding patients with diabetes mellitus. Future randomized controlled trials are necessary to delve deeper into this subject, specifically examining the effects of new antidiabetic treatments. [ABSTRACT FROM AUTHOR]

Kidney transplant (KT) recipients are known to be at risk of developing several cancer types; however, cancer mortality in this population is underinvestigated. Our study aimed to assess the risk of cancer death among Italian KT recipients compared to the corresponding general population. A cohort study was conducted among 7373 individuals who underwent KT between 2003 and 2020 in 17 Italian centers. Date and cause of death were retrieved until 31 December 2020. Indirect standardization was used to estimate standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs). Cancer was the most common cause of death among the 7373 KT recipients, constituting 32.4% of all deaths. A 1.8‐fold excess mortality (95% CI: 1.59‐2.09) was observed for all cancers combined. Lymphomas (SMR = 6.17, 95% CI: 3.81‐9.25), kidney cancer (SMR = 5.44, 95% CI: 2.97‐8.88) and skin melanoma (SMR = 3.19, 95% CI: 1.03‐6.98) showed the highest excess death risks. In addition, SMRs were increased about 1.6 to 3.0 times for cancers of lung, breast, bladder and other hematopoietic and lymphoid tissues. As compared to the general population, relative cancer mortality risk remained significantly elevated in all age groups though it decreased with increasing age. A linear temporal increase in SMR over time was documented for all cancers combined (P <.01). Our study documented significantly higher risks of cancer death in KT recipients than in the corresponding general population. Such results support further investigation into the prevention and early detection of cancer in KT recipients. [ABSTRACT FROM AUTHOR]

Simple Summary: Solid-organ transplant recipients are known to be at higher risk of developing several cancer types, mainly virus-related malignancies. Monitoring trends in the incidence of post-transplant cancers among individuals who received solid organ transplantation helps to improve preventive measures and outcomes. This cohort study aimed to examine, over a 25-year period in Italy, variations in the occurrence of post-transplant cancers among 11,418 recipients of kidney transplantation (KT). Cancer incidence over three periods (1997–2004; 2005–2012; and 2013–2021) was analyzed within the cohort and in comparison with the general population. After multivariate adjustment, both approaches highlighted reduced risks of Kaposi's sarcoma, whereas no statistically significant changes over time in the incidence of other cancers were noted. Accordingly, the results of this study highlighted the need to sustain and strengthen cancer-preventive actions in KT recipients. This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997–2004; 2005–2012; and 2013–2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends. Overall, 1646 post-transplant cancers were diagnosed, with incidence rates/1000 person-years ranging from 15.5 in 1997–2004 to 21.0 in 2013–2021. Adjusted IRRs showed a significant reduction in incidence rates across periods for all cancers combined after exclusion of nonmelanoma skin cancers (IRR = 0.90, 95% confidence interval-CI: 0.76–1.07 in 2005–2012; IRR = 0.72, 95% CI: 0.60–0.87 in 2013–2021 vs. 1997–2004; Ptrend < 0.01). In site-specific analyses, however, significant changes in incidence rates were observed only for Kaposi's sarcoma (KS; IRR = 0.37, 95% CI: 0.24–0.57 in 2005–2012; IRR = 0.09, 95% CI: 0.04–0.18 in 2013–2021; Ptrend < 0.01). As compared to the general population, the overall post-transplant cancer risk in KT recipients was elevated, with a decreasing magnitude over time (SIR = 2.54, 95% CI: 2.26–2.85 in 1997–2004; SIR = 1.99, 95% CI: 1.83–2.16 in 2013–2021; Ptrend < 0.01). A decline in SIRs was observed specifically for non-Hodgkin lymphoma and KS, though only the KS trend retained statistical significance after adjustment. In conclusion, apart from KS, no changes in the incidence of other cancers over time were observed among Italian KT recipients. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) vaccination hesitancy is a threat as COVID-19 vaccines have reduced both viral transmission and virus-associated mortality rates, particularly in high-risk subgroups. Solid organ transplant recipients (SOTRs) are particularly vulnerable, as the underlying causes of their organ failure and the chronic immunosuppression are associated with a lower immune response to COVID-19 vaccines, and with an excessive risk of death due to SARS-CoV-2 infection. We aimed to evaluate COVID-19 vaccination hesitancy and its reasons in a population of SOTRs. Methods: All the SOTRs attending our post-transplant clinics were asked to fill in a vaccination status form with specific validated questions related to their willingness to receive a third vaccine dose. In the case of negative answers, the patients were encouraged to explain the reasons for their refusal. Among the SOTRs (1899), 1019 were investigated (53.7%). Results: Overall, 5.01% (51/1019) of the SOTRs raised concerns regarding the future third dose vaccination. In more detail, hesitancy rates were 3.3% (15/453), 4.2% (7/166), and 7.3% (29/400) among the investigated liver, lung, and kidney transplant recipients, respectively (p = 0.0018). The main reasons for hesitancy were fear of adverse events (30/51, 58.8%) and perceived lack of efficacy (21/51, 41.2%). Conclusions: Full adherence to ongoing or future vaccination campaigns is crucial to prevent, or at least reduce, COVID-19-related morbidity and mortality in fragile patients. The identification of the reasons influencing COVID-19 vaccination hesitancy in these patients is very important to establish appropriate and targeted patient–doctor communication strategies, and to further implement specific vaccination campaigns. [ABSTRACT FROM AUTHOR]

Kidney transplant candidates and kidney transplant recipients (KTRs) are at particular risk of severe complications of COVID-19 disease. In Western countries, mortality in affected hospitalized KTRs ranges between 19% and 50%. COVID-19 vaccination remains the most important measure to prevent the severity of infection in candidates and recipients of kidney transplant. However, the uraemic condition may affect the vaccine-induced immunity in patients with advanced chronic kidney disease (CKD) and in KTRs. Retention of uraemic toxins, dysbiosis, dysmetabolism, and dialysis can diminish the normal response to vaccination, leading to dysfunction of inflammatory and immune cells. In KTRs the efficacy of vaccines may be reduced by the immunosuppressive medications, and more than half of kidney transplant recipients are unable to build an immune response even after four administrations of anti-COVID-19 vaccines. The lack of antibody response leaves these patients at high risk for SARS-CoV-2 infection and severe COVID-19 disease. The aim of the present review is to focus on the main reasons for the impaired immunological response among candidates and kidney transplant recipients and to highlight some of the present options available to solve the problem. [ABSTRACT FROM AUTHOR]

Background and objectives: New-onset diabetes after transplantation (NODAT) represents a primary cause of morbidity and allograft loss. We assessed prevalence and risk factors for NODAT in a population of Italian kidney transplant (KT) recipients. Methods: Data from 522 KT performed between January 2004 and December 2014 were analyzed. Participants underwent clinical examination; blood and urine laboratory tests were obtained at baseline, one, six, and 12-month of follow-up to detect glucose homeostasis abnormalities and associated metabolic disorders. An oral glucose tolerance test (OGTT) was performed at six months in 303 subjects. Results: Most patients were Caucasian (82.4%) with a mean age of 48 ± 12 years. The prevalence of abnormal glucose metabolism (AGM) and NODAT was 12.6% and 10.7%, respectively. Comparing characteristics of patients with normal glucose metabolism (NGM) to those with NODAT, we found a significant difference in living donation (16.6% vs. 6.1%; p = 0.03) and age at transplant (46 ± 12 vs. 56 ± 9 years; p = 0.0001). Also, we observed that patients developing NODAT had received higher cumulative steroid doses (1-month: 1165 ± 593 mg vs. 904 ± 427 mg; p = 0.002; 6-month:2194 ± 1159 mg vs. 1940 ± 744 mg; p = 0.002). The NODAT group showed inferior allograft function compared to patients with NGM (1-year eGFR: 50.1 ± 16.5 vs. 57 ± 20 mL/min/1.73 m2; p = 0.02). NODAT patients were more likely to exhibit elevated systolic blood pressure and higher total cholesterol and triglyceride levels than controls. Conclusions: The prevalence of NODAT in our cohort was relatively high. Patient age and early post-transplant events such as steroid abuse are associated with NODAT development. [ABSTRACT FROM AUTHOR]

Kidney transplant recipients are a vulnerable population at risk of a life-threatening COVID-19 infection with an incidence of death four-times higher than in the general population. The availability of mRNA COVID-19 vaccines has dramatically changed the fate of this infection also within this fragile population. Transplanted patients have an impaired immunological response also to mRNA vaccines. In March 2021, however, we started a vaccination campaign. These preliminary results show that both the incidence of death and of hospitalization dropped from 13% to 2.4% and from 45% to 12.5% compared to the previous outbreaks reported by our group. In univariate analysis, two variables were associated with an increased risk of hospitalization: older age and dyspnea (p = 0.023, p < 0.0001, respectively). In multivariate analysis, dyspnea (p < 0.0001) and mycophenolate therapy (p = 0.003) were independently associated with the risk of hospitalization. The association was even stronger when the two variables were combined (p < 0.0001). Vaccinations did not reduce the incidence of COVID-19 infections among our transplanted patients, but provided certain protection that was associated with a significantly better outcome for this infection. [ABSTRACT FROM AUTHOR]

Background: Recently the protective role of 25-hydroxyvitamin D (25(OH)D) against viral infections has been hypothesized. We evaluated the association between vitamin D status and SARS-CoV-2 infection susceptibility and severity in a cohort of kidney transplanted patients (KTxp). Methods: A total of 61 KTxp with SARS-CoV-2 infection (COV+) were matched with 122 healthy KTxp controls (COV−). Main biochemical parameters at 1, 6, and 12 months before SARS-CoV-2 infection were recorded. Vitamin D status was considered as the mean of two 25(OH)D measures obtained 6 ± 2 months apart during the last year. The severity of SARS-CoV-2 infection was based on the need for hospitalization (HOSP+) and death (D+). Results: 25(OH)D levels were lower in COV+ than in controls [19(12–26) vs. 23(17–31) ng/mL, p = 0.01]. No differences among the other biochemical parameters were found. The SARS-CoV-2 infection discriminative power of 25(OH)D was evaluated by ROC-curve (AUC 0.61, 95% CI 0.5–0.7, p = 0.01). 25(OH)D was not significantly different between HOSP+ and HOSP− [17(8–25) vs. 20(15–26) ng/mL, p = 0.19] and between D+ and D− [14(6–23) vs. 20(14–26) ng/mL, p = 0.22] and had no significant correlation with disease length. Conclusions: During the year preceding the infection, 25(OH)D levels were lower in COV+ KTxp in comparison with controls matched for demographic features and comorbidities. No significant association between vitamin D status and SARS-CoV-2 infection related outcomes was found. [ABSTRACT FROM AUTHOR]

COVID-19 is a life-threatening infection among elderly patients, comorbid patients, or transplanted patients. Lombardy (region of Italy), accounts for 786,324 cases as of 21 April 2021. We retrospectively describe our single Centre experience in 82 adult kidney-transplant patients with COVID-19 infection during two pandemic outbreaks: 27 (first outbreak) and 65 (second outbreak). Thirty-seven patients were hospitalized (HP) and sixty-five were home managed (HM). Infection presented with fever (80%), cough (51%), and dyspnea (33%). HP were older (60 ± 11 vs. 50 ± 14 years, p = 0.001), had more severe respiratory symptoms (dyspnea 62.1%, p < 0.0001–cough 67% p = 0.008), and a longer length of disease (30 ± 28 vs. 21 ± 10, p = 0.04). The incidence of acute kidney injury (AKI) was 29.7% (p < 0.0001). Steroid dosage was increased in 66% of patients (p = 0.0003), while calcineurin inhibitors were reduced by up to one third in 45% of cases, p < 0.0001. Eleven patients died (13%). HM patients recovered completely without sequelae. In the overall cohort, AKI development (p = 0.006 OR 50.4 CI 95% 3.0–836) and age (p = 0.04 OR 1.1 CI 95% 1.0–1.2) were the most important factors influencing the probability of death during the infection. Although we report a relatively low incidence of infection (5.1%) the incidence of death is almost four times higher than it is in the general population. [ABSTRACT FROM AUTHOR]

In 32-kidney transplanted patients (KTxps), the safety and the effects on BMD and mineral metabolism (MM) of one-year treatment with denosumab (DB) were studied. Femoral and vertebral BMD and T-score, FRAX score and vertebral fractures (sVF) before (T0) and after 12 months (T12) of treatment were measured. MM, renal parameters, hypocalcemic episodes (HpCa), urinary tract infections (UTI), major graft and KTxps outcomes were monitored. The cohort was composed mainly of females, n = 21. We had 29 KTxps on steroid therapy and 22 KTxps on vitamin D supplementation. At T0, 25 and 7 KTxps had femoral osteoporosis (F-OPS) and osteopenia (F-OPS), respectively. Twenty-three and six KTxps had vertebral osteoporosis (V-OPS) and osteopenia (V-OPS), respectively. Seventeen KTxps had sVF. At T12, T-score increased at femoral and vertebral sites (p = 0.05, p = 0.008). The prevalence of F-OPS and V-OPS reduced from 78% to 69% and from 72% to 50%, respectively. Twenty-five KTxps ameliorated FRAX score and two KTxps had novel sVF. At T12, a slight reduction of Ca was present, without HpCa. Four KTxps had UTI. No graft rejections, loss of graft or deaths were reported. Our preliminary results show a good efficacy and safety of DB in KTxps. Longer and randomized studies involving more KTxps might elucidate the possible primary role of DB in the treatment of bone disorders in KTxps. [ABSTRACT FROM AUTHOR]

The prevalence and the factors related to cytomegalovirus (CMV) disease (CMVd) during the 1st year of renal transplantation (RTx) and the relationship between CMVd and early and long-term graft and RTx-patient (RTx-p) survival were evaluated. In 505 RTx-p, followed up for 8(5–11) years, data were recorded after 1-(T1) and 12-(T12) months of RTx. CMVd was defined either by CMV replication without clinical signs of disease (CMVr, 43%), or CMV replication with signs of disease (CMVs, 57%). During the 1st year of RTx, 45% of RTx-p had CMVd (CMVd+). CMVd+ patients were older than CMVd− patients. Female gender and Donor CMV-IgG+ (CMV IgG−D+)/recipient IgG- (CMV IgG−R-) status were more prevalent in CMVd+. At T1, CMVd+ had lower albumin, haemoglobin, and higher uric-acid and reactive C-protein than CMVd− and, at T1 and T12, received more steroids. Albumin-T1 was the unique factor in determining CMVd+, maintaining its significance also after the inclusion of IgG−D+/IgG−R− status to the model. CMVs had higher prevalence of CMV IgG-D+/IgG-R- than CMVr. CMVd, CMVr, and CMVs had no impact on graft loss (11% of RTx-p) and RTx-p death (8% of RTx-p). CMVd is highly prevalent during the 1st year of RTx. Albumin-T1 influences CMVd insurgence. CMVd did not impact on RTx and RTx-p loss. [ABSTRACT FROM AUTHOR]

In nine chronic haemodialysis patients a desferrioxamine (DFO) load test (40 mg/kg body-weight) was performed1 year after the beginning of treatment with recombinant human erythropoietin (rHuEpo). The patients were then divided intotwo groups. Group A comprised five patients with a greater mean aluminium (204 ± 28 μg/1) than the four patients in group B. Group A was given a mean dose of 25.8 g (range 14–39 g) of DFO over 6 months. Group B (aluminium values 112 ± 36 μg/1) was never treated with DFO. During the period of observation, plasma iron, serum ferritin and transferrin, as well as iron supplementation, did not differ between the groups.After DFO treatment a second DFO load test was performed.The mean predialysis aluminium value was significantly reduced in group A (204 ± 28 vs 111 ± 72 μg/1; P<0.05), while remaining unchanged in group B (112 ± 36 vsl40±39μg/l; P=ns).In both groups, the doses of rHuEpo necessary to maintain the same haemoglobin valuesdecreased with time, but reduced significantly only in group A (298±105 vs 110 ± 61 μ/kgperweek; δ-63%;P<0.01).Thus, aluminium interferes with the response to rHuEpo in haemodialysis patients, and the correction of aluminium overload with DFO canallow a considerable sparing of rHuEpo. [ABSTRACT FROM PUBLISHER]

In 11 chronic haemodialysis patients we investigated whether the increase in haematocrit during recombinant human erythropoietin (rHuEPO) treatment might alter the long-term efficiency of haemodialysis. After correction of anaemia with rHuEPO (mean Ht 35±2% vs 19±2% at baseline) (p0.001), mean predialysis creatinine and urea did not change, while predialysis phosphate (1.77±0.38 vs 1.51±0.29 mmol/l) were significantly increased (p 0.01). In six of the 11 rHuEPO treated patients a post- versus pre-dialysis haemoconcentration (haematocrit 44% vs 35%) not attributable to different ultrafiltration regimes, was observed. In these 6 patients mean predialysis phosphate, creatinine and urea tended to be higher, but not significantly, in comparison to the remaining 5 patients who did not haemoconcentrate. Dialyser clearances and total extractions for urea, creatinine, phosphate and inulin were compared to those of 11 matched haemodialysis patients with anaemia. No differences were observed either for small and middle molecule clearances or their extractions between rHuEPO and anaemic patients. In conclusion, dialysis efficiency is not affected if haematocrit values are kept about 35%. [ABSTRACT FROM PUBLISHER]