Search

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Re Sartò, Alfieri, Cosmai, Brigati, Campise, Regalia, Verdesca, Molinari, Pisacreta, Pirovano, Nardelli, Gallieni and Castellano.)

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.

Background: direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic., Aim of This Study: evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs., Methods: a multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed., Results: Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m 2 . ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82)., Conclusion: DOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

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 m 2 ; 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.

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.

Patients who have undergone kidney transplantation (KTx) (KTxps) are a distinctive population characterized by the persistence of some metabolic anomalies present during end-stage renal disease. Mineral metabolism (MM) parameters are frequently altered after KTx. These alterations involve calcium, phosphorus, vitamin D, and parathormone (PTH) disarrangements. At present, there is little consensus about the correct monitoring and management of PTH disorders in KTxps. This article presents the prevalence and epidemiologic and clinical impact of post-KTx hyper-PTH. The principal biochemical and instrumental investigations and the therapeutic options for these conditions are also reported., Competing Interests: Disclosure The authors do not have disclosure related to this manuscript to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In 178-kidney transplanted patients (KTxp), the prevalence of hypovitaminosis-D, the presence and novel development of left ventricular hypertrophy(LVH) and the correlations between native Vitamin-D (25OHD) and LVH were evaluated during the 1st year of transplantation (KTx). Clinical and instrumental data were recorded at pre-KTx and at one (T1) and 12 (T12) months after KTx. 25OHD levels were considered sufficient (s25OHD, ≥ 30 ng/dL) or insufficient (i25OHD, < 30 ng/dL). 25OHD correlated at T1 with parathormone(PTH), and at T12 with 25OHD-T1 and PTH-(T1,T12). At T12, s25OHD (15%) had higher 25OH and alkaline phosphatase (ALP), lower Ca, at T1, and lower PTH-(T1, T12) than i25OH-T12. At T1, KTxp with LVH (LVH-T1pos, 42%) were older and with longer dialysis vintage than LVH-T1neg. At T12, KTxp with LVH (LVH-T12pos, 53%) were older, with higher systolic blood pressure (SBP) at T12 than LVH-T12neg. No relation between 25OHD and LVH were found. Novel LVH was found in 14% of KTxp. They were older, had higher SBP-T12 and lower serum albumin-T12 than the others. LVH-modifications and 25OHD were not correlated. Hypovitaminosis-D is highly prevalent in KTxp. LVH correlates with different risk factors according to the time elapsed from KTx. However, during the 1st year of KTx, no relationship between LVH and 25OHD was observed.

Coronary artery calcifications(CACs), are related to the increased cardiovascular mortality during kidney transplantation(KTx). Using coronary-CT performed at 1 month(T0) and 5 years(T5) after KTx we evaluated: (1) the prevalence of CACs; (2) the clinical and biochemical factors related to CACs; 3) the factors implicated with CACs progression. We evaluated 67-pts selected from the 103-pts transplanted in our unit between 2007 and 2008. Clinical and biochemical parameters were recorded at the time of pre-KTx evaluation and for five years after KTx. Coronary-CT for the Agatson score (AS) evaluation was performed at T0 and at T5, and CACs progression was determined. At baseline AS was 45 [0-233]. At T5 AS was 119 [1-413]. At T0, 69% of patients had CACs. Age and dialytic vintage were the main independent variables related to CACs. At T5, CACs were present in 76% of patients. Age was the only independent factor in determining CACs. A progression of CACs was observed in 74% of patients. They were older, had higher CACs-T0 and higher SBP throughout the 5-years. The presence of CACs at T0 and age were the only independent factors in determining the CACs-progression. CACs-T0 had the best discriminative power for CACs progression. CACs prevalence is quite high in KTx patients; Age is strictly related to CACs; Age and the presence of CACs at baseline were the two major factors associated with the progression of CACs during the five years of follow up. CACs-T0 had the best discriminative power for progression of CACs.

Renal biopsy (RBx) informs about kidney transplantation (KTx) prognosis. In our observational study the prevalence of histological anomalies and the prognostic role of CD45, vimentin (VIM) and periostin (POSTN) in KTx-RBx have been evaluated. One hundred forty-six KTx-RBx (2009-2012) were analysed for general histology and in immunohistochemistry for CD45, VIM and POSTN. Clinical data of the 146-KTx patients were collected at the RBx time (T0), 6 and 12 months before and after RBx. Follow-up time was 21 ± 14 months. Glomerulosclerosis was 20% glomeruli/biopsy. Tubular atrophy (TA), Interstitial infiltrate (I-Inf) and interstitial fibrosis (IF) were slight in 21-18% and 25%, moderate in 22-30% and 26% and severe in 30-18% and 28% of patients. Fifty-eight percent of patients had lesions compatible with IF-TA. CD45, VIM and POSTN correlated to each-other and to TA, I-Inf and IF. VIM and POSTN correlated to GS. CD45 and VIM correlated directly to renal function (RF) and 25(OH)VitD, while POSTN inversely to 25(OH)VitD. Thirty patients restarted dialysis (HD+). HD+ had lower T0-eGFR, and higher CD45, VIM and POSTN than HD-. POSTN resulted the strongest in discriminate for HD+ . CD45, VIM and POSTN correlate to each-other and predict graft outcome. POSTN was the strongest in discriminate for HD+. 25(OH)VitD might influence inflammation and fibrosis in KTx.

Chronic metabolic acidosis (CMA) is a common complication of the more advanced stages of chronic kidney diseases (CKD), and is associated with morbidity and mortality of CKD patients and possibly with the progression of renal disease. Nevertheless, there is limited evidence or information on the prevalence, the potential causal factors, the clinical impact and the effects of correction of CMA in kidney transplant recipients. In this review, we briefly look at the more relevant, though scanty, studies which have, over time, addressed the above-mentioned points, with the hope that in the future the interest of transplant nephrologists and surgeons will grow towards this unreasonably neglected issue., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Vascular calcifications (VCs) are a cardiovascular risk factor in patients affected by chronic kidney disease and after kidney transplantation (KTx). We evaluated the prevalence of VCs at the abdominal aortic site in KTx patients at the time of transplantation and 1 year after KTx, exploring the possibly associated factors., Methods: In 107 transplanted patients, the following parameters were evaluated at the first and twelfth month after KTx: the aortic calcification index (ACI), fibroblast growth factor 23, osteoprotegerin (OPG), fetuin A, and clinical and biochemical parameters. Patients were followed up for 2 years after KTx., Results: At the time of KTx, 60% of patients had some degree of VC (ACI>0), whereas 40% had no VC. One year after KTx, VCs worsened in 26% of patients, whereas in 74%, VCs remained stable or improved. The progression of VC was observed almost exclusively in patients with a positive ACI score at the first month. At the multivariate analysis, serum calcium, OPG, and estimated glomerular filtration rate were the only variables independently associated with the progression of VC., Conclusions: VCs at the aortic site are frequent in KTx patients, and in a significant percentage of them, they tend to progress even in the short time. High levels of serum calcium and OPG are significantly associated with the progression of VCs. Whether these associations are based on a cause-effect relationship and their correction might impact on the calcification process could be ascertained by prospective interventional studies.

Hypercalcemia and hypophosphatemia are frequently observed in recipients of a kidney transplant (KTx). Hypercalcemia has been reported in up to 66% of KTx patients. Many factors have been suggested as the putative causal factors; however, the persistence of moderate-severe secondary hyperparathyroidism, associated with a change in the set-point of the Ca-controlled parathyroid hormone (PTH) secretion, is considered to play a prominent role. Hypercalcemia can negatively impact on both the graft and patient outcome, increasing the incidence of nephrocalcinosis, which can induce a worse graft outcome, inducing vascular calcifications, and increasing the incidence of pancreatitis. In addition, severe hypercalcemia after KTx often requires parathyroidectomy, which is not universally considered a safe medical solution in this clinical setting. After KTx, phosphate levels often fall below the normal range, with hypophosphatemia being observed in up to 40% of patients. The putative causal factors for this metabolic alteration are persistent hyperparathyroidism, increased levels of FGF-23, tubular damage secondary to the immunological effects, and toxic and vascular effectors. Hypophosphatemia can negatively impact on either skeletal or muscular systems, contributing to the increased incidence of bone fractures in KTx patients. The current therapeutic options should take into account an accurate pretransplant treatment and screening of the waiting-list patient and should also evaluate the efficacy and safety profile of the new pharmacological tools (calcimimetics) in comparison with the classical surgical approach (parathyroidectomy).

Hypercalcemia is a relatively common finding after kidney transplant, and when correctly evaluated has been reported to be present in around 5-15% of patients. The peak of its incidence can be found after the third month from transplantation and it usually maintains relatively constant levels, even though a moderate attenuation of the phenomenon can be expected in the long term. Many factors have been claimed to cause hypercalcemia after kidney transplant. However, the main recognized factor is the degree of persistent hyperparathyroidism deriving from a long previous history of uremia. It has been suggested that hypercalcemia can be damaging to both graft (induction of nephrocalcinosis, reduction of graft survival) and other organ or system functions (vascular calcification, erythrocytosis, pancreatitis, etc.). However, there is no definitive demonstration of a cause-effect relationship between hypercalcemia and the above-mentioned clinical events. Furthermore, it is not possible to establish to what extent these effects are due to hypercalcemia per se or also to increased PTH levels, which are often associated with hypercalcemia. In addition, there is no definitive evidence that correction of hypercalcemia might solve the above-mentioned clinical events. The best way to reduce the incidence of hypercalcemia is considered to be the optimization of therapy for secondary hyperparathyroidism during the pretransplant period. It has long been thought that parathyroidectomy was the only way to solve the problem of stabilized hypercalcemia associated with moderate-severe persistent hyperparathyroidism after kidney transplant. The introduction of calcimimetics, which have substantially changed the therapeutic approach to secondary hyperparathyroidism in dialysis patients, seems to be promising also in this field. However, many issues need to be clarified before its definitive inclusion into the therapeutic armamentarium of the transplant patient who is already burdened by so many medications.

A new prevention strategy for CMV infection was evaluated in our pediatric kidney transplant unit. This approach comprises a pre-emptive therapy, based upon the monitoring of CMV pp67 mRNA in whole blood by the qualitative NASBA, combined with prophylactic CMV-IG in high risk (R-/D+) children. Thirty-one kidney transplant children were followed for six months with serial measurements of CMV pp67 mRNA in the blood. The R-/D+ patients were given prophylactic CMV-IG for the first 16 wk after transplantation. I.v. ganciclovir was administered upon CMV detection by NASBA and was discontinued after two consecutive negative results. CMV infection, detected by NASBA, developed in 11 (35%) recipients: one (33%) of the R+/D- patients and 10 (72%) of the R-/D+ patients. CMV disease developed in 9.6% of the patients (3/31), exclusively in the R-/D+ group. These three patients presented concurrently with CMV viremia and disease. It is noteworthy that two of the three patients could not receive a complete course of CMV-IG, and one of the latter two subjects had been treated for acute rejection 15 days before CMV infection. Ganciclovir was given for the 11 cases of primary infection, and for three cases of relapsed CMV infection. pp67 NASBA-based pre-emptive ganciclovir therapy, combined with prophylactic CMV-IG in high-risk patients leads to a lower rate of CMV disease, as long as a complete course of CMV-IG has been administered and ganciclovir is given during the period of treatment for acute rejection in high-risk populations.

Allotransplantation of solid organs transfers passenger leucocytes which may give rise to a state of persistent microchimaerism. In this report we describe the case of a patient who developed a solitary plasmacytoma in a transplanted kidney more than 10 years after allografting. The diagnosis was established on the basis of the presence of a monoclonal IgG kappa peak in the serum, and light chain proteinuria, the plasmacytoid features of tumour cells including cell surface expression of IgG, kappa light chains, CD20, CD38 and CD56, the absence of lytic bone lesions and a normal bone marrow biopsy, and the disappearance of the monoclonal IgG peak after graft nephrectomy. A donor origin of the tumour was established by HLA DNA typing of tumour, tumour-free kidney tissue, and peripheral blood leucocytes, respectively.