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Over the last two decades, rituximab (RTX) has played an important role in the treatment of some lymphoproliferative malignancies and immune-mediated diseases. RTX administration is generally safe and well-tolerated, but side effects including late-onset neutropenia, hypogammaglobulinemia, hepatitis B reactivation and rare cases of progressive multifocal leukoencephalopathy have been observed after its administration. Although there are no absolute contraindications regarding its use in people living with HIV (PLWH), the prescription of this drug has been principally limited in patients with oncohematological diseases. In this report, we described the outcome of four PLWH who underwent RTX therapy after the diagnosis of immune-mediated renal disease. The main RTX-associated adverse effects were leukopenia, late-onset neutropenia and decline of CD4+ and CD8+ T-cell counts. In addition, two of the four patients experienced pneumonia requiring hospitalization within six months from the last RTX infusion. We suggest that RTX should be used with caution in PLWH until further evidence emerges on its safety profile in this vulnerable population.

Background and Aims Many studies are available that reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative therapy for chronic kidney disease (CKD) have received lower attention, therefore little is known about how COVID-19 may affect this population. The aim of this study was to analyse the COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program, living in a small area of Northern Italy. Method The study population included CKD patients from the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of AUSL Romagna (Italy) and alive at 1.01.2020. All patients were in conservative therapy and none of them had initiated dialysis or received kidney transplantation. The hospital discharge database was used to identify patients hospitalized with COVID-19 up to 31.07.2020, and the mortality database was used to assess mortality among patients with COVID-19 at the same date. Multivariable logistic regression was used to identify predictors of COVID-19 disease, and Kaplan-Meier survival analysis to identify predictors of COVID-19 mortality. Excess mortality of 2020 compared to mortality in 2015-19 in the PIRP cohort was also estimated. Results COVID-19 incidence among CKD patients was 4.09% (193/4716 patients), while in the general population it was 0.46% (5,195/1,125,574). COVID-19 was more likely in CKD patients with older age (Odds Ratio=1.038), cardiovascular comorbidities (OR=2.217), COPD (OR=1.559) and less likely in patients living in the province of Ravenna (OR=0.468), that was hit later by the first wave of pandemic compared to the other areas of AUSL Romagna. Baseline eGFR was lower in CKD patients with COVID-19 (31.7 vs. 35.8 ml/min/1.73 m2), but this difference did not reach statistical significance (p=0.066). As of 31.07.2020, the crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/4523) in CKD patients without COVID-19 and to 14.5% (4289/29670) in the general population with COVID-19 of the Emilia-Romagna region. Factors associated with mortality of CKD patients with COVID-19 were older age (p=0.034) and the period of COVID-19 onset (p=0.003). The highest crude mortality rate (71.4%) was found in CKD patients for whom COVID-19 onset occurred between 8 and 21 March. The excess mortality of January-July 2020 with respect to the average mortality of January-July 2015-19 in the PIRP cohort was +17.7%, corresponding to 77 excess deaths. March-April was the period with the highest excess mortality (+69.8%), while in January-February a 15.9% lower mortality was observed with respect to the corresponding months of the five previous years. Conclusion In our study, including a cohort of regularly followed up CKD patients, the risk of COVID-19 disease and of COVID-19 related mortality was comparable, or even somewhat higher, to that observed in patients on dialysis and those who received kidney transplantation. The incidence of COVID-19 in CKD patients was higher in the areas of AUSL Romagna earlier affected by the pandemic wave, whereas mortality rates were similar across all areas. CKD patients represent a population very vulnerable to COVID-19 disease, and their protection should be highly prioritized in the models of care and prevention measures.

Background and objectives Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis. Design, setting, participants, & measurements In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25–10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization. Results At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64; P=0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: −16.3 g/m2; 95% confidence interval, −29.4 to −3.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls. Conclusions Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis. Clinical Trial registry name and registration number: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008–003529–17.

Many studies reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative management for chronic kidney disease (CKD) have received attention only recently, therefore less is known about how COVID-19 affects this population. The aim of this study was to provide evidence on COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program and in the population living in the same catchment area. The study population included CKD patients recruited in the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of the Romagna Local Health Authority (Italy) and alive at 1.01.2020. We estimated the incidence of COVID-19, its related mortality and the excess mortality within this PIRP cohort as of 31.07.2020. COVID-19 incidence in CKD patients was 4.09% (193/4,716 patients), while in the general population it was 0.46% (5,195/1,125,574). The crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/4,523) in CKD patients without COVID-19. The excess mortality of March-April 2020 was +69.8% than the average mortality of March-April 2015–19 in the PIRP cohort. In a cohort mostly including regularly followed up CKD patients, the incidence of COVID-19 among CKD patients was strongly related to the spread of the infection in the community, while its lethality is associated with the underlying kidney condition and comorbidities. COVID-19 related mortality was about ten times higher than that of CKD patients without COVID. For this reason, it is urgent to offer a direct protection to CKD patients by prioritizing their vaccination.

BACKGROUND Muscle weakness, incorrect body water distribution and reduced exercise tolerance are the main characteristics found in renal transplant recipients after surgical treatment. Regular physical supervised exercise programs, at moderate intensity, have been promoted to contrast these aspects, while few data are available for long-term unsupervised mixed exercise plans. Bioelectrical impedance vector analysis (BIVA) provides a semi-quantitative evaluation of body cell mass and body water. This study aims to approach the role of the BIVA analysis in the follow-up of Renal Transplant Group (RTG) and analyze the impact of unsupervised exercise program. METHODS Thirteen male RTG and ten healthy subjects, adherent to a tailored exercise program, at moderate intensity and prescribed in an unsupervised way, have been followed up for one year. Every six months all the subjects have been submitted to the ergometric test, echocardiographic exam and an analysis of body composition by bioimpedance. They were compared to a healthy control group (HG). RESULTS A significant reduction of the BMI was observed at the end of the study in the RTG group (T0 24.8±3.2, T12 24.2±3.2 kg/m2; P

Background: Despite the benefits of physical activity on cardiovascular risk in kidney transplant recipients (KTRs), the long-term effects of exercise have been poorly investigated. This is a three-year observational study comparing graft function and cardiovascular risk factors in active KTRs (AKTRs) vs. sedentary KTRs (SKTRs). Methods: KTRs with stable renal function were assigned to active or sedentary group in relation to the level of daily physical activity based on World Health Organization (WHO) recommendations (&lt, 150 or &gt, 150 minutes/week, respectively). Complete blood count, renal function indices, lipid profile, blood pressure and anthropometric measures were collected yearly for an observation period of three years. The comparisons between the two groups were performed by repeated measures analyses of covariance (ANCOVAs), with age as a covariate. Results: Fifty-four subjects were included in the study. Thirty of them were identified as AKTRs (M/F 26/4, aged 45 &plusmn, 12 years) and 24 as SKTRs (M/F 18/6, aged 51 &plusmn, 14 years). Baseline characteristics were similar between the groups except body mass index (BMI) that was significantly higher in SKTRs (p = 0.043). Furthermore, over the three-year observation period, BMI decreased in AKTRs and increased in SKTRs (p = 0.006). Graft function was stable in AKTRs, while it showed a decline over time in SKTRs, as indicated by the rise in serum creatinine levels (p = 0.006) and lower eGFR (p = 0.050). Proteinuria, glucose and uric acid levels displayed a decrease in AKTRs and an increase in SKTRs during the three-year period (p = 0.015, p = 0.004 and p = 0.013, respectively). Finally, concerning lipid profiles, AKTRs had a significant reduction over time of triglycerides levels, which conversely showed a clinically relevant increase in SKTRs (p = 0.014). Conclusions: Our findings indicate that regular weekly exercise training may counteract the increased cardiovascular risks and also prevent graft function decline in KTRs.

Background Following the positive experience of the national project “A transplant...and now it’s time for sport,” the Transplant Reference Center of the Emilia-Romagna Region has pursued the promotion of pre- and post-transplant physical exercise by developing a network. Methods The path involved the transplant centers and operative units (UU.OO) who wanted to target transplant and waiting list patients, who are clinically stable, to perform personalized exercise through a program (supervised or not) prescribed by a specialist in sports medicine. With the collaboration of the Collective Prevention and Public Health Service, the network was established, consisting of the sports medicine centers and the gyms that promote health for adapted physical activity (PS-AMA). To implement the network, training courses for all the professionals involved (doctors, nurses, exercise specialists) and operational meetings in the transplant centers-nephrology units with patients’ associations have been organized. Results To date, there are 14 transplant centers and UU.OO, 9 sports medicine centers, and 45 PS-AMA involved in this network. Seven training courses were organized with the participation of 193 health professionals. Since January 2016, there have been 65 transplanted patients and 5 patients on the waiting list who practice the prescribed exercise. Of these, 45 carry out supervised exercise in PS-AMA; 25 perform autonomous exercise. Each patient is monitored every 6 months. No problems related to the exercise performance were recorded. Conclusions The development of a network of professionals and associations is the key element to raise awareness of physical activity among transplanted and waiting-for-transplant patients, reducing the pathologies associated with a sedentary lifestyle.

Background and aims Despite the excellent long-term outcomes in liver transplant (LT) recipients, several medical complications related to lifestyle still represent an issue. This study examined the effects of a 12-month supervised aerobic and strength training program on the aerobic capacity, muscle strength, metabolic profile, liver function, and quality of life of a cohort of LT recipients. Methods LT recipients with stable liver function were assigned to interventional exercise (group A) or usual care (group B). Aerobic capacity, muscle strength, metabolic profile, liver and kidney function, and health-related quality of life were assessed at baseline and after 6 and 12 months. Group A attended supervised training sessions 3 times per week for 12 months. Group B received general recommendations about home-based exercise. Results Forty patients from 6 Italian LT centers were randomized. Twenty-nine (72.5%, men-to-women ratio 23:6, mean age, 52 ± 8 years) LT recipients completed the study. Baseline characteristics were similar between groups except for body mass index and time from LT. No episode of acute rejection nor increase of transaminases occurred. Maximum workload and body mass index increased in both groups over time, but fasting glucose significantly decreased in group A (94.0 ± 15.0 mg/dL vs 90.0 ± 17.0 mg/dL; P = .037) and increased in controls (95.0 ± 24.0 mg/dL vs 102.0 ± 34.0 mg/dL, P = .04). Upper limb muscle strength increased only in supervised LT recipients. Vitality and general and mental health domains significantly improved after physical exercise. Conclusions Supervised combined training was safe and effective in increasing aerobic capacity, muscle strength, and quality of life and in improving glucose metabolism in stable LT recipients.

Background and aim of the study In hemodialysis patients, sedentarism is a potentially modifiable mortality risk factor. We explored whether healthcare staff’s attitude towards exercise interacts with patient-perceived barriers in modifying the level of physical activity in this population. Methods In this prospective, cross-sectional, multicenter study we recruited 608 adult patients and 330 members of the healthcare staff in 16 hemodialysis units in Italy. We assessed patient-perceived barriers to, and healthcare staff’s attitude towards, exercise by specific questionnaires. We fitted multilevel linear models to analyze the relationships of either barriers or staff’s attitude, and their interaction, with a measure of patient self-reported physical activity (the Human Activity Profile–Adjusted Activity Score [HAP-AAS]), adjusting for multiple confounders. We also employed latent class analysis to dichotomize patients into those endorsing or not endorsing barriers. Results Most barriers were negatively associated with the HAP-AAS (adjusted change attributable to a given barrier ranging between -5.1 [“Feeling too old”, 95% Confidence Interval: -9.4 to -0.8] and -15.6 [“Ulcers on legs and feet”, 95%CI: -24.8 to -6.5]. We found a significant interaction between staff’s attitude and barriers (adjusted P values ranging between 0.03 [“I do not believe that it is physician’s or nurse’s role providing advice on exercise to patients on dialysis”] and 0.001 [“I do not often ask patients about exercise”]). A beneficial effect of a proactive staff’s attitude was evident only in patients not endorsing barriers. Conclusions Barriers and non-proactive staff’s attitude reduce physical activity in hemodialysis patients. Patients not endorsing barriers benefit the most from a proactive staff’s attitude.

AIM To evaluate the effect of a 12-mo supervised aerobic and resistance training, on renal function and exercise capacity compared to usual care recommendations. METHODS Ninety-nine kidney transplant recipients (KTRs) were assigned to interventional exercise (Group A; n = 52) and a usual care cohort (Group B; n = 47). Blood and urine chemistry, exercise capacity, muscular strength, anthropometric measures and health-related quality of life (HRQoL) were assessed at baseline, and after 6 and 12 mo. Group A underwent a supervised training three times per week for 12 mo. Group B received only general recommendations about home-based physical activities. RESULTS Eighty-five KTRs completed the study (Group A, n = 44; Group B, n = 41). After 12 mo, renal function remained stable in both groups. Group A significantly increased maximum workload (+13 W, P = 0.0003), V’O2 peak (+3.1 mL/kg per minute, P = 0.0099), muscular strength in plantar flexor (+12 kg, P = 0.0368), height in the countermovement jump (+1.9 cm, P = 0.0293) and decreased in Body Mass Index (-0.5 kg/m2, P = 0.0013). HRQoL significantly improved in physical function (P = 0.0019), physical-role limitations (P = 0.0321) and social functioning scales (P = 0.0346). No improvements were found in Group B. CONCLUSION Twelve-month of supervised aerobic and resistance training improves the physiological variables related to physical fitness and cardiovascular risks without consequences on renal function. Recommendations alone are not sufficient to induce changes in exercise capacity of KTRs. Our study is an example of collaborative working between transplant centres, sports medicine and exercise facilities.

The aim of this multicenter, prospective study was to explore the possibility of carrying out routine sessions of post-dilution hemodiafiltration with a polyacrylonitrile membrane grafted with heparin (HeprAN) and reduced anticoagulation. Forty-four patients from eight centers were included in the study and treated by means of post-dilution on-line hemodiafiltration with automatic control of TMP, according to three different modalities tested consecutively: phase 1, polyethersulfone filter primed with heparinized saline and anticoagulated with continuous infusion of unfractionated heparin 1000/h; phase 2, HeprAN membrane filter primed with saline without heparin. Anticoagulation: a 1000-unit bolus of unfractionated heparin at the start of session followed by a second one at the end of the second dialysis hour; phase 3, same filter and priming procedure as in phase 2; anticoagulation with nadroparin calcium at the beginning of treatment. Partial or massive clotting of the dialyzer occurred in less than 1% of sessions in phase 1; 10% and 7% in phase 2; and 1% and 2% in phase 3. Clotting limited to the drip chambers was observed in 13%, 34% and 12%, respectively. The study of coagulation parameters showed a better profile when low-molecular weight heparin (LMWH) was used in association with HeprAN membrane, while the generation of TAT complexes did not differ from that observed with the standard anticoagulation modality used in phase 1. Our results suggest that the HeprAN membrane can be used safely in routine post-dilution hemodiafiltration with reduced doses of LMWH.

Introduction It is widely accepted that the risk of malignancies is significantly increased among patients with end-stage kidney disease (ESKD) and after kidney transplantation compared with the general population. Only a few data are available on kidney transplantation waiting list patients. The aim of this study was to investigate solid organ cancer incidence among subjects on the waiting list at a single center. Materials and Methods We retrospectively reviewed the records of all patients enrolled on our kidney transplantation waiting list between August 1, 2008 and July 31, 2010, seeking to evaluate the causes of withdrawal from the list, incidence of cancer, type of neoplasm, and its correlation with clinical features. We estimated the ratio of observed to expected numbers of cancers, the standardized incidence ratio (SIR). Results Among 1184 patients, we excluded 569 patients from the waiting list including 26 (4.56%) who displayed malignancies. The overall incidence of cancer was 0.11 events/person-months and the overall prevalence of cancer was 2.2%. In 97% of patients, the malignant disease was confined to the primitive organ of origin without secondary dissemination. We observed a prevalence of cancers related to ESKD (17; 65.38%). The SIR for all cancer types in our population compared with the general population was 2.22. The SIR for native kidney and thyroid cancers among our population compared with the general population was >10. Conclusion The incidence of cancer was significantly increased among kidney transplantation waiting list patients compared with the general population. Our study highlighted the importance of a careful, targeted neoplastic screening. It could be particularly important for ESKD-related malignancies like native kidney tumors or thyroid cancers.

Background/Aims: The role of physical activity in transplanted patients is often underestimated. We discuss the Italian National Transplant Centre experience, which started in 2008 studying transplanted patients involved in sports activities. The study was then developed through a model of cooperation between surgeons, sports physicians and exercise specialists. Methods: A multicentre study was realized in 120 transplanted patients of which 60 treated with supervised physical activity (three sessions/week of aerobic and strengthening exercises) and 60 controls. We present the results of the first 26 patients (16 males, 10 females; 47.8±10.0 years; 21 kidney, 5 liver transplanted; time from transplant 2.3±1.4 years) who completed 12 months of supervised physical activity. Results: Data showed an increase of peak aerobic power (t=4.535; PConclusion: These preliminary results confirm the positive effects of supervised physical exercise. It can be considered as an input to promote other detailed exercise protocols.

The maintenance of an adequate of quality of life (QoL) represents a critical issue in the management of patients in haemodialysis and is also used to assess the effectiveness of health care programmes. The Consumer Direction Theory of Empowerment (CDTE) implies that greater patient direction in policy formulation and services delivery, together with an increased community integration, endorses a process which leads to a better QOL. The aim of the study was to test a contextualized version of CDTE in an ambulatory for patients in haemodialysis. Sixty-nine patients completed a questionnaire measuring the following variables: Patient direction, family integration, self-efficacy in managing the disease, mental and physical health. The results showed that patient direction and family integration have an indirect effect on QoL, through self-efficacy in managing the disease. The hypotheses were thus confirmed, providing support for the potential of CDTE in the context of health services for haemodialysis patients. Implications for the implementation of health programmes aimed at improving QoL of patients in haemodialysis are discussed, including interventions focused on psychological and contextual factors.

Most of the difficulties when trying to realize the proposal to prescribe physical activity for transplantation patients come from patient attitudes and cultural beliefs that ignore the benefits of exercise, but there also are organizational aspects arising from the difficulties that these patients face in accessing supervised exercise facilities. To address these difficulties, the Italian study project "Transplant … and Now Sport" was developed based on a model of cooperation among transplantation specialists, sports physicians, and exercise specialists organized as a team combining their specific skills to effectively actuate the physical exercise programs. This preliminary report is based on 26 patients (16 male, 10 female; 47.8±10.0 years old; 21 kidney and 5 liver transplantations; time from transplantation 2.3±1.4 years) who performed prescribed and supervised exercises consisting of 3 sessions per week of aerobic and strengthening exercises for 1 year. Preliminary results show a significant decrease in body mass index (t=1.966; P

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Introduction Evaluation of kidney transplant candidates is based on strict exclusion of major pathologies, such as neoplastic disease. The aim of this study is to evaluate epidemiological and clinical impact of tumor disease in an Italian renal transplant waiting list and to propose a screening schedule for neoplastic detection. Materials and methods We retrospectively observed data of patients enrolled on the Emilia-Romagna kidney transplant waiting list between 1st August 2008 and 31st December 2010, evaluating the different causes of getting out from the list, the histologic type and incidence of cancer and the correlation between cancer onset and clinical features. The ratio of observed to expected cancer numbers (standardized incidence ratio, SIR), was estimated. Results We observed 2345 patients; 1297 got out from the waiting list; 57 of them (4,4%) got out because the onset of tumor. The overall incidence rate of cancer was 1354.8 (x 100000 person-year) (1045.9 person-year in patients awaiting for first transplant(FT), 1851.5 person-year in patients awaiting for second transplant(ST)). The overall prevalence of cancer was 2,43% (2.2% in FT, 3.4% in ST) with a SIR of 1.8; In our population the prevalence of cancers related to ESKD was 52.6% with a SIR of 15.8. Conclusion Kidney transplant waiting list patients present a higher incidence and prevalence of cancer compared to general population; it could be important to evaluate them for ESKD related malignancies because of their high incidence.

A 55-year-old Caucasian man who had received a second kidney graft in July 1993, was switched from cyclosporine to tacrolimus in June 2000 due to deterioration of renal function. Thereafter, he began to complain of muscle cramps in both quadriceps with an increased CPK and EMG findings of polyneuropathy. A muscle biopsy demonstrated acute myositis. Prednisone was administered with amelioration of the patient's symptoms, but with persistently increased CPK and myoglobin levels. In February 2001, mycophenolate mofetil was introduced and tacrolimus tapered to 3 mg daily to seek a toxic role of this immunosuppressant, since there was no other cause of myositis. A sudden decrease in CPK was observed, but the complete normalization took place only after its withdrawal in September 2002. This case represents a tacrolimus-associated myositis.

Cobalt is regarded as being responsible for a form of myocardiopathy whose pathogenesis and clinical description must still find a specific place in the range of congestive myocardiopathies. In spite of this, epidemiological studies are not sufficient to prove the role of cobalt in inducing myocardiopathy in hard metal workers. This critical review intends to evaluate if hard metal exposure may induce toxic effects on the heart. In this context, the literature considered ranges from pioneer reports on 'beer drinkers' to the more recent papers concerning cases of patients occupationally exposed; subjects who, after a surgical operation died of fulminant heart failure and, lastly, hard metal workers who were examined for their cardiac function. Various pathogenetic mechanisms related to possible cardiac effects in hard metal workers have been analyzed. The most likely should be the inhibition of cellular respiration due to inhibition of the mitochondrial dehydrogenase.

This article summarizes the present state of the art and some recommendations for solutions to problems identified by the European Congress on Cobalt and Hard Metal Disease on the basis of the papers and posters presented, as well as a round table discussion which produced several dominant questions and revealed areas of weakness and uncertainty. The round table discussion (chairman, Professor E. Capodaglio) focussed on the following aspects: (i) Monitoring (opinion leaders: R. Lauwerys, E. Sabbioni). (ii) Mechanisms of toxicity (opinion leaders: B. Nemery, N.L. Sprince, G. Scansetti). (iii) Health effects (opinion leaders: G. Nordberg, I.B. Andersen). (iv) Diagnosis/health surveillance (opinion leaders: G. Chiappino, S. Hernberg, S. Brown).

Viene fornito uno stato dell'arte riguardo ai principali schemi di terapia immunosoppressiva (terapia standard con schemi a duplice e triplice terapia, schema personalizzato con assenza di steroidi, minimizzazione calcineurina, senza inibitoro della calcineurina) per i pazienti trapiantati di rene. L'articolo fornisce inoltre le indicazioni sui livelli ematici efficaci dei farmaci immunosoppressori

The main points to note in terms of strategies in renal failure and the impact of lipids are: 1) Timing and typing of dyslipidemia; 2) Occurrence of dyslipidemia in the course of strategies (conservative, dialysis and transplantation); 3) How the strategies can handle the impact of lipids. Analysis of point 1 confirms what a complex profile uremic dyslipidemia presents, involving the type, class, composition and enzyme systems involved in lipid metabolism. In conservative and dialysis, type IV (triglycerides) predominates; in transplantation, type II (cholesterol). Examination of point 2 shows the non obligatory relationship between dyslipidemia and the various strategies of treatment. Lipid abnormalities, type IV or II, occur in 50-60% of patients. Uremic factors for dyslipidemia include: 1) enhanced hepatic stimulation or altered removal in conservative strategies; 2) the same causes plus “specific” promotors in dialysis (dialysis fluid, plasticizer leaching; bioincompat-ibility, etc.); 3) steroid therapy and other “accessories” in transplantation. A genetic predisposition is very likely present in all patients. Point 3, finally, analyzes the various “supplements” that each strategy requires to cope with the lipid impact. Generic rules (ranging from doing nothing, to diet, drugs, etc.) are of value in all strategies when dyslipidemia occurs. More specific rules include: a) Conservative strategies: appropriate dietetic optimization and modulation (protein-lipid-carbohydrate ratio in terms of calories); b) Dialysis: timing treatment and improving biocompatibility; c) Transplantation: reducing steroids as much as possible.

Immunological evaluation by panel-reactive antibody (PRA) and determination of anti-HLA specificity are important phases in the evaluation of patients awaiting kidney transplantation. The main causes of immunization are previous solid organ transplantation, hemotransfusion, and pregnancy. It is also possible that immunogenicity can be triggered by vascularized tissue grafts. Immune induction by cryopreserved bone prostheses is not yet understood. A 19-year-old patient with osteosarcoma had undergone resection of the left proximal tibia with reconstruction using human bone in 1997. The donor HLA typing was as follows: A3, A29 (19); B44 (12), Bw4; DR13 (6), DR7, DR52, DR53. The patient was subsequently enrolled onto the waiting list for cadaveric donor kidney transplantation due to chronic kidney failure caused by cisplatin toxicity. Pretransplantation immunological screening using the complement-dependent cytotoxicity (CDC) technique revealed a PRA of 63%. IgG antibody specificities were detected against class I and class II donor antigens, specifically anti-A3, B44, DR7 antibodies, using flow cytometry (Tepnel Luminex). Further immunological studies using single HLA specificity analysis (LSA Class I degrees -II degrees , Tepnel-Luminex) showed direct antibodies against all donor antigen specificities. This case showed immune induction after the implantation of bone prosthesis in a kidney transplant candidate, underlining the importance of the availability of HLA typing data of donors of a human prosthesis.

INTRODUCTION: Double-kidney transplantation is performed using organs from marginal donors with a histological score not suitable for single kidney transplantation. The aim of this study was to verify the results obtained with double-kidney transplantation in terms of graft/patient survivals and complications. PATIENTS AND METHODS: Between September 2001 and September 2006. 26 double-kidney transplantations were performed in our center. Indications for surgery were: chronic glomerulonephritis (n = 17), polycystic disease (n = 4), reflux nephropathy (n = 1), hypertensive nephroangiosclerosis (n = 4). The kidneys were all perfused with Celsior solution and mean cold ischemia time was 16.7 +/- 2.5 hours. In all cases, a pretransplant kidney biopsy was performed to evaluate the damage (mean score: 4.3). Immunosuppression was tacrolimus-based for all patients. RESULTS: Eighteen patients had good renal postoperative function, while the other eight displayed acute tubular necrosis. Two of the patients who had severe acute tubular necrosis never recovered renal function. There was only one episode of acute rejection, while the incidence of urinary complications was 31%. There were two surgical reoperations for intestinal perforation. Graft and recipient survivals were 82.7% and 100%, and 78.9% and 94% at 3 and 36 months, respectively. CONCLUSIONS: Double-kidney transplantation is a safe strategy to face the organ shortage. The score used in this study is useful to determine whether a kidney should be refused or suitable for single- or dual-kidney transplantation. The results of our experience are encouraging, but the series is too small to allow a conclusion.

Background: A few patients, after receiving solid organ transplantation, return to performing various sports and competitions; however, at present, data no study had evaluated the effects of endurance cycling races on their renal function. Methods: Race times and short form (36) health survey questionnaires of 10 kidney transplant recipients (KTR) and 8 liver transplant recipients (LTR) transplanted recipients involved in a road cycling race (130 km) were compared with 35 healthy control subjects (HCS), also taking laboratory blood and urine tests the day before the race, at the end of the race, and 18 to 24 hours after competing. Results: The 3 groups showed similar race times (KTR, 5 hours 59 minutes ± 0 hours 39 minutes; LTR, 6 hours 20 minutes ± 1 hour 11 minutes; HCS, 5 hours 40 minutes ± 1 hour 28 minutes), similar short form (36) health survey scores, and similar trend of laboratory parameters which returned to baseline after 18 to 24 hours. After the race, there was an increase in creatinine (0.24 mg/dL; effect size [ES] = 0.78; P < 0.001), urea (22 mg/dL; ES = 1.42; P < 0.001), and a decrease of estimated glomerular filtration rate (−17 mL/min; ES = 0.85; P < 0.001). The increase of blood uric acid was more remarkable in HCS and KTR (2.3 mg/dL; ES = 1.39; P < 0.001). The KTR showed an increase of microalbuminuria (167.4 mg/L; ES = 1.20; P < 0.001) and proteinuria (175 mg/mL; ES = 0.97; P < 0.001) similar to LTR (microalbuminuria: 176.0 mg/L; ES = 1.26; P < 0.001; proteinuria: 213 mg/mL; ES = 1.18; P < 0.001), with high individual variability. The HCS had a nonsignificant increase of microalbuminuria (4.4 mg/L; ES = 0.03; P = 0.338) and proteinuria (59 mg/mL; ES = 0.33; P = 0.084). Conclusions: Selected and well-trained KTR and LTR patients can participate to an endurance cycling race showing final race times and temporary modifications of kidney function similar to those of HCS group, despite some differences related to baseline clinical conditions and pharmacological therapies. Patients involved in this study represent the upper limit of performance currently available for transplant recipients and cannot be considered representative of the entire transplanted population.

A pretransplant positive cross-match is a contraindication for kidney transplantation, unlike in liver transplantation (OLT). In combined liver kidney transplantation (LKT) it is hypothesized that liver can protect kidney from rejection. We report the case of a 35-year-old woman on renal replacement therapy with gastrointestinal tract compression due to a hematoma following spontaneous liver rupture (May 2004). She was affected by amyloidosis, treated with a bone marrow autotransplantation (2001). The liver rupture was surgically untreatable, so an LKT was proposed. Panel-reactive antibody was 80% to 100% (complement dependent cytotoxicity) with specific anti-HLA antibodies (enzyme-linked immunosorbent assay). A compatible donor was found (July 2004). The cross-match before LKT was positive for B and T cells (score 8): an emergency OLT was performed. Immediately after liver reperfusion the cross-match result was less positive (6) for T cells. After 6 hours it was negative for T and slightly positive for B cells (4): the kidney was transplanted. The immunosuppressive therapy was: alemtuzumab, steroids, and tacrolimus. Renal function immediately recovered. On day 7 a rejection episode was successfully treated by increasing steroids (intravenous bolus). At discharge hepatic and renal function were normal (creatinine 1 mg/dL). They are stable after 1 year. This case showed LKT efficacy even in complex immunological situations. Many immunological mechanisms, still not defined, are hypothesized about the protective role of the liver. This case confirmed experimental data that highlighted that in vivo in humans a cross-match can change from positive to negative after OLT giving highly sensitized patients the possibility for LKT.

Combined liver and kidney transplantation (CLKT) has been increasingly used in recent years: 13 of our 19 cases were performed in the last 2 years being 3.2% of our liver transplantation (LT) and kidney transplantation (KT) activity. Only three of them were not on hemodialysis and the scheduling of a CLKT meant being at the top of the waiting list. We accepted only ideal donors and had no case of liver and only one case of kidney delayed graft function. Two deaths occurred during the first postoperative month, due to acute respiratory distress syndrome and multiorgan failure, both in patients with adult polycystic disease who were in poor nutritional condition due to a late indication for CLKT. We had two late deaths, one due to a native kidney tumor at 7 years and one at 8 years due to alcoholic cirrhosis recurrence. The late survival of our patients was 77.3% with all surviving patients showing good liver and kidney function. We planned not to do the KT in the case of a positive preoperative cross-match; but the only positive case became negative 8 hours after LT when we performed the KT. The patient is well after 2 years. The liver does not always protect the kidney if there are preformed antibodies, but we should try every possible technique not to lose the possibility of doing both transplants, because in case of LT alone the patients loses his top position on the CLKT waiting list and often waits years for a kidney.

In isolated liver transplantation pretransplant renal failure is a major mortality risk, there are no guidelines at the moment to establish the indications for a combined liver-kidney transplantation (LKT). In irreversible chronic renal failure (CRF) not on dialysis, nephrological evaluation is required to assess the need for a simultaneous kidney transplantation. There are no experiences about the functional contribution of native kidneys post-LKT. Herein we have reported the case of two patients who underwent LKT in 2004 due to CRF, not yet on dialysis. At the moment of LKT, the first patient (polycystic kidney disease) had a glomerular filtration rate (GFR) = 29 mL/min, and the second recipient (vascular nephropathy and diabetes), a GFR = 33 mL/min. In both cases we did not observe delayed graft function. At discharge the serum creatinine was 1.1 and 1.0 mg/dL, respectively, which was maintained during follow-up. In both cases renal scintigraphy with Tc-99 DMSA was performed to evaluate the functional contributions of transplanted versus native kidneys. In the first case scintigraphy at 9 months after LKT demonstrated an 81% contribution from the transplanted kidney, 9% from the right and 10% from the left native kidneys. In the second case, at 3 months after LKT, the functional contributions were 76%, 10%, and 14%, respectively. The transplanted kidney nephron mass may avoid the need for hemodialysis in the early posttransplant period; in the midterm it may help to maintain residual renal function. As in other combined transplant programs (heart-kidney, kidney-pancreas) with irreversible CRF, a GFR < or = 30 to 35 mL/min may be an indication for LKT, but we need more experience.

Combined liver kidney transplantation (LKT) has the potential to provide a complete recovery of liver and kidney failure; the literature reports an increase in LKT in the last few years and an improvement in patient and graft survival. In our experience 15 patients underwent LKT from 1997 to 2005. The mean age was 50 +/- 9 years (range 34 to 63). The patients were affected by viral (n = 9), alcoholic (n = 1), polycystic (n = 2), cholangitis (n = 1), cholestatic (n = 1), or amyloidotic (n = 1) chronic hepatopathy. Chronic renal failure (CRF) was due to polycystic kidney disease (n = 4), IgA (n = 2), interstitial nephropathy (n = 2), glomerulonephritis (n = 4), amyloidosis (n = 1), vascular nephropathy (n = 1), of unknown end-stage renal disease (n = 1). Twelve of 15 patients were on renal dialysis treatment, three patients had moderate/severe CRF. Two patients had previously been transplanted (kidney). All patients were selected based upon blood group identity and negative cross-match before kidney transplant. Histocompatibility matching (HLA) was not included in the selection criteria. We did not observe delayed graft function. After a mean follow-up was 23 +/- 32 months (range 5 to 99), 12 subjects show, normal hepatic and renal function. At the beginning of our experience two patients in bad clinical condition died within 3 months because of sepsis, and one died because of a malignancy after 7 years. Both organs were functioning well in the deceased patients. Survival analysis confirms LKT efficacy: at 5 years follow-up patient survival is 86%, graft survival censored for death 100%. Only two subjects had an acute rejection episode in the first year; the kidney rejection incidence was lower than that reported for an isolated kidney transplant (13% vs 21%).

Three hundred sixty-five patients who underwent cadaver donor kidney transplantation between 1993 and 1998 were divided into four groups: 40 immunized patients with at least one peak panel-reactive antibody (PRA) value more than 50 %, 11 hyperimmunized patients with more than three peak PRA values over 50 %, 10 retransplanted patients and 304 control patients. Before transplantation, we ascertained the antibody specificities against individual HLA antigens (Prastat Sangstat ELISA method for HLA typing of first donor, husbands of multiparous women and potential donors against whom candidates gave positive cross-matches); thus, patients underwent transplantation excluding the presence of the HLA antigens previously detected and looking for high HLA (class I and II) compatibility. Actuarial graft survival after 12 months was satisfactory in all groups: 87 % immunized, 81 % hyperimmunized and 80 % retransplanted vs 92 % controls. Renal function at the end of the first year was similar and the number of rejection episodes in the first 3 months did not significantly differ.

A multicentre trial (11 nephrology centres) was carried out to test the effects of ibopamine, an orally active dopamine-like drug, on the progression of chronic renal failure. For a 2-year period 189 chronic renal failure patients (serum creatinine level 1.5-4.0 mg/dl) were observed. They were homogeneous for basic nephropathy, degree of residual renal function, blood pressure, and proteinuria. the patients were randomly divided into two groups: 96 took ibopamine at a dosage of 100 mg/day (group A) and 93 served as controls (group B). All were on a low-protein diet (mean 0.8 g/kg body weight). By the end of the observation period, the rate of decrease of the renal function indexes in time proved significantly slower (1.8 times) in group A than in group B. The survival curves for renal function (pre-established end points were creatinine level increases equal to or > 20% and equal to or > 40% of the basal values) proved significantly better (p < 0.02 and p < 0.002 respectively) in group A than in group B. The mean plasma creatinine values rose by 17% in group A and by 36% in group B. The creatinine clearance decreased by 5% in treated patients and by 14% in the controls. Statistical analysis ruled out any possible centre effect. The trial suggests that low-dosage ibopamine administration may be used as a valid and safe pharmacological adjunct for retarding the progression of renal failure in patients with mild or moderate chronic renal impairment.

The results of a survey on workers potentially exposed to cobalt in the Bergamo Province are reported. Its aim is to assess the number of workers at risk of developing respiratory disease due to the inhalation of metallic cobalt. Interest was shown after an examination of 11 cases of ‘hard metal disease’, which we diagnosed, in workers who came from different production areas and had different degrees of exposure. A first group of 45 factories with potential cobalt exposure was identified by consulting the archives of the Local Sanitary Units (USSL) and of the Chamber of Commerce, and by use of the telephone directory and requesting information from the producers and users of Widia tools. A second group of 2039 factories was selected from those industrial activities where we had previously ascertained the presence of grinding operations using hard metal tools with diamond wheels. This study is related to all the factories in the first group and 10% of the factories in the second group. More than 304 inspections were carried out. In this context 403 exposed workers were identified. Workplace air measurements (250 samples) and biological monitoring (>600 samples) to determine the exposure levels to cobalt were performed. The results show an unexpected diffuse occupational exposure in different production areas where the airborne cobalt is frequently underestimated and higher than the TLV.

Eight hard metal workers exposed to cobalt containing dust (four producers of stone-cutting cobalt-diamond wheels and four grinders of hard metal tools) and affected by interstitial lung fibrosis have been examined. A close relationship between cobalt exposure and clinical findings was observed in six patients who were still working. The clinical picture ranged from minor symptoms to manifestations resembling those of hypersensitivity pneumonitis, with fever, weight-loss, non-productive cough and dyspnea. A restrictive impairment of the ventilatory function was prevalent. The chest roentgenogram of one patient showed a diffuse reticular nodular pattern, while the others presented a mild reticular accentuation of the interstitium. In five patients, bioptic specimens of the lung parenchyma showed interstitial collagenic fibrosis with inflammatory cells infiltrating the alveolar septa. An increased number of lymphocytes and polymorphs was reported in the bronchoalveolar lavage (BAL) fluid from seven patients. Giant multinucleated cells were present in the BAL of four subjects while an inversion of the helper-suppressor ratio was evident in those patients who were still exposed to cobalt when BAL was performed. In this study, the causal role of metallic cobalt inhalation in the etiology of the lung disease is examined and discussed.

The induction of cardiac effects in hard metal workers is uncertain. This study investigates cardiac function of a group of 31 hard metal workers with or without pulmonary disease. The average duration of exposure to cobalt containing dusts was 10.4 years (range 1–30), while the environmental levels of cobalt exposure ranged from 0.09 to 13.6 mg/m3 Co. Cardiac function has been studied by: EGG (electrocardiogram), exercise test (ET), ECG 24 h according to Holter (ECGH), echocardiogram (ECHO) and radionuclide angiocardiography with 99Tc (RNA). The aims of this work were (i) to show the existence of cobalt myocardiopathy in the workers analyzed and, (ii) to find an early indicator of cardiac dysfunction which could be used in the clinical examination of hard metal workers. Within the group of patients with hard metal lung disease, cases of myocardiopathy of doubtful aetiology have been found. The cardiac indexes obtained through RNA show ventricular dysfunction in healthy hard metal workers which could be a manifestation of initial pulmonary artery hypertension or of an early occult cor pulmonale due to an unknown fibrotic lung disease.

Flow cytometry (FC) may be considered as a fundamental technique in studying cell biology and pathology. It combines the quantitative character of biochemical methods with the multiparametric capacities of microscope analysis in a high-precision process for rapid analysis of individual cell characteristics. Three original FC techniques routinely applied in the field of renal transplantation are reported in the present study. They concern the donor—recipient cross-match test, the morphological analysis of urinary sediment and the modulation of the density of various membrane antigens on the lymphocyte surface. A common factor underlies all these methods: they aim to provide the physician with a reliable diagnostic tool in clinical renal transplantation.

We measured the serum concentration of alpha-1-acid glycoprotein (AAG) in 30 healthy subjects (controls), in 54 patients with various degrees of residual renal function (group I), and in 98 patients in the terminal phase of chronic renal failure (CRF) on both conservative and dialytic therapy (group II). A positive correlation between the logarithm of serum AAG and serum creatinine levels was found in group I. Serum AAG increased significantly when serum creatinine rose above 10 mg/dl. This fact would indicate that a retention of the substance occurs as the renal function falls. The mean serum concentration of AAG was significantly higher in group II patients, with no difference between those on conservative therapy and those on maintenance hemodialysis. However, levels above normal were present in only a minority of cases. We conclude that the serum AAG measurement maintains its diagnostic value as an acute phase reactant also in the terminal phase of CRF.

Growth differentiation factor 15 (GDF15) is a stress molecule produced in response to mitochondrial, metabolic and inflammatory stress with a number of beneficial effects on metabolism. However, at the level of skeletal muscle it is still unclear whether GDF15 is beneficial or detrimental. The aim of the study was to analyse the levels of circulating GDF15 in people of different age, characterized by different level of physical activity and to seek for correlation with hematological parameters related to inflammation. The plasma concentration of GDF15 was determined in a total of 228 subjects in the age range from 18 to 83 years. These subjects were recruited and divided into three different groups based on the level of physical activity: inactive patients with lower limb mobility impairment, active subjects represented by amateur endurance cyclists, and healthy controls taken from the general population. Cyclists were sampled before and after a strenuous physical bout (long distance cycling race). The plasma levels of GDF15 increase with age and are inversely associated with active lifestyle. In particular, at any age, circulating GDF15 is significantly higher in inactive patients and significantly lower in active people, such as cyclists before the race, with respect to control subjects. However, the strenuous physical exercise causes in cyclists a dramatic increase of GDF15 plasma levels, that after the race are similar to that of patients. Moreover, GDF15 plasma levels significantly correlate with quadriceps torque in patients and with the number of total leukocytes, neutrophils and lymphocytes in both cyclists (before and after race) and patients. Taken together, our data indicate that GDF15 is associated with decreased muscle performance and increased inflammation.