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When possible, living donor transplantation represents the best therapeutic strategy for patients suffering from chronic renal failure. Studying the donor allows a complete and thorough clinical, laboratory and instrumental assessment that guarantees good organ function whilst protecting the health of the donor. The main parameters considered within this framework are age, renal function, nephrological complications, comorbidities (diabetes, hypertension, obesity, etc.), malignancies, and infection. Moreover, particular attention is paid to the sociopsychological aspects of the donation, particularly related to the donor, the recipient, and the entire family situation.

Immunological evaluation by panel reactive antibody (PRA) and determination of anti-HLA specificity is an important phase in the assessment of patients awaiting kidney transplant. The main causes of immunization are previous solid organ transplants, blood transfusions, and pregnancy; immunogenicity can also be triggered by vascularized tissue grafts. Immune induction by cryopreserved bone allografts is not yet fully understood. We report the case of a 19-year-old patient with osteosarcoma who underwent resection of the left proximal tibia with reconstruction using human bone in 1997 (donor typing: A3, A29 (19) - B44 (12), Bw4 - DR13 (6), DR7, DR52, DR53). The patient was subsequently placed on the waiting list for a cadaver donor kidney transplant because of chronic kidney failure caused by cisplatin toxicity. Pretransplant immunological screening using the CDC (complement dependent cytotoxicity) technique revealed a PRA of 63% and anti-A3 and anti-A68 antibodies. The presence of IgG antibody specificity against class I and class II donor antigens (specifically anti-A3, B44, DR7 antibodies) was highlighted using flow cytometry (Tepnel-Luminex). Further immunological studies using single HLA specificity analysis (LSA Class I - II - Tepnel-Luminex) detected direct antibodies against all donor antigen specificities. This is the first reported case of immune induction after a bone graft in a kidney transplant candidate. It underlines the importance of the availability of HLA typing data of all human allograft donors.

The correct and constant management of transplant waiting lists is necessary for the optimal utilization of the limited number of organs available for transplantation. The guidelines regarding placement on transplant waiting lists (absolute and relative contraindications) are well documented, even though they are in constant development. The criteria for the monitoring of patients on waiting lists, however, are not so well defined; this aspect is subject to careful evaluation on account of the widening of the criteria for transplantation suitability, the increase in the average age of patients, a rise in the number of enrolments and, as a result, prolonged waiting time (in Italy, the average time spent on a waiting list is 37 months). During the waiting period, a greater risk of clinically significant comorbidities and mortality, above all from cardiovascular events, has been noted (the annual mortality is 5-7% in the US, 1.3% in Italy). An in-depth clinical and instrumental study of patients with chronic renal failure is necessary when screening eligible candidates for transplant programs, individualizing therapeutic strategies, and identifying patients for whom the risks outweigh the potential benefits. Clinical and instrumental monitoring, as well as adequate treatment of comorbidities during the waiting period, can help improve the post-transplant outcome. This work examines the study algorithms and monitoring procedures for patients on kidney transplant waiting lists.

Cardiovascular disease is the leading cause of mortality and morbidity in renal transplant recipients as well as the leading cause of death with a functioning graft. The high cardiovascular risk is attributable to the prolonged exposure to multiple traditional and nontraditional risk factors in the pretransplant and posttransplant period. Particular attention must be paid to cardiovascular screening of candidates for kidney transplantation. After a transplant, treatment and prevention strategies should be focused on the modifiable risk factors including smoking, dietary habits, physical activity, weight control, hypertension, and dyslipidemia. Further studies on these factors are needed to better define the pharmacological approaches (hypotensive or hypolipemic drugs) and therapeutic targets. In view of the role of immunosuppressive therapy in the onset or worsening of several risk factors, it is important to tailor the treatment approach and dosage to the cardiovascular risk profile of the individual patient.

Some endoscopic features of duodenal mucosa are marker of mucosal injury, the most common cause being celiac disease (CD). The aim of this study was to prospectively assess the diagnostic value of the endoscopic markers for the diagnosis of CD in the adult population undergoing routine upper endoscopy.This was a prospective multicenter study conducted at 37 Italian endoscopic centers. A total of 509 consecutive patients submitted to routine upper endoscopy who presented one or more of following endoscopic markers were included: 1) mucosal mosaic pattern in the bulb and/or descending duodenum (DD); 2) nodularity in the bulb and/or DD; 3) scalloping of Kerkring's folds; 4) reduction in the number or absence of folds in the DD. 4 biopsies samples were taken from descending duodenum. In patients with histological findings consistent with CD, according to Oberhuber classification, sierologic test (EMA, tTGA) were performed for confirm the diagnosis.At endoscopy, 249 patients showed an isolated marker; 260 subjects showed a coexistence of more than one marker; 369 patients (72.5%) presented mucosal lesions at histological examination and in 347 of these patients the diagnosis of CD was confirmed by serologic markers (94.0%). For 10 patients the diagnosis remained uncertain because of negative sierology and exclusion of other other cause of mucosal lesions. The diagnosis of CD was made in 61.3% patients who showed the mosaic pattern, in 65.7% of patients with nodular mucosa, in 64.4% of patients with scalloping of folds, in 40.2% of patients with reduction of folds, and in 61.5% of patients with loss of folds and in 83.6% of patients who showed the coexistence of more than one marker. The endoscopic markers overall had a PPV of 68% for the diagnosis of CD; the markers that singularly have demonstrated a higher correlation with CD are: mosaic mucosa of DD (PPV 65.0%), nodular mucosa of the bulb and DD (PPV 75.5%), and scalloping of folds (PPV 64.4%).The study confirms the important role of endoscopy in the diagnostic process of CD not only for the bioptic sampling in patients with clinical suspicion of CD, but especially for the opportunity to evaluate alterations of the duodenal mucosa suggestive of CD in the general population and, consequently, to identify those patients who should undergo a duodenal biopsy.

Assessment of quality of life in patients with different degrees of chronic kidney disease is an important issue because of its impact on clinical decisions and financial resource management in the health-care system. The aim of this study was to assess whether a generic instrument like the SF-36 questionnaire is able to discriminate three different populations of patients with different degrees of renal disease (pre-ESRD, ESRD, TxR). Five hundred sixty-three patients from 12 Italian nephrology units completed the SF-36 scales by themselves. The results from these samples were compared with those from the general population. Univariate analysis and multivariate regression were used. The generic SF-36 questionnaire proved to be a powerful instrument to discriminate populations with different degrees of chronic renal failure. The quality of life of patients on dialysis is significantly worse than that of the normal population and other patients with less severe renal function impairment.

Renal transplantation is the treatment of choice for patients with end-stage renal disease. In recent years a major improvement has been observed in short-term graft survival, but there has been no corresponding improvement in long-term survival. Chronic allograft dysfunction (CAD) is an anatomical and clinical alteration that can lead to the loss of the transplanted organ without any specific cause. The pathogenesis of CAD, which still remains to be fully clarified, involves both immunological factors (acute rejection, subclincial rejection, HLA mismatches between donor and recipient, noncompliance, etc) and non-immunological factors (marginal donor ischemia/reperfusion injury, infection, cardiovascular risk factors, nephrotoxicity, etc). Immunosuppressive therapy represents one of the strategies for the prevention of CAD. The introduction into clinical practice of novel immunosuppressive agents with no or lower nephrotoxicity, like mycophenolate mofetile, rapamycin and everolimus, will make therapeutic strategies aimed at decreasing the incidence of CAD feasible.

Renal allograft loss in the long term may be due to the death of a patient with a functioning graft or to chronic allograft nephropathy. One of the most important factors in the development of chronic allograft nephropathy is drug nephrotoxicity. The term nephrotoxicity comprises two distinct forms of renal injury: acute and chronic. Immunosuppressive drugs, and in particular calcineurin inhibitors, have a variety of side effects including nephrotoxicity. The nephrotoxicity associated with calcineurin inhibitors is well known; this association has also been described for the newer agents.We reviewed a large number of recent studies that attempted to reduce the toxicity of immunosuppressive regimens.A number of low-toxicity protocols have been developed. Encouraging results have been obtained with regimens that reduce or eliminate nephrotoxicity-inducing calcineurin inhibitors and with regimens that reduce or eliminate steroids, which are responsible for many diseases that may lead to the death of the patient, even with a functioning graft.All immunosuppressive drugs may be nephrotoxic, even if they act through different mechanisms. Combining different drugs at low dosage would therefore seem the best solution. It is not yet clear which regimens will be the most effective from the point of view of maximizing patient and graft survival, minimizing rejection, and minimizing adverse events.

Kidney transplant patients show a significantly elevated incidence of gastrointestinal disorders. Protonic pump inhibitors (PPI) are considered to be the correct therapy in the treatment of peptic ulcers, as they have proven to be safe and efficient. The metabolization of the PPIs mainly occurs on a hepatic level; therefore, there is no need to change the therapy accordingly, as there is with the inhibitors of the histamine receptors (anti-H2). The PPIs currently available are omeprazole, pantoprazole, lansoprazole, esomeprazole, rabeprazole which present different pharmacokinetic characteristics and different metabolic routes which are responsible both for differences in terms of efficacy between the different molecules, and for the possible side-effects they may have. All the PPIs, apart from rabeprazole, are metabolized through an oxidization and sulphurization processes which involves the enzymatic system of the P450 cytochrome. The rabeprazole metabolism is different from the other molecules of the same category in that it only moderately involves the CYP450 (CYP3A4 and CYP2C19) from the moment its metabolization begins through nonenzymatic routes and 80% is involved in a thioether non enzymatic reduction mechanism. Consequently, rabeprazole represents: a) a potentially low pharmacological interaction with immunosuppressive drugs; b) a pharmacokinetic aspect much less subject to interindividual differences between one patient and another, due to genetically determined polymorphisms of the CYP2C19 and of the CYP3A4. Moreover, rabeprazole may be administered safely in standard doses with no need to change the dosage of the other pharmaceutical drugs taken simultaneously in nephropathic patients, patients undergoing dialysis and transplanted patients.

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A case of jaundice due to canalicular cholestasis during amiodarone therapy is reported. A definite diagnosis was attained by ultrastructural evidence of a phospholipidosis pattern, a characteristic amiodarone-induced injury. Jaundice occurred within the third month of therapy. Serum bilirubin levels continued to increase in the two weeks following drug withdrawal. A slow decrease was observed in the following three months. Only four cases of jaundice associated with amiodarone therapy have been reported until now.

Hemoperfusion is a blood purification technique involving direct contact between blood and adsorbent substances (sorbents). There are three basic kinds of sorbent: activated charcoal, immunoadsorbents, resins. Following our previous experience on charcoal hemoperfusion, a new coated anionic exchange resin for blood purification specifically designed to remove phosphates was experimentally employed in animals. 3 pigs, in which uremia had been surgically induced, underwent 6 extracorporeal hemoperfusion sessions (2 per pig) with a cartridge containing 100 gr of resin. The phosphate clearance proved satisfactory, values being 120 ml/min after 10' and around 80 ml/min after 2 hours. The biocompatibility of the resin and of the coating membrane was satisfactory. The negligible variation in pH and plasma bicarbonate during all sessions confirmed the low absorption by the tested resin of other blood anions competing with phosphate.

A new coated anionic exchange resin for blood purification specifically designed to remove phosphates was experimentally employed in animals. 3 pigs, in which uremia had been surgically induced, underwent 6 extracorporeal hemoperfusion sessions (2 per pig) with a cartridge containing 100 gr of resin. The phosphate clearance proved satisfactory, values being 120 ml/min after 10' and around 80 ml/min after 2 hours. The biocompatibility of the resin and of the coating membrane was satisfactory. The negligible variation in pH and plasma bicarbonate during all sessions confirmed the low absorption by the tested resin of other blood anions competing with phosphate.

To assess the relevance of HBe/anti-HBe system and DNA polymerase activity in patients on regular dialysis treatment, we prospectively studied 38 patients on haemodialysis, who were chronic carriers of HBs Ag (range 6-66 months), and 26 HBs Ag negative dialysis patients as controls. HBe Ag was present in 74%, DNA polymerase in 60%, and anti-HBe in 13% of HBs Ag positive patients. After a mean follow-up of 23.5 months, only 2 patients, who had been HBe Ag positive, had cleared HBs Ag, and 1 of them had turned to anti HBs positivity. Among the patients who were still HBs Ag positive, only 1 had lost HBe Ag, without developing anti-HBe. Throughout the study, SGOT and SGPT levels were significantly raised in HB virus carriers as compared to controls. In the HBs Ag positive group, the presence of HBe Ag and/or DNA polymerase characterized a subgroup with the most striking abnormalities in enzyme levels. The caused of death in the HBs Ag positive group were not related to liver disease. Viral replication usually takes place in HB virus carrier state, and the underlying liver disease, are not major problems at present in patients on chronic haemodialysis.

Acute Renal Failure(ARF)is a severe clinical event characterized by a sudden reduction in renal function.This apparently well defined condition may be the result of different etiological and pathogenetic mechanims which largely determine the type of renal lesions and influence the immediate outcome and long-term prognosis.

The present report deals with a medium-term programme using biofiltration on a group of 10 patients, who underwent a regular reduced-time schedule (3 procedures per week, 3 hours duration each) lasting up to 12 months. A polyacrylonitrile AN 69 S membrane was used together with a substitution fluid containing Na and bicarbonate. Hematochemical and nutritional parameters were regularly checked to evaluate the efficacy of treatment. Biocompatibility of materials was evaluated by humoral and cellular immunological tests.

Twenty patients suffering from severe hypertension associated with renal failure have been treated with Minoxidil. Ten patients, not on RDT, had a residual Creatinine clearance between 7-71 ml/min; 10 were on hemo-dialytic treatment. Before starting on Minoxidil, all patients had been unsuccessfully treated with an association of traditional anti-hypertensive drugs (blood pressure 200.24/125.6 mmHg). Minoxidil administration dramatically lowered the blood pressure in all cases. After 1 week of treatment the mean decrease in DBP was 22.7%; after 1 month 28.1%, and after 3 months 32.9%. At 6, 12, and 18 months the results were substantially unaltered. Minoxidil dosage ranged from 5 to 50 mg/day over the initial phase; by the third month the daily dose was between 5 and 25 mg/day. Previous anti-hypertensive drugs were suspended in all cases and not subsequently resumed. Furosemide and Propranolol were the only exceptions to counteract the Minoxidil induced fluid retention and tachycardia. The main side effec...

To assess the relevance of HBe/anti-HBe system and DNA polymerase activity in patients on regular dialysis treatment, we prospectively studied 38 patients on haemodialysis, who were chronic carriers of HBs Ag (range 6-66 months), and 26 HBs Ag negative dialysis patients as controls. HBe Ag was present in 74%, DNA polymerase in 60%, and anti-HBe in 13% of HBs Ag positive patients. After a mean follow-up of 23.5 months, only 2 patients, who had been HBe Ag positive, had cleared HBs Ag, and 1 of them had turned to anti HBs positivity. Among the patients who were still HBs Ag positive, only 1 had lost HBe Ag, without developing anti-HBe. Throughout the study, SGOT and SGPT levels were significantly raised in HB virus carriers as compared to controls. In the HBs Ag positive group, the presence of HBe Ag and/or DNA polymerase characterized a subgroup with the most striking abnormalities in enzyme levels. The caused of death in the HBs Ag positive group were not related to liver disease. Viral replication usually takes place in HB virus carrier state, and the underlying liver disease, are not major problems at present in patients on chronic haemodialysis.

A new coated charcoal for hemoperfusion in uremia was investigated in 14 patients with end stage renal disease who underwent hemoperfusion or combined hemodialysis-hemoperfusion (39 seances). Investigations concerned removal of small molecules, coagulation and hematological status and amino acids and some hormones equilibrium. Clinical observations were also made in all patients. The methacrylate-coated charcoal enabled the removal of "toxins" up to 5000 daltons and the total solute removal did not significantly differ from previous hemoperfusion systems. However, the new coating membrane showed improved biocompatibility, in terms of clinical side effects and/or platelet and fibrinogen alterations.

The capacity of charcoal to absorb endogenous and exogenous toxins is well established. It removes substances of higher molecular weight than standard dialysis membranes. The regular use of charcoal hemoperfusion as an adjunct to hemodialysis in chronic uremia is a real prospect capable of improving the patient's clinical and laboratory condition and/or reducing the weekly time of treatment. In line with our previous experience, 5 consenting informed patients on regular dialysis treatment from 9 to 35 months (residual creatinine clearance 0-1.8 ml/min, mean diuresis 350 ml) were treated without interruption for 5-8 months according to a schedule including two combined hemodialysis/hemoperfusion procedures instead of the previous three hemodialysis sessions. Patients were on adequate dialysis and their clinical, metabolic and laboratory conditions were stable. In the hemodialysis/hemoperfusion procedure a cartridge containing 150 g of methacrylate-coated activated charcoal with high biocompatibility was inserted in the dialysis circuit in series with a flat plate or hollow fiber dialyzer. Clinical, laboratory and metabolic conditions remained unchanged in all patients despite the one third reduction in dialysis hours per week. The tolerance of treatment was good: platelets, white cells and fibrinogen were unaffected. The marked reduction in weekly time of treatment led to a more satisfactory personal and social rehabilitation, enabling more patients to be treated with the same facilities.

This study provides a comparative evaluation of the losses of free amino acids which take place in the various artificial substitutive therapies for chronic uraemia (conventional haemodialysis, haemofiltration, haemoperfusion, continuous ambulatory peritoneal dialysis, intermittent peritoneal dialysis). The highest loss was found during haemofiltration sessions, the lowest in continuous ambulatory peritoneal dialysis. The differing loss rates do not influence patients' plasma amino acid patterns either in the short or in the long term (up to 12 months). Moreover, no currently available artificial therapy can correct the basic uraemia-related alterations of plasma amino acid patterns.

Pretransplant donor biopsy (PTDB)-based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score

Background and aims The effectiveness of adalimumab in the treatment of ulcerative colitis is under debate. Although controlled trials have shown that adalimumab is significantly better than placebo, the absolute clinical benefit is modest. We report data on the effectiveness of adalimumab in a cohort of ulcerative colitis patients treated in 22 Italian centres. Methods All patients with active disease treated with adalimumab were retrospectively reviewed. Co-primary endpoints were clinical remission at weeks 4, 12, 24 and 54. Secondary endpoints were sustained clinical remission, steroid discontinuation, endoscopic remission and need for colectomy. Results Eighty-eight patients were included. Most patients had received previous infliximab treatment. Clinical remission rates were 17%, 28.4%, 36.4% and 43.2% at 4, 12, 24 and 54 weeks respectively. Twenty-two patients required colectomy. Clinical remission and low C-reactive protein at week 12 predicted clinical remission at week 54 (OR 4.17, 95% CI 2.36–19.44; OR 2.63, 95% CI 2.32–14.94, respectively). Previous immunosuppressant use was associated with a lower probability of clinical remission at week 54 (OR 0.67, 95% CI 0.08–0.66) and with a higher rate of colectomy (HR 9.7, 95% CI 1.46–9.07). Conclusion In this large “real-life” experience adalimumab appears effective in patients with otherwise medically refractory ulcerative colitis. Patients achieving early remission can expect a better long-term outcome.

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