[Therapeutic Plasma Exchange in a Patient with Chronic Hemodialysis and a New Diagnosis of Myasthenia Gravis].

Case ReportC.S.T. (♂, 71 years old) is a patient with multiple and severe comorbidities, undergoing thrice-weekly chronic hemodialysis since 2008 due to the progression of post-lithiasic uropathy. Over the past 2 months, the patient had been experiencing progressive ptosis of the eyelids, muscle weakness, and ultimately dysphagia and dysarthria that emerged in the last few days. Urgently admitted to the Neurology department, electromyography (EMG) was performed, leading to a diagnosis of predominant cranial myasthenia gravis (with borderline anti-acetylcholine receptor antibody serology). Prompt treatment with pyridostigmine and steroids was initiated. Considering the high risk of acute myasthenic decompensation, therapeutic plasma exchange (TPE) with centrifugation technique was promptly undertaken after femoral CVC placement. TPE sessions were alternated with hemodialysis. The patient's condition complicated after the third TPE session, with septic shock caused by Methicillin-Sensitive Staphylococcus Aureus (MSSA). The patient was transferred to the Intensive Care Unit (ICU). Due to hemodynamic instability, continuous veno-venous hemodiafiltration (CVVHDF) with citrate anticoagulation was administered for 72 hours. After resolving the septic condition, intermittent treatment with Acetate-Free Biofiltration (AFB) technique was resumed. The patient completed the remaining three TPE sessions and, once the acute condition was resolved, was transferred back to Neurology. Here, the patient continued the treatment and underwent a rehabilitation program, showing significant motor and functional recovery until discharge. Conclusions. The multidisciplinary interaction among Nephrologists, Neurologists, Anesthesiologists, and experts from the Immunohematology and Transfusion Medicine Service enabled the management and treatment of a rare condition (MG) in a high-risk chronic hemodialysis patient.

[New Mutation of CYP24A1 in a Case of Idiopathic Infantile Hypercalcemia Diagnosed in Adulthood].

Mutations in the 24-hydroxylase gene CYP24A1 have been recognized as causes of childhood idiopathic hypercalcemia (IIH), a rare disease (incidence <1:1,000,000 live births) characterized by increased vitamin D sensitivity, with symptomatic severe hypercalcemia. IIH was first described in Great Britain two years after the start of a program of vitamin D supplementation in milk for the prevention of rickets, manifesting in about 200 children with severe hypercalcemia, dehydration, growth failure, weight loss, muscle hypotonia, and nephrocalcinosis. The association between the epidemic occurrence of IIH and vitamin D administration was quickly attributed to intrinsic hypersensitivity to vitamin D, and the pathogenic mechanism was recognized in the inactivation of Cytochrome P450 family 24 subfamily A member 1 (CYP24A1), which was identified as the molecular basis of the pathology. The phenotypic spectrum of CYP24A1 mutation can be variable, manifesting predominantly with childhood onset and severe symptomatology (severe hypercalcemia, growth retardation, lethargy, muscle hypotonia, dehydration), but also with juvenile-adult onset forms with nephrolithiasis, nephrocalcinosis, and alterations in phosphocalcium homeostasis. We describe the case of a patient in whom the diagnosis of IIH was made in adulthood, presenting with finding of nephrocalcinosis in childhood, and with subsequent onset of severe hypercalcemia with hypercalciuria, hypoparathyroidism, hypervitaminosis D, and recurrent renal lithiasis. Genetic investigation revealed the presence in homozygosity of the c_428_430delAAG_p.Glu143del variant in the CYP24A1 gene with autosomal recessive transmission, a mutation not reported in the literature.

The Kidney Donor Profile Index (KDPI) of marginal donors allocated by standardized pretransplant donor biopsy assessment: distribution and association with graft outcomes.

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<4 [median KDPI: 87; interquartile range (IQR): 78-94] and 62 with a score=4 [median KDPI: 87; IQR: 76-93]; 102 dual transplants [median KDPI: 93; IQR: 86-96]) and 248 single standard transplant controls (median KDPI: 36; IQR: 18-51). PTDB-based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80-90 and of 37% for kidneys with a KDPI of 91-100. Although 1-year estimated GFRs were significantly lower in recipients of marginal kidneys (-9.3, -17.9 and -18.8 mL/min, for dual transplants, single kidneys with PTDB score<4 and =4, respectively; p<0.001), graft survival (median follow-up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 [95% confidence interval: 0.80-1.79; p=0.38]). In conclusion, PTDB-based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.

[VISPA's group (evaluation of the implementation strategies of the measurements instruments adopted in the Italian nursing practice)]. / Come imparare a fare ricerca nell'infermieristica: sintesi di un'esperienza applicativa.

An innovative teaching strategy focused on problem based approach rather than theorical aiming to facilitate the learning of the research methodology in advanced nursing student has been introduced. Through out a qualitative evaluation of the diary kept by the student nurses involved, advantages and disadvantages of this innovative approach have been evaluated. This paper reports a synthesis of the teaching strategy and its impact on the competences in the research methodology as it has been perceived by the students participants.

The influence of intraoperative central venous pressure on delayed graft function in renal transplantation: a single-center experience.

INTRODUCTION: Delayed graft function (DGF) is a common complication in kidney transplantation. We sought to evaluate possible correlates for DGF including intraoperative parameters, focusing on fluid replacement and central venous pressure (CVP) values among patients undergoing kidney transplantation at our center. METHODS: One hundred fifty-five cadaveric donor transplantations performed at our center between 2001 and 2005 were selected for the study. We compared intraoperative parameters together with 15 other clinical and socio-demographic recipient and donor variables among patients experiencing DGF (n = 58) versus those with immediate graft function (IGF; n = 97). All significant variables at P < .05 upon univariate analysis were entered into a multivariate logistic regression model to identify risk factors for DGF. RESULTS: CVP at awakening of ≤8 mm Hg (odds ratio [OR] = 3.53; 95% confidence interval [CI], 1.63-7.63), fluid input during surgery ≤2.250 mL (OR = 2.12; 95% CI, 1.00-4.51), and recipient age ≥50 years (OR = 2.72; 95% CI, 1.11-6.68) were the strongest correlates of DGF. CONCLUSIONS: Our data suggested that reduced intraoperative perfusion as measured using CVP monitoring might increase DGF risk. This study provides the rationale to further investigate the optimal CVP target during this surgery.

Donor-specific anti-HLA antibodies after bone-graft transplantation. Impact on a subsequent renal transplantation: a case report.

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.

Hyperimmunized patients awaiting cadaveric kidney graft: is there a quick desensitization possible?

On all kidney waiting lists the 10% to 20% of patients who have antibodies against more than 80% of a panel of HLA antigens (panel reactive antibody [PRA] >80%) are difficult to transplant. The best solution for these patients is to find a compatible donor, ideally a full match, who yields a negative crossmatch test (CMX). If this is not possible, desensitization treatment (high-dose) intravenous immunoglobulin (IVIG) or plasmapheresis (PP) + low-dose IVIG is possible with good results in living donor kidney transplantation mainly if the antibody titer is low. It may also be offered to patients awaiting cadaveric donors too after a long waiting time; however, when applied for several months, it has the obvious disadvantage of giving the patient the risk for long-lasting immunologic weakness without the certitude of finding a kidney. In one of our recent cases of combined liver plus kidney transplantation, a positive CMX became negative 8 hours after the liver operation; the kidney was transplanted with a good result which lasted over 3 years. This observation suggested the possibility of a quick desensitization protocol in selected patients with a large (but not strong) immunization who probably are the majority. Patients sensitized to IVIG and with low titer PRA could be given a single PP + low-dose IVIG (what can be done within the time limit of cadaveric donor kidney transplantation) with good probability of turning an initial positive CMX to negative with the possibility of performing the operation and the advantage of giving the immunosuppression only when the kidney is present.

Combined liver-kidney transplantation--S. Orsola experience: nephrological aspects.

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%).

Combined liver-kidney transplantation with preformed anti-HLA antibodies: a case report.

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.

[Renal transplantation and malignancies: A single-centre experience (25 years)]. / Trapianto renale e neoplasie maligne: esperienza a lungo termine (25 anni) di un singolo centro.

BACKGROUND: The prevalence of post-transplant malignancies, in renal transplant recipients, is higher than that expected in age and sex-matched controls from the general population, and there is a markedly increased incidence of certain cancers. METHODS: In 1137 renal transplant recipients (1020 from cadaveric and 117 from living donors, M/F 771/366) performed at the S. Orsola Renal Transplantation Centre since 10/1976 to 9/2001, we studied the post-transplant cancer prevalence, the correlation between cancer prevalence and population characteristics, the risk factors (smoke, cancer history, positive HBsAg and antiHCV infection) and the immunosuppressive therapy. RESULTS AND CONCLUSIONS: The prevalence of malignancies was 3.86% (52 malignancies in 44 patients). The period between transplant and diagnosis of malignant disease was 59 +/- 85 months. Skin cancer was the most common (n=16; 30.7%), followed by lymphoproliferative disorders (n=8; 15.4%), Kaposi s sarcoma (n=6; 11.5%), uterine cancer (n=6; 11.5%), renal carcinoma of native kidney (n=5; 9.6%), cancer of breast/stomach/pancreas and urinary bladder (n=2; 3.8%) and other cancers (n=5; 9.6%). The mean duration of dialysis before transplantation was longer in cancer patients (41+/- 32.1 vs. 33.5 +/- 32.4 months). We found a correlation between types of malignancies and viral infection in NH-lymphoma (EBV positive 4/4) and skin cancer (HZV positive 13/16). We also detected a correlation between Aza and skin cancer (16/22) and CyA and lymphoproliferative disorders (7/8).

Application of Prastat ELISA in the determination of anti-HLA specificity for immunized patients awaiting kidney transplant: five years' experience.

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.

Immune response following fresh arterial homograft replacement for aortoiliac graft infection.

INTRODUCTION: this prospective study defines the immune response to fresh arterial homograft replacement for graft infection. MATERIALS AND METHODS: ten patients who underwent ABO-compatible homograft transplantation were studied for anti-HLA antibody production, and CD3-CD4-CD8-positive lymphocytes subset. Immunological studies were performed preoperatively, and at early (1, 3, 7 days) and late (1, 3, 6, 12, 18, 24 months) follow-up. All patients received immunosuppressive treatment with cyclosporine (1-3 mg/kg/day). Abdominal CT scans were performed postoperatively at the 1, 6, 12, 18, 24 months follow-up. RESULTS: preoperatively, antibodies could not be detected. Postoperatively, as from 1st month post-transplant, a progressive increase in % PRA was observed in all patients, up to the 12th month of follow-up. Subsequently, at 18 and 36 months, a progressive decrease in % PRA was detected. Data showed that the recipient antibodies were directed against donor-specific antigens. During the immediate postoperative period (1, 3, 7 days) CD3- and CD4-positive T lymphocytes slightly increased, whereas CD8 simultaneously decreased. Later, CD3 and CD4 progressively decreased and CD8 increased. Clinically, all patients were cured of infection at late follow-up. CT scans showed thickening of the aortic wall (range: 2.5-4.5 mm), with no signs of aneurysmal degeneration. CONCLUSIONS: fresh arterial homografts are immunogenic. Implanted homografts induce a strong anti-HLA antibody response, similar to chronic rejection, in spite of immunosuppressive treatment.

Ureteral stenosis after kidney transplantation. A study on 869 consecutive transplants.

Ureteral obstruction with impaired urine flow is the most common urological complication following renal transplantation. From December 1976 to December 1997, 869 kidney grafts were performed by our kidney transplantation group, 96 from living related donors and 773 from cadaver donors (736 first grafts and 37 regrafts). A stricture of the ureter (SU) was observed in 27 cases with a follow-up ranging from 18 months to 18 years after the graft and 11 months to 11 years after the treatment of the SU. In six patients, SU was immediately apparent and limited to the anastomosis: they were obviously technical flaws. In all the other patients, there was a free interval ranging from 2 months to 11 years after surgery; the SU usually involved the entire ureter, suggesting multiple etiologies. Repeated urinary infections could be a cause but immunological problems might be more determinant. In our series, acute rejection was more common than chronic so that the correction of SU was followed in many cases by a good and long lasting result (up to 11 years). In our experience, SU was not a dangerous complication even in patients in whom for different reasons (mainly refusal of treatment) the therapy was delayed - even if anuria occurred, no case of graft loss or serious damage were observed. At the beginning of our experience, the diagnosis of SU was based on urography, and therapy has always been re-operation. For 15 years, the diagnosis of SU has been based on routine echographic surveillance, which was intensified after each rejection, and the first treatment of SU in the last 8 years was re-operation in early technical SU and interventional radiology (balloon dilatation with or without temporary stent) in other cases. When it failed or in case of recurrence, surgical correction was performed utilizing the native ipsilateral or contralateral ureter for a uretero-ureterostomy.

Beta2-microglobulin and low-flux synthetic dialyzers.

The aim of this study was to compare the effect on beta2-microglobulin (beta2-M) plasma levels of dialyzers with 3 low-flux synthetic membranes and regenerated cellulose (Cuprophan) in 12 chronic dialysis patients. The synthetic membrane materials chosen were low-flux polymethylmethacrylate (PMMA), low-flux polysulfone (PS 400), and polycarbonate-polyether (Gambrane). Adequate and comparable removal of small solutes was provided by dialyzers with all 4 membrane materials used under similar conditions. A significant reduction of beta2-M plasma levels was seen only with Gambrane while the other 2 synthetic membrane materials gave rise to increases similar to those known to occur with Cuprophan. After correction for the hemoconcentration caused by ultrafiltration, dialysis with Gambrane showed a 24% lower plasma beta2-M level while the beta2-M concentrations with the other 3 membrane materials were practically unchanged. In addition, the efficiency of Gambrane dialyzers in beta2-M removal was able to significantly lower the predialysis plasma beta2-M levels after only 5 dialysis sessions. The hemocompatibility of the 3 synthetic low-flux membranes as judged by the white blood cell (WBC) count and complement activation was similar and therefore cannot be used to explain the different beta2-M plasma levels. In anticipation of gaining further insight into the mechanisms of accumulation and deposition of beta2-M in dialysis patients, a worthwhile approach may be to use a low-flux membrane such as Gambrane which combines removal with protection against potential activating factors in the dialysis fluid.

Mismatch-specific anti-HLA antibody production following aorta transplants.

In this study, we have investigated the nature and magnitude of the immunological response after implantation of human aortic segments. Five recipients of aortic segment replacement were studied for anti-HLA antibody production (specificity and Ig class), CD3, CD4, and CD8 T cell subpopulation dynamics, and aortic wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were first detected 1-3 months after implantation and persisted in high concentrations for at least 1 year. Computer tomography scanning showed a progressive thickness of the aortic wall. Also the absolute number of CD3, CD4, and CD8 positive lymphocytes increased progressively after implantation. In conclusion, as was observed earlier for heart valve allografts, human implanted aortic segments induce a strong anti-HLA antibody response in recipients. We speculate that these antibodies have the potential to harm the implant, for example, by having an impact on luminal narrowing.

A comparison of dialysers with low-flux membranes: significant differences in spite of many similarities.

The solute removal characteristics and haemocompatibility of low-flux dialysers containing Cuprophan, cellulose acetate, polymethylmethacrylate (PMMA), and polycarbonate-polyether (Gambrane) membranes were compared in a multicentre cross-over clinical trial. While all four dialysers provided comparable removal of urea and creatinine, the dialyser containing PMMA membrane showed a reduced ability to remove phosphate compared to that containing Cuprophan membrane. Significant beta 2-microglobulin removal was obtained with the dialyser containing Gambrane membrane, whereas the other three dialysers had no impact on plasma beta 2-microglobulin concentrations. The ability to activate complement, measured as changes in the plasma concentrations of C3a des Arg and the terminal complement complex, and to produce leukopenia was greater for the dialyser containing Cuprophan membrane than for the other three. The ability to activate complement and cause leukopenia was not consistent among the remaining three dialysers and the degree of leukopenia could not be predicted from the level of complement activation. Neutrophil degranulation, as indicated by the release of elastase-alpha 1-proteinase inhibitor, occurred to a greater extent with the dialysers containing Cuprophan and Gambrane membranes. None of the dialysers was overtly thrombogenic as judged by changes in platelet count and plasma concentrations of the thrombin-antithrombin III complex. Our results demonstrate that although there are many similarities between dialysers containing low-flux membranes, there are also significant differences. These differences may enable improvements in therapy, while allowing continued use of low-flux dialysers.