West Nile virus transmission through organ transplantation in north-eastern Italy: a case report and implications for pre-procurement screening.

PURPOSE: West Nile virus (WNV) transmission through organ transplantation occurs rarely and screening of organ donors for WNV infection remains controversial. This report describes the case of WNV encephalitis in a kidney recipient and the case of asymptomatic WNV infection in the organ donor, both observed at Treviso Hospital, northeastern Italy. After briefly reviewing the literature, we discuss the implications for WNV screening. METHODS: We reviewed medical, laboratory and epidemiological records at our hospital, and the literature concerning cases of organ-transmitted WNV infections and WNV screening of organ donors in Italy and worldwide. RESULTS: The kidney recipient was the first confirmed case of WNV infection notified in northeastern Italy in 2011, and the first case of WNV infection in a cluster of four transplant recipients who acquired the infection from a common organ donor. The organ donor, whose WNV infection was only retrospectively diagnosed by IgM detection, represents the index case of a WNV outbreak in the Treviso Province. Screening of her blood prior to organ recovery did not show detectable levels of WNV nucleic acid with the use of quantitative real-time polymerase chain reaction. CONCLUSIONS: This report emphasizes that transplant-acquired WNV neuroinvasive disease can be particularly severe. We suggest that pre-procurement screening of organ donors by testing blood with both WNV IgM capture ELISA and a sensitive nucleic acid testing should be adopted during the transmission season in the present Italian epidemiological setting.

Tacrolimus is highly effective in both dual and triple therapy regimens following renal transplantation. Spanish and Italian Tacrolimus Study Group.

This open, multicenter, randomized, parallel-group study evaluated the efficacy and safety of tacrolimus-based dual and triple therapy regimens. For this 3-month study (with 12-month follow up), 491 adult renal transplant patients were randomized and received either dual therapy (tacrolimus/corticosteroids; 246 patients) or triple therapy (tacrolimus/corticosteroids/azathioprine; 245 patients). Patient survival rates at months 3 and 12 were 99.2 (dual) vs 99.6% (triple) and 97.8 vs 98.7%, respectively. Graft survival rates at months 3 and 12 were 94.1 (dual) vs 95.4% (triple) and 92.8 vs 93.3%, respectively. After 3 months, the incidences of treated acute rejection were 28.8 (dual) and 29.7% (triple); and 7.6 (dual) and 5.4% (triple) for corticosteroid-resistant acute rejections. Between months 4 and 12, three new first rejections were reported, (dual: 2, triple: 1). For leukopenia (1.3 vs 11.7%; P < 0.001) and anemia (14.8 vs 23.0%, P = 0.026), significantly higher incidences were reported in the triple therapy group. The incidence of de novo insulin-dependent diabetes was 5.6 (dual) and 4.0% (triple) at month 3. In terms of efficacy, no difference between the treatment groups was observed.

Attitudes and knowledge about transplantation in dialyzed patients requesting a cadaveric kidney graft.

AIM: Eighty-two patients answered a multiple choice questionnaire aimed at identifying their presumed and actual knowledge regarding transplantation, given immediately before evaluation by our transplant team for inclusion on our kidney transplant waiting list. SUBJECTS, METHODS AND RESULTS: A total of 78% stated that they had no or incomplete knowledge of transplantation and 22% were very well informed. The mean score for technical knowledge of transplantation (duration, requirement for removal of native kidneys, possibility of obtaining a second transplant, duration of immunosuppressive therapy and duration of the risk of rejection) was 3.1 +/- 0.15 SEM (maximal possible score 5), that for risk knowledge (risks of infections, unpleasant side effects, hypertension, diabetes mellitus, viral infections and cancer) was 1.4 +/- 0.15 (maximal possible score 6). A total of 23% knew that the spouse could donate a kidney, 74% stated that only a blood relative could and 3% that living donation was impossible. CONCLUSIONS: There is scarce knowledge about transplantation, especially with regard to the risks and living donation.

Vesicoureteral reflux after kidney transplantation: clinical significance in the medium to long-term.

103 patients who received a cyclosporine-treated primary cadaver kidney transplant (TX) at our center between 1985 and 1989, whose graft survived for more than 1 year and who accepted to undergo voiding cystography after TX were analyzed and grouped according to the highest grade (regardless to whether active or passive) of vesicourteral reflux (VUR): group 0, absent (n = 14); group 1-2, grade I or II (n = 62); group 3, grade III (n = 27). Patient follow-up ranged from 5 to 10 (median 7) years. Patient and graft survivals and prevalence of hypertension (defined as the persistent need of antihypertensive therapy), did not differ significantly between groups (Mantel-Cox test p: n.s. in all cases). GFR (Cockroft and Gault) and proteinuria were evaluated with ANOVA for repeated measures at 1, 2, 3, 4 and 5 years in the 96 patients (group 0: 13, group 1-2: 56, group 3: 27) whose grafts lasted for 5 years or more. Neither GFR values (p: n.s.) nor GFR behaviour over time (p: n.s.) differed between groups, although a progressive decline of GFR was noted in all groups (p < 0.002). Proteinuria neither showed any significant differences between groups in values (p: n.s.) or behaviour over time (p: n.s.), nor any trend in behaviour over time in all groups as a whole (p: n.s.). Finally, in the first 5 years after TX the 3 groups did not differ for number of urinary tract infections (UTIs) (mean value for all patients: 2.5, range 0-22, episodes/pt/5 years) (p: n.s.), or for number of UTIs with leukocyturia (mean 0.6, range 0-6, episodes/pt/5 years) (p: n.s.), or for number of febrile UTIs (mean 0.3, range 0-5, episodes/pt/5 years) (p: n.s.), or for number of UTIs with sepsis (mean 0.1, range 0-2, episodes/pt/5 years) (p: n.s.). The same results were obtained when, instead of episodes/ pt/5 years, percentages of patients without or with 1 or more of such episodes in the same period were considered. In conclusion, VUR does not seem to be hazardous for the transplanted kidney in the medium to long-term.

Influence of length of time on dialysis before grafting on kidney transplant results.

The outcome of kidney transplantation was evaluated in 246 nondiabetic, CsA-treated recipients of primary cadaver transplant, divided into 4 groups according to length of time on dialysis: group < or = 2, 0-24 months; group 2-5, 25-60 months; group 5-15, 61-180 months; group > 15, over 180 months. The 4 groups did not differ in graft survival, proteinuria (g/die), or estimated GFR values at 1, 2, 3, 4, and 5 years after grafting. They did not differ in the frequency of cataract, hip osteonecrosis, tumors, or posttransplant diabetes mellitus at 3 years after grafting. Ocular hypertone (p < 0.02), tendon ruptures (p < 0.001), arterial occlusive disease of lower limbs (p < 0.01), cholelithiasis (p < 0.05), and chronic hepatitis--which occurred only in anti-HCV and/or HBs Ag-positive patients--(p < 0.001), were more frequent in group > 15, and in all these cases but ocular hypertone a linear trend of increasing frequencies with increasing dialytic age was statistically significant. Group 5-15 had the lowest patient survival (p < 0.02). Moreover, a progressive decline of patient survival with increasing dialytic age was noted in groups < or = 2, 2-5, and 5-15. Unexpectedly, group > 15 had remarkably good survival, and this finding denies the hypothesis of a purely linear decline of patient survival after transplantation with increasing dialytic age.

Importance of donor/recipient body weight ratio as a cause of kidney graft loss in the short to medium term.

The importance of the donor/recipient body weight ratio (DRBWR) as a cause of kidney graft loss was evaluated in 112 non-diabetic, ciclosporin-treated, first cadaver kidney transplant recipients. According to the DRBWR, the patients were divided into three groups: 'low' (< or = 0.80), 'medium' (0.81-1.20), and 'high' (> 1.20). The three groups did not differ in patient or graft survival, and the DRBWR was not a predictor of graft failure at multivariate analysis (Cox models), even after only patients with graft survivals > 1 year were considered. The three groups did not differ in glomerular filtration rate (GFR) and proteinuria 6-60 months after renal transplantation. When the 55 patients with a follow-up period > 4 years were considered, no differences between groups were found in GFR or GFR evolution over time. Hypertension was significantly less frequent in group 'high' (Mantel-Cox p = 0.04), but very likely as a consequence of uneven recipient gender (an independent predictor of hypertension at multivariate analysis) distribution between groups, the significance being lost when survival curves were rebuilt by stratifying for recipient gender. DRBWR never resulted as a significant predictor of GFR at multivariate analysis when GFR values 6-60 months after transplantation were analyzed. We conclude that the DRBWR has no major effects on kidney graft function and survival in the short to medium term.

Verticillium peritonitis in a patient on peritoneal dialysis.

We describe a case of peritonitis due to Verticillium spp. in a 33-year-old farmer on continuous ambulatory peritoneal dialysis (CAPD) for 3 months for end-stage renal failure due to chronic pyelonephritis. The etiologic agent was a hyaline hyphomycete which we report as a new human opportunistic pathogen. The fungus was isolated from the peritoneal fluid culture and from the tip of the catheter; identification was made on the basis of macroscopic and microscopic features. The patient had previously been admitted to our hospital for peritonitis caused by mixed enteric flora and treated for 8 days with intraperitoneal broad-spectrum antibiotic therapy. Five days after discharge he was readmitted for severe abdominal pain and cloudy drainage fluid. Two days of intraperitoneal broad-spectrum antimicrobial therapy produced no clinical improvement. Intravenous fluconazole and oral flucytosine were administered upon identifying the fungus. After another 2 days without improvement, peritoneal dialysis was discontinued and the catheter removed. Antimycotic therapy was continued for 4 days with complete resolution of the peritonitis. The patient chose to start hemodialysis and was discharged in good clinical condition.

Clinical significance of vesicoureteral reflux after kidney transplantation.

In this study 103 out of our 125 CsA-treated patients who received between January 1985 and December 1989 a first cadaver kidney transplant that functioned for at least one year were studied with voiding cystography (VC) for vesicoureteral reflux (VUR). All patients had an external uretero-neo-cystostomy. VUR occurred in 89 (86.4%) patients. Patients were grouped according to VUR: absence of VUR (group 0), VUR grade I-II (group 1-2), and VUR grade III (group 3). The 3 groups were comparable for male/female ratio, cause of renal failure, cause of donor death, recipient and dialytic age, immunosuppressive therapy, follow-up, time of VC performance after transplantation. At 6 months and 1, 2, 3, 4, and 5 years after transplantation graft function, number of rejection episodes, and number of urinary tract infections (UTIs) were similar in the 3 groups. In groups 1-2 and 3 hypertension was more frequent than in group 0 and occurred even after the 6th month (whereas this did not happen in group 0), but the differences between the 3 groups were not significant. However, when only the 13 patients who were followed for 5 years were considered, the prevalence of hypertension after 5 years was significantly higher in groups 1-2 and 3 (both 100.0%) than in group 0 (33.3%) (chi-square = 7.88; p < 0.02). Finally, 4.5% of patients with VUR and no patients without VUR had septic episodes linked to UTIs, but the difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of hypertension as a damaging factor for kidney grafts under cyclosporine therapy.

The relative importance of glomerular filtration rate (GFR) and hypertension (permanent need for antihypertensive drugs) for the prognosis of kidney grafts was studied in 135 cyclosporine-treated primary cadaver kidney transplant recipients whose grafts lasted more than 1 year. The start point of 1 year after transplantation was chosen because hypertension developed within the first year in all our hypertensive patients. Graft prognosis in hypertensive patients was not significantly worse than that of normotensive patients; moreover at multivariate analysis, age at transplantation and GFR at 1 year (P = 0.014), but not hypertension, were significant prognostic factors for the graft. At logistic regression, GFR was a significant variable for hypertension (P = 0.009), but hypertension was not a significant variable for renal failure at 1 year (GFR < or = 0.83 mL/sec [50 mL n]; P, NS). Accordingly, hypertension per se resulted much more as a consequence of reduced renal function than as a direct cause of graft damage. However, when hypertensive patients were divided into controlled and uncontrolled, uncontrolled hypertensive patients had the worst prognosis (P = 0.03), and blood pressure control proved a strong prognostic factor for the graft, even after GFR was considered (P = value of the model considering blood pressure control, GFR, and age at transplantation: 0.007). Our data suggest that, apart from being an expression of reduced renal function, hypertension is also a direct kidney graft damaging agent, a role that can be controlled by strict reduction of blood pressure levels.

Influence of donor age on cadaver kidney graft function and survival: univariate and multivariate analyses.

The influence of donor age on the outcome of kidney transplantation (TX) was evaluated in 169 patients who received a primary cadaver kidney transplant at our center between September 16, 1984, and December 31, 1990. All the patients received cyclosporin A as part of the immunosuppressive protocol. Patients were grouped according to donor age: low donor age (LDA; donor age range 12-25 years), medium donor age (MDA; range 26-50 years) and higher donor age (HDA; range 51-66 years). There were no differences between groups in graft and patient survival, and multivariate analysis did not show any effect of donor age on those parameters. Proteinuria/day and number of rejection episodes did not differ between groups either. Immediate diuresis was more frequent in group LDA than in the other two groups (73.8, 54.7 and 57.1%, respectively; p < 0.05) and immediate diuresis resulted as a weak positive prognostic factor for graft outcome at multivariate analysis (p = 0.05). At both univariate and multivariate analyses, donor age resulted inversely correlated with creatinine clearance (CCr) at every period after TX but the 5th year, with r2 from 0.12 to 0.23 (p < 0.01). The LDA group had significantly better CCr than the HDA group at every period after TX but for the 5th year (the MDA group behaved intermediately).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term survival on renal replacement therapy for primary hyperoxaluria type I.

We describe the case of a patient in end-stage renal failure due to primary hyperoxaluria type I (PH1) who started hemodialysis in 1977 and is still alive and active. The diagnosis of PH1 was first suspected after a bone biopsy performed in 1981 to investigate hyperparathyroidism. Oxalosis recurred as early as 3 months after transplantation in a cadaver kidney grafted in 1987; nevertheless, graft function remained good enough to make possible the discontinuation of dialysis treatment for 5 months and thereafter to have only 1 dialysis a week for 17 months. The diagnosis of PH1 has been recently confirmed despite the patient being already anuric by means of the determination of plasma oxalate and glycolate levels as well as by determining hepatic alanine:glyoxylate amino-transferase.

Dynamics of bone aluminum over one year of functioning renal graft.

The concentration of aluminum (Al) in serum, urine, and bone, as well as bone histomorphometry parameters were studied before and 1 year after kidney transplantation (Tx) in 20 dialyzed patients. One year after Tx, serum Al fell significantly from 50.3 +/- 8.8 to 23.9 +/- 2.7 micrograms/l, (53% fall). Bone Al content also decreased significantly from 62.9 +/- 9.0 to 36.5 +/- 7.0 micrograms/kg bone weight, but urine Al excretion was still above normal. The repeat bone histomorphometric examination showed a good recovery of bone resorption which correlated well with serum parathyroid hormone levels, but poorer recovery of indices of bone formation and of the extent of Al deposits in the bone as shown by aluminum staining.

[Heart valve involvement in systemic lupus erythematosus: an echocardiographic study]. / Interessamento valvolare cardiaco nel lupus eritematoso sistemico: studio ecocardiografico.

The purpose of this study was to evaluate the spectrum of morphologic and functional cardiac involvement in a selected population of patients with systemic lupus erythematosus (SLE) by means of echocardiography. Thirteen patients (2 male and 11 female) affected by SLE, mean age 41.9 years (range, 21-64), underwent M-Mode, two-dimensional and Doppler echocardiography. Eleven patients had renal disease and 3 of them were undergoing dialysis. One patient had findings of active disease. Six patients had systemic hypertension. None had a history suggestive of rheumatic fever or infective endocarditis. At echocardiographic study nine patients demonstrated findings of valvular involvement. These alterations were defined, according to the echocardiographic features, in two types: vegetation (verrucous Libman-Sacks endocarditis) and thickening. Vegetations were present in 6 patients, involving the mitral valve in all six and the aortic valve in three. The mitral valve vegetations were more frequent on the subannular portion of the posterior leaflet. Seven patients had valvular thickening: involvement of both mitral and aortic valve was present in five, and isolated mitral or aortic valve lesions in the remaining two patients. Combined valvular vegetation and thickening were observed in 4 patients. Eight patients had mild valvular dysfunction on Doppler examination: five isolated mitral regurgitation, two combined mitral and aortic regurgitation and one combined mitral stenosis and regurgitation. In agreement with previous reports, our study shows that valvular involvement in SLE is relatively frequent. Echocardiography can identify additional patterns of valvular lesions different from the known "verrucous Libman-Sacks endocarditis". The degree of valvular dysfunction is not important.

[Mass transfer of magnesium in hemodialysis]. / Mass-transfer del magnesio in emodialisi.

The rate of mass-transfer (MT) of magnesium during hemodialysis was studied in thirty-five patients with hypermagnesemia (Mg = 3.75 +/- 0.72 mg/dl) undergoing chronic hemodialysis. The aim of the study was to verify which is the best dialytical approach to remove the excess of magnesium. The concentration of Mg in the dialysate was of 1.82 mg/dl for all patients. MT was -0.51 +/- 0.36 g and no statistical difference was found between patients treated with cuprophan hollow fibers dialyzers, PAN and cuprophan plates. Mg MT is not correlated with dialysis duration (r = -0.23; p:ns), urea clearance (r = -0.08; p:ns), KT/V index (r = -0.03; p:ns), blood flow (r = -0.15; p:ns). In conclusion from our data, in agreement with other Authors, reduction of serum Mg levels is more convenient by obtained by a decrease in Mg concentration in the dialysate under 1.82 mg/dl, in order to increase the blood-dialysate concentration gradient.

[Plasma levels of atrial natriuretic peptide and its relationship with arterial blood pressure before and after peritoneal dialysate infusion]. / Livelli plasmatici del peptide natriuretico atriale e rapporti con la pressione arteriosa prima e dopo il carico del liquido di dialisi peritoneale.

The acute modifications of atrial natriuretic peptide (ANP) plasma levels due to intraperitoneal dialysate infusion and the relationship between ANP and arterial blood pressure were studied in 17 patients on continuous ambulatory peritoneal dialysis (CAPD). ANP plasma levels were 159.18 +/- 87.06 pg/ml 30' minutes after 2.000 ml of peritoneal dialysate filling (t = 2.55; p less than 0.02). There was no correlation between ANP and arterial blood pressure neither before (r = -0.10; p = n.s.), nor after intraperitoneal dialysate infusion (r = 0.05; p = n.s.).