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Biomedical subjects

A Aroldi

Publications and source records attributed to A Aroldi.

At least 19 recordsLinked to original sources

Risk factors associated to kidney stones in primary hyperparathyroidism.

Nephrolithiasis is the most important clinical manifestation of primary hyperparathyroidism (PHPT), although nowadays this disorder is often asymptomatic. Clinical or biochemical differences between PHPT patients with and without nephrolithiasis have not been clearly identified in most of the previous studies. The aim of the study was to investigate clinical and biochemical parameters in kidney stone former (SF) and non-stone former (NSF) patients with PHPT in order to identify potential risk factors. Serum and plasma samples from 55 consecutive patients (43 females, 12 males) with PHPT were collected after overnight fasting; 24-h urine collection and a fresh sample of urine for sediment analysis were obtained from all patients. Clinical data were recorded in all. Out of 55 patients, 22 had kidney stones, which were symptomatic in 73%. SFs showed circulating PTH, total and ionized calcium, 1,25 dihydroxyvitamin D3, urinary calcium excretion and 24-h urine oxalate levels significantly higher than NSFs. Hypercalciuria was often concomitant with massive quantities of calcium oxalate crystals in urine sediment. Hypercalciuria and relatively high oxaluria were associated with stone formation with an odds ratio (OR) of 4.0 and 7.0, respectively, which rose to 33.5 when they coexisted. Hypomagnesuria and hypocitraturia were common in at least one third of all PHPT patients, but they were not associated to an increased OR. As expected, they were positively correlated with urine calcium excretion, suggesting that calcium, magnesium and citrate are commonly regulated at renal level. In conclusion, hypercalciuria, higher oxalate excretion and severe PHPT are associated with kidney stones in PHPT.

Aged↗

Natural history of hepatitis C virus infection in adult renal graft recipients.

AIM: To study the natural history of hepatitis C virus infection in renal transplantation, 464 HbsAg negative patients were prospectively studied from 1989. METHODS: AntiHCV was tested by ELISA II and HCVRNA by Amplicor HCV RNA tests. RESULTS: Two hundred nine patients were antiHCV positive (C+). HCVRNA was confirmed in 89% of C+ patients. Compared with the 255 anti-HCV negative (C-), C+ had undergone longer periods of dialysis (P = .0001), were more transfused (P = .01), and included more retransplants (P = .002). Immunosuppression was azathioprine (AZA) plus steroids in 133 and cyclosporine (CsA) in 331 patients. Liver biopsy showed chronic active hepatitis in 50, cirrhosis in 8, and fibrosing cholestatic hepatitis in 2 patients. Histologic progression of liver disease was confirmed in 18 of 26 patients. The causes of death in 84 patients (51 C+ vs 33 C-) were cardiovascular disease in 49%, sepsis in 13%, liver failure in 14%, neoplasia in 21%, and hepatocarcinoma in 2%. The 14-year patient survival was 75% in C+ and 86% in C- (P = .002). By multivariate analysis, age (>40) (P = .001) and C+ (P = .019) correlated with a worse patient survival. If patients were stratified according to age (<40 vs > or =40), younger C+ patients had a lower survival probability (P = .03). The 14-year graft survival was 44% in C+ vs 60% in C- patients (P = .001) but pure graft survival was similar (68% in C+ vs 72% in C-) (P = .13). CONCLUSION: The presence of C+ significantly reduced both patient and graft survival in the long-term with liver failure being the second most frequent cause of death.

Adult↗

From cyclosporine to the future.

Most of the experience acquired in our unit with cyclosporine (CsA) comes from randomized trials. A first trial demonstrated that CsA-treated patients had a better 10-year graft survival than azathioprine-treated patients. A second trial showed equivalence between double therapy with CsA plus steroids and triple therapy with CsA, steroids, and azatioprine. A third trial showed similar 2-year graft survival with CsA monotherapy and triple therapy. A larger multicenter study that compared three different CsA-based regimens showed similar long-term graft survival with monotherapy, double therapy, and triple therapy. However, patients given monotherapy had less frequent steroid-related side-effects. Finally a more recent multicenter international trial showed that the rate of acute rejection can be reduced without increasing side effects by adding the monoclonal antibody basiliximab to the triple therapy. By reviewing our cumulative experience with CsA we found a mean graft half-life of 18.7 years for cadaver renal transplant recipients and 31.9 for the living transplant recipients. No significant attrition of graft function was found for patients with grafts functioning at 15 years. Two important issues with the present immunosuppression concern the long-term nephrotoxicity of calcineurin inhibitors and the cardiovascular disease, which is at least in part related to the use of steroids. To face these problems, we are currently involved in two multicenter trials, one comparing sirolimus plus mycophenolate mofetil to sirolimus plus low-dose CsA, while the other trial compares certican plus CsA to certican plus CsA plus corticosteroids.

Clinical Trials as Topic↗

Design of a trial comparing sirolimus plus mycophenolate mofetil versus sirolimus plus cyclosporine.

We present the study design of a prospective, multicenter, randomized trial aimed at comparing the effects of two different combinations of sirolimus. Renal transplant recipients will be allocated to receive either sirolimus and mycophenolate mofetil (group A) or sirolimus and cyclosporine (group B). The primary endpoint will be the graft function at 3, 6, 12, 24, 36, 48, and 60 months. A number of secondary endpoints will also be considered. To obtain a significant difference in the primary endpoint 180 patients will be enrolled.

Adult↗

Effect of increased arterial resistance index on long-term outcome of well-functioning kidney grafts.

An abnormal vascular status is present in the transplanted kidney. To define whether vascular factors might influence kidney function of the graft, the renal volume, blood flow and vascular resistance of a group of healthy subjects were compared with those of a group of well functioning renal transplants by color Doppler ultrasonography. Sixty healthy subjects and 75 well functioning cadaver renal transplant recipients were compared by color Doppler ultrasonography. Subsequently, 15 couples of donors and recipients of a living related renal graft were compared to observe the differences between the two organs of the same subject in a different environment. The variables studied were: the diameters and the volume of the kidney, renal blood flow and renal resistance index (RI). The group of cadaver renal transplant patients showed higher mean blood pressure (P = 0.009), higher serum creatinine levels (P = 0.0001) and lower endogenous creatinine clearance (P < 0.0001) than healthy controls. The length (P < 0.00001) and volume (P < 0.001) of the kidneys of cadaver transplanted patients were significantly greater than those of healthy subjects, while the length and volume of the living donors kidneys were identical to those of the recipients. RI, measured on renal vessels, showed lower values in healthy subjects and in kidney donors than in transplanted patients (P < 0.00001). Well functioning transplanted kidneys showed increased renal arterial RI. This non-immunologic factor did not appear to be detrimental with renal function in time, at least until 50 months after successful grafting.

Adult↗

The clinical status of cadaveric renal transplant patients treated for 10 year with cyclosporine therapy.

In this paper we assessed the clinical status of 150 cadaveric renal transplant patients who received cyclosporine without interruption for 10 yr. The mean creatinine clearance was 59.2 +/- 15.71 at 1 yr and 55.6 +/- 24.91 mL/min at 10 yr (p = 0.039). Patients were subdivided into four quartiles according to the mean creatinine clearance at 1 yr. The 14 patients with the lowest quartile showed a significant decrease of creatinine clearance from the 1st to 10th year (from 31.5 +/- 5.83 to 24.8 +/- 14.00 mL/min; p = 0.038) while no difference between the mean creatinine clearance at 1 and at 10 yr was found in the other three quartiles. At 10 yr, 84.6% patients needed antihypertensive therapy, a rate similar to that seen at 1 yr (81.4%). The mean plasma cholesterol (253 +/- 57.8 mg/dL) and triglyceride (197 +/- 113.1 mg/dL) at 10 yr were similar to those found at +/- yr (243 +/- 48.2 and 201 +/- 143.0 mg/dL, respectively). Most patients have a high degree of rehabilitation 10 yr after uninterrupted cyclosporine therapy and all patients but 3 were able to work.

Adult↗

Effects of three immunosuppressive regimens on vertebral bone density in renal transplant recipients: a prospective study.

The influence of three different immunosuppressive regimens with cyclosporine (CsA) on the development of osteopenia in renal transplant patients was assessed. Fifty-three adults with first kidney transplants participated in a randomized trial to analyze the efficacy of three different immunosuppressive regimens: CsA alone (group 1), CsA plus steroids (group 2), and CsA plus steroids plus azathioprine (group 3). Lumbar spine bone mineral density was assessed by dual energy x-ray absorptiometry every 6 months for 18 months. The values for trabecular mass were expressed as bone mineral density and as a fraction of the standard deviation of the mean of the normal value for patient's sex and decade of age (Z-score). Statistical analysis was performed on Z-score and "Z-score change" (value after 6 months minus the basal value at transplantation). At the 18th month, the Z-score increased significantly in treatment group 1 without steroids (P=0.006) and decreased significantly in steroid-treated groups 2 (P<0.001) and 3 (P<0.001). Comparing the two genders, Z-score decreased less in premenopausal women than in men (P=0.018). "Z-score change" did not correlate with steroid dosage, was high in patients with high basal bone mineral density, and was directly associated with the duration of dialysis (P=0.008). In conclusion, premenopausal transplant recipients showed a lower decrease of lumbar bone mineral density than men. In transplant recipients given CsA with steroids, lumbar bone mineral density decreased significantly, while it increased significantly in patients given CsA alone.

Adult↗

Increased detection of antibody to hepatitis C virus in renal transplant patients by third-generation assays.

To assess the sensitivity and specificity of third-generation assays for antibody to hepatitis C virus (anti-HCV), sera from 244 renal transplant patients (113 positive for anti-HCV enzyme-linked immunosorbent assay [ELISA]-2) were studied. Hepatitis C virus RNA was detected by a reverse-transcripted nested polymerase chain reaction. Antibody to HCV was detected by ELISA-3 in 108 (96%) ELISA-2-positive samples. Five (4%) ELISA-2-positive sera were negative by both ELISA-3 and polymerase chain reaction. In the anti-HCV-negative group, six (5%) additional cases were ELISA-3-positive; three of these were confirmed by recombinant immunoblot assay-3 (RIBA-3) and polymerase chain reaction. Recombinant immunoblot assay-3 was used to resolve 82 RIBA-2-indeterminate and three RIBA-2-negative sera. Using RIBA-3, 49 (60%) RIBA-2-indeterminate samples were positive, five (6%) ELISA-3-negative samples were negative, and 28 (34%) were remained indeterminate. Recombinant immunoblot assay-2-negative samples were indeterminate with RIBA-3. Hepatitis C virus RNA was detected in all RIBA-3-positive and 58% of the RIBA-3-indeterminate samples. Third-generation assays for anti-HCV are more sensitive and specific than second-generation assays in renal transplant patients.

Adolescent↗

Cancer incidence in 854 kidney transplant recipients from a single institution: comparison with normal population and with patients under dialytic treatment.

In this retrospective historical study, we compared the incidences of malignancies observed among 854 renal transplant recipients (RT) with at least 1 yr of follow-up, with the incidences of neoplasias among patients under regular dialytic treatment (RDT) and a control population from Northern Italy. Cox's proportional hazard model was used in RT recipients in order to evaluate the prognostic factors related to the development of neoplasia. Seventy six out of 854 RT patients (8.9%) developed some malignant neoplasia: 46% of these 76 were cutaneous neoplasias including melanomas, and the remaining 54% non cutaneous cancers: 33% miscellaneous tumors (MT), mostly adenocarcinomas, 17% Kaposi's sarcomas (KS), 4% non-Hodgkin's lymphomas (NHL). Malignancies had a higher incidence (p < 0.01) among RT recipients than among control and RDT patients. However, MT were equally frequent among the three groups. RDT patients on the contrary, had similar incidence of neoplasias when compared to the control population, but showed a lower incidence of squamous cell carcinomas (SCC). The risk ratios (RR) for the most frequent neoplasias among RT recipients vs. control population were: 224.7 for KS, 7.4 for NHL, 6.2 for SCC, 5.7 for basal cell carcinomas (BCC), 4.0 for MT. The risk of developing a de novo neoplasia was of about 13% at 10 yr and of 34% at 20 yr. In RT recipients, Cox's proportional analysis showed that age > 40 at transplantation and male sex were the only risk factors associated with an increased incidence of neoplasias, while no difference was observed between conventional (azathioprine+methylprednisolone: Aza+MP) and CsA therapy or in CsA monotherapy vs. double or triple therapy. However, KS occurrence correlated both with CsA dose (RR 15.2 for monotherapy; 12.5 for double therapy; 2.98 for triple therapy) and with 10 or more i.v. methylprednisolone pulses for treatment of rejection (RR 5.2). We conclude that in our series CsA does not increase the risk for development of neoplasias, when compared to conventional immunosuppression.

Adolescent↗

A randomized trial comparing triple-drug and double-drug therapy in renal transplantation. Analysis at 7 years.

This is the 7-year update of a randomized trial comparing triple (TT) and double (DT) immunosuppressive therapy in renal transplantation. At 7 years, patient survival rate was 85% in DT vs. 87% in TT (P = NS); graft survival rate was 73% in DT and 68% in TT (P = NS); pure graft survival was 86% in DT vs. 77% in TT (P = 0.096). The 7-year graft survival rate was 67% for cadaver graft recipients vs. 92% for living-related graft recipients (P = 0.044). No difference in the slopes of plasma creatinine between the two groups was observed. Ten DT and 13 TT patients changed their original therapy: statistical analysis, however, was carried out according to intention to treat. Both CsA levels and doses were significantly higher in DT than in TT group (P < 0.001) at any time point up to the 7th year. At univariate analysis, a living-related donor kidney (P = 0.044) and immediate recovery of renal function (P < 0.001) were the only two parameters associated with graft survival at 7 years. At multivariate analysis, only early graft function recovery was correlated with late graft survival (RR = 10.480). Thus, even in the longterm, there is no difference between DT and TT, either in patient or in graft survival: at the doses we used, TT had a lower prevalence of late side effects than DT, however, long-term pure graft survival was better, although not significantly, in DT than in TT. The possibility of a safe shift from one regimen to the other one makes the two treatments complementary rather than alternatives.

Adult↗

Hypertension after renal transplantation.

In 212 cyclosporine-treated renal transplant recipients with stable graft function at 1 year and with potential follow-up of 5 years the prevalence of arterial hypertension was 81.6% at 1 year and 81.2% at 5 years. The logistic regression analysis showed that the presence of hypertension before transplantation (P = 0.0001; odds ratio 3.5), a plasma creatinine level higher than 2 mg/dL at 1 year (P = 0.0001; odds ratio 3.8), and a maintenance therapy with corticosteroids (P = 0.008; odds ratio 3.3) were positively associated with hypertension at 1 year after transplantation. The mean number of graft failures between 1 and 5 years was significantly higher and the mean reciprocal of plasma creatinine was significantly worse at 1 and 5 years in patients with noncontrolled hypertension than in normotensive patients or in patients with hypertension well controlled by drugs. We also investigated the potential protective role of nifedipine. The episodes of acute tubular necrosis (four versus three), of acute rejections (28 versus 29), the mean arterial pressure at 1 year (105 +/- 9 versus 104 +/- 9 mm Hg) and 5 years (105 +/- 10 versus 108 +/- 12 mm Hg), and the mean plasma creatinine level at 1 year (1.4 +/- 0.4 versus 1.6 +/- 0.4 mg/dL) and 5 years (1.8 +/- 1 versus 1.9 +/- 1 mg/dL) were similar in 52 patients who were given nifedipine for at least 4 years and 58 hypertensive patients who never took calcium channel blockers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗