Biomedical subjects
Publications and source records attributed to L Del Vecchio.
A group of 20 patients affected with thyroid carcinoma, all from Southern Italy, was typed for HLA-A, -B, -C and -DR antigens. Sixteen of them (80%) typed for DR1, while in the control group (120 unrelated healthy individuals from the same region) only 22 (18.3%) shared the same antigen (chi 2 = 32.96). The data indicate a highly significant association between the HLA-DR1 gene and the thyroid carcinoma.
Morphological, cytochemical, immunological and clinical features of 19 adult patients with T cell acute lymphoblastic leukemia (T-ALL) were investigated at the time of diagnosis and were compared with those of 34 adult patients affected by B cell acute lymphoblastic leukemia (B-ALL). Immunophenotypic studies employing a wide panel of monoclonal antibodies (mAbs) revealed a heterogeneous pattern of antigen expression in the five T-ALL groups that were identified on the basis of blast T cell differentiation levels. PAS (periodic acid Schiff) negativity and focal AP (acid phosphatase) positivity, as well as white blood cell count and serum lactic dehydrogenase levels, were significantly related to T-ALL when compared with B-ALL. On the contrary, no statistically significant difference was demonstrated in the clinical outcome.
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UNLABELLED: Proteinuria has been shown to play a causal role in the progression towards ESRD of IgA nephropathy (IgAN). We demonstrated that steroids are effective in reducing proteinuria and preserving renal function. AIM: to evaluate the long-term effect of steroids in IgAN patients (6th year evaluation) and better clarify the role of proteinuria reduction in slowing down the progression. METHODS: multicenter randomized controlled trial of 86 adult IgAN patients with serum creatinine < or = 1.5 mg/ dL and moderate proteinuria. They received either supportive therapy or methylprednisolone 1-g i.v. for three days at months 1, 3, and 5, plus oral prednisone (0.5 mg/kg every other day for six months). RESULTS: Proteinuria significantly decreased in the treated patients (from 2.0+/-0.60 g/24 h at baseline to 1.0+/-0.68 g/24 h at six months) and remained stable till the 6th year (0.67+/-0.5 g/24 h), it slightly decreased in the control group. Six-year renal survival was significantly better in the steroid than in the control group: 9 patient (20.9%) in the steroid group and 15 (34.8%) in the control group reached the primary end-point of a 50% increase in serum creatinine from baseline. Five controls and none of the steroid-treated patients started dialysis. Steroid-treated patients did not experience any major side effects during follow-up. CONCLUSIONS: Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN patients. Early reduction of proteinuria could also be marker of a persistent reduction in its levels over time and of a better outcome in the long term.
In our department, hemodialysis vascular accesses with graft, are used in patients with impairment of native distal and proximal arteriovenous fistulas (AVF-E). The aim of this study was to compare the survival of grafts of different materials (PTFE vs. bovine vein) in these patients. From 1991 to 1999, we prospectively evaluated 53 patients (35 women, 18 men, age 68 +/- 11 years, on dialysis for 70 +/- 65 months). Fifty-three PTFE, 10 reinforced PTFE, and 22 bovine vein grafts were placed. We evaluated the primary patency (PP) (days between fistula placement and the last dialysis before thrombosis occurred) and the secondary patency (SP) (days between fistula placement and the last dialysis treatment before it was considered lost) by separating PTFE survival from that of bovine veins. In the same patients, we also evaluated the survival of the native arteriovenous fistulas (AVF-E) during the pregraft period. Furthermore, we evaluated 404 patients (172 women, 232 men, age 65 +/- 14 years, on dialysis for 50 +/- 53 months) in whom only AVF-E were placed during the same follow-up period. Graft and AVF-E survival were calculated according to the Kaplan-Meier method. In patients with grafts, the PP at 1 year was 17.4% for PTFE and 23.9% for bovine veins. At 12 months, the SP of bovine veins was significantly higher than that of PTFE (81,9% vs. 50%, p < 0.04). In the patients who only had AVF-E, the PP and SP was, respectively, 43% at 12 months and 52.4% at 50 months. A preliminary experience in 22 patients with a 20 month follow-up confirms better survival of bovine veins than PTFE (p < 0.04).
Some antihypertensive drugs may have a renoprotective effect, that is partially independent of their ability to reduce blood pressure. ACE-inhibitors are safe and effective agents that are capable of reducing proteinuria and preventing CRF progression. The results of the AIPRI extension study suggest that they may also have a long-term renoprotective effect. ACE gene polymorphism may partially influence the response to these agents. Angiotensin II receptor 1 antagonists (AT1RA) are effective in reducing proteinuria, but their clinical impact is still a matter of study. It has been shown that non-dihydropyridine and some dihydropyridine calcium channel blockers (CCBs) reduce proteinuria and are also renoprotective, but there is a lack of large-scale prospective randomised trials. Given that the use of various drugs is usually needed to achieve good blood pressure control in patients with CRF, the possibility that a combination of ACE-inhibitors with CCBs or ATIRAs may have an additive renoprotective effect is intriguing.
Corticosteroids have had variable success in IgA nephropathy (IgAN). Our previous trial with a six-month course of steroids in IgAN patients showed they were effective in reducing the risk of renal function deterioration and proteinuria, but this effect seemed to decrease in the long term. This new randomised trial was designed to prospectively evaluate whether adding low-dose azathioprine to steroids improves long-term renal survival in adult biopsy-proven IgAN patients with proteinuria > or = 1 g/24 h and plasma creatinine < or = 2.0 mg/dl. The patients will be treated with steroids (methylprednisolone 1 g i.v. for three consecutive days at months 1, 3 and 5, plus oral prednisone 0.5 mg/kg every other day for six months) plus azathioprine 1.5 mg/kg/day for six months or steroids alone with the same schedule. Altogether a minimum of 346 patients should be enrolled within a four-year recruitment period. The planned duration of follow-up is five years.
The characteristics of the dialytic population have substantially changed over the past 30 years, becoming older and with a greater number of coexisting diseases. The considerable evolution in treatment modalities has lead to a significant increase in the efficacy and tolerability of dialysis. However, physicians have to deal with illnesses in long term dialysis survivors that may be a consequence of inadequate renal replacement therapy rather than of the dialysis procedure per se. Cardiovascular diseases are the leading cause of death and, although many of the risk factors are the same as in the general population (i.e. hypertension), some appear to be specific to CRF (i.e. hyperparathyroidism, anaemia). Age is the most important demographic factor associated with increased mortality. The increasing incidence of ESRD diabetic patients, as well as malnutrition, also contribute to higher mortality in RRT. The therapeutic answer to a worsening in clinical condition is adequate medical care (starting in the conservative phase), with particular attention being given to correcting anaemia, hypertension, volume overload and hyperparathyroidism, and preventing malnutrition. Treatment modalities also play a crucial role. Data suggest that adequate dialytic dose (and possibly time) can reduce morbidity and mortality, and on-line sodium and potassium modelling can improve intradialytic cardiovascular stability and reduce arrhythmias. Long-term treatment with synthetic high-flux membranes may confer some beneficial effect on beta2-m amyloidosis-related morbidity and may also reduce mortality. Family and social support greatly affect the quality of life of the patients. However technologically advanced, no procedure can succeed unless it is performed in the context of humanised health care directed towards patient needs.
Patients with end-stage renal disease (ESRD) appear to be at high risk for GBV-C/HGV infection. This information has been obtained with virological techniques (RT-PCR) but few serological data exist. A prototype enzyme immunoassay has now been developed to detect antibodies against the putative envelope protein (E2) located on the surface of the GBV-C/HGV virion particle. We studied the prevalence of GBV-C/HGV infection, as detected by RT-PCR and anti-E2 GBV-C/HGV antibody, in a cohort of chronic dialysis patients (n=157) and renal transplant (RT) recipients (n=77); as a control group, 136 healthy blood donors were tested. The total prevalence of GBV-C/HGV in ESRD was 23% (54/234). The frequency of GBV-C/HGV viremia was 7.7% (18/234) in ESRD and 4.4% (3/68) among healthy blood donors; the prevalence of anti-E2 GBV-C/HGV was 15% (36/234) and 8.8% (12/136) in ESRD and controls, respectively. No relationship was seen between anti-E2 GBV-C/HGV antibody (or GBV-C/HGV viremia) and age, sex, time on renal replacement therapy, anti-HCV, HBsAg and transfusion requirement. No statistical association was observed between GBV-C/HGV and AST/ALT activity. Two of 54 GBV-C/HGV positive patients (3.7%) had raised ALT but were negative for HBV/HCV. In the majority of patients (35/36, 97%) the presence of anti-E2 GBV-C/HGV antibody was linked with the loss of GBV-C/HGV viremia from serum. In conclusion, GBV-C/HGV infection, as detected by RT-PCR and anti-E2 antibody, was common in ESRD, and the rate of infection was higher than in controls. No association was seen between GBV-C/HGV and various demographic or clinical factors. A small group of GBV-G/HGV positive patients tested negative for HBV/HCV and had raised ALT. In many patients exposed to GBV-C/HGV infection the virus was cleared. The clinical significance of GBV-C/HGV in ESRD remains controversial. Prospective studies with additional serological assays are in progress.
Health care organisations and financial factors (particularly treatment reimbursement rates) may influence the management of ESRD. We analysed the organisation of renal replacement therapy (RRT) in Italy, focusing on RRT population trends, patient distribution by treatment modality and provision, reimbursement rates, accreditation and quality control. Data from the Italian Dialysis and Transplant Registry and market research studies indicate that Italy has one of the highest dialysis and treatment acceptance rates in Europe. There is a high rate of hemodialysis (HD) and good use of peritoneal dialysis (PD), whereas the prevalence of transplanted patients is lower than the European mean. Dialytic treatment in private centers is limited by law to HD (mainly in Central-Southern Italy) and covers nearly 25-30% of the demand for RRT which means that, although Italy has a public national health care system, the provision of RRT is based on a "mixed" model. Regions with a higher prevalence of "private" dialysis have more dialysis centers, but a lower prevalence of PD since it is not permitted in private facilities, and fewer transplanted patients. The "public" system is not an automatic guarantee of quality and efficacy, and the "private" system is not necessarily a synonym of poor quality treatment due to its need to make a profit. The coexistence of private and public facilities (if well balanced and integrated) may in fact help overcoming bureaucracy in the public administration in relation to the demand for innovation and improving performances by means of fair competition.
In recent years, a target blood pressure (BP) of at least 125/75 mmHg has been sought in order to reduce the rate of progression of chronic renal failure (CRF) and cardiovascular mortality. Some antihypertensive agents, such as ACE inhibitors, calcium channel blockers and angiotensin receptor antagonists (and perhaps endothelin converting enzyme inhibitors and endothelin antagonists), may also reduce CRF progression because they block some of the pathogenetic mechanisms involved in renal damage. Although this effect seems to be partially independent of BP reduction, it is still not clear whether these drugs are really superior to other antihypertensive agents when low BP is achieved. However, the possibility that combination treatments with some of these drugs may confer additive or even synergistic renoprotective effects other than BP control is not only fascinating, but also important because multidrug antihypertensive regimens are required anyway to manage BP adequately in the majority of patients with CRF.
Immunosuppressive treatment of IgA Nephropathy (IgAN) with chronic renal failure (CRF) is still a controversial issue, because of scepticism on expected results and possible side effects of therapy. There is a "point of no return" (serum creatinine of 3 mg/dL), after which the deterioration of renal function becomes inevitable. We report the case of a 24-year-old woman, with advanced IgAN (serum creatinine > 3 mg/dL), who experienced remission of proteinuria and long-lasting stabilisation of renal function, after treatment with a 6-month steroid course. Literature information on the therapy for advanced phases of IgAN is inadequate. Our multicenter randomised controlled trial, aimed at evaluating the effects of a 6-month steroid course, included 18 patients with mild CRF at baseline. The ten patients that we treated experienced better renal survival than the eight patients who received no steroids, with an expected renal survival of 29.5 and 6.5 years, respectively. In a prospective study of patients with serum creatinine of 1.6 - 2.9 mg/dl, Ballardie and Roberts compared 19 patients treated with immunosuppressive drugs and 19 control patients: renal survival at 5 years was 72% in treated and 5% in control patients. Goumenos et al. retrospectively evaluated 39 patients treated with steroids and azathioprine and 22 untreated patients: a non-progressive course was observed in 79.5% of treated patients and in 36% of untreated patients. Tsuruya et al. retrospectively examined 26 patients treated with steroids and cyclophosphamide and 19 untreated patients: the expected renal survival was of 5.2 years in treated and 4.8 years in untreated patients, respectively. Prospective controlled trials are essential for evaluating the real effectiveness of immunosuppressive therapy in IgAN patients with impaired renal function. We have recently proposed a study to compare steroids alone and steroids plus azathioprine, because it is mandatory to look for safe and effective therapies that delay as much as possible the start of dialysis, also in patients with already established CRF.
CRF increases its incidence and prevalence, with increased social and cost burden, while life expectance decreases, mainly due to cardiovascular comorbidity. Recent clinical studies demonstrated the slowing of the renal damage by low - protein diet and the reduction of proteinuria by lowering blood pressure. A good control of anemia and calcium - phosphate balance reduces the cardiovascular risks. Stopping smoking improves survival but lipid-lowering and anti-inflammatory drugs need more studies. It has been demonstrated that an early intervention of nephrology care reduces morbidity and mortality (illness and death incidence) and reduces costs.
A case with coexisting chronic lymphocytic leukemia (CLL) and chronic myelomonocytic leukemia (CMML) is described. A 74-year-old man with a typical B-CLL also showed sustained peripheral blood and bone marrow monocytosis. Typical myelodysplastic changes and monosomy 7 were also found. Cytographic and immunophenotypic analysis confirmed the presence of two distinct cell populations, i.e., lymphoid and monocytoid. Both malignancies presented an extraordinarily benign prognosis. It remains uncertain whether monocytosis was either the expression of a distinct myelomonocytic clone or the progeny of a B/monocytic bipotential precursor able to feed both leukemic phenotypes.
BACKGROUND: Darbepoetin alpha is a novel erythropoiesis stimulating protein with unique properties as compared to recombinant human erythropoietin (rHuEPO), including a three-fold longer elimination half-life that allows for less frequent dosing. This study was aimed at testing the efficacy and safety of darbepoetin alpha in a large number of chronic dialysis patients switched from rHuEPO. METHODS: Nine hundred and fifty dialysis patients in stable treatment with rHuEPO were switched to darbepoetin alpha. Patients receiving rHuEPO 2 or 3 times weekly were switched to once weekly darbepoetin alpha and those receiving rHuEPO once weekly were switched to once every other week darbepoetin alpha. Patients received darbepoetin alpha by the same route of administration (SC or IV) as the one used for rHuEPO. The unit doses of darbepoetin alpha (10-150 microg) were titrated to maintain haemoglobin concentration within -1.0 and +1.5 g/dL of the individual mean baseline haemoglobin levels and between 10 and 13 g/dL for 24 weeks. RESULTS: The mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was statistically but not clinically significant [-0.10 g/dL (95% CI: -0.18, -0.02]. In general, the geometric mean weekly dose of study drug from screening/baseline to evaluation period remained substantially unmodified [(from 26.10 micro g/wk to 25.90 microg/wk; percentage change -0.40% (95% CI: -3.78, 3.10)]. Overall, darbepoetin alpha was well tolerated. CONCLUSIONS: The treatment of anaemia of a large dialysis patient population with unit dosing of darbepoetin alpha is effective and safe in maintaining target haemoglobin concentration at reduced dose frequency.
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Survival of uremic patients on dialytic treatment is significantly worse compared with that of the general population, mainly because of cardiovascular disease (CVD) excess. Anemia, a frequent and relatively early complication of impaired renal function, can considerably worsen the outcome for these patients. Due to the induced alterations on cardiovascular structures, first, left ventricular hypertrophy, anemia is not only a condition significantly impairing quality of life, but also a serious threat for the long-term survival of patients undergoing dialysis. Several studies actually showed the existence of a clear inverse association between hemoglobin (Hb) levels and mortality or hospitalization rates in patients with renal failure. Although the benefits of a partial correction of Hb levels, even in terms of left ventricular hypertrophy regression, have been well documented, it remains unclear whether starting the treatment in a very early phase of the disease or achieving a complete normalization of Hb levels above the target values recommended by current guidelines can provide further advantages, at least in selected patient groups. However, ongoing clinical trials, particularly the CREATE and the ACORD, will be able to clarify better which anemia correction practices can ensure the best results both for quality of life and for cardiovascular status; and therefore, for the long-term survival of patients with renal disease.
End-stage renal disease (ESRD) is a social and economical threat worldwide. Much has been done in previous decades to develop new treatments, but we remain a long way from being satisfied. Recently, growing attention has been paid to polytherapeutic approaches to chronic kidney disease (CKD) to control different causal factors involved in progression and in the meantime, and reduce them as much as possible. Starting from a paper published in the British Medical Journal, which suggested the use of a polypill to prevent cardiovascular events in the general population, I tried to apply a similar approach in the nephrology setting, focusing my attention on therapeutic strategies to slow down CKD progression, which could possibly be included in a 'anti-dialysis polypill'. Among these strategies, I selected the effect of the inhibition of the renin-angiotensin system, the use of statins and anemia correction. Unfortunately, this approach is not applicable theoretically, due to the lack of a sufficient number of randomized clinical trials calculating the relative risk, in particular concerning the use of statins and the treatment of anemia. However, while awaiting new therapeutical approaches to be more selective and efficacious, a treatment combination seems to be, together with better implementation of single therapies, the only possible strategy to apply.