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.

Adult↗

PubMedDate not supplied

Survival of prosthetic grafts of different materials after impairment of a native arteriovenous fistula in hemodialysis patients.

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).

Aged↗

PubMedDate not supplied

Correlation between argyrophilic nucleolar organizer region counts and labelling index in multiple myeloma.

The correlation between the bromodeoxiuridine (BrdU)-labelling index (LI) of plasma cells and a new proliferation marker, the Argyrophilic Nucleolar Organizer Regions (AgNORs), was investigated in 44 myeloma patients at diagnosis. A preliminary analysis was made to verify the reproducibility of the assessment of plasma cell infiltration (PC%) in bone marrow aspirates, used to collect cells for LI determination, and in bone marrow biopsies, used for AgNORs evaluation. Although an overall good correlation was observed between PC% in biopsies and aspirates (r=0.58, p=0.001), the ratio between PC% in biopsies and in aspirates ranged form 0.35 to 7.5. Only 17 patients (38.6%) were within the 0.5-1.5 range. A positive correlation between LI and AgNORs was observed in these patients (r=0.68, p=0.003), whereas the correlation was lost in patients with higher ratio between PC% in biopsies and in aspirates (r=0.08, p=0.69). The prognostic significance of AgNORs was confirmed by survival analysis, showing a reduced survival for patients with high (>4.4) AgNOR counts (14 months vs 35 months, p=0.004). The AgNORs analysis therefore allows the simultaneous evaluation of myeloma cell infiltration, degree of differentiation and kinetics of growth in bone marrow biopsies. AgNOR counts deserve to be included in the procedures for diagnosis and prognostic evaluation of myeloma patients.

Biopsy↗

PubMedDate not supplied

An influence diagram for assessing GVHD prophylaxis after bone marrow transplantation in children.

Graft-versus-host disease (GVHD) represents one of the major complications of allogeneic bone marrow transplantation (BMT). Nevertheless, the occurrence of mild GVHD could be desirable in high-risk leukemic patients, due to a relapse-preventing effect known as the graft-versus-leukemia (GVL) effect. Given that different prophylactic interventions are available to prevent GVHD development, the decision problem consists in assessing both type and dosage of the drugs in order to avoid or induce GVHD, according to the specific patient's condition. The decision problem can be represented and solved by using an influence diagram. The choice of this formalism allows using new available methods for building and updating the model of the decision problem. The qualitative structure of the model and the conditional probabilities were first derived by combining literature results with a medical expert's judgement. More specifically, probabilities were initially assigned as ranges rather than as point values. Then, conditional probabilities were updated, by using a learning algorithm, as new cases became available. The authors analyzed 50 cases of pediatric patients affected by either malignant or nonmalignant diseases, undergoing BMT and receiving GVHD prophylaxis. They used the first 25 cases to adjust the initially assigned conditional probabilities, then checked the model obtained on the remaining patients. The overall performance for GVHD prediction was about 80%.

Algorithms↗

PubMedDate not supplied

Management of graft-versus-host disease in paediatric bone marrow transplant recipients.

We discuss clinical strategies for the prophylaxis and treatment of both acute and chronic graft-versus-host disease (GVHD) with particular attention to children. Grades II to IV acute GVHD occur in 10 to 50% of patients given an allogeneic transplantation of haemopoietic stem cells (HSCT) from a genotypically HLA-identical donor. A significantly higher incidence and severity of the disease is reported in patients receiving transplants from partially matched family donors or unrelated volunteers. Younger individuals or patients receiving HSCT from younger donors develop GVHD less frequently than do older recipients. Severe acute GVHD is characterised by a significant decrease in survival probability, even though the graft-versus-leukaemia activity associated with both acute and chronic GVHD may reduce the risk of leukaemia relapse. Prophylaxis of acute GVHD usually consists of in vivo post-grafting immunosuppression with cyclosporin alone or in combination with methotrexate; methotrexate alone can be considered in leukaemia patients with a high risk of relapse. In recent years, tacrolimus is increasingly being used instead of cyclosporin, alone or in combination with methotrexate. In vitro T cell depletion in paediatric patients is usually reserved for those with transplants from partially matched family donors or unrelated volunteers. The treatment of patients with grades II to IV acute GVHD should be immediate and aggressive, as the quality and duration of the response directly correlates with survival. The overall response rate to treatment is often unsatisfactory, ranging from 40 to 50% of cases. First-line treatment usually consists of corticosteroids. In patients not responding to corticosteroids, antilymphocyte globulin and monoclonal antibodies directed towards lymphocytes and/or cytokines produced during GVHD are employed, but with variable success. Patients experiencing acute GVHD are also prone to develop chronic GVHD. whose classical treatment is based on the use of cyclosporin and corticosteroids. More recently, encouraging results in the treatment of patients with chronic GVHD have been reported with the use of extracorporeal photochemotherapy. Other drugs, such as ursodeoxycholic acid, etretinate and clofazimine, are under evaluation.

Acute Disease↗

PubMedDate not supplied

Rhabdomyosarcoma with primary osteolytic lesions simulating non-Hodgkin's lymphoma.

We report the case of an 8-year-old child presenting with the pathological fracture of two vertebral bodies due to bone lytic lesions. Physical and instrumental examinations did not show any further evidence of disease. However, bone marrow aspirate showed an infiltrate of poorly differentiated cells. When the child was transferred to the Department of Pediatrics, lymphoblastic leukemia was suspected. Although the morphology of the bone marrow biopsy could have suggested a lymphoblastic lymphoma, further immunochemical and immunological studies together with the study of tissue surface antigens resulted in a diagnosis of embryonal rhabdomyosarcoma with an unusual presentation.

Antigens, Differentiation↗

PubMedDate not supplied

The renoprotective effect of antihypertensive drugs.

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.

Angiotensin II↗

PubMedDate not supplied

[The long-term use of a dialysate with high sodium content in short-term hemodialysis].

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Adolescent↗

PubMedDate not supplied

The effect of membrane permeability on ESRD: design of a prospective randomised multicentre trial.

The different permeability of high-flux and low-flux dialysis membranes results in different removal capacity, particularly for uremic toxins of middle and large molecular weight. High-flux dialysers have been evaluated in clinical and epidemiological studies for their effect on mortality, morbidity, dialysis-related amyloidosis, nutritional status, response to erythropoietin treatment, dialysis tolerance and the preservation of residual renal function. Many of these studies, however, lack a prospective design and randomised treatment allocation, or have too few patients and too short a follow-up. Therefore, this clinical trial was designed to prospectively investigate the long-term effect of membrane permeability on clinical outcome in a larger number of patients. The primary objective is to compare the effect of membrane permeability on mortality of patients on bicarbonate hemodialysis and treated with a minimum dialysis dose. Patients included in the study should have been on hemodialysis for no longer than one month and have serum albumin 4 g/dl or lower. Patients will be randomised to either the experimental or the control group. During the four-week run-in period the treatment parameters will be established in order to achieve the required dialysis dose. During the maintenance period of three to five years regular visits are scheduled to record clinical and laboratory parameters, to measure Kt/V and to adapt the treatment parameters. Altogether a minimum of 660 patients should be enrolled within a two-year recruitment period.

Humans↗

PubMedDate not supplied

Antiphospholipid (aPL) antibodies in end-stage renal disease.

Data are few and conflicting about the prevalence and risk factors for antiphospholipid (aPL) antibodies in end-stage renal disease (ESRD). We studied the prevalence, risk factors and clinical manifestations of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) among ESRD patients (chronic hemodialysis (HD) patients and kidney transplant recipients) and blood donors. LA was assessed in a large cohort (n=180) of patients by the activated partial thromboplastin time (aPTT), dilute Russel's viper venom test (dRVVT) and lupus anticoagulant-sensitive aPTT reagent (PTT-LA). IgM- and IgG-aCL were measured by a solid-phase enzyme-linked immunosorbent assay (ELISA) in 111 patients (61.5%). The prevalence of aPL was low but, it was higher in ESRD than blood donors (8.8% (16/180) vs. 0%, P=0.005); the frequency of aCL was also higher in ESRD than controls (10.8% (12/111) vs. 0%, P=0.002). LA was similar in the study and control groups (2.2% (4/180) vs. 0%, NS). Among HD patients and kidney allograft recipients there was no difference in LA (3.9% (4/101) vs. 0% (0/79), NS) and aCL frequency (18.6% (8/43) vs. 5.9% (4/68), NS). aPL was not associated with sex, age, time on HD, post-transplantation follow-up, ESRD etiology, thrombotic or hemorrhagic events, or type of HD membrane; however, these findings must be interpreted with caution, given the low frequency of aPL. In one HD patient LA activity was associated with multiple thrombosis of the access graft and native veins. In summary, the prevalence of aPL in ESRD is low but nevertheless higher than controls; LA does not appear to be related to membrane bio-incompatibility and it may be linked to vascular thrombosis; the lack of concordance between LA and aCL was apparent. Further studies are needed to clarify the issue of aPL in ESRD. LA testing should be incorporated into the diagnostic evaluation of recurrent thrombotic episodes in patients on HD.

Adult↗

PubMedDate not supplied

Combined treatment with steroids and azathioprine in IgA nephropathy: design of a prospective randomised multicentre trial.

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.

Adolescent↗

PubMedDate not supplied

Changes in the clinical condition of haemodialysis patients.

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.

Age Factors↗

PubMedDate not supplied

GBV-C/HGV infection in end-stage renal disease: a serological and virological survey.

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.

Female↗

PubMedDate not supplied

The treatment of IgA nephropathy.

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Glomerulonephritis, IGA↗