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Biomedical subjects

F Locatelli

Publications and source records attributed to F Locatelli.

At least 271 records · Page 15Linked to original sources
PubMed1996

Restricted TCR repertoire and long-term persistence of donor-derived antigen-experienced CD4+ T cells in allogeneic bone marrow transplantation recipients.

We investigated the contribution of transfer of Ag-experienced donor T cells to the immune reconstitution of allogeneic bone marrow transplantation (BMT) recipients. To this purpose, we used a combination of cell culture methods to isolate tetanus toxoid (TT)-specific T cell clones, and a sensitive and specific heteroduplex analysis to monitor the presence of a particular clonotype using TCR N region sequences. We document that patients after BMT display a small response to TT, entirely accounted for by few donor-derived clones. These patients show a strong polyclonal response to TT vaccination; however, the T cell clones transferred with the transplant can still be detected within the polyclonal T cell lines for up to at least 5 yr after BMT. We also demonstrate that vaccination of donors with TT before BMT results in a more relevant transfer of Ag-experienced T cells, allowing the recipients to mount a strong polyclonal response without need of vaccination. These findings provide a rationale for vaccinating donors to optimize adoptive transfer of protective T cell immunity into recipients, and suggest the possibility of using preventive T cell adoptive therapy in conjunction with marrow infusion.

Adult↗
PubMed1996

Effects of activation and inhibition of cAMP-dependent protein kinase on long-term habituation in the crab Chasmagnathus.

On sudden presentation of a danger stimulus, the crab Chasmagnathus elicits an escape response that habituates promptly and for a long period. We have previously reported that administration of a cAMP-permeable analog (CPT-cAMP) along with a phosphodiesterase inhibitor (IBMX) improves long-term habituation (LTH). In present experiments we studied the effect of systemic administration of the protein kinase A (PKA) activator Sp-5,6-DCl-cBIMPS and that of the PKA inhibitor Rp-8-Cl-cAMPS on LTH tested 24 h after a weak training protocol (5 trials of danger stimulus presentation) or a strong training protocol (15-30 trials), respectively. A 50 microliters pre-training injection of 75 microM Sp-5,6-DCl-cBIMPS, and to a lesser degree of 25 microM, improved retention of the habituated response but not affect short-term habituation (STH). Like pre-training injection, post-training administration of Sp-5,6-DCl-cBIMPS proved to exert a facilitatory action on retention though with 75 microM dose only. Conversely, both pre- and post-training injection of 25 microM Rp-8-Cl-cAMPS impaired LTH without affecting STH. Thus, the PKA activator Sp-5,6-DCl-cBIMPS enables a weak training to produce LTH while the PKA inhibitor Rp-8-Cl-cAMPS impairs LTH when a strong training is given. Activation of crab PKA by Sp-5,6-DCl-cBIMPS and its inhibition by Rp-8-Cl-cAMPS were assessed using an in vitro PKA activity assay. These results provide independent evidences supporting the view that PKA plays a key role in long-term memory storage in this learning paradigm.

Amnesia↗
PubMed1996

Cancer among patients on renal replacement therapy: a population-based survey in Lombardy, Italy.

Longer and better survival of End-Stage Renal Disease (ESRD) patients undergoing renal replacement therapy (RRT) is now associated with a higher prevalence of new elderly patients receiving renal replacement therapy (dialysis). In order to help clarify the association of cancer risk with RRT, the incidence of cancer in a population-based cohort of uraemic patients in the Region of Lombardy, northern Italy, was undertaken using data from the Lombardy Regional Dialysis and Renal Transplant Registry. A total of 479 cases of cancer of all sites was recorded in this population. There were statistically significantly elevated risks of primary liver cancer, kidney cancer, thyroid cancer, lymphoma and multiple myeloma. When the data were examined according to primary renal diseases, there did not appear to be any particular association between excess cancer risk and the underlying pathology. While some caution must be expressed in interpreting these data, due to the relatively small numbers of cases expected in many of the disease entities, the results indicate an excess of renal-cell and liver carcinomas and lymphomas in patients receiving RRT and highlight the necessity of careful follow-up and awareness of these associations, together with the need for early detection of such tumours.

Aged↗
PubMed1996

Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.

BACKGROUND: Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases. METHODS: In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis. RESULTS: At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group. CONCLUSIONS: Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.

Adult↗
PubMed1996

Mutations in the erythropoietin receptor gene are not a common cause of Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is an inherited pure red blood cell aplasia that often requires lifelong transfusional support. The origin of the imperfect erythrogenesis is not known. The existence of more than one molecular basis for DBA is indicated by its different modes of inheritance and widely variable clinical phenotypes. Several erythroid growth factors have been thought to have a role in the pathogenesis of DBA. However, there is neither molecular nor clinical evidence for the involvement of stem cell factor or interleukin-3. The observation of elevated erythropoietin (EPO) concentrations and an impaired in vivo and in vitro response to pharmacologic doses of recombinant human EPO has suggested a defective EPO function in the pathogenesis of DBA. We have investigated the possible involvement of the EPO receptor (EPO-R) gene in 23 patients by screening its coding sequence for mutations using single-strand conformation polymorphism (SSCP). A Southern blot and hybridization with an EPO-R probe was also performed on DNA from seven patients. No causal mutations were identified. The absence of concordant segregation of the disease with the EPO-R gene in two informative families ruled out its role in their DBA children. These findings demonstrate that DBA is not commonly associated with EPO-R gene mutations.

Base Sequence↗
PubMed1996

Postnatal variations of growth hormone bioactivity and of growth hormone-dependent factors.

OBJECTIVE: To evaluate whether the low insulinlike growth factor I (IGF-I) levels that are observed in the neonate depend on the biological inactivity of the molecular forms of growth hormone (GH) or on the immaturity of the hepatic GH receptors during the early postnatal period. MATERIALS AND METHODS: Serum samples were collected from 60 normal full-term neonates on day 5 and at 1 and 4 months of age to evaluate the GH concentrations by using both an immunofluorometric assay and Nb2 cell bioassay, as well as the GH-binding protein, IGF-I, and IGF-binding protein 3 values by radioimmunoassay. RESULTS: Five-day-old neonates showed significantly higher (P < .001) mean +/- SEM GH levels that were measured by using the immunofluorometric assay (27.22 +/- 1.62 micrograms/L) and Nb2 cell bioassay (3.56 +/- 0.14 U/mL) compared with those levels in 11 prepubertal children who were studied as control subjects (1.26 +/- 0.28 micrograms/L and 0.74 +/- 0.08 U/mL, respectively). At 1 and 4 months of age, GH values that were measured by using both the immunofluorometric assay (9.15 +/- 0.89 and 2.58 +/- 0.32 micrograms/L, respectively) and Nb2 cell bioassay (2.52 +/- 0.11 and 1.71 +/- 0.15 U/mL, respectively) were decreased significantly (P < .001). In 5-day-old neonates, we observed significantly lower (P < .001) serum GH-binding protein (9.73% +/- 0.42%), IGF-I (67.63 +/- 5.20 ng/mL), and IGF-binding protein 3 (1.46 +/- 0.17 mg/L) concentrations compared with those in the prepubertal children (30.74% +/- 2.01%, 210 +/- 25 ng/mL, and 3.08 +/- 0.22 mg/L, respectively). At 1 month of age, serum GH-binding protein (16.00% +/- 0.70%) and IGF-binding protein 3 (2.96 +/- 0.30 mg/L) values were increased significantly (P < .001), while IGF-I levels (72.55 +/- 7.6 ng/mL, P = .09) were not increased. Serum IGF-I values were increased significantly (P < .005) at 4 months of age (97.94 +/- 9.68 ng/mL). CONCLUSION: The interaction of bioactive molecular forms of GH with the increased hepatic GH receptors induces the rise in postnatal IGF-I levels in early infancy.

Age Factors↗
PubMed1996

Constitutional trisomy 8 as first mutation in multistep carcinogenesis: clinical, cytogenetic, and molecular data on three cases.

Three patients, with constitutional trisomy 8 mosaicism (CT8M), who developed a malignancy are reported. The diagnoses were refractory anaemia, acute lymphoblastic leukaemia, and idiopathic myelofibrosis. In the child with acute leukaemia, the CT8M was diagnosed at birth due to severe dysmorphisms and malformations; the other two patients showed a milder phenotype, and the CT8M was diagnosed only after the finding of trisomy 8 in neoplastic cells. The review of eight similar, previously reported cases and the clinical, cytogenetic, and molecular studies performed in our patients led us to make the following observations: (I) CT8M predisposes to neoplasms, preferentially to myelo- or lymphoproliferative diseases; (2) a gene dosage effect for glutathione reductase in red blood cells was seen in two of our patients; (3) the wide phenotypic variation of CT8M was confirmed: trisomy 8 in neoplastic cells of phenotypically near-normal cases may be misinterpreted as acquired; and (4) molecular studies suggested a postzygotic origin of the trisomy in our three cases, with the supernumerary chromosome being of paternal origin in one case and of maternal origin in the other two. We postulate that the trisomy 8 in neoplasms may often occur by mitotic nondisjunction in an early embryonic multipotent cell and that what is usually interpreted as an acquired trisomy 8 may in fact be CT8M. The constitutional trisomy 8 would act as a pathogenetically important first mutation in multistep carcinogenesis. Whenever trisomy 8 is found in malignancies, the patient should be reevaluated clinically to exclude CT8M, and CT8M patients should be monitored for the possible development of malignancies.

Anemia, Refractory↗
PubMed1996

Frequency of donor cytotoxic T cell precursors does not correlate with occurrence of acute graft-versus-host disease in children transplanted using unrelated donors.

Bone marrow transplantation (BMT) from unrelated volunteers is frequently associated with both increased incidence and increased severity of acute graft-versus-host disease (GVHD). In the last years, it has been suggested that the analysis of the frequency of cytotoxic T lymphocyte precursors (CTLp) of unrelated HLA-matched donors can be used to detect disparity for HLA class I antigens and as a predictive test for development of severe GVHD. In this report, we summarized our experience regarding 20 pediatric patients affected by various hematological disorders, receiving allogeneic BMT from unrelated donors. HLA class I and II antigens of donor/recipient pairs were determined by means of serological typing, whereas molecular typing of HLA-class II antigens of patients and their potential donors was performed using PCR-SSP and PCR-fingerprinting techniques. CTLp values, estimated using limiting dilution analysis, were high (range, 1:7000-1:40,000) in 9 of 20 patients, while the other 11 children had low or undetectable levels (< 1:100,000) of CTL precursors. CTLp frequency was compared with the incidence and severity of GVHD observed after BMT. Our data demonstrate that the frequency of donor CTLp does not statistically correlate either with the occurrence of clinically significant acute GVHD or with disparity for HLA-class II molecular typing between donor and recipient. In particular, 4 of the 10 evaluable patients with an undetectable CTLp frequency developed grade IV, III, II, and IV acute GVHD, respectively. Although the limited number of subjects studied does not allow us to draw any firm conclusion, our data suggest a certain caution in considering this test suitable for the selection of potential donors.

Acute Disease↗
PubMed1996

Peripheral blood stem cell collection from healthy donors for allogeneic transplantation.

There is great interest in the use of peripheral blood stem cells (PBSC) for allogeneic transplantation, based on the good results seen with autologous PBSC infusion. Reasonable caution exists regarding the use of allogeneic PBSC for transplantation because of donor toxicities due to rhG-CSF administration and the risk of graft-versus-host-disease (GVHD) in the recipient because of the large number of T-cell infused. We present preliminary data on allogeneic PBSC collections and transplantation in ten patients affected by advanced leukemia (eight patients), severe aplastic anemia (one patient) and sickle cell anemia (one patient). Seven donors were HLA-identical siblings, while the other three were mismatched for three, two and one locus, respectively. All donors received rhG-CSF at a dose of 12 micrograms/kg for a mean of 5 days. Leukaphereses were performed with the aim of collecting a minimum of 5 x 10(6)/kg (recipient's weight) CD 34+ cells. Collection timing was determined by monitoring CD 34+ cells in the donor's peripheral blood from the second day of rhG-CSF therapy. The PBSC collections yielded a mean of 10.05 x 10(8) MNCs/kg and of 10.48 x 10(6) CD 34+ cells/kg (recipient's weight). PBSC were immediately infused after collection in patients given myeloablative therapy. Engraftment was observed in each patient at a mean of 13.2 days for an absolute neutrophil count (ANC) more than 0.5 x 10(9)/L and of 26.5 days for a platelet count of more than 20 x 10(9)/L. Eight patients experienced no or moderate acute GVHD, whereas two patients died of grade 4 GVHD, notwithstanding GVHD prophylaxis with cyclosporine and prednisone. Two other patients died of viral and fungal infections, respectively, despite prophylaxis. The remaining six patients are alive between 58 and 430 days after transplant. Our results document that allogeneic PBSC are capable of engraftment after a myeloablative regimen. Controlled trials are necessary to compare the potential benefits of this approach with the results obtained in allogeneic bone marrow transplantation.

Adolescent↗
PubMed1996

Effect of a new model of hemodialysis potassium removal on the control of ventricular arrhythmias.

The primary aim of this multicenter, prospective, randomized cross-over study was to clarify whether a new model of hemodialysis (HD) potassium (K) removal using a decreasing intra-HD dialysate K concentration and a constant plasma-dialysate K gradient (treatment B) is capable of reducing the arrhythmogenic effect of standard HD, which has a constant dialysate K concentration and decreasing plasma-dialysate K gradient (treatment A). The secondary aim was to verify whether this new model is clinically safe. In treatment B, the initial dialysate K concentration had to be 1.5 mEq/liter less than the plasma K concentration, and exponentially decrease to 2.5 mEq/liter at the end of HD. Forty-two chronic HD patients with an increase in premature ventricular complexes (PVC) during dialysis were enrolled from 18 participating centers, and randomly assigned to either sequence 1 (ABA) or sequence 2 (BAB). A pool of 333 of 378 expected ECG Holter recordings were checked for signal quality; 269 (71%) from 36 patients (86%) had a satisfactory signal quality and 108 were selected for analysis (1 per patient per period). There was a difference in the natural logarithm of the increase in PVC/hr and PVC couplets/hr during HD between treatments A and B (1.70 +/- 1.59 vs. 1.09 +/- 1.76 and 0.94 +/- 0.86 vs. 0.64 +/- 1.01, a reduction of 36% and 32%, P = 0.011 and 0.047, respectively) without any carry over effect (P = 0.61 and 0.24, respectively). The fact that this decrease of one third is due to a lower plasma-dialysate K gradient is supported by the observation that it was more evident during the first than the last two hours of HD (a reduction in the natural logarithm of the increase in PVC/hr and PVC couplets/hr of 60% and 60%, P 0.002 and 0.009, vs. 26% and 17%, P = 0.098 and 0.332, respectively): the initial plasma-dialysate K gradient was 2.3 times lower during treatment B than during treatment A, without adversely affecting pre-HD plasma K levels. These results could have a considerably clinical impact not only because of the possibility of physiologically decreasing the arrhythmogenic effect of HD, but also because this effect can be considered a "marker" of the electrophysiological derangement induced by the administration of standard HD three times a week for years ("electric disequilibrium syndrome").

Aged↗
PubMed1996

ESRD patient mortality with adjustment for comorbid conditions in Lombardy (Italy) versus the United States.

The present study evaluated end-stage renal disease (ESRD) patient survival in Lombardy, Italy, and the United States (U.S.) using data from two registries, the Lombardy Dialysis and Transplant Registry (RLDT) and the U.S. Renal Data System (USRDS), respectively. For this purpose, 4,196 white patients (2,900 from the USRDS Case Mix Severity Study and all 1296 from RLDT) who started renal replacement therapy in 1986 and 1987 were studied. Compared to Lombardy patients, those in the USA were significantly older (mean age 59.9 +/- 16.4 vs. 55.9 +/- 14.7 years), had a lower proportion of males (53.7 vs. 62.1%), a greater proportion with diabetic nephropathy (29.9 vs. 9.7%) and a significantly greater proportion of patients with the recorded comorbid conditions (heart disease, peripheral vascular disease, cirrhosis, cachexia, malignancy). U.S. patients were less frequently treated with peritoneal dialysis (PD) by day 30 of ESRD (21.2 vs. 30.7). Survival was compared in the Cox proportional hazard regression model, using age, sex, comorbid conditions and early modality of treatment as explanatory covariates. Overall, 48% of the 4196 patients died during the 48 to 72 months follow-up to 12/31/91. Per 100 patient-years the gross death rate for USRDS patients was 28.7 compared to 13.0 of RLDT patients. The unadjusted death relative risk for RLDT was 0.439, that is, 56% lower death rate compared to USRDS patients. Age, sex, diabetic status, each of the recorded comorbid conditions and treatment modality were significantly related to survival and included in the model. The Cox cumulative survival adjusted for all these explanatory covariates survival was for U.S. patients 84.4% at one year, 67.0% at two years and 33.4% at five years, and for RLDT patients 88.3% at one year, 75.9% at two years and 45.9% at five years. The relative mortality risk (RR) for the patients treated in Lombardy adjusted for all the reported covariates was 29% lower than for US patients (RR = 0.71; P < 0.0001). This comparative risk varied significantly by age (P < 0.0001) and was 65 percent lower for Lombardy compared to U.S. patients in the age range 25 to 44 years (RR = 0.35) and about 20% lower for patients over age 65 years (RR = 0.80). This relative risk was mainly related to hemodialysis and was not statistically significant for PD patients. The observed lower mortality risk in Lombardy was less pronounced when adjusted for demographic and comorbid covariates, but was still large and therefore suggests the need for further studies regarding treatment related factors and unmeasured patient factors, particularly in hemodialysis patients.

Adult↗
PubMed1996

Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters. The Italian Cooperative Dialysis Study Group.

There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage (in terms of treatment tolerance, nutritional parameters and pre-treatment beta-microglobulin levels) over a traditional membrane (Cuprophan). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan hemodialysis (Cu-HD), low-flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 +/- 10.46 mg/liter (23%) and in hemodiafiltration of 6.35 +/- 12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes (P = 0.032). The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications.

Adolescent↗
PubMed1996

Role of allogeneic bone marrow transplantation from an HLA-identical sibling or a matched unrelated donor in the treatment of children with juvenile chronic myeloid leukaemia.

Seven children (age range 1.8-11 years) with juvenile chronic myelomonocytic leukaemia (JCML) received an allogeneic bone marrow transplantation (BMT), four from an HLA-identical sibling and three from a matched unrelated donor. In the four children transplanted using an HLA-identical sibling, conditioning regimen included busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM), whereas graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine-A (Cs-A). The preparative regimen was well tolerated and all patients engrafted promptly. None of the patients have relapsed and all four children remain in haematological remission after an observation time of 7, 24, 25 and 48 months, respectively. Of the three children given BMT from an unrelated volunteer, one was < 2 years of age and she received the BU/CY/L-PAM regimen. In view of the increased risk of graft rejection described in patients transplanted from unrelated donors, we chose to prepare the other two patients with fractionated total body irradiation (TBI), thiotepa and CY. Cs-A, short-term methotrexate and Campath-1G in vivo were employed to prevent GVHD in this group of patients. Graft failure with autologous reconstitution of haemopoiesis occurred in the child given the chemotherapy-based regimen. One of the two girls given TBI relapsed after BMT; therefore only one of the three patients who received a marrow transplant from a matched unrelated donor survives in complete haematological remission 10 months after BMT. Our study suggests that the conditioning regimen we employed for allogeneic BMT from a compatible sibling is an effective means of eradicating the leukaemic clone. In our experience, results obtained using unrelated donors are less satisfactory and, at present, the use of such donors seems to be riskier and associated with a lower success rate as compared with BMT from an HLA-identical sibling.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Recombinant human G-CSF-mobilized peripheral blood stem cells for second allogeneic transplant after bone marrow graft rejection in children.

Two children affected by severe aplastic anaemia and sickle cell anaemia rejected the allogeneic bone marrow transplantation from an HLA-matched unrelated volunteer and an HLA-identical sibling, respectively. In both cases a second transplant using granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) was performed. Donors were the HLA-haploidentical mother and the same HLA-identical sibling who was employed for the first marrow allograft, respectively. Treatment with G-CSF and PBSC collection were well tolerated. Both patients had engraftment of donor haemopoiesis and did not experience severe graft-versus-host disease. These cases confirm that PBSC transplant should be considered as a feasible treatment to reverse graft failure in paediatric patients.

Anemia, Aplastic↗
PubMed1996

Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italian Cooperative Study Group.

AIMS: To identify the prognostic factors possibly related to end-stage renal failure development. SUBJECTS AND METHODS: The prognostic factors affecting chronic renal failure progression were analysed in 456 patients who had participated in a formal, multicentre, prospective randomized trial aimed at verifying the role of protein restriction in slowing down or halting the progression of chronic renal failure. The 24-month follow-up foreseen by the protocol was completed by 311 patients and 69 reached an end-point. An inductive analysis on patient survival was made by using the Cox proportional hazard regression model, using a stepwise procedure in order to select only those factors which are significantly associated with survival. For each individual risk factor, a univariate descriptive analysis of survival was performed using the Kaplan-Meier technique. RESULTS: Underlying nephropathy, baseline plasma creatinine, proteinuria, and plasma calcium were all shown to be related to end-stage renal failure onset. Hypertensive patients (mean blood pressure > 107 mmHg) had a worst cumulative renal survival but the degree of proteinuria was even more important as a prognostic factor of renal death than hypertension. The cumulative renal survival of patients whose proteinuria decreased during the trial follow-up was better than those of patients without changes. However, the interaction between baseline lying mean blood pressure and proteinuria was not significant. CONCLUSIONS: Only primary renal disease and proteinuria were related to renal survival, being baseline plasma creatinine confounding factor. By blocking the possible causal role of proteinuria and hypertension, end-stage renal failure could be prevented in a significant percentage of patients.

Adolescent↗
PubMed1996

Influence of membranes on morbidity.

Haemodialysis, a life-saving treatment extending the life of many people for up to more than 20 years, causes acute complications and symptoms and long-term uraemic complications affecting the patient's morbidity and mortality. These inadequacies have been attributed not only to the dialysate composition but also to the membrane. In evaluating the benefits of biocompatible membranes reported in the literature, we have taken into account nutritional aspects, infections, cardiovascular effects, long-term effects, the potential renoprotective effect and patients with acute renal failure survival. In spite of the wide literature on biological effects of biocompatibility of dialytic membranes, stressing the superiority of synthetic membranes, proven causal relationships between clinical diseases and biological reactions are scarce and the true impact of biological effects on the clinical state is still debatable. The results of prospective randomized controlled trials in patients with chronic renal failure are conflicting. Large trials with long follow-up times are needed to further clarify the effects of biocompatible membranes and different treatment modalities on morbidity and mortality of patients on chronic replacement therapy, but these trials are difficult because of randomization and high patient drop-out rates. However, the results of the two controlled trials on patients with acute renal failure stress the importance of biocompatible membranes. Only cost is in favour of the use of cuprophane membranes, especially in patients with acute renal failure.

Acute Kidney Injury↗