Is the type of protein in the diet more important than its quantity for slowing progression of chronic renal insufficiency?
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Animals↗
Biomedical subjects
F Locatelli
Publications and source records attributed to F Locatelli.
Intradermal versus intramuscular hepatitis b re-vaccination in non-responsive chronic dialysis patients: a prospective randomized study with cost-effectiveness evaluation.
BACKGROUND: It has been calculated that 30% of chronic uraemic patients fail to produce antibodies to HBsAg antigen after hepatitis B (HB) vaccination. Low-dose intradermal (i.d.) inoculations and supplementary intramuscular (i.m.) injections have been reported to improve the response rate in previous non-responder chronic uraemic patients, but no cost-effectiveness evaluations have been made about this issue. METHODS: We re-vaccinated 50 chronic dialysis patients, who did not have any detectable anti-HBs antibody after a reinforced protocol of hepatitis B vaccine given by i.m. route, with hepatitis B recombinant DNA yeast vaccine (80 micrograms) by intradermal (25 patients) or intramuscular (25 patients) administration (randomly allocated). We used the same amount of HBsAg in order to exclude the confounding effect of the dose level administered on the immune response of uraemic patients. We studied, over a 20-month follow-up, the persistence of anti-HBs antibodies in our responder vaccinees. We made a comparison between the costs of our re-vaccination protocol and the other re-vaccination strategies that have been recently suggested. RESULTS: One month after completion of re-vaccination protocol, seroconversion rates (100% vs 48%, P = 0.008) and proportion of patients who elicited protective anti-HBs titres (96% vs 40%, P = 0.0001) were significantly higher in i.d. compared to i.m. patients. The levels of anti-HBs expressed as geometric mean titres and 95% confidence intervals (GMT (95% CI)), were significantly increased in i.d. than in i.m. groups, 100 (44-187) vs 26 (14-52) mUI/ml (P = 0.018). At month 12, the seroconversion rates were 57 vs 14% in i.d. and i.m. groups respectively (P = 0.158); the seroprotection rate was higher in i.d. individuals in comparison with i.m. patients, 50 vs 0%, P = 0.072. At month 20, the seroconversion rates were 54 and 0% among i.d. and i.m. patients respectively (P = 0.055); the seroprotection rate was higher in i.d. than in i.m. group (30 vs 0%, P = 0.2). At month 20, the median anti-HBs titres in i.d. patients were 21 mUI/ml, and GMT (95% CI) were 20.9 (2-54) mUI/ml. No important general or local side-effects were observed. The cost of our schedule was $92 US whereas the costs of other re-vaccination protocols ranged between 138 and $807 US. CONCLUSIONS: Our results show that the unresponsiveness to recombinant yeast-derived vaccine may be mostly reversed by repeated low-dose i.d. injections of the same agent. In spite of an equal amount of HBsAg received, i.d. hepatitis B re-vaccination shows higher immunogenicity compared to i.m. administration over a 20-month observation period. Cost-effectiveness analysis demonstrated that the intradermal administration of HB vaccine is the most clinically effective re-vaccination strategy; it is also the most unexpensive one. We strongly recommend low-dose intradermal inoculations in order to re-vaccinate chronic dialysis patients who fail to respond to hepatitis B vaccination.
Adult↗
Influence of hepatitis C virus (HCV) viraemia upon serum aminotransferase activity in chronic dialysis patients.
BACKGROUND: There are many reports concerning HCV in dialysis patients and most of them conclude that the clinical and biochemical features of hepatitis C are often silent in chronic dialysis patients. Elevated levels of serum alanine aminotransferase activity are a sensitive measure of hepatocellular injury, but so far the relationship between anti-HCV and ALT among chronic dialysis patients has been considered imperfect. To our knowledge, however, such an issue has not been adequately addressed. METHODS: Demographic, biochemical, and virological data from 506 patients undergoing chronic dialysis treatment in four dialysis units in Lombardy, northern Italy were collected in order to assess the influence of virological and host factors on serum aminotransferase values. RESULTS: Analysis of covariance showed that positivity for anti-HCV antibody was significantly associated with raised serum AST (P = 0.0001) and ALT (P = 0.0001) levels in the dialysis patients of the whole study group. Logistic regression analysis performed in the subset of patients tested for HCV viraemia and genotype showed that detectable HCV RNA in serum is a strong predictor of raised AST (P = 0.0001) and ALT (P = 0.000001) values. Gender showed an independent weak influence on AST levels (P = 0.055), serum levels of ferritin were significantly (P = 0.042) associated with AST values, the coexistence of HBsAg infection and positivity for anti-HCV antibody was independently associated with raised ALT levels (P = 0.016). The other factors (including positivity for anti-HCV) showed no independent effect on serum aminotransferase levels when they were matched with HCV viraemia in our multivariate analysis. HCV RNA positive patients showed serum AST (P < 0.008) and ALT levels (P < 0.0001) higher than HCV RNA negative patients. There was no relationship between HCV genotypes and liver enzymes. CONCLUSIONS: Our data show that detectable HCV RNA in serum is a strong independent predictor of raised aminotransferase values in chronic dialysis patients; the relationship between serum aminotransferase values and anti-HCV antibody was exclusively related to the association between raised aminotransferase values and HCV viraemia; HCV RNA positive patients show higher hepatic enzyme levels than dialysis patients with no detectable HCV RNA; no association between HCV genotype and serum aminotransferase activity was apparent.
Adult↗
Hepatitis G virus infection in chronic dialysis patients and kidney transplant recipients.
BACKGROUND: The cloning of the hepatitis G virus (HGV), a novel RNA virus of the Flaviviridae family, has been very recently developed. HGV is known to be parenterally transmitted and has been detected in several patients with cryptogenic hepatitis. However, little information exists about the epidemiology of HGV infection in renal patients. We studied 178 chronic dialysis patients and 11 renal transplant individuals to evaluate prevalence, risk factors, and clinical manifestations of HGV infection in this population. METHODS: Hepatitis G virus infection has been detected by a modified PCR technology which incorporates digoxigenin-labelled nucleotides into the amplicon. Primers from the non-coding region and the NS-5 region of HGV are utilized for a single round amplification. Using a streptavidin surface and a biotin-labelled capture probe, the labelled nucleic acid is bound through the capture probe to the surface, and the amplified nucleic acid is detected using antibody to digoxigenin. RESULTS: HGV RNA was detected in 6% of chronic haemodialysis (HD) patients (11/172), 36% of renal transplant recipients (4/11), and 17% (1/6) of patients on peritoneal dialysis treatment (CAPD). There were no significant differences between HGV positive and negative patients on chronic HD treatment with regard to several demographic, biochemical and virological features. However, the frequency of anti-HCV antibody was significantly higher in HGV-positive than HGV-negative patients (9/11 (82%) vs 51/161 (32%), P = 0.006). In the whole group of HGV RNA-positive patients, 78% (11/14) had a history of blood transfusion requirements, 14/16 (87%) had co-infection with HCV, and 1 (6%) had co-infection with HBsAg. There was no significant association between HCV genotypes and HGV RNA positivity. Six (37.5%) of 16 HGV RNA-positive patients showed raised aminotransferase values in serum. CONCLUSIONS: Patients on maintenance dialysis and kidney transplant recipients are at increased risk of HGV infection; HGV is very frequently associated to hepatitis C co-infection, regardless of HCV genotype. HGV may be transmitted by blood transfusions but transmission routes other than transfusion are possible; 37.5% of HGV RNA-positive patients showed raised serum aminotransferase levels. Further investigations are necessary to clarify the role of HGV infection in the development of liver disease in this clinical setting.
Aged↗
Dialysis patient outcomes in Europe vs the USA. Why do Europeans live longer?
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Europe↗
CD56/neural cell adhesion molecule expression in primary extranodal Ki-1/CD30+ lymphoma. Report of a pediatric case with simultaneous cutaneous and bone localizations.
We describe the clinicopathologic features of an unusual case of CD30+/CD50+ T-cell lymphoma in a child who presented with simultaneous primary extranodal cutaneous and bone localizations. The expression of CD56 (neural cell adhesion molecule, or NCAM) is rare in non-Hodgkin's lymphomas other than in a group of haematopoietic/lymphoid neoplasms of natural killer and natural killer-like T-cells, which usually involve extranodal sites and often pursue an aggressive clinical behavior. Coexpression of CD30 and CD56 in T-cell lymphomas is exceedingly rare, and its biological significance is unknown. Our patient responded well to an intensive chemotherapy regimen, and she is now in complete remission 4 years after discontinuation of chemotherapy. Expression of NCAM could be regarded as responsible, in part, for the extranodal localization of lymphoma cells; expression of CD56 also might contribute to the definition of a subset of CD30+ lymphomas with distinctive clinicopathologic features.
Alkaline Phosphatase↗
Biocompatibility in haemodialysis: fact and fiction.
Several of the pro-inflammatory pathways that are activated in patients during dialysis have the potential of producing many side effects. These occur three times a week, accompanying dialysis, and are particularly intense in patients dialysed with so-called 'bioincompatible' membranes. Despite the proven biological superiority of biocompatible membranes, we lack definitive evidence that complement and cell activation three times a week over a period of years is detrimental to patients, because the results of prospective randomized studies are conflicting. Although they do not lead to a decrease in acute clinical symptoms, epidemiological studies suggest that semi-synthetic and synthetic membranes may reduce morbidity and mortality in dialysis patients. Further large scale, prospective and randomized trials with a long follow-up are needed in order to clarify the clinical effects of biocompatibility per se, the increasingly recognized clinical importance of high-flux treatments and the possible interaction between biocompatibility and membrane flux.
Biocompatible Materials↗
High frequency of Epstein-Barr virus (EBV) lymphoblastoid cell line-reactive lymphocytes in cord blood: evaluation of cytolytic activity and IL-2 production.
We investigated natural immunity towards autologous EBV lymphoblastoid cell lines (EBV-LCL) in the cord blood. Cord blood lymphocytes (CBL) from 20 healthy neonates were examined together with three EBV+ and one EBV- adult donors. We found that high frequencies of EBV-LCL-reactive cytotoxic lymphocytes, ranging from 1/190 to 1/12,205 were detectable in EBV- and EBV+ donors, as well as in the cord blood of 15 out of 20 neonates. Surface phenotype analysis, depletion experiments with MoAbs specific for T and natural killer (NK) lymphocyte subsets, and T lymphocyte cloning procedures strongly indicate virus-specific cytotoxic T lymphocytes (CTL) as the major population responsible for the lysis of autologous EBV-LCL in EBV+ donors. Conversely, a high frequency of NK cells seems to be involved in the killing activity observed in neonates and in the EBV- donor. Frequencies of EBV-LCL-induced IL-2-producing lymphocytes were high in EBV+ donors (range 1/2247-1/6633) and heterogeneous, but consistent, in cord blood (range 1/5072-1/57,819) and in the EBV- adult (1/17,148). CD8+ lymphocytes were responsible for IL-2 production in EBV+ individuals, while CD4+ T cells were charged with this role in cord blood and in the EBV- donor. These data demonstrate that CBL are able to develop a strong innate immunity, directed against autologous EBV-infected cells, mediated by both NK cells and CD4+ T lymphocytes. This characteristic may be relevant for protection against viral infections in both neonates and patients given cord blood transplantation (CBT).
Adult↗
Optimization of sodium removal in paired filtration dialysis by single pool sodium and conductivity kinetic models.
Sodium removal is one of the main factors affecting intradialytic cardiovascular stability and interdialytic hypertension, and its removal should therefore be individualized. The aims of this study were: (1) to test the ability of a single-pool variable volume (SPVV) sodium kinetic model (NaKM) to optimize sodium removal in paired filtration dialysis (PFD), and (2) to test a SPVV conductivity kinetic model (CKM) in order to verify whether CKM can be used as an alternative for NaKM in estimating sodium balance. The mean difference between the NaKM-predicted and measured end-PFD plasma water ionized sodium concentrations was 0.00 +/- 0.55 mEq/l, which means that the model has an imprecision of < or = 1.1 mEq/ l. The mean difference between predicted and measured sodium removal was 0.21 +/- 16.86 mEq/session, which means a model overestimate of 0.21 mEq/session. The mean difference between the CKM-predicted and measured end-PFD ultrafiltrate conductivity was 0.01 +/- 0.05 mS/cm, which means an inaccuracy of the model of 0.01 mS/cm and an imprecision of < or = 0.1 mS/cm. The regression in the ionized sodium concentration measured in plasma or blood on the conductive values of the ultrafiltrate shows an error of < or = 2 mEq/l in the prediction of the ionized sodium concentration in blood by means of ultrafiltrate conductivity measurements. These results demonstrate that both models make it possible to obtain a level of dialytic sodium removal that is almost equivalent to interdialytic sodium loading. Moreover, given that it does not require blood sampling and the possibility of making repeated and inexpensive ultrafiltrate conductivity measurements, the CKM allows online monitoring of programmed sodium removal.
Convection↗
Molecular epidemiology of hepatitis C virus infection in dialysis patients.
There are very few data on the molecular biology of hepatitis C virus (HCV) infection in dialysis patients. 101 patients undergoing dialysis treatment in 4 units in the Lombardy, northern Italy, were analyzed by RT-PCR for HCV viremia, by line probe assay technology for HCV genotyping and by a serological analysis for detecting type-specific antibodies. 61 of 101 (60%) patients showed detectable HCV RNA in serum; HCV genotype 2a was dominant (30/53 = 57%), followed by HCV genotype 1b (20/53 = 37%). There was no relationship between HCV genotyping and the clinical or demographic features of the patients. The antibody response toward the c33-c, c100-3, and 5-1-1 antigens was more frequent in HCV genotype 1b compared with genotype 2a (p = 0.046, p = 0.001 and p = 0.0001, respectively). The antibody levels to NS-3 and NS-4 HCV proteins were significantly higher in patients with-HCV genotype 1b in comparison with HCV 2a-infected individuals (p = 0.0001). There was a high level (82%) of agreement between HCV genotyping by RT-PCR and the assessment of type-specific antibodies by serological analysis; further, it was possible to detect type-specific antibodies in 6 of 22 (27%) patients in whom PCR amplification was unsuccessful. In conclusion, HCV subtype 2a was dominant in our population of HCV-infected dialysis patients, dialysis patients infected by different genotypes showed similar demographic and clinical characteristics, the antibody response toward the NS-3- and NS-4-related antigen of HCV was genotype dependent. There was a high level of agreement between HCV genotyping by RT-PCR and the detection of type-specific antibodies by serological analysis. As significant biological differences may exist among HCV strains, the assessment of HCV types may be very useful in the routine clinical activity of nephrologists in dialysis units.
Adult↗
'Pulse oral' versus intravenous calcitriol therapy in chronic hemodialysis patients. A prospective and randomized study.
The aim of this prospective and randomized study was to compare the efficacy, side effects, and costs of 'pulse oral' versus intravenous calcitriol in the treatment of secondary hyperparathyroidism in hemodialysis (HD) patients. A total of 20 patients were randomized to receive over a 4-month period pulse orally administered calcitriol (pulse oral group; n = 10) or intravenous calcitriol (intravenous group; n = 10). All patients used standard dialysate calcium (1.75 mmol/l) throughout the study period. In accordance with the study design calcium dialysate concentrations were reduced when this was necessary to avoid hypercalcemic crises. The patients were stratified into two subgroups according to their initial serum PTH levels: patients with mild or moderate degree of hyperparathyroidism (17 patients) and patients with severe hyperparathyroidism (3 patients). Intravenous and pulse oral cacitriol did not significantly reduce serum PTH concentrations in patients with severe hyperparathyroidism (1,157 +/- 156 vs. 807 +/- 228 pg/ml [corrected], p = 0.09). Intermittent calcitriol, administered by intravenous or oral route, significantly reduced serum PTH levels (326 +/- 119 vs. 109 +/- 79 pg/ml [corrected], p = 0.0001) in patients with mild or moderate hyperparathyroidism. In patients with mild or moderate hyperparathyroidism, intravenous calcitriol significantly reduced PTH concentrations at the end of the 1st month, before the increase of serum ionized calcium levels, whereas 'pulse oral' calcitriol significantly suppressed parathyroid activity at the end of the 2nd month. Calcium dialysate concentration was reduced in 9 out of 10 (90%) patients of the pulse oral group and in all patients (10/10) of intravenous group. The incidence of hypercalcemic crises was 24% (39/160) in the pulse oral group and 14% (27/160) in the intravenous group. Analysis of costs showed that intravenous calcitriol was more expensive compared to pulse oral calcitriol. These data indicate that intermittent intensive calcitriol therapy, regardless of the route of administration, is effective in suppressing parathyroid activity in HD patients with mild or moderate hyperparathyroidism. In contrast, intermittent calcitriol therapy has a limited ability to achieve sustained serum PTH reductions in HD patients with severe hyperparathyroidism. Intravenous calcitriol was more expensive than pulse oral calcitriol, and we recommend the use of pulse oral calcitriol in HD patients with mild or moderate secondary hyperparathyroidism.
Administration, Oral↗
Pulmonary complications and respiratory function changes after bone marrow transplantation in children.
We prospectively assessed the frequency of pulmonary complications and the natural course of lung function after bone marrow transplantation (BMT), as well as the effect of several risk factors in a homogeneous group of 39 children who underwent allogeneic or autologous BMT for haematological malignancies between 1992 and 1995. Four patients developed pneumonia within the first 3 months and three 3-6 months after BMT. A considerable percentage of acute bronchitis was recorded throughout the follow-up. Three patients died after the 6 month visit because of pneumonia (two patients) and pulmonary aspergillosis (one patient). No patients had obstructive lung disease syndrome. At 3 months after BMT, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and transfer factor of the lung for carbon monoxide (TL,CO) significantly decreased, but FEV1/FVC ratio and maximal expiratory flow at 25% of FVC remained unchanged, suggesting a restrictive defect with diffusion impairment. At 18 months, there was a progressive recovery in lung function, although only 11 patients had normalized. Seropositivity for cytomegalovirus had a significant effect on lung function whereas graft-versus-host disease also had an effect, although it was not statistically significant. Baseline respiratory function, type of transplant, type of conditioning regimen and respiratory infections did not significantly affect the outcome of BMT. The high frequency of severe lung function abnormalities found in this study, suggests a careful functional monitoring in all subjects undergoing bone marrow transplantation, even in the absence of respiratory symptoms.
Adolescent↗
Intensified and high-dose chemotherapy with granulocyte colony-stimulating factor and autologous stem-cell transplantation support as first-line therapy in high-risk diffuse large-cell lymphoma.
PURPOSE: In our previous study with MACOPB, we identified a high-risk group of patients with a poor 3-year survival rate of 29%. These patients were defined as having at diagnosis advanced-stage disease with high tumor burden (TB) and elevated lactate dehydrogenase (LDH) level or bone marrow (BM) involvement. A novel therapeutic scheme was investigated to improve the outcome of these patients. PATIENTS AND METHODS: Fifty patients with high-risk diffuse large-cell lymphoma (DLCL) were enrolled. The therapeutic scheme includes three phases: induction with 8 weeks of MACOPB; intensification with a 3-day course of mitoxantrone 8 mg/m2 plus high-dose cytarabine (HDARA-C) 2 g/m2 every 12 hours plus dexamethasone 4 mg/m2 every 12 hours (MAD protocol) and granulocyte colony-stimulating factor (G-CSF) 5 microg/kg on days 4 to 17 to harvest peripheral-blood progenitor cells (PBPC); consolidation with carmustine (BCNU), etoposide, ARA-C, and melphalan (BEAM) regimen; plus autologous stem-cell transplantation (ASCT) with PBPC, marrow, or both. RESULTS: Thirty-six patients (72%) achieved a complete response (CR), 11 (22%) showed no response (NR), and three (6%) died of toxicity. Among the 22 PRs or NRs after the induction phase, 56% of patients achieved a CR with subsequent intensified therapy. With a median follow-up duration of 32 months, the overall survival and failure-free survival rates were 56% and 50%, respectively. The disease-free survival rate is 69% at 32 months. Leukapheresis after MAD and G-CSF yielded a median of 32 x 10(6)/kg CD34+ cells and 80 x 10(4)/kg granulocyte-macrophage colony-forming units (CFU-GM). Thirty-nine patients were autografted and 11 did not undergo ASCT: six because of disease progression, four due to toxicity, and one because of patient refusal. The median times to achieve engrafment were 11 days (range, 7 to 19) to a neutrophil count greater than 0.5 x 10(9)/L and 12 days (range, 8 to 60) to a platelet count greater than 50 x 10(9)/L. CONCLUSION: This sequential scheme with intensified and high-dose chemotherapy with ASCT is feasible with moderate toxicity and may improve the outcome in high-risk DLCL.
Adult↗
Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.
PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS: Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P < .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P < .01). CONCLUSION: Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.
Bone Marrow Transplantation↗
An ontology-based framework for guideline-driven medical practice.
This paper describes a general framework for clinical practice guidelines development, dissemination and use. We propose an ontological description of the medical knowledge and of the organizational context, in order to produce clinical guidelines which, on one hand, can be widely shared between different institutions and, on the other, can be efficiently tailored to consider the peculiarities of each clinical context.
Acute Disease↗
The Hoyeraal-Hreidarsson syndrome: the presentation of the seventh case.
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Anemia, Aplastic↗
Factors affecting progression of renal insufficiency.
The aim of this study was to analyze the factors affecting chronic renal insufficiency (CRI) progression at diagnosis (markers of progression), their spontaneous or therapy-induced behavior, and their relationship to CRI progression during follow-up. The underlying disease is the 'determinant factor' of progression and although clinical trials usually report crude cumulative renal survival without taking into account concomitant risk factors, it is known that diabetic nephropathy, polycystic kidney disease, and glomerulonephritis are more progressive than nephroangiosclerosis and interstitial nephropathy. Among the 'effect modifiers,' the baseline level of renal function, hypertension, and proteinuria are the most important. The adverse synergistic effects of proteinuria and high blood pressure have been confirmed, and the importance of correcting hypertension (systemic and glomerular) and proteinuria for slowing disease progression has also been demonstrated. The potential adverse role of a high-protein intake, strongly suggested by experimental studies and the clinical data of uncontrolled trials, has been challenged by the data coming from large controlled trials. The role of lipids needs to be clarified by prospective randomized trials, but the effects of therapeutic interventions aimed at correcting lipid abnormalities seem very promising. The association between the DD genotype of the gene encoding the angiotensin-converting enzyme (ACE) and an increased risk of renal function loss is under evaluation with the aim of identifying the patients who may most benefit from ACE inhibition.
Biomarkers↗
Long-term progression of chronic renal insufficiency in the AIPRI Extension Study. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.
The Angiotensin-converting-enzyme Inhibition on Progressive Renal Insufficiency (AIPRI) Study showed that the ACE inhibitor benazepril provides protection against loss of renal function in patients with chronic renal insufficiency (CRI) caused by various renal diseases. As a result of unexpectedly low mortality in the placebo group, there was a substantial imbalance in mortality during the course of this study (8 patients on benazepril vs. 1 on placebo). The aim of the extension study was to follow-up the patients from the AIPRI core study until autumn 1996, focusing on CRI progression and mortality. Data collection was post hoc. Patients were treated according to investigators' usual practices, without knowledge of the core study trial medication or (initially) the core trial results. A new primary efficacy parameter was defined as the time from the start of core study treatment to the occurrence of the first event in the combined composite end-point of dialysis, renal transplantation or death related to renal disease. Serial serum creatinine levels and all-cause mortality were also recorded. The median total follow-up for core + extension periods was 6.6 years. Many patients from both treatment groups (64% on benazepril and 61% on placebo) received ACE inhibitors during follow-up. In the intention-to-treat analysis of the core + extension data, only 79 of 300 patients from the benazepril group, compared to 102 of the 283 patients from the placebo group needed dialysis or renal transplantation, or died related to renal disease (P < 0.013, log-rank test). The mortality imbalance seen in the core trial was not evident with the longer follow-up (25 deaths in the benazepril and 23 in the placebo group, before dialysis). These data clearly demonstrate a long-term beneficial effect in patients randomized to take benazepril during the core study, but because treatment during the extension period was not randomized, the results of this intention-to-treat analysis need to be interpreted with care.
Angiotensin-Converting Enzyme Inhibitors↗