Kinin-dependent hypersensitivity reactions in hemodialysis: metabolic and genetic factors.

Although the association of angiotensin I-converting enzyme inhibitors (ACEis) with a negatively charged membrane is thought to be responsible for hypersensitivity reactions (HSRs) during hemodialysis, we hypothesize that these complications are due to changes in plasma aminopeptidase P (APP) activity and genotype. To test this hypothesis, we measured plasma APP activity in 14 patients who suffered HSR (HSR+) while dialyzed with an AN69 membrane and simultaneously treated with an ACEi. APP activity was also studied in a control group (n=39) dialyzed under the same conditions, but who did not suffer any side effect (HSR-). We found significantly decreased plasma APP activity (P=0.013) in HSR+ subjects as well as altered degradation of endogenous des-Arginine(9)-bradykinin, with a significantly lower beta value (P<0.001). The same analytical approach was taken in 171 relatives of HSR+ patients. Variance component analysis suggested that genetic differences may explain 61% of the phenotypic variability of plasma APP activity (P<0.001) and the kinetic parameters that characterized kinin degradation. We also showed that the C-2399A single-nucleotide polymorphism at the XPNPEP2 locus was a significant predictor of APP activity in the 39 HSR- controls (P=0.029). Furthermore, a recessive genetic model for the A allele disclosed a significant difference in mean APP activity by genotype (P<0.001). Finally, our study defined the nonspecific inhibition of recombinant APP by some ACEis. In conclusion, this paper highlights the complexity of HSR in hemodialysis, suggesting, as with angioedema, that these rare, but life-threatening adverse events are governed by several metabolic and genetic factors.

[Membrane biocompatibility in dialysis: the role of absorption]. / Biocompatibilité des membranes de dialyse: le rôle de l'adsorption.

Membrane biocompatibility is a concept that have gained clinical relevance. How to define a "biocompatible membrane" in hemodialysis is still object of discussion. Intermediate biochemical reactions, measured in the blood are more relevant than clinical events to document membrane's quality. In the absence of prospective studies, it is not possible to document that the constant use of a dialysis membrane governs risk of death in the hemodialyzed patient. Nevertheless, some clinical criteria are relevant, such as hemocompatibility, i.e. clotting of the extracorporeal circuit and heparin consumption, hypersensitivity reactions, denutrition associated with the "microinflammatory" stress induced by the hemodialysis session, occurrence of beta 2 microglobulin-derived amyloidosis. Synthetic membranes are credited of higher biocompatibility than cellulosic membranes. In general, they are highly permeable to peptides and proteins of the middle molecular range that contain some uremic toxins. In addition to be "highly permeable", allowing convective transfert, some synthetic membranes (polymethylmetacrylate, polyacrylonitrile, polyamide) bind proteins. Protein adsorption into synthetic membrane results from electrical charges distribution both at the surface and in the bulk of the membrane. Ionic interactions are the main contribution to protein adsorption, but rheological conditions, surface rugosity, and porosity or gel consistency play also a role. Consequently, some membranes can bind cytokines and oxygen species, other bind endotoxins. Recently, it has been demonstrated that heparin coating was possible with the AN69-ST membrane, resulting in improved hemocompatibility and significant lessening of heparin requirements during the sessions. It appears that adsorption characteristics govern biocompatibility. For clinical practice, a classification of various membranes according to these properties must be taken into account.

The effects of an ACE inhibitor and a calcium antagonist on the progression of renal disease: the Nephros Study.

BACKGROUND: The renoprotective effect of ACE inhibition in chronic renal disease is well established but the studies on effects of calcium antagonists on progression of renal disease and on proteinuria have given varying results. METHODS: We conducted an open long-term randomized prospective multi-centre study comparing the combination of ramipril and felodipine ER (F) with either drug alone in non-diabetic renal disease. Included were patients with uncontrolled hypertension (diastolic blood pressure (DBP)) > or =95 mmHg on treatment with a diuretic and a beta-blocker. Fifty-one patients received the combination of R and F, 54 patients R, and 53 patients F. The treatment goal was a DBP <90 mmHg and a similar BP reduction in the three groups. Mean doses at the last visit were 5+5, 10 and 9 mg, respectively, after a mean treatment time of nearly 2 years. The progression of renal impairment was studied by serial measurements of serum creatinine, iohexol clearance, and albuminuria. RESULTS: The reduction in supine systolic (S) BP and DBP expressed as median values were -19.0/-14.5,-14.3/-15.0 and -13.5/-13.3 mmHg in the R+F, R, and F groups, respectively. There was no significant difference between the groups. When correction for the acute drug effect was performed the R+F group had a slower progression rate of the renal disease (loss of glomerular filtration rate (GFR) ml/min/year) compared with the F group (P<0.05) but not to the R group (P>0.20). There was a rise in albuminuria after 2 years in the F group (P<0.05), but no significant change was found in the other groups. CONCLUSIONS: In patients with non-diabetic renal disease the combination of an ACE inhibitor and a calcium antagonist in reduced doses used in addition to baseline therapy with beta-blockers and diuretics, tended to cause a better BP reduction as each drug per se. The R+F treatment also caused a slower progression of the renal disease compared with F alone. The combination treatment seems to afford better BP control and appears to be a favourable therapeutic option in patients with renal disease and hypertension.

[Chronic renal failure and hypertension in community cardiology practice]. / Insuffisance rénale chronique et hypertension en pratique cardiologique de ville.

OBJECTIVE: A sustained increase in the incidence of vascular nephropa-thies has been recently documented in western countries and correlated with aging. Renal failure is often ignored in patients with hypertension and its diagnosis made too late, at the stage of replacement therapy, with an increased mortality rate and prolonged hospitalization time. In clinical practice, the diagnosis of renal insufficiency is based on the measurement of serum creatinine, which depends on muscular mass, gender and age of the subject and is regulated by glomerular filtration. Therefore, serum creatinine level does not give a correct estimate of renal function. According to Good Clinical Practice recommendations, serum creatinine must be used to calculate creatinine clearance, a surrogate of glomerular filtration. To avoid methodological constraints of clearance measurement with precise urine recollection, the index proposed by Cockcroft and Gault is highly reliable and widely used. PATIENTS AND METHOD: An epidemiological survey has been carried out to measure the prevalence of renal insufficiency in hypertensive patients regularly followed by cardiologists. This open, transverse study compared estimates of renal function based upon serum creatinine level and creatinine clearance using the Cockcroft and Gault's formula. Among 1,000 private cardiologists randomly selected in metropolitan France, 707 entered the study. During the last week of May 2000, they included 2,100 hypertensive patients using a questionnaire describing individual patient's demographic and clinical characteristics. RESULTS: The mean age of hypertensive patients was 65.9 +/- 12.2 years. They used antihypertensive drugs for a mean 10.3 +/- 7.7 years. The prevalence of renal failure, as defined by a creatinine clearance lower than 60 ml/min, was 32%, whereas 61% of the patients had a creatinine clearance below 80 ml/min. In contrast, 71% of the patients were subjectively considered to have a normal renal function. This discrepancy reflects underdiagnosis of mild to moderate renal failure. Hypertensive patients with renal failure did not present with excess cardiovascular risk factors and comorbidities when compared with those having a normal renal function. Prevalence of type 2 diabetes and hypercholesterolemia was similar in both groups. CONCLUSION: The present study outlines the discrepancy between theoretical knowledge and practical assessment of renal insufficiency in handling hypertensive patients, in the particular setting of cardiologist practice. In order to suppress this gap, the Cockcroft and Gault formula must be widely used. It is suggested that body weight, in addition to gender and age, may be printed together with serum creatinine concentration on the biology form given to patient.

Filtration of native and glycated beta2-microglobulin by charged and neutral dialysis membranes.

BACKGROUND: It has been postulated that protein glycation and formation of advanced glycation end products (AGE) are among toxic factors in chronic uremia, whether the renal disease is of diabetic or nondiabetic origin. In this setting, AGE-modified beta2-microglobulin (beta2m) may favor dialysis beta2m-related dialysis amyloidosis. Consequently, efficient removal of modified beta2m by highly permeable dialysis membranes is as important as removal of native beta2m to postpone the development of dialysis amyloidosis. METHODS: To define the role of dialysis membrane surface electronegativity on plasma protein transfer, an in vitro model was used to test the interactions of native and glycated beta2m with various highly permeable dialysis membranes. An experimental circuit with minidialyzers was used. The neutral high-flux polysulfone membrane (PS), the electronegative polymethylmetacrylate membrane (PMMA), the electronegative AN69 membrane and a modified AN69 membrane, the surface of which was neutralized with polyethyleneimine (AN69-PEI), were tested using both native beta2m and the more acidic glycated beta2m. Protein mass transfer and binding to the membrane were measured. RESULTS: Mass transfer of glycated beta2m was significantly decreased through all membranes tested when compared with native beta2m. This result was due to the increased molecular weight of beta2m, which became less permeable to porous membranes, whereas adsorption of both native and glycated beta2m to membranes, due to ionic interactions, decreased similarly with AN69 and AN69-PEI, but remained unchanged with PS and PMMA. Moreover, surface neutralization of AN69 membrane did not alter its core binding capacity, since beta2m absorption accounted for 98 and 97% and glycated beta2m for 83.7 and 81.4% of the protein removed with AN69 and AN69-PEI, respectively. CONCLUSION: Clearance of glycated beta2m through highly permeable neutral and negatively charged membranes was lower than that of native beta2m, reflecting a decreased sieving coefficient for the neoformed higher molecular weight and conformationally altered molecule. The binding capacity of the neutral PS was roughly half that of the charged membranes. Neutralizing surface electronegativity of the AN69 membrane with PEI did not alter its binding capacity. These results suggest that it would be useful for dialysis protocols to include comparative studies of both serum native and modified beta2m in order to prevent beta2m-amyloidosis.

Virological and histological responses to one year alpha-interferon-2a in hemodialyzed patients with chronic hepatitis C.

BACKGROUND: alpha-Interferon-2a (IFNalpha) alone is a therapy of limited proven benefit for non-uremic patients with chronic hepatitis C virus (HCV) infection. In dialyzed patients, such an effect is suggested on small short-term studies without sufficient clinical and virologic follow-up to document any sustained effect. PROTOCOL: Twelve chronically hemodialyzed patients with chronic hepatitis C and waiting for renal transplantation were included in a prospective open study of treatment with IFNalpha. We used, as did others, doses of 3 million units (MU), three times a week, but for a longer period of treatment of 12 months. Follow-up was continued for 6 months after the end of IFNalpha in order to document any sustained biochemical, virological and histological responses. RESULTS: Aminotransferase levels returned to the normal range within 1-2 months of treatment in all patients in whom they had been elevated at baseline. At 1 month of treatment, serum HCV-RNA was not detected in 5 (41%) patients and in 9 (75%) at 12 months. A sustained virological response was documented in 4 (33%) patients 6 months after the end of treatment. Relapse occurred in 5 patients within 2 months after IFNalpha withdrawal. HCV genotype was not predictive of any sustained response. At inclusion, using the histologic Metavir scoring system, half of the patients had low-grade cytolytic activity and none had cirrhosis. After IFNalpha, liver biopsy specimens were available from 9 patients and showed histologic improvement in 3. IFNalpha tolerance was poor, inducing a 5% mean weight loss and the acute rejection of two nonfunctioning kidney grafts. CONCLUSION: This study documents that administration of IFNalpha at 3 MU three times a week, for 12 months, in hemodialysis patients with chronic hepatitis C was efficient for clearing the serum of HCV-RNA in 75% of the patients. A sustained response was maintained in one third of these patients after cessation of IFNalpha, and was predicted by the early serum clearance of the virus within the first 2 months of treatment. We confirm that a 12-month treatment period carries a higher sustained response rate than shorter treatment periods. These encouraging results call for larger studies in uremic patients, using IFNalpha alone or in association with new antiviral drugs.

[How to prevent the complications of chronic renal insufficiency]. / Comment prévenir les complications de l'insuffisance rénale chronique.

The early diagnosis of renal disease and the treatment of its potential complications are mandatory to postpone end-stage renal failure. The serum creatinine level and its derived Cockcroft's index which allows estimate of glomerular filtration rate, is the variable upon which relies the medical strategy. To slow down the progression of renal insufficiency, both the cause of renal disease and its consequences on hemodynamics and metabolic regulations must be treated. The impact of protocols combining appropriate dietetic recommendations and drugs are well documented to treat hypertension and malnutrition. For metabolic disturbances and anemia, at least before end-stage failure, preventive protocols are less well established. Nevertheless, the renal patient must be educated and prepared for dialysis and renal transplantation since the early beginning of renal insufficiency. He must be immunized against HBV and harboring a functional arterio-venous fistula for those allocated to hemodialysis.

Evaluation of the safety and efficacy of telmisartan and enalapril, with the potential addition of frusemide, in moderate-renal failure patients with mild-to-moderate hypertension.

The effect on renal function and efficacy of the angiotensin II AT1-receptor blocker (ARB), telmisartan, were compared with those of the angiotensin-converting enzyme inhibitor, enalapril, for the treatment of mild-to-moderate hypertension (diastolic blood pressure [DBP] 95-114 mmHg) in the presence of moderate renal failure (creatinine clearance [Ccr] 30-80 ml/minute). The study was multicentre, double-blind, double-dummy and active-controlled in design, with patients randomised in a 2:1 ratio to receive telmisartanor enalapril. After a two-week placebo run-in period, the 71 eligible patients received either telmisartan, 40 mg, orenalapril, 10 mg, once-daily for four weeks. Thereafter, doses were titrated to telmisartan 80 mg or enalapril 20 mg once-daily if supine trough DBP was still > or =90 mmHg. After a further four weeks, dose titration was again performed, as required, to telmisartan, 80 mg,or enalapril, 20 mg, or frusemide was given in addition if the double dose was already being administered. Mean Ccr decreases of 4.6% for telmisartan and 2.8% forenalapril were not clinically significant. Adverse events occurred in 12 (26.7%) telmisartan-treated patients and in 12 (46.2%) patients receiving enalapril. The mean reduction in supine trough DBP from baseline to the last available value was 12.5 mmHg for telmisartan,compared with 11.9 mmHg for enalapril. A full (reduction of >or=10 mmHg) or partial (reduction of 7-9 mmHg) response occurred in 78% of telmisartanpatients and 65% of enalapril patients. In the enalapril group, 43% of patients required frusemide, compared with 29% of those in the telmisartan group. In conclusion, telmisartan lacks detrimental effect on renal function, is effective in the treatment of mild-to-moderate hypertension in patients with moderate renal failure,and is comparable to enalapril.

[Severe Schonlein-Henoch nephritis in adults. A report of twenty cases]. / Les néphropathies sévères du purpura rhumatoïde de l'adulte. A propos de vingt observations.

Twenty patients with severe Schönlein-Henoch nephritis were selected on a histologically basis of diffuse proliferative endo- and/or extracapillary glomerulonephritis during a period of 12 years in Champagne-Ardenne. There were 15 men and 5 women, mean age 44.1 years. An infectious history was found in 40%, an urinary tract cancer in 15%. In all cases there was purpura, in 80% joint pain and in 50% digestive symptoms. Clinical presentation at diagnosis included, in all cases, hematuria (gross in 50%) and proteinuria (of nephrotic range in 80%); there was hypertension in 60% and renal failure in 80%. Histology found, in all cases, mesangial IgA and often C3 deposits, with a diffuse endocapillary proliferation in 10%, extra-capillary proliferation in 30% and both endo-extracapillary in 60%; 45% of the patients had crescents in greater than 50% of glomeruli. The outcome, after steroid and immunosuppressive treatment, was end-stage renal failure in 25%, moderate renal failure in 20%, or normal renal function in 55% with a mean follow-up period of 4.6 years. These severe nephritis were associated with repetitive and often necrotic purpura, frequent joint pain and severe digestive symptoms. The analysis of initial renal presentation confirmed the bad prognosis of nephrotic syndrome, renal failure and especially hypertension, which were well correlated with the severity and diffusion of proliferative lesions. Despite a worse known prognosis, these nephritis responded to an aggressive and early treatment.

Detection of subclinical abdominal hernia by peritoneal scintigraphy.

This study investigated the incidence of subclinical abdominal hernia in patients starting peritoneal dialysis (PD). From April 1995 to August 1999, every new patient without clinical evidence of abdominal leakage underwent peritoneal scintigraphy. A total of 59 patients were enrolled in the study. Imaging of the peritoneal cavity was performed by mixing 74 MBq (2 mCi) of 99 m technetium sulfur colloid with 2 L of 1.36% dextrose peritoneal dialysis solution. Sequential gamma camera static images were obtained at 0 minutes, 60 minutes, and after drainage. Ten abdominal hernias (2 diaphragmatic leaks, 8 inguinal hernias) were observed in ten patients (6 males, 4 females; mean age: 65.1 years). One patient with diaphragmatic leak recovered partial renal function and stopped continuous ambulatory peritoneal dialysis (CAPD); the other was switched to automated peritoneal dialysis (APD). Among the eight patients with inguinal hernia, six had no clinical manifestations within eight months of follow-up. Two patients became symptomatic at 15 months and 25 months respectively. They underwent surgical repair. In CAPD patients without obvious abdominal hernias, peritoneal scintigraphy at onset of dialysis discovered 17% positive cases. The technique of scintigraphy is safe, with a low radiation exposure. Surgical repair for maintenance on CAPD is not always necessary, and a change in the PD strategy may be useful.

Influence of in vivo hemoglobin carbamylation on HbA1c measurements by various methods.

Increased carbamylated hemoglobin formed in erythrocytes during uremia may interfere with HbA1c assays, but few studies compared directly both parameters. We measured carbamylated hemoglobin by HPLC in 45 non-diabetic uremic patients (16 with acute and two with chronic renal failure, 27 with transplant recipients) as 57.8 +/- 22.3 microg carbamylvaline/g Hb (mean +/- standard deviation) vs. 31.6 +/- 5.1 in 15 controls (+83%, p < 0.001). In these samples, HbA1c was evaluated by three ion-exchange HPLC methods, 1: Diamat (BioRad), 2: A1c2.2 (Tosoh) and 3: HA8140 (Menarini), and one immunoassay method (Tinaquant II Roche). Whichever the method, mean HbA1c values obtained increased in patients with high (> 60 microg carbamylvaline/g Hb) vs. low (< 45) carbamylated hemoglobin values (+0.08 to 0.25% of total Hb), but differences were not significant. Minor peaks on the chromatograms were however increased in parallel to carbamylated hemoglobin. HbA1c values over 6% were found in 4, 1, 2 and 0 samples, with HPLC 1, 2, 3 and immunoassay, respectively. Fructosamine values were not significantly altered. Our results show that Hb adducts, whether due to carbamylation or to other chemical reactions, interfere to a variable extent with different HbA1c assay methods, and confirm that HbA1c values should be interpreted with caution in uremic patients.

Kinetics of carbamylated haemoglobin in acute renal failure.

BACKGROUND: Carbamylation of proteins by isocyanic acid, the reactive form of cyanate derived from urea, is increased in uraemia and may contribute to uraemic toxicity. Kinetics of carbamylation that may reflect uraemic toxicity is not clearly defined in acute renal failure (ARF). METHODS: Twenty-eight patients with ARF and 13 with chronic renal failure (CRF) were included in the study in order to determine changes in carbamylated haemoglobin concentration (CarHb) in ARF. The usefulness of this parameter for differentiating ARF from CRF was also investigated. CarHb was measured by high-performance liquid chromatography after acid hydrolysis. RESULTS: Mean CarHb level (expressed as microg carbamyl valine per gram (CV/g) Hb) was significantly higher in ARF (54.3+/-5.2) than in normal subjects (31.6+/-1.3). On admission, CarHb level was correlated with duration of ARF prior to hospitalization in the intensive care unit (r(2)=0.723, P<0.001). CarHb was significantly higher at recovery in the subgroup of patients requiring haemodialysis than in the subgroup not requiring haemodialysis (82. 4+/-11.3 vs 46.7+/-5.2, P<0.01). Similarly dialysis patients lost more weight (8.6+/-1.4 vs 2.7+/-0.5 kg, P<0.005) and had higher averaged blood urea levels in the 20 days prior to recovery (17. 6+/-1.9 vs 11.3+/-1.8 mol/l, P<0.05). After recovery, CarHb level decreased at a rate of 0.219 microg CV/g Hb per day in patients with reversible renal insufficiency. CarHb concentration was higher in patients with CRF. A cut-off CarHb value of 100 microg CV/g Hb had a sensitivity of 94% and a positive predictive value of 94% for differentiating ARF from CRF. CONCLUSIONS: Kinetics of CarHb showed a near normal red blood cell life span in ARF. Changes in CarHb enabled, with a good sensitivity, the distinction to be made between patients who recovered from ARF and those with sustained renal impairment, whether due to prior CRF or resulting from parenchymal sequelae. Measurement of CarHb is valuable at clinical presentation of ARF in patients with an unknown medical history of renal disease.

Cytomegalovirus-related disease and risk of acute rejection in renal transplant recipients: a cohort study with case-control analyses.

The relationship between a cytomegalovirus (CMV) infection and the acute rejection of a renal transplant is not well established. The aim of the study was to document whether the clinical presentation of a CMV infection as a diffuse inflammatory disease or as a clinically asymptomatic illness is a risk factor of acute renal transplant rejection. One hundred and ninety-two consecutive renal transplant recipients were included in a historical cohort study for exposed-non exposed analyses. CMV infection after transplantation was the exposure factor. Before transplantation, 113 patients had antibodies against CMV and 79 were seronegative. The patients were divided into three groups: Group 1 consisted of 64 patients who had neither clinical signs of CMV disease nor CMV serological changes after transplantation, Group 2 consisted of 77 seropositive patients with asymptomatic viremia, and Group 3 consisted of 51 seropositive patients with clinical signs of diffuse inflammation that included fever, neutropenia, and various visceral involvements (CMV disease). Groups 2 and 3, the seropositive patients, were paired with Group 1 patients. Acute rejection was considered as CMV-induced when it occurred within one month following viremia, during the first year after transplantation. Transplant patients with CMV disease, had a significant likelihood of developing acute rejection after CMV infection or reactivation (P < 0.01). The odds ratio for developing rejection was 5.98, 95% confidence interval: 1.21-29.40. Such a link was not documented for recipients with asymptomatic CMV infection. In conclusion, CMV disease, but not asymptomatic viremia, is a risk factor of acute renal transplant rejection. On epidemiological grounds, these results support the hypothesis that factors controlling both the viral replication and the diffuse inflammatory process are implicated in acute graft rejection.

[Cytomegalovirus infection, a risk factor for acute graft rejection in renal transplant recipients. A case-controlled study]. / La maladie à cytomégalovirus, facteur de risque de rejet aigu d'allogreffe rénale. Etude exposés/non exposés.

OBJECTIVES: We studied the relationship between cytomegalovirus infection and episodes of acute rejection after infection in renal graft recipients at the Reims University Hospital from 1989 to 1995. PATIENTS AND METHODS: Two exposed versus nonexposed analyses were conducted, one (series 1) for CMV infection and the other (series 2) for CMV disease. For each analysis, exposed recipients were matched with nonexposed recipients for date of graft (+/- 6 months). Risk of acute rejection was assessed with univariate analysis then with multivariate analysis using logistic regression. RESULTS: Among the 192 graft recipients included, 64 developed CMV infection, 77 had an infection (series 1) and 51 had CMV disease (series 2). In series 1, only failure of renal graft was a significant risk factor of acute rejection (OR = 10.4; 95% Cl 1.9-56.3). CMV infection was not a significant risk factor (OR = 1.06; 95% Cl 0.2-5.6). Conversely, in series 2, there was a 6-fold increase in the risk of acute rejection in recipients who developed CMV disease (OR = 5.98; 95% Cl 1.21-29.4). CONCLUSION: The fact that CMV disease and not CMV infection is a risk factor of acute rejection in renal transplant recipients is an argument for implicating a general inflammatory reaction characteristic of CMV disease in the pathogenesis of acute rejection. This finding favors preventive treatment of CMV infection.

Assessment of acetate free continuous veno-venous hemofiltration in acute renal failure.

Among the limitations of continuous renal replacement therapy (CRRT) in patients with severe acute renal failure (ARF) and cardiovascular instability is the use of acetate in the substitution fluid. Acetate is required to maintain acidity of the polyelectrolytic solution to avoid calcium carbonate precipitation in the presence of bicarbonate. In addition, in patients with cardiovascular instability, acetate metabolism is impaired and further compromises hemodynamics. A new CRRT technique is proposed in which bicarbonate is used as a buffer, but the acetate requirements are cancelled: acetate free veno-venous hemofiltration (AF-CVVH). This technique allows control of acid-base disturbances independent of urea removal. This preliminary report describes the feasibility of the technique based on separate infusion of water and electrolytes administered prefiltration, and isotonic sodium bicarbonate administered post filtration. The setting of the technique, adapted to the PRISMA device (Hospal, Lyon, France), was based on a model predicting the bicarbonate infusion rate for a target plasma bicarbonate level. The AF-CVVH was compared with conventional, continuous veno-venous hemofiltration (CVVH) in a crossover study that showed AF-CVVH allowed fastest control of acidosis, avoiding 70 to 80 mmol/d of acetate transfer to the patient. Urea removal was similar with both techniques. It was concluded that AF-CVVH, when compared with CVVH, has the main advantage of separately controlling urea retention and metabolic acidosis in patients with severe ARF and cardiovascular instability.

Long-term follow-up of acute renal failure caused by angiotensin converting enzyme inhibitors.

Angiotensin converting enzyme (ACE) inhibitors are useful in the treatment of hypertension and heart failure. However, acute renal failure (ARF) may occur in patients who are taking these drugs in situations associated with decreased glomerular filtration pressure, such as dehydration caused by acute diarrhea or diuretic therapy. Sixty-four patients who were admitted to the intensive care unit for ARF associated with ACE inhibitor therapy were followed for more than 5 years. In this historical retrospective study, we documented that 45 patients were treated for hypertension (group I) and 19 were treated for heart failure (group II). Their mean age was 71.2+/-11.6 years. Patients with ARF presented with overt dehydration in 91% and 84% of the cases in groups I and II, respectively. Hypovolemia was caused by diuretics or gastrointestinal fluid loss. Bilateral artery-renal stenosis or stenosis in a solitary kidney was documented in 22% and 10% of patients in groups I and II, respectively. The probability of survival was 91% and 49% at 1 year and 64% and 18% at 5 years, for groups I and II, respectively. Acute renal failure required hemodialysis in seven patients, but none of them became dialysis dependent. In the subgroup of patients with preexisting chronic renal failure, all the patients except for one who belonged to group II died within 2 years. In both groups, after resolution of ARF, plasma creatinine concentration returned to baseline level and the course of renal function was not significantly worsened. In conclusion, ARF associated with ACE inhibitors is likely to occur in many patients without renal artery stenosis after unexpected dehydration, especially in older patients with congestive heart failure. In both groups of patients, in the absence of preexisting chronic uremia, recovery of renal function occurred without sequelae, even after an episode of acute tubular necrosis requiring dialysis.