Medication misuse in hospitalized patients with renal impairment.

OBJECTIVES: The potential consequences of medication misuse in renal impairment have not been assessed in a population of in-patients. The purpose of this study was to determine the frequency and potential consequences of a lack of dosage adjustment in hospitalized patients with renal impairment. DESIGN: Order sheets for in-patients having a creatinine above 0.7 mg/dl were analysed. We considered the appropriateness of prescriptions for medications having potential nephrotoxicity and/or eliminated through renal excretion or metabolism (TEM medications) and having manufacturer's guidelines for dosage adjustment in renal impairment. MAIN MEASURES: On the basis of these guidelines, each line of prescription was rated as 'appropriate order', 'inappropriate dosage', or 'contra-indicated order'. Experts also rated prescriptions as potentially fatal or severe, serious, significant, or without potential for increased adverse effects. RESULTS: Two hundred and two order sheets were completed for 164 patients. They totalled 1469 lines of prescription, 85% of which were TEM medications, with guidelines for dosage adjustment for 71% of them (n = 886). Of these 886 prescriptions, 34% were inappropriate, 14% being contra-indicated and 20% with inappropriate dosage given the patient's renal function. Among the 202 order sheets, 75% included at least one inappropriate prescription. Sixty-three per cent included at least one prescription with potentially adverse consequences, 3% of these having potentially fatal or severe consequences. CONCLUSION: This study confirms that physicians do not take into account sufficiently patient renal function when prescribing. In light of these results, improving the quality of drug prescription in patients with renal impairment could be of importance for improving the quality of care.

Erythropoietin enhances recovery after cisplatin-induced acute renal failure in the rat.

BACKGROUND: Erythropoietin (Epo) is a growth factor whose synthesis mainly takes place in the kidney. Epo has been shown to support the growth not only of erythroid progenitor cells but also of certain other cell types. We attempted to establish whether Epo enhances the recovery from acute renal failure induced by cisplatin. METHODS: Sprague-Dawley rats were randomized into three groups. In the cisplatin group, animals received one intraperitoneal injection of cisplatin (6 mg/kg) and a daily injection of placebo for 9 days. In the cisplatin+Epo group, animals received intrapertoneal cisplatin and a daily injection of Epo (100 IU/kg) for 9 days. In the control group, animals received both placebo preparations alone. Para-aminohippuric acid and inulin clearances were determined after 4 and 9 days to evaluate renal blood flow and glomerular filtration rate. In addition, light microscopy and immunohistochemistry examinations were performed, and in situ proliferating cell nuclear antigen (PCNA) staining was done to estimate the degree of renal tubular cell regenerative activity. The potential role of epithelial growth factor (EGF) was evaluated by semi-quantitative assessment of EGF immunostaining. RESULTS: Renal blood flow and glomerular filtration rate decreased significantly in cisplatin and cisplatin+Epo groups versus control group at day 4. However, at day 9, they both were significantly greater in cisplatin+Epo-treated animals than in rats that had received cisplatin alone. Tubular cell regeneration was significantly enhanced at day 4 in cisplatin+Epo group, compared with cisplatin and control groups respectively. EGF immunostaining was not significantly different between the three groups. CONCLUSION: Epo significantly enhanced the rate of recovery from acute renal failure induced by cisplatin. PCNA staining indicated that Epo might act directly via stimulation of tubular cell regeneration.

Blood oxidative stress and lipoprotein oxidizability in haemodialysis patients: effect of the use of a vitamin E-coated dialysis membrane.

BACKGROUND: Oxidative stress has been shown in haemodialysis patients in relation with an increased production of free radicals due to membrane-induced complement and leukocyte activation. In order to minimize membrane bioincompatibility and thereby oxidative stress, more compatible filters have been perfected. Among them, a high-flux vitamin E-coated membrane (CL-EE) has been proposed recently. In vivo, little data is available on the consequences of the use of vitamin E-coated membranes. In the present study, the effects of a 3-month use of CL-EE dialysis membranes compared to conventional membranes have been evaluated in 12 haemodialysis patients on the blood oxidative stress status before and after the dialysis session. METHODS: We determined the lipid peroxidation status (plasma thiobarbituric acid-reactive substances) and antioxidant defence (erythrocyte Cu,Zn-superoxide dismutase and plasma and erythrocyte glutathione peroxidase activities, plasma vitamin E, beta-carotene, vitamin A and total antioxidant status). Also, we simultaneously determined the antioxidant content and the copper oxidizability of isolated low density- and high density-lipoproteins (LDLs and HDLs). RESULTS: The main consequence observed under these conditions was a marked enrichment of plasma with vitamin E, which was also significantly and selectively noted in HDLs (no changes in LDL vitamin E content), perhaps related to a specific storage capacity for vitamin E in HDLs of haemodialysis patients. The beta-carotene content of plasma, LDLs and HDLs was also higher after use of vitamin E-coated membranes than after use of high-flux biocompatible membranes. HDL copper oxidizability was reduced (as shown by an increased lag time) before dialysis after use of CL-EE membranes compared to conventional membranes, whereas LDL oxidizability remained unchanged. CONCLUSION: A 3-month use of vitamin E-coated membranes resulted in a significant increase in plasma and HDL vitamin E content, associated with a lower oxidizability of HDLs, which could be beneficial for haemodialysis patients.

Consequences of the diabetic status on the oxidant/antioxidant balance.

It has been shown that elevated extra- and intra-cellular glucose concentrations result in an oxidative stress, which is defined as an imbalance between prooxidants and antioxidants. Several mechanisms seem to be involved in the genesis of this oxidative stress, which has been reported both in experimental diabetes in animals and in type 1 and type 2 diabetic patients: glucose autoxidation, protein glycation and formation of advanced glycation endproducts, and the polyol pathway. Reciprocally, oxidative stress is involved in the origin of type 1 diabetes, especially via the apoptosis of pancreatic beta-cells, as well as insulin resistance in type 2 diabetes. Glucose control plays an important role in the prooxidant/antioxidant balance. Macromolecules such as molecules of extracellular matrix, lipoproteins and deoxyribonucleic acid are also damaged by free radicals in diabetes mellitus. A supplementation with antioxidants has been proposed as a complementary treatment, and some antidiabetic agents may by themselves have antioxidant properties independently of their role on glucose control. The aim of this paper was to review the consequences of the diabetic status on the oxidant/antioxidant balance.

Prognostic relevance of a scoring system based on clinical and biological parameters in early chronic lymphocytic leukemia.

INTRODUCTION: Among patients with indolent form of B-cell chronic lymphocytic leukemia, some of them will progress into more advanced stages. To better define this subpopulation of patients, we attempted to define some parameters capable of predicting a pejorative clinical outcome. MATERIALS AND METHODS: Eighty-eight previously untreated patients with B-cell chronic lymphocytic leukemia in Binet stage A were analysed to study the prognostic value of simple serological variables: soluble CD23 (sCD23), beta2 microglobulin (beta2m), lactate-dehydrogenase activities and albumin level. Results were compared to other conventional clinical and biological parameters by univariate and multivariate statistical analysis. RESULTS: Our data show that: (1) among those studied, sCD23 >50 u/ml was the only serological significant parameter clearly correlated with disease progression and (2) stage A" patients (hemoglobin level between 100 and 120 g/l and/or lymphocytosis >30.10(9)/l), axillary lymph nodes and hypogammaglobulinemia were found to be other variables associated with a pejorative outcome. These four variables enabled the establishment of a scoring system, capable of predicting disease progression since 66% of the patients with a score < or =2 are going to evolve into advanced stages vs 12% with a score <2. Furthermore, the time to progression is shortened when the score is increasing. CONCLUSION: Our findings show the prognostic relevance of a scoring system including sCD23 level. This score could be taken into account in the treatment strategy of B-cell chronic lymphocytic leukemia.

Duocart biofiltration: a new method of hemodialysis.

DuoCart biofiltration (DCB) is a new hemodialysis method using a dialysate with only sodium chloride and bicarbonate obtained from two separate powder cartridges (BiCart and SelectCart, Gambro, Sweden). The ionic complement is directly reinfused in postdilution mode, using one 2 L bag of a specially designed sterile solution. The adaptation of the quantity of these infused substances to their removal through the dialysis membrane is made possible by repeated measurements of ionic dialysance (D), which are automatically performed every 30 min by the Diascan module, systematically available on the Integra dialysis monitor (Hospal, Italy), and by subsequent modification of the infusion rate (Q(R)). An appropriate kinetic model was used to determine the composition of the reinfusion solution (mM: 57 K, 47 Ca, 14.5 Mg, 180 Cl), the conductivity dialysate (set at 14.8 mS/cm) and the ratio Q(R)/D (set at 1/28). This ratio is kept constant by updating Q(R) after each measurement of D. The implementation of this technique requires an Integra dialysis monitor equipped with a two-powder-cartridge dialysate generation system. Fifteen dialysis sessions were performed (duration: 213+/-38 min; blood flow: 238+/-26 ml/min; ultrafiltration rate: 16+/-6 ml/min). The per-dialytic changes of ion plasma concentrations were monitored and found to be within the predicted range. The results substantiate the feasibility of this new hemodialysis method that presents several advantages: dialysate concentrates are in powder form, an alkaline and acetate-free dialysate is used with superior dialysate biocompatibility, no precipitation of Ca and Mg carbonate occurs in the dialysate circuit, the supply of calcium and potassium is easily adapted to individual patients' needs by change in the composition of the reinfusion solution, and a calcium-free dialysate that facilitates citrate anticoagulation is used.

[The plasma antioxidant status and trace elements in patients with familial hypercholesterolemia treated with LDL-apheresis]. / Statut plasmatique en antioxydants et en oligoéléments de patients atteints d'hypercholestérolémie familiale traités par LDL-aphérèse.

Oxidation of low density lipoprotein is involved in the pathogenesis of atherosclerosis. Epidemiological studies suggest a negative correlation between the occurrence of cardiovascular diseases and blood concentrations of lipophilic antioxidants such as vitamin A and E and beta-carotene. Trace elements such as selenium, zinc and copper are involved in the activity of antioxidant enzymes: glutathione peroxidase and superoxide dismutase. The aim of this work was to determine the antioxidant and trace elements status of patients with very severe hypercholesterolemia and who were treated by dextran sulphate low density lipoprotein apheresis, in comparison with two control populations: one constituted by normocholesterolemic subjects and the other by hypercholesterolemic patients before treatment. Our results showed that, as compared with normocholesterolemic subjects, patients treated by LDL-apheresis were not deficient in vitamin E, beta-carotene and copper but had low plasma levels of selenium, zinc and vitamin A. The low selenium and vitamin A levels were due to the treatment by LDL-apheresis by itself, while the hypercholesterolemia of these patients might have provoked the low plasma levels of zinc. This study pointed out the interest of a supplement of selenium, zinc and vitamin A in patients treated by LDL-apheresis.

Is ionic dialysance a valid parameter for quantification of dialysis efficiency?

The on-line measurement during hemodialysis of ionic dialysance provides an estimation of urea clearance with a good and already proven correlation. Some discrepancies remain controversial, and the influence of the dialyzer membrane is still being debated. Eighty-eight measurements of ionic dialysance (ID) were performed with a Diascan module (Hospal R&D, Int., Lyon, France), 51 with cellulosic membranes, and 37 with synthetic membranes, chosen according to their surface charges. The ID was compared to the urea clearance (UK) measured from the blood (n=16) and dialysate (n=88) sides. The ID is closely correlated (r=0.91) but significantly (p < 0.01) lower than the UK by 5% (ID/UK=0.95+/-0.06). The correlation is improved by a semilogarithmic regression analysis (r=0.93). Regarding the influence of the membrane charge, a slight difference is only evidenced for UK < 180 ml/min whereby ID is closer to the urea clearance for the charged membranes (ID/UK=0.98+/-0.05 for charged membranes versus 0.95+/-0.05 for noncharged membranes, p < 0.05). The discrepancy between ID and UK could be related with the difference in the blood distribution volume of urea and that of electrolytes. The good correlation provides the major argument for ID being used as a monitoring parameter of the delivered dialysis dose. Having integrated the discrepancy between ID and UK, prescription can be guided by ID for delivering the adequate normalized dialysis dose as defined by Kt/V.

Antioxidant status of elderly chronic renal patients treated by continuous ambulatory peritoneal dialysis.

BACKGROUND: An oxidative stress has been reported in patients with chronic renal failure (CRF) treated by haemodialysis. To our knowledge, only scant information is available concerning CRF patients treated by continuous ambulatory peritoneal dialysis (CAPD) with regard to their redox and nutritional status. METHODS: The oxidative stress and the biological nutritional status were evaluated in 20 elderly CRF patients treated by CAPD, compared with a control group of 30 elderly non-CRF patients. Plasma peroxidation products were assayed as thiobarbituric acid-reactive substances (TBARS), and two enzymatic antioxidant systems were determined: erythrocyte superoxide dismutase (SOD), glutathione peroxidase activity in plasma (P-GSH-Px) and in erythrocytes (E-GSH-Px). Selenium, vitamin E, beta-carotene and vitamin A were evaluated as plasma non-enzymatic antioxidants. Nutritional status and iron status were assessed by determining serum albumin, prealbumin, iron, ferritin and transferrin concentrations. RESULTS: Plasma TBARS concentration was high in both groups (CAPD: 1.37 +/- 0.06 mumol/l versus non-CRF: 1.41 +/- 0.06 mumol/l; P = NS), compared with usual values (0.60 to 1.20 mumol/l), on account of the patients' ages. SOD and E-GSH-Px activities were normal in both groups. A significant lowering in P-GSH-Px activity was observed only in CAPD patients (211 +/- 14 U/l, usual values: 480 to 650 U/l). Plasma selenium concentration, decreased in both groups, was significantly lower in CAPD than in non-CRF patients (P < 0.01). Plasma vitamin E, beta-carotene and vitamin A concentrations were significantly enhanced only in CAPD patients (P < 0.0001, P < 0.005 and P < 0.0001, respectively. Biological nutritional markers were similar in both groups and within usual values. CONCLUSIONS: This study demonstrated the existence of an oxidative stress in CAPD-treated elderly CRF patients, evidenced by a decrease in plasma selenium levels and in P-GSH-Px activity. However, plasma TBARS were not higher in CAPD patients than in age-matched non-CRF control subjects, probably on account on the patients' ages.

Comparative acute nephrotoxicity of FK-506 and ciclosporin in an isolated in situ autoperfused rat kidney model.

The acute hemodynamic effects of ciclosporin A (Cs-A; 40 and 20 mg/kg), FK506 (1.5 and 0.4 mg/kg), and their vehicles were studied in an in situ autoperfused rat kidney model. Cs-A (60 +/- 7 and 66 +/- 5% of the initial value, respectively; p < 0.05 vs. control group) and FK506 (89 +/- 3 and 77 +/- 3% of the initial value respectively; p < 0.05 vs. control group) induced a significant fall in renal blood flow. Cs-A significantly increased the renal vascular resistance, whereas FK506 had no effect. The glomerular filtration rate (inulin clearance) declined significantly in all groups. Cremophore and FK506 vehicle had no hemodynamic effect on the glomerular filtration rate. In our model, FK506 had less vasoactive effects on the renal hemodynamics than Cs-A.

Antioxidant status of hypercholesterolemic patients treated with LDL apheresis.

Oxidation of low density lipoprotein is involved in the pathogenesis of atherosclerosis. Epidemiological studies suggest a negative correlation between the occurrence of cardiovascular diseases and blood concentrations of lipophilic antioxidants such as vitamins A and E and beta-carotene. Trace elements, such as selenium, zinc, and copper, are involved in the activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. The aim of this study was to determine the antioxidant and trace element status of patients with severe hypercholesterolemia who had been treated with dextran-sulphate low-density lipoprotein apheresis in comparison with two control populations, normocholesterolemic subjects and untreated hypercholesterolemic patients. Our results showed that, patients treated with LDL apheresis, compared with normocholesteromic subjects, were not deficient in vitamin E, beta-carotene, and copper, but had lower plasma levels of selenium, zinc, and vitamin A. The low selenium and vitamin A levels were due to the LDL-apheresis treatment, and the hypercholesterolemia might have provoked the low plasma levels of zinc. The study pointed out the potential benefits of supplemental selenium, zinc, and vitamin A in patients being treated with LDL apheresis.

Pharmacologic profile of iobitridol, a nonionic iodinated contrast medium.

The present article combines and summarizes the preclinic studies carried out in vitro and in vivo to determine the pharmacologic and biochemical profile of iobitridol, a new nonionic iodinated low-osmolality contrast medium (CM). The effects of this product on the main hemodynamic, bronchopulmonary, neurologic, renal, blood chemistry and electrophysiologic parameters and RBC morphology were studied in detail in comparison with CM in the same chemical category or with reference substances of the same osmolality. The in vivo studies were performed under conditions resembling clinical use. Iobitridol showed an excellent pharmacologic and biochemical profile, which was identical or superior to that of other products in its category.

Glutathione antioxidant system as a marker of oxidative stress in chronic renal failure.

A profound imbalance between oxidants and antioxidants has been suggested in uremic patients on maintenance hemodialysis. However, the respective influence of uremia and dialysis procedure has not been evaluated. Circulating levels of copper-zinc superoxide dismutase (CuZn SOD), glutathione peroxidase (GSH-Px), and reductase (GSSG-Rd), total GSH and GSSG were determined in a large cohort of 233 uremic patients including 185 undialyzed patients with mild to severe chronic renal failure, and 48 patients treated by peritoneal dialysis or hemodialysis. Compared to controls, erythrocyte GSH-Px and GSSG-Rd activities were significantly increased at the mild stage of chronic uremia (p < .001), whereas erythrocyte CuZn SOD activity was unchanged, total level of GSH and plasma GSH-Px activity were significantly decreased, and GSSG level and GSSG-Rd activity were unchanged. Positive Spearman rank correlations were observed between creatinine clearance and plasma levels of GSH-Px (r = .65, p < .001), selenium (r = .47, p < .001), and GSH (r = .41, p < .001). Alterations in antioxidant systems gradually increased with the degree of renal failure, further rose in patients on peritoneal dialysis and culminated in hemodialysis patients in whom an almost complete abolishment of GSH-Px activity was observed. In conclusion, such disturbances in antioxidant systems that occur from the early stage of chronic uremia and are exacerbated by dialysis provide additional evidence for a resulting oxidative stress that could contribute to the development of accelerated atherosclerosis and other long-term complications in uremic patients.

Evaluation of renal function in 60 long-term survivors of bone marrow transplantation.

Although the acute nephrotoxicity of bone marrow transplantation is well documented, long-term follow-up studies are scanty. Renal function was evaluated in 60 long-term survivors of allogeneic (24 patients) or autologous (36 patients) bone marrow transplantation (BMT) with a mean follow-up of 2 yr. Renal function tests included serum creatinine, GFR (inulin clearance), effective RPF (p-aminohyppurate clearance), urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase excretion, and renal tomography. The mean serum creatinine level was 83 +/- 3 and 93 +/- 3 mumol/L before and after grafting, respectively (P < 0.05). The mean GFR (93 +/- 3 mL/min) and effective RPF (419 +/- 16 mL/min) were significantly lower than in healthy controls (120 +/- 3 and 500 +/- 1 mL/min; P < 0.05) and than in candidates for BMT matched for age and hematologic diseases (117 +/- 3 and 469 +/- 11 mL/min; P < 0.05). Thirty-four patients had a fall in the GFR of at least 20%. Patients who received total body irradiation had significant lower creatinine clearance (86 +/- 3 mL/min) and GFR (86 +/- 3 mL/min) than the controls and the patients who received high-dose chemotherapy (100 +/- 4 and 104 +/- 5 mL/min; P < 0.05). These results suggest that subclinical renal dysfunction occurs frequently in marrow graft recipients, especially those who undergo total body irradiation.

Non-invasive monitoring of effective dialysis dose delivered to the haemodialysis patient.

Assessment of normalized dialysis dose Kt/V actually delivered to the patient carries the drawback of requiring several blood or dialysate samplings and urea concentration measurements. In order to easily quantify Kt/V, we validate here the routine implementation of an original technique for the non-invasive, on-line, and fully automatic estimation of total mean urea clearance. This estimation is obtained from the measurement by a conductivity method of the effective ionic dialysance DR, which is the dialysance of electrolytes taking into account ultrafiltration and recirculation. The observed increase in DR with ultrafiltration rate and decrease in DR with elevation of access recirculation ratio show that the estimation of DR is affected by ultrafiltration and recirculation in a consistent manner. The mean value Keff of ionic dialysance DR was compared with the value Kdc of effective urea clearance obtained by dialysate collection during 12 haemodialysis sessions. The similarity (magnitude of variation 5%) between the ionic dialysance Keff and the effective urea clearance Kdc supports the validity of the equivalence between the transfer characteristics of electrolytes and urea through the dialyser membrane. Given an estimate of the urea distribution volume V, this estimation of effective urea clearance by ionic dialysance measurement allows an on-line estimation of the normalized dialysis dose Kt/V actually delivered to the patient.

[Intravenous glucose tolerance test in the functional exploration of segmental pancreatic autografts in the dog]. / L'épreuve d'hyperglycémie provoquée par voie intraveineuses dans l'exploration fonctionnelle de l'autogreffe pancréatique segmentaire chez le chien.

The aim of the present study is based on the comparison of intravenous tolerance testing before and after segmental pancreas autotransplantation in the dog. The results show that such testing must take in account the "glucose diffusion space", using the same glucose load in order to avoid the bias related to the post-operative loss of body weight.

Comparative nephrotoxicity of carboplatin and cisplatin in euvolemic and dehydrated rats.

The aim of this study was to compare the renal tolerance of cisplatin and carboplatin in euvolemic and dehydrated rats. A total of 79 euvolemic or dehydrated male rats were randomly assigned to receive cisplatin (5 mg/kg body weight, i.p.), carboplatin (40 mg/kg body weight, i.p.) or vehicle. Body weight, serum creatinine, creatinine clearance, fractional excretion of sodium and urinary NAG excretion were recorded on days 1 and 5. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and renal histology were determined on day 5. In the euvolemic and dehydrated control and carboplatin groups we observed no change in serum electrolytes, serum creatinine, creatinine clearance, GFR and ERPF. In the euvolemic and dehydrated control groups we observed no change in urinary NAG excretion. Carboplatin induced a slight but significant increase in urinary NAG excretion. In dehydrated rats carboplatin induced a significantly higher increase in urinary NAG excretion than in euvolemic rats. Cisplatin induced a marked and significant decrease in GFR and ERPF, and a significant increase in NAG. Dehydration markedly potentiated cisplatin nephrotoxicity. Euvolemic rats treated with cisplatin exhibited slight renal lesions with a mean score which was similar to the control group. The most extensive lesions were observed in euvolemic and dehydrated cisplatin treated rats with tubular necrosis in the outer stripe of the medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of serum copper determination by colorimetric and atomic absorption spectrometric methods in seven different laboratories. The S.F.B.C. (Société Française de Biologie Clinique) Trace Element Group.

An interlaboratory collaborative trial was conducted on the determination of serum copper using two different methods, based on colorimetry (test combination Copper, Boehringer Mannheim, Mannheim, Germany) and flame atomic absorption spectrometry (FAAS). The general performance of the colorimetric method was below that of FAAS, except for sensitivity and linear range, as assessed by detection limit (0.44 versus 1.32 mumol/L) and upper limit of linearity (150 versus 50 mumol/L). The range of the between-run CVs and the recovery of standard additions were, respectively, 2.3-11.9% and 92-127% for the colorimetric method and 1.1-6.0% and 93-101% for the FAAS method. Interferences were minimal with both methods. The two techniques correlated satisfactorily (the correlation coefficients ranged from 0.945-0.970 among laboratories) but the colorimetric assay exhibited slightly higher results than the FAAS method. Each method was transferable among laboratories.