Hemoglobin level variability in hemodialysis patients treated with epoetin-ß during 1 year.

AIM: This analysis was performed to assess the prevalence and the factors associated with hemoglobin (Hb) variability during treatment with erythropoiesis-stimulating agents (ESA) in France. METHODS: Hb variability was evaluated in a subgroup of hemodialysis (HD) patients of the French cohort DiaNE. Eligible patients had received epoetin-ß at least 6 months before entering DiaNE, 12 months during DiaNE and had no missing monthly Hb measurements. Up and down excursions (Hb variations > 1.5 g/dl with duration > 8 weeks) were assessed. RESULTS: Of the 499 patients evaluated in this analysis, 295 (59%) had Hb levels inside the target range of 11 - 13 g/dl at baseline. The number of patients with constantly stable Hb level inside the target range decreased from baseline to 27.5% at 6 months and 10.8% at 12 months. More than 70% of patients experienced Hb variability. The number of excursions was 1.7 ± 0.8 per patient/year. The amplitude of up excursions was 2.8 ± 1.0 g/ dl with a duration of 14.7 ± 4.7 weeks. The amplitude of down excursions was 2.6 ± 0.9 g/dl with a duration of 14.5 ± 4.6 weeks. The main factors associated with Hb variability were number of epoetin-ß dose changes, adverse events and iron therapy changes. CONCLUSION: Hb variability is frequent in French ESA-treated HD patients and closely related to practices. Further efforts are needed to improve anemia management.

[Evaluation of patient compliance among hypertensive patients treated by specialists]. / Evaluation de l'observance par l'interrogatoire au cours du suivi des hypertendus dans des consultations spécialisées.

OBJECTIVES: To evaluate compliance with antihypertensive therapy by a self-report in patients referred to hypertension specialists. METHODS: We studied 484 treated hypertensive subjects referred to several hypertension clinics and who were treated since at least one year. Patients were asked to fill in the Compliance Evaluation Test (CET), a questionnaire with 6 questions previously validated to assess factors that could affect medication compliance. We defined patients as "good compliant" when "No" was answered to the 6 items, as "minor noncompliant" when 1 or 2 "Yes" were answered, and as "noncompliant" when 3 or more "Yes" were answered. A good agreement was demonstrated between CET score and compliance evaluated by the number of pills missed during the previous month according to patient interview. RESULTS: We observed 8% of "noncompliant", 53% of "minor noncompliant" and 39% of "good compliant". [table: see text] Logistic regression analysis including age, sex, education level, blood pressure level and the number of antihypertensive tablets confirm the statistical differences observed. CONCLUSIONS: In clinical practice, a method of assessing medication compliance is to ask the patient for a self-report interview. We demonstrated that the compliance evaluation test is able to detect factors usually associated with poor compliance (young age, elevated blood pressure, number of tablets per day). The use of the compliance evaluation test may help physicians to face the problem of nonadherence among their hypertensive patients.

Pulmonary giant bulla in Wegener's granulomatosis.

The association of lung emphysema with severe systemic antineutrophil cytoplasm antibodies (ANCA)-positive vasculitis, such as Wegener's granulomatosis is unusual since only four cases have been described previously. We report the first case of a 30 year-old smoker man presenting with biopsy-proven Wegener's granulomatosis, who developed a bullous emphysema during severe active lung vasculitis, in association with positive ANCA disclosing an anti-myeloperoxydase pattern. Alpha 1-antitrypsin deficiency, a known risk factor of lung emphysema recently found to be associated with anti-proteinase 3-positive vasculitis, was not present in this patient. Cigarette smoking, in association with severe lung vasculitis, might have contributed to the development of this emphysematous lesion.

Treatment of failed native arteriovenous fistulae for hemodialysis by interventional radiology.

BACKGROUND: We studied the feasibility, technical problems, safety, and effectiveness of percutaneous declotting of thrombosed native arteriovenous fistulae for hemodialysis. METHODS: Between 1992 and 1998, 93 declotting procedures were performed in 73 consecutive upper limb native fistulae (forearm 56 and upper arm 17), and 162 procedures were performed in 78 prosthetic grafts using manual catheter-directed thrombo-aspiration, with or without previous urokinase infusion. Detection of restenosis by clinical surveillance led to redilation or stent placement. Rethrombosis in four forearm and six upper arm fistulae were treated by 20 further declottings by aspiration. RESULTS: The initial success was 93% in the forearm and 76% in the upper arm (99% in grafts). The complications included one pulmonary embolism, one acute pseudoaneurysm, and one blood depletion requiring transfusion. Primary patency rates at one year were 49% in the forearm and 9% in the upper arm (14% in grafts). Secondary patency rates were 81 and 50% at one year, respectively (83% in grafts). Reinterventions were necessary every 19.6 months in the forearm and every 5.7 months in the upper arm (every 6.4 months in grafts, P < 0.05). Stents were placed in 11% of forearm fistulae and in 41% of upper arm fistulae (45% of grafts) for treatment of acute rupture (5 out of 19), stenosis recoil (6 out of 19), and early (< 6 months) recurring stenosis (8 out of 19). CONCLUSIONS: The percutaneous declotting of forearm fistulae by manual catheter-directed thrombo-aspiration was effective in more than 90% of cases and yielded 50% primary and 80% secondary patency rates at one year. The results were poorer in upper arm fistulae. The need for maintenance reinterventions was three times smaller in forearm fistulae than in upper arm fistulae and grafts.

Early glomerular dysfunction in patients with sickle cell anemia.

The purpose of this study was to analyze the determinants of glomerular filtration in nonnephrotic young adult patients with sickle cell anemia (SCA). We prospectively screened 14 patients with homozygous SCA who had normal plasma creatinine concentrations and normal or moderately elevated albuminuria (< 1 g/d). Inulin, paraaminohippuric acid, and dextran clearances were evaluated and compared with values obtained from a control group (age-matched healthy volunteers). SCA patients had a significantly higher glomerular filtration rate and effective renal plasma flow than controls (146 +/- 9 mL/min/1.73 m2 v 120 +/- 3 mL/min/1.73 m2 [P < 0.01] and 1,052 +/- 69 mL/min/1.73 m2 v 709 +/- 38 mL/min/1.73 m2 [P < 0.001], respectively). We found no correlation between glomerular filtration rate or effective renal plasma flow and hematocrit. Fractional clearance of neutral dextran was significantly elevated in SCA patients for all radii between 3.4 and 5.4 nm. Theoretical analysis of dextran transport through a heteroporous membrane model revealed a slight increase in the mean radius (ro) of restrictive pores (5.68 nm v5.50 nm; P < .001) and no significant difference in shunt pathway (omega o) values. Among the other hemodynamic parameters, the most significant change was a dramatic increase in ultrafiltration coefficient (41.3 +/- 3.6 mL/mm Hg/min/1.73 m2 v 25.1 +/- 2.6 mL/mm Hg/min/1.73 m2; P < 0.001). Our results suggest that hyperfiltration in SCA patients is associated not only with enhanced renal perfusion but also with an alteration in glomerular permeability and with an increase in Kf. This change in Kf is fully in agreement with the large increase in glomerular area previously described in SCA patients. Based on our results and those of previous morphologic studies, we propose that enhanced transglomerular trafficking of macromolecules associated with podocyte stretch lesions (defects) induced by glomerular hypertrophy may play a role in the genesis of this particular form of focal segmental glomerulosclerosis, which is associated with SCA.

Acute renal effects of AT1-receptor blockade after exogenous angiotensin II infusion in healthy subjects.

In 10 healthy normotensive volunteers on a normal sodium diet, we evaluated the renal effects of a single oral dose of 50 mg of irbesartan (SR 47436, BMS 186295), an angiotensin II AT1-receptor antagonist, in baseline conditions and during an exogenous angiotensin II infusion (2.5 ng/kg/min). We used a double-blind, placebo-controlled, crossover design. Hormones, blood pressure, renal hemodynamics, and urinary electrolytes were measured during each phase. To examine further the determinants of glomerular filtration at the microcirculation level, fractional clearance of neutral dextran was performed, and sieving curves were applied on a hydrodynamic model of ultrafiltration. Irbesartan administration was followed by an increase in active renin and plasma angiotensin II concentrations and renal plasma flow without change of systemic blood pressure, glomerular filtration rate, or plasma aldosterone concentration. Irbesartan did not affect either sieving curves or glomerular ultrafiltration determinants. Angiotensin II infusion at 2.5 ng/kg/min elicited a slight pressor response accompanied by a decrease in glomerular filtration rate and renal plasma flow and an enhancement of fractional dextran clearance over the radius range explored (3.4-5.4 nm). The transcapillary glomerular pressure gradient deltaP and the ultrafiltration coefficient kf were computed to increase by 9% and to decrease by 23%, respectively, without change in intrinsic membrane properties. Pretreatment with irbesartan prevented all these effects of angiotensin II.

Renal tolerance of gadolinium-DOTA and gadolinium-DTPA in rats.

RATIONALE AND OBJECTIVES: Although gadolinium chelates are mainly eliminated by the kidney, there is limited information about their effects. The renal tolerance of these compounds on renal function in an in vivo rat model are evaluated. METHODS: A combination of renal ischemia and intrarenal iodinated contrast agent infusion (diatrizoate) led to a reproducible and reversible model of acute renal failure (n = 5). Using this model, the renal tolerance of gadolinium DOTA (Gd-DOTA) (n = 10) and gadolinium DTPA (Gd-DTPA) (n = 10) were evaluated. The effects of the association of Gd-DOTA with diatrizoate (n = 5) on renal function also were assessed. RESULTS: Gadolinium DOTA induced no change in serum creatinine and creatinine clearance. Gadolinium DTPA induced a significant increase in serum creatinine (50 to 83 +/- 5 and 70 +/- 6 mumol/L) before and at 24 and 48 hours, respectively (P < .05), and a decrease in creatinine clearance from 1.6 +/- 0.1 to 0.8 +/- 0.1; 1.2 +/- 0.1 mL/mL before and at 24 and 48 hours, respectively (P < .05). In this model, Gd-DOTA did not modify the renal tolerance of diatrizoate as assessed with serum creatinine and creatinine clearance. CONCLUSIONS: Gadolinium DOTA is not nephrotoxic and can be infused in association with iodinated contrast media. In this model, Gd-DTPA induced reversible renal failure.

Long-term renal effect of cisplatin in man.

Although the acute nephrotoxicity of cisplatin has been well documented, long-term follow-up studies are scanty. We have evaluated the renal function in 35 patients who have had completed therapy with cisplatin at least 3 months before the study. All patients had normal serum creatinine levels before chemotherapy. Evaluation of renal function included: serum creatinine, glomerular filtration rate (inulin clearance), effective renal plasma flow (p-aminohippurate clearance), urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase excretion, and renal tomography. The median cumulated dose of cisplatin was 603 +/- 37 mg/m2. The mean serum creatinine level was 78 +/- 21 and 88 +/- 3 mumol/l before and after chemotherapy, respectively (p < 0.05). Mean glomerular filtration rate (92 +/- 4 ml/min) and effective renal plasma flow (362 +/- 21 ml/min) were significantly lower than in controls (110 +/- 3 and 436 +/- 24 ml/min). The mean enzymuria and the renal size remained within the normal range. In 12 patients who were reevaluated 12 and 24 months later, glomerular filtration rate and effective renal plasma flow remained stable. These results suggest that at usual dosages cisplatin is associated with a nonprogressive loss of renal function which is of a moderate degree.

Functional evaluation of normal and ischemic kidney by means of gadolinium-DOTA enhanced TurboFLASH MR imaging: a preliminary comparison with 99Tc-MAG3 dynamic scintigraphy.

The functional value of TurboFLASH MR imaging in the assessment of dynamic contrast enhancement and renal perfusion anomalies was evaluated in seven patients, who also underwent renal scintigraphy in baseline conditions. The basal renograms obtained from MAG-3 scintigraphy (mercapto acetyl triglycine, MAG3-S) and from Gd-DOTA-enhanced turboFLASH MRI were compared. After hydration, the protocol used consisted in breath-hold coronal turboFLASH acquisitions after IV bolus of Gd-DOTA (4 s every 20 s during 10 min) for MRI, and IV bolus of 370 MBq of 99mTc-MAG3 followed by 60 frames of 1 s and then 120 frames of 10 s for MAG3-S. Relative renal functions were computed for both methods by calculation of the integral of the uptake phase between the first and the second minute. Renograms exhibited 10 normal and 4 ischemic kidneys. There was a close correlation between the contrast enhancement of MRI and isotopic uptake in normal and ischemic kidneys. Global renograms of MRI correlated with MAG3-S (r = .82, p < .001) with similar curve shape and time to peak. Relative renal function of the right and left kidney were closely correlated in all patients (r = .98, p < .001), although there was a tendency for MR to overestimate MAG3-S evaluation in kidneys with severe basal dysfunction. Enhanced turboFLASH provides noninvasive assessment of renal perfusion in patients with renovascular disease. Accurate renograms are obtained with dynamic-enhanced MRI, but the relative renal function seems to be overestimated in low values of ischemic kidneys, and needs further comparative evaluation.

[Definitive end-stage chronic kidney failure after cisplatin treatment]. / Insuffisance rénale chronique terminale définitive après traitement par le cisplatine.

Renal failure secondary to CDDP is due to acute tubular necrosis and is usually reversible. We report 4 cases of definitive renal failure secondary to administration of cisplatin (CDDP). Three women and one man, mean age 40 +/- 8 years (24 to 64 years), at onset of dialysis are reported. They had received 1 to 4 courses of CDDP for an endometrial carcinoma (n = 2), a breast carcinoma or a thymoma. The mean total dose of CDDP was 447 +/- 169 mg (160 to 900 mg). There was no additional nephrotoxic drug. Before treatment serum creatinine concentration was normal (77 +/- 7 mumol per liter) in all patients. In 2 cases dehydration (due to vomiting and use of mannitol) occurred during CDDP treatment. One patient was treated 30 days after a nephrectomy. At the onset of dialysis, renal ultrasound was normal. In 3 cases dialysis was necessary within 15 days following chemotherapy. In one case renal function deteriorated progressively to end stage renal failure 12 months after CDDP treatment. Dialysis was performed in 3 cases by hemodialysis and in one patient by peritoneal dialysis. All patients remained more than 6 months on dialysis. Three patients died from their cancer. One patient, being considered cured from his thymoma, is currently being evaluated for a kidney transplantation. Our observations outline the potential severity of CDDP nephrotoxicity. Systemic hydration with serial serum creatinine measurements are mandatory during and after CDDP administration these patients.

[Renal effects of endothelins]. / Effets rénaux des endothélines.

Since the discovery of endothelin in 1988, numerous studies have been undertaken to evaluate their physiopathologic role. There is three types of endothelin ET-1, ET-2 and ET-3, which probably play an essential role in renal and cardiovascular homeostasis. Their principal actions consist in an increase of the arterial pressure, a negative inotrope and chronotrope effect, a coronary vasoconstriction, a decrease in cardiac output and a fall in the renal blood flow and glomerular filtration rate. An elevation of endothelin level has been reported in numerous clinical conditions. However the interest of these descriptions remains unclear. Indeed the absence of pharmacological inhibitors of the synthesis or effect of endothelin prevent the understanding of the interest of these abnormalities. Furthermore the endothelins should not be considered as a hormone but as a paracrine substance.

[Extracapillary and necrotizing glomerulonephritis without immunoglobulin deposits: clinical presentation, prognostic factors and response to treatment. Apropos of 42 cases]. / Glomérulonéphrite extracapillaire et nécrosante sans dépôt d'immunoglobulines: présentations cliniques, facteurs pronostiques et réponse au traitement. A propos de 42 cas.

Forty-two cases of pauci-immune necrotizing glomerulonephritis were reviewed on a 10 years period. Selection was exclusively based on histological criteria, i.e. at least one elementary lesion of extracapillary proliferation and/or glomerular necrosis, without immunoglobulin deposits. Mean age was 56. Thirty per cent of patients presented with normal or non-worsening renal function. At least one extra-renal sign was present in 66% of patients. ANCA were found in 9/20 cases. Death occurred in 12 patients. Age over 60 and oligo anuria were the most predictive factors for the fatal outcome. Half of the patients were on dialysis at the end of their follow-up. The renal function at presentation was the main predictive variable for renal outcome. Severe tubular necrosis was associated with a poorer renal evolution whereas treatment with cyclophosphamide led to frequent improvement in this retrospective study.

Chronic cisplatin nephropathy in rats.

The long-term renal effects of cisplatin have been very poorly studied. Therefore we investigated the chronic renal effects of various doses of cisplatin in three groups of male Sprague-Dawley rats. Group I received two injections of 5 mg/kg body weight (bw) at 4-week intervals, group II four injections of 2.5 mg/kg bw at 4-weeks intervals, and group III one injection of 5 mg/kg bw and four injections of 2.5 mg/kg bw at 4-weeks intervals. Controls received an equivalent amount of isotonic saline. Each group was evaluated 1, 3, or 6 months after the last injection of cisplatin. One, 3 and 6 months after the last injection, cisplatin induced a marked decrease in glomerular filtration rate (GFR) evaluated as clearance of [99mTc]DTPA and creatinine clearance in all treated rats. Urinary NAG excretion remained unaltered. At 3 months post-cisplatin treatment GFR was significantly less (P < 0.05) in group III (0.18 +/- 0.02 ml/min/100 g bw) when compared with group I (0.23 +/- 0.02 ml/min/100 g bw) or II (0.23 +/- 0.04 ml/min/100 g bw). In group I GFR was similar 1 month (0.24 +/- 0.02), 3 months (0.23 +/- 0.02) and 6 months (0.23 +/- 0.03 ml/min/100 g bw) after cisplatin treatment. Cisplatin induced atrophy and dilatation of tubules with mononuclear cell infiltration associated with cyst formation. The glomerular and tubulointerstitial lesions were significantly enhanced in group III when compared with groups I and II. This study indicates that repeated administration of cisplatin may induce a chronic tubulointerstitial nephropathy associated with a marked decrease in GFR, which is stable over time. The incidence and severity of chronic cisplatin toxicity is dose-related and is not modified by dividing the dose.

Renal tolerance of AMI 25.

The objective of this study was to evaluate the renal tolerance of a new magnetic resonance contrast agent, AMI 25. This agent has an affinity for the reticuloendothelial system and is used for the detection of focal liver lesions. A combination of renal ischemia and intra-arterial iodinated contrast agent infusion (diatrizoate) leads to a reproducible and reversible model of acute renal failure in the rat. Using this model, AMI 25 was perfused directly into the aorta at the dose of 1 ml/kg--ten times the dose used in humans. AMI 25 induced no change in serum creatinine (45 +/- 7, 40 +/- 6, 40 +/- 9 mumol/L before infusion and at 24 and 48 hours, respectively), in creatinine clearance (2.1 +/- 0.6, 2.1 +/- 0.6, 2.1 +/- 0.6 mL/mn), or in urinary N-acetyl glucosaminidase (NAG) excretion (72 +/- 16, 98 +/- 12, 58 +/- 9.8 mumol hour-1/mmol creatinine). Blinded histologic analysis of 11 kidneys perfused with AMI 25 revealed no abnormalities, whereas diatrizoate induced acute tubular necrosis in four of the seven kidneys examined. In our animal model, AMI 25 has no nephrotoxicity, even at ten times the expected clinical dose for humans.

Renal vasoconstriction after low and high osmolar contrast agents in ischemic and non ischemic canine kidney.

We have assessed the effect of contrast media on renal blood flow before and after inducing renal ischemia. Diatrizoate, iopamidol and ioxaglate were injected within 15 seconds at 20 min intervals, at the dose of 1 ml/kg during a control period and 15 min after applying an aortic clamp to reduce the renal perfusion pressure to 70 mmHg. During the control period iopamidol, ioxaglate (17 +/- 13%) and diatrizoate (16 +/- 2%) induced a comparable decrease in renal blood flow (RBF). During the ischemic period the effects of diatrizoate on renal hemodynamic were dramatically enhanced. Ioxaglate andiopamidol induced a 20 +/- 12 and a 32 +/- 9% decrease in RBF at 1 minute, respectively. Iopamidol induced an increase in renal vascular resistance (RVR) from 0.8 +/- 0.08 to 1.46 +/- 0.26 mmHg min/ml (p less than 0.05). Ioxaglate induced an increase in RVR from 0.8 +/- 0.09 to 1.36 +/- 0.38 (p less than 0.05). Diatrizoate induced a 77 +/- 10% decrease in RBF and a maximum increase in RVR at 1 minute from 0.9 +/- 0.09 to 26 +/- 12 mmHg min/ml. There was still a 36 +/- 14% and a 23 +/- 13% decrease in RBF 10 and 20 min after diatrizoate administration. These changes were significantly higher than those observed with all contrast media during the control period and low osmolar contrast media during the ischemic period. We have thus shown that ischemia potentiates the renal vascular effect of contrast media.(ABSTRACT TRUNCATED AT 250 WORDS)