Difference in the homocysteine-lowering effect of folic acid in haemodialysis patients with and without occlusive vascular disease.

BACKGROUND: Hyperhomocysteinaemia has been identified as an independent cardiovascular risk factor and is found in more than 85% of patients on maintenance haemodialysis. Previous studies have shown that folic acid can lower circulating homocysteine in dialysis patients. We evaluated prospectively the effect of increasing the folic acid dosage from 1 to 6 mg per dialysis on plasma total homocysteine levels of haemodialysis patients with and without a history of occlusive vascular artery disease (OVD). METHODS: Thirty-nine stable patients on high-flux dialysis were studied. Their mean age was 63 +/-11 years and 17 (43%) had a history of OVD, either coronary and/or cerebral and/or peripheral occlusive disease. For several years prior to the study, the patients had received an oral post-dialysis multivitamin supplement including 1 mg of folic acid per dialysis. After baseline determinations, the folic acid dose was increased from 1 to 6 mg/dialysis for 3 months. RESULTS: After 3 months, plasma homocysteine had decreased significantly by approximately 23% from 31.1 +/- 12.7 to 24.5 +/- 9 micromol/l (P = 0.0005), while folic acid concentrations had increased from 6.5 +/- 2.5 to 14.4+/-2.5 microg/l (P < 0.0001). However, the decrease of homocysteine was quite different in patients with and in those without OVD. In patients with OVD, homocysteine decreased only marginally by approximately 2.5% (from 29.0 +/- 10.3 to 28.3 +/- 8.4 micromol/l, P = 0.74), whereas in patients without OVD there was a significant reduction of approximately 34% (from 32.7+/-14.4 to 21.6+/-8.6 micromol/l, P = 0.0008). Plasma homocysteine levels were reduced by > 15% in three patients (18%) in the group with OVD compared with 19 (86%) in the group without OVD (P = 0.001), and by > 30% in none of the patients (0%) in the former group compared with 13 (59%) in the latter (P = 0.001). CONCLUSIONS: These results indicate that the homocysteine-lowering effect of folic acid administration appears to be less effective in haemodialysis patients having occlusive vascular disease than in those without evidence of such disease.

Repeated transient anuria following losartan administration in a patient with a solitary kidney.

We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.

[Kinetics of potassium transfer during hemodialysis]. / Cinétique des transferts de potassium en cours d'hémodialyse.

INTRODUCTION: In order to study whether the removal of potassium in haemodialysis patients could be increased, we analyzed the kinetics of potassium transfer in the dialyzer. METHOD: 40 patients were included in the study. We studied: a) in vitro potassium exchanges between erythrocytes and plasma; b) plasma and erythrocyte potassium concentrations at dialyzer input and output; c) potassium transfers into the dialysate, using plasma clearance and direct measurement in the collected dialysate and d) erythrocyte potassium concentrations at the beginning and the end of dialysis. RESULTS: In vitro, there is virtually no potassium transfer between erythrocytes and plasma. In vivo, erythrocyte potassium concentration is not affected by the dialyzer (98.7 +/- 6.4 mmol/l to 97.7 +/- 7.5 mmol/l, p = NS). Potassium transfer levels determined by calculated plasma clearance were similar to values obtained by measuring potassium in dialysate (0.71 +/- 0.10 mmol/min vs 0.68 +/- 0.10 mmol/min, p = NS). These results suggest that erythrocytes do not participate in potassium exchange in the dialyzer. This was confirmed by measured erythrocyte potassium concentrations, which were the same at the beginning and the end of dialysis (104.0 +/- 5.6 mmol/l vs 104.2 +/- 5.0 mmol/l, p = NS).

Diffusion kinetics in blood during haemodialysis and in vivo clearance of inorganic phosphate.

Contradictory data are reported in the literature concerning the diffusion kinetics of inorganic phosphates (iPh) between red blood cells and plasma during haemodialysis. Accordingly, we performed mass balance and equilibration studies to analyze the diffusion kinetics of iPh in vivo and in vitro. Mass balance analysis shows that iPh is only cleared from the plasma volume and thus that it practically does not diffuse from red blood cells to plasma during the short time lapse of blood transit through the haemodialyzer. In vitro equilibration studies of blood drawn at the filter outlet show that at room temperature there is a slow, limited, and almost linear net efflux of iPh during the 4 h that follow blood drawing. Our results point out: (1) that the in vivo clearance of iPh should be exclusively determined as plasma clearance, and (2) that for accurate clearance determinations the iPh concentrations should be measured in blood samples centrifuged within at most 1 h after blood drawing. Whole-blood clearance determinations--as well as the in vitro dialyzer data--largely overestimate (>30%) the real in vivo dialyzer performance.

End-stage renal failure after irbesartan prescription in a diabetic patient with previously stable chronic renal insufficiency.

We report the case of a 78-year-old hypertensive diabetic patient without evidence of renal artery stenosis who had moderate chronic renal insufficiency, which had been stable for several years under low-dose captopril therapy, and who rapidly developed acute renal failure when irbesartan was prescribed. Unfortunately the medication was not stopped promptly and the patient never recovered his basal renal function and had to undergo chronic hemodialysis. This observation emphasizes the importance of a careful monitoring of renal function in patients receiving angiotensin II receptor antagonists.

Water-soluble vitamin levels in patients undergoing high-flux hemodialysis and receiving long-term oral postdialysis vitamin supplementation.

The prescription of multivitamin supplements for dialysis patients is routine practice, but the doses prescribed differ greatly from one dialysis center to another. Few data are available concerning long-term vitamin supplementation and its effects on patients either on high-flux hemodialysis or receiving postdialysis supplementation. For several years, we have systematically prescribed to our patients an oral postdialysis multivitamin supplement containing thiamine hydrochloride 100 mg, riboflavin 20 mg, pyridoxine hydrochloride 50 mg, folic acid 6 mg, and ascorbic acid 500 mg. The aim of this study was to perform a cross-sectional long-term evaluation of the vitamin levels in patients who received this vitamin supplement for at least 12 months. We also were interested in investigating the plasma oxalic acid and total homocysteine levels associated with the long-term prescription of these vitamin supplements. Thirty-three patients on high-flux dialysis were studied. Vitamin levels and/or vitamin-dependent enzymatic activities were within the normal range (N) in all patients. The mean results (+/-SD) were plasma ascorbic acid 13.6 +/- 6.4 mg/L (N > 4), plasma folate 14.1 +/- 1.1 microg/L (N > 3), for vitamin B1, alpha-ETK 1.02 +/- 0.02 (N < 1.18) and ETKo 100 +/- 13 U/L (N > 70), for vitamin B2, alpha-EGR 1.00 +/- 0.07 (N < 1.52) and EGRo 1282 +/- 213 U/L (N > 672), and for vitamin B6, alpha-EGOT 1.34 +/- 0.10 (N < 1.8) and EGOTo 380 +/- 84 U/L (N > 228). Plasma oxalic acid was higher than normal in all patients (mean = 61 +/- 15 micromol/L, N < 33). However, all patients had oxalic acid levels within the range reported in the literature for patients not taking extra ascorbic acid. Mean total homocysteine was 24 +/- 8 micromol/L with only 4 patients (12%) having normal levels (N < 15). In conclusion, the postdialysis supplement given provides adequate vitamin levels in almost all patients in the long term. Postdialysis prescription allows an optimal compliance with the treatment, is well accepted by the patients, and is cost-effective.

[Multi-systemic toxicity of colchicine and renal failure: apropos of a case]. / Toxicité multisystémique de la colchicine et insuffisance rénale: à propos d'un cas.

The use of colchicine can produce various side effects, but multiorgan toxicity is rare. We report the first Swiss case of multiorgan toxicity involving typical neuromuscular lesions. Muscular biopsy is a valuable tool in confirming the diagnosis. Renal insufficiency and hepatobiliary diseases are predisposing factors for such complications. Colchicine pharmacology in the case of renal insufficiency is discussed.

Urea kinetic modeling: an in vitro and in vivo comparative study.

The urea kinetic model (UK) and the direct dialysis quantification method based on dialysate collection (DDQ) were used to determine the urea distribution volume (V) identified with the total body water and the urea generation rate (G) for different dialysis times, both in vivo during short hemodialysis (N = 20) and in vitro using an experimental single-pool urea system (N = 10). Both UK and DDQ allowed a satisfactory in vitro estimation of V and G for all dialysis times. On the other hand in vivo V and G estimations by both methods showed an increase of more than 50% between the determinations performed after 30 minutes of dialysis and at the end of dialysis. Our theoretical analysis shows that the in vivo changes of V are compatible with those expected for a two-compartment system in which one compartment is cleared faster than the other. Furthermore, given that urea is allowed to equilibrate in the body at the end of dialysis, DDQ permits an accurate estimate of V, G and PCR even for short hemodialysis, which UK does not.

[A flow divider which permits, during hemodialysis, the continuous collection of a representative sample of dialysate]. / Un diviseur de flux qui permet, en cours d'hémodialyse, le recueil continu d'un échantillon représentatif du dialysat.

Dialysis efficiency is evaluated by the measurement of transfer of urea as well as of other important solutes such as sodium, potassium, phosphates etc. from the blood to the dialysate. These determinations are usually made by using clearances, but, because of the internal dynamics in the blood itself, reliable measurements taken in this way are impossible for most of the solutes of interest. Our system avoids these difficulties and provides accurate results. A reference method requires the determination of the volume and the concentration of the effluent dialysate. This is used in research work, but for obvious reasons, it is not suitable to a daily clinical context. Several authors proposed a system based on a pump, in order to sample continuously a fraction of the dialysate. However, they have to assume a constant flow of the latter. The system described here has the advantage of collecting a representative sample of the whole dialysate regardless of flow and concentrations variations during dialysis. It is suitable to a clinical context, easy to use and silent.

Diffusion kinetics of urea, creatinine and uric acid in blood during hemodialysis. Clinical implications.

In order to elucidate some conflicting data reported in the literature the diffusion kinetics between red blood cells (RBC) and plasma during dialysis were studied for urea, creatinine and uric acid. Several complementary studies were performed. According to our results urea diffuses very rapidly from RBC to plasma and is almost at equilibrium at the dialyser outlet; thus the extraction of urea during dialysis is from both plasma and RBC. On the other hand creatinine and uric acid hardly diffuse at all from RBC to plasma during blood transit through the hemodialyser and these solutes are thus extracted mainly from plasma. As a consequence an important in-vitro equilibration process occurs for both solutes in blood drawn at the dialyser outlet; the equilibration rate is greatly temperature-dependent and to achieve complete equilibrium at room temperature, up to 6 to 12 hours were needed for creatinine and 2 to 3 hours for uric acid. Moreover, in the case of creatinine, but not for uric acid, a RBC/plasma disequilibrium was also found in blood drawn at the dialyser inlet; this finding is in contrast with previous reports and suggests that with high-efficiency dialysis modalities the interval between two successive RBC transits through the dialyser may be insufficient for complete equilibration of slowly equilibrating solutes. The clinical implications of these findings with respect to the in-vivo dialyser performance and clearance determinations are discussed.

Water soluble vitamins in chronic hemodialysis patients and need for supplementation.

Forty-three patients on chronic hemodialysis who before the present study had only received a low-dose supplement of folic and ascorbic acid were studied prospectively for one year. After baseline values were obtained in month one, increasing doses of postdialysis vitamin supplements were prescribed for the vitamins which were found to be insufficient in order to determine the minimal amount of oral postdialysis supplement necessary to normalize vitamin levels. According to our results no systematic supplement was indicated for biotin, riboflavin or vitamin B12. For folic acid and vitamin C, supplementation with lower doses than those prescribed in many dialysis units allowed optimal vitamin levels in the majority of patients; 2 to 3 mg/week (300 to 400 micrograms/day) of folic acid and of 1000 to 1500 mg/week (150 to 200 mg/day) of vitamin C was considered sufficient. A severe pyridoxine deficiency was present in most (> 80%) unsupplemented patients, either as judged by pyridoxal-5-phosphate determinations in plasma or determination of specific enzyme activation in erythrocytes (EGOTo and alpha-EGOT); a postdialysis supplement of at least 100 to 150 mg/week of pyridoxine hydrochloride (> 15 to 20 mg/day) corrects this deficiency. The activity of the thiamine-dependent enzyme transketolase in erythrocytes (ETKo) was insufficient in 35% and marginal in 21% of the patients, while whole blood thiamine determined simultaneously in 10 of the ETKo-deficient patients was within the normal range. These results suggest that in uremia insufficient transketolase activity may be related to inhibition of the enzymatic system rather than to true vitamin deficiency. On a long-term basis a supplement of 200 to 300 mg/week of thiamine hydrochloride (30 to 45 mg/day) restored ETKo to satisfactory levels in most patients; whether this supplement is to be recommended warrants further studies.

[Hyperkalemia during prolonged use of angiotensin II-converting enzyme inhibitors in end-stage renal insufficiency]. / Hyperkaliémie lors d'inhibition prolongée de l'enzyme de conversion de l'angiotensine II dans l'insuffisance rénale terminale.

Hyperkalemia is a severe complication of end-stage renal failure. To evaluate whether ACE inhibitors may even worsen the propensity to develop hyperkalemia in this condition, we have analyzed retrospectively pre-dialytic blood pressure and serum potassium in 15 patients on chronic hemodialysis before and during long-term ACE inhibition. This treatment induced a significant drop in blood pressure (from 173 +/- 3/90 +/- 2 to 159 +/- 5/85 +/- 2 mm Hg [p < 0.05]), whereas serum potassium increased from 4.9 +/- 0.2 to 5.5 +/- 0.2 mM (p < 0.05), irrespective of the dosage of ACE inhibitor and of the residual diuresis. Hyperkalemia was well tolerated and was corrected in all patients by dialysis; treatment was discontinued in only one case. In conclusion, ACE inhibitors represent effective antihypertensive treatment in end-stage renal failure. However, long-term ACE inhibition may be accompanied by a worsening of hyperkalemia, which could be accounted for by a reduced effect of aldosterone on extrarenal potassium homeostasis.

Acute encephalopathy due to thiamine deficiency (Wernicke's encephalopathy) in a chronic hemodialyzed patient: a case report.

We report the case of a patient with terminal renal disease on chronic hemodialysis who developed acute thiamine deficiency as confirmed by erythrocyte transketolase determinations. The patient presented with a confusional state and severe memory disturbances, but other classical features of Wernicke's encephalopathy were absent. Almost all central nervous system symptoms rapidly disappeared after thiamine therapy. Therefore the possibility of thiamine deficiency must be considered in patients on chronic dialysis who present with central nervous system disturbances, even if all of the classical features of Wernicke's encephalopathy are not present.

[Renal and neurological toxicity of acyclovir. Apropos of a case]. / Toxicité rénale et neurologique de l'acyclovir. A propos d'un cas.

The occurrence of anuria and stupor in a patient treated with acyclovir afforded the opportunity to discuss the renal and neurological toxicity of this drug. Acute renal insufficiency by crystallization of acyclovir and intratubular obstruction is a not infrequent side effect. The risk depends on the dose, the administration mode, the patient's state of hydration and preexisting renal failure. The evolution is typified by a rapid onset (after 24-48 h) and a prompt recovery after ending the treatment. The demonstration in urinalysis of crystals within leukocytes helps to establish the diagnosis. Neurological involvement can vary from confusion to coma. The cerebrospinal fluid is normal and the electroencephalogram shows diffuse slowing. A favorable outcome after ending treatment is the rule. Awareness of the risk factors associated with renal and neurological toxicity should lead to a reduction of its frequency.

[Subglottic stenosis: unrecognized type of presentation of Wegener's granulomatosis]. / Sténose sous-glottique: mode de présentation méconnu de la granulomatose de Wegener.

Most patients with Wegener's granulomatosis initially present with upper airway symptoms, persistent rhinosinusitis or otitis media. We report the case of a young female who presented with progressive dyspnea, inspiratory stridor and barking cough due to a subglottic stenosis. We would like to stress this often unrecognized type of presentation. The differential diagnosis, the limitations of histopathological examinations, and the interest of looking for anticytoplasmic antibodies in the diagnosis of Wegener's granulomatosis, are briefly discussed.

[A comparative approach to models of urea kinetics in hemodialysis treatment]. / Une approche comparative des modèles de la cinétique de l'urée dans le traitement par hémodialyse.

The importance of mathematical modeling in dialysis arose recently as a consequence of the achievement of individualized treatment therapies. Two distinct models were used in our center, namely the urea kinetic model (UK) and the direct dialysis quantification (ddq), for the estimation of the urea distribution volume (V) and the urea generation rate (G). It turned out that, for the same patient, they provided us with different results. The basic hypotheses on which the two models rely are poorly described in the literature. The aim of this paper is an attempt to fill this gap and to show that the discrepancy observed between the two models is not surprising at all. The study also shows that from a theoretical viewpoint, ddq is more appropriate than UK for the estimation of V and G. The question of the intrinsic quality of ddq is not discussed here.