[Clinical and economic significance of iron replacement in anemia treated with recombinant human erythropoietin in patients on hemodialysis]. / Klinický a ekonomický význam dusledné náhrady zeleza pri lécbe anémie rekombinantním humánním erytropoetinem u hemodialyzovaných nemocných.

BACKGROUND: Anaemia is a common phenomenon encountered in patients on hemodialysis. Although treatment with rHuEPO therapy is effective, it may fail even at high doses. As rHuEPO efficacy depends on the bioavailability of iron, we monitored the effect of consistent iron supplementation on hematocrit levels and rHuEPO dosage. METHODS AND RESULTS: 24 patients of our outpatient dialysis centre were included in this study. The mean age was 59 years. The age group over 60 included 14 patients. The mean duration of dialysis treatment was 23.8 months. The patients were followed for 6 months according to the NKF-DOQI (National Kidney Foundation Dialysis Outcomes Quality Initiative) recommendations for the treatment of anaemia. Following values were examined monthly: hematocrit, transferin saturation (TSAT) and ferritin. Iron and rHuEPO dosage was adjusted accordingly. Genetic tests for haemochromatosis were conducted in 4 patients with the highest value of TSAT and ferritin. TSAT increased from a mean of 15.9% to 35.9% (p < 0.001). In 23 patients (96%) TSAT levels were within the recommended range after the treatment. Hematocrit increased from 27.7% to 35.7% (p < 0.001). The recommended value of 33% was achieved in 18 patients (75%). The weekly dose of eHuEPO fell from 3958 IU (International Unit) to 2042 IU (p < 0.001), i.e. 1857 IU of rHuEPO were saved per week, per patient. The average dose of iron administered was 157 mg per week. The average level of ferritin rose from 457 micrograms/k to 1387 micrograms/l (p < 0.001). All results were comparable, even in the group of the senior's selected cases. Genetic testing for haemochromatosis showed mutation H63D in heterozygous state of HFE gene in 2 of 4 patients with the highest value of TSAT and ferritin. Sufficient iron supplementation leads to a significant rise in hematocrit and a concomitant decrease of required rHuEPO doses. TSAT, and not ferritin, is a good marker of iron bioavailability. CONDITIONS: The financial savings due to decreased rHuEPO requirements are 20 times higher than the costs related to iron supplementation, calculated in relation to prices valid for the Czech Republic in 1999. Cause and effect of increased level of ferritin should be carefully studied.

Effects of low-protein diet supplemented with ketoacids and erythropoietin in chronic renal failure: a long-term metabolic study.

Ketoacids (KA) and recombinant human erythropoietin (rHuEPO) may each, on their own, influence the metabolic status of patients with chronic renal failure (CRF). A long-term prospective randomized study was designed to monitor the metabolic and nutritional status and progression of CRF using three therapeutic protocols: (A) low-protein diet (LPD) with 0.6 g of protein and 35 kcal/kg/day, with recombinant human erythropoietin (rHuEPO) at a dose of 40 U kg/week and keto acids (KA) 100 mg/kg/day, (Group I), (B) LPD and rHuEPO (Group II), and (C) LPD only (Group III). A total of 105 patients (50M/55F), aged 26-78 years, CCr 22-36 ml/min, were monitored at the beginning, and at every 6 months for 3 years in the above three study groups. Group I comprised 35 patients, Group II 38 patients and Group III 32 patients. During follow-up, a significantly smaller decrease in GFR (CCr, Cin) and in I/SCr, and an increase in serum albumin, transferrin, leucine, body mass, index and HDL-cholesterol were found in Group I (all p < 0.01). In addition, significant decreases were also seen in proteinuria, renal fractional leucine excretion and serum triglycerides level (p < 0.01). Co-administration of LPD, rHuEPO and KA thus constitutes an effective alternative to conservative management of CRF, delaying in follow-up period progression of renal failure and correction of metabolic parameters.

Effect of a keto acid-amino acid supplement on the metabolism and renal elimination of branched-chain amino acids in patients with chronic renal insufficiency on a low protein diet.

The aim of our study was to evaluate the effect of a low-protein diet supplemented with keto acids-amino acids on renal function and urinary excretion of branched-chain amino acids (BCAA) in patients with chronic renal insufficiency (CRI). In a prospective investigation 28 patients with CRI (16 male, 12 female, aged 28-66 yrs, CCr 18.6 +/- 10.2 ml/min) on a low-protein diet (0.6 g of protein /kg BW/day and energy intake 140 kJ/kg BW/day) for a period of one month were included. Subsequently, this low protein diet was supplemented with keto acids-amino acids at a dose of 0.1 g/kg BW/day orally for a period of 3 months. Examinations performed at baseline and at the end of the follow-up period revealed significant increase in the serum levels of BCAA leucine (p < 0.02), isoleucine (p < 0.03), and valine (p < 0.02) while their renal fractional excretion declined (p < 0.02, p < 0.01 resp.). Keto acid-amino acid administration had no effect on renal function and on the clearance of inulin, para-aminohippuric acid. Endogenous creatinine and urea clearance remained unaltered. A significant correlation between fractional excretion of sodium and leucine (p < 0.05) and a hyperbolic relationship between inulin clearance and fractional excretion of BCAA (p < 0.01) were seen. Moreover, a significant decrease in proteinuria (p < 0.02), plasma urea concentration and renal urea excretion and a rise in albumin level (p < 0.03) were noted. We conclude that in patients with CRI on a low protein diet the supplementation of keto acids-amino acids does not affect renal hemodynamics, but is associated--despite increases in plasma concentrations--with a reduction of renal amino acid and protein excretion suggesting induction of alterations in the tubular transport mechanisms.

Diets enriched in menhaden fish oil, seal oil, or shark liver oil have distinct effects on the lipid and fatty-acid composition of guinea pig heart.

The purpose of this investigation was to determine whether diets supplemented with oils from three different marine sources, all of which contain high proportions of long-chain n-3 polyunsaturated fatty acids (PUFA), result in qualitatively distinct lipid and fatty acid profiles in guinea pig heart. Albino guinea pigs (14 days old) were fed standard, nonpurified guinea pig diets (NP) or NP supplemented with menhaden fish oil (MO), harp seal oil (SLO) or porbeagle shark liver oil (PLO) (10%, w/w) for 4-5 weeks. An n-6 PUFA control group was fed NP supplemented with corn oil (CO). All animals appeared healthy, with weight gains marginally lower in animals fed the marine oils. Comparison of relative organ weights indicated that only the livers responded to the diets, and that they were heavier only in the marine-oil fed guinea pigs. Heart total cholesterol levels were unaffected by supplementing NP with any of the oils, whereas all increased the triacylglycerol (TAG) content. The fatty-acid profiles of total phospholipid (TPL), TAG and free fatty acid (FFA) fractions of heart lipids showed that feeding n-3 PUFA significantly altered the proportions of specific fatty-acid classes. For example, all marine-oil-rich diets were associated with increases in total monounsaturated fatty acids in TPL (p < 0.05), and with decreases in total saturates in TAG (p < 0.05). Predictably, the n-3 PUFA enriched regimens significantly increased the cardiac content of n-3 PUFA and decreased that of n-6 PUFA, although the extent varied among the diets. As a result, n-6/n-3 ratios were significantly lower in all myocardial lipid classes of marine-oil-fed guinea pigs. Analyses of the profiles of individual PUFA indicated that quantitatively, the fatty acids of the three marine oils were metabolized and/or incorporated into TPL, TAG and FFA in a diet-specific manner. In animals fed MO-enriched diets in which eicosapentaenoic acid (EPA) > docosahexacnoic acid (DHA), ratios of DHA/EPA in the hearts were 1.2, 2.2 and 1.5 in TPL, TAG and FFA, respectively. In SLO-fed guinea pigs in which dietary EPA approximately DHA, ratios of DHA/EPA were 0.9, 3.4 and 2.1 in TPL, TAG and FFA, respectively. Feeding NP + PLO (DHA/EPA = 4.8), resulted in values for DHA/EPA in cardiac tissue of 2.1, 10.6 and 2.9 in TPL, TAG and FFA, respectively. In the TAG and FFA, proportions of n-3 docosapentaenoic acid (n-3 DPA) were equal to or higher than EPA in the SLO- and PLO-fed animals. The latter group exhibited the greatest difference between the DHA/n-3 DPA ratio in the diet and in cardiac TAG and FFA fractions (7, 3.4 and 3.1, respectively). Quantitative analysis indicated that > or = 85% of the n-3 PUFA were in TPL, 7-11% were in TAG, and 2-6% were FFA. Specific patterns of distribution of EPA, DPA and DHA depended on the dietary oil. Both the qualitative and quantitative results of this study demonstrated that in guinea pigs, n-3 PUFA in different marine oils are metabolized and/or incorporated into cardiac lipids in distinct manners. In support of the concept that the diet-induced alterations reflect changes specifically in cardiomyocytes, we observed that direct supplementation of cultured guinea pig myocytes for 2-3 weeks with EPA or DHA produced changes in the PUFA profiles of their TPL that were qualitatively similar to those observed in tissue from the dietary study. The factors that regulate specific deposition of n-3 PUFA from either dietary oils or individual PUFA are not yet known, however the differences that we observed could in some manner be related to cardiac function and thus their relative potentials as health-promoting dietary fats.

Incidence of analgesic nephropathy among patients undergoing renal replacement therapy in Czech Republic and Slovak Republic. The Group of Czech and Slovak Nephrologists.

BACKGROUND: The occurrence of analgesic nephropathy (AN) among renal replacement therapy patients in former Czechoslovakia is not known. Previous surveys were not based on representative samples and lacked uniform criteria for diagnosing the disease. METHODS: Incidence of AN in former Czechoslovakia was investigated in patients commencing renal replacement therapy in 24 (1/3 of all) dialysis centres from 1 January to 31 December 1992. Patients showing an unclear renal diagnosis (n = 149) were investigated with an interview and renal imaging techniques. The diagnosis of AN was withheld or rejected on the base of recently published diagnostic criteria demonstrating that a decreased renal mass of both kidneys combined with bumpy contours and/or papillary calcifications had a high performance for diagnosing AN (Nephrol Dial Transplant 1992; 7: 479-486). RESULTS: Based on the renal imaging criteria, AN was diagnosed in 30 of 328 registered patients, resulting in an AN incidence of 9.1% while the EDTA data only mentioned an incidence of 4.8% (period 1986-1989). The products most commonly abused were analgesic mixtures containing two analgesic substances combined with caffeine and/or codeine. CONCLUSIONS: AN was found to be a common disease in the Czech and Slovak Republics. The disease was diagnosed using reliable renal imaging criteria.

Effects of dietary cod liver oil on fatty-acid composition and calcium transport in isolated adult rat ventricular myocytes and on the response of isolated hearts to ischemia and reperfusion.

Three-week-old male and female rats were placed either on standard rat chow or chow supplemented with 10% cod liver oil for 12 weeks. Animals fed cod liver oil demonstrated reduced body weights. Cod liver oil feeding produced a significant reduction in the ratio of (n - 6)/(n - 3) fatty acids in phospholipids of the isolated myocytes. The primary changes included a significant decrease in arachidonic acid (20:4, n - 6) and elevations in eicosapentaenoic acid (20:5, n - 3) and docosahexaenoic acid (22:6, n - 3). Furthermore, isolated myocytes from cod liver oil fed rats exhibited an enhanced 45Ca2+ uptake, although 45Ca2+ release was unaffected. Dietary cod liver oil had little effect on cardiac response to ischemia and reperfusion. Thus, neither developed force or resting tension was significantly affected by diet, although the latter tended to be elevated in hearts from cod liver oil fed animals. Release of creatine kinase was unaltered by diet. The release of 6-ketoprostaglandin F1 alpha from isolated hearts was significantly reduced by dietary cod liver oil, likely due to the reduced levels of arachidonic acid. Our study indicates that dietary cod liver oil and subsequent changes in phospholipid fatty-acid content are accompanied by changes in Ca2+ transport in isolated cardiac myocytes. However, this diet produces little effect on the cardiac response to acute ischemia and reperfusion.