Heart remodeling in patients with predialysis phase of chronic renal failure

AIM: To investigate remodeling of the heart in patients with predialysis phase of chronic renal failure (CRF). MATERIAL AND METHODS: Patients with predialysis phase of CRF (n = 61; serum creatinine 412.4 +/- 242.69 mumol/l), essential hypertension (EH) (n = 35) and healthy volunteers (n = 20) were assessed with echocardiography. The patients were not significantly different by the level of systolic and diastolic blood pressure, age and gender. RESULTS: Left ventricular mass index (LVMI) was increased in 53(86.9%) patients with CRF. LVMI was not different in patients with CRF and EH (189.9 +/- 71.35 vs. 165.0 +/- 41.83 g/m2; p = 0.3). Relative wall thickness was similar in patients with serum creatinine < 200 mumol/l and patients with more elevated serum creatinine (57.2 +/- 10.33 vs 58.31 +/- 13.33; p = 0.9). The ejection fraction lower than 50% was detected in 14(22.9%) patients with CRF. Multivariate regression analysis showed that LVMI was independently related to systolic blood pressure (p = 0.004) and level of hemoglobin (p = 0.004). Diastolic dysfunction (early and atrial peak filling velocities ratio < 1.0) was detected in 13(50%) from 26 investigated patients with CRF. The independent influence of hemoglobin on isovolumic relaxation time (p = 0.04) and early and atrial peak filling velocities ratio (p = 0.02) are shown. CONCLUSION: In patients with predialysis phase of CRF left ventricular hypertrophy (LVH) is extremely common including patients with mildly elevated serum creatinine. The treatment of patients with renal pathology and normal function must include measures not only to correct renal process but also to prevent development of LVH.     

Soluble interleukin-2 receptors in the serum of patients with chronic renal failure

The levels of soluble form of the interleukin-2 receptor (sIL-2R) were evaluated in the peripheral blood of 29 patients with chronic renal failure (CRF) using enzyme-linked immunosorbent assay. All patients had undergone hemodialysis and the mean (+/- S.D.) BUN was before hemodialysis was 80.9 +/- 22.4 mg/100 ml. The mean level of sIL-2R was 1146 +/- 258 U/ml, which was significantly higher than the level (288 +/- 118 U/ml) in 12 individuals with a normal BUN level (p = 0.01). In patients with CRF, the elevated sIL-2R level was not influenced by hemodialysis, and not correlated with creatinine or beta 2-microglobulin levels. The kidneys may play an important role in the catabolism of serum sIL-2R. The elevated sIL-2R level may be related to compromised immunoregulation in CRF.     

Use of angiotensin-converting enzyme inhibitors in chronic kidney insufficiency

AIM: To study effects of ACE inhibitors in patients with diffuse renal diseases at the stage of chronic renal failure (CRF). MATERIAL AND METHODS: Acute changes in renal filtration and in renal hemodynamics in response to 100-200 mg captopril were studied in 7 patients with CRF and 6 patients with intact renal function. Effects of long-term ACE inhibitors were retrospectively studied in 50 patients with CRF (27 men, 23 women, mean age 46.0 +/- 1.9 years, 7 patients were over 60 years old). Sixteen patients were selected from this group who were followed up for a long time. They were examined for CRF progression rate when given conventional antihypertensive treatment and after treatment with ACE inhibitors. RESULTS: Acute response to ACE inhibitors was the following: SCF fell by 18.4% on the average by the end on therapy week 1; by the end of week 3 renal hemodynamics showed stability, SCF returned to normal, effective renal plasm flow rose by 16.9%, serum potassium rose significantly after 7 days of treatment but did not reach 6 mmol/l. Effects of long-term ACE inhibitor in CRF: the treatment was discontinued after 30-60 days in 12 of 50 patients because of high creatinine (> 20%); in 38 patients ACE inhibitor had a pronounced antihypertensive and antiproteinuric action for 2-3 years, creatinine growth inhibited. Progression of CRF became slow. CONCLUSION: ACE-inhibitors in CRF had a nephroprotective effect but blood creatinine levels should be controlled especially within the first 1-2 months of treatment.     

Pharmacokinetics of ofloxacin in severe chronic renal failure

The pharmacokinetics of ofloxacin were studied in patients with severe renal impairment. In five healthy subjects and nine patients with chronic renal failure (CRF) (creatinine clearance [CCR] less than 20 ml/min) receiving 100 mg of ofloxacin orally in the fasted state, the serum concentration was measured over the subsequent 48 hours. Intracorporeal dynamics were examined, employing a one-compartment open model. Ofloxacin levels were measured using the paper disk method. The half-life of ofloxacin was markedly prolonged, to 23.1 +/- 7.0 hr in the CRF group versus 2.9 +/- 0.5 hr for healthy subjects. In the CRF group, the maximum concentration and area under the curve were greater than in healthy subjects. There were no significant differences in volume of distribution between the two groups. The renal clearance of ofloxacin decreased from 261.0 +/- 46.6 ml/min in healthy subjects to 8.0 +/- 4.7 ml/min in the CRF group and correlated significantly with CCR in the CRF group (r = .88, P less than 0.01). There were no significant differences in nonrenal clearance between the two groups. The 24-hour renal excretion of ofloxacin averaged 91.9 +/- 5.4% and 14.1 +/- 5.5% of the dose in the healthy and CRF groups, respectively. In three hemodialysis patients on the regular hollow-fiber dialyser, the dialysance of ofloxacin was about 50% that of creatinine. Based on these findings, a reduction in the dose of ofloxacin is necessary in patients with CRF. In the hemodialyzed patients, its high dialyzability should be considered when deciding dose regimens.     

Hyperhomocysteinemia and end-stage renal disease: determinants and association with cardiovascular disease in Tunisian patients.

The study reports on plasma total homocysteine (tHcy) levels in Tunisian patients with chronic renal failure (CRF) and those treated with hemodialysis (HD) and renal transplant (RT). The aims of the study were to identify the determinants of tHcy concentration and to test the association between hyperhomocysteinemia and atherothrombotic disease in end-stage renal disease (ESRD). A total of 35 CRF patients on conservative treatment, 50 HD patients, and 30 RT recipients, and 31 age- and sex-matched healthy subjects were included. Plasma tHcy was assessed by a fluorescent-polarizing immunoassay method. Multivariate analysis was applied to identify the main determinants of tHcy concentration and to assess the relationship between hyperhomocysteinemia and cardiovascular disease. Plasma mean tHcy concentration was significantly increased (p < 0.001) in CRF patients (mean +/- SD) (28.9 +/- 9.8 micromol/l), in HD patients (29.4 +/- 11.1 micromol/l), and in RT (19.3 +/- 6.3 micromol/l) patients compared to controls (11.9 +/- 4.1 micromol/l). Multivariate analysis using GLM ANOVA modeling demonstrated that tHcy was significantly higher in males (p = 0.02), and was related to age (p = 0.008), albumin (p = 0.005), vitamin B12 (p = 0.002), folate (p = 0.00001), and creatinine clearance (p = 0.0008). However, tHcy was not associated with C-reactive protein and did not significantly differ between CRF, HD, or RT patients. The upper quartile of tHcy concentration was significantly associated with atherothrombotic cardiovascular disease (unadjusted odds ratio (OR) = 3.09; 95% CI, 1.11-8.61; p = 0.01). This association remained significant after adjusting for sex, age, hypertension, and smoking (multi-adjusted OR = 4.78; 95% CI, 1.92-11.9; p = 0.0008). The mean tHcy concentration was 2 to 3 times higher in ESRD patients than in subjects with normal renal function. This increase could be related to glomerular filtration rate reduction and functional B vitamins deficiency, but was not associated with inflammation. The upper quartile of tHcy concentrations confers 4.78-fold increased independent risk for atherothrombotic events in ESRD patients.     

Red blood cell calcium level in chronic renal failure: effect of continuous ambulatory peritoneal dialysis

Red blood cell (RBC) calcium, calcium 45 influx, and calcium extrusion as indicated by Ca-stimulated, Mg-dependent adenosine triphosphatase (CaATPase) was determined in patients with chronic renal failure (CRF), patients with CRF receiving continuous ambulatory peritoneal dialysis (CAPD) treatment, and controls. Cell calcium, which in the controls was 5.5 mumol/L of cells, was elevated in patients with CRF--30.6 +/- 6.8 mumol/L of cells (p less than 0.002)--and in patients receiving CAPD-23.6 +/- 6.7 mumol/L of cells (p less than 0.02). Basal CaATPase activity in controls was 850.7 +/- 66.7 nmol inorganic phosphate per milligram of protein per hour. It was suppressed in patients with CRF and patients receiving CAPD: 504.9 +/- 34.4 nmol inorganic phosphate per milligram of protein per hour and 618.2 +/- 47.3 nmol inorganic phosphate per milligram of protein per hour, respectively (p less than 0.01). Calmodulin-stimulated CaATPase revealed a pattern similar to that of CaATPase basal activity. RBC calcium showed an inverse correlation with CaATPase activity (r = -0.935, p less than 0.005) in patients with CRF. Calcium influx was increased in patients with CRF and in patients receiving CAPD: 12.00 +/- 1.34 mumol/L of cells per hour and 13.60 +/- 1.70, respectively, compared with 4.61 +/- 0.39 mumol/L of cells per hour in controls (p less than 0.001). Patients with CRF have elevated RBC calcium levels mainly related to decreased extrusion and to increased influx. CAPD fails to improve substantially these abnormalities. Plasma vanadium levels were markedly elevated in patients undergoing hemodialysis and marginally in patients receiving CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peritoneal function and adequacy calculations: current programs versus PD Adequest 2.0.

OBJECTIVE: Our current programs (CPs) were compared to PD Adequest 2.0 (PD-A) for calculations of peritoneal membrane transport and dialysis adequacy. DESIGN: Thirty peritoneal equilibration tests (PETs) and 24-hour balances (24hBs) were conducted and calculated using our CPs and PD-A. PATIENTS AND METHODS: Thirty hospital-controlled peritoneal dialysis (PD) patients were studied. The inclusion of correction factors (for glucose or plasmatic water) and of residual volume, and the use of 3 or 6 peritoneal samples were analyzed to discover the differences between programs. The main outcome measures were peritoneal permeability and adequacy parameters, evaluated by Student t-test (mean and paired comparisons) and linear regression for correlation. RESULTS: No significant differences were found in D/P values for small solutes. At the first step, mass transfer area coefficient (MTAC) urea and MTAC creatinine were significantly higher in DP-A than in CP, but MTAC glucose did not differ. The causes of differences were: (1) inclusion of a correction factor for aqueous plasmatic concentration of small solutes in CP; (2) lack of Inclusion of residual volume in peritoneal volumes in CP; and (3) use of 6 peritoneal samples in CP versus 3 in PD-A. At the second step, when the input data were made equivalent for both programs, the differences disappeared for MTAC urea, creatinine, and glucose (mean comparison), but creatinine and glucose remained different by paired comparison. Similar results were obtained when a correction for plasmatic aqueous concentration was applied to the data in both programs [MTAC urea: 22.60 +/- 4.27 ml/min (CP) vs 22.43 +/- 4.61 mL/min (PD-A), nonsignificant, r= 0.97; MTAC creatinine: 9.76 +/- 3.83 mL/min (CP) vs 10.61 +/- 3.07 mL/min (PD-A), nonsignificant, r = 0.98; MTAC glucose: 13.30 +/- 3.12 mL/min (CP) vs 11.87 +/- 3.41 m/min (PD-A), nonsignificant, r= 0.92]. Creatinine and glucose were different by paired t-test. No significant differences were found in Kt/V and urea generation rate. Weekly creatinine clearance [WCCr: 70.71 +/- 16.71 L (CP) versus 79.33 +/- 18.73 L (PD-A), p < 0.001] and creatinine generation rate [CrGR: 0.56 +/- 0.18 mg/min (CP) versus 0.61 +/- 0.19 mg/min (PD-A), p < 0.001) were significantly higher in PD-A than In CP owing to the lack of creatinine correction according to glucose concentration In the PD-A adequacy program. Finally, normalized protein nitrogen appearance according to Bergstr?m [1.09 +/- 0.20 g/kg/d (CP) versus 1.03 +/- 0.21 g/kg/d (PD-A), p = 0.01] was different owing to the different algorithms and normalization method: standardized body weight in CP and actual body weight in PD-A. CONCLUSIONS: Provided that equivalent data are used, PD-A and CP yield similar results. The PD-A program needs external correction of data input: (1) for plasmatic water concentration in MTAC calculations, and (2) for peritoneal glucose interference with creatinine analysis (Jaffé method) In WCCr and CrGR calculations; otherwise, It may give falsely optimistic results.     

Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20-21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100+/-18 pg/ml) and low calcitriol levels (10.6+/-4.3 pg/ml) compared with normal rats [N1: 14+/-2.5 pg/ml (P<0.001) and 18.2+/-4.2 pg/ml (P<0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2+/-5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4+/-8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87+/-17 pg/ml) and low calcitriol levels (9.3+/-1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.     

Kinetics, dynamics, and bioavailability of bumetanide in healthy subjects and patients with chronic renal failure

Six patients with chronic renal failure (CRF group) and four healthy subjects (HS group) were given 5 mg oral and intravenous doses of bumetanide in a random, crossover design. The CRF group had significantly lower plasma and renal clearances, resulting in a five-to sixfold reduction in the fractional urinary excretion of the drug. The percent free drug in plasma for the CRF group was more than double that for the HS group, and significant correlations were observed for volume of distribution at steady state vs. percent free (r = 0.661; P less than 0.05), nonrenal clearance vs. percent free (r = 0.796; P less than 0.01), and renal clearance vs. creatinine clearance (r = 0.995; P less than 0.001). Although bioavailability was relatively consistent among the HS (0.664 +/- 0.112) and CRF (0.689 +/- 0.149) groups, the absorption-time profiles were more irregular for both groups. Cumulative sodium excretion and overall efficiency of response to bumetanide did not differ significantly between the two routes of administration in either group.     

Plasma bone Gla protein concentrations in healthy adults. Dependence on sex, age, and glomerular filtration

Plasma bone Gla protein (BGP) was determined by radio-immunoassay in 266 healthy adults, men (n = 132) and women (n = 134), aged 20-79 years. In the women aged 30-69 years, plasma BGP increased significantly with age (r = 0.44, p less than 0.001), and a particularly steep increase was seen from 1.1 +/- 0.5 (mean +/- 1 SD) in the fifth decade to 2.0 +/- 1.4 nmol/l in the seventh decade. In men, aged 30-69 years, no correlation was found between plasma BGP and age (r = -0.07, NS). Plasma bone Gla protein is removed from the circulation mainly by the kidneys and the increased plasma BGP in the women could be caused by decreased renal clearance. The interrelationship was analysed by means of partial correlation. When creatinine clearance was held constant in women, BGP still correlated positively with age (r = 0.40, p less than 0.001), but not with creatinine clearance (r = 0.003, NS) when age was fixed. Plasma BGP was significantly increased above normal in 35 patients with chronic renal failure (10.2 +/- 14.6 nmol/l). Non-linear regression analysis showed that plasma BGP was within the normal range when 24-h creatinine clearance was greater than 30 ml/min, and large increases in plasma BGP did not occur until the 24-h creatinine clearance was below 20 ml/min. We conclude that, in normal subjects and patients with mild to moderate renal failure, plasma elevations of BGP reflect increased bone turnover rather than decreased renal clearance.     

Heterogeneity of plasma glucagon. Circulating components in normal subjects and patients with chronic renal failure.

Plasma immunoreactive glucagon (IRG) concentrations were measured in 36 patients with chronic renal failure (CRF) and 32 normal subjects. In addition, the components of circulating IRG were analyzed by gel filtration in the fasting state and after physiological stimuli. Fasting IRG was elevated (P less than 0.001) in CRF patients (534 +/- 32 pg/ml) compared with the levels found in healthy subjects (113 +/- 9 pg/ml). Oral glucose suppressed plasma IRG in CRF patients from a basal level of 568 +/- 52 to a nadir of 354 +/- 57 pg/ml (120 min). This degree of suppression (38%) was comparable to that found in normal subjects (basal = 154 +/- 20 to 100 +/- 23 pg/ml) at 120 min (35%). Intravenous infusion of arginine (250 mg/kg) resulted in a 71% rise in IRG in CRF patients and a 166% increase in normal subjects. Gel filtration of fasting plasma from CRF patients showed three major peaks. The earliest (A) was found in the void volume (mol wt greater than 40,000) and constituted 16.5 +/- 4.7% of the elution profile. The middle peak (B) eluted just beyond the proinsulin marker (approximately 9,000 mol wt) and constituted the largest proportion of the elution profile (56.5 +/- 3.4%). The third peak (C) coincided with the standard glucagon and [125I]glucagon markers (3,485 mol wt) and comprised 27.0 +/- 4% of the IRG profile. In contrast, only peaks A and C were found in fasting plasma of normal subjects (53.6 +/- 10.4% in A and 46.4 +/- 10.4 in C). After oral glucose, glucagon immunoreactivity in the 3,500 mol wt peak (C) was markedly suppressed, while the B peak in patients with CRF declined to a lesser extent. The A peak in both groups was unchanged. After an arginine infusion only the C peak increased in both groups of subjects. Gel filtration of plasma in 3 M acetic acid gave similar profiles to those obtained in glycine albumin buffer. Exposure of serum to trypsin indicated that the B and C peaks were digestible, while the A peak was resistant to the action of the enzyme. In one sample, peak C increased after a 2-h exposure of serum to trypsin. We conclude that circulating IRG in normal subjects and patients with CRF is heterogenous. The hyperglucagonemia of renal failure is largely due to an increase in IRG material of approximately 9,000 mol wt, consistent with proglucagon, although the 3,500 mol wt component is also considerably elevated (threefold). The significance of circulating IRG levels should be interpreted with caution until the relative biological activity of the three components is established.     

Possible mechanisms of polyuria in progressive chronic renal failure

AIM: Elucidation of the role of saluresis and osmotic diuresis in renal function of patients with chronic renal failure. MATERIAL AND METHODS: The trial included 68 subjects, among them 25 patients with chronic renal failure (CRF) of the third and fourth degree aged 16 to 72 years. Enzyme immunoassay was used to measure osmolality, sodium, potassium, magnesium, calcium and creatinine concentrations in the serum and urine as well as urine prostaglandin E2. RESULTS: Renal function was studied in CRF patients with a 75-90% fall of glomerular filtration rate. Creatinine clearance was 19.9 +/- 0.96, it varied in different patients from 10.6 to 29.7 ml/min. It is shown that diuresis does not correlate with the total ion excretion (Na+ plus K+)(r = 0.946, p < 0.0001). A correlation was found between excretion of these ions and Mg2+ ions this indicating location of reabsorption reduction in the thick ascending limb of Henle loop. In CRF patients (Na+ plus K+) excretion correlated with PGE2 excretion (r = 0.65, p < 0.0001). CONCLUSION: It is suggested that at this stage of chronic renal failure the mechanism of a diuresis increase is not due to osmotic diuresis but rather to secretion of prostaglandin E2 which inhibits cation reabsorption and stimulates diuresis. Differences are considered between osmotic diuresis and different types of saluresis; their possible mechanisms are discussed.     

Metabolic effects of keto acid--amino acid supplementation in patients with chronic renal insufficiency receiving a low-protein diet and recombinant human erythropoietin--a randomized controlled trial

Supplement with keto acids/amino acids (KA) and erythropoietin can independently improve the metabolic sequels of chronic renal insufficiency. Our study was designed to establish whether a supplementation with keto acids/amino acids (KA) exerts additional beneficial metabolic effects in patients with chronic renal insufficiency (CRF) treated with a low-protein diet (LPD) and recombinant human erythropoietin (EPO). In a prospective randomized controlled trial over a period of 12 months, we evaluated a total of 38 patients (20 M/18 F) aged 32-68 years with a creatinine clearance (CCr) of 20-36 ml/min. All patients were receiving EPO (40 U/kg twice a week s.c.) and a low-protein diet (0.6 g protein/kg/day and 145 kJ/kg/day). The diet of 20 patients (Group I) was supplemented with KA at a dosage of 100 mg/kg/day while 18 patients (Group II) received no supplementation. During the study period, the glomerular filtration rate slightly decreased (CCr from 28.2 +/- 3.4 to 26.4 +/- 4.1 ml/min and 29.6 +/- 4.8 to 23.4 +/- 4.4 ml/min in groups I and II, respectively and Cin); this however was more marked in Group II (Group I vs. Group II, p < 0.01). The serum levels of urea also declined (p < 0.01), more pronouncedly in Group I (p < 0.025). In Group I, there was a significant rise in the levels of leucine (p < 0.01), isoleucine (p < 0.01), valine (p < 0.02) and albumin (p < 0.01) and a decrease in protein-uria (p < 0.01). Analysis of the lipid spectrum revealed a mild yet significant decrease in total cholesterol and LDL-cholesterol (p < 0.02), more pronounced in Group I. In Group I, there was a decrease in plasma triglycerides (from 4.2 +/- 0.8 down to values a low as 2.2 +/- 0.6 mmol/L; p < 0.01) whereas HDL-cholesterol levels increased (from 0.9 +/- 0.1 to 1.2 +/- 0.1 mmol/L, p < 0.01). A further remarkable finding was a reduction in the serum concentration of free radicals (p < 0.01). We conclude that a KA supplementation in patients with CRF receiving LPD and EPO potentiates the beneficial effects on metabolism of proteins, amino acids and surprisingly, also lipids. Long-term co-administration of KA, EPO and LPD was also associated with a delay in progression of renal insufficiency and a reduction in proteinuria. Thus, concomitant administration of KA and EPO during a low-protein diet presents an effective treatment modality in the conservative management of CRF.     

Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in patients with chronic kidney diseases

BACKGROUND: NO synthesis is inhibited by the dimethylarginine (DMA) ADMA, which accumulates, similar to SDMA, in the plasma of patients suffering from chronic renal failure (CRF). ADMA and possibly SDMA contribute to hypertension and atherosclerosis in patients with chronic renal disease: ADMA inhibits directly eNOS, whereas SDMA competes with the NO precursor arginine for uptake into the cells. METHODS: In 26 control persons and 221 patients with kidney diseases of different stage as were CRF, end stage renal disease (ESRD), and patients after renal transplantation (RT), the plasma concentrations of ADMA (c(ADMA)), SDMA (c(SDMA)) and 20 endogenous amino acids (AA) were measured by HPLC and correlated to blood pressure, cardiac events, endothelial dysfunction, and diabetes mellitus. RESULTS: Both ADMA (1.04+/-0.04 vs. 0.66+/-0.04 microM) and SDMA (2.69+/-0.12 vs. 0.49+/-0.03 microM) were significantly (p<0.001) elevated in all patients compared to healthy controls, whereas arginine concentration (51.4+/-2.3 vs. 76.0+/-5.2 microM) was decreased in dependence on the degree of kidney disease. In RT patients, SDMA levels were significantly decreased, but c(ADMA) remained enhanced. A strong correlation was found between SDMA and both serum urea and creatinine in CRF and RT patients. A linear correlation was found between ADMA and cholesterol concentrations in RT patients. Hypertension in CRF was accompanied by a further increase in the concentration of DMAs. There was no relation between DMAs and the occurrence of peripheral arterial occlusive disease or cerebrovascular diseases. In patients with cardiac diseases, c(SDMA) was additionally increased only in the CRF group. CONCLUSIONS: In patients with chronic kidney disease, c(ADMA) and c(SDMA) are significantly increased but cardiovascular diseases are evidently not correlated to changes in DMA concentrations in this group of patients.     

Correlation between fractional reabsorption of sodium and erythropoietin dose in peritoneal dialysis patients.

BACKGROUND: Erythropoietin (EPO) deficiency of chronic renal failure (CRF) may be a functional consequence of decreased glomerular filtration rate and fractional reabsorption of sodium (FR(Na)). Decreased FR(Na) reduces renal oxygen consumption and increases tissue oxygen pressure, resulting in less EPO production. We hypothesized that, in CRF patients, there is a positive relationship between EPO production and FR(Na) and that, in such patients receiving EPO, a negative correlation is expected between FR(Na) and EPO dose. METHODS: Creatinine clearance, FR(Na), serum iron, transferrin, transferrin saturation, ferritin, and intact parathyroid hormone (iPTH) levels were measured in 91 peritoneal dialysis patients. The correlation between EPO dose and FR(Na) was studied. RESULTS: Mean EPO dose was 7076 +/- 4821 units/week and mean FR(Na) was 93.40% +/- 6.14%. A negative correlation was found between EPO dose and FR(Na) (r = -0.28, p < 0.01), and a positive correlation was found between both ferritin and iPTH and EPO dose (r = 0.39, p < 0.001 and r = 0.35, p < 0.002 respectively). After adjusting for the effect of creatinine clearance, ferritin, and iPTH, there was still a significant correlation between EPO dose and FR(Na) (p < 0.05). CONCLUSION: In CRF patients there is a negative correlation between FR(Na) and EPO dose, which supports the hypothesis that EPO deficiency may be related to the decreased renal oxygen-consuming work of sodium reabsorption.     

Diagnosis of left-ventricular diastolic dysfunction in patients with predialysis chronic renal failure

AIM: To specify effectiveness of different methods for assessment of diastolic function in patients with pre-dialysis chronic renal failure (CRF). MATERIAL AND METHODS: Forty non-diabetic pre-dialysis CRF patients (20 males and 20 females, mean age 51 +/- 11 years) were studied. Serum creatinine was 209.3 +/- 117.4 mcmol/l. 19 patients had chronic heart failure (CHF) of NYHA class I-III. M-mode echocardiography and Doppler echocardiography were performed. Transmitral and pulmonary venous flows were assessed by Doppler echocardiography and the flow propagation velocity (Vp) was estimated by color M-mode Doppler echocardiography. The ratio of peak E-wave velocity of transmitral flow to Vp (E/Vp) was calculated. All the patients had preserved systolic function (ejection fraction > 45%). RESULTS: Interpretation of transmitral flow was difficult in 16 (40.0%) patients. During Valsalva's manoeuvre the E-wave peak velocities, the A-wave velocities and the ratio E/A were decreasing. However, we did not reveal any correlation between E/A and NYHA class of heart failure (r = 0.18; p = 0.32). Interpretation of pulmonary venous flow was possible only in 24 (60.0%) patients. Vp estimation by color M-mode Doppler echocardiography improved evaluation of diastolic function in 15 of 16 patients with problems of transmitral flow assessment. A negative correlation was revealed between NYHA class and Vp (r = -0.39; p = 0.013) and a positive correlation was between NYHA class and E/Vp (r = 0.45; p = 0.004). CONCLUSION: Vp assessed by color M-mode Doppler echocardiography improves the diagnosis of diastolic dysfunction in patients with chronic renal insufficiency. This method has an advantage over pulmonary venous flow investigation. The Valsalva's manoeuvre is low-effective for differential diagnosis of transmitral flow types.     

Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial

OBJECTIVE: We evaluated the renoprotective effects as reflected by short-term changes in albuminuria of dual blockade of the renin-angiotensin system (RAS) by adding an angiotensin II receptor blocker (ARB) to treatment with maximal recommended doses of an ACE inhibitor (ACEI) in patients with type 2 diabetes and nephropathy. RESEARCH DESIGN AND METHODS: A total of 20 patients (17 men and 3 women) with type 2 diabetes along with hypertension and nephropathy were enrolled in this double-blind, randomized, two-period, crossover trial of 8 weeks of treatment with the ARB candesartan 16 mg daily and placebo added in random order to existing treatment with lisinopril/enalapril 40 mg daily or captopril 150 mg daily. At the end of each treatment period, we evaluated albuminuria in three 24-h urinary collections by turbidimetry, 24-h ambulatory blood pressure (ABP) using the Takeda-TM2420, and glomerular filtration rate (GFR) by the (51)Cr-EDTA plasma-clearance technique. RESULTS: During monoblockade of the RAS by ACEI treatment, albuminuria was 706 (349-1,219) mg/24 h [geometric mean (IQR)]; 24-h ABP was 138 +/- 3/72 +/- 2 mmHg (mean +/- SE); and GFR was 77 +/- 6 ml x min(-1) x 1.73 m(-2) (mean +/- SE). During dual blockade of the RAS by addition of candesartan 16 mg daily, there was a mean (95% CI) reduction in albuminuria of 28 (17-38) compared with ACEI alone (P < 0.001). There was a modest reduction in systolic/diastolic 24-h ABP of 3/2 mmHg (-2 to 8 systolic, -2 to 5 diastolic; NS). Changes in albuminuria did not correlate to changes in ABP. Addition of candesartan 16 mg daily induced a small, insignificant decrease in GFR of 4 (-1 to 9) ml x min(-1) x 1.73 m(-2). CONCLUSIONS: Dual blockade of the RAS provides superior short-term renoprotection independent of systemic blood pressure changes in comparison with maximally recommended doses of ACEI in patients with type 2 diabetes as well as nephropathy.     

Osteocalcin and urinary hydroxyproline/creatinine ratio in the differential diagnosis of primary hyperparathyroidism and hypercalcaemia of malignancy

Osteocalcin (serum bone-Gla protein, sBGP), serum alkaline phosphatase (sAP) and urinary hydroxyproline/creatinine ratio (uOH-Prol/creatinine) have been measured in 21 patients with primary hyperparathyroidism (PHPT) and in nine patients with hypercalcaemia of malignancy (HM). A positive linear correlation between sBGP and uOH-Prol/creatinine ratio (y = 0.023 + 0.0025x; r = 0.705; p less than 0.01) and between sBGP and sAP (y = 35.6 + 2.14x; r = 0.430, p less than 0.05), have been observed in the PHPT patients. No correlation was found in the HM patients. PHPT patients have been grouped according to their uOH-Prol/creatinine ratio (group A: uOH-Prol/creatinine greater than 0.034; group B: uOH-Prol/creatinine less than or equal to 0.034). Group A presented sBGP higher than the control group (11.06 +/- 5.7 vs. 4.2 +/- 1.2 ng/ml; p less than 0.001) (mean +/- SD). Group B presented sBGP similar to the control group (4.4 +/- 1.96 ng/ml) (mean +/- SD). Group A presented serum calcium (sCa) higher than group B (3.11 +/- 0.28 vs. 2.78 +/- 0.09 mmol/l; p less than 0.01) (mean +/- SD). In HM patients uOH-Prol/creatinine ratio was elevated as compared with the control group (0.074 +/- 0.036 vs. 0.024 +/- 0.004; p less than 0.001) (mean +/- SD), but sBGP was normal or low (range: indetectable-5.1 ng/ml). The simultaneous estimations of sBGP and uOH-Prol/creatinine ratio improve the differential diagnosis between these two forms of hypercalcaemia: high uOH-Prol/creatinine ratio with concomitant high sBGP point to the presence of PHPT. Elevated uOH-Prol/creatinine ratio with normal or low sBGP suggest the existence of HM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipid peroxidation as a possible mechanism of erythrocyte damage in patients with chronic kidney failure on hemodialysis]

Ten patients with chronic renal failure (CRF) treated by hemodialysis (HD) were examined. All the patients demonstrated remarkable anemia. The red blood cell count was (2.7 +/- 0.2) x 10(12)/I the concentration of hemoglobin 79.5 +/- 5.6 g/l, on the average, hematocrit 23.2 +/- 1.8%. The content of malonic dialdehyde in the patients' red blood cells was far greater than in controls, amounting to 132% (per 1 ml of hemolysate), 134% (per 1 mg of protein) (p < 0.05). Catalase and glutathione peroxidase activity in the patients' red blood cells did not differ from that in controls. Superoxide dismutase activity reduced by 43% as compared to that in donors (p < 0.001). The authors review possible mechanisms of lipid peroxidation (LPO) and a decrease of antioxidant defense in red blood cells of CRF patients on hemodialysis. It is concluded that activation of LPO processes and the decrease of antioxidant defense produce a noticeable destructive effect on the integrity of the red blood cell membrane. They also influence the development of hemolysis.