The effect of vitamin B6 and folate supplements on plasma homocysteine and serum lipids levels in patients on regular hemodialysis.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascular events. The aim of this study was to show the results of the reduction of homocysteine in end stage renal failure patients on hemodialysis, as it is known, have higher levels of homocysteine than other groups of subjects. METHODS: Plasma homocysteine concentration was determined before and after the administration of vitamin B6 and folic acid in 12 patients (males: 6) on regular dialysis therapy. Mean monthly fasting serum concentrations of total cholesterol (TCHOL), HDL-chol, LDL-chol and triglycerides (TRG) were determined for a period 68 months (12-120 months) before and 26 months after the administration of vitamin B6 and folic acid. RESULTS: Mean serum concentrations for folic acid and vitamin B12 before and after the administration were: folic acid: 5.03 +/- 4.9 and 18.0 +/- 19.2 ng/mL, (p < 0.0001) and B12: 456 +/- 257 and 514.38 +/- 307 pg/mL respectively). Plasma homocysteine was reduced significantly after the administration of above drugs (from 47 +/- 14 to 29 +/- 9 micromol/mL, p < 0.001). This reduction of homocysteine resulted in a modification of the patients' lipidemic profile: Serum LDL-chol was decreased significantly (119 +/- 38 mg/dL to 110 +/- 35 mg/dL, p<0.005). TCHOL and TRG were also decreased but not significantly (190 +/- 45 mg/dL to 187 +/- 43 mg/dL and 116 +/- 63 mg/dL to 108 +/- 47 mg/dL respectively)). Serum concentrations HDL-chol were increased significantly (from 42 +/- 10 mg/dL to 47 +/- 10 mg/dL, p < 0.001). The atherogenic index for cholesterol, LDL/HDL, was 1.6 times lower after the drugs receiving (before: LDL/HDL = 3.1 and after: LDL/HDL = 2.5, p < 0.001). CONCLUSIONS: These results indicate that the folate and vitamin B6 supplementation resulted in reduction of homocysteine levels and improvement of lipidemic profile in regular dialysis patients.

Membranous glomerulonephritis: a morphometric study.

Archival material from 45 renal biopsies with a diagnosis of idiopathic membranous glomerulonephritis (MGN) were studied by computer-aided image analysis in order to evaluate the prognostic significance of glomerular and interstitial morphometry in MGN. The control group consisted of thirty seven normal renal biopsy specimens. The surface area, the perimeter, the major axis length and the shape factor of renal glomeruli as well as the percentage of the interstitial fibrosis were measured. All the morphometric parameters related to the size of glomeruli had significantly higher values in the patient group (p = 0.000 for all the parameters). However, no significant difference of the glomerular size between different stages of MGN was observed. In contrast, the percentage of interstitial fibrosis increased as the MGN stage rose (median values: 10.3% in stage 1, 14.2% in stage II, 26.9% in stage III, 28.9% in stage IV and 34.2% in stage V, Kruskal-Wallis ANOVA H = 37.645, p = 0.000). In the multivariate analysis the percentage of interstitial fibrosis was the only independent prognostic factor (p = 0.013). Our findings suggest that, in membraneous glomerulonephritis, the interstitial fibrosis increases as the MGN stage progresses, while the size of renal glomeruli has increased at a very early stage of the disease. This fact may indicate that interstitial fibrosis, not glomerular lesions, is mainly responsible for the reduction of renal function.

Effectiveness and metabolic effects of perindopril and diuretics combination in primary hypertension.

The effectiveness as well as the metabolic effects of the combination of diuretics [hydrochlorothiazide (HCT) vs indapamide (IND)] and perindopril (P) in 14 patients (7 male, 7 female) aged 37-62 years with mild idiopathic hypertension were studied. Following a 4-week wash-out period and a 4-week period of monotherapy with P (4 mg/daily), IND (2.5 mg/daily) or HCT (25 mg/daily) was added for 4 weeks. Selection of the diuretic agent was random. Following a 4-week wash-out period from the diuretic, in which only P was given, the alternative diuretic was administered for another period of 4 weeks. P decreased blood pressure levels significantly. However, the drug was more efficacious in patients with higher plasma renin activity (PRA). Combination treatment induced an additional decrease in the blood pressure levels, mainly in patients with lower PRA. The combination of P + HCT was more effective than the combination P + IND. The addition of either HCT or IND evoked a small but statistically significant increase in serum glucose levels while fasting as well as during the 75 g oral glucose challenge. However, insulin levels did not change significantly during the study. Small but not statistically significant changes in serum electrolytes and lipid parameters were observed during the various phases of the study, while a statistically significant increase in the serum uric acid was noticed when the combination P + HCT was given. We conclude: (1) P in small doses is an effective and safe antihypertensive agent, (2) PRA has a predictive value in determining the effectiveness of P treatment, (3) the combination of P with small doses of HCT or IND is more efficacious than P alone, (4) the combination treatment has adverse effects in the carbohydrate tolerance, while there are not significant changes in serum electrolyte and lipid parameters.

Elevated interleukin-1 beta in the circulation of patients with essential hypertension before any drug therapy: a pilot study.

Immune system disturbances have been implicated in the pathogenesis of essential hypertension. The aim of this study was to determine the levels of the interleukin-1 beta and soluble interleukin-2 receptors in serum samples from 114 hypertensive patients before any drug therapy because there are no well-established data regarding these immunologic mediators in essential hypertension. We found increased levels of interleukin-1 beta in 59.6% of patients, while soluble interleukin-2 receptors were not detected. The interleukin-1 beta levels were significantly higher in patients than in healthy controls (P = 0.0001). We conclude that patients with essential hypertension have high levels of interleukin-1 beta but not indicators of cellular immune activation in their sera. Further studies are in progress in order to confirm, explain and assess the clinical utility of the above findings.

Long-term effects of low molecular weight heparin on lipid parameters in hemodialysis patients.

OBJECTIVE: The long-term effects of the replacement of conventional heparin by low-molecular weight heparin (LMWH) on lipid parameters were examined in a large group of hemodialysis patients. EXPERIMENTAL DESIGN: One-year prospective investigation. SETTING: Renal units. PATIENTS: A total of 93 patients aged 12-63 years old receiving hemodialysis for 51 (1-172) months were studied. None of the patients had primary hyperlipidemia, diabetes mellitus, or other secondary causes of dyslipidemia. INTERVENTIONS: In all patients administration of LMWH was introduced in doses 2500-5000 units. MEASURES: Baseline values of lipoprotein profile prior to the intervention were compared with results obtained after 3, 6 and 12 months of LMWH. RESULTS: During of LMWH treatment a small but statistically significant decrease of total and HDL cholesterol (from 200 +/- 45 mg/dl to 185 +/- 42 mg/dl, p < 0.01, and from 45 +/- 11 mg/dl to 42 +/- 10 mg/dl, p < 0.05, respectively), as well as Apo B (from 128 +/- 36 mg/dl to 121 +/- 35 mg/dl, p < 0.001) was noticed. Moreover, triglycerides decreased significantly (from 175 +/- 73 mg/dl to 146 +/- 62 mg/dl, p < 0.001). The beneficial effects of LMWH were more pronounced in patients with dyslipidemia (total cholesterol > 200 mg/dl, or triglycerides > 200 mg/dl) before the replacement of conventional heparin. CONCLUSION: The long-term use of LMWH instead of conventional heparin for anticoagulation during dialysis has beneficial effects on the lipoprotein profile, especially in patients with dyslipidemia.

The influence of Coenzyme Q10 on total serum calcium concentration in two patients with Kearns-Sayre Syndrome and hypoparathyroidism.

Two patients with Kearns-Sayre Syndrome and hypoparathyroidism were treated with alfacalcidol (1a-OH D3) and total serum calcium concentration remained within normal range for a long period. After two months of combined therapy with Coenzyme Q10 (CoQ10), hypercalcemia was noticed and as a result, 1a-OHD3 was gradually discontinued. Normal total serum calcium concentration was obtained with CoQ10 monotherapy while the replacement of CoQ10 with placebo led to hypocalcemia. The mechanism of action of CoQ10 is difficult to explain. Since the parathormone level remained unchanged during CoQ10 or placebo therapy, we speculate that the capacity of producing an active form of vitamin D in mitochondria of proximal tubules was restored by CoQ10 therapy.

Effect of an acute oral protein load on microalbuminuria in uninephrectomized patients in relation to the time since nephrectomy.

To evaluate the effect of an acute oral protein load (OPL) on urinary albumin excretion (UAE) in uninephrectomized subjects with a negative Albustix test, in relation to the time since nephrectomy, the UAE was determined by a double-antibody 125I radioimmunoassay in 3-hour urine collections before and after 150 g OPL under conditions of moderate physical activity in 18 subjects who underwent unilateral nephrectomy more than 10 years (346.5 +/- 178.60 months) before evaluation and had a mean basal creatinine clearance (CCr) of 45.3 +/- 14 ml/min (group 1), in 21 subjects who underwent unilateral nephrectomy less than 10 years (31.5 +/- 28 months) before evaluation and had a mean basal CCr of 76.0 +/- 22 ml/min (group 2), and in 16 normal volunteers (controls) with a mean basal CCr of 103.1 +/- 12 ml/min. The UAE was higher in group 1 as compared with either group 2 or controls at both basal state (90.8 +/- 65, 19.6 +/- 17, and 11.0 +/- 5 micrograms/min/100 CCr for groups 1 and 2 and controls, respectively; p < 0.001) and after OPL (92.0 +/- 65, 43.6 +/- 24, and 12.0 +/- 5 micrograms/min/100 CCr for groups 1 and 2 and controls, respectively; p < 0.001). However, the increase in UAE following OPL was significant (p < 0.001) only in group 2 patients. In all patients, the basal UAE was negatively correlated with basal CCr (r = 0.63; p < 0.001) and positively correlated with the time since nephrectomy (r = 0.73; p < 0.001) and with both systolic (r = 0.57; p < 0.001) and diastolic blood pressures (r = 0.69; p < 0.001). CCr calculated using 3-hour urine collections increased more in controls (11.2 +/- 44.2%) than in patient groups 1 (1.6 +/- 0.89) and 2 (7.7 +/- 3.7%; p < 0.001). Basal CCr calculated using 24-hour urine collections the day before the test was negatively correlated with the time since nephrectomy in group 1 (r = -0.69; p < 0.001) and positively correlated with the time since nephrectomy in group 2 (r = 0.89; p < 0.001). Multiple regression analysis revealed that the relationship between CCr and duration of uninephric state was independent of age or systolic and diastolic blood pressures in both patient groups. These results suggest that UAE increase significantly after an OPL in subjects who have been nephrectomized less than 10 years before the study and have basal CCr values higher than 50% of normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid abnormalities in chronic uremic patients. Response to treatment with gemfibrozil.

Seventy-four patients with end stage renal failure were studied. Forty-six of them were on hemodialysis (HD) while 28 were on continuous ambulatory peritoneal dialysis (CAPD). In addition 56 nondialysis chronic renal failure (NDCRF) patients with various degree of renal failure were also studied. In all groups serum triglyceride concentrations were significantly higher and HDL cholesterol concentrations were significantly lower compared to age- and sex-matched controls. Total and LDL cholesterol were significantly higher in the NDCRF and CAPD patients compared to controls. In 55 patients (20 on HD, 13 on CAPD and 22 NDCRF) with severe hypertriglyceridemia or diminished HDL cholesterol gemfibrozil 300 mg b.i.d. per os was given for 6 months. Drug treatment reduced significantly serum triglycerides in all groups of patients and increased the levels of HDL cholesterol in CAPD patients. Moreover, a statistically significant decrease of the levels of total and LDL cholesterol was noticed in HD and NDCRF patients. During treatment no significant side effects were observed and liver and muscle enzymes remained within normal values.

Effect of intravenous calcium infusion on indices of activity of the parathyroid glands and on urinary calcium and sodium excretion in normotensive and hypertensive subjects.

The effect of an intravenous calcium gluconate load (10 mg/kg over 5 min) on plasma ionized calcium concentration, parathyroid hormone (PTH), and the rate of urinary excretion of calcium, sodium, and nephrogenous cyclic adenosine monophosphate (NcAMP) was examined in 26 patients with essential hypertension and 27 age- and sex-matched normotensive subjects. Prior to calcium administration hypertensives had lower plasma ionized calcium concentration (P < .01) and higher PTH levels (P < .001) and excreted more calcium (P < .05) and NcAMP (P < .001) in the urine compared to normotensives. Following calcium infusion, plasma ionized calcium did not differ significantly between the two groups, but PTH levels remained higher in the hypertensive subjects at both 60 min (P < .001), and at 120 min (P = .02) post-load. Post-load values for both urinary calcium excretion and urinary sodium excretion were significantly higher in the hypertensive subjects than in the control group. Both before and after calcium infusion, urinary calcium excretion was positively correlated with urinary sodium excretion in each of the two groups, but for the same level of sodium excretion, hypertensives excreted more calcium in the urine, compared to normotensives, both before (P < .05) and after calcium infusion (P < .001). A positive correlation between basal plasma renin activity (PRA) values and plasma ionized calcium values obtained before (r = 0.42, P = .03) or at 60 min (r = 0.41, P = .03) and 120 min (r = 0.42, P = .03) after calcium infusion existed only in the hypertensive subject group. Post-load urinary sodium excretion values were negatively correlated to basal PRA values in both groups (r = -0.55, P < .01 and r = -0.58, P < .01 for hypertensives and normotensives, respectively), but a similar negative correlation between post-load urinary calcium excretion values and basal PRA values existed only in the hypertensive subject group (r = -0.50, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Urine calcium excretion, nephrogenous cyclic-adenosine monophosphate and serum parathyroid hormone levels in patients with essential hypertension.

To evaluate the role of calcium and the parathyroid gland in the pathophysiology of essential hypertension, creatinine clearance, urinary excretion of sodium, calcium and nephrogenous cyclic adenosine monophosphate (NcAMP) and serum parathyroid hormone (PTH) levels were measured in 25 newly diagnosed essentially hypertensive patients before institution of any treatment and in 25 age- and sex-matched normal volunteers. While no significant differences in creatinine clearance, serum total calcium levels or 24-hour sodium excretion existed between the two groups, hypertensives had a higher mean (+/- SD) 24-hour calcium excretion rate (199.0 +/- 44.7 vs. 152.8 +/- 33.6 mg, p less than 0.001), a higher mean NcAMP excretion rate (2.54 +/- 0.8 vs. 1.87 +/- 0.5 nmol/100 ml glomerular filtrate, p less than 0.001) and a higher mean serum PTH concentration (1.87 +/- 0.6 vs. 1.53 +/- 0.4 ng/ml, p less than 0.001) than the normotensives. A significant positive correlation existed between calcium and sodium excretion in both hypertensives (r = 0.66, p less than 0.001)) and normotensives (r = 0.67, p less than 0.001), but given the same levels of creatinine clearance and sodium excretion, hypertensives excreted more calcium than normotensives (p less than 0.001)). In both hypertensives and normotensives, serum PTH levels were positively correlated with NcAMP excretion (r = 0.42, p less than 0.05, and r = 0.41, p less than 0.05, respectively) and the ratio of urinary sodium to urinary calcium excretion (r = 0.59, p less than 0.001, and r = 0.75, p less than 0.001), respectively). The above results suggest that in essential hypertension, increased activity of parathyroid glands may occur as a consequence of increased urinary calcium losses which are presumably due to an intrinsic defect in renal calcium handling.

Vasopressin in end-stage renal disease: relationship to salt, catecholamines and renin activity.

The blood pressure changes and behavior of vasoactive hormones after various stimuli were studied in eighteen patients with end-stage renal disease maintained on chronic hemodialysis. Group A patients (n = 9) were not subject to intra- or post-dialysis hypotensive episodes, and Group B (n = 9) frequently had such episodes. A 500 ml hypertonic saline infusion produced no change in blood pressure in either group, despite significant rise of vasopressin levels in both. Plasma renin activity levels were similar and became appropriately suppressed by the infusion in both groups, whereas norepinephrine rose significantly only in Group A, but not Group B where it was already higher at baseline. The regular dialysis session produced, as expected, a significantly more profound hypotensive effect in Group B, but was accompanied in both groups by decrease in vasopressin and increase in plasma renin activity. Norepinephrine change differed in the two groups: it decreased in Group A as expected from its capacity to be dialyzed, but rose in several hypotensive patients in Group B, indicating appropriate response to baroreceptor stimulation and leading to an unchanged average. These findings suggest that dialysis-induced hypotensive episodes are not necessarily associated with autonomic neuropathy or with abnormal patterns of vasopressor hormone response to stimuli. They also shed new light on the factors regulating vasopressin secretion under these circumstances, since they indicate that the osmoreceptor and/or sodium-sensitive receptor may be a more dominant mechanism in the regulation of vasopressin release than the volumetric mechanism responding to fluid volume changes.