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Biomedical subjects

J Vlachojannis

Publications and source records attributed to J Vlachojannis.

13 recordsLinked to original sources

Increased renal excretion of endothelin-1 in nephrotic patients.

BACKGROUND: Renal function is influenced by direct and indirect action of endothelins. They reduce renal blood flow and glomerular filtration. The aim of the present study was to determine plasma and urinary endothelin-1 (ET-1) in two major categories of renal patients and to compare them with normal subjects. METHODS: Endothelin-1 was measured in the plasma and urine of patients with chronic renal disease and reduced glomerular filtration rate (GFR), and in patients with proteinuria due to glomerular dysfunction with unaffected GFR. A group of healthy subjects was used as a reference. RESULTS: Plasma endothelin-1 was increased in all patients to 60 +/- 13 pg/ml independent of GFR compared to 29 +/- 5 pg/ml in normal subjects (P < 0.001). The endothelin-1 load was decreased to 1190 +/- 450 pg/ml/1.73 m2 in patients with reduced GFR, compared to 2780 +/- 690 pg/ml/1.73 m2 of normal subjects, whereas in patients with glomerular damage and normal GFR, it was increased to 5480 +/- 1910 pg/ml/1.73 m2 (P < 0.01). ET-1 was found to be excreted and reabsorbed by the renal tubules by the same mechanisms as sodium and potassium, because its secretion fraction changes in parallel to those of the above ions. The excreted endothelin increased to 730 +/- 420 and 710 +/- 250 pg/ml/1.73 m2 (P < 0.01) in the two categories of patients respectively, compared to 290 +/- 100 pg/ml/1.73 m2 in the normal group. The excretion fraction of patients with normal GFR was similar to normal subjects, while it appeared to increase in patients with reduced GFR (P < 0.01). CONCLUSIONS: In the development of renal disease the plasma endothelin concentration is independent of the renal filtration capability and endothelin may be involved in functional and anatomical changes of the kidney as a causal factor or resulting from the renal disease.

Adult

Increased endothelin-1 content in the platelets of hemodialysed patients.

Patients undergoing hemodialysis, present platelets (PLTs) with physiological dysfunction. Aggregated PLTs stimulate endothelin-1 (ET-1) secretion from endothelial cells. In turn, ET-1 abolishes PLT aggregation. The aim of this study was to determine any presence of ET-1 in the PLTs of hemodialysed patients and to compare its levels with normal subjects. Platelets, isolated from hemodialysed patients, revealed lower aggregation (76 +/- 13%) compared with healthy subjects (96 +/- 2%). Plasma ET-1 was increased in hemodialysed patients 23.5 +/- 3.2 fmol/ml, vs. 10.9 +/- 1.6 fmol/ml in normal subjects. Immunoreactive endothelin-1 was detected in the platelets of both groups. The intraplatelet ET-1 of hemodialysed patients was 13.8 +/- 3.1 fmol/mg protein, vs. 7.9 +/- 1.3 fmol/mg protein in normal individuals. Total RNA was isolated from platelets and reverse transcriptase-mediated polymerase chain reaction (RT-PCR) revealed no presence of the preproET-1 mRNA in either normal or hemodialysed platelets. This suggests that ET-1 is internalized from the plasma. In summary, platelets contain but do not express ET-1. The increased levels of ET-1 in the platelets of the hemodialysed patients may be partly responsible for their lower aggregation.

Adult

Differences in calcium kinetic pattern between CAPD and HD patients.

To assess the effect of different dialysis modalities on calcium turnover, we studied 57 patients on maintenance hemodialysis treatment (HD) and 38 patients on continuous ambulatory peritoneal dialysis (CAPD) with tracer kinetic studies using two calcium isotopes (45Ca by mouth and 47Ca intravenously). The two groups were comparable in age, sex and prevalence of diabetes. The groups did not differ in their serum concentrations of intact parathyroid hormone (iPTH), calcium, inorganic phosphate and 1,25-dihydroxyvitamin D. 25-hydroxy-vitamin D and alkaline phosphatase were found to be significantly higher in HD patients. Despite these similarities, CAPD patients showed a significantly lower calcium kinetic response as measured by calcium retention and plasma calcium efflux than HD patients. Mean calcium retention was 39.5% in HD patients compared to 31.2% in the CAPD group (p < 0.05). Plasma calcium efflux was significantly lower in the CAPD group (2.7 vs 3.2 respectively; p < 0.01). iPTH correlated with calcium retention and plasma calcium efflux in HD patients (r = 0.69 and r = 0.67 respectively). In CAPD patients, the correlation coefficient between iPTH and calcium retention was markedly lower (r = 0.54), whereas no correlation was found between iPTH and plasma calcium efflux (r = 0.08). In addition, the slope of the correlation curve were higher in HD patients (p < 0.01 and p < 0.001, respectively), indicating a better response of this patient group to the action of parathyroid hormone. Our data are in accordance with recently published results showing that the dialysis modality has a major impact on bone turnover and on the progression of uremic bone disease. It has been shown that CAPD is an independent risk factor for the development of the adynamic form of renal bone disease. This finding may be explained by the lower response of calcium turnover to the action of PTH as shown here with tracer kinetic studies.

Adult

Evidence for abnormal calcium homeostasis in patients with adynamic bone disease.

To investigate whether the derangements in calcium kinetics in patients with renal osteodystrophy are similar in the various histologic forms of this metabolic bone disease, 43 patients on chronic maintenance dialysis underwent calcium kinetic studies using the double isotope technique, iliac crest bone biopsies for mineralized bone histology and histomorphometry and determinations of serum indices of calcium and bone metabolism. Intestinal calcium absorption was not different among the three histologic groups. However, women exhibited lower calcium absorption in each histologic form (P < 0.01). Patients with predominant hyperparathyroid bone disease showed plasma calcium efflux, calcium accretion rate and calcium retention markedly above normal values. Patients with low turnover bone disease exhibited a normal or slightly decreased plasma calcium efflux and calcium accretion rate together with a disproportionately low calcium retention. Patients with mixed uremic osteodystrophy presented with a calcium kinetic profile intermediary to the two other forms. Good relationships existed between plasma calcium efflux, calcium accretion rate, calcium retention and histomorphometric parameters of bone turnover as well as serum levels of parathyroid hormone. However, no serum parameter could indicate with certainty the underlying bone disease. These findings demonstrate that adynamic bone disease does not merely represent an academic finding but is characterized by a very low bone capacity to buffer calcium and inability to handle an extra calcium load. This is particularly relevant for the daily care of end-stage renal failure patients presently receiving higher than ever amounts of vitamin D and calcium salts.

Adolescent

Decrease in peritonitis rate by integrated disconnect system in patients on continuous ambulatory peritoneal dialysis.

The prevention of peritonitis is of major concern for successful long-term continuous ambulatory peritoneal dialysis (CAPD) treatment. The effect of a Y-system on peritonitis incidence and patient morbidity was observed in a comparative, retrospective single-center analysis over a period of 5 years. The integrated disconnect system prolonged the peritonitis-free period from 1:11 patient-months, observed with the conventional system, to greater than 1:50 patient-months. The rate of hospitalization was reduced by 45%.

Humans

Effect of recombinant human erythropoietin on iron balance in maintenance hemodialysis: theoretical considerations, clinical experience and consequences.

Iron deficiency is the main reason for insufficient response to rEPO therapy. Serum ferritin and transferrin saturation give valuable information on storage iron and iron transport. Iron demand for correction of anemia can easily be estimated after HCT (vol%) x average blood volume (dl) = mg iron. Inadequate iron supply of the bone marrow in the presence of sufficient storage iron in the RES develops frequently under rEPO, possibly explaining the improvement of bone marrow response to rEPO by concomitant intravenous iron supply. The reasons of functional iron deficiency are still speculative.

Anemia

CAPD in elderly patients with cardiovascular risk factors.

Twenty-nine elderly patients (greater than 70 years) on CAPD treatment were compared with 30 younger patients (less than 55 years). Biochemical parameters did not differ between the two groups, apart from blood sugar which was higher in the older patient group. Ultrafiltration rates were almost identical. CAPD-specific complications also did not differ in the two patient groups. Arterial hypertension was well-controlled on CAPD and the proportion of patients requiring antihypertensives fell significantly. 8% of the old patients and 52% of the young patients required antihypertensive medication after 12 months of therapy compared to 38% and 81% before commencement of CAPD. Improvement of hemodynamic parameters was especially pronounced in older patients, who had cardiac risk factors in a high percentage of cases. Age and cardiac risk factors had the highest impact on the outcome, thus explaining the higher mortality in the older patient group. Older patients with renal insufficiency can be treated with CAPD leading to equally good results as those documented for younger patients.

Actuarial Analysis

Factors influencing transperitoneal calcium balance during CAPD.

A dialysate containing a calcium concentration of 1.75 mmol/L has been the standard in CAPD for a long time. This concentration was chosen to achieve a positive calcium balance to suppress hyperparathyroidism. In the measurement of peritoneal calcium mass transfer, conflicting results have been published, with positive and negative calcium balances reported. These differences have been explained by differences in the filtration rate, and a negative correlation between the filtration rate and the peritoneal calcium mass transfer can be found. Whereas nearly all patients in this study had a negative calcium balance using a glucose solution of 3.86%, a wide variation was found for the 1.36% glucose solution. There were several patients who had a positive calcium balance despite a positive filtration rate. The explanation for this finding lay in differences in serum concentrations of calcium, and especially differences in the size of the total exchangeable calcium pool that contains the plasma calcium compartment. A negative correlation between peritoneal calcium balance and the size of the total exchangeable calcium pool could be demonstrated. This finding may explain the differences in the peritoneal calcium flux reported in the literature. As an enlargement of the exchangeable calcium pool correlates with the progression of vascular calcification, therapeutic efforts should be directed toward prevention of an enlargement of this pool.

Adult

In vivo rheologic effects of lipid apheresis techniques: comparison of dextran sulfate LDL adsorption and heparin induced LDL precipitation.

The effects of two different LDL apheresis techniques, heparin-induced LDL precipitation (HELP) and dextran sulfate LDL adsorption (DSA), were compared in six patients with familial hypercholesterolemia. Total and LDL cholesterol were effectively lowered with both techniques. The reduction of serum triglycerides was more pronounced with DSA, whereas the reduction of HDL cholesterol was more pronounced with HELP. Single sessions using both techniques immediately reduced whole blood and plasma viscosity, as well as erythrocyte aggregation. Serum fibrinogen decreased by 62% (HELP) and 11% (DSA). Maintenance lipid apheresis administered 1 time per week resulted in a sustained reduction of total and LDL cholesterol and was associated with a sustained improvement in blood flow properties. Data suggest that besides serum fibrinogen, serum lipoproteins may adversely effect the rheologic characteristics of blood.

Adsorption

Altered pattern of calcium kinetics in hemodialysis patients after parathyroidectomy.

Six HD patients with severe secondary hyperparathyroidism (sHPT) underwent studies of calcium kinetics prior to and after parathyroidectomy (PTX) with autotransplantation. Postoperatively, patients received vitamin D and calcium supplementation. Before PTX, a markedly elevated bone turnover was found, with increased fluxes of calcium from plasma into the exchangeable calcium pool. This pool was three times larger than normal, indicating a high risk of extraosseous calcifications. Despite a marked fall in parathyroid hormone (iPTH) levels after PTX, bone cell activity was maintained, as indicated by elevated values for Ca retention. Although Ca efflux from plasma into other compartments of the exchangeable pools remained above normal, the size of the total exchangeable calcium pool markedly decreased after PTX, indicating that PTX with autotransplantation, followed by vitamin D therapy, can normalize bone turnover and shift the balance of calcium flux towards mineralized bone. Reduction in the exchangeable calcium pool may explain the clinical finding that extraosseous calcifications regress in some patients after PTX.

Adult

Calcium kinetic studies in patients on CAPD: improvement of secondary hyperparathyroidism without concomitant improvement of calcium turnover.

OBJECTIVE: An association between the development of low turnover osteopathy and the form of dialysis treatment, that is, continuous ambulatory peritoneal dialysis (CAPD), has been described. To examine the effect of a year-long CAPD treatment on calcium (Ca) turnover, 12 patients were studied prior to and one year after initiation of CAPD treatment with a dialysate calcium of 1.75 mmol/L. DESIGN: A prospective analysis. SETTING: Academic teaching hospital dialysis unit. PATIENTS: Twelve patients with an average age of 54.8 years (range: 23-76 years) at commencement of dialysis and after 13 months of CAPD treatment. MEASUREMENTS: Calcium kinetic studies were performed using two calcium isotopes: 45Ca as an oral tracer and 47Ca as an intravenous tracer. Measurements of plasma and whole body activities were performed over a four-week period. From these measurements, kinetic parameters describing calcium turnover in different compartments were studied. These measurements were repeated after a mean time of 13.4 months. Patients were not treated with vitamin D, but received aluminum- and calcium-containing phosphate binders, in order to keep inorganic phosphate below 2.0 mmol/L and calcium within the normal range. RESULTS: After one year on CAPD, serum levels of calcium increased from 2.2 mmol/L to 2.35 mmol/L. Inorganic phosphate also increased from 1.4 mmol/L to 1.9 mmol/L, despite increased use of oral phosphate binders. Serum levels of intact parathyroid hormone (IPTH) decreased from 51.2 pmol/L to 28.3 pmol/L. Alkaline phosphatase did not change, nor did serum levels of vitamin D. Despite improvement of serum IPTH levels and better control of serum calcium, the kinetic parameters describing calcium turnover in the different calcium pools did not improve. In addition, the calcium retention of bone remained below normal range and did not rise. Perhaps more importantly, the relationship between Ca efflux and Ca retention did not change. While Ca retention remained low, plasma Ca efflux was normal. This imbalance was seen at the beginning of CAPD and did not change under CAPD. CONCLUSION: These data demonstrate that, after one year of CAPD treatment without vitamin D treatment, calcium turnover did not improve, despite a significant fall in serum IPTH levels. Studies on a larger number of patients are warranted to verify these results.

Adult