Parameters influencing blood erythropoietin levels of renal transplant recipients during the early post-transplantation period.

AIM: Renal transplantation is accompanied by restoration of renal function and endogenous erythropoietin production. The purpose of this study was to investigate the time-related changes of endogenous erythropoietin secretion in the early renal post-transplant period and the influence of various parameters to this process. METHODS: Fifty-eight patients were enrolled in the study and followed up for 3 months after successful renal transplantation. Erythropoietin levels were measured at regular intervals and correlated with renal function, cold ischemia time and immunosuppressive regimen used. RESULTS: Two peaks of serum erythropoietin levels were observed: an early peak that occurred within two days after transplantation and a late one, between weeks 2 and 4, which resulted in increased blood hemoglobin levels. Factors that were found to correlate with erythropoietin levels were delayed graft function, cyclosporine use and prolonged cold ischemia time. Serum creatinine did not correlate to erythropoietin levels although the reduction of serum creatinine preceded the rise of erythropoietin levels. Normal hemoglobin values were restored about three months after successful renal transplantation. CONCLUSION: Serum erythropoietin levels increase during the early post-transplantation period resulting in correction of anemia three months after a successful renal transplantation. Restoration of allograft function is a prerequisite for erythropoietin secretion, while cold ischemia time and immunosuppressive regimen affect graft function.

Paramedian vertical palatal bone height for mini-implant insertion: a systematic review.

Paramedian insertion of orthodontic mini-implants is increasingly used to anchor molar distalizers. The aim of this review was to systematically examine the available measurements of vertical palatal bone height (VBH). PUBMED, MEDLINE and the Cochrane Controlled Trials Register were searched using specific search terms. Hand searches of bibliographies of articles were also performed to identify studies measuring VBH or bone thickness in the human palate. Sixteen studies were included, arising from 19 published articles. Repeat presentations were excluded. Ten of the 11 computed tomogram (CT)-based studies presented data from 956 orthodontic patients on average VBH and its variation at a range of palatal sites. Individual data were not available, and pooling of data was not feasible because of heterogeneity of subjects, different measurement sites, different CT methods and their associated software. The compilation of data did indicate that the region 3-4mm behind the incisive foramen and 3-9mm lateral to the midpalatal suture should normally provide sufficient VBH to anchor molar distalizers. The risks of unwanted effects during distalization should be small, but the limitations listed above and the small numbers of studies available impair the precision of the estimates and do not allow the results to be generalized. Paramedian anchorage in the anterior palate can be recommended for molar distalization but, given the great inter-individual variability of the palatal bone height, it must be preceded by reliable CT-based imaging in patients identified by routine investigations as being at risk.

Ezetimibe is effective in the treatment of persistent hyperlipidemia of renal allograft recipients.

INTRODUCTION: Ezetimibe is a hypolipidemic agent acting via inhibition of cholesterol absorption from the small intestine. The effectiveness and safety of long-term administration of ezetimibe was evaluated in renal allograft recipients with persistent hyperlipidemia. PATIENTS AND METHODS: 67 renal allograft recipients with post-transplantation hyperlipidemia resistant to statins were included in the study; 11 were treated with ezetimibe (10 mg/day) alone and 56 with ezetimibe and statin. The effectiveness of ezetimibe was assessed by determination of total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C) and triglycerides (TR). Its safety was determined by liver enzymes (ALT, AST), LDH, CPK, serum creatinine and blood levels of immunosuppressive drugs (cyclosporine, tacrolimus, everolimus, sirolimus) over the follow-up period of 18±6 months. RESULTS: A significant reduction of TC and LDL-C blood levels by 25% and 34% respectively, was observed during the first month of treatment with ezetimibe (p<0.001). This reduction was maintained for the whole period of ezetimibe administration. Renal function remained stable over the follow-up period, while no changes of the blood levels of immunosuppressive drugs were observed. Liver enzymes, LDH and CPK remained normal in all patients except for one diabetic patient who developed rhabdomyolysis. Apart from gastrointestinal symptoms in 2 patients, no other side effects were observed. CONCLUSION: Combination of ezetimibe with statins represents an effective and safe regimen for treatment of persistent hyperlipidemia in renal allograft recipients.

Willow species and aspirin: different mechanism of actions.

Many believe that willow is the natural source of aspirin. However, willow species contain only a low quantity of the prodrug salicin which is metabolized during absorption into various salicylate derivatives. If calculated as salicylic acid, the daily salicin dose is insufficient to produce analgesia. Salicylic acid concentrations following an analgesic dose of aspirin are an order of magnitude higher. Flavonoids and polyphenols contribute to the potent willow bark analgesic and anti-inflammatory effect. The multi-component active principle of willow bark provides a broader mechanism of action than aspirin and is devoid of serious adverse events. In contrast to synthetic aspirin, willow bark does not damage the gastrointestinal mucosa. An extract dose with 240 mg salicin had no major impact on blood clotting. In patients with known aspirin allergy willow bark products are contraindicated.

A systematic review on the sambuci fructus effect and efficacy profiles.

The berries of European elder are used in traditional German medicine for various complaints. Due to insufficient research data, elderberry fruit was not monographed by the German Commission E at the end of the last century. A comprehensive review of the literature was conducted to summarize the pharmacological and clinical effects of elderberry fruit. Several databases and other sources were searched to identify in vitro and animal studies, and clinical trials investigating elderberry fruit preparations. For the latter, the level of evidence was evaluated as described previously. Elderberry fruit preparations may provide antioxidant, antiviral and antiproliferative effects in vitro. One animal experiment and one clinical trial were able to back the antioxidative impact in terms of a weak antilipidemic effect. Antibacterial and antiinflammatory effects seem possible, but need further support. In rats, an aqueous elderberry fruit extract produced central depression and analgesia and an ethanol fruit extract improved acetic acid-induced colitis. Several in vitro studies together with two exploratory studies in humans and one open study in chimpanzees indicate that the aqueous elderberry extract Sambucol may be useful for the treatment of viral influenza infections. These promising effects of elderberry fruit preparations from experimental and clinical studies should be backed by more rigorous studies before these preparations are recommended in the prevention of diseases and in treatment schedules.

Medicinal use of potato-derived products: a systematic review.

In the traditional medicine of Europe, raw potatoes are used for gastrointestinal disorders, and topical potato preparations as a hot pack for pain or for softening furuncles. The aim of this study was to review the literature and summarize the data on the medicinal use of potato-derived products. Several databases and other sources were searched to identify clinical trials investigating potato-derived preparations. The trials were analysed for quality. Five trials were identified; two open uncontrolled studies, two open controlled studies and one double-blind study. These results stimulate further investigation of oral potato juice concentrate in patients with dyspeptic complaints, of potato proteinase inhibitor II for weight reduction, and of topical potato proteins for preventing protease-induced perianal dermatitis. We recommend that future studies have a confirmatory design.

A systematic review on the effectiveness of willow bark for musculoskeletal pain.

Since ancient times preparations from Salix species have been used to alleviate pain. The aim of this study was to update the evidence of the effectiveness of willow bark products in the treatment of musculoskeletal pain. OVID(MEDLINE), PUBMED, Silverplatter, and CENTRAL and manual searches were used to identify clinical trials investigating Salix preparations. Authors SC and JEV extracted the data independently and discussed disagreements. Seven manuscripts were identified, reporting four trials with confirmatory and four with exploratory study designs. Three manuscripts presented the same trial data: repetitious reports were excluded. One confirmatory and two exploratory studies indicate a dose-dependent analgesic effect not inferior to rofecoxib in patients with low back pain. In one exploratory and one confirmatory study conflicting results were achieved in participants with osteoarthritis. No significant effect was seen in a confirmatory study in patients with rheumatoid arthritis, but this study was grossly underpowered. All studies investigated ethanolic extracts with daily doses up to 240 mg salicin over periods of up to six weeks. Minor adverse events occurred during treatment. The review provides moderate evidence of effectiveness for the use of ethanolic willow bark extract in low back pain. Further studies are required to find out if treatment of osteoarthritis and rheumatoid arthritis requires extract with higher doses than 240 mg salicin per day.

Microchimerism in peripheral blood and urine in renal transplant recipients: preliminary results.

The role of microchimerism in peripheral blood and urine of renal transplant recipients remains a matter of debate, depending on the sensitivity of the methods used for detection. We studied 17 female renal transplant recipients who had received renal allografts from male donors. Polymerase chain reaction (PCR) was applied to blood and urine for the microsatellite markers D1S80, DYZ1, TH01, and kalphai SE33. Detection of DYZ1 that is present only on the Y chromosome was considered proof for microchimerism. No microchimerism was detected in peripheral blood, whereas it could be detected in the urine of 8/17 (48%) patients. There were no differences between patients with and without microchimerism regarding patient age, dialysis vintage, immunosuppression, time post-transplantation, and allograft function as measured using serum creatinine, creatinine clearance, and proteinuria. Two patients in each group showed chronic allograft dysfunction. These findings raise questions regarding the role of microchimerism in renal transplantation.

Systematic review on the safety of Harpagophytum preparations for osteoarthritic and low back pain.

Harpagophytum products are a treatment option for osteoarthritic and low back pain. The aim of this study was to review the safety of treatment with Harpagophytum procumbens. The databases OVID(MEDLINE), PUBMED and COCHRANE COLLABORATION LIBRARY were searched back to 1985 for studies with Harpagophytum procumbens. Twenty-eight clinical trials were identified of which 20 stated adverse events. In none of the double-blind studies was the incidence of adverse events during treatment with Harpagophytum procumbens higher than during placebo treatment. Minor adverse events occurred in around 3% of the patients, mainly gastrointestinal adverse events. A few reports of acute toxicity were found but there were no reports on chronic toxicity. Since the dosage used in most of the studies is at the lower limit and since long-term treatment with Harpagophytum products is advisable, more safety data are urgently needed.

Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis.

UNLABELLED: The aim of this study was to evaluate the prevalence of vitamin D deficiency in chronic renal failure (CRF) patients on peritoneal dialysis (PD) and to correlate the findings with various demographic and renal osteodystrophy markers. METHOD: This cross-sectional, multicenter study was carried out in 273 PD patients with a mean age of 61.7 +/- 10.9 years and mean duration of PD 3.3 +/- 2.2 years. It included 123 female and 150 male patients from 20 centers in Greece and Turkey, countries that are on the same latitude, namely, 36-42 degrees north. We measured 25(OH)D3 and 1.25(OH)2D3 levels and some other clinical and laboratory indices of bone mineral metabolism. RESULTS: Of these 273 patients 92% (251 patients) had vitamin D deficiency i.e. serum 25(OH)D3 levels less than 15 ng/ml, 119 (43.6%) had severe vitamin D deficiency i.e., serum 25(OH)D3 levels, less than 5 ng/ml, 132 (48.4%) had moderate vitamin D deficiency i.e., serum 25(OH)D3 levels, 5-15 ng/ml, 12 (4.4%) vitamin D insufficiency i.e., serum 25(OH)D3 levels 15 - 30 ng/ml and only 10 (3.6%) had adequate vitamin D stores. We found no correlation between 25(OH)D3 levels and PTH, serum albumin, bone alkaline phosphatase, P, and Ca x P. In multiple regression analyses, the independent predictors of 25(OH)D3 were age, presence of diabetes (DM-CRF), levels of serum calcium and serum 1.25(OH)2D3. CONCLUSION: We found a high prevalence (92%) of vitamin D deficiency in these 273 PD patients, nearly one half of whom had severe vitamin D deficiency. Vitamin D deficiency is more common in DM-CRF patients than in non-DM-CRF patients. Our findings suggest that these patients should be considered for vitamin D supplementation.

The remission of nephrotic syndrome with cyclosporin treatment does not attenuate the progression of idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults, is usually treated by combination of corticosteroids with cytotoxic drugs. In cases resistant to this regimen, the use of cyclosporin A (CsA) is followed by frequent remissions of the nephrotic syndrome. AIM: The purpose of this study was to estimate the effectiveness of prednisolone and small doses of CsA as first-line treatment of nephrotic patients with IMN, in relation to the progression of the disease, based on functional and histological changes. PATIENTS AND METHODS: Sixteen patients, with nephrotic syndrome due to IMN and well-preserved renal function, were treated with prednisolone (starting dose: 0.5 mg/kg bw/day) and CsA (starting dose: 3 mg/kg bw/day) for 24 months. A repeat renal biopsy was performed after 18 months of treatment in 10 patients with remission of nephrotic syndrome, to estimate the activity of the disease and to identify any features of CsA toxicity. RESULTS: Remission of the nephrotic syndrome was observed in 14 out of 16 patients after 5 +/- 2 months of treatment. Complete remission was observed in 8 and partial remission in 6 patients (urinary protein was reduced from 6.9 +/- 3.4-0.2 +/- 0.06 g/24 h and 1.2 +/- 1.0 g/24 h, respectively, p < 0.01). The renal function was well preserved in 13 out of 16 patients over a 24-month period of treatment. Deterioration of renal function was observed in 3 patients (creatinine clearance reduced from 86 +/- 21-37 +/- 17 ml/min, p < 0.05) who had either persistent nephrotic syndrome or frequent relapses. Relapses of the nephrotic syndrome were observed in 5 of 14 patients. Repeat renal biopsies showed that glomerular sclerosis, tubulointerstitial injury, vascular hyalinosis and stage of the disease were deteriorated in most patients. Isometric vacuolization of tubular epithelial cells was observed in 2 of 10 patients. CONCLUSION: IMN nephrotic patients treated with prednisolone and low doses of cyclosporin A showed a high remission rate of nephrotic syndrome. However, progression of chronic histological lesions was found in repeat renal biopsies. This suggests that cyclosporin can frequently induce remission of nephrotic syndrome in IMN patients, but even low doses of the drug are not free of potential renal toxicity.

Endothelin-1 in the kidney and urine of patients with glomerular disease and proteinuria.

BACKGROUND: Endothelin-1 (ET-1) is a strong vasoconstrictive peptide that is involved in the pathogenesis of arterial hypertension. There is increasing evidence, based on studies in experimental animals, that endothelin-1 is produced by tubular epithelial cells in response to activation by filtered protein and is involved in the development of renal scarring. The aim of this study is to examine the distribution of ET-1 in the renal tissue of patients with heavy proteinuria and to estimate the changes in its urinary excretion after immunosuppressive therapy. PATIENTS AND METHODS: Twenty-four patients with severe proteinuria (7.5 +/- 6.5 g/24 h) due to different types of glomerular disease and normal renal function (creatinine clearance 91 +/- 14 ml/ min) were investigated. All patients underwent a renal biopsy and commenced on immunosuppressive therapy with corticosteroids and cyclosporin A. The localization of ET-1 in the renal tissue was examined by immunohistochemistry and compared to control renal tissue from 9 patients who underwent nephrectomies because of hypernephroma. In patients with proteinuria, endothelin-1 excretion in the urine at diagnosis was determined by radioimmunoassay and compared to that of 14 healthy subjects. A second measurement of urinary ET-1 excretion was performed after remission of proteinuria or 6 months after the initiation of treatment in patients with persistent nephrotic syndrome. RESULTS: ET-1 in renal tissue of patients and controls was localized within the cytoplasm of endothelial cells. In nephrotic patients, it was also localized within the cytoplasm of tubular epithelial cells. Urinary ET-1 levels were higher in nephrotic patients compared to healthy subjects (746 +/- 180 ng/24 h vs 410 +/- 112 ng/ml, p < 0.001). In 17 of 24 patients who showed remission of proteinuria with immunosuppressive therapy, the urinary ET-1 levels decreased (from 803 +/- 168 ng/24 h to 511 +/- 80 ng/24 h, p < 0.001) whereas in 7 patients with persistent proteinuria, urinary ET-1 excretion remained elevated. CONCLUSIONS: The increased urinary excretion of ET-1 in patients with severe proteinuria followed by a significant decrease after remission ofproteinuria with immunosuppressive treatment, along with its expression within tubular epithelial cells, suggests a possible relationship between proteinuria and renal ET-1 production.

Transforming growth factor-beta(1) and myofibroblasts: a potential pathway towards renal scarring in human glomerular disease.

BACKGROUND/AIMS: The cellular and humoral factors involved in the development and progression of renal scarring have not been fully investigated. Transforming growth factor-beta (TGF-beta(1)) is considered to be the main fibrogenic growth factor and it is implicated in the pathogenesis of renal fibrosis in experimental and clinical nephropathies. On the other hand, collagen III is an important component of the extracellular matrix. In this study we attempted to identify any possible links between TGF-beta(1) and collagen III synthesis and expression with the expression of myofibroblasts in the evolution of renal scarring in human glomerular diseases. METHODS: We studied retrospectively 40 patients with various types of primary and secondary glomerulonephritis (GN), with either proliferative or nonproliferative pattern, with emphasis on the renal synthesis of TGF-beta(1) and collagen III (detected by in situ hybridization) and their expression (detected by immunohistochemistry) as well as myofibroblast expression. The possible links of TGF-beta(1) expression with myofibroblast distribution (alpha-smooth muscle actin, alpha-SMA(+) cells) and with conventional histopathology and renal function was also examined. RESULTS: TGF-beta(1) protein and mRNA were detected in the renal tubular epithelial cells and interstitium and to a lesser extent within glomeruli of patients with GN. Collagen III was mainly detected in the interstitium (peritubular and periglomerular areas) and to a lesser extent in the glomeruli. Messenger RNA for collagen III followed a similar peritubular and periglomerular distribution to that of TGF-beta(1) and alpha-SMA(+) interstitial cells. The intensity of interstitial TGF-beta(1) protein expression was significantly related to the degree of interstitial fibrosis (r = 0.628, p < 0.01), tubular atrophy (r = 0.612, p < 0.01), interstitial collagen III expression (r = 0.478, p < 0.05), and serum creatinine values (r = 0.722, p < 0.001). Also there was a close positive correlation between the severity of interstitial myofibroblast expression and interstitial TGF-beta(1) (r = 0.412, p < 0.05), as well as collagen III (r = 0.409, p < 0.05). In addition, a significant correlation was found between glomerular TGF-beta(1) expression and severity of glomerulosclerosis (r = 0.620, p < 0.01). CONCLUSION: The results of this study suggest that TGF-beta(1) plays an important role in the pathogenesis of fibrosis developing in human kidney, during the evolution of glomerular disease. Interstitial myofibroblasts may contribute to interstitial fibrosis through the synthesis and release of both TGF-beta1 and collagen III.

Polymorphonuclear leukocyte rigidity is defective in patients with chronic renal failure.

BACKGROUND: The purpose of the study was to investigate the rigidity of polymorphonuclear leukocytes (PMNs) in non-dialysed chronic renal failure (CRF) and haemodialysis (HD) patients. METHODS: PMN rigidity as well as tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) plasma levels were assessed in 10 early-stage CRF, 10 late-stage non-HD, and 10 HD patients, before and during dialysis. In HD patients both cellulose acetate and polysulphone membranes were used. Ten healthy subjects served as controls. Rigidity was tested by counting the deformability in morphologically passive PMNs by the micropipette method. Cytokine levels were measured by enzyme-linked immunosorbent assay. RESULTS: PMN rigidity was significantly increased in end-stage CRF patients regardless of HD but not in early-stage CRF. In HD patients PMN rigidity increased significantly 60 min after initiation of HD. There was an increase of TNF-alpha and IL-1beta levels in end-stage non-HD and HD patients and a further increase at 60 min after initiation of HD. The percentage of morphologically activated PMNs was increased only during dialysis. The nature of the HD membrane had no influence on rigidity, PMN activation, or cytokine production. CONCLUSIONS: The results indicate that PMN rigidity is defective in end-stage chronic CRF patients and is further increased 60 min after initiation of HD, regardless of the nature of the HD membrane used. PMN activation, increased TNF-alpha and IL-1beta levels, or a direct PMN impairment may cause the observed cell rigidity.

Continuous ambulatory peritoneal dialysis is responsible for an increase in plasma norepinephrine.

OBJECTIVE: To investigate the reason for increasing norepinephrine (NE) levels reported in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Norepinephrine was measured in the plasma and peritoneal dialysate of CAPD patients (n = 22) and in the plasma and the urine of healthy subjects (n = 20). It was also measured in the plasma of patients with chronic renal failure (CRF) (n = 15) and patients on hemodialysis (HD) (n = 15). RESULTS: It was found that NE was increased in CAPD patients compared with healthy individuals (687+/-221 pg/mL vs 199+/-25 pg/mL, p < 0.01). The daily removal of NE from the peritoneum of CAPD patients was lower compared with the amount of NE excreted in the urine of healthy subjects. Plasma NE increased after infusion of peritoneal dialysate. In 15 new patients on CAPD, it was found that NE plasma levels increased from 329+/-67 pg/mL before initiation of dialysis, to 584+/-173 pg/mL after 12 months of treatment (p < 0.01). Finally, plasma NE in CAPD patients (687+/-221 pg/mL) was significantly higher compared with the already increased levels in patients on HD or with CRF (406+/-143 pg/mL and 378+/-142 pg/mL, respectively). CONCLUSIONS: It is concluded that CAPD in patients with end-stage renal disease is responsible for a progressive increase of plasma norepinephrine.

Technetium-99m-tetrofosmin for parathyroid scintigraphy: comparison to thallium-technetium scanning.

UNLABELLED: The efficacy of 99mTc-tetrofosmin for the detection of parathyroid lesions was investigated prospectively in patients with hyperparathyroidism referred for surgical treatment. METHODS: Twenty-seven patients with primary and 18 with tertiary hyperparathyroidism were studied. Twelve patients had undergone one or more previous neck explorations. Static imaging with 201Tl was performed first, immediately followed by a 30-min 99mTc-tetrofosmin dynamic study. Delayed views of up to 3 hr postinjection were also obtained. Technetium-99m-pertechnetate was used for thyroid delineation. The tetrofosmin/99mTc-pertechnetate subtraction scan (TF/TC), the single-tracer washout technique and the thallium/technetium subtraction (TL/TC) were compared. Quantification of relative uptakes of tracers in the thyroid and abnormal parathyroids was accomplished by measuring activity within regions of interest. Kinetics of tetrofosmin in the thyroid and abnormal parathyroids were studied by evaluating the plots of the parathyroid to thyroid ratios against time as well as by calculation of the half-clearance times from the slow component of the time-activity curves. RESULTS: The overall sensitivity, specificity and accuracy of TF/TC and TL/TC were 76%, 92% and 83% and 52%, 85% and 65%, respectively. The respective sensitivities were 87% and 70% for adenomas and 72% and 46% for hyperplasia. The parathyroid-to-thyroid activity ratios of tetrofosmin were significantly higher than those of thallium (p < 0.001). The tetrofosmin single-tracer washout study was less accurate than the subtraction technique (overall sensitivity and specificity, 70% and 69%, respectively). The washout properties of tetrofosmin in abnormal parathyroids were not substantially different from those in the thyroid, with a few exceptions (p = 0.4). No correlation of half-clearance times with parathyroid size, degree of early uptake, parathyroid hormone levels or histology could be established. Comparing adenomas to hyperplasia in respect to tetrofosmin retention, a statistically significant difference was observed (p = 0.005). CONCLUSION: Technetium-99m-tetrofosmin is suitable for parathyroid imaging. The kinetic properties of this agent in parathyroid and thyroid tissues do not warrant differential washout protocols. The diagnostic impact of the observed difference in tetrofosmin kinetics between parathyroid adenomas and hyperplasia requires further investigation.

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.

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.

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.