Use of hormonal parameters of phospho-calcium metabolism as a means of discriminating bone and joint disorders in patients with renal insufficiency

Serum carboxyterminal parathyroid hormone (PTH) concentration (homologous measurement of the 53-84 fragment and heterologous bovine measurement) has been measured and correlated with both clinical and radiological findings of secondary hyperparathyroidism (HPT), studied quantitatively according to a score published in literature, in 95 patients with chronic renal failure on maintenance hemodialysis. Mean serum PTH concentration (53.84) is statistically higher in patients with severe clinical and radiological evaluation of HPT than in patients with moderate or slight manifestations of HPT (M +/- DS: 515.8 +/- 243.7 pg/ml VS 271.3 +/- 166.1 pg/ml p less than 0.001). However, even with high serum concentration, serum PTH level does not allow to predict HPT severity, suggesting a retention of PTH fragments in serum without biologic activity probably.     

Potassium in skeletal muscle in untreated primary hypertension and in chronic renal failure, studied by X-ray fluorescence technique

Muscle biopsy specimens form 22 patients with primary hypertension, 10 patients with chronic renal failure and 21 healthy normotensive controls were analyzed using a Kevex 0600 X-ray spectrometer. Muscle potassium (MK), calcium (MCa), sulphur (MS) and phosphorus (MP) were determined. In the patients with primary hypertension, MK was decreased compared to the controls (p less than 0.001), MCa was increased (p less than 0.05), MS was decreased (p less than 0.05) and no difference was seen in MP. In the patients with chronic renal failure, MK was decreased compared to the controls (p less than 0.001), MCa showed no difference compared to the controls, whereas both MP and MS were lower (p less than 0.05 and p less than 0.001). It was concluded that intracellular potassium is low both in primary hypertension and chronic renal failure. In chronic renal failure the potassium decrease is probably secondary to loss of cellular potassium capacity, whereas in primary hypertension an inhibition of the sodium, potassium, adenosine triphosphatase is suggested as the cause of the low potassium.     

Deranged mineral content in the bone of patients with chronic renal failure, estimated by computed tomography

To evaluate the extent of renal osteodystrophy in patients with chronic renal failure, the CT numbers of the lateral condylus and mid-shaft of the femur were measured. To adjust for variation due to measurement conditions, calibration phantom was simultaneously scanned with the femur. The CT numbers of the lateral condylus were significantly lower than the control in both nondialyzed (p less than 0.005) and dialyzed patients (p less than 0.05). The CT numbers of the mid-shaft of the femur in dialyzed patients correlated significantly to the duration of hemodialysis (r = 0.807, p less than 0.001). In 15 patients subjected to both CT scan and the photon absorptiometry, the CT numbers of the lateral condylus positively correlated to the mineral content of the radial (r = 0.57) and ulnar (r = 0.69) bones as calculated by photon absorptiometry. These results indicate that the CT scan can be used to estimate bone mineral content quantitatively, and is useful tool for evaluating renal osteodystrophy in patients with chronic renal failure.     

Renal osteodystrophy in predialysis patients without stainable bone aluminum. A cross-sectional bone-histomorphometric study

Histomorphometry was performed on transiliac bone biopsies, double-labeled with tetracycline, from 60 consecutively admitted patients (20 women) at various stages of chronic renal failure (CRF). Eleven patients (1 woman) had normal bone resorption and formation indices. Bone resorption and osteoid formation increased with progression of renal failure, but abnormal values were seen even at slightly elevated creatinine levels. Mineralization lag time increased with CRF duration; prolonged values were only seen in patients with polycystic kidney disease or chronic pyelonephritis with advanced CRF. All patients with impaired mineralization also had increased bone resorption. Diabetes mellitus did not protect against skeletal lesions. The biochemical tests were too insensitive to predict type or severity of bone disease, and hand X-rays had no diagnostic value in early stages of renal osteodystrophy.     

Serum angiotensin-converting enzyme levels in patients with chronic renal failure

Disagreement concerning serum angiotensin-converting enzyme (ACE) levels in patients with chronic renal failure has been observed in recent reports. Because ACE is considered as a useful tool for the diagnosis and management of sarcoidosis, and because chronic renal failure may be associated with sarcoidosis, the present work was designed to reinvestigate the possible changes of serum angiotensin-converting enzyme activity in a series of 36 non-hemodialysed consecutive patients with chronic non-sarcoid renal failure. Enzyme activity was significantly lower (p less than 0.004) in the patients (15.8 +/- 5.0 units/ml, mean value +/- 1 SD) than in 47 healthy controls (20.2 +/- 7.6 units/ml, mean value +/- 1 SD). Serum angiotensin-converting enzyme and creatinine clearance values were significantly correlated in these patients (p less than 0.0002). These results indicate that, in non-hemodialysed patients with chronic renal failure, serum angiotensin-converting enzyme levels may not be useful in establishing the diagnosis of sarcoidosis.     

Osteocalcin in chronic hemodialysis patients as an additional parameter in the diagnosis of advanced secondary hyperparathyroidism

Osteocalcin (OC), also called Bone Gla Protein (BGP), is a bone matrix protein of 5800 MW synthesized by osteoblasts. Since OC is mainly metabolized in the kidney, its blood concentration is altered in renal failure. The relationship between OC and the calcium-phosphorus regulating hormones (parathyroid hormone, calcitonin) and the biochemical parameters of bone metabolism (serum calcium, serum phosphorus and serum alkaline phosphatase) was studied in 30 patients on chronic hemodialysis (mean age: 51 years; mean duration of dialysis treatment: 39 months). OC levels were significantly elevated in all patients on chronic hemodialysis (34.7 +/- 31.5 ng/ml) when compared to healthy subjects (6.25 +/- 1.39 ng/ml, p less than 0.001). In 2 patients the OC levels were excessively high (127.54 ng/ml; 148.02 ng/ml), which was associated with severe renal osteodystrophy due to secondary hyperparathyroidism. When divided into 2 groups in the patients with secondary hyperparathyroidism the mean OC value was markedly elevated (50.5 +/- 12.7 ng/ml) compared to the patients without secondary hyperparathyroidism (24.1 +/- 2.8 ng/ml) (p less than 0.05). 70 per cent of the patients on chronic hemodialysis with OC levels greater than 30 ng/ml showed moderate to severe scintigraphic findings of bone disease. In neither of the 2 groups could a correlation between OC and serum alkaline phosphatase be demonstrated. The results indicate, that OC levels could be useful additional parameter in hemodialyzed patients with secondary hyperparathyroidism and OC levels could reflect bone formation in these patients.     

Histomorphometric profile of bone fluorosis induced by prolonged ingestion of Vichy Saint-Yorre water. Comparison with bone fluorine levels

Nine transiliac bone biopsies from 7 patients with skeletal fluorosis due to prolonged ingestion of often high quantities of Vichy Saint-Yorre water were analyzed. Four of these patients also suffered from a chronic renal failure. A histomorphometric study was possible in 8 out of the 9 biopsies. The measurement of bone fluoride content, and a microradiographic examination, were performed on all bone samples. The radiologically evident osteosclerosis observed in each patient was confirmed by the significant increase of trabecular bone volume. Furthermore, the osteoid surfaces were very extended but the thickness of osteoid seams was normal in 6 out of 8 cases. Two biopsies demonstrated a morphological evidence of osteomalacia with abnormally thick osteoid seams. Calcification rate, measured in one of these 2 cases after tetracycline double labeling, was extremely low (less than 0.20 micron/d). The bone fluoride content was significantly high in each specimen (greater than 0.40 bone ash%) and correlated with relative osteoid volume (r' = 0.91) and thickness index of osteoid seams (r' = 0.83). Histologically, bone tissue showed modifications classically reported in the various types of skeletal fluorosis (formation defects, mottled bone with mottled periosteocytic lacunae). In conclusion, the prolonged administration of Vichy Saint-Yorre water containing 8.5 mg of fluoride ion per liter, provokes a skeletal fluorosis. This intoxication appeared very quickly if the patient suffered from an even mild renal failure. Once again, it is shown that a disturbed renal function predisposes to an excessive retention of fluoride.     

Hepatic morphology in cardiac dysfunction: a clinicopathologic study of 1000 subjects at autopsy.

Chronic passive congestion (CPC) and centrilobular necrosis (CLN) are well recognized pathologic changes, but their exact relationship to different forms of cardiac dysfunction is uncertain. We reviewed clinical data and hepatic, renal, and adrenal morphology related to cardiac dysfunction in 1000 autopsy subjects at The Johns Hopkins Hospital whose hearts had been studied after postmortem arteriography and fixation in distention. Fourteen pathologic variables, including body and organ size, and microscopic changes graded on a semiquantitative scale, and 18 clinical variables including congestive heart failure, shock, and cardiovascular disease, were analyzed statistically. Distinct patterns of cardiac dysfunction emerged for the two spectra of hepatic morphologic change. Among patients with variable CPC, but slight or absent CLN, the amount of CPC was predicted in a multivariate analysis by severity of right-sided congestive heart failure. CPC severity correlated with cardiac weight and chamber enlargement (P less than 0.001). Among patients with variable CLN, but slight or absent CPC, CLN was predicted by profound hypotension and by renal failure. In addition, CLN, but not CPC, was significantly correlated with renal acute tubular necrosis (P less than 0.001) and adrenal cortical medullary junction necrosis (P less than 0.05), two lesions associated with shock. Among all 1000 patients CPC and CLN were highly significantly correlated (P less than 0.001). The results show that hepatic CPC arises from conditions producing elevated systemic venous pressure but that CLN arises from reduced systemic arterial pressure; and the presence of one potentiates the development of the other.     

Ultrasonography methods in the diagnosis of renal osteodystrophy

Bone disease, i.e. renal osteodystrophy, is commonly seen in patients with chronic renal failure. It encompasses all the disorders of mineral and bone metabolism associated with chronic renal insufficiency, i.e. secondary hyperparathyroidism, retention and accumulation of beta 2 microglobulin and aluminum. The most frequent cause of renal osteodystrophy is secondary hyperthyroidism, with a consequence of high turnover bone disease. Secondary hyperparathyroidism, i.e. increased parathyroid hormone (PTH) secretion and parathyroid gland hyperplasia, develops early in the course of chronic renal insufficiency. Hypocalcemia, phosphate retention and deficiency of calcitriol stimulate PTH synthesis and secretion and parathyroid cell proliferation, i.e. hyperplasia. Parathyroid cell proliferation is initially polyclonal (diffuse hyperplasia), and later it is monoclonal or multiclonal (nodular hyperplasia). Calcitriol receptors as well as calcium-sensing receptors are significantly reduced in parathyroid glands in nodular hyperplasia. Patients with such parathyroid gland hyperplasia are often resistant to vitamin D therapy. A specific form of bone disease is beta 2 amyloidosis. Destructive arthropathy, cystic changes and carpal tunnel syndrome are clinical manifestations of dialysis-related amyloidosis, which is one of the major complications in patients on longterm hemodialysis. Aluminum intoxication leads to the low turnover bone disease and consequential osteomalacia or aplastic bone lesions, the cause of which has not yet been fully clarified. Ultrasound can be a useful, economical and noninvasive method in the evaluation of renal osteodystrophy. Ultrasound waves are very important for noninvasive imaging of soft tissue, especially parathyroid glands, pathologic changes of the joints, and for detection of metastatic calcifications. They are also useful in the evaluation of skeletal status in dialysis patients. Ultrasound waves of a frequency above the limit of human hearing are used in the morphological diagnosis of parathyroid gland. Today, because of its simplicity and non-invasiveness, it is a generally accepted method for the detection of enlarged parathyroid gland in patients with secondary hyperparathyroidism, for the monitoring of pathologic changes, and for making decisions on the method of treatment based on the size and number of parathyroid glands. Ultrasound can distinguish nodal from diffuse parathyroid hyperplasia. Under ultrasound guidance it is possible to perform fine needle aspiration biopsy, to confirm ultrasound findings, and percutaneous inactivation of parathyroid gland (PEI) with alcohol. Ultrasound is useful in the diagnosis of pathologic changes of the musculoskeletal system in patients with beta 2 amyloidosis, to assess the process of its spread, especially in the shoulder joint where the changes are most pronounced (rotator cuff thickness, amyloid deposits as hyperechogenic pads, and detection of fluid in the joint), but it can also be used to examine other joints as well as soft tissue in which metastatic calcifications may occur. Standard ultrasound equipment (pulse-echo) and linear probe of 5-13 MHz are used, also serving for ultrasound examination of the neck, joints and soft tissue. Quantitative bone ultrasonometry is based on different physical characteristics of the ultrasound including: transmission, Speed Of Sound (SOS) in meters/sec and Broad Band Attenuation (BUA) in dB/MHz, and different concepts of the apparatus. These parameters depend on the strength and architecture of the bones and describe better the changes in bone structure in dialysis patients by calculation of the Stiffness Index (QUI), better than the standard bone densitometry by dual-energy x-ray absorptiometry, which only measures bone density. Combined ultrasound measurement of the bone in several locations may be successful in monitoring dialysis patients.     

Total and free thyroid hormone levels in chronic renal failure.

The levels of serum total thyroxine (TT4), triiodothyronine (TT3), free T3, (FT3) free T4 (FT4) and thyrotropin (TSH) were measured in 127 clinically euthyroid patients with varying grades of chronic renal failure (CRF); and 97 healthy individuals. They were grouped as: Group I containing 93 patients on conservative management; Group II containing 34 patients on regular dialysis therapy; and Group III (normals). Group I patients showed significant decrease in TT3, TT4 and FT3 levels (p less than 0.001) as compared to Group III, whereas FT4 and TSH values in group I were not significantly altered. TT3, TT4 and FT3 levels reduced as the severity of renal damage increased. Variations in TT3, TT4, FT3, FT4 and TSH levels in Group II patients were similar to those in Group I, except for a decrease in TSH levels (p less than 0.05) as compared to normals. Several thyroid function tests are abnormal in CRF patients, however, finding of normal FT4 and TSH levels would indicate functional euthyroid status.     

Secondary hyperparathyroidism in chronic renal failure

The metabolic bone disease associated with chronic renal failure has been described collectively by the terms "renal osteodystrophy" or "renal-glomerular-osteodystrophy" and consists of osteomalacia, osteitis fibrosa, and osteosclerosis. The skeletal abnormalities may occur either alone or in combination with one another. An increased concentration of circulating immunoreactive-parathyroid hormone (i-PTH) is a recognized feature of patients with chronic renal failure, and the values are usually much higher than those found in patients with primary hyperparathyroidism associated with a parathyroid adenoma. It must, however, be recognized that the high circulatory concentrations of parathyroid hormone found in patients with chronic renal failure are of immunoassayable material which may or may not be of biological significance in respect of activity. A disturbance in the homeostatic control mechanism governing parathyroid hormone, the secretion rate, its metabolism, and target organ resistance to its action are of major importance in the pathogenesis of some aspects of the metabolic bone disease in patients with chronic renal failure. The pathogenesis of the secondary hyperparathyroidism of chronic renal failure, however, also involves disturbances in cholecalciferol metabolism, phosphate retention, and the uremic state per se.     

Dural ectasia in Loeys–Dietz syndrome: comprehensive study of 30 patients with a TGFBR1 or TGFBR2 mutation

The purpose of this study was to assess the frequency, severity, and clinical associations of dural ectasia (DE) in Loeys–Dietz syndrome (LDS). Database analysis of three German metropolitan regions identified 30 patients with LDS and TGFBR1 mutation in 6 and a TGFBR2 mutation in 24 individuals (17 men; mean age: 31 ± 19 years), as well as 60 age and sex‐matched control patients with Marfan syndrome carrying a FBN1 mutation. DE was present in 22 patients with LDS (73%), and it related to skeletal score points (p = 0.008), non‐skeletal score points (p < 0.001), and to the presence of ≥7 systemic score points (p = 0.010). Similarly, the severity of DE was related to body height (p = 0.010) and non‐skeletal score points (p = 0.004). Frequency (p = 0.131) and severity of DE (p = 0.567) was similar in LDS and Marfan syndrome. DE is a manifestation of LDS that occurs with similar frequency and severity as in Marfan syndrome. Severity of DE may serve as a marker of the overall connective tissue disease severity. LDS may be considered in patients with DE.     

Biochemical evidence of disturbed bone metabolism and calcium homeostasis in two types of autosomal dominant osteopetrosis

Biochemical markers of bone resorption and bone formation were measured in 14 patients with autosomal dominant osteopetrosis, and compared with age- and sex-matched controls. There were eight patients with the radiological type I characterized by diffuse, symmetrical osteosclerosis with pronounced sclerosis of the skull and enlarged thickness of the cranial vault, and six patients with type II characterized by diffuse, symmetrical osteosclerosis, "Rugger-Jersey spine" and "endobones" (bone within a bone) in the pelvis. Serum levels of alkaline phosphatase and osteocalcin in types I and II did not differ from controls indicating normal bone formation. However, a significantly decreased fasting renal excretion of phosphate and hydroxyproline in both types compared with normal controls, suggests a reduced bone resorption. Serum levels of parathyroid hormone (PTH), albumin-corrected calcium, phosphate, and acid phosphatase were normal in type I. In type II serum levels of albumin-corrected calcium and PTH were significantly increased (p less than 0.05 and p less than 0.01). The level of acid phosphatase was markedly increased in this type (p less than 0.01). These findings suggest differences between the two types in calcium homeostasis and bone metabolism, and thus corroborate the evidence that the two radiological types reflect two different disorders of bone resorption.     

不同肾脏疾病时leptin与NPY的水平变化

目的：探讨不同肾脏疾病时血浆瘦素（leptin）和神经肽Y（NPY）的水平变化及意义。方法：应用放射免疫分析对176例不同肾脏疾病患者血清leptin及血浆NPY水平进行检测,并与35例正常人进行对比。结果：与对照组比较,糖尿病肾病、慢性肾功能不全及血液透析前后血清leptin水平均增高显著（P〈0．05;P〈0．01;P〈0．01）。血浆NPY水平在慢性肾功能衰竭和血液透析前后显著增高（P〈0．01;P〈0．01）。其他各组与对照组比较均无显著性差异（P〉0．05）。与血透前比较,血透后leptin和NPY水平明显降低有显著性差异（P〈0．05;P〈0．05）。相关性分析显示,慢性肾功能衰竭组和血液透析组leptin与NPY之间均呈正相关（r=0．68。t=3．62,P〈0．01;r=0．58,t=4．02,P〈0．01）,其他各组间无相关性。结论：慢性肾脏疾病和慢性肾功能衰竭患者存在高leptin、NPY血症;血液透析过程能增加leptin和NPY的清除率,改善患者的营养状态。     

The mast cell and signs of pulmonary fibroblast activation in sarcoidosis

Hyaluronate and type III procollagen propeptide were assayed in bronchoalveolar lavage (BAL) fluids from patients with sarcoidosis. Levels were significantly elevated suggesting increased rates of synthesis of these connective tissue components in the lung. They were strongly related to each other (p less than 0.001) favoring the idea of a common cellular origin, as a suggestion activated fibroblasts. There was a significant inverse correlation (p less than 0.001) between lavage hyaluronate or procollagen propeptide and the clinical severity of the disease process defined by lung volume, diffusion capacity and pulmonary radiological findings. Correlation of clinical findings with lavage cell profiles was poor except for recovered mast cells (p less than 0.001). Lavage mast cell counts were also closely associated with BAL fluid hyaluronate and procollagen peptide (p less than 0.001). These findings may reflect a link between the mast cell, the activation of fibroblasts, and the progress of connective tissue changes in sarcoid lung.     

Preservation of renal structure and function in the rat remnant kidney model of chronic renal failure by enalapril treatment

The remnant kidney model of chronic renal failure was established in rats subject to subtotal (1 7/8) nephrectomy and the evolution of renal injury studied over a period of 6 wk. One wk after subtotal nephrectomy, rats had a mean conscious systolic blood pressure of 158 +/- 5 mm Hg and serum creatinine of 128 +/- 9 mumol/l. Both systolic blood pressure and serum creatinine rose over the next 5 wk in concert with progressive glomerulosclerosis and proteinuria. Enalapril, an angiotensin converting enzyme inhibitor, was administered (5 mg/kg/day) to rats (n = 11) from 1 wk after subtotal nephrectomy. Enalapril lowered systolic blood pressure over the treatment period. Systolic blood pressure was 122 +/- 5 mm Hg compared with 176 +/- 7 mm Hg in untreated rats (p less than 0.001) at 6 wk. Serum creatinine 6 wk after subtotal nephrectomy was 110 +/- 9 mumol/l with enalapril treatment, compared with 159 +/- 21 mumol/l (p less than 0.025) in control animals. Enalapril treated rats had lower urinary protein excretion than controls (15 +/- 3 mg/24 hr vs 85 +/- 22 mg/24 hr, p less than 0.0001) at 6 weeks. Glomerulosclerosis, assessed by blinded histological score, was also reduced in the enalapril treated group (1.79 +/- 0.08 vs 2.36 +/- 0.16, p less than 0.01). Enalapril treatment was associated with a reduction in filtration fraction (51Cr-EDTA/125I-hippurate clearance). At 6 wk, filtration fraction was 0.30 +/- 0.03 in enalapril treated and 0.48 +/- 0.03 in control rats (p less than 0.001). Enalapril treatment in the subtotal nephrectomy model of renal failure preserved renal structure and function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Deep vein thrombosis and pulmonary embolism: the same disease?

The clinical characteristics and 3-month clinical outcome of 7,664 patients with acute deep vein thrombosis(DVT), 3,968 patients with pulmonary embolism(PE), and 2,287 with signs of both DVT and PE were compared. As compared to patients with DVT signs, PE patients were more commonly females, older and had less often cancer, prior VTE or recent surgery. By contrast, they had more often chronic lung disease,chronic heart failure or renal insufficiency. Patients with both DVT and PE signs were also more commonly females and older than those with only DVT signs, but they had more often a prior episode VTE, cancer, chronic lung disease, chronic heart failure or renal insufficiency. As for the 3-month clinical outcome,patients with PE signs had a significantly higher incidence of major bleeding, recurrent PE, fatal PE and overall death than those with only DVT signs,but a lower incidence of recurrent DVT. Besides, patients with DVT and PE signs had an even worse clinical outcome.     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C₁₈ extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 ± 24.9, 178.6 ± 23.0, 167.2 ± 21.8 pg/ml; ANP: 240.2 ± 28.7, 166.7 ± 21.3, 133.0 ± 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 ± 1.8%, ANP 40.2 ± 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 ± 1.0 and 60.3 ± 4. 0 pg/ml in patients with normal LVEDP and 31.7 ± 3.6 and 118.3 ± 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001 or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations. The present results provide support that other factors than volume overload, for example, decreased renal clearance, are also involved in the elevationin BNP and ANP plasma levels in chronic renal failure. The stronger elevation in BNP concentrations in patients with chronic renal failure and in patients with elevated LVEDP and the less pronounced decrease during hemodialysis suggest a different regulation of BNP and ANP plasma concentrations.[/ p]Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide - LVEDP left ventricular end-diastolic pressure Correspondence to: C. Haug     

Study on changes of serum vitamin K1 level and K dependent coagulation factors in patients with coumarin derivatives (warfarin) therapy]

Serum level of vitamin K1 (= phylloquinone, hereinafter K1) and K dependent blood coagulation factors were determined by HPLC in normal subject, liver cirrhosis, hepatocellular carcinoma, acute hepatitis, chronic hepatitis, chronic renal failure with hemodialysis and patients under warfarin therapy. Normal range of serum K1 concentration was decided on 0.20-2.30 (0.87 +/- 0.53, n = 96) ng/ml. Serum K1 level showed no significant differences among normal subject, various diseases and warfarin therapy. Correlation between serum K1 level and F-VII (r = 0.879, p less than 0.001) or protein C activity (r = 0.839, p less than 0.01) was found in patients whose thrombotest was 20% and less. However serum K1 level didn't correlate with any K dependent coagulation factors in patients if thrombotest was over 20%.     

Presence of Apo B48, and relative Apo CII deficiency and Apo CIII enrichment in uremic very-low density lipoproteins

In the present study, lipid and apolipoprotein composition of very low density lipoprotein (VLDL) was analyzed in 39 patients with end-stage renal failure by comparison with 41 healthy subjects. Uremic patients had an increase of serum triglycerides (TG) concentration by comparison with control values. This increase of serum TG was associated with an increase of VLDL which had a normal percent amount of main components. Furthermore a mid-band between VLDL and low density lipoproteins (LDL) on polyacrylamide gel was observed in 22 out of 39 uremic patients but in only 1 out of 41 control subjects. In uremic VLDL Apo B48 was more frequently observed than in control VLDL (p less than 0.05). Furthermore, the content of Apo CII expressed as percent of total Apo C was significantly (p less than 0.001) decreased in uremic VLDL (19.13 +/- 4.54 p. cent) as compared to normal VLDL (23.57 +/- 4.40 p. cent). Apo CIII-O was significantly (p less than 0.001) increased (9.58 +/- 7.19 p. cent vs 5.55 +/- 6.12 p. cent, whereas Apo CIII-1 and Apo CIII-2 distribution was not modified in uremic VLDL. These anomalies were present in uremic patients even when no elevation of fasting serum TG was present. No significant change was observed in uremic patients before their fifth as compared to their first hemodialysis (HD) session, respectively, for any of the parameters studied. Advanced chronic renal failure is associated with a variety of anomalies of TG-rich lipoproteins isolated at d less than 1.006 g/ml which are not reflected by the degree of hypertriglyceridemia and are not corrected by the first four HD sessions.