INR deviations in hemodialyzed patients under low dose oral anticoagulant therapy.

The aim of this retrospective study was to evaluate the International Normalized Ratio (INR) in hemodialyzed uremic patients under treatment with oral anticoagulation drugs. Eleven out of one hundred and forty-two uremic hemodialyzed patients in our unit were included in the study. These 11 patients aged from 70 to 85 (mean: 76 years) were under oral anticoagulation treatment for protection from thromboembolic events. They received 1 mg acenocumarol daily with the therapeutic goal of achieving an INR between 2 and 2.5 units. During the last year, the number of total INR determinations was 129. Based on the INR levels, measurements were classified into three categories of anticoagulation, termed "under-anticoagulation", "target-anticoagulation", and "over-anticoagulation". The number, the percentage, and the mean value (+/-SD) of INR measurements for each category, respectively, were under-anticoagulation: 39, 30%, 1.78 +/- 0.14; target-anticoagulation: 48, 37.5%, 2.20 +/- 0.14; and over-anticoagulation: 42, 32.5%, 3.14 +/- 0.64. The mean value +/-SD of all INR determinations (n=129) was 2.34 +/-0.65. No thromboembolic or major bleeding events occurred in our patients with these INR. In conclusion, in elderly, hemodialyzed uremic patients with indications for oral anticoagulation treatment, adequate and safe INR levels can be achieved in a high proportion without serious deviations from the therapeutic goal by using low doses of drugs. Therefore, oral anticoagulation therapy should not be considered automatically contra-indicated in this patient group.

Combination of sodium thiosulphate, cinacalcet, and paricalcitol in the treatment of calciphylaxis with hyperparathyroidism.

Calciphylaxis (calcific uremic arteriolopathy) is a severe complication of hemodialysis characterized by subcutaneous calcification of the small arteries and tissue necrosis. Our case report is focused on a woman receiving hemodialysis (HD) with diabetes mellitus for 20 years and severe secondary hyperparathyroidism, who presented painful subcutaneous nodules, skin necrosis and ulcerations. As the treatment of calciphylaxis is mainly empirical and controversial, we decided to administer cinacalcet with paricalcitol for the control of hyperparathyroidism and sodium thiosulfate to improve the calcification of the arterioles. Two months after the start of the therapy, parathyroid hormone (PTH) decreased significantly and the skin lesions nearly disappeared. Thus, we believe that the combination of sodium thiosulfate with cinacalcet and paracalcitol is effective for the treatment of calciphylaxis with secondary hyperparathyroidism.

Hematocrit-lowering effect following inactivation of renin-angiotensin system with angiotensin converting enzyme inhibitors and angiotensin receptor blockers.

Several clinical and experimental observations suggest that an intact and activated renin-angiotensin system (RAS) may be an important determinant of erythropoiesis in a variety of clinical conditions, including hypertension, chronic renal insufficiency or failure, chronic obstructive pulmonary disease, and congestive heart failure. Accordingly, RAS inactivation may confer susceptibility to the hematocrit-lowering effects of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Indeed, a dose-dependent decrease in hematocrit is observed within the first month of such therapy. In the majority of patients with hypertension decreases in hematocrit values after RAS inactivation are small and not clinically important. In extreme conditions, however, such as erythrocytosis after successful renal transplantation, secondary polycythemia of chronically hypoxemic COPD patients, erythrocytosis associated with renovascular hypertension, severe cardiac or renal failure, the hematocrit-lowering effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blocker may be profound and even lead to or worsen anemia. Hematocrit reaches its nadir value within three months, and then it remains stable during long-term observations. After discontinuation of RAS blockade, hematocrit values rise gradually over the next three to four months towards the pretreatment levels. The mechanism(s) related to this phenomenon is not yet fully understood, but angiotensin II seems to be responsible for inappropriately sustaining secretion of erythropoietin despite hematocrit elevation and capable to directly stimulate the erythroid progenitors in bone marrow to produce erythrocytes.

Echinocytic transformation and aggregation of red cells in uremic patients.

Isolated rabbit lungs were perfused with washed and resuspended human red blood cells (RBCs) in the presence of drugs known to change the shape and deformability of RBCs. With sodium salicylate (0.5-2 g/l), which causes echinocytosis and increases RBC deformability, lung diffusing capacity for O2 (DLO2) increased by 21%. When chlorpromazine, which induces stomatocytosis and stiffens RBCs, was given (50 mg/l), DLO2 decreased by 18% under chlorpromazine. Comparative experiments with hemoglobin solutions did not reveal any effect of those two drugs either on DLO2 or on pulmonary arterial pressure, which indicates that the effects of sodium salicylate and chlorpromazine were due to changes in RBC shape and deformability. It is concluded that RBC shape and deformability affect pulmonary artery pressure and oxygen diffusing capacity, which may have an influence on oxygen transfer to tissue and hence be of clinical relevance.

Ammonia concentration in the renal veins in unilateral renal artery stenosis with hypertension.

We measured blood ammonia in pre-angioplasty samples from the renal veins, aorta and inferior vena cava of 15 patients with hypertension due to unilateral renal artery stenosis confirmed by arteriography. Patients with renal insufficiency or small kidneys were excluded. Mean ammonia values were microgram/dl: vein of affected kidney, 106.00 +/- 12.75; vein of unaffected kidney, 75.65 +/- 23.10; aorta 61.04 +/- 15.00; vena cava, 62.44 +/- 19.65. The value for the affected kidney was significantly higher than the other three values (p < 0.001). Mean +/- SD DTPA uptake (%) was 42.8 +/- 2.21 in the affected kidney and 56.53 +/- 3.64 in the unaffected kidney. This difference did not correlate significantly with that of the ammonia concentrations tau = -0.292).

Management of claudication and hypertension by stent implantation in a renal transplant recipient.

Graft artery stenosis is one of the main causes of hypertension in renal transplant recipients. We present a rare case of severe common iliac artery stenosis, proximal to the graft artery, that was the cause of accelerated hypertension and claudication in a male renal transplant recipient. After percutaneous balloon angioplasty combined with a Palmaz stent implantation, a dramatic improvement of hypertension and claudication was observed during a 10-month follow-up period.

Transplant renal artery stenosis: hypertension and graft function before and after angioplasty.

We present a case, who after 15 years of renal transplantation developed severe deterioration of her hypertension without alteration in renal function. Colour Doppler sonography revealed a 90% stenosis near the anastomosis of the graft artery to iliac artery, which was successfully and uneventfully corrected by percutaneous balloon angioplasty. Following the procedure the blood pressure control dramatically improved and her antihypertensive regimen returned and remained at baseline for the subsequent year of observation. Renal function remained normal and stable before and after angioplasty.

Abdominal aortic aneurysm and renal artery stenosis: renal function and blood pressure before and after endovascular treatment.

We describe three patients with abdominal aortic aneurysm (AAA) and renal artery stenosis (RAS). These patients were treated by placement of an aortic endograft and angioplasty or stenting of the renal artery. After the procedure renal function improved or remained stable in two patients and deteriorated slightly in one. Blood pressure was reduced in one hypertensive patient and remained normal in the other two normotensive patients. In conclusion, simultaneous treatment of AAA and RAS with aortic endograft placement and renal artery angioplasty with or without stent, is a safe and effective technique for selected high-risk patients.

Influence of radiation treatment on serum transferrin and tumor necrosis factor-alpha.

This study deals with the effect of radiation treatment (RT) on serum transferrin and tumor necrosis factor-alpha (TNF-alpha) in patients with malignant tumors. In 21 patients who received 36-60 Gy in 20 to 30 sessions of RT, serum transferrin and TNF-alpha were determined pre-RT, after 10 to 15 sessions (middle of RT) and after 20 to 30 sessions (end of RT). The values of serum transferrin pre-RT were significantly higher than those in the middle and at the end of RT (p < 0.001). The values of TNF-alpha were increased by RT and were significantly higher at the end of RT as compared to the pre-RT values (p < 0.05). The values of serum transferrin and TNF-alpha show a tendency to negative correlation, either as a whole or separately pre- and under-RT. However, no correlation was statistically significant.

Serum transferrin and ceruloplasmin in patients with cancer of the gastrointestinal and other systems.

Serum transferrin and ceruloplasmin were determined in 20 healthy subjects, 23 patients with cancer of the gastro-intestinal system (G.I.S) and 22 patients with other types of cancer. Serum transferrin in patients with cancer of the G.I.S. was significantly decreased in comparison to that of healthy subjects (p < 0.05) and to that of other cancer patients (p < 0.005), but no significant difference was found between the values of healthy subjects and those with other types of cancer. Serum ceruloplasmin was significantly increased in patients with cancer of the G.I.S. (p < 0.01) and other types (p < 0.05) in comparison to that of healthy subjects. No significant difference was found between patients with cancer of the G.I.S. and those with other cancer types. In conclusion, transferrin was significantly decreased in the serum of patients with cancer of the G.I.S. while ceruloplasmin was significantly increased in both groups of patients with G.I.S. and other types of cancer.

Biotin for diabetic peripheral neuropathy.

Biotin in high doses was given for 1-2 years to three diabetic patients suffering from severe diabetic peripheral neuropathy. Within 4-8 weeks there was a marked improvement in clinical and laboratory findings. It is suggested that in diabetes may exist a deficiency, inactivity or unavailability of Biotin, resulting in disordered activity of biotin-dependent enzyme, pyruvate carboxylase, leading to accumulation of pyruvate and/or depletion of aspartate, both of which play a significant role in nervous system metabolism. Based on our good results, regular biotin administration could be suggested for every diabetic patient for the prevention and management of peripheral neuropathy although extensive randomised clinical trials are required.

Structural changes and variations of uric acid in normal pregnancy.

Fifteen normal pregnant women were studied. Serial measurements of serum total, free and bound uric acid and their clearances were done in early (10-20 weeks), mid- (20-30 weeks) and advanced (30-40 weeks) pregnancy, and after delivery (4-5 weeks). The following was observed. 1. A decrease in early and mid-pregnancy of total and free uric acid (p less than 0.001). 2. A gradual increase from the early to advanced pregnancy of bound uric acid (p less than 0.001). 3. An increase in early and mid-pregnancy of total uric acid clearance and a similar but more pronounced increase of free uric acid clearance (p less than 0.001). These findings explain many differences in previous conflicting reports concerning the metabolic behavior of uric acid, and place future investigation thereof on a more promising basis in normal and abnormal pregnancy.

Pre-HD dilution acidosis, without post-HD contraction alkalosis in uremic patients.

The aim of this study was to verify if the degree of pre-HD acidosis and its correction post-HD is related to body fluid expansion during the interdialytic period. Twelve uremic patients without major problems, with stable hematocrit, with regular and similar HD-session characteristics, but widely varying amounts of body fluid expansion in the interdialytic period were included. Blood samples were collected from arterial line pre- and post-HD, anaerobically in heparinized syringes, for determination of HCO3-, pH and PaCO2 (radiometer Copenhagen ABL 300 Acid-Base Laboratory), in two similar HD-sessions for each patient (12 patients, 24 HD-sessions). The percentage (%) of body weight gain in the interdialytic period was also estimated. For each patient, the mean value of parameters studied in the two HD-sessions was used for the evaluation of findings. According to mean values (+/-SD) of HCO3-, pH and PaCO2 Pre-HD (18.26+/-1.99 mmol/L, 7.31+/-0.03, 36.27+/-2.5 mmHg respectively) and post-HD (26.37+/-1.7, 7.43+/-0.03, 38.43+/-2.10 respectively) patients are acidotic pre-HD and slightly alkalemic post-HD. Correlation between the percentage (%) of interdialytic body weight gain (IBWG) and the values of HCO3-, pH and PaCO2, Pre-HD (r=-0.814, p<0.001; r=-0.931, p<0.001; r=0, 100 NS; respectively) and post-HD (r=-0.958, p<0.001; r=-0.937, p<0.001; r=-0.504 NS; respectively) indicates a significant and negative relationship of IBWG% with HCO3- and pH pre- and post-HD, but not with PCO2. In conclusion, the negative relationship of IBWG% with HCO3- and pH pre- and post-HD indicates that the body fluid expansion during the interdialytic period contributes to a dilutional acidosis pre-HD, but not to a contraction alkalosis post-HD, by the elimination of fluid during the HD-session.

Combined recombinant human erythropoietin-blood letting strategy for treating anemia and iron overload in hemodialysis patients.

We studied the feasibility of treating refractory anemia and post-transfusional serious hemochromatosis in a patient undergoing hemodialysis (3x4 h weekly) for fourteen years, with recombinant human erythropoietin (r-HuEPO) associated with blood-letting. Blood transfusion previously received by the patient at a rate of two units of packed red cells every month for nine years was stopped and r-HuEPO (80 U/kg b.w.) was administered i.v. at the end of each hemodialysis. When Hct increased over 30%, approximately 40 ml of blood was removed per hemodialysis session in an attempt to accelerate iron loss. Excellent control of anemia and hemochromatosis was achieved after seven months of treatment. The patient's general condition and skin pigmentation were significantly improved.

Changes of arterio-venous differences in pH and pCO2 by hemodialysis.

Normally the differences in arterial-venous pH (A-VpH) and veno-arterial pCO2 (V-ApCO2) are small and constant. This study deals with A-VpH and V-ApCO2 and their effect on arterial-venous saturation hemoglobin percentage (A-VSHb%) in uremic patients under hemodialysis (HD). In 17 uremic patients under HD with acetate, blood samples were collected anaerobically in heparinized syringes from artery (fistula) and vein (forearm without fistula) pre- and post-HD. In these samples pH, pCO2 and SHb% were determined and A-VpH, V-ApCO2 and A-VSHb% were estimated. Comparison between the values pre- and post-HD of A-VpH, V-ApCO2 and A-VSHb% shows that these three values were decreased significantly post-HD (p < 0.001). The correlation of all values (pre- and post-HD) of A-VpH and V-ApCO2 with that of A-VSHb% was significant and positive (r = 0.514 p < 0.01, r = 0.505 p < 0.01, respectively).

Re-evaluation of ascorbic acid deficiency in hemodialysed patients.

In 92 uremic patients under chronic hemodialysis without ascorbic acid supplementation, serum ascorbic acid was measured before hemodialysis and between two sessions. The results indicated a more serious ascorbic acid deficiency of patients than in previous studies. This difference might be explained by the highly specific enzymatic method applied in the present study, excluding any potential interference of various serum reducing substances.

Serum ferroxidase I and II in uremic patients under conservative treatment and maintenance hemodialysis.

Serum ferroxidase I (ceruloplasmin) and ferroxidase II activities were studied in 49 uremic patients under conservative treatment, in 79 patients undergoing hemodialysis and in 56 healthy subjects, as controls. Ferroxidase I was significantly higher in both groups of patients. Ferroxidase II was significantly elevated only in patients undergoing chronic hemodialysis. The cause of this difference is not clear, but seems to be of considerable interest.

Changes in erythrocyte calcium and potassium in patients during HD and CAPD.

The purpose of this study was to determine the changes in calcium and potassium content in the red blood cells (RBC) of uremic patients during a hemodialysis (HD) session and a 6/hrs CAPD exchange. RBC calcium and potassium were determined in 20 patients on HD in three blood samples collected at 0'-HD (pre-HD), 45'-HD and 240'-HD (end-HD), in 20 patients on CAPD, in two blood samples, collected at 0' time (pre-inflow) and 120', (solution in peritoneal cavity) during a 6/hrs exchange (4 exchanges / 24 h) and in 20 normal subjects. The mean value (+/-SD) of RBC calcium in controls was 15.6+/-3.75 micromol/L, in hemodialysed patients at 0'-HD, 45'-HD and 240'-HD 51.5+/-8.5, 70.4+/-12.5 and 51.1+/-10 micromol/L respectively and CAPD patients at time 0' and 120 of an exchange 53.6+/-23.4 and 70.6+/-9.2 respectively. These values show that RBC calcium in hemodialysed patients is generally significantly higher (p < 0.0001) than in controls. The value at 45'-HD is also significantly higher (p < 0.0001) than at 0' or 240'-HD. In CAPD patients, at 0' and 120' of a 6/hrs exchange, it is significantly higher (p < 0.0001) than in controls, as is the value at 120' (p < 0.001) in comparison to 0'. The mean value (+/-SD) of RBC potassium at the aforementioned time measurements were 95.9+/-3.34, 92.5+/-4.32 and 93.85+/-3.89 mmol/L respectively for patients on HD, 95+/-3.3 and 94.6+/-5.28 mmol/L respectively for patients on CAPD and 99.1+/-3.70 mmol/L in controls. These values show that RBC potassium of hemodialysed patients is significantly lower in comparison to that of controls (0'-HD: p < 0.01, 45'-HD and 240'-HD: p < 0.001); also the value at 45'-HD and 240'-HD is significantly lower (p < 0.001, p < 0.01 respectively) when compared to that at 0'-HD. In patients on CAPD, at 0' time and 120' during 6/hrs exchange, potassium is significant lower (p < 0.001) in comparison to that of controls. In conclusion, uremic patients present high erythrocyte calcium and low potassium with fluctuation during HD-sessions and CAPD 6/hrs exchange.

A cross-over study of a new low molecular weight heparin (Logiparin) in hemodialysis.

The safety and effectiveness of a low molecular weight heparin (LMWH) of 4500 +/- 1500 Daltons were evaluated in eight hemodialysis (HD) patients, in comparison with unfractionated heparin (UFH). In phase A of the study 3000 +/- 500 anti-factor Xa (AFXa) IU of LMWH were administered in bolus for the three consecutive HD sessions of a week. In phase B, 10000 +/- 2500 IU of UFH were administered to the same patients for the same time. Were observed no significant differences in hematocrit (Ht), platelets (Pt), fibronogen (FG) and prothrombin time (PT). Whole blood activated coagulation time (WBACT) was more prolonged with LMWH, 24 and 48 hours (start of next session) after administration (p < 0.05), and less prolonged at 5, 60, 120, 180, 240 min compared to UFH (p < 0.001). The activated partial thromboplastin time (APTT) and AFXa activity were more prolonged with UFH at 60 and 240 min (p < 0.001). The clinical effectiveness of the two preparations was similar as judged by thrombus formation and compression time. In conclusion, the present study found no real differences between LMWH and UFH, except for prolongation of WBACT 24 and 48 hours after the administration of LWMH. This probably indicates a cumulative effect of the LMWH and needs further investigation.

Telemedicine technology and applications for home hemodialysis.

Home hemodialysis (HD) for the treatment of patients with end-stage renal disease (ESRD) was first put into practice about 30 years ago. In this paper we describe the application of telematics monitoring services (TMS) for supporting patients who need home or satellite HD (SHD). For the clinical trials two modified HD machines were located in the renal unit and a central control station (UNIX workstation with multimedia PC-terminal) was located in another room of the hospital. Bi-directional communication between modified HD machines and central control station was managed via ISDN (Integrated Services Digital Network) links. Using these HD-machines 150 HD sessions were performed in nine patients over a period of five months. This system enabled on-line remote supervision of the HD machine-related functions (air in the blood, leak of blood, low conductivity etc.) and the clinical condition of patients through measurement of blood pressure (BP), pulse rate, PO2 (pulse oxymetry) and electrocardiogram (ECG) from the central control station (CCS). The user checked the type of alarm/warning, its appearance on HD machines and multimedia terminal units (MTU), the action of the protective system and the appearance of consultative messages from CCS on the remote terminal unit RTU. According to the data collected, the disturbances of HD machine function were visible and audible in the CCS and the user messages were always observed on the RTU. No unusual dialysis-associated complications were observed, all data and alarms/warnings were transmitted correctly and patients had adequate HD treatment.