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.

Relation of interdialytic water retention with apparent bicarbonate space, HCO3-, and pH in hemodialyzed uremic patients.

This study determines the relationship between interdialytic water retention (IWR) and acid-base homeostasis in uremic patients under regular hemodialysis (HD). To this aim, in 33 regular bicarbonate HD sessions of 11 uremic patients (three HD sessions of 1 week for each patient), blood samples were received from arterial line immediately pre- and post-HD anaerobically in heparinized syringes and the HCO3-, pH, and pco2 were determined. Also in the studied HD sessions, the IWR was estimated and the apparent bicarbonate space percentage (ABS%) pre- and post-HD was calculated by Fernandez et al. (Eq. 1). The mean +/- SD values pre-HD (ABS% = 54.15 +/- 1.49, HCO3- = 18.54 +/- 2.0 mmol/L, pH = 7.32 +/- 0.02, pco2 = 35.44 +/- 3.10 mmHg) and post-HD (ABS% = 49.88 +/- 0.6, HCO3- = 26.33 +/- 1.6 mmol/L, pH = 7.44 +/- 0.02, pco2 = 37.69 +/- 3.00 mmHg) show metabolic acidosis pre-HD and slight alkalosis post-HD. There was a significant positive correlation between IWR and ABS% pre-HD (r = 0.650, p < .0001) and post-HD (r = 0.655, p < .0001), but a significant negative correlation between IWR and HCO3- pre-HD (r = -0.502, p < .003) and post-HD (r = -0.700, p < .001), as well as between IWR and pH pre-HD (r = -0.516, p < .002) and post-HD (r = -0.377, p < .03). In addition, there was a significantly negative correlation between IWR and pco2 post-HD (r = -0.656, p < .001), but not pre-HD (r = 0.0136, PNS). The significantly positive relationship between IWR and ABS% pre- and post-HD, in combination with the significantly negative correlation between HCO3- and pH pre- and post-HD, indicates that the IWR negatively influences the acid-base homeostasis in hemodialysis patients without residual renal function, and may worsen the cardiovascular physiology and tissue oxygenation of these patients.

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.

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.

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.

Relationship between interdialytic weight gain and acid-base status in hemodialysis by bicarbonate.

The aim of this study was to determine the relationship between interdialytic weight gain and acid-base balance pre- and posthemodialysis in uremic patients undergoing hemodialysis with a high bicarbonate dialysate (39 mmol/L). To this end we studied 8 stable uremic patients on regular hemodialysis thrice weekly who had stable hematocrit values for at least 3 months, similar clinical characteristics including dry weight but widely varying interdialytic weight gain. Arterial line blood samples were collected anaerobically in heparinized syringes pre- and posthemodialysis in 4 consecutive hemodialysis sessions for the determination of pH, Paco2, and HCO3. Prehemodialysis values (mean +/- SD) were pH = 7.34 +/- 0.03, Paco2 = 36.43 +/- 1.4, and Hco3 = 20.1 +/- 1.55. Posthemodialysis values were pH= 7.47 +/- 0.02, Paco2 = 38.72 +/- 2.0, and HCO3 = 27.73 +/- 1.72. In other words, patients were moderately acidemic prior to and moderately alkalemic after the hemodialysis session. Of note, a significant negative correlation was revealed between the interdialytic weight gain and the values of prehemodialysis blood pH (r = -0.721, p < 0.001) and HCO3 (r = -0.836, p < 0.001) and posthemodialysis pH (r = -0.533, p < 0.001), Paco2 (r = -0.623, p < 0.001) and HCO3 (r = -0.815, p < 0.001), suggesting an important role of the interdialytic weight gain on acid-base equilibrium of uremic patients undergoing hemodialysis. Thus, patients with high interdialytic weight gains may require higher bicarbonate concentrations to achieve normal acid-base status whereas patients with low interdialyic weight gains may require lower bicarbonate concentrations to prevent alkalemia at the end of dialysis.

Renal artery stenting for renal insufficiency in solitary kidney in 26 patients.

OBJECTIVE: to present our experience with stent placement in renal arteries in solitary kidneys for treating renal insufficiency. DESIGN: retrospective analysis. MATERIALS: in 26 patients with solitary kidney (17 men, 9 women, mean age: 63 years), presented with renal insufficiency (se-creat >0.144 mmol/l), stent was placed in a stenosed renal artery. We analysed the clinical outcome, based on the level of creatinine at 3 months following the procedure. Clinical benefit was considered when there was a decrease compared to the baseline creatinine by >20% or a stabilisation of the creatinine value (+/-20% of the baseline). RESULTS: in 16 of the 26 patients (62%), clinical benefit was achieved. However, 38% of the study population, renal function continued to deteriorate. Baseline creatinine value was the single best predictor for clinical benefit achievement (odds ratio: 13; 95% confidence intervals: 1.6-107, p=0.01). CONCLUSION: renal stenting results in improvement or stabilisation of renal function in the majority of the patients with solitary kidneys and renal artery stenosis, presenting with renal insufficiency. Because best outcome was observed mainly in those patients with not progressed renal insufficiency, intervention should be focused on that group.

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.

Relation between echinocytosis and erythrocyte calcium content in hemodialyzed uremic patients.

A rise in intracellular calcium concentration in erythrocytes has multiple effects on these cells. The purpose of this study was to determine the changes of calcium content in red blood cells (RBCs) and of echinocyte percentages in uremic patients during hemodialysis sessions. In 30 uremic patients under hemodialysis, the calcium content of RBCs and echinocyte percentages were determined in 3 blood samples collected at 0 min hemodialysis (prehemodialysis), 45 min hemodialysis, and 240 min hemodialysis (end hemodialysis) for a 4 h hemodialysis session. Calcium content of RBCs and echinocytes were also determined in 22 normal subjects (controls). The findings of the present study were that the mean values (+/-SD) of calcium content of RBCs in patients at 0 min hemodialysis, 45 min hemodialysis, and 240 min hemodialysis were 2.00 +/- 1.0, 2.66 +/- 0.87, and 1.62 +/- 0.66 microg/ml respectively and 0.65 +/- 0.07 microg/ml in controls. These values show that the calcium content of RBCs in uremic patients at 0 min hemodialysis, 45 min hemodialysis, and 240 hemodialysis was significantly higher than in controls (p < 0.0001), and that RBC calcium content at 45 min hemodialysis was significantly higher in comparison to that at 0 min hemodialysis (p < 0.001) and to that at 240 min hemodialysis (p < 0.0001), while that at 240 min hemodialysis was significantly lower than at 0 min hemodialysis (p < 0.05). The mean values (+/-SD) of echinocyte percentages in patients at 0 min hemodialysis, 45 min hemodialysis, and 240 hemodialysis were 11.93 +/- 6.18, 17.23 +/- 4.1, and 7.96 +/- 5.67% respectively, and in controls ranged from 0 to 1%. The values in uremic patients show a transient increase of echinocyte percentages at 45 min hemodialysis, which is significant in comparison to that at 0 min hemodialysis (p < 0.001) and to that at 240 min hemodialysis (p < 0.0001). Echinocyte percentages at 240 min hemodialysis were significantly lower to those at 0 min hemodialysis (p < 0.001). Correlation between calcium content of erythrocytes and echinocyte percentages shows a significantly positive relationship at 45 min hemodialysis (r = 0.368, p < 0.05) but no significant relationship at 0 min hemodialysis and 240 min hemodialysis. In conclusion, uremic patients under hemodialysis present with high calcium content in erythrocytes and abnormal erythrocytes like echinocytes. A rapid and transient increase of erythrocyte calcium is also accompanied by transient elevation of echinocytes in the first hour of hemodialysis (45 min hemodialysis), which returns after hemodialysis to lower than prehemodialysis levels.

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.

Is erythrocyte damage prevented by gardos effect in hemodialyzed uremic patients?

The purpose of this study was to determine the changes of calcium and potassium content in red blood cells (RBC) from uremic patients during a hemodialysis (HD) session. In 17 uremic patients on HD, the calcium and potassium content of RBC was determined in 3 blood samples collected at 0 min-HD (pre-HD), 45 min-HD, and 240 min-HD (end-HD) during a 4 h HD session. The calcium and potassium content of RBC also was determined in 20 normal subjects (controls). The mean values (+/-SD) of RBC calcium content in patients at 0 min-HD, 45 min-HD, and 240 min-HD were 1.95 +/- 0.34, 2.82 +/- 0.50, and 2. 05 +/- 0.4 microg/ml, respectively, and in controls 0.61 +/- 0.14 microg/ml. These values show that the RBC calcium in patients was generally significantly higher (p < 0.0001) in comparison to that of controls. The RBC calcium at 45 min-HD was significantly higher as compared to that at 0 min-HD and at 240 min-HD (p < 0.0001). The mean values (+/-SD) of RBCs' potassium in uremic patients at the previously mentioned measurements were 95.9 +/- 3.34, 92.5 +/- 4.32, and 93.85 +/- 3.89 mEq/L, respectively, and in controls 98.46 +/- 2. 30 mEq/L. These values show that RBC potassium of patients was generally significantly lower in comparison to controls (0 min-HD: p < 0.01, 45 min-HD and 240 min-HD: p < 0.001). Potassium decrease also was significantly lower at 240 min-HD (p < 0.01) and even lower at 45 min-HD (p < 0.001) compared to that at 0 min-HD. In conclusion, uremic patients during an HD session present a high calcium and a low potassium content of erythrocytes. These changes may prevent swelling of the cells (Gardos effect).

Cytokine release and serum lipoprotein (a) alterations during hemodialysis.

It has been reported recently that a number of cytokines, mainly tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6, can alter lipid metabolism and produce hyperlipidemia. Studies in hemodialysis (HD) patients have demonstrated increased production of these cytokines during HD. In order to investigate any possible relationship between changes of cytokines and lipid concentrations during HD in the serum of 25 uremic patients on chronic HD using modified cellulose membranes, TNFalpha, IL-1beta, IL-6, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein a (Lp[a]), and total proteins were measured immediately before (pre-HD) and after HD (post-HD), in one session. The post-HD values were corrected according to the hemoconcentration based on the changes in serum total proteins. Serum TNFalpha and IL-1beta levels were significantly increased from 38.24 +/- 17.85 pg/ml and 2. 60 +/- 3.64 pg/ml pre-HD to 48.86 +/- 25.21 and 3.49 +/- 4.08 pg/ml post-HD, p < 0.001 and p < 0.05 respectively. Also Lp(a) levels presented a statistically significant increase post-HD and were almost doubled (pre-HD: 15.41 mg/dl, to post-HD: 27.39 mg/dl, p < 0. 05). Serum IL-6 as well as serum TC, TG, HDL-C, and LDL-C did not show any statistically significant alterations during HD. A significant positive correlation was detected between TNFalpha and Lp(a) values post-HD (r: 0.413, p: 0.04), but not between pre-HD values. No further relationship between serum cytokines and the other estimated lipid parameters was observed, either between pre- or post-HD values. Our results indicate that release of TNFalpha and IL-1beta during HD have no effect on serum lipids concentration, except on Lp(a). It seems that the acute rise of this lipoprotein during hemodialysis may be related with the TNFalpha overproduction.

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.