Bojan Knap

Treatment of hyperlipidemic acute pancreatitis with plasma exchange: a single-center experience.

Of the cases of acute pancreatitis, 1–7% are caused by severe hypertriglyceridemia and can be treated with plasma exchange (PE). We report on a large series of patients with acute hyperlipidemic pancreatitis (HLP) treated with PE. In the 1992–2008 period, 50 patients (45 ± 8 years old, 92% male) with acute HLP were treated with PE, during which 1–2 plasma volumes were exchanged. Heparin was used as anticoagulant in 85% of the procedures, and citrate in the rest. Cholesterol and triglycerides were measured before and after PE. In the 2003–2008 cohort of 40 patients, we retrospectively recorded an Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the first PE session, hospital mortality, and length of hospital stay. A total of 79 PE treatments were done, 1–5 per patient. The volume exchanged was 4890 ± 1300 mL over a duration of 3.5 ± 2 h. During the first PE, the triglycerides were lowered from 58.9 ± 40.8 to 10.8 ± 10.8 mmol/L, and the total cholesterol was lowered from 20.0 ± 7.6 to 5.7 ± 4.3 mmol/L. In 10% of the procedures the plasmafilter was replaced, and in 3% the filter was clotted. Hypotension occurred in 3% of PE and there was one case of gastrointestinal bleeding after PE with heparin anticoagulation. In the 2003–2008 cohort, the median APACHE II score was 5 (range 0–15), the median overall hospital stay was 18 days (range 3–142 days) and the hospital mortality was 15%. To conclude, in acute hyperlipidemic pancreatitis, one to two plasma exchanges effectively reduce the serum triglyceride level. There is a low rate of procedure‐related complications. A mortality rate of 15% is considerable.

Regular Exercise as a Part of Treatment for Patients With End‐stage Renal Disease

Abstract:  Physical inactivity and its negative influence on health and the quality of life is a common problem generally, especially in patients with chronic illness and also in patients with end‐stage renal disease. Motivation for regular physical exercise could be a problem. A supervised outpatient program in a rehabilitation center, a home exercise rehabilitation program and an exercise rehabilitation program during the first hours of the hemodialysis treatment with a bed bicycle ergometer in the renal unit could be carried out. Low intensity aerobic activity has a favorable effect on cardiovascular risk factor, and gymnastics to increase strength, flexibility and coordination, as well as relaxation techniques are very effective exercises in a rehabilitation program. The positive influence of individual regular exercise on health, quality of life, physical exercise capacity, endurance, muscle strength, social, professional and emotional status is also very high in patients. Side effects of exercise are very rare.

Fibroblast Growth Factor 23 and Left Ventricular Mass Index in Maintenance Hemodialysis Patients: Standard Versus Long Nocturnal Hemodialysis

Elevated levels of fibroblast growth factor 23 (FGF23) and phosphorus (P) have been linked to greater risks of left ventricular hypertrophy (LVH) in patients with end stage renal disease (ESRD). The aim of this study was to test if differences exist in a long nocturnal HD group in comparison with a group treated with standard daily thrice weekly dialysis. The attempt was to evaluate if elevated FGF‐23 levels, intact parathyroid hormone and P might be associated with left ventricular mass index (LVMI). Quantitative echocardiographic analyses were performed at baseline in 50 maintenance HD patients (17 women and 33 men, mean age: 56.4 ± 15.35 years, mean HD vintage: 9.06 ± 8.86 years, all patients are on HD thrice a week‐median duration 15 h/week, 10 of them on long nocturnal HD, median duration 24 h/week). LVMIs were calculated. FGF23 was measured in duplicate using a second generation C‐terminal enzyme‐linked immunosorbent assay and log of FGF‐23 values were computed. Mean LVMI was 136.44 ± 44.44 g/m2. Serum FGF‐23 levels were elevated when compared to population data with preserved kidney function (median 1388.5 RU/mL, range 252 to 24 336 RU/mL). There were no correlations recorded between log FGF‐23 levels and LVMI (r = 0.2, P = 0.66). LVMI was significantly lower in HD patients on long nocturnal dialysis procedure (r = −0.31, P = 0.05). Patients treated with long nocturnal HD showed lower LV mass, lower P‐values and higher 25‐OH‐D3 supply. Plasma FGF‐23 concentration was comparable between the groups and was not associated with LVMI in our maintenance HD patients.

Hemodialysis Catheters With Citrate Locking in Critically Ill Patients With Acute Kidney Injury Treated With Intermittent Online Hemofiltration or Hemodialysis

The purpose of the study was to compare the long‐term catheter‐related complications associated with temporary untunneled hemodialysis catheters, locked with citrate in the interdialysis period, inserted in critically ill patients with acute kidney injury, between different catheter insertion sites (femoral vs. jugular and subclavian) and catheter types (single‐lumen [SL] vs. double‐lumen [DL]). In a retrospective clinical study, the long‐term catheter‐related complications in 290 critically ill patients treated with intermittent high‐volume online hemofiltration or hemodialysis between December 2004 and January 2008 were analyzed. Among 534 inserted catheters, 493 (92.3%) were femoral, 29 (5.4%) jugular, and 12 (2.3%) subclavian; 304 (56.9%) were SL and 230 (43.1%) were DL. There were 125 (20.3/1000 catheter days [c.d.]) thrombotic complications, while infectious complications were exceptionally rare, that is, only 13 (2.1/1000 c.d.), of which 10 (1.6/1000 c.d.) were possible catheter‐related bloodstream infections and 3 (0.5/1000 c.d.) exit‐site infections. The incidence rate of all thrombotic complications was significantly lower in all jugular and subclavian vs. all femoral catheters (7.7/1000 c.d. vs. 21.8/1000 c.d., P = 0.01), and in all SL vs. DL catheters (11.4/1000 c.d. vs. 32.2/1000 c.d., P < 0.001). The incidence rate of any possible catheter‐related bloodstream and exit‐site infections was not significantly different in all jugular and subclavian vs. all femoral catheters, neither in femoral SL vs. DL catheters. The major long‐term catheter‐related complications were thrombotic, and significantly more frequent in DL vs. SL catheters. Infectious complications were exceptionally rare, most probably due to the strict catheter care protocol, as well as the routine use of a citrate catheter lock and antibiotic ointment at the catheter exit‐site.

Antioxidant Enzymes Show Adaptation to Oxidative Stress in Athletes and Increased Stress in Hemodialysis Patients

The aim of the study is to compare oxidative stress in hemodialysis patients in controls and in rowers. The patients are a model of decreased antioxidant capacity, and the athletes (rowers) are a model of the highest antioxidant capacity due to their chronic adaptation to demanding training. Thirty‐five subjects participated in the study, 9 patients with end‐stage renal disease treated by hemodialysis, 12 healthy young subjects from the normal population, and 14 rowers. The antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase, as well as non‐transferrin‐bound iron as a promoter of free radical damage, were determined. Blood analysis was taken in dialysis patients in the morning, before the dialysis procedure. There was significantly higher activity of catalase in dialysis patients (catalase 4.26 ± 0.35 mkat/g Hb) compared to the controls (catalase 2.73 ± 0.38 mkat/g Hb) and rowers (catalase 1.71 ± 0.30 mkat/g Hb). Superoxide dismutase activity was significantly lower (10.42 ± 1.46 µkat/g Hb) than in the controls (11.94 ± 1.18 µkat/g Hb) and rowers (14.09 ± 0.92 µkat/g Hb). There was no significant differences between glutathione peroxidase activities in the three groups. Superoxide dismutase and Se were higher in rowers than in dialysis patients (P < 0.05). The concentrations of both non‐transferrin‐bound iron and ferritin were significantly higher in dialysis patients. Hemodialysis patients might have increased oxidative stress, which is characterized by significantly higher erythrocyte enzyme activity of catalase and lower activity of superoxide dismutase. Top rowers had increased superoxide dismutase and glutathione peroxidase, perhaps because of adaptation during training, which was not the case in dialysis patients and controls.

Automated assay for non-transferrin-bound iron in serum samples

Abstract Background: Non-transferrin-bound iron (NTBI) is a powerful promoter of free radical damage and highly toxic to biological systems, resulting in oxidative damage to proteins, lipids and DNA. Methods: This assay is based on the binding of serum NTBI by the chelator nitrilotriacetic acid (NTA) and measurement of the ultrafiltrated Fe-NTA complex with the ferrozine reagent kit by a biochemical analyzer. To determine NTBI at extremely low concentrations, the program parameters for serum iron measurement were modified. Results: Linearity was up to 15 μmol/L with analytical recovery of 93%–103%. The limit of detection was 0.076 μmol/L. The within-run coefficient of variation was 2.37%, 1.23%, and 0.812% at concentrations of 0.338, 1.717, and 5.916 μmol/L, respectively. NTBI concentrations measured after exercise in samples obtained from 14 rowers, divided into two groups, were substantially higher in all samples. The median NTBI concentrations (range) before and after exercise were 0.197 (–0.11 to 0.58), and 3.353 (2.39–8.97) μmol/L, respectively, in older rowers and 0.197 (–0.18 to 1.17), and 1.360 (0.47–2.49) μmol/L, respectively, in younger rowers. Conclusions: With the described modification for serum iron determination, NTBI can be measured with high sensitivity and specificity. The data presented are illustrative examples of the applicability of this assay. Clin Chem Lab Med 2010;48:1427–32.

Effect of Switching to Nocturnal Thrice‐Weekly Hemodialysis on Clinical and Laboratory Parameters: Our Experience

Long or frequent hemodialysis schedules are reported to improve clinical outcomes. We report here our experience with an in‐center, nocturnal, thrice‐weekly hemodialysis program. We retrospectively analyzed the effect of switching 10 patients (8 male, age 45 ± 11 years, renal replacement therapy vintage 12 ± 8 years) from regular, 4–5 h, thrice‐weekly hemodialysis to 8 h nocturnal, in‐center hemodialysis as regards dialysis efficiency, chronic kidney disease‐metabolic and bone disease (CKD‐MBD) parameters, blood pressure, and anemia. With more intense dialysis, the mean predialysis creatinine and urea decreased significantly (1092 ± 195 vs. 961 ± 154 μmol/L, P < 0.01 and 30.8 ± 4.6 vs. 25.5 ± 2.9 mmol/L, P < 0.01), while the decrease in potassium was insignificant (5.9 ± 0.7 vs. 5.6 ± 0.5 mmol/L), but in 3/10 patients, dialysate potassium was increased. Three months after starting nocturnal hemodialysis, no significant influence on pre‐dialysis blood pressure was observed (143/80 vs. 140/80 mmHg), but antihypertensive medications were reduced in two patients. The mean dry weight reduced (74 ± 12 to 72 ± 12 kg) and the mean ultrafiltration increased insignificantly (3123 ± 1174 to 3434 ± 1341 mL). Serum calcium was stable, while phosphate reduced insignificantly (1.5 ± 0.5 to 1.2 ± 0.2 mmol/L), but 6/10 patients were able to discontinue phosphate binders, the dose was reduced in one, and phosphate was added to dialysate in 3/10 patients. Intact parathyroid hormone values were within the target range, except in patients post‐parathyroidectomy. There were no differences in hemoglobin (121 ± 6 vs. 122 ± 8 g/L), and the mean epoetin dose decreased insignificantly (5950 ± 3947 vs. 5250 ± 4238 IU/week). To conclude, improved phosphate and potassium control and reduction in phosphate binders were observed after switching to nocturnal hemodialysis. There was an insignificant reduction of epoetin dose and antihypertensive medications.

Long-Term Citrate Anticoagulation in Chronic Hemodialysis Patients

In some cases, long‐term (>3 months) citrate anticoagulation is needed in maintenance hemodialysis patients due to a persistent bleeding risk. In this retrospective observational study, we present our experience and assess its safety and effects on mineral and bone disorder parameters. Sixteen patients (mean age 67 ± 15 years) were treated with long‐term citrate anticoagulation. The indications were: recurrent gastrointestinal bleeding in nine patients, heparin‐induced thrombocytopenia, retroperitoneal hematoma, chronic subdural hematoma, proliferative diabetic retinopathy, vascular malformations in the brain in one patient, and others in two patients. Metabolic complications and intact parathyroid hormone (iPTH) were analyzed. Citrate anticoagulation was performed for 4 months to 6.3 years (median 12 months). Ionized calcium was stable during the procedures; hypocalcemia (<0.9 mmol/L) was rare (2.1% of procedures), and there was one case of severe symptomatic hypocalcemia. There were no clinically significant acid–base disturbances and no clotting problems. In the short term (1–3 months after starting citrate), the iPTH increased in 73% of patients (from 325 ± 310 to 591 ± 793 pg/L, P = 0.11, N = 11). In the long term (1–2 years), an increase in iPTH was observed in 3/6 patients. The time period (before/after starting citrate) was a significant predictor of iPTH using main‐effects anova (P < 0.001). To conclude, long‐term citrate anticoagulation in chronic hemodialysis patients is safe. Mild hypocalcemia during dialysis with citrate anticoagulation may contribute to a short‐ and long‐term increase in iPTH in these patients. Further studies on long‐term citrate anticoagulation are necessary.

Membrane plasma exchange for the treatment of thrombotic thrombocytopenic purpura.

The aim of our report is to present our 11‐year experience with therapeutic membrane plasma exchange therapy for the treatment of idiopathic thrombotic thrombocytopenic purpura syndrome (TTP). In 56 patients, membrane plasma exchange therapy was initiated immediately and performed once or twice daily until the platelet count normalized. During each plasma exchange procedure, 1–1.5 plasma volumes (3606 ± 991 mL) were replaced with fresh frozen plasma. In 37 females and 19 males (44 ± 21 years), 1066 plasma exchange procedures were performed. The average duration of treatment was 23 ± 17 days. The average number of plasma exchanges was 19 ± 17 per patient. Renal impairment was detected in 36% of patients. At the initiation of plasma exchange treatment, the average platelet count was 31 ± 30 × 109/L and reached 199 ± 95 × 109/L thereafter. Fifty‐two of 56 (93%) patients demonstrated an excellent response to plasma exchange therapy, of whom 48 patients (86%) attained complete remission with a platelet count of more than 100 × 109/L. Four patients died soon after the initiation of plasma exchange therapy, when only 1–3 procedures had been performed. During the follow‐up period, six patients with complete remission had 1–5 subsequent relapses each year. One of them died of acute hemolytic reaction during the tapering of plasma exchange procedures. Three patients underwent additional splenectomy. Our experience with primary TTP supports the plasma exchange treatment with fresh frozen plasma as a mandatory, up‐to‐date therapy. Close monitoring during all 1066 procedures showed no serious side‐effects.

Comparison of the Pharmacological Effects of Paricalcitol Versus Calcitriol on Secondary Hyperparathyroidism in the Dialysis Population.

Management of secondary hyperparathyroidism (SHPT) in dialysis population includes the use of active vitamin D forms, among which paricalcitol was shown to be more effective at reducing parathyroid hormone (PTH) concentrations. A prospective randomized study comparing the effectiveness and safety of peroral paricalcitol and calcitriol in suppressing PTH concentrations in 20 hemodialysis patients was performed comparing the influence of agents on PTH suppression, calcium (Ca) and phosphate (P) level and calcium‐phosphorus product (C×P). The study was performed in an “intent to treat” manner with primary end point in reduction of PTH level in the target area of 150 > PTH < 300 ng/L after 3 months. At the time point 3 months after therapy induction paricalcitol and calcitriol were equally efficient at correcting PTH levels, with paricalcitol showing significantly less calcemic effect than calcitriol.