Use of myoglobin as a marker and predictor in myoglobinuric acute kidney injury.

Serum creatine kinase (CK) is routinely used as a marker in the assessment of rhabdomyolysis and acute myoglobinuric kidney injury (Mb-AKI), while the use of myoglobin is much less explored in this respect. We retrospectively analyzed the incidence of Mb-AKI (creatinine [Cr] > 200 µmol/L) and the need for hemodialysis (HD) in 484 patients (70.5% males) with suspected rhabdomyolysis, grouped according to peak serum myoglobin (A: 1-5 mg/L, B: 5-15 mg/L, C: >15 mg/L). The median peak myoglobin was 7163 µg/L. Both peak Cr and peak CK were significantly higher in group C. The incidence of Mb-AKI was 24.6% in group A, 38.6% in group B (P < 0.01 vs. group A), and significantly higher (64.9%) in group C (P < 0.001 vs. groups A and B). Fifty-one patients (10.5%) needed HD, the proportion increasing from 6.7% in group A, and 12.3% in group B (NS), to 28.1% in group C (P < 0.001 vs. group A, P 0.01 vs. group B), and reaching 36.8% with myoglobin >20 mg/L. Creatine kinase correlated with the severity of rhabdomyolysis, but less so with Mb-AKI. The peak Cr levels were not significantly different between patients divided by CK 60 µkat/L, or grouped into CK tertiles or quartiles. A significant proportion of patients with rhabdomyolysis experienced Mb-AKI, whose frequency increased in parallel with myoglobin levels. Myoglobin levels above 15 mg/L were most significantly related to the development of AKI and the need for HD. Blood myoglobin could serve as a valuable early predictor and marker of rhabdomyolysis and Mb-AKI.

Some kinetic considerations in high cut-off hemodiafiltration for acute myoglobinuric renal failure.

The kinetics of myoglobin in severe rhabdomyolysis and dialysis-dependent myoglobinuric acute kidney injury (Mb-AKI) is still not well elucidated, and more detailed knowledge could improve the now empiric use of rapid extracorporeal myoglobin removal by high cut-off (HCO) hemodialysis treatments. Eighteen adult patients with severe dialysis-dependent Mb-AKI (median serum concentration of myoglobin 57.4 mg/L) participated in the prospective clinical study, assessing myoglobin kinetics during HCO hemodiafiltration (HCO HDF). High initial serum concentrations of myoglobin (median 57.4 mg/L), together with protracted myoglobin appearance in the blood, indicated a large accumulation of myoglobin in body fluids. Extra-renal endogenous metabolic myoglobin clearance was delayed, with a slow exponential fall in serum myoglobin (t½ 35 h). A mean myoglobin clearance of 90-94 mL/min, a reduction ratio of 80%, and a rapid exponential fall (t½ 1 h) in serum and dialysate myoglobin were achieved by HCO HDF. Half of the cumulative myoglobin removal was accomplished in 3-5 h, with an additional removal of 7% each hour thereafter. A 2.4-fold rebound in serum myoglobin followed the HCO procedures. Large amounts of myoglobin are released into the circulation, and its endogenous metabolic clearance in dialysis-dependent Mb-AKI is slow. Owing to its rapid and highly efficient myoglobin elimination, HCO HDF may represent a valuable tool in the initial management of severe Mb-AKI, with a potential for earlier application in the future.

Dialysis patients after kidney graft failure: Slovenian experience.

Increased mortality has been reported in patients starting dialysis after kidney graft failure. In this study we analyzed this subgroup of dialysis patients based on the data from the Slovenian Renal Replacement Therapy Registry. Patients starting dialysis after graft failure in the period between 2004 and 2008 were identified from the registry. Demographic, clinical and treatment data, as well as survival were compared to incident dialysis patients, who were on the waiting list or preparing for enrollment. There were 49 patients starting dialysis after 7.9 ± 6.4 years spent with a functioning graft and a total of 13.7 ± 7.4 years on renal replacement therapy. Their mean age was 48.3 ± 11.0 years (vs. 48.2 ± 13.9 years in incident patients, P = 0.96), 53% were male, and all were on hemodialysis. By the end of 2008, 8 (16%) patients had been re-transplanted (after a median of 27.5 months) and 11 (23%) had died (after a median of 1.4 months of dialysis). The cause of death was infection in five patients, a cardiovascular event in three, malignancy in two, and a cerebrovascular event in one patient. Deceased patients were significantly older, but similar to survivors in other parameters. Unadjusted one- and three-year survival rates after graft failure were both 77%, which was significantly worse than in incident patients (P < 0.001). To conclude, patients after graft failure have increased mortality in the first year after starting dialysis, but patients surviving the first year have good survival thereafter. Studies focusing on the early period after graft failure are necessary to improve outcomes.

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.

High cut-off membrane hemodiafiltration in myoglobinuric acute renal failure: a case series.

Acute renal failure is a major complication of rhabdomyolysis. New membranes for hemodialysis have been developed with a high cut-off pore size allowing efficient removal of myoglobin. We report on six patients treated by hemodiafiltration with a high cut-off membrane (HCO-HDF) for myoglobinuric acute renal failure. Rhabdomyolysis was caused by infection in two patients, by a statin in one patient and a non-traumatic crush in another, and followed cardiovascular surgery in two others. Ten HCO-HDF procedures were performed. A high cut-off hemofilter was used, with citrate anticoagulation and postdilutional fluid substitution of 2-3 L/h, dialysate flow 500 mL/min, and blood flow within 250-300 mL/min. Albumin losses were replaced by infusion of human albumin solution, and the mean myoglobin reduction ratio was 77% (range, 62-89%). An excellent clearance of 81 mL/min (range 42-131 mL/min) was achieved. Nearly 5 g of myoglobin was removed into the dialysate collected in one of the procedures. A high rebound in serum myoglobin, on average to 244% of the post-procedure myoglobin level, was observed. The four patients alive at the time remained anuric for a week. Slow myoglobin elimination with a mean half-time of 39 h (range 19-59 h) was observed in that period. Highly efficient myoglobin removal by high cut-off membrane hemodiafiltration was demonstrated in our patients. Rapid redistribution from the extracellular fluid and sustained myoglobin release were suggested by the high rebound observed. Elimination of myoglobin within the body was shown in our study to occur slowly during the period of anuria.

Citrate anticoagulation during post-dilution hemodiafiltration with a high cut-off (Theralite) membrane.

Citrate anticoagulation has not yet been described for hemodiafiltration (HDF) with high cut-off (HCO) membranes, which can be used in the treatment of cast nephropathy secondary to multiple myeloma. A 57-year-old male patient with multiple myeloma and acute renal failure was treated with HDF using a HCO membrane (Theralite) each or every other day. Due to thrombocytopenia, citrate anticoagulation was done for the first 7 h, and anticoagulant-free HDF was performed for the last hour to avoid citrate accumulation. Magnesium, phosphate, and albumin were measured after 3, 6, and 8 h, and were replaced as necessary. Thirty-two post-dilution HDF procedures (8 h each, infusate 24 L) were performed with blood flow at 300-330 mL/h; sodium citrate 4% was infused at 300 mL/h and 1 mol/L calcium chloride was infused at a mean rate of 14.6 ± 1.1 mL/h. Calcium-free dialysate/infusate was used. Ionized calcium was stable (1.10 ± 0.06 before and 1.08 ± 0.06 mmol/L after HDF). Magnesium was stable (0.67 ± 0.12 before and 0.68 ± 0.05 mmol/L after HDF), with an average 390 ± 180 mg per procedure, substituted orally. There was no metabolic alkalosis or hypernatremia after the procedures, and no significant clotting was noted. The total/ionized calcium ratio (1.87 ± 0.22 before vs. 1.56 ± 0.20 after 6 h) and the corrected/ionized calcium ratio (2.02 ± 0.21 before vs. 1.88 ± 0.27 after 6 h) decreased during HDF, indicating no citrate accumulation. Citrate anticoagulation was effectively performed during 8 h of HCO membrane HDF. There were no side effects of citrate anticoagulation, nor were any signs of citrate accumulation noted.

Vascular access in children on chronic hemodialysis: a Slovenian experience.

The aim of our study was to report our experience with arteriovenous fistulas (AVFs) and non-cuffed central venous catheters (CVCs) in children and adolescents with end-stage renal disease (ESRD) on hemodialysis (HD). The children with ESRD (18 years or younger) who were hemodialyzed at the Center of Dialysis and Transplantation, Children's Hospital, Ljubljana, in the period between December 1998 and December 2010 were included in our retrospective study. We recorded the data considering the CVCs and AVFs used for HD. Thirty-one children (13 females, 18 males) with ESRD received HD treatment. The mean patient age when HD was started was 13.3 ± 3.4 years. Altogether, 35 AVFs were created, and the primary failure rate was 25.7% (9/35). The time to maturation was 4.0 ± 2.5 months. The mean patency of the AVF was 42.5 ± 51.9 months. Seventy-seven CVCs (non-cuffed) were inserted in the observation period; 89.6% of the CVCs were inserted in the jugular vein, and citrate locking was used in the interdialysis period. The CVCs were removed after 0.1-17.4 months (3.6 ± 3.7 months). The incidence of bacteremia was 0.9 episodes per 1000 catheter days. The preferred vascular accesses for pediatric hemodialysis are native AVFs; however, a single lumen, non-cuffed, citrate-locked CVC placed in a jugular vein can be acceptable as a long-term vascular access when AVF cannot be constructed or used.

Two single-lumen noncuffed catheters in the jugular vein as long-term vascular access: a preliminary report.

Two single-lumen, noncuffed catheters in the same jugular vein have been used as preferred vascular access in our hemodialysis (HD) and apheresis patients in past years. The aim of this retrospective study was to analyze the clinical outcome of such a vascular access and the reasons for catheter removal. In 129 adult patients, aged 69 ± 13 years, 56% males, treated by HD (121 patients) or apheresis (8 patients), two single lumen, pre-curved 8 Fr catheters (Medcomp, Harleysville, PA, USA) inserted into the same jugular vein were used as vascular access between January 2009 and April 2010. The catheters were inserted into the left jugular vein in 21 patients, and into the right jugular vein in 108 patients. A 30% solution of trisodium-citrate was used as a locking solution, and 2% mupirocin ointment was routinely applied to the exit site. The catheters were removed in 86 patients after 1-288 days, median 17.5 days. In 74 patients, there was either no need for further dialysis or an arteriovenous fistula was constructed (17 patients). In 10 patients, wire exchange was performed for correction of a displaced functional catheter (after 6-201 days), and in only two patients the catheters were removed due to infection on days 10 and 184. The longest period of a catheter functioning without intervention was 387 days. Fifteen patients died with functional catheters left in place (duration 1-387 days). In four patients, the catheters were still functional at the time of analysis (duration 198-268 days). Another nine patients were transferred to other dialysis centers (after they had been followed up at our center lasting for 1-63 days), with no data on their outcome after transfer. Fifteen patients were lost to follow up after insertion. Two single-lumen, noncuffed catheters in the same jugular vein, locked with 30% citrate, seem to be a safe and long lasting method of vascular access for hemodialysis and apheresis in some patients, but further prospective studies are needed to evaluate the clinical outcome of this type of vascular access.

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.

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 x 10(9)/L and reached 199 +/- 95 x 10(9)/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 x 10(9)/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.

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.

Vascular access recirculation in hemodialysis patients with two noncuffed, single-lumen, jugular catheters in the same jugular vein.

Having achieved excellent results with single-lumen temporary hemodialysis catheters as a long-term vascular access in our center, in this study we examined the amount of vascular access recirculation in the case of using two single-lumen catheters in a single jugular vein. In 11 adult end-stage renal disease patients on chronic hemodialysis (HD), vascular access recirculation was studied using a thermodilution technique during dialysis at our center. The vascular access in all patients consisted of two pre-curved, 15 cm-long, 8-Fr catheters inserted in the right jugular vein. Recirculation measurements were performed with the blood flow set to 250 mL/min in all patients. In five patients, additional measurements were performed with the blood flow set to 200 mL/min. During 16 HD procedures, 55 recirculation measurements were taken. The rate of recirculation was <15% in 50 measurements, between 15% and 20% in four measurements, and >20% in one measurement. The average recirculation rate during a single procedure was <15% in 10 patients, and 16.2% in one patient. We did not find any significant differences in the recirculation rates measured either at higher or lower blood flow rates. The clinical importance of vascular access recirculation was noted in a single patient. Vascular access recirculation in hemodialysis patients with two single-lumen catheters in the same jugular vein is mostly acceptable. Some measures for preventing clinically important recirculation are also suggested.