Lennart Lundberg

Low-dose atorvastatin in severe chronic kidney disease patients: a randomized, controlled endpoint study.

Objective. There have been no endpoint studies with statins for patients with severe renal failure. The purpose of this prospective, open, randomized, controlled study was to investigate whether atorvastatin (10 mg/day) would alter cardiovascular endpoints and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 (creatinine clearance < 30 ml/min). Material and methods. The study subjects comprised 143 patients who were randomized either to placebo (controls; n=73; mean age 69.5 years) or to treatment with atorvastatin (n=70; mean age 67.9 years). The patients included were either non-dialysis (n=33), haemodialysis (n=97) or peritoneal dialysis (n=13) patients. Analysis focused on the primary endpoints of all-cause mortality, non-lethal acute myocardial infarction, coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty. Statistical analysis for endpoint data was mainly by intention-to-treat. Results. Primary endpoints occurred in 74% of the subjects. There was no difference in outcome between the control and atorvastatin groups. The 5-year endpoint-free survival rate from study entry was ≈20%. Atorvastatin was withdrawn in ≈20% of patients due to unacceptable side-effects. In the atorvastatin group, low-density lipoprotein (LDL) cholesterol was reduced by 35% at 1 month and then sustained. The controls showed a progressive reduction in LDL cholesterol until 36 months. Conclusions. Although atorvastatin reduced total and LDL cholesterol effectively it was not beneficial regarding the long-term outcomes of cardiovascular endpoints or survival. In contrast to other patient groups, patients with severe chronic kidney disease, especially those on dialysis, seem to derive limited benefit from this lower dose of atorvastatin.

Granulocyte elastase, beta-thromboglobulin, and C3d during acetate or bicarbonate hemodialysis with Hemophan compared to a cellulose acetate membrane.

Twenty-two patients were dialysed in a cross-over design using Hemophan® or cellulose acetate membranes. The dialysate buffer was acetate (n = 12) or bicarbonate (n = 10). Blood was sampled at 0, 15, 60 and 180 min and mean values were adjusted for changes in total protein in each sample. At 15 min during dialysis a decrease in leukocytes and platelets occurred with both membranes, irrespective of the buffer (Wilcoxon, p < 0.006). During dialysis, increases were found in granulocyte elastase inhibitor complex (E-α1-PI), β-thromboglobulin and C3d. β2-microgrobulin was not significantly changed in blood after dialysis with Hemophan® or cellulose acetate membranes with bicarbonate buffer. Side effects were more pronounced at 180 min during dialysis with bicarbonate in patients using cellulose acetate than with Hemophan® (p = 0.021, n = 8). Hemophan® seemed to be more favourable than cellulose acetate membranes in regard to leukopenia and E- α1-PI. The dialysate buffer may also alter membrane biocompatibility.

Safety and efficacy of atorvastatin in patients with severe renal dysfunction

Objective. To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min. Material and methods. This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. Results. The follow-up period was a mean of 20±14.4 months (range 1–36 months) for those on atorvastatin versus 22±12.7 months (range 0.5–36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; −23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; −35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1–30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache. Conclusion. Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.

Lipoprotein lipase responds similarly to tinzaparin as to conventional heparin during hemodialysis

BackgroundLow molecular weight (LMW) heparins are used for anticoagulation during hemodialysis (HD). Studies in animals have shown that LMW-heparins release lipoprotein lipase (LPL) as efficiently as unfractionated (UF) heparin, but are less able to retard hepatic uptake of the lipase. This raises a concern that the LPL system may become exhausted by LMW-heparin in patients on HD. We have explored this in the setting of clinical HD.MethodsTwenty patients on chronic hemodialysis were switched from a primed infusion of UF-heparin to a single bolus of tinzaparin. There were long term follow up of variables for the estimation of dialysis efficacy as well as of the LPL release during dialysis and the subsequent impact on the triglycerides.ResultsThe LPL activity in blood was higher on tinzaparin at 40 but lower at 180 minutes during HD. These values did not change during the 6 month study period. There were significant correlations between the LPL activities in individual patients at the beginning and end of the 6 month study period and between the activities on UF-heparin and on tinzaparin, indicating that tissue LPL was not being exhausted. Triglycerides were higher during the HD-session with tinzaparin than UF-heparin. The plasma lipid/lipoprotein levels did not change during the 6 month study period, nor during a 2-year follow up after the switch from UF-heparin to tinzaparin. Urea reduction rate and Kt/V were reduced by 4 and 7% after 6 months with tinzaparin.ConclusionOur data demonstrate that repeated HD with UF-heparin or tinzaparin does not exhaust the LPL-system.

Skin and Plasma Autofluorescence During Hemodialysis: A Pilot Study

Skin autofluorescence (AF) is related to the accumulation of advanced glycation end products (AGEs) and is one of the strongest prognostic markers of mortality in hemodialysis (HD) patients. The aim of this pilot study was to investigate whether changes in skin AF appear after a single HD session and if they might be related to changes in plasma AF. Skin and plasma AF were measured before and after HD in 35 patients on maintenance HD therapy (nine women and 26 men, median age 68 years, range 33-83). Median dialysis time was 4 h (range 3-5.5). Skin AF was measured noninvasively with an AGE Reader, and plasma AF was measured before and after HD at 460 nm after excitation at 370 nm. The HD patients had on average a 65% higher skin AF value than age-matched healthy persons (P < 0.001). Plasma AF was reduced by 14% (P < 0.001), whereas skin AF was not changed after a single HD treatment. No significant influence of the reduced plasma AF on skin AF levels was found. This suggests that the measurement of skin AF can be performed during the whole dialysis period and is not directly influenced by the changes in plasma AF during HD.

Backdiffusion or bicarbonate may stimulate complement activation during haemodialysis with low-flux membranes.

Backdiffusion of dialysate during haemodialysis with low-flux membranes and the use of bicarbonate dialysatebase, may increase the risk for contamination. The influence on the complement system was studied by altering the flux of acetate or bicarbonate dialysate base across the membrane. Eight patients were dialysed with a transmembrane pressure of 100 mm Hg (group I) during the first 60 min to standardize the ultrafiltration (UF) and acetate as dialysate. In eight other patients (group II) the UF was “set at zero” ml during the first 60 min using an FCM 10-1 monitor (Gambro) and bicarbonate as base. The groups were dialysed three times on two hollow-fiber membranes made of Hemophan® and cellulose acetate (CA). Blood samples were taken at 0, 15, 60 and 180 min, and analysed for plasma protein, haematocrit and complement C3d. In group II there was a reduction in plasma protein concentration at 15 and 60 min (p<0.002) for Hemophan and at 60 min (p<0.01) using CA. C3d was increased at 15 min for both filters (p<0.03). The reduction of protein in group II was followed by changes in the haematocrit, indicating a backdiffusion of dialysate, which may contribute to the concomittant increase in C3d.

Formation of Blood Foam in the Air Trap During Hemodialysis Due to Insufficient Automatic Priming of Dialyzers

We were encouraged to investigate the reasons for large amounts of foam observed in bloodlines during hemodialysis (HD). Foam was visible in the venous air trap within the Artis Gambro dialysis device. Estimates of the extent of foam were graded (0-no foam, 10-extensive foam) by two persons that were blind to the type of dialyzer used. Thirty-seven patients were involved in the dialysis procedures. Consecutive dialyses were graded using dialyzers from Fresenius Medical Care (CorDiax dialyzers that were used for high flux HD-FX80 and FX100, and for hemodiafiltration-FX1000). The extracorporeal circuit was primed automatically by dialysate using Gambro Artis software 8.15 006 (Gambro, Dasco, Medolla Italy, Baxter, Chicago, IL, USA). The priming volume recommended by the manufacturer was 1100 mL, whereas our center uses 1500 mL. Extensive amounts of blood foam were visual in the air traps. Although the manufacturer recommended extension of priming volume up to 3000 mL, this did not eliminate the foam. Microbubble measurement during HD revealed the air to derive from the dialyzers. When changing to PF210H dialyzers (Baxter) and using a priming volume of 1500 mL, the foam was significantly less (P < 0.01). The extent of foam correlated with the size of the FX-dialyzer surface (P = 0.002). The auto-priming program was updated to version 8.21 by the manufacturer and the extent of foam in the air trap using FX dialyzers was now reduced and there was no longer a difference between FX and PF dialyzers, although less foam was still visible in the venous air trap during several dialyses. In conclusion, this study urgently calls attention to blood foam development in the venous air trap when using Artis devices and priming software 8.15 in combination with Fresenius dialyzers. Updated auto-priming software (version 8.21) of Artis should be requested to reduce the extent of foam for the Fresenius dialyzers. Other interactions may also be present. We recommend further studies to clarify these problems. Meanwhile caution is warranted for the combined use of dialysis devices and dialyzers with incompatible automatic priming.

Skin and Plasma Autofluorescence During Hemodialysis: A Pilot Study: Thoughts and Progress

Skin autofluorescence (AF) is related to the accumulation of advanced glycation end products (AGEs) and is one of the strongest prognostic markers of mortality in hemodialysis (HD) patients. The aim of this pilot study was to investigate whether changes in skin AF appear after a single HD session and if they might be related to changes in plasma AF. Skin and plasma AF were measured before and after HD in 35 patients on maintenance HD therapy (nine women and 26 men, median age 68 years, range 33-83). Median dialysis time was 4 h (range 3-5.5). Skin AF was measured noninvasively with an AGE Reader, and plasma AF was measured before and after HD at 460 nm after excitation at 370 nm. The HD patients had on average a 65% higher skin AF value than age-matched healthy persons (P < 0.001). Plasma AF was reduced by 14% (P < 0.001), whereas skin AF was not changed after a single HD treatment. No significant influence of the reduced plasma AF on skin AF levels was found. This suggests that the measurement of skin AF can be performed during the whole dialysis period and is not directly influenced by the changes in plasma AF during HD.

Skin and Plasma Autofluorescence During Hemodialysis

Skin autofluorescence (AF) is related to the accumulation of advanced glycation end products (AGEs) and is one of the strongest prognostic markers of mortality in hemodialysis (HD) patients. The aim of this pilot study was to investigate whether changes in skin AF appear after a single HD session and if they might be related to changes in plasma AF. Skin and plasma AF were measured before and after HD in 35 patients on maintenance HD therapy (nine women and 26 men, median age 68 years, range 33-83). Median dialysis time was 4 h (range 3-5.5). Skin AF was measured noninvasively with an AGE Reader, and plasma AF was measured before and after HD at 460 nm after excitation at 370 nm. The HD patients had on average a 65% higher skin AF value than age-matched healthy persons (P < 0.001). Plasma AF was reduced by 14% (P < 0.001), whereas skin AF was not changed after a single HD treatment. No significant influence of the reduced plasma AF on skin AF levels was found. This suggests that the measurement of skin AF can be performed during the whole dialysis period and is not directly influenced by the changes in plasma AF during HD.