Detoxification as a treatment goal in hepatic failure.

Acute liver failure (ALF) is a dramatic clinical syndrome with high mortality because of cerebral oedema (type A hepatic encephalopathy) and multi-organ failure. With intensive care medicine and emergent liver transplantation being the mainstay of treatment, alternatives to transplantation are increasingly needed. Ammonia has been recognised as a major toxin in patients with ALF. It can be effectively removed by haemodialysis, haemofiltration and artificial liver support (a combination of extracorporeal toxin absorption and haemodialysis). Previous studies of extracorporeal detoxification, however, have either not specifically targeted ammonia or were hampered by poor biocompatibility and obsolete pathophysiological assumptions, ultimately failing to improve the prognosis. Moreover, most patients were treated only late after the emergence of advanced HE and multi-organ failure, while detoxification should prevent these complications. Acute-on-chronic liver failure (AOCLF) occurs in the setting of chronic liver disease and has an equally poor prognosis. Here, the goals of extracorporeal blood detoxification are renal support and haemodynamic stabilisation in order to support recompensation. Patients with AOCLF, unfortunately, are at a risk for treatment-related complications including bleeding, thrombocytopenia, hypotension and acute renal failure, making biocompatibility a critical issue. Peritoneal dialysis could possibly emerge as a more biocompatible way of treating refractory hepatorenal syndrome. This article will critically analyse the pathophysiological concepts and goals of extracorporeal detoxification in acute and chronic liver diseases.

Effective use of cinacalcet for the treatment of secondary hyperparathyroidism in Austrian dialysis patients--results of the Austrian cohort of the ECHO study.

BACKGROUND: Despite extensive use of standard therapy for secondary hyperparathyroidism (sHPT) in dialysis patients, still most patients do not achieve the recommended treatment targets. In a pan-European observational study (ECHO), the effectiveness of the calcimimetic cinacalcet for the treatment of sHPT was evaluated in real-world clinical practice. A sub-analysis of the entire Austrian study cohort is presented. METHODS: Adult dialysis patients who had initiated cinacalcet therapy were included. Data on biochemical parameters of bone and mineral metabolism (intact parathyroid hormone [iPTH], calcium [Ca] and phosphorus [P]) and concurrent medication were collected 6 months prior to the initiation of cinacalcet, at initiation (baseline) and after up to 12 months of active treatment. RESULTS: A total of 320 patients (mean age (±SD): 56 (±14) years) from 34 Austrian dialysis centres were enrolled. At baseline, patients presented with elevated serum iPTH (median 605 pg/ml) and hyperphosphataemia (median 2.1 mmol/l). After 12 months of cinacalcet treatment, serum iPTH (median percentage change -48%), calcium (-2%) and phosphorus (-6%) decreased. The greatest iPTH reduction (-66%) was found in patients with most severe sHPT (>800 pg/ml at baseline). The proportion of patients achieving the recommended NKF/K-DOQI(™) treatment targets increased from baseline to month 12 for iPTH (3-36%) and phosphorus (24 to 39%) and remained stable for calcium (51 to 50%), respectively. No patient had all 3 parameters simultaneously within NKF/K-DOQI(™) treatment targets at baseline, while 7% of patients achieved this treatment goal after 12 months. During the study the use of the phosphate binder sevelamer remained fairly stable, while the relative percentage use of calcium-based phosphate binders increased and the usage of aluminium-containing binders decreased; vitamin D analogue use remained stable. CONCLUSION: Additional use of cinacalcet improved biochemical parameters of bone and mineral metabolism and enabled more patients to achieve and maintain the KDOQI(™) treatment targets for serum iPTH, calcium and phosphorus.

Treatment of Hemodialysis-Associated Adynamic Bone Disease with Teriparatide (PTH1-34): A Pilot Study.

BACKGROUND: Adynamic bone disease (ABD) is caused by a relative or absolute parathyroid hormone (PTH) deficiency. Teriparatide (PTH1-34) is an osteoanabolic agent in clinical use. Here, it was hypothesized that treatment with teriparatide improves bone mineral density (BMD) of ABD patients. PATIENTS AND METHODS: Seven hemodialysis patients with ABD and a median iPTH level of 22 pg/ml were evaluated in this open-label, prospective, 6-month observational pilot-study. All patients received 20 µg teriparatide/day subcutaneously. Serologic bone markers, BMD and coronary artery calcification (CAC) were measured at baseline and after 6 months. RESULTS: Teriparatide therapy led to a significant increase in lumbar spine (0.885 ± 0.08 vs. 0.914 ± 0.09 g/cm(2), p < 0.02), but not femoral neck (0.666 ± 0.170 vs. 0.710 ± 0.189 g/cm(2), p = 0.18) BMD. Compared to pretreatment values, calculated monthly changes in BMD improved significantly in both the lumbar spine and femoral neck (p < 0.02). Changes in serologic markers of bone turnover and CAC scores were not statistically significant. CONCLUSION: Teriparatide therapy might improve low BMD in hemodialysis patients with ABD. Further clinical studies are needed to establish teriparatide as a therapeutic option for dialysis patients with ABD.

Comparison of two dialysers (AN69ST vs. FX100) for heparin-free dialysis in patients with oral anticoagulation.

BACKGROUND: Heparin-free dialysis (HFD), i.e. only priming of the dialyser and no systemic heparinization, might reduce the risk of bleeding in dialysis patients receiving oral anticoagulation. The efficacy of HFD with two different membranes [polyacrylonitrile (AN69ST) vs. polysulphone (FX100)] was therefore investigated. METHODS: In a crossover design, 10 patients were treated with either membrane for 1 week (total 30 sessions). Weekly Kt/V and urea reduction rate (URR) were measured and thrombus formation evaluated by measurement of D-dimer and inspection of the air traps and dialyser. RESULTS: Change of clotting markers was similar with both membranes. Complete thrombosis occurred in 3/30 patients with the AN69ST and in 1/30 patients with the FX100 membrane. Kt/V did not differ between the groups, but the URR was slightly higher with the FX100. CONCLUSION: HFD prevents dialyser occlusion in the majority of patients treated with oral anticoagulants. Both polysulphone and polyacrylonitrile membranes seem to be equally effective.

Changes of coronary calcification after kidney transplantation.

BACKGROUND: Coronary artery calcification (CAC) in patients with end-stage renal disease is driven by uremia and increased serum calcium and phosphate levels. Improvement in calcium-phosphate homeostasis and uremia by kidney transplantation therefore might favorably influence CAC. METHODS: We measured the extent of CAC by using multidetector computed tomography in 31 patients immediately after transplantation and at 6 and 12 months' follow-up. Baseline and follow-up measurements were compared, and the effect of atherogenic factors on CAC progression was determined by means of multivariate regression analysis. RESULTS: Mean total Agatston score increased significantly from baseline to 6 months (716 +/- 980 [SD] versus 916 +/- 1,307; P < 0.001), but remained unchanged at 12 months' follow-up (890 +/- 1,263; P = not significant). Progression of calcification was present only in patients with a baseline total Agatston score higher than 10. In these patients, the score increased from 964 +/- 1,028 to 1,234 +/- 1,385 (P < 0.001) at 6 months and remained stable thereafter (1,199 +/- 1,338; P = not significant). Duration of pretransplantation dialysis treatment and smoking were identified as independent predictors of posttransplantation CAC progression. Conversely, changes in calcium and phosphate levels were not associated with calcification. CONCLUSION: This study shows that CAC progresses during the early posttransplantation course, but slows between 6 and 12 months after transplantation. The extent of early calcification is influenced mainly by dialysis treatment duration and smoking.

Complete renal tubular acidosis late after kidney transplantation.

BACKGROUND: Neither the prevalence nor the associated risk factors of late post-transplant renal tubular acidosis (RTA) are known. METHODS: We conducted a cross-sectional study with 576 patients for more than 12 months after kidney transplantation, and a glomerular filtration rate (GFR) >40 ml/min. RTA was diagnosed by measurement of the urine anionic gap, urine pH and plasma potassium during acidosis, and fractional bicarbonate excretion after bicarbonate loading. Uni- and multi-variable analysis were used to isolate factors associated with post-transplant RTA, and with the different RTA subtypes. RESULTS: All patients (n = 76) had distal post-transplant RTA. A significant association with the presence of RTA was found for the intake of tacrolimus or renin-angiotensin-aldosterone blockers, the Parathyroid hormone level and the GFR. Type Ia (classic, distal), type Ib (hyperkalaemic, voltage-dependent), rate-limited and type IV RTA were present in 37, 14, 21 and 28% of the patients. Acute transplant rejection was the only significant different parameter between the RTA subtypes and more often present in patients with type Ia or Ib RTA. CONCLUSIONS: We conclude that a significant fraction of stable long-term renal transplant recipients with adequate graft function develop post-transplant RTA, with a preponderance for type Ia and type IV, and absence of type II. In addition, acute transplant rejection seems to have an influence on the subtype of RTA present post-transplantation.

The effect of oral anticoagulation on clotting during hemodialysis.

BACKGROUND: Between 5% and 10% of hemodialysis patients are treated with oral anticoagulants. It is currently unknown whether additional anticoagulation with heparin or low-molecular-weight heparin (LMWH) is needed to prevent clotting during hemodialysis. METHODS: In this prospective, randomized, cross-over study 10 patients treated with oral anticoagulants (phenprocoumon) received either no additional anticoagulation or low dose dalteparin (bolus of 40 IU/kg body weight) before dialysis. Efficacy of hemodialysis was measured by normalized weekly Kt/V and urea reduction rate (URR). Thrombus formation was evaluated by measurement of D-dimer and inspection of air traps and dialyser. RESULTS: The median international normalized ratio (INR) did not differ between both observation periods (phenprocoumon 2.2(2 to 3) vs. dalteparin 2.1(2 to 2.9). The anti-Xa level in dalteparin patients was 0.33 (0.27 to 0.38) IU/mL after 2 hours and 0.16 (0.03 to 0.23) IU/mL after 4 hours of hemodialysis. The median increase of D-dimer was significantly higher in patients without additional dalteparin therapy during hemodialysis (DeltaD-dimer 0.23 microg/mL vs. 0.03 mug/mL) (P= 0.0004). Complete thrombosis of the dialyser membrane occurred in one patient in the phenprocoumon group but in none with combined treatment. The extent of thrombosis in the arterial and venous air trap and dialyser was significantly less in patients with additional dalteparin therapy (P= 0.0014, P= 0.0002, and P= 0.0005, respectively). Weekly Kt/V and URR was similar in both groups. CONCLUSION: Standard oral anticoagulation with an INR between 2 and 3 is insufficient to prevent clotting during hemodialysis. Additional low dose anticoagulation with a LMWH or heparin is necessary to facilitate treatment.