Proteinuria after kidney transplantation is accompanied by an increased risk of graft failure. In this single-center, placebo-controlled, double-blind trial we studied whether vitamin D receptor activator paricalcitol might reduce proteinuria. Patients with urinary protein-to-creatinine ratio (UPCR) ?20 mg/mmol despite optimization of the renin angiotensin aldosterone system (RAAS) blockade were randomly assigned to receive 24 weeks' treatment with 2 µg/day paricalcitol or placebo. Primary endpoint was change in UPCR, and main secondary endpoints were change in urinary albumin-to-creatinine ratio (UACR) and 24-h proteinuria. Analysis was by intention to treat. One hundred and sixty-eight patients undergo randomization, and 83 were allocated to paricalcitol, and 85 to placebo. Compared with baseline, UPCR declined in the paricalcitol group (-39%, 95% CI -45 to -31) but not in the placebo group (21%, 95% CI 9 to 35), with a between group difference of -49% (95% CI -57 to -41; P ( 0.001). UACR and 24-h proteinuria decreased only on paricalcitol therapy and significantly differed between groups at end-of-treatment (P ( 0.001). Paricalcitol was well tolerated but incidence of mild hypercalcemia was higher than in placebo. In conclusion, addition of 2 µg/day paricalcitol lowers residual proteinuria in kidney transplant recipients. Long-term studies are needed to determine if the reduction in proteinuria improves transplant outcomes (ClinicalTrials.gov, number NCT01436747).
COBISS.SI-ID: 5134252
BACKGROUND & AIMS: Physical performance deficits in kidney failure predict mortality and quality of life. We aimed to quantify deficits in multiple motor abilities, investigate associations of lean and fat tissue content with test results and analyzed performance of sarcopenic individuals with adipose tissue excess. METHODS: Ninety hemodialysis patients and 140 healthy controls performed 6-minute walk test, gait speed measurement, sit-to-stand and time up and go tests, upper extremity handgrip and tapping tests, Stork balance and forward bend flexibility tests. Human Activity Profile questionnaire was used to assess habitual activity. Body composition was measured by bioimpedance analysis. RESULTS: Relative performance deficit of dialysis patients in age, sex, height and comorbidity adjusted estimated marginal means was largest for balance and flexibility (-52 and -33%), followed by lower extremity deficits in sit-to-stand, time up and go and 6-minute walk tests (-29, -19 and -15%, respectively), p ( 0.05 for all comparisons. Upper extremity performance was less affected. Lean tissue index associated significantly positively with five and fat tissue index associated significantly negatively with two out of nine tests. Sarcopenic overweight and obese individuals exhibited significant deficits mainly in lower extremity tests with worse composite lower extremity score when compared to other categories of body composition. CONCLUSIONS: Patients with hemodialysis treated kidney failure have largest functional deficits in balance, flexibility and lower extremity functions. Lean and fat mass associate oppositely with physical performance measures and individuals at unfavorable extremes of these indices express significantly impaired lower extremity functions.
COBISS.SI-ID: 3844268
BACKGROUND: Regional citrate anticoagulation has been associated with enhanced biocompatibility in hemodialysis, but the optimal dose of citrate remains to be established. Here, we compared parameters related to cellular activation during in vitro dialysis, using two doses of citrate. METHODS: Human whole blood, anticoagulated with either 3 mM or 4 mM of citrate, was recirculated in an in vitro miniaturized dialysis setup. Complement (C3a-desArg), soluble platelet factor 4 (PF4), thromboxane B2 (TXB2), myeloperoxidase (MPO), as well as platelet- and red blood cell-derived extracellular vesicles (EV) were quantified during recirculation. Dialyzer fibers were examined by scanning electron microscopy after recirculation to assess the activation of clotting and the deposition of blood cells. RESULTS: Increases in markers of platelet and leukocyte activation, PF4, TXB2, and MPO were comparable between both citrate groups. Complement activation tended to be lower at higher citrate concentration, but the difference between the two citrate groups did not reach significance. A strong increase in EVs, particularly platelet-derived EVs, was observed during in vitro dialysis for both citrate groups, which was significantly less pronounced in the high citrate group at the end of the experiment. Assessment of dialyzer clotting scores after analysis of individual fibers by scanning electron microscopy revealed significantly lower scores in the high citrate group. CONCLUSIONS: Our data indicate that an increase in the citrate concentration from 3 mM to 4 mM further dampens cellular activation, thereby improving biocompatibility. A concentration of 4 mM citrate might therefore be optimal for use in clinical practice.
COBISS.SI-ID: 4962220
Association of higher serum levels of uremic toxins and inflammatory markers with poorer physical performance is understudied. We measured the six-minute walk test (6MWT), 10 repetition sit-to-stand test (STS-10), handgrip strength (HGS), and Human Activity Profile (HAP) questionnaire score in 90 prevalent hemodialysis patents, with low comorbidity to reduce the potential confounding of concomitant disease. Midweek pre-dialysis serum levels of asymmetric dimethyl-arginine (ADMA), beta2-microglobulin (B2M), high-sensitivity C-reactive protein (hs-CRP), indoxyl sulfate (IS), insulin-like growth factor 1 (IGF-1), interleukin 6 (IL-6), myostatin, and urea were analyzed as predictor parameters of physical performance measures in adjusted models. Serum levels of most measured toxins were not significantly related to performance, except for ADMA, which was significantly related to poorer performance in the STS-10 test (B = 0.11 % 0.03 s, p ( 0.01). Higher hs-CRP was associated with poorer results in the 6MWT (B = %2.6 % 0.97 m, p ( 0.01) and a lower HAP score (B = %0.36 % 0.14, p = 0.01). There were no other significant associations found. We conclude that inflammation may be a more important pathway to physical impediment than uremic toxemia. This suggests that there is a large physical rehabilitation potential in non-inflamed uremic patients.
COBISS.SI-ID: 4610417
The authors discuss and oppose the original article in the journal Critical Care Medicine, claiming that use of dialysate containing citrate as its component is not the equivalent of regional citrate anticoagulation using calcium free dialysate and citrate infusion.
COBISS.SI-ID: 4605356