Press office era-edta congress 2010 | albersconcept | jakobstrasse 38 | 99423 weimar | germany

Press Office ERA-EDTA Congress 2011 | albersconcept | Jakobstrasse 38 | 99423 Weimar | Germany 25 June 2011
LBCT 5
Lowering LDL cholesterol with ezetimibe/simvastatin does not significantly slow down
CKD progression

The SHARP-study1 has shown that lowering LDL cholesterol leads to a significant, 17% proportional reduction in major atherosclerotic events among CKD-patients. It has been suggested that lowering LDL cholesterol in subjects without marked kidney failure might also cause a slight reduction in CKD progression rate. To date it has not been clear whether lowering LDL also has a favourable effect on renal disease progression in the case of advanced CKD. This was another of the issues addressed by the SHARP study2, which compared in over 9,000 CKD patients the administration of 10 mg ezetimibe plus 20 mg simvastatin versus a placebo. In the ezetimibe/simvastatin group, fewer patients reached the end point "end stage renal disease" (ESRD): 1057 (33.9%) vs. 1084 (34.6%) but the difference was not significant [p = 0.41]. The results were comparable for the end point "ESRD or death", which was reached with ezetimibe/simvastatin by 47.4% vs. 48.3% [p = 0.34] and for the end point "ESRD or doubling of baseline serum creatinine" by 38.2% vs. 40.2% [p = 0.10]. These results were comparable in all the CKD stages and subgroups. 1 Baigent C, Landray MJ, ReithC et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011, Jun 8 [epub ahead of print]. 2 EFFECT OF LDL-CHOLESTEROL LOWERING ON RENAL DISEASE PROGRESSION AMONG PATIENTS WITH CHRONIC
KIDNEY DISEASE: RESULTS OF THE STUDY OF HEART AND RENAL PROTECTION (SHARP). Lewis D et al. the SHARP
Investigators
Abstract No. 2509
Although Ezetimibe/simvastatin treatment had been proven to reduce atherosclerotic events among CKD-patients in the SHARP-study, it had no significant influence on the progression rate of CKD or on ACR after 2.5 years in the same patient population. LBCT 6
No improvement in cardiovascular outcome due to optimised treatment quality with
intensified therapy of risk factors

Cardiovascular comorbidity in CKD patients is dramatically high. Most patients fail to reach the end stage of renal insufficiency with mandatory dialysis but die in the pre-dialysis stages. The MASTERPLAN study3 aimed to evaluate whether strict implementation of all the current treatment guidelines with the aid of "nurse practitioners", which keeps an eye on treatment targets, leads to a better cardiovascular outcome in CKD patients. The randomised, controlled study was able to enrol 788 CKD patients (eGFR 20-70 mml/min/1.73m²) in nine Dutch clinics. The patients were assigned at random either to the control group (CG: normal, customary nephrological treatment) or to the intervention group (IG: intensified treatment with the aid of "nurse practitioners"). The primary endpoint was a composite of myocardial infarction, stroke and cardiovascular death. It occurred in 20.1/1,000 persons years in the intervention group and in 23.2/1,000 person years in the control group [HR=0.87]. There was no significant difference, although the patients in the intervention group had a significantly lower blood pressure (132/77 vs. 135/79 mmHg, p< 0.001), a lower LDL cholesterol (2.39 vs. 2.50 mmol/l; p = 0.008) and less proteinuria (0.65 vs. 0.77 g/day; p = 0.04). They received more frequently statins (80% vs. 76%; p = 0.002), aspirin (67% vs. 57%; p<0.001), and vitamin D (46% vs. 41%; p = 0.02) and a larger number of antihypertensives (3.16 vs. 3.04; p = 0.04). On the other hand, there were no significant differences between the groups in terms of nicotine abuse, body weight, physical activity or salt consumption. Despite intensified therapy of risk factors and better clinical values and chemical laboratory values it was not possible to significantly improve cardiovascular outcome in the intervention group.
LBCT 7
Open-label study confirms the benefits of tacrolimus therapy with prolonged release
in de novo kidney transplant patients

After kidney transplantation all patients receive immunosuppression to prevent the organ from being rejected. Various drugs are available for this, one of these being tacrolimus (Tac). There are tacrolimus products that release their active substance immediately (Tac BID) and
3 Effect of a multifactorial intervention with the aid of nursepractitioners on cardiovascular outcome in patients with
chronic kidney disease: results of the MASTERPLAN study. Van Zuilen A, Dulger A, Bots M et al.
Abstract No. 2511

others that release it in a prolonged manner (Tac QD). The open-label OSAKA study4
compared these two drug forms in various doses.
1,251 adult kidney transplant patients were randomised 1:1:1:1. They received either0.2
mg/kg/d Tac BID (Arm 1) or 0.2 mg/kg/d Tac QD (Arm 2) or 0.3 mg/kg/d Tac QD (Arm 3)
plus, in all three arms, mycophenolate mofetil (MMF) plus corticosteroids (CS) over a period
of 24 weeks. Patients in Arm 4 received 0.2 mg/kg/d Tac QD + MMF + basiliximab + CS as a
perioperative bolus. Tac and MMF began preoperatively. The target ranges for Tac troughs
were 10-15 ng/ml (Days 0-14), 5-12 ng/ml (Days 15-42) and 5-0 ng/ml (Days 34-168).
The administration of 0.2 mg/kg/d of a tacrolimus product with prolonged Tac release led to
the achievement of target blood level in more patients within the first few days after
transplantation than with an identical-dose product with immediate Tac release. The 0.3
mg/kg/d initial dose regime with prolonged release Tac, on the other hand, did not confer any
additional benefits but resulted in more levels within the potentially toxic range.
Consequently, this open-label study backs up the previous results regarding the favourable
properties of prolonged release tacrolimus.

LBCT 8
Which SHPT therapy should be used?

Chronic renal insufficiency frequently involves secondary hyperparathyroidism (SHPT) which, during the course of the disease, often leads to severe bone and vascular complications. Controlled SHPT is therefore absolutely essential. SHPT therapy using the selective vitamin D receptor (VDR) activator paricalcitol or using the calcimimetic cinacalcet reduces the iPTH levels (intact parathormone) but to date there have been no comparative investigations into the effectiveness or concomitant symptoms of the two therapies. It is known that as a selective vitamin D receptor activator, paricalcitol can, under certain circumstances, lead to hypercalcaemia. Cinacalcet, on the other hand, influences the calcium level in the opposite direction and the therapy can, under certain circumstances, lead to hypocalcaemia. The IMPACT SHPT study (Evaluation of the Effectiveness of Paricalcitol Versus Cinacalcet With Low-Dose Vitamin D) is an international randomised phase IV open-label multi-centre study that investigated 272 HD patients over a period of 28 weeks. The patients received either paricalcitol (additive cinacalcet for hypercalcaemia) or cinacalcet plus low-dose vitamin D. In this interim analysis5 the paricalcitol group 78% of patients achieved an iPTH reduction of ≥30% and 65% achieved a reduction of ≥50% whilst in the cinacalcet group the figures were 50% and 36% of patients.
4 EARLY POST TRANSPLANT LEVELS IN DE NOVO RENAL RECIPIENTS ON TACROLIMUS PROLONGED
RELEASE VS TACROLIMUS IMMEDIATE RELEASE - THE OSAKA STUDY. Viklicky O, Kamar N and the
OSAKA study investigators
Abstract No. 2505
5 INTERIM ANALYSIS OF PARICALCITOL VERSUS CINACALCET TREATMENT IN MANAGEMENT OF
SECONDARY HYPERPARATHYREOIDISM (SHPT) IN PATIENTS ON HEMODIALYSIS. Ketteler M, Martin KJ,
Cozzolino M et al.
Abstract No. 2510
Concerning side effects, 4 of 69 patients developed hypercalcaemia in the paricalcitol arm, while 27 of 59 patients developed hypocalcemia in the cinacalcet arm. It can therefore be stated that in this interim analysis using paricalcitol a larger percentage of patients achieved iPTH reductions of 30% and 50% respectively than using cinacalcet plus low-dose vitamin D. Hypercalcaemia incidence with paricalcitol was far lower than hypocalcaemia incidence with cinacalcet plus vitamin D.

Source: http://www.eraedta2011.org/images/LBCT_2_press_Embargoed%20until%2025-06-11_16.15_pm.pdf