[Pharmacotherapy in patients with reduced kidney function]. / Besonderheiten der Pharmakotherapie bei eingeschränkter Nierenfunktion.

Pharmacotherapy in patients with reduced kidney function Abstract. Pharmacotherapy in patients with chronic kidney disease (CKD) requires careful assessment of renal function and a profound knowledge of dose adaption principles and pharmacological characteristics of the drugs used. Of importance, non-renal clearance is also affected by impaired kidney function. Direct acting anticoagulants play an increasingly important role in daily clinical practice also in patients with impaired kidney function. Limited data suggest possible use even in end stage renal disease. GLP-1-agonists and SGLT-2-inhibitors are new treatment modalities for type 2 diabetes mellitus. The efficacy of glucose lowering by SGLT-2-inhibitors steadily declines with impaired kidney function; however, positive effects on cardiovascular outcomes seem to be preserved in advanced CKD. NSAIDs affect renal hemodynamics as well as tubular function. Severe renal side effects may be observed especially when used in combination with RAAS-inhibitors and diuretics.

Switch to an everolimus-facilitated cyclosporine A sparing immunosuppression improves glycemic control in selected kidney transplant recipients.

BACKGROUND: Mammalian target of rapamycin inhibitors (mToRi) allow calcineurin inhibitor (CNI) sparing therapy in renal transplant recipients with possible beneficial effects on the long-term allograft function and cardiovascular risk. The influence of mToRi on glucose metabolism is still under discussion. METHODS: In a retrospective analysis, renal allograft recipients switched from a cyclosporine A (CsA) to an everolimus (EVR)-based immunosuppression in the first year after transplantation were compared with patients on continued CsA treatment. At 6-month intervals, the prevalence of impaired fasting glucose (IFG) and new onset of diabetes after transplantation (NODAT) were assessed. RESULTS: A total of 146 renal transplant recipients were included. The cumulative prevalence of IFG and NODAT 30-months post-transplantation was significantly lower in patients switched to an immunosuppression with EVR compared to patients on continued CsA treatment (10% vs 22%, P=.049). However, patients switched to EVR showed a higher incidence of acute cellular rejections in the first 12 months (23% vs 11%, P=.048). CONCLUSION: EVR-based immunosuppression was associated with a similar or even improved glycemic control and improved renal function. However, due to higher rejection rates, patients switched to EVR should be carefully selected as rejection therapy with steroids counteracts the benefit in glycemic control.

Sustained low efficiency dialysis using a single-pass batch system in acute kidney injury - a randomized interventional trial: the REnal Replacement Therapy Study in Intensive Care Unit PatiEnts.

INTRODUCTION: Acute kidney injury (AKI) is associated with a high mortality of up to 60%. The mode of renal replacement therapy (intermittent versus continuous) has no impact on patient survival. Sustained low efficiency dialysis using a single-pass batch dialysis system (SLED-BD) has recently been introduced for the treatment of dialysis-dependent AKI. To date, however, only limited evidence is available in the comparison of SLED-BD versus continuous veno-venous hemofiltration (CVVH) in intensive care unit (ICU) patients with AKI. METHODS: Prospective, randomized, interventional, clinical study at a surgical intensive care unit of a university hospital. Between 1 April 2006 and 31 January 2009, 232 AKI patients who underwent renal replacement therapy (RRT) were randomized in the study. Follow-up was assessed until 30 August 2009. Patients were either assigned to 12-h SLED-BD or to 24-h predilutional CVVH. Both therapies were performed at a blood flow of 100 to 120 ml/min. RESULTS: 115 patients were treated with SLED-BD (total number of treatments n = 817) and 117 patients with CVVH (total number of treatments n = 877).The primary outcome measure, 90-day mortality, was similar between groups (SLED: 49.6% vs. CVVH: 55.6%, P = 0.43). Hemodynamic stability did not differ between SLED-BD and CVVH, whereas patients in the SLED-BD group had significantly fewer days of mechanical ventilation (17.7 ± 19.4 vs. 20.9 ± 19.8, P = 0.047) and fewer days in the ICU (19.6 ± 20.1 vs. 23.7 ± 21.9, P = 0.04). Patients treated with SLED needed fewer blood transfusions (1,375 ± 2,573 ml vs. 1,976 ± 3,316 ml, P = 0.02) and had a substantial reduction in nursing time spent for renal replacement therapy (P < 0.001) resulting in lower costs. CONCLUSIONS: SLED-BD was associated with reduced nursing time and lower costs compared to CVVH at similar outcomes. In the light of limited health care resources, SLED-BD offers an attractive alternative for the treatment of AKI in ICU patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00322530.

Acute effects of calcineurin inhibitors on kidney allograft microperfusion visualized by contrast-enhanced sonography.

BACKGROUND: Calcineurin inhibitors induce detrimental vascular remodeling, which may be one cause of chronic allograft failure. Real-time contrast-enhanced sonography (CES) is a relatively new technique in providing quantitative information on microvascular tissue perfusion in kidney allografts in more detail. The purpose of the study was to explore whether acute changes of kidney allograft microperfusion due to the administration of cyclosporine A (CsA) and tacrolimus (Tac) can be evidenced using real-time CES. METHODS: In an explorative single-center clinical trial, renal parenchymal tissue perfusion of 32 stable kidney allograft recipients was evaluated with CES before and 2 hr after the intake of CsA or Tac. In addition to laboratory and clinical parameters, Doppler indices and estimated glomerular filtration rate were measured. RESULTS: Although systolic and diastolic blood pressure and color Doppler indices did not significantly differ, there was a significant decrease of renal blood flow 2 hr after the intake of CsA compared with baseline (4.78±2.31 dB/s, 49%, respectively). In contrast, kidney allograft microperfusion was neither significantly reduced in patients receiving CsA paralleled by calcium channel blockers nor significantly reduced in patients receiving Tac. Furthermore, there was a significant correlation between renal blood flow obtained before drug administration and kidney function. CONCLUSIONS: CES revealed a 49% reduction of kidney allograft microperfusion 2 hr after the intake of CsA, which might be abrogated by calcium channel blockers. In comparison to CsA, Tac did not result in a significant decrease of kidney blood flow.

ABO-incompatible kidney transplantation enabled by non-antigen-specific immunoadsorption.

BACKGROUND: ABO-incompatible kidney transplantation performed after desensitization with antigen-specific immunoadsorption (IA) results in good outcomes. However, a unique single-use IA device is required, which creates high costs. METHODS: From August 2005 to August 2010, 19 patients were desensitized for ABO-incompatible living donor kidney transplantation. Six patients treated with a single-use antigen-specific IA device and 12 patients treated with a reusable non-antigen-specific IA device were analyzed. RESULTS: Six patients who received antigen-specific IA had a median of 5 IA treatments and 12 patients with non-antigen-specific IA had a median of 6 IA treatments preoperatively. Median average titer drop in Coombs technique was 1.2 in antigen-specific IA and 1.7 in non-antigen-specific IA. In two patients with antigen-specific IA and four patients with non-antigen-specific IA, additional plasmapheresis treatments were necessary for recipient desensitization. Despite six treatments with antigen-specific IA and 12 plasmapheresis treatments, one patient with a starting isoagglutinin titer of 1:1024 (Coombs) could not be transplanted. The 18-month graft survival rate for the 17 ABO-incompatible living donor kidney transplants was 100%. One male recipient who was desensitized with antigen-specific IA died 44 months after transplantation from sudden cardiac death with a serum creatinine of 1.2 mg/dL. At last follow-up, a median of 13 months after transplantation, median serum creatinine for 16 patients was 1.5 mg/dL, median glomerular filtration rate as estimated by the modification of diet in renal disease formula 54 mL/min/1.73 m, and median urinary protein-to-creatinine ratio 0.1, with no differences between treatments. CONCLUSIONS: A reusable non-antigen-specific IA device allows high number of treatments at reasonable cost, and at the same time might deplete human leukocyte antigen-alloantibodies.