Cumulative costs of immunoadsorption and plasma exchange.

<p>Circles and triangles depict earliest timepoints of adsorber change due to reduced adsorption capacity (every 25 treatments for Immunosorba, every 35 treatments for Globaffin).</p

Effects of direct renin inhibition versus angiotensin II receptor blockade on angiotensin profiles in non-diabetic chronic kidney disease

<p><b>Background:</b> Direct renin inhibition (DRI) is clinically inferior to other blockers of the renin–angiotensin system (RAS). Thus far, the underlying molecular causes of this finding remain unknown.</p> <p><b>Methods:</b> Twenty four patients with non-diabetic chronic kidney disease (CKD) stages III–IV and albuminuria were randomized to DRI or angiotensin receptor blocker (ARB). Employing a novel mass-spectrometry method, the concentrations of renin, aldosterone and plasma angiotensin peptides [Ang I, Ang II, Ang-(1-7), Ang-(1-5), Ang-(2-8), Ang-(3-8)] were quantified before and after an 8-week treatment.</p> <p><b>Results:</b> While blood pressure, renal function and albuminuria decreased comparably in both groups, profound RAS component differences were observed: DRI led to a massive renin increase, while suppressing both vasoconstrictive (Ang I and Ang II) and vasodilatory RAS metabolites (Ang-(1-7) and Ang-(1-5)). In contrast, ARB led to a four-fold increase of Ang I and Ang II, while Ang-(1-7) and Ang-(1-5) increased moderately but significantly. With ARB treatment, a decreased aldosterone-to-Ang II ratio suggested efficacy in blocking AT1 receptor.</p> <p><b>Conclusions:</b> DRI therapy abolishes all RAS effector peptides. ARB increases both vasoconstrictive and vasodilative angiotensins, while this is accompanied by efficient blockade of vasoconstrictive effects. These differential molecular regulations should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients.Key messages</p><p>Direct renin inhibition leads to a complete and lasting abolition of both classical and alternative RAS components.</p><p>Angiotensin receptor blockade leads to effective receptor blockade and up-regulation of alternative RAS components.</p><p>Differential molecular regulations of the RAS should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients.</p><p></p> <p>Direct renin inhibition leads to a complete and lasting abolition of both classical and alternative RAS components.</p> <p>Angiotensin receptor blockade leads to effective receptor blockade and up-regulation of alternative RAS components.</p> <p>Differential molecular regulations of the RAS should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients.</p

Long-Term Outcome of Anti-Glomerular Basement Membrane Antibody Disease Treated with Immunoadsorption

<div><p>Background</p><p>Anti-glomerular basement membrane (GBM) antibody disease may lead to acute crescentic glomerulonephritis with poor renal prognosis. Current therapy favours plasma exchange (PE) for removal of pathogenic antibodies. Immunoadsorption (IAS) is superior to PE regarding efficiency of antibody-removal and safety. Apart from anecdotal data, there is no systemic analysis of the long-term effects of IAS on anti-GBM-disease and antibody kinetics.</p><p>Objective</p><p>To examine the long-term effect of high-frequency IAS combined with standard immunosuppression on patient and renal survival in patients with anti-GBM-disease and to quantify antibody removal and kinetics through IAS.</p><p>Design</p><p>Retrospective review of patients treated with IAS for anti-GBM-antibody disease confirmed by biopsy and/or anti-GBM-antibodies.</p><p>Setting</p><p>University Hospital of Vienna, Austria.</p><p>Participants</p><p>10 patients with anti-GBM-disease treated with IAS.</p><p>Measurements</p><p>Patient and renal survival, renal histology, anti-GBM-antibodies.</p><p>Results</p><p>Anti-GBM-antibodies were reduced by the first 9 IAS treatments (mean number of 23) to negative levels in all patients. Renal survival was 40% at diagnosis, 70% after the end of IAS, 63% after one year and 50% at the end of observation (mean 84 months, range 9 to 186). Dialysis dependency was successfully reversed in three of six patients. Patient survival was 90% at the end of observation.</p><p>Conclusion</p><p>IAS efficiently eliminates anti-GBM-antibodies suggesting non-inferiority to PE with regard to renal and patient survival. Hence IAS should be considered as a valuable treatment option for anti-GBM-disease, especially in patients presenting with a high percentage of crescents and dialysis dependency due to an unusual high proportion of responders.</p></div

Extracorporal treatment and concomitant immunosuppression.

<p>Extracorporal treatment and concomitant immunosuppression.</p

Renal function and patient survival.

<p>Renal function and patient survival.</p

Baseline characteristics of patients treated.

<p>Baseline characteristics of patients treated.</p

Anti-GBM antibody kinetics and renal function in patient #7 (2a) and patient #10 (2b).

<p>Antibody values at diagnosis, before and after IAS, 12 hours in between sessions and up to 6 weeks; arrows depict daily IAS sessions. Grey area depicts negativity of the assay.</p

Dynamics of serum-creatinine of individual patients.

<p>Observation period from start of IAS until 5 years. White coloured time points depict positive anti-GBM antibody testing.</p

Anti-GBM antibody levels from start of immunoadsorption until end of observation.

<p>Mean values ± standard deviation of all patients measured with ELISA depicted. Grey area denotes negativity of the assay.</p

Sex-Specific Differences in Hemodialysis Prevalence and Practices and the Male-to-Female Mortality Rate: The Dialysis Outcomes and Practice Patterns Study (DOPPS)

<div><p>Background</p><p>A comprehensive analysis of sex-specific differences in the characteristics, treatment, and outcomes of individuals with end-stage renal disease undergoing dialysis might reveal treatment inequalities and targets to improve sex-specific patient care. Here we describe hemodialysis prevalence and patient characteristics by sex, compare the adult male-to-female mortality rate with data from the general population, and evaluate sex interactions with mortality.</p><p>Methods and Findings</p><p>We assessed the Human Mortality Database and 206,374 patients receiving hemodialysis from 12 countries (Australia, Belgium, Canada, France, Germany, Italy, Japan, New Zealand, Spain, Sweden, the UK, and the US) participating in the international, prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) between June 1996 and March 2012. Among 35,964 sampled DOPPS patients with full data collection, we studied patient characteristics (descriptively) and mortality (via Cox regression) by sex. In all age groups, more men than women were on hemodialysis (59% versus 41% overall), with large differences observed between countries. The average estimated glomerular filtration rate at hemodialysis initiation was higher in men than women. The male-to-female mortality rate ratio in the general population varied from 1.5 to 2.6 for age groups <75 y, but in hemodialysis patients was close to one. Compared to women, men were younger (mean = 61.9±standard deviation 14.6 versus 63.1±14.5 y), were less frequently obese, were more frequently married and recipients of a kidney transplant, more frequently had coronary artery disease, and were less frequently depressed. Interaction analyses showed that the mortality risk associated with several comorbidities and hemodialysis catheter use was lower for men (hazard ratio [HR] = 1.11) than women (HR = 1.33, interaction <i>p</i><0.001). This study is limited by its inability to establish causality for the observed sex-specific differences and does not provide information about patients not treated with dialysis or dying prior to a planned start of dialysis.</p><p>Conclusions</p><p>Women's survival advantage was markedly diminished in hemodialysis patients. The finding that fewer women than men were being treated with dialysis for end-stage renal disease merits detailed further study, as the large discrepancies in sex-specific hemodialysis prevalence by country and age group are likely explained by factors beyond biology. Modifiable variables, such as catheter use, showing significant sex interactions suggest interventional targeting.</p><p><i>Please see later in the article for the Editors' Summary</i></p></div