The Safety and Short-Term Efficacy of Aliskiren in the Treatment of Immunoglobulin A Nephropathy – A Randomized Cross-Over Study

<div><p>Background</p><p>Laboratory research and previous study suggest that aliskiren, a direct renin inhibitor, has anti-proteinuric effects. We conducted a randomized crossover study to evaluate the anti-proteinuric effect of aliskiren in patients with immunoglobulin A (IgA) nephropathy.</p><p>Methods</p><p>We studied 22 patients with biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Patients were randomized to either oral aliskiren 300 mg/day or placebo for 16 weeks and then crossed over to the other treatment arm after a washout period. Proteinuria, estimated glomerular filtration rate (eGFR), blood pressure, and serum potassium were monitored.</p><p>Results</p><p>After aliskiren treatment, there was a significant reduction in proteinuria in 4 weeks (1.76±0.95 to 1.03±0.69 g:g-Cr, p<0.0001), which remained at a low level throughout the treatment period. There was a significant difference in proteinuria between the aliskiren and placebo groups from 4 to 16 weeks after treatment (p<0.01 for all comparisons). After aliskiren treatment, there were modest but statistically significant reductions in eGFR (57.2±29.1 to 54.8±29.3 ml/min/1.73 m², p = 0.013) and diastolic blood pressure (72.6±12.3 to 66.2±11.2 mmHg, p<0.0001). None of the patient developed severe hyperkalemia (serum potassium ≥6.0 mmol/l) during the study period.</p><p>Conclusions</p><p>Aliskiren has anti-proteinuric effect in patients with IgA nephropathy and persistent proteinuria despite ACE inhibitor or ARB. Further studies are needed to confirm the renal protecting effect of direct renin inhibition in chronic proteinuric kidney diseases.</p><p>Trial Registration</p><p><a href="http://tinyurl.com/bvez4qn" target="_blank">ClinicalTrials.gov NCT00870493</a></p></div

The Effect of Neutral Peritoneal Dialysis Solution with Low Glucose-Degradation-Product on the Fluid Status and Body Composition – A Randomized Control Trial

<div><p>Background</p><p>Previous studies report conflicting results on the benefit of peritoneal dialysis (PD) patients treated with low glucose degradation product (GDP) solution. The effects of low GDP solution on body fluid status and arterial pulse wave velocity (PWV) have not been studied.</p><p>Methods</p><p>We randomly assigned 68 incident PD patients to low GDP (Intervention Group) or conventional solutions (Control Group); 4 dropped off before they received the assigned treatment. Patients were followed for 52 weeks for changes in ultrafiltration, residual renal function, body fluid status and arterial PWV.</p><p>Result</p><p>After 52 weeks, Intervention Group had higher overhydration (3.1 ± 2.6 vs 1.9 ± 2.2 L, p = 0.045) and extracellular water volume (17.7 ± 3.9 vs 15.8 ± 3.1 L, p = 0.034) than Control Group. There was no significant difference in PWV between groups. There was no significant difference in residual renal function between the Groups. Intervention Group had lower ultrafiltration volume than Control Group at 4 weeks (0.45 ± .0.61 vs 0.90 ± 0.79 L/day, p = 0.013), but the difference became insignificant at later time points. Intervention Group had lower serum CRP levels than Control Group (4.17 ± 0.77 vs 4.91 ± 0.95 mg/dL, p < 0.0001).</p><p>Conclusion</p><p>Incident PD patients treated with low GDP solution have less severe systemic inflammation but trends of less ultrafiltration, and more fluid accumulation. However, the effects on ultrafiltration and fluid accumulation disappear with time. The long term effect of low GDP solution requires further study.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00966615" target="_blank">NCT00966615</a></p></div

Change in pulse wave velocity (PWV) during the study period.

<p>(A) carotid-femoral; and (B) carotid-radial PWV. Whister-box plots, with boxes indicate median, 25th and 75th percentiles, whiskers indicate 5th and 95th percentiles. P values depict the comparison between the Intervention and Control Groups by the unpaired Student’s t test. (Grey box, Intervention Group; White box, Control Group).</p

Serum C-reactive protein (CRP) during the study period.

<p>Error bars denote standard deviations; P values denote the comparison between the Intervention and Control Groups by the Student’s t test. (Grey box, Intervention Group; White box, Control Group).</p

Fluid removal, dialysis adequacy, and residual renal function during the study period.

<p>(A) ultrafiltration volume by peritoneal dialysis; (B) urine output; (C) weekly total Kt/V; and (D) residual glomerular filtration rate (GFR). Error bars denote standard deviations; P values denote the comparison between the Intervention and Control Groups by Mann-Whitney U test. (Grey box, Intervention Group; White box, Control Group).</p

Body composition and fluid status during the study period.

<p>(A) body weight; (B) extracellular-to-intracellular fluid (E:I) ratio; (C) overhydration (OH); (D) lean tissue mass (LTM); (E) adipose tissue mass (ATM); (F) total body water (TBW); (G) extracellular water (ECW); and (H) intracellular water (ICW). Error bars denote standard deviations; P values denote the comparison between the Intervention and Control Groups by the unpaired Student’s t test.</p

Peritonitis and hospital admission during the study period.

<p>CVD, cardiovascular disease.</p><p>Peritonitis and hospital admission during the study period.</p

Consort diagram of the trial profile.

<p>Consort diagram of the trial profile.</p

Baseline characteristics of the patients.

<p>Data are presented as mean ± standard deviation.</p><p>Baseline characteristics of the patients.</p

Circulating Bacterial-Derived DNA Fragment Level Is a Strong Predictor of Cardiovascular Disease in Peritoneal Dialysis Patients

<div><p>Background</p><p>Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients.</p><p>Methods</p><p>We measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival.</p><p>Results</p><p>The average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 – 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005).</p><p>Conclusions</p><p>Circulating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients.</p></div