fumarates and Glomerulonephritis--IGA

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.. 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.. 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 m(2), 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.. 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.. ClinicalTrials.gov NCT00870493.

Topics: Adult; Amides; Antihypertensive Agents; Blood Pressure; Cross-Over Studies; Female; Fumarates; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Hyperkalemia; Male; Middle Aged; Proteinuria; Renin; Treatment Outcome

Aliskiren is a relatively new oral direct renin inhibitor (DRI) that has been increasingly used for the treatment of diabetic nephropathy and hypertension. Its potential efficacy in nondiabetic chronic kidney diseases that are driven by renin-angiotensin system activation remains to be explored.. From a teaching and regional hospital in Hong Kong between July 2009 and March 2010, patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in whom the ratio of protein to creatinine, as measured in early morning urine samples, remained >113 mg/mmol (1000 mg/g), despite receiving the maximum recommended dose of losartan (100 mg daily) were recruited to receive additional DRI treatment. They were followed prospectively for 12 months with changes in proteinuria as the main outcome measure.. Twenty-five consecutive patients were enrolled. Treatment with aliskiren for 12 months reduced the mean urinary protein-to-creatinine ratio by 26.3% (95% confidence interval, 20.1-43.6; P = 0.001 versus baseline), with a reduction of ≥ 50% in 24% of patients. There were significant reductions in plasma renin activity (P < 0.0001) and serum interleukin-6 (P < 0.05) and transforming growth factor-β (P = 0.01) levels, compared with baseline. Two patients (8%) developed mild allergic reactions and six (24%) had transient hyperkalemia (K >5.5 mmol/L) during the study.. Aliskiren confers an antiproteinuric effect in IgAN patients with significant residual proteinuria, despite receiving the recommended renoprotective treatment. Further prospective randomized trials are warranted to examine its long-term renoprotective potential. This trial is registered with the ClinicalTrials.gov number NCT00922311.

Topics: Adult; Amides; Antihypertensive Agents; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Fumarates; Glomerulonephritis, IGA; Hong Kong; Humans; Interleukin-6; Kidney Function Tests; Losartan; Male; Middle Aged; Odds Ratio; Pilot Projects; Prospective Studies; Proteinuria; Risk Assessment; Severity of Illness Index; Time Factors; Transforming Growth Factor beta; Treatment Outcome; Urinalysis

The long-term clinical outcomes in biopsy proven IgAN patients treated with aliskiren on top of a maximally tolerated dose of ACEi/ARB remain unknown.. Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality. Secondary outcome measures included changes in mean UPCR, blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up.. Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.

Topics: Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cohort Studies; Fumarates; Glomerulonephritis, IGA; Humans; Hyperkalemia; Propensity Score; Renin

The early suspension of Altitude trial in recent years has induced most nephrologists and cardiologists to abandon Aliskiren use. Consequently, the potential usefulness of the direct renin inhibition in IgA glomerulonephritis remained an under-investigated therapeutic option.. We report the case of a 53 years old IgA GMN patient unresponsive to all conventional anti-angiotensin-2 agents, steroids and immunosuppressants, in which the administration of Aliskiren permitted to achieve and maintain a complete proteinuria remission in the absence of any adverse event.. Aliskiren might represent a valid and safe therapeutic option in IgA GMN, although further investigations would be needed to confirm this conclusion.

Topics: Amides; Biopsy, Needle; Drug Administration Schedule; Drug Resistance, Multiple; Drug Therapy, Combination; Follow-Up Studies; Fumarates; Glomerulonephritis, IGA; Humans; Immunohistochemistry; Immunosuppressive Agents; Irbesartan; Male; Middle Aged; Prednisone; Ramipril; Retreatment; Time Factors; Treatment Outcome