lisinopril and Glomerulonephritis--IGA

Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children.. This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoing lisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy.. There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups.. We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy.. Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp .

Topics: Adolescent; Child; Child, Preschool; Drug Therapy, Combination; Female; Glomerulonephritis, IGA; Humans; Kidney Glomerulus; Lisinopril; Losartan; Male; Prospective Studies; Proteinuria; Severity of Illness Index; Treatment Outcome

Previous randomized controlled trials evaluating the efficacy of mycophenolate mofetil (MMF) in patients with immunoglobulin A nephropathy (IgAN) have produced varying results.. Double-blind placebo-controlled randomized controlled trial.. 52 children, adolescents, and adults with biopsy-proven IgAN in 30 centers in the United States and Canada. Entry criteria: age older than 7 to younger than 70 years; urine protein-creatinine ratio (UPCR), ≥0.6g/g (males) or ≥0.8g/g (females); and estimated glomerular filtration rate ≥ 50mL/min/1.73m(2) (≥40mL/min/1.73m(2) if receiving angiotensin-converting enzyme inhibitor). Mean age, 32±12 (SD) years; 62% men; and 73% white.. Lisinopril (or losartan) plus a highly purified omega-3 fatty acid (Omacor [Pronova Biocare]) was given to 94 patients for 3 months; 52 of the patients with persistent UPCR≥0.6g/g (males) and ≥0.8g/g (females) were randomly assigned to MMF or placebo (target dose, 25-36mg/kg/d) in addition to lisinopril/losartan plus Omacor.. Change in UPCR after 6 and 12 months treatment with MMF/placebo and 12 months after the end of treatment.. UPCR measured on 24-hour urine samples. Glomerular filtration rate estimated with the Schwartz (age < 18 years) or Cockcroft-Gault (age ≥ 18 years) formula.. 44 patients completed 6 months of treatment with MMF (n=22) or placebo (n=22). The trial was terminated early at the recommendation of the Data Monitoring Committee because of the lack of benefit. No patient achieved a complete remission (UPCR<0.2g/g). Mean UPCRs at randomization and after 6 months were 1.45 (95% CI, 1.16-1.75) and 1.40 (95% CI, 1.09-1.70) for MMF and 1.41 (95% CI, 1.17-1.65) and 1.58 (95% CI, 1.13-2.04) for placebo, respectively. The mean difference in UPCR change between these groups (MMF minus placebo) was -0.22 (95% CI, -0.75 to 0.31; P=0.4). Adverse events were rare apart from nausea (MMF, 8.7%; placebo, 3.7%); one of these MMF patients withdrew.. Low patient enrollment and short follow-up.. MMF did not reduce proteinuria significantly in patients with IgAN who had persistent proteinuria after lisinopril/losartan plus Omacor.

Topics: Adolescent; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Child; Creatinine; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Eicosapentaenoic Acid; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Lisinopril; Losartan; Male; Middle Aged; Mycophenolic Acid; Proteinuria; Remission Induction; Treatment Outcome; Young Adult

Even in children with mild immunoglobulin (Ig)A nephropathy (IgA-N) showing minimal/focal mesangial proliferation, persistent proteinuria seems to be a risk factor for progression of the disease, indicating the need for an effective and safe treatment even in such cases. Studies carried out to date have indicated that angiotensin-converting enzyme inhibitors (ACEIs) reduce urinary protein excretion and preserve renal function in adult IgA-N. However, no prospective study of ACEI only for childhood IgA-N has yet been carried out. In this prospective single-arm pilot trial, we administered lisinopril (0.4 mg/kg per day) as therapeutic treatment to 40 children with mild IgA-N with proteinuria [morning urinary protein/creatinine ratio (uP/Cr) >or= 0.2 g/g]. Thirty-three patients reached the primary endpoint (uP/Cr < 0.2) during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan-Meier method was 80.9%. Mean uP excretion was reduced from 0.40 to 0.18 g/m(2)/day (p < 0.0001). Of the 40 patients treated, five (12.5%) showed dizziness, and four of these five needed the lisinopril dose reduced. However, lisinopril therapy was continued in all patients during the 2-year treatment period. No other side effect, such as cough, was observed. We conclude that the efficacy and safety of lisinopril is seemingly acceptable for the treatment of children with mild IgA-N.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Child; Child, Preschool; Dizziness; Female; Glomerular Mesangium; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Lisinopril; Male; Pilot Projects; Prospective Studies; Proteinuria; Treatment Outcome

IgAN is the most common type of glomerulonephritis in the world. Between 15 and 40 percent of adults and children diagnosed with IgAN eventually progress to ESRD. Despite the need for effective treatment strategies, very few RCTs for IgAN have been performed. The most effective therapies for IgAN appear to be corticosteroids, ACEi, and FOS that contain a high concentration of omega 3 fatty acids. While ACEi and FOS are generally well tolerated with minimal side effects, the use of high dose steroids over a long course of therapy is often associated with significant morbidity.. The objective of the study is to test the hypothesis that treatment with the immunosuppressive agent, MMF, will lead to significant and sustained improvement in urinary protein excretion in patients with IgAN who have been pre-treated (and continue to be treated) with ACEi and FOS compared to a placebo control group of patients receiving comparable doses of ACEi and FOS without MMF.. After a three month treatment period with the ACEi, lisinopril and the FOS, Omacor, 100 (2 x 50) patients with IgAN and a urinary P/C ratio > or = 0.6 (males) and > or = 0.8 (females) and an estGFR > or = 40 ml/min/1.73 m2 will be randomized to treatment with either MMF or placebo for one year. All patients will be followed off study drug for a second year, but will continue treatment with lisinopril and Omacor for the two year duration of the study. The primary outcome measure of change in urine P/C ratio will be assessed at the end of years one and two.

Topics: Angiotensin-Converting Enzyme Inhibitors; Docosahexaenoic Acids; Drug Combinations; Drug Therapy, Combination; Eicosapentaenoic Acid; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Lisinopril; Male; Mycophenolic Acid; Proteinuria; Research Design; Treatment Outcome

We evaluated blood concentrations of bcl-2, a proto-oncogene that can inhibit apoptotic phenomena, in a group of patients with immunoglobulin A (IgA) nephropathy. Concentrations of bcl-2 were higher in patients with proteinuria than in those without proteinuria. A 6-month course of 5 mg/day lisinopril given to subjects with proteinuria significantly reduced blood bcl-2 concentrations and caused a reduction in proteinuria. Therefore increased blood bcl-2 concentrations may be considered an index of risk in subjects with IgA nephropathy, and the positive effects of angiotensin-converting enzyme inhibitors on proteinuria in patients with IgA nephropathy may be attributed, at least in part, to their effect on the mechanisms that regulate apoptosis. This is of fundamental importance in resolving glomerular hypercellularity in the course of glomerulonephritis.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Apoptosis; Female; Genes, bcl-2; Glomerulonephritis, IGA; Humans; Lisinopril; Male; Middle Aged; Proteinuria; Proto-Oncogene Mas; Treatment Outcome

The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in patients with renal disease is well known, but the results of clinical studies appear to vary considerably from a partial decrease to a fall of 100% in urinary protein excretion. This may have been due to the use of different doses of ACE inhibitor, different renal pathology and non-standardized sodium intake. In 16 proteinuric patients with biopsy-proven IgA nephropathy, with normal renal function and blood pressure, maintained at controlled sodium intake < or = 80 mEqII, the efficacy of increasing doses of the ACE inhibitor lisinopril was studied. The lisinopril doses were 5, 10, 15 and 20 mg, administered for 4 weeks. Between each dose increment a placebo period of 3 weeks was interposed. Proteinuria stepwise decreased from the control period by 39%, 44%, 61% and 67% with lisinopril at 5, 10, 15 and 20 mg, respectively. The blood pressure decreased by 22% with lisinopril 5 mg; a similar fall was observed with the dose increment. Although the glomerular filtration rate remained unchanged, the renal plasma flow increased by 21%, 26%, 24% and 28% and the filtration fraction increased by 28% mean. The ACE plasma levels decreased by 33%, 64%, 76% and 83%. A close correlation was found between an increase in lisinopril dosage and the fall in urinary protein excretion (r = 0.88, p < 0.001). The antiproteinuric effect of lisinopril is dose-related and may be attributable to some extent to the fall in systemic (and intraglomerular) blood pressure, but it is best attributed to the modification of glomerular sieving function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Pressure; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Kidney; Lisinopril; Male; Middle Aged; Peptidyl-Dipeptidase A; Proteinuria

Topics: Child; Glomerulonephritis, IGA; Humans; Lisinopril; Losartan; Proteinuria

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Child; Drug Therapy, Combination; Glomerulonephritis, IGA; Humans; Lisinopril; Male; Prednisolone; Ribonucleosides; Valsartan

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticholesteremic Agents; Cholesterol; Diet, Reducing; Female; Glomerulonephritis, IGA; Hematuria; Humans; Lisinopril; Lovastatin; Middle Aged; Obesity; Proteinuria; Weight Loss