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[Long-term administration of cyclosporine A in patients with IgA nephropathy]
Background:
IgA nephropathy is the most common glomerulonephritis all over the world and a considerable proportion of the patients reaches end-stage renal failure. Yet the standard treatment for the patients with progressive course and/or great proteinuria is currently lacking. All suggested treatment protocols, including short-term treatment with cyclosporine A had equivocal results. Therefore we decided to try long-term cyclosporine treatment.
Methods And Results:
We treated 6 patients (4 males, 2 females, age 21-31 years) with bioptically proven IgA nephropathy and proteinuria over 3.5 g/24 hrs with or without nephrotic syndrome non responding to corticosteroid therapy administered for at least 3 months. Patients with serum creatinine greater than 200 mumol/l and/or glomerulosclerosis in more than 50% of glomeruli in renal biopsy were excluded. Pts were given cyclosporine A in initial dose 5 mg/kg bw/day then titrated aiming to the serum concentration of 70-150 ng/ml. Prednisone 5-10 mg on alternate days was given with cyclosporine. Proteinuria decreased during first month of therapy from 4.66 +/- 0.43 g/day to 1.38 +/- 0.29 g/day (p < 0.01) and remained low after one year of treatment (0.59 +/- 0.14 g/day, p < 0.001). Glomerular filtration rate (creatinine clearance) did not change during first month of therapy (1.25 +/- 0.21 ml/s vs. 1.38 +/- 0.29 ml/s), but slightly decreased after one year of treatment (1.05 +/- 0.14 ml/s, p < 0.05). We also calculated ratio of proteinuria to glomerular filtration rate (g/l) to assess the role of hemodynamic changes in the decrease of proteinuria. This ratio was 53.80.10(-3) +/- 15.20.10(-3) before cyclosporin therapy, it decreased significantly after one month (11.56.10(-3) +/- 3.24.10(-3), p < 0.05) and achieved the lowest value after one year of therapy (6.78.10(-3) +/- 4.25 .10(-3) +/- 4.25.10(-3), p < 0.01). Serum cholesterol also significantly decreased after 12 months of therapy (6.21 +/- 0.62 vs. 5.41 +/- 0.45 mmol/l, p < 0.05).
Conclusions:
CyA significantly lowered moderate to high proteinuria with much less decrease of glomerular filtration rate in 6 patients with IgA. Significant decrease of proteinuria/GFR ratio strongly suggests some non-hemodynamic mechanisms of cyclosporine action in these patients. Therapy was well tolerated and side-effects were not so severe to require cyclosporine withdrawal.
Insights
Long-term cyclosporine treatment significantly reduced proteinuria in IgA nephropathy patients with minimal impact on kidney function. This therapy was well-tolerated, offering a promising option for managing this common kidney disease.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Context:
- IgA nephropathy is the most prevalent glomerulonephritis globally, often leading to end-stage renal failure.
- Current treatments for progressive IgA nephropathy with significant proteinuria are limited and yield equivocal results.
- Short-term cyclosporine A treatment has shown inconsistent efficacy in IgA nephropathy patients.
Purpose:
- To evaluate the efficacy and safety of long-term cyclosporine A treatment in patients with IgA nephropathy and significant proteinuria.
- To assess the impact of long-term cyclosporine A on proteinuria, glomerular filtration rate, and proteinuria/GFR ratio.
- To investigate potential non-hemodynamic mechanisms of action for cyclosporine in IgA nephropathy.
Summary:
- Six patients with IgA nephropathy and proteinuria >3.5 g/24h, unresponsive to corticosteroids, received long-term cyclosporine A (CsA).
- Proteinuria significantly decreased from 4.66 g/day to 0.59 g/day after one year (p < 0.001), with a minimal decline in glomerular filtration rate.
- The proteinuria/GFR ratio decreased significantly, suggesting non-hemodynamic effects of CsA, and the therapy was well-tolerated.
Impact:
- Long-term cyclosporine A therapy effectively reduces proteinuria in IgA nephropathy patients.
- This treatment offers a potential therapeutic strategy for IgA nephropathy with significant proteinuria and progressive disease.
- The findings suggest cyclosporine A may act through non-hemodynamic pathways, warranting further investigation.