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Published on: November 1, 2018
Intensive versus conventional therapy to slow the progression of idiopathic glomerular diseases
Stefano Bianchi1, Roberto Bigazzi, Vito M Campese
1Unità Operativa Nefrologia Spedali Riuniti di Livorno, Livorno, Italy.
Insights
Intensive therapy combining ACE inhibitors, ARBs, statins, and spironolactone significantly slowed chronic kidney disease progression compared to conventional therapy. However, this approach increased adverse events and treatment discontinuation.
Area of Science:
- Nephrology
- Pharmacology
- Internal Medicine
Background:
- Idiopathic glomerular diseases often lead to progressive chronic kidney disease (CKD).
- Renin-angiotensin system (RAS) inhibition slows CKD progression but does not halt it.
- Statins and spironolactone offer potential benefits in slowing CKD progression, alone or with RAS inhibition.
Purpose of the Study:
- To compare the efficacy and safety of an intensive therapeutic regimen versus conventional therapy in patients with idiopathic chronic glomerulonephritis.
- To evaluate the impact of intensive therapy on estimated glomerular filtration rate (eGFR) and proteinuria over three years.
Main Methods:
- A randomized open-label study involving 128 patients with idiopathic chronic glomerulonephritis and eGFR >30 mL/min/1.73 m(2).
- Intensive therapy group received RAS inhibitors (ACE inhibitors plus ARBs), high-dose statin, and spironolactone.
- Conventional therapy group received ACE inhibitors and low-dose statin.
Main Results:
- Intensive therapy significantly reduced proteinuria (urine protein-creatinine ratio from 2.65 to 0.45 g/g) and preserved eGFR (64.6 to 62.9 mL/min/1.73 m(2)).
- Conventional therapy also reduced proteinuria (2.60 to 1.23 g/g) but resulted in a significant decrease in eGFR (62.5 to 55.8 mL/min/1.73 m(2)).
- Intensive therapy led to more adverse events, including hyperkalemia, and higher discontinuation rates.
Conclusions:
- An intensive therapeutic approach combining ACE inhibitors, ARBs, high-dose statins, and spironolactone is more effective in retarding CKD progression than conventional therapy.
- This intensive regimen, while beneficial for proteinuria and eGFR, is associated with increased risks of adverse effects and treatment cessation.
Background:
Chronic kidney disease (CKD) caused by idiopathic glomerular diseases usually is progressive. Inhibition of the renin-angiotensin system (RAS) retards, but does not abrogate, CKD progression. Statins and spironolactone may decrease the rate of CKD progression independently or in addition to RAS inhibition.
Study Design:
Randomized open-label study.
Setting & Participants:
We recruited 128 patients (82 men and 46 women) with a clinical diagnosis of idiopathic chronic glomerulonephritis and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m(2) (range, 36-102 mL/min/1.73 m(2)), and urine protein-creatinine ratio ranging from 1.1-5.2 g/g.
Intervention:
Intensive therapy (a combination of RAS inhibitors [angiotensin-converting enzyme [ACE] inhibitors plus angiotensin receptor blockers [ARBs] plus a high-dose statin and spironolactone) versus conventional therapy (a regimen based on ACE inhibitors with a low-dose statin).
Outcomes:
Changes in eGFR, proteinuria, and adverse events after 3 years of therapy.
Results:
With intensive therapy, urine protein-creatinine ratio decreased from 2.65 (range, 1.1-5.2) to 0.45 (0.14-1.51) g/g (P < 0.001) and eGFR did not significantly change over time (64.6 +/- 2.1 vs 62.9 +/- 2.9 mL/min/1.73 m(2)). With conventional therapy, urine protein-creatinine ratio decreased from 2.60 (range, 1.32-5.4) to 1.23 (0.36-3.42) g/g (P < 0.001) and eGFR decreased from 62.5 +/- 1.7 to 55.8 +/- 1.9 mL/min/1.73 m(2) (P < 0.001). Comparison of the decreases in proteinuria and GFR between intensive versus conventional therapy was significantly different starting in the 1st and 12th months, respectively. Systolic blood pressure was lower with intensive than conventional therapy (113.5 +/- 1.4 vs 122.7 +/- 1.2 mm Hg; P < 0.01). We found an inverse relationship between percentage of decrease in proteinuria and change in eGFR (P < 0.001). Patients on intensive therapy were more likely to develop adverse events, such as hyperkalemia (9 vs 3 patients in the conventional therapy group) and discontinue therapy (15 vs 8 patients in the conventional therapy group).
Limitations:
Open-label design.
Conclusions:
A more intensive therapy that includes a combination of ACE inhibitors and ARBs plus high-dose statins and spironolactone may retard CKD progression more effectively than conventional therapy based on ACE inhibitors plus low-dose statin, but may lead to more adverse effects and discontinuation of therapy.
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