Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease S Bianchi, R Bigazzi and VM Campese Kidney International advance online publication 11 October 2006

Background  prevalence of CKD increasing result of an ongoing epidemic of obesity, metabolic syndrome, diabetes mellitus.  Several factors contribute to progression of CKD derangements of renal hemodynamics, vasoactive hormones such as angiotensin II and norepinephrine, cytokines, growth factors, oxidative stress, and inflammation

 RAAS important role in the progression of CKD  inhibition of RAAS with ACEIs, ARBs  retard CKD progression  “renoprotective effects” reduction of systemic arterial glomerular pr. inhibition of angiotensin II-related effects on mesangial cell proliferation and fibrosis.

 ‘aldosterone synthesis escape’ neither ACEIs nor ARBs progression of CKD ACEIs,ARBs not predictably suppress aldosterone leaving detrimental effects of aldosterone unabated  clinical evidence for a role of aldosterone in CKD progression is scanty  prospective, randomized open-label study to evaluate the effects of spironolactone

MATERIALS AND METHODS

82 patients (conventional therapy) 83 patients (spironolactone 25 mg/day) enrolled 165 CKD pts (106 males and 59 females) baseline evaluation each clinic visit at 1, 3, 6, 9, 12 months BP, heart rate, blood sample spot morning urine samples

Exclusion criteria  diabetes mellitus, renovascular or malignant HTN  secondary glomerular disease, malignancies  myocardial infarction  cerebrovascular accident within the 6 mo.  congestive heart failure, hepatic dysfunction  potassium >5 mEq/l, eGFR <30 ml/min/1.73m 2  History of allergy to ACEIs or ARBs  patients treated with steroids, NSAIDs, immunosuppressant

RESULTS

Table 1. Clinical characteristics at baseline of pts treated with conventional therapy and conventional therapy plus spironolactone 25 mg/day

Table 2. BP, estimated GFR and serum potassium levels at baseline and during f/u in pts treated with conventional therapy and conventional therapy plus spironolactone

Table 3. Effect of spironolactone on proteinuria in pts with eGFR 60 ml/min/1.73m2

Table 4. Effect of spironolactone 25 mg/day on renal function in pts with eGFR 60 ml/min/1.73m 2

Table 5. Clinical characteristics at baseline and end of study in pts treated with spironolactone in addition to ACEIs alone, ARBs alone, or a combination of ACEIs and ARBs

Figure 1. This slide shows the percent reduction of proteinuria from baseline in pts treated with spironolactone (25 mg/day) in addition to conventional therapy divided on basis of their eGFR ( 60 ml/min/1.73m 2 ).

Figure 2. This slide shows the percent decline in eGFR in pts treated with spironolactone and conventional therapy.

Figure 3. This slide shows the regression line between baseline plasma aldosterone levels and proteinuria in the 165 pts included in the study (r=0.766, P<0.0001).

Conclusion  spironolactone may reduce proteinuria and retard renal progression in chronic kidney disease patients.