Sorry this is a bit late. Mr Benny Efendie emailed me with some clarifications from his lecture, I'm pasting the relevant parts directly from the email :
Actually proposed mechanisms of ACEI reducing proteinurea is because they reduce the pressure on glomerulus, so minimizing the damage and also recent studies reveal that they may reduce mesangial cell growth and matrix production which contribute to the proteinurea.
This is the positive side of ACEI/ARB.
But at the same time they will cause decrease in GFR, and then acute renal failure or deterioration of renal failure. This drug-induced nephropathy is likely to occur if the patient already has risk factors, like hypovolaemia or already got severe renal failure, or bilateral renal artery stenosis (unilateral is still ok, not too bad) or using other concurrent nephrotoxic drugs like NSAIDs. And contraindication here is more for patients with renovascular disease, not other type of renal diseases. This is the negative side of ACEI/ARB.
In conclusion: as in other drugs, ACEIs are like a double-edged sword, doctors must weigh the risk and benefit before prescribing them. According to BNF 55 (latest version): For Captopril, the dosage must be reduced according to the degree of renal impairment.
max. initial dose 25 mg daily (do not exceed 100 mg daily) if creatinine clearance 20*40 mL/minute;
max. initial dose 12.5 mg daily (do not exceed 70 mg daily) if creatinine clearance 10*20 mL/minute;
max. initial dose 6.25 mg daily (do not exceed 37.5 mg daily) if creatinine clearance less than 10 mL/minute
Below is the explanation about ACEI and proteinurea from the Goodman & Gilman pharmacology:
Diabetes mellitus is the leading cause of renal disease. In patients with type 1 diabetes mellitus and diabetic nephropathy, captopril prevents or delays the progression of renal disease (Lewis et al., 1993). Renoprotection in type 1 diabetes, as defined by changes in albumin excretion, also is observed with lisinopril (Euclid Study Group, 1997). The renoprotective effects of ACE inhibitors in type 1 diabetes is in part independent of blood pressure reduction. Specific renoprotection by ACE inhibitors is more difficult to demonstrate in type 2 diabetics, with some studies providing positive results (Ravid et al., 1993, 1996, 1998), whereas others do not demonstrate blood pressure-independent renoprotection (Brenner and Zagrobelny, 2003). In addition to attenuating diabetic nephropathy, ACE inhibitors also may decrease retinopathy progression in type 1 diabetics (Chaturvedi et al., 1998). ACE inhibitors also attenuate the progression of renal insufficiency in patients with a variety of nondiabetic nephropathies (Maschio et al., 1996; GISEN Group, 1997; Ruggenenti et al., 1998, 1999b; Kshirsagar et al., 2000; Praga et al., 2003) and may arrest the decline in GFR even in patients with severe renal disease (Ruggenenti et al., 1999a).
Several mechanisms participate in the renal protection afforded by ACE inhibitors. Increased glomerular capillary pressure induces glomerular injury, and ACE inhibitors reduce this parameter both by decreasing arterial blood pressure and by dilating renal efferent arterioles. ACE inhibitors increase the permeability selectivity of the filtering membrane, thereby diminishing exposure of the mesangium to proteinaceous factors that may stimulate mesangial cell proliferation and matrix production, two processes that contribute to expansion of the mesangium in diabetic nephropathy. Since angiotensin II is a growth factor, reductions in the intrarenal levels of angiotensin II may further attenuate mesangial cell growth and matrix production.
Happy Studying
Ben Luke
