ACE inhibitors and PD

Back to the subject of ACE inhibitors again. There are a number of reasons why ACEi might be particularly beneficial for patients on PD and two recent editorials in KI and CJASN laid these out very well.

1. Preservation of the peritoneal membrane
2. Preservation of residual renal function

Peritoneal mesothelial cells produce angiotensin II in response to glucose and dialysis solutions. This stimulates the release of pro-inflammatory TNF-alpha and IL-6 and also leads to upregulation of profibrotic factors (TGF-beta) and angiogenic factors such as VEGF.

This causes increased submesothelial zone thickness and neoangiogenesis which leads to increased vascular permeability and small solute transport. This in turn leads to faster absorption of glucose with subsequent loss of the osmotic gradient and UF failure. This ‘high transport’ state is associated with a worse long-term prognosis.

As Lisa mentioned in a previous post ACE inhibitors appear to have a beneficial effect on this process. They have been shown to decrease the expression of TGF-beta and VEGF in the peritoneum in response to glucose.

When rats were exposed to high glucose concentrations and were treated with enalapril or placebo, ACE inhibitor-treated rats had reduced TGF-B levels, reduced peritoneal thickness and improved UF. There have been a small number of mostly retrospective studies in humans comparing patients on and off ACE inhibitors and although no survival benefit has been noted, ACE inhibitors have been shown to increase Kt/V and prevent the increase in small solute transport possibly preserving UF in the long term.

The CANUSA and ADEMEX studies both found that the most important factor in predicting survival on PD was residual renal function. In the CANUSA study, for every 5L/week increase in residual function, there was a 12% increase in survival. Peritoneal clearance and peritoneal UF were not associated with survival. Increased residual function has been associated with better BP control, less LVH and a decreased risk of peritonitis.

In small trials, both ramipril and valsartan have been shown to decrease the rate of loss of residual function in patients on PD and at the end of one year, patients treated with ACE inhibitors were less likely to be anuric. This effect was independent of BP control and was seen in normotensive as well as hypertensive patients.

So the question arises, should we be using ACE inhibitors routinely in PD patients even if they are normotensive? The jury is still out on that one and larger studies are needed to determine the answer.