Progression of Glomerular disease txt

This is the low-bandwidth, text alternative to the video Progression after glomerular injury, from the post Progression of Glomerular Diseases.

Progression of glomerular diseases

Neil Turner – Aug 2020

So this is the last (4 of 4) in the string of short presentations about glomerular disease. It talks about what happens after you’ve had glomerular injury.

What happens

The graph tracks the reciprocal creatinine of a patient who had an episode of small vessel vasculitis at the beginning of this graph 5 years back, here. It’s showing  glomerular filtration rate improved a bit, and then slowly over the next five years declined to end-stage renal disease, even though they had been free of active inflammation for four years.

This is not a rare scenario, and of course it’s something that we want to do as much as possible to prevent.

So what’s the story, what’s going on here? Well, we do know quite clearly what the prognostic markers for showing this kind of trend are.

Prognostic markers for long term renal outcomes

      • Creatinine
      • Proteinuria
      • Blood pressure
      • (and if available) Renal biopsy evidence of tubulo-interstitial scarring

So the first one is, the more severe the damage in the first place, the less early recovery you get – the higher your risk of deteriorating in the long term. So that’s creatinine or glomerular filtration rate.

The second marker – and all of these markers are quantitative, so the worse they are, the worse your prognosis, the second marker is proteinuria. This is a very strong correlation actually, so that higher levels of proteinuria greatly increase your risk of developing worsening kidney failure. Even if you have quite good levels of creatinine.

And the third one is high blood pressure.

If you’ve had a kidney biopsy there’s a fourth factor available. If you see a lot of scarring, partly in glomeruli but even more influential on prognosis, in the tubulointerstitial region of the renal cortex, this is an indicator of previous damage. A bit like creatinine, but it’s another powerful risk factor to add on.

Preventing progression

We do know some things that will help prevent progression of renal injury in circumstances like this.

INEFFECTIVE OR LIMITED INTERVENTIONS

      • Low protein diet
      • Lipid lowering therapy

We used to recommend a low protein diet because this seemed to work in animal models. But often in animal models you weren’t controlling other things very well, such as blood pressure. And so although a  low-protein diet does work in animal models, in humans it’s been much less effective, and that may partly be because of control of other things, but the people on the lowest protein diets actually did rather poorly. You can become quite malnourished. You naturally lose appetite with renal failure. And if you’re also on a low protein diet, that it may not be good for you. So generally avoid high protein, but low-protein diet not recommended.

Lipid control has been tried. Lipids do run high in patients with renal disease. It turns out that they don’t slow down the progression of renal disease very much. But they’re probably justified in many patients by the other risk factors that patients have. So if they are hypertensive or just have chronic kidney disease they’re at greater risk of cardiovascular disease. There is RCT evidence for benefit at CKD3 or worse.

EFFECTIVE INTERVENTIONS

      • Blood pressure
      • ACE inhibitors and ARBs
      • Other drugs on the way

Blood pressure was actually the earliest and most convincing factor to have an impact. But it turns out that not just blood pressure control, but the use of things that interfere with angiotensin.

So ACE inhibitors or angiotensin receptor blockers, appear in patients with proteinuria to further reduce the risk, compared to just blood pressure control. And this is quite a powerful effect.

We’re really hoping that new drugs will come along, and the prospects are looking quite bright. Watch this space.

Further info

These issues are dealt with further in the session on chronic kidney disease. They are  applicable much more widely in primary care and other specialties, not just to nephrologists.

Thanks for listening.