My CHF patient is on diuretics; but now he/she is azotaemic….what should I do?
I don’t know about you guys but I think I left vet school with the distinct impression that too much diuretic can lead to reduced arterial pressure and thus reduced renal perfusion and azotaemia.
This simple picture does seem to have now been superseded. I like this up-to-date summary from the human literature:
Change in renal function associated with drug
treatment in heart failure: national guidance
Andrew L Clark, Paul R Kalra, Mark C Petrie, Patrick B Mark, Laurie A Tomlinson, Charles RV Tomson
Heart 2019;105:904–910
https://heart.bmj.com/content/heartjnl/105/12/904.full.pdf
It’s worth working our way through their main points with a little commentary.
‘Clinicians receive varying advice from cardiologists, nephrologists and other physicians.‘
…yes I can believe that!
‘The variation reflects the lack of robust evidence: designing and delivering randomised studies with management strategies directed both by changes in renal function and clinical response would be very complex‘
OK, that certainly applies to dogs and cats too.
‘Anxiety about rises in creatinine (and the associated falls in estimated glomerular filtration rate [eGFR]) can lead to underprescription of ACEI and ARBs. The tendency to withdraw ACEI and ARB has been exacerbated by the international adoption of the term ‘acute kidney injury’ (AKI) to describe acute changes in kidney function and by the inclusion of these drugs, which can also protect against progressive proteinuric kidney damage, in lists of drugs termed ‘nephrotoxic’. …..The results from clinical trials suggest that fears about renal function may be misplaced‘
The landscape of human heart failure differs substantially from that in cats and dogs. The majority of affected people suffer ‘Heart Failure with reduced Ejection Fraction’ (HFrEF) due to, for example, ischaemic heart disease. Whereas, at least in dogs, heart failure with preserved ejection fraction is commoner. As previously blogged, the evidence for ACEI in dogs with mitral valve disease isn’t compelling but I believe the same argument for diuretics is potentially applicable.
‘Venous congestion also causes an inflammatory response within the renal parenchyma. Decongestion by diuretics can thus result in an increase in GFR, and withdrawal of diuretics from patients with stable chronic heart failure can cause tubular injury‘
OK, so in cats and dogs with right-sided congestive failure (either primary right-sided pathology or pulmonary arterial hypertension in its various forms including secondary to left-sided failure) relief of congestion with diuretics might be important to preserve renal function.
‘Although higher diuretic dose in CHF is associated with worse outcome, the reason is that higher doses of diuretics are a marker of more severe heart failure. ……In patients with heart failure, the initial rise in creatinine is usually not due to intrinsic kidney injury but to a change in haemodynamics. Because patients with heart failure commonly have reduced renal function, even a small decline in renal function may produce a rise in creatinine large enough to trigger an alert and the stopping of prognostically vital medication’
In fact there is little evidence that diuretics are the cause of kidney injury in any species. This is a decent, fairly recent summary of the human situation:
Loop diuretics, renal function and clinical outcome in patients with heart failure and reduced ejection fraction
Kevin Damman John Kjekshus John Wikstrand John G.F. Cleland Michel Komajda Hans Wedel Finn Waagstein John J.V. McMurray
https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.462
To quote those authors:
‘Loop diuretics are often prescribed in patients with chronic heart failure (HF) to manage symptoms and signs of congestion, but their effect on (long term) clinical outcomes is uncertain. The acknowledged effectiveness of loop diuretics for the management of congestion, the potential for non‐adherence to precipitate admissions and a meta‐analysis of heterogeneous studies suggested that these agents do reduce admissions for worsening congestion. However, no large, prospective, randomized, placebo‐controlled trial has been conducted to assess the effectiveness of loop diuretics in improving clinical outcome in patients with chronic HF‘
and….
‘Importantly, our results do not support the notion that higher doses of loop diuretics are associated with a faster decline in estimated GFR, suggesting that, from a renal perspective, higher dosages of diuretics could possibly safely be prescribed. However, our results may suggest that the lowest possible diuretic dose to achieve effective decongestion or euvolaemia could be preferred over higher doses’
That’s not an argument for running placebo-controlled trials for diuretics: just a statement of fact to emphasize that there’s little hard evidence on which to base decisions.
In summary, in cats and dogs it seems reasonable to advise that the optimal dose of diuretic in CHF is ‘just enough to control congestive (pulmonary or systemic) signs regardless of any azotaemia’.
