15 | How to confidently treat and care for PLN patients

PodcastRenal
Written By Laura Jones

Today, we’re talking all about a renal disease that’s more common than you think - protein-losing nephropathy, aka PLN.

 

I never knew that PLN existed before moving into referral practice - I just thought patients had CKD, and they were all managed in the same way. But protein-losing nephropathy is a really important renal disease, and these patients are at risk of significant complications. Today, we’ll discuss what PLN is, how it happens, and the ways we can best treat and care for these patients.

What is protein-losing nephropathy?

PLN is a renal disorder characterised by the loss of proteins through the glomerulus within the nephron, causing marked proteinuria.

There are several causes of proteinuria in our patients - we can characterise these as either pre-glomerular proteinuria, which is where patients have high numbers of circulating proteins in the bloodstream,

Glomerular proteinuria, which is where there is a problem with the glomerulus causing protein loss into the urine,

Or post-glomerular proteinuria, which is where the source of protein is after the glomerulus. For example, renal tubular injury, or infection, inflammation, or neoplasia lower in the urinary tract.

Patients with PLN have glomerular proteinuria. This is due to a problem with their glomerular filtration barrier - causing proteins to ‘leak’ from the bloodstream, through the glomerulus and into the glomerular filtrate (and ultimately into the urine).

Which patients get PLN?

PLN can be seen in both dogs and cats, but it is seen far more frequently in dogs. There are several causes of PLN, including glomerulonephritis, inherited glomerulopathy, and amyloidosis. Some breeds are predisposed to developing PLN, and some infectious diseases, endocrinopathies, and inflammatory diseases can cause PLN to develop, too.

Let’s look at glomerulonephritis…

Glomerulonephritis is an immune-mediated condition, where immune complexes are present inside the glomerulus, which change the permeability of the capillaries in the glomerular wall.

This causes them to become ‘leaky’ and in turn, causes protein loss.

This type of glomerular disease is often idiopathic, but can also occur secondary to heartworm, tick-borne diseases, severe inflammatory disease, diabetes mellitus, hyperadrenocorticism, the administration of prolonged high-dose steroids, and neoplasia.

And what about amyloidosis? 

Amyloidosis is caused by the abnormal deposition of amyloid, an insoluble protein, within tissue. Where amyloid is deposited, inflammation is generally seen in response, and the deposition of large amounts of amyloid can cause organ dysfunction.

Amyloidosis often occurs within the glomerulus, but can also occur in extra-renal tissues, including the liver and spleen. Amyloidosis is familial in several breeds, including Shar Peis and Abyssinian cats.

And what about glomerulopathies?

Familial glomerulopathy is an inherited disorder of the structure and function of collagen in the body. This leads to a deficiency of collagen within the glomerulus, causing it to not function properly.

What are the signs we see in a PLN patient?

In the early stages of the condition, many patients will be asymptomatic.

Weight loss and lethargy are usually the first signs seen - the severity of this can vary, from gradual weight loss in patients with moderate proteinuria to rapid and marked weight loss in patients with severe disease.

Hypertension is also common in proteinuric patients, especially those with PLN. We know that hypertensive damage can occur to certain organs - known as ‘target organs’, including the eyes, the CNS, and the kidneys themselves. Depending on the degree of hypertensive damage present, signs of target organ damage - such as visual deficits, retinal haemorrhage or detachment - may also be seen.

As more of the plasma protein albumin is lost in the urine, changes to the patient’s fluid balance will be seen. This occurs because albumin is responsible for maintaining colloidal oncotic pressure - keeping fluid within our blood vessels. When albumin leaves the intravascular space, the vessels don’t have as much oncotic pressure to hold water within the blood. This causes leaking of fluid into tissues and body cavities - resulting in pitting oedema (especially on the ventral abdomen and distal limbs) +/- ascites and/or pleural effusion.

The most severe complication of PLN is thromboembolic disease. This is seen because antithrombin III, a protein which stops blood clots from forming when they shouldn’t, is also lost into the urine through the ‘leaky’ glomerulus. This means our PLN patients are in a hypercoagulable state and are prone to thromboembolism. On top of this, proteinuria can contribute to mild thrombocytosis (increased platelet levels) and increased platelet sensitivity, further contributing to coagulation abnormalities.

And what about diagnosing these patients?

Like many of our other medical conditions, we diagnose PLN based on a combination of bloods, urine analysis and imaging. We’ll also want to measure blood pressure in these patients, just like our CKD cases - but unlike many other renal conditions, the only way to definitively diagnose an underlying glomerular disease is with a renal biopsy.

Beginning with bloods…

On biochemistry, BUN, creatinine and phosphate are usually increased, though not always - it depends on the degree of renal dysfunction that the PLN has caused.

Hypoalbuminaemia or panhypoproteinaemia (where TP, globulin and albumin is low) is common, especially in severe cases.

Haematology may be unremarkable, though anaemia can be seen in CKD patients due to the loss of erythropoietin and a mild thrombocytosis may be present in hypercoagulable patients.

On the topic of coagulation, if you have access to viscoelastic testing or thromboelastography, you often see a wide trace, and a high MCF, because these clots are stronger than normal and harder to break down. 

What about urine analysis?

Moving on to urine analysis, an elevated protein creatinine ratio is classically seen in these patients. This is often very elevated, up to about 15 (for context, a patient is classed as proteinuric if their UPC is above 0.4-0.5, depending on the species).

And finally, looking at imaging and sampling…

There are no specific changes that we see on ultrasound that tell us our patient has PLN. Instead, we’re using ultrasound to examine the size and structure of the kidneys, look at the corticomedullary definition, look for changes to other organs, identify any other causes of the patient’s renal disease, and guide sample collection.

As I mentioned, the only way to definitively diagnose the patient’s underlying glomerular disease is with a renal biopsy. We don’t do this in all cases, because this procedure is technically challenging and not without risk. Biopsies are taken from the renal cortex because there is an increased risk of complications such as haemorrhage when sampling the renal medulla. Samples need to be examined in-house to ensure glomeruli are present, then submitted to a specialist laboratory for immunofluorescent and electron microscopy.

So you’ve diagnosed your patient. Let’s talk treatment!

Once your patient has had their diagnostics, it’s time to get stuck in with planning their treatment and nursing care.

We treat PLN using a combination of:

ACE inhibitors, such as benazepril, which decrease proteinuria and delay the onset of renal failure. These work by interrupting the RAAS - the renin, angiotensin and aldosterone system, which manipulates both blood pressure and, in turn, the pressure within the glomerulus.

Antihypertensive agents, such as amlodipine which is a calcium channel blocker, and reduces systemic blood pressure

Diuretics, where needed - such as spironolactone - to minimise oedema caused by hypoalbuminaemia

Antithrombotics, such as clopidogrel (which stops platelets sticking together) or rivaroxaban (which is a factor Xa inhibitor) to prevent thromboembolic complications

And immunosuppressant medications to treat any immune-mediated glomerular diseases. We usually avoid prednisolone unless we know the disease is steroid-responsive since steroids themselves can cause proteinuria.

And then on top of this, it’s all about supportive treatment and good quality nursing care - which is where we come into the mix!

Our priorities when nursing these patients are:

  • To restore appropriate fluid balance

  • To provide nutritional support

  • To monitor the patient closely, particularly for signs of thromboembolic disease

  • To provide general nursing care

And we’re chatting through all of those in today’s episode!

So as you can see, protein-losing nephropathy is very different to CKD or AKI - and PLN patients can be a bit of a challenge to manage, especially if they decide to start throwing clots! To nurse them effectively, we need a good understanding of the disease, and what the consequences of it are for our patients - so that we can plan the care that meets their specific needs.

Did you enjoy this episode? If so, I’d love to hear what you thought - screenshot it and tag me on instagram (@vetinternalmedicinenursing) so I can give you a shout out, and share it with a colleague who’d find it helpful!

Thanks for learning with me this week, and I’ll see you next time!

References and Further Reading

Laura Jones
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