Acute protein losing nephropathy causes and treatment options? Friday conundrum : )

RE: Acute protein losing nephropathy causes and treatment options? Friday conundrum : )

hilary warner — Tue, 28 Nov 2023 14:42:01 GMT

Hi Mayank,

Whoops, I thought I had advised before ran a low dose dex after the last message and scanned abdomen. No evidence of HAC on low dose test initial Cortisol 115 supressed to < 27.6 sustained. Urine cortisol was 12.1

We had a period of eating RC sensitivity with a little c/n food and was VE liver support. for October the liver support was inadvertently stopped after a short bout of diarrhoea and being put on a GIT support clay.

Ruby is now refusing to eat anything( last 24 hours) Ultrasound scan normal layering of intestines but increased thickness to 3.5-4.5mm The stomach mucosal layer appears to be hyperechoic to normal, and seems to have acid reflux. Azotaemia has recured. This does respond to i/v fluids or has so far but the not eating is causing an issue with also not wanting to drink.

I have gone over her HP results for the liver with a colleague and they noted there was extrahepatic haematopoiesis. The rbc count has reduced from 40% to 37% with no signs of haemorrhage.

RE: Acute protein losing nephropathy causes and treatment options? Friday conundrum : )

Mayank Seth — Mon, 27 Nov 2023 14:58:54 GMT

Hi Hilary

To me the ALT elevation sounds like its secondary to the GI signs and the UPC elevation probably is too. Did you ever test this dog for HAC? I'll confess I'm not sure what CN is? Did you try the Purina HA diet?

I would be very worried if you think you have reason to beleive the patient may be bleeding as most chronic GI/pancreatitis cases don't do this. HAC could be contributing if present. Have you done an ultrasound recently to look at the GI tract/pancreas?

I would focus on ctronl of the GI/pancreatic disease and I suspect that the UPC and ALT would follow. Cyclosporine may ahve a role in this but I worry about starting it in an inappetant dog. It sounds like nutrition, analgesia and antacids may be the way to start, with intorduction of an immunosuppressive if required.

Good luck!

Mayank

RE: Acute protein losing nephropathy causes and treatment options? Friday conundrum : )

hilary warner — Wed, 22 Nov 2023 12:35:09 GMT

Continuing the saga of this little dog.

We have tried various diets and were doing well on RC sensitivity with a little bit of CN until the protein loosing nephropathy started.

The Protein loosing nephropathy settled to 1.8 when we stopped the cn and added in chicken and rice. We seemed to have a relatively stable period with the liver with ALT mid 200's. We have had a flare up of liver enzymes ALT 1400 ( liver support was inadvertantly stopped for around 6 weeks over October and start of Nov.) We have had an acute flare up of Liver with ALT increased to 1400 now reducing as back on liver support. There is now a PLN with UPC highest we have had at over 4 in Oct we had reduced this to 1.8 and urine had started to concentrate. Is it time to start this little one on cyclosporine?

Today she is not keen to eat and has pain in her right cranial dorsal qaudrant this may be associated with a GIT bleed as reduced pcv and raised urea more on a general azotaemia.

Again thank you for input in this case. The owners have declined renal biopsy.

RE: Acute protein losing nephropathy causes and treatment options? Friday conundrum : )

Mayank Seth — Wed, 02 Aug 2023 23:42:37 GMT

Hi Hilary

A Low Dose Dex is almost always the better test for Cushings and it is what I would do here. The main exception to this would be if you are looking for iatrogenic disease. For a really detailed discussion on this I would direct you to https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.12192

I was thinking about this dog after the last post, wondering if I would ahve the conviction to do a trilostane trial for "atypical hyperadrenorticism" if the LDDST was not compatible. If the GI signs have settled with diet and the PU/PD is a consistent feature of the current problem, I might be tempted but lets save that discussion until you get this result!

RE: Acute protein losing nephropathy causes and treatment options? Friday conundrum : )

hilary warner — Wed, 02 Aug 2023 21:30:32 GMT

I have seen the dog again today, we are on a mixture of sensitivity food and some c/n. She used to have a ravenous appetite until recently.

Ultrasound scan adrenals L reported 0.75-0.83cm and R 0.77cm.

Will book in for check if HAC. I have usually done a low dose dex test but would an ACTH stim be better in this case and if so why?

RE: Acute protein losing nephropathy causes and treatment options? Friday conundrum : )

Mayank Seth — Mon, 31 Jul 2023 21:54:46 GMT

Hi Hilary

Thanks for the detailed info! If I were to summarise (and cherry pick the bits that I like!) I would say that you ahve a dog that has a persistant elevation in liver enzymes with ALT>Alkp and concurrent hypercholesterolaemia, concurrent persistent TLI elevation, vacuolar hepatopathy with peri-portal chronic inflammation, intermittent GI signs, polyphagia and more recent PU/PD with development of proteinuria somewhere along the way. Some of the clinical signs have been responsive to a GI diet.

Its difficult without speaking to the pathologist and reviewing the detail of the liver histopath but this doens't really seem like a classic chronic hepatitis to me - the periportal inflammation is commonly seen as a reaction to inflammation elsewhere in the GI tract, being reacted to as the portal blood hits the liver. The vaculoar component goes with the high Alkp/cholesterol and speaks more to a systemic metabolic issue.

I know you ahve a normal cPLI but the intermittent signs, high TLI and the rest of the picture make me wonder about a component of pancreatitis at play here. The vaculoar hepatopathy, raised Alkp, cholesterol, polyphagia, PU/PD and proteinuria all sound like cushings could be at play here and a normal cortisol:crea ratio woudlnt necessarily put me off more specific testing (LDDST) given the weight of the evidence suggesting it.

I think ACE inhibiotion is a perfectly reasonable thing to do for this dog given the proteinuria. Diet choice is a bit more tricky - you would ideally want low fat (in case of pancreatitis), low protein (due to the PLN) and GI friendly. Purina HA (dry) ticks all of these boxes so I would try this (there can be palatbility issues but if the dog is ravenous...).

I wouldn't rush to immunosuppress this dog in the near future - the liver doesn't sound like it necessarily warrants it, the GI signs seem like they may be diet responsive and you don't yet know if the proteinuria is secondary or if it will control with protein reduction/ACE inhibition.

Hope that gives some pointers to guide the next few steps but do let us know how it pans out or if we can help more!

RE: Acute protein losing nephropathy causes and treatment options? Friday conundrum : )

hilary warner — Sun, 30 Jul 2023 23:18:23 GMT

Apologies if the below is rather long winded. I have been reading around hepatitis in dogs and dysbiosis.

Dog was taken on from RSPCA in July 2019, was apparently on a special diet but not exactly sure what or why but it was not continued. Had recurrent otitis no infectious agent identified just very waxy- managed with cleaning and Recicort , after several months was under control.

Looks to be a Yorkshire terrier type/cross.

Intermittent diarrhoea, and gastric upset, used to have severe wind. Always seemed hungry and was food obsessed. Sometimes would seem depressed usually associated with GIT upset.

Bloods taken in Nov 2020 Total protein 77 ALB 36.8 and globulin 40.3. Liver enzymes mildly elevated ALT 193 ALKP 419, Elevated BA, Cholesterol and triglycerides. TLI high > 50, folate low 6.4 Cobalamin and cPL normal.

Faecal tests 2020 all negative for infectious agent.

Bloods in July 2022 TP 81, ALB 40.2 glob 40.9 ALT233, ALPK 595 Cholesterol 13.42 TLI high, folate high 18.8

July 2022 FNA of mildly enlarged LN caudal to liver and cranial to lesser curvature of stomach- normal to mildly reactive. 4 x samples from the liver were taken from different sites, histology varied from nodular hyperplasia, Hepatitis, portal and peri acinar lymphocytic, and plasmocytic, fibrosis, hyperplastic nodules and vacuolar hepatopathy, and Hepatitis with moderate vacuolar hepatopathy.

At this time a mammary mass- a adenoma was also removed.

Aug 2022. TP82.5, ALB 41.2, ALT 275 ALKP 758 GGT < 2 GLDH 142.8 ; BA fasting 9; BA post prandial 52.6 Cholesterol 13.7 Mild non regenerative anaemia.

Sept 2022 Anaemia improved Remaining results similar to Aug 2022

Oct 2022 recurrent diarrhoea and clostridia perfringens detected in faeces

Dec 2022 TP 85, ALB 40 Glob 45, ALT 237, ALKP 763 BA pre 10 post 29 Chol 13.2 Haematology normal.

Dec 2022 Infected Anal glands- thick green matter in both. swab taken, after initially trying to treat this with oral antibiotics it is now being managed with antibiotic infused directly into the glands which has proved more successful this has now been done around 3 times

Feb 2022 bloods repeated with faeces and canine dysbiosis indexx the latter was markedly elevated. Bloods Similar to before with now high folate 20.2

June 2023 bloods in house Urea and SDMA mildly elevated liver enzymes and protein similar to before

July 2023 Bloods similar to June 2023

June 2023 Cortisol:crea ratio in urine 12.1

Urine s.g in Sept 2020 was 1.045 Protein + some amorphous protein but no infectious agent identified in-house.

Urine s.g June 2023 1.024 and protein ++

Urine s.g July 2023 1.024 Protein ++++- stained slide amorphous protein UPC i house 7.25

After your e-mail I have sent urine to external lab and s.g 1.025, UPC 3.4 No crystals bacteria seen and non cultured.

From July 2022 we have tried on prescription liver diets with liver support, probiotic was added in in Feb 2022, these diets have not settled the symptoms of recurrent diarrhoea as I would have hoped. In May this year the owners were unable to obtain the usual liver support diet and the dog was reluctant to eat the new food. When the diarrhoea recurred this June there was also an increase in thirst and appetite was poor. Urine was poorly concentrated compared to before. I changed from a liver support diet to a gastric diet with some convalescent diet. Since starting this the patient seems much brighter and there has been no more diarrhoea.

My main concern now is the damage caused to the kidneys by the PLN that has developed and the obvious hyperechogenicity of the renal cortex seen July 2023 not previously noted on various scans including one carried out in June 2022 by a colleague with additional imaging certification.

I have started on benazipril, 21st July 2023 along with the GIT & recovery/convalescent diet. Since these changes have been started the patient seems much brighter is eating better and thirst has reduced.

My thoughts at present are this dog seems to have a chronic hepatitis I am not certain if gut flora are a contributing factor. The deterioration in June seems to be associated with a change in the type of liver support diet being fed but I am now thinking the liver support diet has not been as beneficial as it was expected to be. I am not certain if I should be trying to treat the chronic hepatitis with drugs.

Please let me know if the information above is what you were expecting and in a format you were expecting it in.

The owners are not keen on renal biopsy and I understand from what you have written that given the hepatitis it might be worth considering treating this with cyclosporine as the PLN is likely caused from this flaring up.

RE: Acute protein loosing nephropathy causes and treatment options? Friday conundrum : )

Mayank Seth — Sat, 22 Jul 2023 12:55:37 GMT

Hi Hilary

Sounds like a bit of a mash up of different things going on here - poor dog!

Echoing what Dinu has said, it would be good to know about the bloods and a bit more info before really getting into this case - I'm not sure what is going on with the liver as I don't really recognise diet as a substantial component of the management of most manifestations of chronic hepatitis. Has it helped? Is this acutally a reactive hepatitis due to GI disease in that instance?

I assume the dog is not azotaemic and proteins are normal? Any other bloodwork abnormalities, active urine sediment or clinical signs? What's the USG? Are you sure the UPC is new? What's the BP doing? One of the reasons I ask is that in a toy breed dog with raised liver enzymes and high UPC the first thing I would think of is Cushings, although this wouldn't explain the picky appetite (unless a pituitary tumour or similar) nor would it ewxplain the ultrasound findings (which are admittedly very non-specific).

To try and answer your questions directly (although perhaps not helpfully?):

-The chronic hepatitis form of lepto is generally considered its own distinct entity rahter than somehting that has been documented to turn into an acute hepato-renal issue. Additionally, lepto isn't really consdred as a cause of non-azotaemic chronic PLN so I'm not sure there is an easy link to be made between these conditions. Having said that, any inflammatory disease (the hepatitis?) can be a trigger for PLN.

-Kidney biopsy would be indicated if you ahve excluded non-renal causes of the UPC (in particular lower urinary tract disease, infectious cases and significant triggers such as neoplasia). I haven't had one go wrong but I get specialist radiologists to take most of mine and the severe haemorrhage rate is reported upto 10%. If you do take a biopsy its REALLY important that this goes to a renal pathology unit that can do immunoflourescence etc rather than your normal path lab. There are guides on how to collect and prepare the samples but its best to speak to the lab first andf obtain specialist media to store the samples for shipping etc. Most people in the UK use the European VEterinary Renal Pathology Service.

-I would not be inclined to use steroids here - with or without a biopsy. The IRIS guidelines generally shy away from steroids in most cases of PLN and recomend pretty much any other immunosuprressive in the first instance (with a non-evidence based leaning to mycophenolate). It would help to understand the liver a bit more before making specific recomendations on this front but cyclopsorine has a recongised potential benefit for liver/GI/kidneys...

Do keep us updated!

Mayank

RE: Acute protein loosing nephropathy causes and treatment options? Friday conundrum : )

Dinu Catilina — Sat, 22 Jul 2023 08:33:51 GMT

Internal medicine is not my thing but as a few ideas:

Have you done any bloods? What is the BUN and Cre?
Lepto can be diagnosed easily but I've never seen a case of chronic lepto
I did biopsy kidneys in the past, mainly in puppies to help breeders understand if the disease is congenital/hereditary. I did not see any complications and it was done ultrasound guided but you can cause severe haemorrhage if you biopsy the renal artery/vein.
Yes, it would be wrong to just put on steroids, I would rather have a diagnosis first.

Hope this helps!

RE: Acute protein loosing nephropathy causes and treatment options? Friday conundrum : )

hilary warner — Fri, 21 Jul 2023 19:04:05 GMT

Just found a link ref chronic hepatitis https://onlinelibrary.wiley.com/doi/10.1111/jvim.15467

Does anyone know if this can trigger PLN.