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CASE NOTES

Severe crescentic membranoproliferative glomerulonephritis in an Australian White lamb

Glanville E and Watt B, Central Tablelands Local Land Services, Bathurst and Winkenwerder E and Pinczowski P, Elizabeth Macarthur Agricultural Institute, Menangle

Posted Flock and Herd June 2025

INTRODUCTION

A glomerulopathy syndrome has been recently reported in several Australian White lambs and has been colloquially dubbed 'Australian White Kidney disease (AWKD)'. The cause of AWKD is unknown and is suspected to be a hereditary, congenital condition. A 2024 Flock and Herd case note describes this emerging disease in multiple cases of rapid-to-sudden death in two-week- to two-month-old Australian White lambs from six unrelated properties across NSW investigated by Elizabeth Macarthur Agricultural Institute (EMAI, Menangle, NSW) between 2021 and 2024 (Winkenwerder and Pinczowski, 2024). The case reported here is consistent with these earlier cases.

HISTORY

A producer managing a flock of approximately 50 Australian White ewes with lambs at foot reported the rapid deterioration from lethargy to death of a previously healthy, well-grown, eight-week-old lamb. The lamb had been marked and had received its first clostridial vaccination. This case was not submitted for examination but was discussed with the local District Veterinarian (DV). A second lamb was reportedly also unwell at this time. It was a five-week-old, unmarked ewe lamb with a two-to-three-week history of being lethargic, slow to rise and lagging behind the ewe (as described by the producer). No specific clinical signs were observed by the producer. The DV advised a post-mortem if the lamb succumbed which it subsequently did. Both lambs were born to ewes vaccinated against clostridial disease.

NECROPSY FINDINGS

A well-grown 8kg ewe lamb with moderate abdominal distension was presented for necropsy on 25 September 2024. The lungs were multifocally heavy and dark pink with rib compression lines and on cut section the tissue was firm, homogenous and dark pink. The trachea contained white/pink foam. The heart appeared normal grossly. The liver was diffusely dark red with sharp edges. The large bowel was gas filled.

Both kidneys were markedly abnormal. Bilaterally, they were pale and cut section revealed significant hydronephrosis and markedly dilated renal pelvises. Renal cortices were mottled tan to salmon-pink with light and dark pink striations. In the right and left kidneys the cortices were 1.5cm and 1cm thick respectively. The medullas were markedly reduced in size, represented by scant, multifocal, irregular dark pink areas adjacent to the renal pelvis. There were two blind-ended tubular structures attached to the bladder serosa by connective tissue that contained dark brown material. These were later identified as regressive umbilical arteries.

Image of lamb post-mortem showing pulmonary oedema
Figure 1. Right side, pulmonary oedema and atelectasis with rib compression lines and diffuse hepatic congestion (photo Bruce Watt)
Image of lamb post-mortem showing hydronephorsis
Figure 2. Right kidney, hydronephrosis with a pale tan cortex and scant pink medulla surrounding a markedly dilated renal pelvis (photo Bruce Watt)
Image of lamb post-mortem showing hydronephrosis with cortical striations
Figure 3. Left kidney, hydronephrosis with numerous cortical striations suggesting glomerulonephritis (photo Bruce Watt)
Image of lamb post-mortem showing regressed umbilical arteries
Figure 4. Bladder and regressing umbilical arteries (photo Bruce Watt)

Histopathological findings

Histopathological evaluation of the kidney showed a severe, diffuse, chronic, active, segmental, membranoproliferative glomerulonephritis with glomerular parietal epithelial hypertrophy, crescent formation, glomerular haemorrhage, and associated tubular degeneration and necrosis and interstitial fibrosis. Masson’s trichrome showed multifocal red nodules within the glomerular capillary walls, which is typically associated with immune complex or complement deposits.

Other findings included moderate, subacute, periacinar to midzonal, hepatocellular degeneration and necrosis, and moderate, acute pulmonary oedema with mild, multifocal, alveolar necrosis.

Ancillary test results

Erysipelothrix and Leptospira spp. PCR were performed on formalin-fixed kidney. DNA from these agents was not detected.

Discussion

This report describes an unusual case of chronic, crescentic, membranoproliferative glomerulonephritis (MPGN) in a five-week-old, Australian White lamb. These findings are consistent with previously reported cases of AWKD. The exact cause of these kidney changes has not yet been elucidated. In humans, the latest Kidney Disease Improving Global Outcomes (KDIGO) Glomerular Disease guideline recommendations suggest MPGN should be subclassified into three categories based on composition of glomerular deposits:

a. immunoglobulin/immune complex mediated (ICGN);

b. complement-mediated, also referred to as C3 glomerulopathy (C3G); or

c. membranoproliferative pattern without immune complexes or complement glomerulonephritis (GN)15.

Whilst current classification of glomerular disease in dogs is moving to align with current human guidelines, most published studies regarding MPGN in domestic animals use the traditional classification system. This system divides MPGN into three types (I, II, and III) based on the location of glomerular deposits identified by transmission electron microscopy (TEM)5,18. This traditional method of classification is not optimal as it is based on morphology rather than the pathogenic process and has led to confusion when diagnosing and treating MPGN18.

In both humans and domestic animals the most common form of MPGN is due to immune complex deposits, which frequently occur secondary to bacterial infections such as Erysipelothrix spp., chronic dermatitis, polyarthritis, or rarely with other chronic infections (e.g. Streptococcus equi subsp. equi in horses)4,8,9. In this case, Erysipelothrix spp. were not detected in the kidney, and no chronic infections in other tissues were observed grossly or microscopically. Viral infections are also associated with ICGN, such as hepatitis B and C in humans, canine adenovirus 1 in dogs, feline leukaemia virus in cats, bovine viral diarrhoea virus in persistently infected cattle, equine infectious anaemia virus in horses, and classical and African swine fever viruses, and porcine circovirus in pigs4,9,17,20. Other less common causes in domestic animals include protozoal or helminth infections, or autoimmune diseases4. In this case, immune-mediated MPGN is considered less likely based on the age of the animals, negative Erysipelothrix and Leptospira spp. PCR tests, and lack of histological evidence of concurrent chronic inflammatory processes.

Complement-mediated GN is rarely reported in either humans or domestic animals14,21. It is caused by dysfunction of the complement system associated with hereditary and spontaneous mutations, or rarely autoantibodies, of complement factors or complement-regulating protein genes9. Immunofluorescence (IF) is necessary to differentiate C3G from ICGN, which was not possible in this case or similar cases examined at EMAI as ovine IF techniques have not been widely developed. C3G can be further subdivided into C3 glomerulonephritis (C3GN), and dense deposit disease (DDD) based on the ultrastructural appearance of electron-dense deposits under TEM11. DDD has been reported in Norwegian Yorkshire pigs due to a hereditary mutation in the factor H gene12. In other cases of AWKD evaluated at EMAI with similar histological patterns, there were electron-dense deposits within the glomerular basement membrane, however these deposits were not described as the characteristic “sausage-like” deposits described with DDD4.  

The final category, membranoproliferative pattern without immune complexes or complement glomerulonephritis, is rarely reported in humans and domestic animals and represents a wide group of inherited or acquired disorders15. It is characterised by the absence of immune complex or complement deposits under TEM. This category encompasses a wide range of diseases, including but not limited to: Alport syndrome reported in dogs associated with an X-linked mutation in type IV collagen genes, the chronic phase of thrombotic microangiopathies reported in several species, and sickle-cell-anaemia-associated GN in humans2,13,15,22. As with DDD, TEM findings were not supportive of diseases within this category, which is consistent with the other cases of AWKD evaluated by EMAI.

It should be noted that familial C3 hypocomplementaemia-associated glomerulonephritis has been reported in Finnish Landrace sheep, Brittany Spaniel dogs, and Bernese Mountain dogs6,10,16. In all three of these reports, animals developed type I MPGN, which is characterised by subendothelial deposits of complements and immunoglobulins6,10,16. Unfortunately, these cases cannot be categorised in accordance with the new KDIGO Glomerular Disease guidelines, and therefore its only possible to speculate on the pathogenesis. Hypocomplementaemia has been associated with all types of MPGN, but they manifest due to different mechanisms of complement activation1. It is theorised that low complement levels can cause MPGN by making animals more susceptible to infections, or due to the impairment of IC clearance by complement-mediated pathways3,4. This case, and other histologically similar cases, somewhat resemble the changes described with hypocomplementaemia-associated MPGN in Finnish Landrace sheep, however further IF/IHC staining is necessary to determine if these cases share similar features as described in Finnish Landrace sheep.

AWKD is an emerging syndrome reported in several Australian White flocks in NSW since 2021. The case definition is Australian White lambs up to two months of age with non-specific signs preceding rapid deterioration and death, or sudden death. In AWKD cases, tests for infectious disease agents are negative. The kidney histopathology consistently reveals severe membranoproliferative glomerulonephritis, with crescent formation, glomerular haemorrhage, and non-obstructive hydronephrosis. The age, breed, absence of any positive tests for infectious disease agents or evidence of other chronic inflammatory processes, and the histopathology changes mean this case fits the case definition of AWKD. AWKD is suspected to be a congenital, hereditary disease, and its cause is currently being investigated.

Bilateral non-obstructive hydronephrosis was also observed in this case. Interestingly, this finding has been reported in half of AWKD cases, with no identifiable obstruction. The cause of this hydronephrosis is unknown. In humans, non-obstructive hydronephrosis can be due to vesicoureteric reflux, partial obstruction of the ureteropelvic junction, physiological changes, diabetes insipidus, or idiopathic7,19. It is possible in this case that a stenosis or partial obstruction may have been missed, as the urogenital tract is small in lambs, and normal diameters of the ovine ureter and urethra have not been reported in literature.

The concurrent liver and lung changes were likely secondary changes associated with renal failure. Reduced renal function causes sodium retention and fluid overload, leading to pulmonary oedema, hypertension, congestive heart failure, and subsequently hepatic congestion.

This case is the most recent addition to a series of AWKD cases in NSW recorded by the veterinary pathology team at the EMAI. The EMAI pathology team is working with the EMAI biotechnology team and contacts at the University of Sydney, with a genetic investigation determining possible causative mutations underway.

REFERENCES

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