PULMONARY FIBROSIS IN RENAL ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA) ASSOCIATED VASCULITIS IN TASMANIA OVER A 10 YEAR PERIOD

S KUO1, PG TAN2, A GRAVER1, S YEW1, R YU1, L JEFFS1, MD JOSE1.3, M MATHEW4, R RAJ4, D COOKE4, G KIRKLAND1

1Renal Unit, Royal Hobart Hospital, Tasmania; 2Renal Unit, Monash Medical Centre, Melbourne, Victoria; 3School of Medicine, University of Tasmania; 4Renal Unit, Launceston General Hospital, Tasmania

Aim: To determine if pulmonary fibrosis associated with ANCA-associated vasculitis (AAV) is a significant clinical problem in Tasmanian patients diagnosed with Renal AAV.

Background: Pulmonary fibrosis, a well recognised condition with limited treatment options, has been associated with AAV in medical literature. To our knowledge, it has not been reported in Australian populations.

Methods: We conducted a retrospective, exploratory study using a state-wide renal biopsy database and identified all Tasmanians newly diagnosed with pauci-immune crescentic glomerulonephritis between 2004 and 2013. Clinical details were collected from medical records. Presence of pulmonary fibrosis was defined as typical computed tomography scan findings of pulmonary fibrosis and/or diagnosis by a respiratory physician.

Results: Preliminary data from this time period identified 60 patients who were newly diagnosed with pauci-immune glomerulonephritis, of whom 6 (10%) (median age 69, 67% male) were diagnosed with pulmonary fibrosis. 5 patients (83%) were MPO positive and 1 patient (17%) was PR3 positive. 2 patients were diagnosed with pulmonary fibrosis 12 months before the renal AAV diagnosis, 1 had concurrent diagnosis and 2 were diagnosed after. No statistically significance difference in clinical outcome was found between the two cohorts. 2 of the patients with pulmonary fibrosis had a symptomatic and objective improvement in lung function with azathioprine treatment.

Conclusions: This retrospective study suggests that pulmonary fibrosis associated with renal AAV is a relatively common problem in the Tasmanian population. Further, larger studies would be required to delineate its clinical significance. Immunosuppressive treatment may be of respiratory benefit in these patients.

SYSTEMIC LUPUS ERYTHEMATOSUS MASQUERADING AS ATYPICAL HAEMOLYTIC URAEMIC SYNDROME

S KUO1, A GRAVER1, G KIRKLAND1, R YU1

1 Royal Hobart Hospital, Hobart, Tasmania

Background: Thrombotic microangiopathy (TMA) can result from multiple pathologies including thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome (HUS). Autoimmune diseases such as Systemic Lupus Erythematosus (SLE) can cause secondary HUS. Eculizumab (anti-C5 monoclonal antibody) is approved for treatment of atypical HUS (aHUS) and has been reported as treatment for TMA secondary to SLE.

Case Report: A 66-year-old female presented with new onset congestive cardiac failure secondary to malignant hypertension. Abnormal pathology results on initial testing included haemoglobin 94 g/L, platelets 44 /nL, and creatinine 143 µmol/L.

Blood film suggested TMA, prompting plasmapheresis commencement; this was discontinued with confirmation of adequate ADAMTS13 activity (153%). Subsequent testing identified positive anti-antinuclear antibody (640 speckled) and extractable nuclear antigens (anti-SSA and anti-SSB), but negative anti-double stranded DNA. Testing for shiga toxin-producing Escherichia coli was negative. Eculizumab was therefore commenced as treatment for aHUS. Interestingly, C3, and more so C4, were low.

Eculizumab failed to produce any clinical improvement, so a renal biopsy was performed. Light microscopy demonstrated TMA; immunofluorescence was non-specific (positive IgM, IgA, C1q and lambda light chain; negative IgG and kappa light chain) and electron microscopy showed deposits consistent with Lupus nephritis. Treatment was consequently changed to conventional Lupus nephritis therapy, which resulted in rapid achievement and maintenance of clinical remission.

Conclusion: SLE can present as TMA, and should be considered a differential in patients diagnosed with aHUS but unresponsive to Eculizumab. Renal biopsy remains an important diagnostic tool in these patients.

ACUTE POST-STREPTOCOCCAL GLOMERULONEPHRITIS- A CASE REPORT AND EPIDEMIOLOGICAL DATA FROM THE NORTHERN TERRITORY OF AUSTRALIA

S CHATURVEDI1, R BOYD 2, P MORRIS1, V KRAUSE2

 

1Department of Paediatrics, Royal Darwin Hospital, Darwin, Northern Territory; 2Centre for Disease Control, Department of Health, Darwin, Northern Territory

Aim: We discuss a typical case presentation of Acute Post-Streptococcal Glomerulonephritis (APSGN) and highlight the heavy burden of APSGN in the Northern Territory (NT) over 26 years.

Background: APSGN is an inflammatory kidney disease caused by prior infection with nephritogenic strains of Group A Streptococcus (GAS). It is a notifiable disease in the NT with data collection established in 1991. The case definition of a confirmed case is a clinically compatible illness and laboratory evidence. Probable cases require clinical evidence only.

Case Report: A 13 year old Indigenous girl was admitted to hospital with gross haematuria, edema, and hypertension with history of impetigo and sore throat 2 weeks previously. Laboratory results revealed elevated ASOT (467 IU/ml), elevated serum creatinine 103 µmol/L, nephrotic range proteinuria, low C3< 0.2gm/L (0.83-2.02), and negative ANA.  Her serum creatinine continued to rise over 2 weeks and she had persistent hypertension. Given the prolonged renal impairment, she underwent a kidney biopsy which revealed diffuse proliferative glomerulonephritis with 37% crescents.

Epidemiological data: Over the 26 years (1991-2016), there were 777 notifications of APSGN, of which Indigenous people comprised 94 %. Males represented 411 (53%) episodes and median age was 7 years (range 0-64).

Conclusions: APSGN notifications in the NT remain high, with an upward trend and affect almost exclusively the Indigenous population. While the upward trend may reflect better surveillance measures, it may also signal a higher burden of GAS or change in organism virulence. The results emphasise the need for continued and improved public health response including education, reduction and early treatment of GAS infections, capacity for secondary prophylaxis of contacts and recognition of potential long term renal impact.

HAEM PIGMENT-INDUCED CHRONIC KIDNEY DISEASE IN A PATIENT WITH GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY

M WAINSTEIN1,2, W JAMES2

1Royal Darwin Hospital, Darwin, Northern Territory; 2Lismore Base Hospital, Lismore, New South Wales

Background: Glucose-6-phophate dehydrogenase (G6PD) is a key enzyme in the pentose-phosphate pathway which protects cells from oxidative stress. Exposure to such stress in patients with G6PD deficiency can lead to intravascular haemolysis and acute kidney injury which is generally self-limiting with resolution of the haemolytic episode. The pathogenesis of kidney injury in this condition is thought to be driven by haem pigment-induced tubular cytotoxicity, obstruction and vasoconstriction. We present the case of a patient with severe G6PD deficiency and mild but progressive kidney disease attributed to chronic haemolysis.

Case Report: A 68 year-old Philipino woman was referred to clinic with a creatinine of 126 umol/L and eGFR 34 ml/min which had declined from 48 ml/min four years earlier. Her medical history was significant for G6PD deficiency with severe enzyme deficiency (7%) but no overt haemolytic episodes, myelodysplastic syndrome, iron deficiency anaemia and hypertension. She admitted to infrequent use of NSAIDs and medicinal herbs. Investigations revealed a haemoglobin of 89 g/L with evidence of haemolysis (LDH 1702 u/L, Haptoglobin 0.2 g/l and Bilirubin 35 umol/L) as well as iron deficiency. Urine showed a trace of protein and a bland sediment. A renal biopsy showed marked amounts of intracytosplasmic haemosiderin in the tubules, mild tubulointerstitial fibrosis and normal glomeruli. When evaluating LDH levels and renal function over the past four years, no correlation was found to indicate an episodic pattern. The patient was treated supportively, advised to stop taking NSAIDs and herbs and avoid pro-oxidative drugs in the future.

Conclusions: Patients with severe G6PD deficiency and chronic, subclinical, haemolysis are at risk of chronic kidney disease from prolonged exposure to haem pigment and its nephrotoxic effects.

WARFARIN VS NEW ORAL ANTICOAGULANT IN PRIMARY ADULT NEPHROTIC SYNDORME ASSOCIATED VENOUS THORMBOEMBOLISM

T HAN1, C HAN1, Z THET1

1Department of Nephrology, Central Queensland Hospital and Health Service, Rockhampton, QLD

Background: Overall incidence of venous thormboembolism (VTE) in adult nephrotic syndorme (NS) is 25-30%. The pathophysiology of VTE in NS is complex and poorly understood. A quality study on the topic of optimal VTE prevention/treatment in patients with NS is scarce with a lack of randomized controlled trials in the subject area. Hypoalbuminemia itself can lead to altered pharmacokinetics and pharmacodynamics of medications, although this topic is infrequently considered in daily clinical practice.

Case report: A sixty year old male patient without significant comorbidities was diagnosed with pulmonary embolism (PE) when admitted with suspected acute pyelonephritis. His thrombophilia screen was negative. The patient was discharged home with highly protein bound new oral anticoagulant (NOAC;Rivaroxaban 15mg BD for 3 weeks followed by 20mg OD). Patient was compliant with his medications.. Whilst on rivaroxaban for 5 months, he had new onset unilateral renal vein thrombosis (RVT) and recurrence of bilateral PE. He was subsequently diagnosed with membranous nephropathy which was treated successfully with modified Pontecelli regime. His unilateral RVT and recurrence of bilateral PE were successfully treated with warfarin.

Conclusions: Highly protein bound NOAC may not be efficacious in NS associated VTE. Possible explanations for failure to treat or prevent VTE with NOAC include selective inhibition of coagulation cascade by NOAC and inadequate or unsustained plasma levels of highly protein bound NOAC in hypoalbuminemic state. Lack of requirement for routine drug level monitoring of NOAC is currently considered as an advantage, but it may be a major disadvantage in preventing or treating VTE in adult patients with NS.

A RETROSPECTIVE ANALYSIS OF LUPUS NEPHRITIS IN THE INDIGENOUS AND NON-INDIGENOUS POPULATIONS IN THE NORTHERN TERRITORY: TREATMENT, OUTCOMES AND CHALLENGES

P SUBRAMANI1,2, CY YEAP2, S THOMAS1, B PAWAR1, S CHERIAN1,2, S BRADY3, W MAJONI2,4,5

1Alice Springs Hospital, Div. of Medicine, Dept. of Nephrology, Alice Springs, NT; 2Royal Darwin Hospital, Div. of Medicine, Dept. of Nephrology, Darwin, NT; 3Alice Springs Hospital, Div. of Medicine; 4Flinders Medical School, NT Medical Program; 5Menzies School of Health Research, NT

Aim: To analyse the prevalence, treatment, outcome and challenges of lupus nephritis (LN) in the Northern Territory

Background: There is a high incidence of systemic lupus erythematous amongst Indigenous Australians with rates of LN being reported as high as 52%. A recent study in Central Australia demonstrated poor outcomes of LN in this population despite advances in treatment, presumably due to disadvantage across a range of socioeconomic indicators including education, housing and employment. Unfortunately, direct comparison with non-Indigenous Australians proved difficult due to small sample size. Here we aim to expand on the previous study by analyzing all cases of LN in the Northern Territory (NT) from 1999 to December 2016.

Method: The electronic medical records of all patients with biopsy proven LN at Royal Darwin Hospital and Alice Springs Hospital between 1999 and December 2016 were reviewed.

Results: There were 51 patients with LN, 36 were Indigenous. The majority of patients had class III or IV LN, with 13 patients demonstrating features of class V LN. The majority of patients with Class III or IV LN were commenced on the current recommended induction regime of mycophenolate or cyclophosphamide plus glucocorticoid. A higher incidence of serious infective complications was observed in the Indigenous group. 9 patients, 8 of who were Indigenous progressed to end stage kidney disease. There were 6 deaths, all Indigenous.

Conclusion: Despite advances in treatment, outcomes of LN in the Indigenous population in the NT continue to lag behind non-Indigenous peers. Whilst socioeconomic status may play an important role in these differences, a closer study to identify modifiable social and/or biological determinants of outcome is necessary in order to bridge the gap.

IgA-MEDIATED ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE

A SIRIWARDANA1, F PETTIT1

1Department of Renal Medicine, St George Hospital, Kogarah, NSW

Background: Anti-glomerular basement membrane (anti-GBM) disease is an aggressive glomerulonephritis mediated by IgG autoantibodies against the glomerular basement membrane. IgA-mediated anti-GBM is rare and has been described in the literature in fewer than 15 cases. Optimal therapy for these patients is unknown and renal prognosis is poor. Case report: A 74 year old male was hospitalised with a 1-week diarrhoeal illness and acute kidney injury with creatinine 299μmol/L, microscopic haematuria and heavy proteinuria. Past medical history included irritable bowel syndrome, skin cancers and a current smoking habit. Imaging studies and vasculitic screen (including anti-GBM antibodies) were unremarkable. Creatinine partially improved with intravenous fluids. Over following weeks creatinine rose to 335μmol/L and renal biopsy showed a focal proliferative necrotising glomerulonephritis with 70% crescents (50% cellular) and linear GBM staining for IgA. He received pulse and oral steroids, oral cyclophosphamide, and plasma exchange. Despite 5 weeks of therapy, creatinine rose to 450μmol/L with persistent microscopic haematuria and nephrotic-range proteinuria. Repeat renal biopsy showed persistent active crescenteric glomerulonephritis with strong IgA linear GBM staining and moderate acute tubular injury. Serum IgG anti-GBM antibodies remained negative. High dose steroids and oral cyclophosphamide were continued. Creatinine rose to 652μmol/L. His course was complicated by a febrile illness and likely drug-induced neutropenia. Prednisone was weaned, cyclophosphamide ceased and dialysis is imminent. Conclusion: IgA-mediated anti-GBM disease is a rare clinical and histopathological entity. This case adds to the limited literature and is in keeping with the suggestion that IgA-mediated anti-GBM disease confers poor renal prognosis.

ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE AND THE EYE

D POTTER1, G LIEW 2, 3, A MAKRIS1, B CLELAND1

1Liverpool Hospital, Liverpool, New South Wales; 2Westmead Hospital, Westmead, New South Wales; 3Sydney University, Camperdown, New South Wales.

Background: Anti-glomerular basement membrane (GBM) disease is a rare disease estimated to affect 0.5-2 cases per million of the population. Autoantibodies against the alpha 3 subunit of type 4 collagen are pathogenic in anti-GBM disease and the subunit is classically considered to be restricted to the basement membrane of the glomerulus and lung. Studies using autoantibodies from anti-GBM patients and mouse monoclonal autoantibodies have demonstrated additional sites of binding within the choroid and retina of the eye, lens capsule, cochlea and choroid plexus. Direct ocular injury in anti-GBM disease, however, has only been reported once.

Case Report: A 45 year old female presented with fever, haematuria and acute renal failure with a creatinine of 254umol/L. Anti–GBM antibodies were detected in serum with a titre of >200IU/ml (reference <20IU/ml). Renal biopsy demonstrated a crescentic glomerulonephritis with linear basement membrane IgG staining on immunofluorescence.  She received aggressive treatment with methylprednisolone followed by oral prednisolone, plasma exchange and intravenous cyclophosphamide. Six weeks after diagnosis she developed blurred vision in the left eye. Ophthalmology evaluation with optical coherence tomography demonstrated acute invasion of a choroidal neovascular membrane into the retina of the left eye. This was highly atypical in view of her age and lack of prior eye disease, trauma or macular degeneration. She received anti-vascular endothelial growth factor (VEGF) injections with an excellent response.

Conclusions: Our patient had acute choroidal neo-revascularisation without clear precipitating cause. Deposition of anti-GBM autoantibody within the choroid would induce this pathology and is supported by evidence of the subunit and autoantibody at this site. This case highlights that clinicians should consider other sites beyond the kidney and lung in anti-GBM disease.

JEJUNAL ULCERATION DUE TO GRANULOMATOSIS WITH POLYANGITIS

D POTTER1, S BAWEJA2, W JAMES2,

1Liverpool Hospital, Liverpool, New South Wales; 2Lismore Hospital, Lismore, New South Wales

Background: Granulomatosis with Polyangitis (GPA) is a chronic multisystem condition primarily affecting the upper airway, lung and kidney. It is characterised by necrotising vasculitis of small to medium arteries with granulomatous inflammation. Gastrointestinal GPA has been noted in up to 24% of autopsy series but reported clinical manifestations are rare. Ileum and colon the primary affected areas often presenting as acute perforation and bleeding. In a case series of six patients none had jejunal involvement and in another of thirteen patients only two had jejunal pathology.

Case Report: A 40 year old male presented with two weeks of colicky epigastric pain without vomiting, altered bowel habit or malaena. Clinical examination revealed a tender abdomen without peritonism. He had renal failure with a creatinine of 255umol/L. Eight years prior he was treated for necrotising glomerulonephritis due to GPA with prednisolone and cyclophosphamide but subsequently was lost to follow up. Repeat renal biopsy demonstrated fibroepithelial crescents, an interstitial inflammatory cell infiltrate and widespread global and segmental glomerulosclerosis. Contrast tomography of the abdomen demonstrated thickening of proximal bowel loops and haziness to upper abdominal fat planes. Endoscopy revealed two jejunal ulcers without perforation. Biopsy demonstrated ill-defined granuloma formation with focal evidence of ischaemia. He received steroids for jejunitis secondary to GPA with an excellent response.

Conclusions: Gastrointestinal GPA is rare and limited primarily to descriptions of acute ileal and colonic abnormalities. Our case had subtle symptoms without major gastrointestinal signs at remote time from his diagnosis, suggesting gastrointestinal GPA may more common than in the literature and at risk for under evaluation. Gastrointestinal complications of GPA are important as delayed diagnosis may lead to fatal outcomes.

C1Q DEPOSITION IN A CASE SERIES OF CHILDREN WITH HENOCH-SCHÖNLEIN PURPURA AND POSITIVE STREPTOCOCCAL SEROLOGY

A MCKAY1, N GRAF1,2, P KIRWAN3, D HAHN1, A DURKAN1,2

1The Children’s Hospital at Westmead, Sydney, NSW; 2 University of Sydney, NSW; 3Concord Repatriation General Hospital, Sydney, NSW,

Background: Henoch Schönlein nephritis affects 20-54% of children presenting with Henoch Schönlein Purpura (HSP). Histopathologic findings of HSP nephritis are varied however typically include mesangial glomerulonephritis with dominant or co-dominant IgA deposition. IgG, IgM, fibrinogen and C3 deposition may also occur. C1q deposition however is rare and raises the suspicion of lupus nephritis. We describe the clinical course and pathological findings in 3 children with HSP nephritis, positive streptococcal serology and the rare finding of positive C1q staining.

Case Report: Three male children presented with clinical features of HSP and renal involvement (nephrotic range proteinuria +/- renal impairment) within a 2 month period. In all three cases the ASOT and DNAseB were elevated. In two, the serum C3 and C4 were reduced and in the other case there was isolated C4 reduction. Histopathology demonstrated mesangial proliferation with IgA deposits, C1q deposition and subepithelial electron dense deposits. The children were treated with steroids, mycophenolate and lisinopril. Two of the three cases responded well with resolution of proteinuria at 3 months and one case has ongoing proteinuria.

Conclusions: C1q deposition has previously been considered a rare finding in HSP nephritis. However, in our case series we demonstrate C1q staining in three patients presenting within a short time frame to our tertiary children’s hospital. Further investigation is required to investigate if C1q deposition is a feature of more severe HSP nephritis associated with streptococcal infection.

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