Glomerulonephritis
GIM StR teaching October 2019 Charlotte Bebb Case 1
24 year old female with a past history of ulcerative colitis requiring pancolectomy 3 years previously. At that time she had a very stormy post op course complicated by a DVT treated with warfarin for 6 months. In Feb 2019 she had surgery to create a pouch and then presented in May 2019 with swollen, painful left leg. A DVT was confirmed on Doppler. Initial investigations: Hb 140, WC 10.5, Plt 400 Na 144, K 3.8, Ur 3.1, Creat 55, eGFR >90ml/min ALP 204, ALT 24, GGT 44, Bil 4, Alb 22 She was discharged on warfarin and returned 2 months later with a swollen R leg. A thrombophilia screen showed antithrombin 3 deficiency. What is the most likely diagnosis? Nephrotic syndrome Nephrotic syndrome
Proteinuria >3.5g/day Hypoalbuminuria Oedema Hypercholesterolaemia Lipiduria Main causes of nephrotic syndrome (age 15-65)
Membranous nephropathy (24%) Minimal change (16%; 80% <15yrs) Focal segmental glomerulosclerosis (12%; 55% blacks) Membranoproliferative GN (7%) IgA nephropathy (6%) Systemic disease (30%) Diabetes, amyloid, SLE Investigations in nephrotic patient
U&E, Albumin Myeloma screen FBC HbA1C Clotting screen Hep B and C Urine dipstick HIV Urine protein quantification (PCR) ANA Lipids Complement Renal USS Cryoglobulin Complications of nephrotic syndrome
Negative nitrogen balance and muscle wasting Hypovolaemia Acute kidney injury Thrombosis Hyperlipidaemia Infection Thrombosis
Increased incidence venous and arterial thromboemboli (eg DVT, Renal VT) 10-40% of patients Decreased levels of antithrombin III, increased platelet activation, fibrinogen, factor V, VII, vWF Immobility, Volume contraction More common in membranous GN No definite evidence for prophylactic anticoagulation Infections
Bacterial infections Primary pneumococcal peritonitis Cellulitis (beta-haem strep) Loss of IgG and complement factor B impairs ability to eliminate encapsulated organisms General treatment of nephrotic syndrome
Oral diuretics - may require high dose due to diuretic resistance Salt restriction ACE inhibitors to reduce proteinuria (even if normotensive) Thromboembolic prophylaxis Cholesterol lowering Minimal change
Commonest cause of nephrotic syndrome in children
Relapsing and remitting course Usually steroid responsive (75% in 4 months)
Does not progress to renal failure FSGS
Primary, secondary and genetic forms More common in black individuals May progress to ESRD 40% respond to steroids May recur post transplant Membranous Nephropathy
Subepithelial immune deposits
Most idiopathic Associations SLE, hep B and C, drugs Malignancy in 20% esp lung, breast and GI
Prognosis variable 40% progression to ESRD Spikes on silver stain at 15yrs Treatment complex Case 2
20 year old caucasian female admitted with pleuritic chest pain for 4 days. Prior to this she had diarrhoea and vomiting for 2 days and then developed swelling of her hands and feet. Examination: T 38, P 80, BP 160/100. SOA to knees, periorbital oedema, reduced air entry L base with bronchial breathing LMZ and pleural rub. Urine dip 4+ blood, 3+ protein.
Investigations: CXR – Effusion / consolidation L base Hb 105, WCC 4.0, Plt 146, APTT 35/29, PT 14/14 Na 138, K 5.1, Urea 11.9, Creat 183, eGFR 28ml/min ALP 70, ALT 121, GGT 127, Alb 28, Bili 20
What is the differential diagnosis and what is the most likely diagnosis? Systemic lupus erythematosis Diagnostic tests
Raised ESR, normal CRP Haematuria and proteinuria Abnormal renal function, cytopenias Prolonged APTT (test for APL) Low C3 and C4 Positive ANA +ve dsDNA, may have ENA SLE and the kidney
Up to 60% of patients get renal involvement Proteinuria (100%), nephrotic (50%), microscopic haematuria (80%), renal impairment (40-80%) Biopsy: Class I - minimal changes Class II - Mesangial disease Class III - Focal proliferative Class IV - Diffuse proliferative Class V - Membranous Class III and IV require immunosuppression Treatment - prednisolone with cyclophosphamide or mycophenolate Case 4
A 21 year old medical student presents on the surgical admissions unit with a two day history of macroscopic haematuria. He recently developed a viral URTI and sore throat. He has had a previous similar, but less severe, episode after a viral infection. Otherwise fit and well. Examination unremarkable. Blood pressure 165/95mmHg. Urine dip 3+ protein 4+ blood.
Investigations: Na 137, K 4.3, Urea 9.1, Creat 135, eGFR 50ml/min Albumin 35, LFTs normal, CRP 10
What is the differential diagnosis and what is the most likely diagnosis? IgA nephropathy IgA nephropathy / HSP
Mesangial proliferative GN with IgA deposits Extrarenal in HSP - skin, joints, gut Commonest glomerular disease in West
Abnormality in IgA immune system leads to deposition of IgA immune complexes in glomeruli leading to inflammation and scarring
Associated with ALD, cirrhosis, coeliac, dermatitis herpetiformis, ank spond, RhA, sarcoid, hep B IgA - clinical features
Macroscopic haematuria (40-50%) Loin pain Follows infections Asymptomatic haematuria and proteinuria (30-40%) Proteinuria and nephrotic syndrome (5%) Acute renal failure (<5%) Crescentic IgA Tubular occlusion by red cells Chronic kidney disease (up to 50% ESRD at 20 years) HSP - clinical features
Palpable purpuric rash on extensor surfaces Polyarthritis Abdominal pain (gut vasculitis) Renal abnormalities usually transient IgA nephropathy - renal pathology
Mesangial matrix increase Mesangial hypercellularity Mesangial IgA deposits IgA - treatment
Difficult - nothing proven ACE inhibitors Prednisolone? Fish oils? Prednisolone and cyclophosphamide Case 3
Previously fit and well 77 year old lady presented with a 6 month history of malaise and lethargy associated with arthralgia, weight loss and loss of appetite. Blood tests done by the GP 6 weeks prior to admission showed Hb 98 (normocytic), ESR 80, Creat 90, eGFR 51ml/min. On admission she was pale but haemodynamically stable, apyrexial, BP 140/80, mild ankle oedema, clear chest.
On admission further investigations: Na 132, K 4.7, Ur 17.7, Creat 219, eGFR 18ml/min ALP 181, ALT 27, GGT 22, Bili 8, Alb 25 CRP 91 Hb 86, WC 11.2, Plt 442 Urine dip 3+blood, 3+ protein
What is the differential diagnosis? Vasculitis and RPGN Anti-neutrophil cytoplasmic antibodies in disease
Granulomatosis with polyangiitis Cytoplasmic cANCA Proteinase 3 (PR3)
Microscopic polyangiitis Perinuclear pANCA Myeloperoxidase (MPO)
Eosinophilic granulomatosis with polyangiitis
Atypical ANCA: IBD, SBE, RhA, liver disease, CF Clinical features (MPA/GPA)
Fever, malaise, arthralgia, weight loss Renal involvement pauci-immune crescentic GN (90/80%) Purpuric rash (40%) Lung Haemorrhage (50/90%) Pulmonary nodules or cavities (GPA) ENT/eye: Sinusitis, rhinitis, saddle nose, otitis media, ocular inflammation (GPA) (35/90%) Neurological – Mononeuritis multiplex (15/70%) Gut vasculitis (50%) Renal pathology (GPA/MPA)
Fibrinoid necrosis and crescent formation Granulomatous inflammation in GPA Natural history and treatment
Pre-treatment most died in 12 months 1yr renal and patient survival 70-80% Prednisolone and cyclophosphamide or rituximab Possibly plasma exchange for severe disease Convert to azathioprine and pred at 3 months Treat for 2-5 years Monitor carefully for relapse Significant complications associated with treatment (infections, osteoporosis) Summary
Nephrotic syndrome Presentation Causes Complications Glomerulonephritis SLE IgA / HSP Pauci-immune GN
Always dip the urine and take a full history! A quick case
70yo male Shortness of breath Haemoptysis Oligoanuric Creatinine 1000
Suggest a diagnosis Rapidly progressive glomerulonephritis
Renal failure over days / weeks Proteinuria (<3g) Microscopic haematuria Red cell casts Crescents (cellular proliferation in Bowmans space) Extra-renal manifestations Causes of RPGN
Goodpastures / Anti-GBM Vasculitis (ANCA associated) Wegeners Microscopic polyangiitis Pauci-immune crescentic GN Immune complex SLE Post-strep GN IgA / HSP Endocarditis Investigations in RPGN
CRP Chest Xray AntiGBM Transfer factor ANCA ECG ANA, dsDNA Echo Complement FBC ASO titre LFT Immunoglobulins Hep B&C Cryoglobulins Goodpastures / antiGBM disease
AKI and lung haemorrhage due to antiGBM AntiGBM specific for alpha3 chain of type IV collagen (in GBM and alveolar BM) Lung haemorrhage - insult to lungs eg smoking or infection to reveal antigen Short history and severe Treat with plasma renal failure exchange (daily for 14 Renal recovery unlikely if days), prednisolone and creatinine>600 or oliguric cyclophosphamide Causes of Goodpastures syndrome
RPGN and lung haemorrhage AntiGBM abs (20-40%) Goodpastures disease Systemic vasculitis associated (60-80%) Granulomatous polyangiitis Microscopic polyangiitis SLE Churg Strauss HSP Behcets disease Mixed essential cryoglobulinaemia Rheumatoid vasculitis Drugs: penicillamine, hydralazine, propylthiouracil An interesting case
20yo male ESRF, sensorineural deafness Undergoes renal transplant After 1 month he presents with acute renal failure
What is the diagnosis and why? Case - answer
Acute anti-GBM disease in a patient with Alport syndrome Alports mutation in type IV collagen alpha5 React to type IV collagen in transplant as a neoantigen Occurs in 5% Alports patients post transplant Poor prognosis Another case
64yo male Vomiting, confusion, weight loss Purpuric rash on legs 2/52 ago Lisinopril, Aspirin, lansoprazole Temp 37.6, BP 170/60, systolic murmur GP bloods – creat 139 Urine dip 3+ blood, 3+ protein Case – further Ix
CT head – normal CRP 250, ALP 400, GGT 160 Creat 360 Hb 105, WC 12.9, Plt 330 C3 0.9, C4 undetectable
What diagnostic investigation would you do? Causes of low complement
Low C3 and C4 (classical pathway) Lupus nephritis Mixed essential cryoglobulinaemia (C4 low, low normal C3) MPGN type I Low C3 (alternative pathway) Postinfectious GN MPGN type II (C3nef) Atheroembolic disease Haemolytic uremic syndrome Membranoproliferative GN
Type I (subendothelial deposits) Cryoglobulinaemia • Hep C (70-90%), endocarditis, Hep B, collagen vascular disease, CLL, lymphoma Infections, hereditory or acquired complement deficiencies (C4nef) Type II (dense deposits in mesangium) C3nef +/- partial lipodystrophy Factor H deficiency Type III (subendo, GBM and subepithelial) Like I, Terminal Nef MPGN - clinical
Renal Microscopic haematuria and proteinuria (35%) Nephrotic syndrome (35%) Chronically deteriorating renal function (20%) Rapidly progresssive renal failure (10%) Cryoglobulin Weakness Arthralgia Purpura - extremities, ulcerative vasculitic lesions Cryoglobulinaemia
Immunoglobulins that precipitate in the cold Type I Monoclonal IgG, IgA or IgM Haematological malignancies, MGUS Type II Polyclonal IgG and monoclonal IgM (RhF) Hep C, CLL, lymphoma, essential Type III Polyclonal IgG and polyclonal IgM Infections (Hep B and C, EBV, CMV, endocarditis, leprosy, schistosomiasis, toxoplasmosis, malaria) SLE, RhA, lymphoprolif disorders, chronic liver disease)