Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

My email address: sr 1220@ic.ac.uk S l i d e s b a s e d o f f : A d e l e S c h i f f AKI + Glomerulonephritis Shruti Rajendra MedEd Y3 Written Exam Lectures 2025 Acute Kidney Injury ACUTE decrease in renal function (acute renal failure), due to insult to the kidneys CAUSES Risk Factors 1. PRE-RENAL CAUSES 1. CKD 2. INSTRINSIC /RENAL CAUSES 2. Otherorgan failure/chronic disease (eg. heart 3. POST-RENAL CAUSES failure, liver disease, diabetes mellitus) 3. History of AKI Presentation 4. Drugs with nephrotoxic potential (eg. NSAIDs, aminoglycosides (eg. gentamicin)) within the • Asymptomatic past week • Reduced urine output 5. Use of iodinated contrast agents within the • Arrythmias • Pulmonary + peripheral oedema past week • Uraemia 6. Age of ≥65 years • Dehydration 7. Oliguria • Nausea Sudden rapid reduction in eGFR with or without oliguria/anuria AKI: Pre-Renal Causes Decreased kidney perfusion 1. Shock Hypovolemia Vascular insult (hypovolaemia, 1. Tachycardia Causes: cardiogenic or 2. Hypotension 1. NSAIDs distributive) 3. Cool peripheries 2. ACEi/ARBs 2. Low Volume 3. Contrast 3. Hypovolemia Causes: 4. Renal Artery Stenosis Renovascular • Acute haemorrhage disease • Burns • Diuresis • GI losses • Sepsis + acute pancreatitis Mx: Fluid resuscitation ifserve Low Volume: Heart or liver failureAKI: Renal Causes 1. Dysfunction in the glomeruli (acute 35% of cases are due to intrinsic damage to the glomeruli, renal glomerulonephritis) tubulesor interstitium ofthe kidneysthemselves 2. Tubules (acute tubular necrosis) 3. Interstitial (acute interstitial nephritis) 4. Renal vessels (haemolytic uraemia syndrome or vasculitides) 5. Tumour Lysis Syndrome 6. Rhabdomylosis AKI: Tubular Renal Causes • Two Types: Ischemia + Nephrotoxins Toxins Ischaemia Direct effect of nephrotoxin of tubular cells 1. Damage to tubular cells secondary to prolonged Endogenous Toxins: ischemia (decreased blood 1. MYOGLOBIN (rhabdomyolysis) – (sign: dark urine flow(eg. from HF, renal following trauma/crush) artery stenosis)) 2. URIC ACID (tumour lysis syndrome) 2. Shock 3. MONOCLONAL LIGHT CHAINS (multipleMyeloma) 3. Sepsis Exogenous toxins: 1. AMINOGLYCOSIDES 2. RADIOCONTRAST AGENTS 3. LEAD 4. NSAIDs 5. CISPLASTIN AKI: Tubular Renal Causes Features: Histopathological Features: 1. AKI: raised urea, creatinine, potassium • Tubular Epithelium Necrosis: loss of nuclei and detachment of tubular 2. Muddy brown casts in urine (MSU) cells from the basement membrane • Dilation of the tubulesmay occur • Necrotic cellsobstruct tubular lumen Management: • It is reversible in around 21 days Stages: • Can develop profound diuresis 1. Oliguric phase (monitor fluids) 2. Polyuric phase 3. Recovery phase AKI: Acute Interstitial Nephritis Immune mediated damage of renal interstitium Presentation Causes 1. Rash 1. Type 4hypersensitivity (most common) – often due to 2. Fever medication: 3. Arthralgia • NSAIDs 4. Eosinophilia • Thiazide diuretics 5. Hypertension • Penicillin • Rifampicin Investigations • Allopurinol • PPIs • White cell casts on urinalysis 2. SLE, sarcoidosis, Sjogren’s syndrome • Sterile pyuria 3. Infection • Histology: marked interstitial oedema and interstitial infiltrate in the connective tissue between renal tubules Recovery occurs in weeks ofremoving the causative reagent.AKI Vascular: Haemolytic Uraemic Syndrome (HUS) • Seen in young children Causes Investigations • Classic presentation= young child following bloody diarrhoea Primary 1. FBC: • Complement • Haemolytic anaemia: (low Hb) TRIAD dysregulation • Coombs NEGATIVE 1. AKI • Thrombocytopenia 2. Microangiopathic haemolytic anaemia Secondary • Shiga toxin-producing 2. Blood film: schistocytes and helmet 3. Thrombocytopenia E.coli (STEC) 0157:H7 – cells most common cause in children 3. U&Es – AKI • 'verotoxigenic’, • 'enterohaemorrhagic’ 4. Stool culture: looking for evidence of • Pneumococcal infection STEC infection • HIV 5. PCR: for Shiga toxins Otherrare causesinclude SLE, drugs and cancer.AKI: Vascular Thrombotic Thrombocytopenia VASCULAR THROMBOTIC = HAEMOLYTIC URAEMIC + NEUROLOGICAL + TEMPERATURE THROMBOCYTOPENIA SYNDROME SYMPTOMS Pentad of: Occurs due to a defect in 1. AKI ADAM-TS-13 enzyme 2. Microangiopathic Management = Plasmapheresis haemolytic anaemia 3. Thrombocytopenia 4. Temperature 5. Swinging CNS signsAKI: Post-renal causes Caused by obstruction to urinary outflow • Luminal (eg. kidney stone) – pain, anuria (urethra), renal colic (ureters) • Mural (eg. tumour of urinary tract, strictures) • Due to external compression (eg. benign prostatic hypertrophy, pelvic cancer) Investigations: USS Management: find and fix causeAKI: Investigations ACUTE decrease in renal function (acute renal failure), due to insult to the kidneys 1. Bloods: CRP, FBC, U&Es, LFTs, Clotting, CK U&Es 2. Urinalysis 1. Sodium 2. Potassium 3. Fluid Assessment: membranes and cap-refill 3. Urea 4. Creatinine 4. ABG/VBG Hep, HIV, Vasculitic screen, myeloma screen, anti-GMB 5. ECG 6. CT-KUB + Renal USS (no obvious cause)Acute Kidney Injury Stage Creatinine Urine Output Stage 1 Increase in creatinine to 1.5-1.9 Reduction in urine output to <0.5 times baseline, or mL/kg/hour for ≥ 6 hours (6-12h) Increase in creatinine by ≥26.5 µmol/L ((≥0.3 mg/dL) Stage 2 Increase in creatinine to 2.0 to Reduction in urine output to <0.5 2.9times baseline, or mL/kg/hour for ≥12 hours Stage 3 Increase in creatinine to ≥ 3.0 1. Reduction in urine output to times baseline, or <0.3 mL/kg/hour for ≥24 hours, Increase in creatinine to ≥353.6 or ANURIA for 12hours µmol/L or 2. The initiation of kidney replacement therapy, or, 3. In patients <18 years, decrease in eGFR to <35 mL/min/1.73 m2 USE THE PARAMETER THAT GIVES WORST DISEASE STAGEAcute Kidney Injury Diagnostic Criteria Referral Criteria 1. Renal transplant 1. Rise in creatinine of 26µmol/L 2. ITU patient with unknown cause of AKI or more in 48hours OR >= 50% 3. Vasculitis/ glomerulonephritis/ tubulointerstitial rise in creatinine over 7days OR nephritis/ myeloma 4. AKI with no known cause 2. Fall in urine output to < 5. Inadequate response to treatment 0.5ml/kg/hour for more than 6 hours in adults(8 hours in 6. Complications of AKI children) OR 7. Stage 3AKI 8. CKD stage 4or5 3. >= 25% fall in eGFR in children / 9. Qualify for renal replacement hyperkalaemia / youngadults in 7days. metabolic acidosis/ complications of uraemia/ fluid overload (pulmonaryoedema)Acute Kidney Injury Management 1.ABC assessment 2.Find and treat the cause 3.Stop any NEPHROTOXIC drugs 4.Fluid management 5.Treat complications 6.Dialysis if neededAKI: Management Nephrotoxic Drugs Suspend renally excreted drugs IndicationsforacuteDialysis 1. NSAIDs 1. Metformin • Acidosis – ie. severe metabolic acidosis 2. ARBs/ACEi 2. Lithium with pH of <7.20 3. Diuretics 3. Digoxin • Electrolyte imbalance – ie. persistent 4. Certain antibiotics Adjust renally excreted drugs hyperkalaemiaof >7mmol (aminoglycosides) (eg. opioids) • Intoxication (poisoning) • Oedema – refractory pulmonary oedema • Uraemia – but only if complications Pre-renal AKI: give fluids if the patient is hypovolaemic; give occur (eg. encephalopathy or intravenous antibiotics if the patient is septic; stop pericarditis) nephrotoxic drugs. Renal AKI: nephrology review is often required to identify less common causes of AKI If there is hypervolemia, offload with IV Post-renal AKI: catheterisation and urology review diuretics or dialysis AKI: COMPLICATIONS Complications Metabolic acidosis presents as: 1. Fluid Overload • Confusion 2. Metabolic Acidosis • Tachycardia • Kussmaul’s breathing 3. Uremia 4. Hyperkalemia • Nausea and vomiting Fluid overload presents as: Management is IV/POsodium bicarbonate and dialysis ifrefractory • Pulmonary oedema (crackles) • Raised JVP Uraemia presents as: Management is IV • Uraemic encephalitis furosemide/GTN infusion + (confusion/lethargy) haemodialysis ifrefractory • Uraemic pericarditis Management is haemodialysis Acute Kidney Injury: Hyperkalaemia Symptoms Stage Management • Arrhythmia 1. Mild: 5.5-6 1. Cardiac monitor • Muscle weakness 2. Moderate: 6.1-6.5 2. Calcium Gluconate 10% • Cramps 3. Severe: >6.5(or any K with ECG changesor 30mls IV: to protect the • Hypotension symptoms) heart • Bradycardia 3. 10U Soluble insulin: drives K into cell 4. 50ml of 50% glucose: to ECG changes avoid hypoglycaemia 5. Stop cause and monitor K + 1. Tall tented T waves 6. Haemodialysis if refractory 2. Widened QRS 3. Absent Pwaves Patient may also benefit from: 4. Prolonged PR • Salbutamol nebulisers interval • IV furosemide 5. Sinusoidal Wave • IV sodium bicarbonateHyperkalaemia ECG SBA 1 (question) A 70 year old man comes in complaining of constant thirst and has recently been feeling nausea. A series of blood are run, revealing a creatinine of 2 times his past blood test a month ago.On further questioning, he admits to only passing urine once in the last 24 hours. Which of the following is not a intrinsic renal cause of this man’s acute kidney injury? a) Acute Tubular Necrosis b) Acute Interstitial Nephritis c) Rhabdomyolysis d) Benign Prostatic Hyperplasia e) Multiple myeloma SBA 1 (answer) A 70 year old man comes in complaining of constant thirst and has recently been feeling nausea. A series of blood are run, revealing a creatinine of 2 times his past blood test a month ago.On further questioning he admits to only passing urine once in the last 24 hours. Which of the following is not a intrinsic renal cause of this man’s acute kidney injury? a) Acute Tubular Necrosis b) Acute Interstitial Nephritis c) Rhabdomyolysis d) Benign Prostatic Hyperplasia e) Multiple myelomaGlomerulonephritis Definition: inflammation and damage to glomeruliGlomerulonephritis 1. NEPHRITIC SYNDROME 2. NEPHROTIC SYNDROME NEPHROTIC SYNDROME NEPHRITIC SYNDROME 1. Massive Proteinuria (>3.5 g/d): foamy urine 1. Hematuria: red cell casts 2. Hypoalbuminemia (<25g/L) 2. Proteinuria 3. Oedema: Peripheries + Eyes + Lungs 3. Oedema 4. Hyperlipidemia + Lipiduria: fatty casts on 4. Progressive renal impairment microscopy 5. Hypertension • Protein COAL Protein HOB • Cholesterol ↑ Haematuria • Oedema Oedema • Albumin ↓ Blood pressure ↑ • Lipids↑Nephritic Syndrome Nephritic syndrome is a type of proliferative Symptoms: glomerulonephritis with progressive renal impairment • Proteinuria: (1-3.5 g/day) • Haematuria: red cell casts Causes: • Oedema • Hypertension • Rapidly proliferative glomerulonephritis (RPGN) ➢ Type 1: Goodpasture's syndrome/Anti-GBM syndrome ➢ Type 2: Pauci-immune ➢ Type 3: Immune complex mediated • Membranoproliferative glomerulonephritisType 1: Goodpastures Syndrome / Anti-GBM Disease • Most common in men:20-30, Diagnosis 60-70 yrs • HLA DR2 1. Light Microscopy: crescent shape • pANCA +ve (25%) 2. Immunofluorescence: linear deposition of IgG along the • Type II hypersensitivity basement membrane reaction 3. Anti-GBM (glomerular basement membrane) antibodies Symptoms: Kidney+ Lungs Management 1. Nephritic syndrome: haematuria, 1. Plasma exchange proteinuria, oedema, hypertension (plasmapheresis) 2. Haemoptysis 2. Steroids 3. Shortness of breath 3. CyclophosphamideType 2: Pauci Immune Granulomatosis with Microscopic Eosinophilic granulomatosis with Polyangiitis (Wegner’s) polyangiitis polyangiitis (Churg-Strauss) KeySymptoms: KeySymptoms: Keysymptoms: 1. Epistaxsis 1. Purpuric rash 1. Asthma 2. Sinusitis 2. Necrotising vasculitis 2. Peripheral nephropathy 3. Dyspnoea 3. Nephritic syndrome 3. Nephritic syndrome 4. Haemoptysis 5. Nephritic syndrome • NO granulomatosis • Eosinophilia • pANCA +ve • Granulomatous inflammation • SADDLE SHAPED NOSE • Serum IgE high • cANCA +ve • pANCA +ve Other pANCA +ve Conditions: 1. Ulcerative colitis (70%) 2. Primary sclerosing Management cholangitis(70%) 1. Steroids 3. Anti-GBM (25%) 2. Cyclophosphamide (immunosuppressive) 4. Crohn’s (25%) 3. Plasma exchangeType 3: Immune Complex Mediated 1. Post-Streptococcal Glomerulonephritis 2. IgA nephropathy 3. Henoch Schoenlein Purpura (HSP) 4. Systemic Lupus Erythema (SLE)Post-Streptococcal Glomerulonephritis SEVERAL WEEKS after group A beta- Imaging: haemolytic streptococcus infection • Electron microscopy: subepithelial 'humps' caused by lumpy Key Symptoms: immune complex deposits of IgG and C3 1.Nephritic syndrome • Immunofluorescence: granular or 'starry sky' appearance 2.Fever 3.Smokey urine 4.Infection weeks ago Management: Supportive Bloods: 1. Raised anti-streptolysin O titre - confirms the diagnosis of a recent streptococcal infection 2. LowC3IgA Nephropathy (Berger’s) • 1-2 days after gastro-intestinal Investigations infection/upper-respiratory tract infection • Light microscopy: mesangial proliferation • Electron microscopy+ Immunofluorescence: immune complex • Young males deposition in mesangium • Histology: mesangial hypercellularity, positive • Formation of IgA immune complex immunofluorescence for IgA & C3 that deposits in the mesangium Management Key Symptoms 1. Isolated haematuria + minimal proteinuria + normal GFR:no 1. Episodic macroscopic haematuria treatment; onlyfollow up 2. Infection very recently 2. Persistent proteinuria + normal/slightly reduced GFR : ACE inhibitors Can overlap with Henoch Schonlein 3. Active disease (eg. falling GFR) or failure to respond to ACE Purpura (HSP) inhibitors: immunosuppression with corticosteroidsHenoch-Schonlein Purpura (HSP) • Children Investigations: Henoch-Schonlein Purpura (HSP) and Haemolytic Uraemia • IgA mediated small syndrome (HUS) can be confusing as: vessel vasculitis • Similar to IgA nephropathy • Post-gastro-intestinal • Positive • Both occurin children infection/upper- immunofluorescence for respiratory tract IgA & C3 • Both have classic presentation of child with recent infection ‘upset stomach’ and ‘diarrhoea’ with renal symptoms and dark urine Management: Key Symptoms: • Self-limiting + 1/3 relapse 1. Purpuric rash - • Supportive Distinguishing factors are: buttocks and extensor Haemolytic Uraemic Henoch-Schonlein Purpura surfaces Syndrome (HUS) (HSP) 2. Abdominal pain Blood diarrhoea Abdominal pain 3. Polyarthritis 4. IgA nephropathy – Jaundice Polyarthritis haematuria can be macroscopic (ie. Thrombocytopenia Purpuric rash nephriticsyndrome) Haemolytic anaemia IgA nephropathySystemic Lupus Erythematosus (SLE) Class IV (diffuse proliferative Management: glomerulonephritis)is the most common and severe form 1. Manage hypertension 2. Glucocorticoids with either mycophenolate or cyclophosphamide Investigations: 1. Renal biopsy: glomeruli shows endothelial and mesangial proliferation, 'wire-loop' appearance + capillary wall may be thickened 2. Electron microscopy: subendothelial immune complex deposits 3. Immunofluorescence: granular appearanceMembranoproliferative Glomerulonephritis 1. Type 1: most common, caused by immune complex deposition – classical component pathway – chronic infection Hep B/C 2. Type 2: C3 – alternative component pathway – mixed nephrotic + nephritic picture 3. Type 3: very rare Associated with hepatitis C GBM rebuilt on top of deposits causingTRAM TRACKING APPEARANCE on microscopy Mixed nephrotic + nephritic picture SBA 2 (question) A 54 year old man comes in complaining of blood in his urine. He is quite distressed thatthis could be prostate cancer and regrets not coming in sooner. On examination, his blood pressure is very high, although he says he get’s nervous at the doctors. Blood results reveal a raised anti-streptolysin O titre and on further questioning he does admit to having a stomach bug a few weeks ago but thought this was due to a bad takeaway. What is the most likely diagnosis? a) Prostate cancer b) Post-streptococcal Glomerulonephritis c) Systemic Lupus Erythema d) IgA nephropathy e) Granulomatosis with Polyangiitis SBA 2 (Answer) A 54 year old man comes in complaining of blood in his urine. He is quite distressed thatthis could be prostate cancer and regrets not coming in sooner. On examination, his blood pressure is very high, although he says he get’s nervous at the doctors. Blood results reveal a raised anti-streptolysin Otitre and on further questioning he does admit to having a stomach bug a few weeks ago butthought this was due to a bad takeaway. What is the most likely diagnosis? a) Prostate cancer b) Post-streptococcal Glomerulonephritis c) Systemic Lupus Erythema d) IgA nephropathy e) Granulomatosis with Polyangiitis SBA 3 (question) A 65 year old man comes in, after being urged by his partner. His partner is concerned as he has recently been coughing up some blood. He has also noticed some blood in his urine and has been feeling swollen around the legs and has been very sniffly and short of breath but claims this to be due to the weather. Blood results reveal that he iscANCA+ve What is the most likely diagnosis? a) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) b) Good-Pastures syndrome c) Tuberculosis d) Lung Cancer e) Granulomatosis with Polyangiitis (Wegner’s) SBA 3 (question) A 65 year old man comes in, after being urged by his partner. He is a long term smoker and his partner is concerned as he has recently beencoughing up some blood. He has also noticed some blood in his urine and has been feeling swollen around the legs and has beenvery sniffly and short of breath but claims this to be due to the weather. Blood results reveal that he iscANCA+ve What is the most likely diagnosis? a) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) b) Good-Pastures syndrome c) Tuberculosis d) Lung Cancer e) Granulomatosis with Polyangiitis (Wegner’s)Nephrotic Syndrome NON-PROLIFERARTIVE 1. Massive Proteinuria (>3.5 g/d):foamy urine 2. Hypoalbuminemia (<25g/L) 3. Oedema: Peripheries + Eyes + Lungs Primary Causes 1. Minimal Changes Disease 4. Hyperlipidemia + Lipiduria: fatty casts on 2. Membranous Glomerulonephritis microscopy 3. Focal Segmental Glomerulosclerosis • Protein COAL • Cholesterol ↑ Secondary Causes • Oedema 1. Diabetic nephropathy • Albumin ↓ 2. Amyloidosis nephropathy • Lipids ↑Minimal Changes Disease • Nephrotic Syndrome Investigations: • Idiopathic • Triggered by immunological 1. Bloods: U+Es, FBC, CRP insult 2. Light Microscopy: minimal change • Children and young adults • Associated with Non-Hodgkin’s 3. Electron Microscopy: podocyte effacement and effacement of foot lymphoma processes • Infectious mononucleosis Presentation: Management: 1. Nephrotic syndrome • Corticosteroids 2. Normotension 3. Face swelling • Cyclophosphamide – 4. Eczema ifsteroid resistant 5. Asthma Membranous Glomerulonephritis • Most common nephrotic syndrome in ADULTS Management: Prognosis: • Subepithelial deposition of immune complexes on basement membrane • ACEi / ARBs • 1/3 : spontaneous remission • Many spontaneously • 1/3 : remain proteinuric improve • 1/3 : develop end stage renal failure Presentation: Risk Factors: • Immunosuppression 1. Nephrotic syndrome 1. Autoimmune • If symptomatic: • Response to steroids is generally low 2. Oedema 2. Hep B/C corticosteroids + immunosuppression 3. Xanthelasma 3. Syphilis 4. Asymptomatic 4. Malignancy 5. NSAIDs It is a diagnosis of 6. Gold exclusion. 7. Lithium Investigation: • Definitive: renal biopsy • Electron microscopy: basement membrane thickening + spike + dome (glomerular matrix on top of IC deposits + podocyte effacement • Granular immunofluorescence +ve PLAS2Focal Segmental Glomerulonephritis Caused by injury to podocytes Risk Factors: Symptoms: 1. HIV 2. Heroin 1. Nephrotic symptoms 3. Congenital 4. INF treatment 2. Fatigue 3. Asymptomatic Investigations: 1. Renalbiopsy: focal segmental areas of mesangial collapse + sclerosis Symptomatic 2. Electron microscopy: effacement of foot management: processes of podocytes CorticosteroidsDiabetic Nephropathy Kidney damage caused by type 1 or type 2 diabetes All patients should be screened annually using urinary albumin:creatinine ratio (ACR) Investigations: • Should be an early morning specimen 1. Glucose in urine • ACR > 2.5= microalbuminuria 2. Microalbuminuria 3. Light microscopy: Management: • Kimmelstiel-Wilson nodule + glomerular damage • BM thickening Diabetic control + ARBs/ ACEis to lower pressure in glomerulus • Dietary protein restriction • Tight glycaemic control • BP control: aim for < 130/80 mmHg • ACE inhibitor or angiotensin-II receptor antagonist ➢ Should be started if urinary ACR is≥ 3 mg/mmol ➢ Dual therapy with ACE inhibitors and angiotensin-II receptor antagonist should not be started • Control dyslipidaemia with statinsAmyloidosis Nephropathy Secondary to amyloidosis Abnormal amyloid protein deposits lead to tissue damage in kidney Investigations: 1. Biopsy: nodular glomerulosclerosis 2. Congo Red Stain + Polarizing light: Apple green birefringence SBA 4 (question) A 10 year old boy with a history of asthma comes in with his mother complaining of facial swelling and urinalysis reveals massive proteinuria. What is the mostly likely diagnosis? a) Minimal Changes Disease b) Membranous Glomerulonephritis c) Focal Segmental Glomerulosclerosis d) Diabetic Nephropathy e) Amyloidosis Nephropathy SBA 4 (question) A 10 year old boy with a history of asthma comes in with his mother complaining of facial swelling and urinalysis reveals massive proteinuria. What is the mostly likely diagnosis? a) Minimal Changes Disease b) Membranous Glomerulonephritis c) Focal Segmental Glomerulosclerosis d) Diabetic Nephropathy e) Amyloidosis Nephropathy