Renal Conditions Aaqid Akram MBChB (2013) Clinical Education Fellow

Objectives Understand the anatomy and physiology of the nephron Understand, recognise and initiate treatment for AKI Understand the different causes of AKI Understand how to diagnose and stage CKD Understand where the diuretics work with regards to the nephron

Renal Function Urinalysis Serum Creatinine [Urea] Creatinine Clearance (CC) Estimated Glomerular Filtration Rate (eGFR) Inulin/isotopic GFR Urine Albumin Albumin Creatinine Ratio (ACR)

Acute Kidney Injury (AKI) Serum Creatinine – >26 increase within 48 hours – X1.5 increase within 7 days Oliguria/Anuria – <0.5ml/kg/hr for 6 hours 25% reduction in eGFR within 7 days

Other Investigations Urinalysis FBC / U+E / CRP Blood / Urine MC+S Serum Immunoglobulins / Autoantibodies CXR / AXR USS KUB CT KUB / Urogram

Management ABCDE Correct Electrolytes – (Na / K / Ca / PO4 / glucose) Rehydrate Stop Nephrotoxics Identify cause and treat Vigilance for acute complications – Hyperkalaemia / Acidosis / Pulmonary Oedema – ?RRT if unresponsive to treatments for above

Pre Renal Post Renal Renal

Pre Renal Causes Volume depletion Oedematous states Hypotension Cardiovascular Renal hypoperfusion

Post Renal Calculus Blood Clot Papillary Necrosis Urethral Stricture Prostatism Retroperitoneal Fibrosis Malignancy

Renal Causes Glomerular Tubular Injury Acute Interstitial Nephritis Vascular Disease Eclampsia

Syndromes Nephrotic Proteinuria +++ Hypoalbuminaemia Oedema Podocyte damage 80% glomerulonephritis Na + Fluid restriction Diuretic Treatment Nephritic Proteinuria + Haematuria / Red Cell Casts Hypertension Deteriorating renal function More acute May lead on from nephrosis Treat underlying cause

Glomerular disease Immune mediated inflammation Primary – no associated disease elsewhere Secondary - part of systemic disease Minimal Change Focal – some glomeruli Segmental – part of glomerulus Diffuse – all glomeruli

Minimal Change Disease Electron microscopy – fusion of foot processes 2-4 years old (90% nephrosis in children) Nephrotic picture – Selective proteinuria – Normal renal function – Normal blood pressure – Increased risk of infections Atopy / Hodgkin’s Does not progress to end stage kidney disease

Focal Segmental Glomerulosclerosis Light microscopy – Some glomeruli show segmental scarring Electron microscopy - Fusion of foot processes Nephrosis – older children / young adults Nephritis picture may also present 4 month prednisolone (high dose) May progress to end stage renal disease HIV – collapsing glomerulopathy

Membranous Nephropathy Light Microscopy – Diffuse thickening of glomerular basement membrane Granular deposits Most common cause of nephrotic syndrome Alternate months steroids with chlorambucil or cyclophosphamide May progress to end stage renal disease

Mesangiocapillary Glomerulonephritis AKA membranoproliferative glomerulonephritis Proliferation of mesangial cells Thickening of basement membrane HCV / chronic infections / SLE Rare Steroids – no proven benefit ½ develop end stage renal disease

Mesangial Proliferative Glomerulonephritis Mesangial cell proliferation Matrix expansion IgA deposition (IgA Nephropathy) – Berger’s Disease – URTI followed by visible haematuria Henoch-Schönlein Purpura HLA B35/ HLA D4 / Coeliac / ALD / HIV Prednisolone / Immunosuppression Slow progression to end stage renal disease

Diffuse Proliferative Glomerulonephritis Widespread hypercellularity – Infiltrating inflammatory cells – Proliferation of mesangial + endothelial cells Immunoglobulin deposition around capillary loops Nephritic syndrome following infection Streptococcal infection Very good recovery without treatment

Focal Segmental Proliferative Glomerulonephritis Secondary to systemic disease – SLE – Alport’s Syndrome (familial nephritis) Haematuria Progressive CKD Sensorineural hearing loss Several ocular abnormalities Segmental necrosis of capillary loops – May lead to cresenteric glomerulnephritis

Cresenteric Glomerulonephritis Evolution from other glomerulonephritis Goodpasture’s syndrome – Glomerular basement membrane autoantibodies – ½ pulmonary haemorrhage Systemic vasculitis May progress to end stage disease within a few months if no treatment given – Prednisolone – Cyclophosphamide – Plasma exchange

Acute Tubular Necrosis Low BP (ischaemic) Nephrotoxic drugs (Toxic) Muddy brown casts in urine AKI protocol Treat underlying cause Good prognosis

Acute Interstitial Nephritis 15% AKI Most cells fibroblasts – Endocrine function Drug hypersensitivity reaction (60%) Idiopathic / Infection / Immune Eosinophilia (true diagnosis – biopsy) Withdraw / Treat cause

Chronic Kidney Disease Presence of abnormal kidney function (eGFR <60) / structure > 3 months Failure = eGFR< 15 / dialysis / transplant Often subclinical – Regular checks if high risk or abnormalities seen Creatinine may remain normal even after 50% loss of renal function

StageImpairmenteGFR (ml/min/1.73m 2 ) 1Normal>90 2Mild aModerate bModerate Severe Established Renal Failure<15 / dialysis Add p to denote presence of proteinuria

Systemic Vasculitis Wegener’s Granulomatosis – Autoimmune vasculitis affecting endothelial cells – ENT/lungs/kidneys (haemoptysis/haematuria) – c/pANCA – Cyclophosphamide / rituximab / prednisolone Churg-Strauss – Associated with asthma – Antimyeloperoxidase antibodies – Cyclophosphamide / rituximab / prednisolone Polyarteritis Nodosa – No glomerulonephritis

Systemic Diseases SLE Sjögren’s Syndrome Myeloma – Paraprotein casts – Hypercalcaemia – Hyperviscosity Haemolytic Uraemic Syndrome – Microangiopathic haemolytic anaemia – Thrombocytopenia – AKI

Objectives were: Understand the anatomy and physiology of the nephron Understand, recognise and initiate treatment for AKI Understand the different causes of AKI Understand how to diagnose and stage CKD Understand where the diuretics work with regards to the nephron