Chronic Renal Failure

1. Chronic Renal Failure Ayesha Ejaz 5th Year Working Group ayesha@peerassisted.org peerassisted.org

2. Learning objectives: CRF • Causes • Investigation • Complications • Management • Renal replacement therapy • Nephrotic and nephritic syndrome • Basic principles: • Renovascular disease • Thrombotic thrombocytopenic purpura • Diabetic nephropathy

3. Case scenario 36 year old female, GP referral, presents to medical unit with nocturia, nausea and generalised pruritis. PMH: enuresis and UTI in childhood. 5 year history of hypertension. BP 150/90 mmHg Serum creatinine 1200 umol/L (58-124 umol/L)

4. Investigations: acute or chronic? • Hypertension – suggests chronic process. • FBC (normochromic, normocytic anaemia) • Repeat U&Es (↑Urea, ↑Cr, exclude↑K) – compare with previous U&Es, if available. • Bone mineral screen (↓Ca, ↑PO4, ↑alk phos) - 2°hyperparathyroidism (↑PTH) • Renal osteodystrophy • Skeletal X-Ray Longmore et al. Oxford Handbook of Clinical Medicine. 7th edition. p294

5. Investigations: acute or chronic? Renal osteodystrophy – 2o hyperparathyroidism Vascular calcification Subperiosteal resorption Tuft erosion Taken from Veighy K. Cunningham J. Medicine 2011; 39(7): 418

6. Investigations: acute or chronic? • Urinalysis – proteinuria +/- haematuria indicates glomerular disease. • Renal Ultrasound • Exclude obstruction (hydronephrosis, hydroureter) • Usually small in CRF (<9cm) • Normal/large kidneys – polycystic, DM, amyloidosis • Additional imaging in CRF • MR angiography – renal artery stenosis • DMSA scan – renal scars • Renal Biopsy, esp if normal-sized kidneys Walbaum D. Kluth D. Medicine 2007; 35(7): 356

7. Percutaneous renal biopsy – complications (1) • Bleeding – main complication. • Transient microscopic haematuria occurs in almost all patients. • Gross haematuria 3-5%. • Hypotension 2o to bleeding in ~2%. • Blood transfusion required in <1% • Severe bleeding requiring surgery in <1% • Nephrectomy rate 0.3%  Severe bleeding if renal artery, aorta or venous collaterals punctured – very rare. Whittier W. Korbet S. Indications for and complications of renal biopsy. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2011.

8. Percutaneous renal biopsy – complications (2) • Additional complications • Pain > 12 hours, due to haematoma formation and capsular stretching, or ureteral obstruction due to blood clot. Rx paracetamol (not NSAIDs, due to risk of bleeding) • Formation of AV fistulas – usually self-limiting, thought to be fairly common (9%). • Perirenal infection – 0.2%. More likely in patients with pre-existing kidney infection. Whittier W. Korbet S. Indications for and complications of renal biopsy. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2011. Salama A. Renal biopsy. Medicine 2011; 39(6): 339

9. Causes of CRF (1) Case scenario: • Childhood Hx of UTIs and enuresis • indicative of vesicoureteric reflux. • can lead to scarring and renal failure in adulthood. • Reflux nephropathy Walbaum D. Kluth D. Medicine 2007; 35(7): 356

10. Causes of CRF (2) Common causes of CRF: • Hypertension • Diabetes • Glomerulopathies • IgA nephropathy • Minimal change nephropathy • Focal segmental glomerulosclerosis (FSGS) • Congenital/Inherited Feest T. Medicine 2007; 35(8): 440-1 Longmore et al. Oxford Handbook of Clinical Medicine. 7th edition. p294 Kumar P. Clark M. Clinical Medicine. 7th edition p625.

11. Causes of CRF (3) • Renovascular disease (renal artery stenosis) • Fibromuscular disease • Atherosclerosis • Obstructive • Prostatic hypertrophy, nephrolithiasis • Drug-induced • NSAIDs, aminoglycosides, penicillins, PPi, diuretics. Longmore et al. Oxford Handbook of Clinical Medicine. 7th edition. p294 Kumar P. Clark M. Clinical Medicine. 7th edition p625.

12. Causes of CRF (4) Rare causes: • Renal vasculitis • SLE, microscopic poyangiitis, Wegener’s granulomatosis, polyarteritis nodosa • Myeloma • Nephrocalcinosis (2o to sarcoidosis, TB) • Haemolytic uraemic syndrome (HUS) • Thrombotic thrombocytopenic purpura (TTP) Longmore et al. Oxford Handbook of Clinical Medicine. 7th edition. p294 Kumar P. Clark M. Clinical Medicine. 7th edition p625.

13. Rare causes: Renal vasculitis SLE, microscopic poyangiitis, Wegener’s granulomatosis, polyarteritis nodosa Myeloma Nephrocalcinosis (2o to sarcoidosis, TB) Haemolytic uraemic syndrome (HUS) Thrombotic thrombocytopenic purpura (TTP) Signs/symptoms of rare causes Fever, arthralgias, rashes Haemoptysis – Wegener’s, microscopic polyangiitis Hyperuricaemia, hypercalcaemia, bone pain, lytic lesions Haemolysis, thrombocytopenia, typically follows a febrile illness (gastroenteritis 2oE. coli 0157) Purpuric rash, thrombocytopenia, haemolysis (↑LDH), neurological dysfunction Causes of CRF (4) Longmore et al. Oxford Handbook of Clinical Medicine. 7th edition. p294 Kumar P. Clark M. Clinical Medicine. 7th edition p625.

14. Stages of chronic kidney disease Walbaum D. Kluth D. Medicine 2007; 35(7): 358

15. Features/Complications of CRF (1) • Features of underlying systemic disease • Features of uraemia: • Nausea, vomiting, anorexia, weight loss, malaise, pruritus, hiccoughs, chest pain 2o to uraemic pericarditis, asterixis, myoclonus • Anaemia • Renal osteodystrophy • Cardiovascular disease • ‘Restless legs’ • Carpal tunnel syndrome – 2o to amyloidosis Kumar P. Clark M. Clinical Medicine. 7th edition.

16. Features/Complications of CRF (2) • Nocturia/polyuria • GI • ↑risk of reflux oesophagitis, PUD, acute pancreatitis • Nephrogenic systemic fibrosis • Gadolinium contrast agent (MRI) • Metabolic abnormalities • Gout, dyslipidaemia • Others – calciphylaxis, malignancy Walbaum D. Kluth D. Medicine 2007; 35(7): 356 Kumar P. Clark M. Clinical Medicine. 7th edition.

17. Nephrogenic systemic fibrosis Long-standing nephrogenic systemic fibrosis. There is diffuse thickening, induration and hyperpigmentation of lower legs with inhibition of joint flexion. Taken from Grobner T. Prischl F. Kidney Int 2007;72: 260-4

18. Management of CRF (1) • Refer early to nephrologist • Treat reversible causes • Stop nephrotoxic drugs • Relieve obstruction • Cardiovascular disease • ACEi/ARB – reduce BP and proteinuria • Statin, if 10-year cardiovascular risk ≥20% • Low dose aspirin, in CKD stage 1-3 SIGN guidelines. Diagnosis and management of chronic kidney disease 103. Longmore et al. Oxford Handbook of Clinical Medicine. 7th edition. p294 Tomson C. Bailey P. Medicine 2011; 39(7): p408

19. Management of CRF (2) • Anaemia • Exclude Fe deficiency, erythropoietin • Pruritis • Skin rehydration, antihistamine, correction of anaemia • Renal osteodystrophy • Alfacalcidol and Ca supplements, Calcichew (binds PO4 in gut) • Restless legs • Gabapentin, clonazepam • Hyperkalaemia • Dietary restriction, calcium resonium Longmore et al. Oxford Handbook of Clinical Medicine. 7th edition. p294 Tomson C. Bailey P. Medicine 2011; 39(7): p408

20. When to consider dialysis: CRF • Pericarditis/pleuritis • Progressive uraemic encephalopathy/neuropathy: (confusion, asterixis, myoclonus, wrist or foot drop, seizures) • Significant bleeding diathesis 2o to uraemia • Fluid overload not responsive to diuretics • Hypertension (unresponsive to meds) • Refractory metabolic disturbances (hyperkalaemia, metabolic acidosis, hypercalcaemia, hypocalcaemia, and hyperphosphataemia) • Persistent nausea and vomiting • Evidence of malnutrition Ismail N. Indications for initiation of dialysis in chronic kidney disease. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2011.

21. When to consider dialysis: ARF • Refractory fluid overload – e.g. pulmonary oedema. • Hyperkalemia (K+>7 mmol/L), or rapidly rising potassium levels • Signs of uraemia, such as pericarditis, neuropathy, or an otherwise unexplained decline in mental status • Metabolic acidosis (pH <7.1) • Certain alcohol and drug intoxications e.g. lithium

22. Renal replacement therapy (1) • Haemodialysis • AV fistula formation, diffusion of waste product/toxins across semi-permeable membrane, counter-current flow of dialysate. • s/e – disequilibration syndrome, hypotension, arrhythmias, AV fistula: thrombosis, stenosis, aneurysm, steal syndrome, ischaemia. Temporary line: infection, blockage • Haemofiltration • Blood filtered across a semi-permeable membrane, waste products removed by convection (positive hydrostatic pressure across membrane). More expensive but less haemodynamic instability, used in critically ill. Longmore et al. Oxford Handbook of Clinical Medicine. 7th edition. p296

23. Renal replacement therapy (2) • Peritoneal dialysis (PD) • Dialysate enters peritoneal cavity via Tenckhoff catheter. Waste products diffuse across peritoneum membrane. • s/e peritonitis, exit-site infection, loss of membrane function, catheter malfunction, sclerosing peritonitis • Continuous ambulatory PD • Automated PD • Renal transplant – cadaveric donor or living match

24. Questions?

25. Relative Active renal/perirenal infection Anatomic abnormalities of kidneys (e.g. horseshoe) Small hyperechoic kidneys Skin infection over biopsy site Hydronephrosis Multiple, bilateral cysts Renal tumour Absolute Uncontrolled severe hypertension Uncontrollable bleeding diathesis Uncooperative pt Solitary native kidney Percutaneous renal biopsy - contraindications Whittier W. Korbet S. Indications for and complications of renal biopsy. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2011. Health and Public Policy Committee. American College of Physicians. Ann Intern Med. 1988;108(2):301

26. Nephritic Haematuria Proteinuria Hypertension Urine: ‘smoky’ – red cell casts Nephrotic Proteinuria >3g/24 hours Hypoalbuminaemia <30g/L Oedema Hyperlipidaemia ↑risk of thromboembolism Urine: ‘frothy’ – severe proteinuria Nephritic vs Nephrotic