JULIAN WRIGHT Consultant Nephrologist Manchester Royal Infirmary

1. Renal Failure – Acute and Chronic JULIAN WRIGHT Consultant Nephrologist Manchester Royal Infirmary

4. Acute renal failure – hard to define

5. Acute renal failure – not hard to recognise

6. Definition of Acute Renal Failure • No agreed definitions • UKRA Guidelines: “Decline of renal excretory function over hours or days …recognized by the rise in serum urea and creatinine” • Liano et al, KI 50:811(1996) >177 µmol/L • Doubling of serum creatinine • Use of Renal Replacement Therapy

7. Acute vs Chronic Renal Failure • Anaemia • Renal size • Tolerance of severe uraemia • Metabolic bone disease • hypocalcaemia • secondary hyperparathyroidism

8. Diagnosis of Acute Renal Failure • History and examination • Routine bloods • Extra bloods – bicarbonate, CK, CRP + blood cultures • ECG • CXR • GN screen - immunology, dipstick urine • Renal USS • Biopsy

9. The renal ‘troponin’ • Cystatin C endogenous cysteine proteinase inhibitor stable and constant rate of production by all nucleated cells freely filtered by glomerulus not secreted by tubules increases 2-3 days prior to creatinine

10. The renal ‘troponin’ • Urinary excretion of kidney injury molecule-1 neutrophil gelatinase associated lipocalcin IL-18

11. ARF: causesLiano et al, 1996 Acute tubular necrosis 45% Prerenal 21% Acute on chronic renal failure 13% Obstructive 10% Glomerulonephritis (primary & secondary) 3% Acute tubulointerstitial nephritis 2% Vasculitis 1.5% Vascular 1% Other 3.5%

12. Acute renal failure – Rasmusan, 1982

13. Classification of Acute Renal Failure The Undergraduate Classification works fine! Pre Renal = Circulatory Failure = “Shock” Renal = The cells of the kidney Post Renal = Obstruction

14. Pre-renal Acute Renal Failure • Volume depletion • Decreased effective blood flow • Renal vasoconstriction • Altered intra-renal haemodynamics • Increased renal vein pressure

15. Urine electrolytes in Pre-renal ARF Avid Na & H2O reabsorption Osmolality > 600 Na < 20mmol/l

16. Urine electrolytes in ATN Impaired Na & H2O reabsorption Osmolality < 400 Na > 20mmol/l

18. Intrinsic Acute Renal Failure • Acute tubular necrosis • Acute interstitial nephritis • Acute glomerulonephritis • Acute vascular syndromes • Intratubular obstruction

19. ARF - management • Calcium gluconate – 10mls 10% (20-30 mins) • Insulin dextrose – 10 units Humulin S in 50ml 50% glucose over 10 minutes • Salbutamol nebs 2.5mls 2hrly • Get the ‘fluid balance’ right • Remove causes – drugs, sepsis • Furosemide • Calcium resonium (4-6 hours to work) • Laxatives • Bicarbonate • Renal replacement therapy

21. ARF managementFluids Examine the patient – fluid status • Replace deficits • Balance I & O • Account for insensible losses • Leave sufficient volume space for Rx and nutrition.

22. Furosemide • Loop diuretic – decrease oxygen consumption by decreasing Na transport – less ischaemic injury • Increases urinary flow – reduce intratubular obstruction and backleak of filtrate • Help with fluid management

23. Furosemide • Does not prevent ARF post cardiac surgery • Increases risk of ARF when given to prevent contrast nephropathy • Mannitol – osmotic diuretic • Decreases cell swelling, scavenge free radicals, induce intrarenal prostaglandin – renal vasodilatation

24. Dopamine • Synthesised in proximal tubular cells from L-Dopa • DA-1 receptor in vasculature and proximal and basolateral proximal tubular membranes cause renal vasodilatation and decreased Na tubular reabsorption • DA-2 receptor less sensitive to dopamine – sympathetic nerve terminals innervating blood vessels

25. Dialysis in acute renal failure • Start HD/CVVH: • if established oliguria is present • if any (serious) complications of uraemia are present • refractory hyperkalaemic • refractory acidosis • if (serious) fluid overload is present • if serum urea >50 mmol/l (?)

28. Advantages of IHD • Rapid solute removal • Rapid volume removal • Effective for some drug intoxications • Rapid correction of electrolytes disturbances

29. Advantages of continuous RRT • Slower volume removal – greater haemodynamic stability • Absence of volume or solute fluctuation over time

31. Summary Acute Renal Failure • Common • Serious • Work out the causes and consequences • Treatment is logical in many cases – and reduces mortality • Early organ support • If it could be supplied IHD may be as good in ICU setting

32. Complications of chronic kidney disease

33. Stages of CKD

34. Malnutrition Inflammation Atherosclerosis Syndrome UREMIA Infection Inflammation Fluid Overload Hypertension High CRP Acute Phase response CYTOKINES Congestive Heart failure High fibrinogen High Lp(a) Low albumin Athero sclerosis Malnutrition DEATH Bergstrom and Lindholm AJKD 1998

35. Complications • Hypertension • Left ventricular hypertrophy • Anaemia • Renal bone disease • Acidosis • Cardiovascular co-morbidity and death

36. Hypertension and CKD: NEOERICA % Stage1 Stage2 Stage3 Stage4 Stage5 GFR60 GFR<60

37. Blood Pressure and Progression of CKDAIPRD Study Group 1860 patients with non-diabetic kidney disease Meta-analysis of 11 RCTs of ACEIs RR Systolic BP (mmHg) Jafar et al, Ann Intern Med 2003;139:244-252

38. Blunting of nocturnal ‘dipping’ in BPFarmer, Goldsmith, NDT 1997

39. Hypertension • Causes of hypertension in CKD Salt and water overload Activated RAA system • Life-style management • Drugs A B C D • Blockade of renin-angiotensin system

40. REIN STUDY

41. Proteinuria is strongly associated with renal progression R20.06,-0.25,p<0.001

42. Left ventricular hypertrophy • Causes Concentric LVH – hypertension Eccentric LVH – fluid overload, anaemic LV dilatation – maladaptive

44. Left Ventricular Hypertrophy(Prevalence)

48. Chalk Cheese

49. Anaemia Targets • Patients with CRF should achieve Hb > 10g/dL within 6 months of seeing a nephrologist • Serum ferritin > 100µg/l (transferrin saturation >20%)

50. Anaemia • Causes • Iron deficiency Erythropoietin deficiency GI blood loss Malnutrition Hepcidin – affects iron metabolism • Effect on patients quality of life