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Advanced Chronic Kidney Disease

Advanced Chronic Kidney Disease. Anand Vardhan Consultant Nephrologist Manchester Institute of Nephrology & Transplantation North West British Geriatrics Society Meeting 29 th March 2011 Manchester Royal Infirmary. Chronic Kidney Disease. Definition:

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Advanced Chronic Kidney Disease

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  1. Advanced Chronic Kidney Disease Anand Vardhan Consultant Nephrologist Manchester Institute of Nephrology & Transplantation North West British Geriatrics Society Meeting 29th March 2011 Manchester Royal Infirmary

  2. Chronic Kidney Disease • Definition: • Kidney damage OR GFR less than 60mL/min/1.73m2 • for 3 months or more, regardless of cause • Kidney damage • Active urinary sediment • Structural renal/tract abnormalities • Biopsy proven disease • Exclude: • Acute Kidney Injury (AKI/ARF/ATN) • Acute Pyelonephritis / Acute Interstitial Nephritis • RPGN/RPRF Levey et al, Ann Intern Med 2006; 145:247-54

  3. Recommendations forDiabetic Nephropathy - NICE • uACR • first morning sample preferred • ensure no UTI • eGFR (4V MDRD equation) • Repeat twice in 3-4 months to confirm • Men < 2.5; Women < 3.5 • Heavy proteinuria • uACR ≥70 mg/ mmol • uPCR ≥100 mg/mmol • Urinary protein excretion ≥1 g/24 h • refer for specialist opinion

  4. Suspect non-diabetes cause if: • Absence of retinopathy • Severe/resistant hypertension • Heavy proteinuria uACR > 70 • Haematuria • Rapid decline in eGFR • Systemic illness • (positive renal immunology screen)

  5. Diabetic Kidney Disease • Pathological classification • Clinical Stages of diabetic kidney disease • Stages of CKD

  6. 1. Pathological classification - DN Renal Pathology Society – Pathologic Classification of Diabetic Nephropathy J Am Soc Nephrol 2010 Apr 21 (4) 556-63

  7. Light Microscopy Renal Pathology Society – Pathologic Classification of Diabetic Nephropathy J Am Soc Nephrol 2010 Apr 21 (4) 556-63

  8. 2. Diabetic NephropathyClinical Stages • Stage 1 Hyperfiltration (GFR high) • Stage 2 GFR high or normal • Microalbuminuria (30-300 mg/24h) • Likely to progress to end-stage renal disease (ESRD) • Stage 3 (overt proteinuria) • >300 mg of albumin in a 24-hour period • Hypertension typically develops during stage 3. • Stage 4 (late-stage diabetes) • Progressive Glomerular damage • Increasing albuminuria • Falling GFR, creatinine abnormal, hypertension • Stage 5 (end-stage renal disease, ESRD) • GFR <10 mL/min • RRT required: HD/PD/Transplantation • Or NOT 25-40% Type I 5-15% Type II

  9. 3. Stages of CKD UK CKD Guidelines September 2005 www.renal.org

  10. Renal Physiology – Factoids • Kidneys = 0.4% of total body weight • 20% of cardiac output (4ml/g/min) • 1 litre per minute! • 40 times higher than average tissues • Not for oxygenation • Not for nutrition • But for establishing an efficient GFR

  11. 0.8 – 1.2 million Nephrons per kidney • Established at 36 weeks gestation • 25% renal blood flow = glomerular filtrate • 125 ml/min or 150 - 200 L per day! • 70 kg adult has 42 L total body fluids • Most reabsorbed by renal tubules • Urine output 1.5 – 2 L per day

  12. Assessment of Renal Function • Renal blood flow • Glomerular Filtration (GFR) • Tubular Functions • Reabsorptive functions (Glu, aa, Pi, Na, HCO3) • Urine concentration & dilution • Excretory functions (H+, K+, creatinine) • Endocrine Functions • Activation of Vitamin D, Renin, EPO

  13. Normal GFR (mL/min/1.73m2) • Measured • Healthy young men: 130 • Healthy young women: 120 • Declines by 1mL/min/1.73m2 annually after age 40y • Calculated (estimated) • Uses creatinine and other parameters as basis for calculation

  14. Serum Creatinine 120 umol/L Serum Creatinine 120 umol/L

  15. Increased Muscle Mass Normal Muscle Mass Normal Muscle Mass Reduced Muscle Mass Creatinine Input Plasma Pool Content Output Kidney Normal Kidneys Diseased Kidneys Normal Kidneys Diseased Kidneys Effect of Muscle Mass on Serum Creatinine

  16. Cockroft and Gault formula • eGFR = ([140-age] x wt (kg) ) x 1.23 (M) • Creatinine (umol/l) • Modifications required for children & obese subjects • Can be modified to use Surface Area • Nephron 1976:16;31-41 • 4V MDRD formula • (abbreviated form, GFR ml/min/1.73m2) • Males: eGFR = 186 x [Creat/88.4]-1.154 x age-0.203 • Females: eGFR = 138 x [Creat/88.4]-1.154 x age-0.203 • (x 1.21 if African-American) • Levey et al Ann Intern Med 2006; 145: 247-54

  17. Caveats • MDRD formula not validated in: • Children (<18 yrs or elderly >75 yrs) • Counahan-Barrat formula for children • Acute Renal Failure • Pregnancy • Oedematous states • Muscle Wasting disease states • Amputees • Malnourished

  18. Limitations of the MDRD formula • Confidence intervals: • 90% confidence intervals are quite wide i.e. • 90% of patients will have a measured GFR within 30% of their estimated GFR • 98% have measured values within 50% of the estimated value • For an individual patient values will be much more consistent than this, just as creatinine values are - e.g. a 20% fall in eGFR is certain to reflect an important change.

  19. Precision of eGFR

  20. S Creatinine 120 umol/L Age 75 yrs Weight 45 Kg MDRD eGFR 40 ml/min/1.73m2 C&G eGFR 25 ml/min S Creatinine 120 umol/L Age 30 yrs Weight 120 Kg MDRD eGFR 66 (79) ml/min/1.73m2 C&G eGFR 135 ml/min

  21. Malaysia 58% Canada 51% Mexico 50% USA 45% New Zealand 41% Australia 31% UK RR 22% Most others 20-44% Low incidence countries Romania, Russia, Norway Prevalence of Diabetic ESRD Diabetic CKD/ESRD 2010: A Progress Report Mark E Williams, Seminars in Dialysis 23, 2, 2010 129-133

  22. UK ESRD by age – 2009 RR report

  23. Criteria for referral to Renal services(unless known terminal illness/comorbidity) • Estimated GFR • CKD 5 <15 Immediate referral • CKD 4 15 – 29 Urgent referral (routine referral if known to be stable) • CKD 3 30 – 59 Routine referral if: • Microscopic haematuria • Urinary PCR > 45 mg/mmol • Unexplained anaemia (Hb <11g%) • Abnormal K+>6, Ca++<2.1, Pi>1.6 • Systemic illness, e.g. SLE, arthritis • Uncontrolled BP (>150/90 on 3 agents) • Fall in GFR >5ml/min in 12/12 • Fall in GFR >15% after ACEI/AIIRB • CKD 1-2 >60 Referral not required (unless other problems present)

  24. Referral irrespective of eGFR • Immediate referral for: • Malignant hypertension • Hyperkalemia (potassium >7.0 mmol/l) • Urgent referral for • Proteinuria with oedema & low serum albumin (Nephrotic Syndrome) • Routine referral for: • Dipstick proteinuria and urine PCR >100 mg/mmol • Dipstick proteinuria and microscopic haematuria • Macroscopic haematuria but urological tests negative

  25. CKD Complications stage-wise Stage 1 Hypertension - more frequent than non CKD patients Stage 2 Hypertension frequent Mild elevation of parathyroid hormone Stage 3 Hypertension common Decreased calcium absorption Reduced phosphate excretion More marked elevation of parathyroid hormone Altered lipoprotein metabolism Reduced spontaneous protein intake Renal anaemia Left ventricular hypertrophy Stage 4 Metabolic acidosis Hyperkalaemia Decreased libido Stage 5 Salt and water retention causing apparent heart failure Anorexia / Nausea / Vomiting Pruritus (itching without skin disease) Overt uraemia with uraemic pericarditis

  26. Management of CKD 4 & 5 • UK CKD Guidelines • SIGN Guidelines! • ERBP (ERA-EDTA)!! • NKF-DOQI Guidelines (K/DOQI)!!! • CARI Guidelines!!!! • KDIGO Guidelines!!!!!

  27. http://www.renal.org/home.aspx

  28. http://www.renal.org/whatwedo/InformationResources/CKDeGUIDE.aspxhttp://www.renal.org/whatwedo/InformationResources/CKDeGUIDE.aspx

  29. Management of CKD 4 • Counselling & patient education • Treatment of Primary disease • Nutritional management • Blood pressure control • Safe use of ACE inhibitors & ARB • Lipid management

  30. Complications • Anaemia, bone, fluid, electrolyte, acidosis • Medication review • Immunisation • Vascular / peritoneal access • Transplant work-up • Conservative management

  31. Specific Management of CKD 5 • DIALYSIS • HD – Hospital based Home • PD – CAPD/APD or aAPD • TRANSPLANTATION • CONSERVATIVE

  32. Most important question in CKD 5 • When should dialysis be commenced? • eGFR based criteria • Uremic symptoms • Failing Nutrition • Fluid overload/Heart failure • Pre-/Post operatively

  33. End-of-life care in CKD 5 • Liverpool Care Pathway for the Dying Patient (LCP) June 2008 • http://www.renal.org/pages/pages/posts/new-lcp-guidelines-for-ckd-4538.php

  34. Management of CKD - Summary  Risk Stage 1&2 Stage 3 Stage 4 Stage 5 Normal/GFR Mod  GFR Severe GFR ESRD Screen for CKD Reduce CVS risk • Diagnose cause • Treat the cause • Monitor U&E • Slow progression • Reduce CVS risk • As in Stage 1&2 + • Anaemia SHPT • Nutrition Fluid Acidosis Immunise • Avoid reno-toxics • As in Stage 3 + • Treat complications • Immunise again • Prepare for RRT • As in Stage 4 + • DIALYSIS HD/PD • TRANSPLANT • CONSERVATIVE Smoking Exercise Cholesterol Blood Pressure (ACEI/ARB) Aspirin EPO Alfacalcidol Bicarbonate Diuretic Choice of modality Vascular access Transplant workup Living donor End of Life Care

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