1. Management of Chronic Kidney Disease Kate Culley ST3 College road Surgery

2. What is CKD? The gradual, substantial, and irreversible reduction in the excretory and homeostatic functions of the kidney characterised by progressive destruction of renal tissue over time

3. Why does it matter? Estimated ~ 1 in 5 men and 1 in 4 women between 65-74y has some degree CKD. More common in South Asian/black Cardiovascular disease is the most common cause of death in patients with CKD. Cardiovascular mortality doubled in patients with a GFR below 70 ml/minute.

5. eGFR Used to measure severity kidney damage. Calculation based on serum creatinine level, age, sex, race. Most widely based on MDRD equation Normal GFR is approximately 100mls/min/1.73m 2 Stages of CKD based on eGFR

6. eGFR is estimated GFR calculated by the abbreviated MDRD equation: 186 x (Creat / 88.4) -1.154 x (Age) -0.203 x (0.742 if female) x (1.210 if black)

7. * Structural (eg APCKD), functional (eg proteinuria) or biopsy proven GN

8. Problems with eGFR It is only an estimate.  Less accurate extremes of body type; low BMI, amputees.  It is not valid in pregnant women or in children  Underestimates function in kidney donors Some racial groups may not fit the MDRD equation well. MDRD equation tends to underestimate normal function.  Routine reporting of eGFR values >90 is not recommended  Most labs report all values over 60 as >60.  Significant (e.g. 20%) rise in creatinine while eGFR is >60 important + likely reflects real change in GFR. Creatinine level must be stable  Calculation assumes creatinine stable over days or longer.  They are not valid if it is changing. MDRD equation is not valid for under-18s

9. http://guidance.nice.org.uk/nicemedia/live/12069/42119/42119.pdf

10. Newly diagnosed CKD Review all previous measurements of creatinine Review all medication including OTC Urinalysis: haematuria + proteinuria suggest GN Clinical assessment Repeat creat < 2w to exclude rapid progression. Enter into a chronic disease management register Check criteria for referral

11. When to refer eGFR less than 15: immediate referral Estimated GFR 15-29: urgent referral (routine if known to be stable) Estimated GFR 30-59: routine referral if:  Progressive fall in GFR/increase in serum creatinine  Microscopic haematuria  Urinary ACR > 45 mg/mmol  Unexplained anaemia (Hb < 11 g/dL); abnormal K, Ca, PO4  Suspected systemic illness, e.g. SLE  Uncontrolled HT (>150/90 mmHg on 4 antihypertensives) Estimated GFR 60-89: referral not required unless other problems present

12. ‘Other problems’ irrespective of GFR Immediate referral for: Malignant hypertension Hyperkalaemia (K >7.0 mmol/L) Urgent referral for: Proteinuria with oedema and low serum albumin Routine referral for: Macroscopic haematuria but urological tests negative Dipstick proteinuria + uPCR ratio > 100 mg/mmol Dipstick proteinuria + microscopic haematuria

13. Information needed for referral Urinary symptoms PMH DH Examination Urine dip Urine ACR/ PCR Bloods (Hb, U+Es, creat, alb, Ca, PO4, chol, HbA1c) All previous serum creat values with dates Results of renal USS if appropriate

14. CKD 3 management in primary care Risk factor management Annual Hb, K, Ca, PO4 If Hb < 11 g/dL and other causes excluded refer Renal USS in patients with lower urinary tract symptoms, refractory hypertension, unexpected fall in GFR. Immunise against influenza and pneumococcus. Regular meds review Avoid nephrotoxics including NSAIDs Check PTH at diagnosis:  if raised check serum 25-hydroxyvit D  if low treat with ergocalciferol or cholecalciferol with Ca supplement (not calcium phosphate).  Repeat PTH at 3 months and refer if still raised.

15. Additional management for CKD 4-5 Should all have been referred 3-monthly tests: eGFR, Hb, Ca, PO4, HCO3, PTH. Dietary assessment. Immunisation against hepatitis B. Ix/ Tx PO4 retention and hyperparathyroidism. Timely provision of dialysis depending on choice. Correction of acidosis. Risk factor management

16. Renal replacement therapy Includes haemodialysis, peritoneal dialysis, CAPD or renal transplantation Indications:  Serum creatinine greater than 500 mmol/L.  Symptoms: pericarditis, encephalopathy, peripheral neuropathy, intractable gastrointestinal symptoms, failure to thrive and malnutrition.  Severe metabolic acidosis: bicarb<12 mmol/L.

17. Management of complications Water and electrolyte balance Anaemia Acidosis  Treated with sodium bicarbonate Hyperphosphataemia  Treat with dietary restriction, dietary PO4 binders + CaCO3 Hypocalcaemia  Prescribe Ca supplements +/- calcitriol. Hyperparathyroidism  Reduce hyperphosphataemia  Prescribe 1,25-dihydroxycholecalciferol and maintain a normal Ca Malnutrition  Must be avoided.  Controversy as to the benefits of protein restriction.  Emphasis is to maintain good nutrition.

18. CKD and Blood pressure targets * Applies to all stages of CKD * Systolic < 140 (aim 120-139 mm Hg) Diastolic < 90 mm Hg If diabetes or proteinuria (ACR>70 or PCR>100) 130/80 mm Hg ACE-I or ARB should be included in  HT + urinary ACR>30  DM and microalbuminuria  ACR ≥ 70 mg/mmol with / without hypertension

19. Always check U+Es 1-2 weeks after starting ACE inhibitor Recheck after dose increase Advise stopping ACEI with dehydrating illness Counsel women of child bearing age ACE-Is If creatinine rises >30% or GFR fall >25%, repeat tests, consider other causes including volume depletion, NSAID use. If no explanation stop drug, consider investigation for renal artery stenosis. Do not discontinue for lesser changes in eGFR/creatinine – repeat in 1-2w

20. IndicatorPointsPayment stages Records CKD 1 The practice can produce a register of patients aged 18 years and over with CKD (US National Kidney Foundation: Stage 3 to 5 CKD). 6— Management CKD 2 The percentage of patients on the CKD register whose notes have a record of blood pressure in the previous 15 months. 640–90% CKD 3 The percentage of patients on the CKD register in whom the last blood pressure reading, measured in the previous 15 months, is 140/85 mmHg or less. 1140–70% CKD 5 The percentage of patients on the CKD register with hypertension and proteinuria who are treated with an ACE inhibitor or angiotensin II receptor blocker (unless a contraindication or adverse effect is recorded). 940–80% CKD 6 The percentage of patients on the CKD register whose notes have a record of a urinary albumin:creatinine ratio (or protein:creatinine ratio) test in the previous 15 months. 640–80% CKD and QOF

21. Thank you Any comments or questions?

22. References http://guidance.nice.org.uk/nicemedia/live/12069/42119/42119.pd f http://guidance.nice.org.uk/nicemedia/live/12069/42119/42119.pd f http://pathways.nice.org.uk/pathways/chronic-kidney-disease http://www.patient.co.uk/doctor/Chronic-Kidney-Disease-and-its- Management.htm http://www.patient.co.uk/doctor/Chronic-Kidney-Disease-and-its- Management.htm http://www.renal.org/whatwedo/InformationResources/CKDeGUI DE.aspx http://www.renal.org/whatwedo/InformationResources/CKDeGUI DE.aspx http://www.renal.org/eGFRcalc/GFR.pl

24. It is only an estimate. A significant error is possible. eGFR is most likely to be inaccurate in people at extremes of body type, for example malnourished, amputees. It is not valid in pregnant women or in children. Underestimates funtion in kidney donors. Confidence intervals: confidence intervals are quite wide, e.g. 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. Race: Some racial groups may not fit the MDRD equation well. It was originally validated for US white and black patients. For Afro Caribbean black patients, eGFR was 21% higher for any given creatinine in the MDRD study. So if race was not included in the estimate you have, it should be increased by approx. 20% for a black patient. In the UK white population the equation seems to work quite well -may not perform so well in all racial groups. Not so good near normal: The MDRD equation tends to underestimate normal or near- normal function, so slightly low values should not be over-interpreted. Furthermore, laboratory differences in creatinine estimations may make significant differences. Routine reporting of eGFR values >90 is not recommended and many labs are now reporting all values over 60 as >60. Note however that a significant (e.g. 20%) rise in creatinine while eGFR is >60 may still be important as it will usually reflect a real change in GFR. Creatinine level must be stable: eGFR calculations assume that the level of creatinine in the blood is stable over days or longer. They are not valid if it is changing. Age: The MDRD equation is not valid for under-18s. Use the Counahan-Barrat method for children

25. Newly diagnosed CKD Review all previous measurements of serum creatinine to estimate GFR and assess rate of deterioration. Review all medication including over-the-counter drugs; particularly consider recent additions (e.g. diuretics, non-steroidal anti-inflammatory drugs (NSAIDs), or any drug capable of causing interstitial nephritis, such as penicillins, cephalosporins, mesalazine, diuretics). mesalazine Urinalysis: haematuria and proteinuria suggest glomerulonephritis, which may progress rapidly. Clinical assessment: e.g. look for sepsis, heart failure, hypovolaemia, palpable bladder.heart failure hypovolaemia Repeat serum creatinine measurement within 5 days to exclude rapid progression. Check criteria for referral (above). If referral not indicated, ensure entry into a chronic disease management register and programme.

26. Management of complications Water and electrolyte balance:  Patients with chronic kidney disease (CKD) pass normal volumes of urine. Precise restriction of fluid intake is only required for patients with oliguric end-stage renal failure. The usual recommendation is for a daily intake of daily urinary output plus 500 ml (for insensible losses).  Patients should avoid binge drinking and be vigilant in replacing extra fluid losses in hot weather and during episodes of diarrhoea or vomiting.  Severe acute volume overload may require high-dose loop diuretics or dialysis.  Dietary restriction to 60 mmol/day each of sodium and potassium is appropriate but compliance is greatly improved with sensible and flexible dietary advice.  Loop diuretics (with the addition of a thiazide diuretic if resistant) improve sodium balance and blood pressure.  Hyperkalaemia is treated with dialysis if the potassium level rises above 7 mmol/L. Otherwise, treatment is directed towards the cause, e.g. excess fruit, chocolate or coffee, gastrointestinal haemorrhage, acidosis or tissue necrosis. Hyperkalaemia with the GFR still above 10 ml/min may be due to hyporeninaemic hypoaldosteronism in patients with diabetes, hypoadrenalism or as a result of treatment with ACE inhibitors.ACE inhibitors Anaemia: See separate article Anaemia in Chronic Renal Disease.Anaemia in Chronic Renal Disease Acidosis:  Chronic acidosis aggravates hyperkalaemia, inhibits protein synthesis and accelerates calcium loss from bone.  Treated with sodium bicarbonate as long as the patient can tolerate the increased sodium load, as additional sodium may cause fluid overload and worsen hypertension. Hyperphosphataemia:  Occurs late in chronic kidney disease.  Treated with dietary restriction, dietary phosphate binders and calcium carbonate. Hypocalcaemia:  Prescribe calcium supplements, with or without calcitriol. Hyperparathyroidism:  Reduce hyperphosphataemia by diet and phosphate binders.  Prescribe 1,25-dihydroxycholecalciferol and maintain a normal calcium level.  Secondary hyperparathyroidism starts early in chronic renal failure (CRF) and is difficult to treat when it becomes established.  Secondary hyperparathyroidism may lead to tertiary hyperparathyroidism if not treated effectively. Malnutrition:  Must be avoided, although protein restriction can slow progression of renal failure.  Restriction of dietary protein slows the progress of glomerulosclerosis in residual nephrons in animal experimental models.  There remains controversy as to the benefits of protein restriction for treatment. Although patients are advised against high-protein diets, low-protein diets are not usually recommended and the emphasis is to maintain good nutrition.