1. Chronic kidney disease Juliet Bell

2. Introduction CKD is common and frequently unrecognised More common with increasing age. Often exists together with other conditions More common in south asian, and afro-caribbean Lack of specific symptoms are often not diagnosed, or diagnosed late when CKD is at an advanced stage.

3. Definition CKD (or renal failure) is characterised by a gradual decline in kidney function over time. Can be categorised into –Kidney damage: indicated by persistent proteinuria, haematuria or anatomical abnormality –Decreased kidney function: indicated by a glomerular filtration rate (GFR) of less than 60ml/min/ 1.73m 2 which persists for more than 3 months

4. At risk groups Diabetes Hypertension Cardiovascular disease Structural renal tract disease, renal calculi or prostatic hypertrophy Multisystem diseases with potential kidney involvement – eg SLE Family history of stage 5 CKD or hereditary kidney disease. Opportunistic detection of haematuria or proteinuria Patient on nephrotoxic drugs

5. Early Detection Early treatment of CKD and its complications can delay or prevent progression to ESRD Annual SrCr checks recommended for estimation of GFR, urine dipstick for patients known to have a high risk of developing CKD.

6. Assessing Renal function Inulin – excreted unchanged in the urine, –provides accurate GFR assessment. –Expensive, time consuming Serum creatinine (SrCr) –Simple to measure, Inexpensive –Routinely used to assess renal function –Not always accurate and can be influenced by many factors. Equations use SrCr to estimate GFR

7. Estimated eGFR Current clinical standards recommend using the modification of diet in renal disease (MDRD) equation to estimate GFR. GFR (ml/min/1.73m 2 ) = 175 x (SrCr [umol/L]/88.4) -1.154 x age(years) -0.203 x 0.742 if female, x 1.21 if african or african caribbean Normal GFR is roughly 100ml/min/1.73m 2

8. Testing kidney function DoH recommends that eGFR is reported alongside serum creatinine to allow physicians to detect renal impairment. Correct for ethnicity: multiply eGFR by 1.21 for african or african-caribbean ethnicity Make allowance for biological and analytical variance of serum creatinine (+5%) when interpreting changes in egfr Advise no meat for 12 hours before the test Interpret with caution in people with extreme muscle mass. [Also in pregnancy, oedematous states, muscle wasting disorders, amputees and malnourished people, and in acute renal failure.] Test annually in all at risk groups

9. Cockgroft and Gault Creatinine Clearance CrCl (ml/min) = F x (140 – age[years]) x weight (kg) SrCr (umol/L) Where F = 1.23 in males and 1.04 in females No evidence to demonstrate that these are interchangeable. Used for drug dosing in patients with renal function

10. Kidney Damage Haematuria Proteinuria Albuminuria Can be determined by dipstick test Haematuria can be classified as nephrological or urological and will require further investigation if there is no obvious cause – eg uti Proteinuria – sign of kidney disease and associated with a more rapid decline in kidney function.

11. Testing for haematuria Persistent invisible haematuriaAction To differentiate, in the absence of proteinuria, from transient haematuria. Confirm persistent invisible haematuria by 2 out of 3 positive reagent strips. With or without proteinuriaInvestigate for urinary tract malignancy in appropriate age group Without proteinuriaFollow up annually with repeat testing for haematuria, proteinuria/albuminuria, GFR and blood pressure monitoring as long as the haematuria persists. Use reagent strips rather than urine microscopy Evaluate further if there is a result of 1 + or more Do not use urine microscopy to confirm a positive result

12. Testing for proteinuria Use ACR in preference to PCR as it has greater sensitivity. Do not use reagent strips If ACR > 30mg/mmol and < 70mg/mmol, confirm by subsequent early morning sample. If ACR > 70mg/mmol repeat sample not needed Proteinuria defined as ACR > 30mg/mmol If ACR > 70mg/mmol – consider specialist referral In patients with diabetes consider microalbuminuria as clinically significant: –Men: ACR > 2.5mg/mmol –Women: ACR > 3.5mg/mmol

13. Investigation If eGFR < 60ml/min/1.73m 2 in first test: –Repeat within 2 weeks –Quantify ACR (early morning sample) –Check for haematuria If eGFR > 60ml/min/1.73m 2 –Interpret with caution as estimates of GFR become less accurate as true GFR increases. –Strong suspicion of CKD Check for haematuria Quantify ACR (early morning sample) Repeat Test (significant reduction in renal function if rise in serum creatinine concentration of > 20%)

14. Stages of CKD StageEgfr (ml/min/1.73m 2 ) DescriptionTypical testing frequency 1> 90Normal or increased GFR, with other evidence of kidney damage. 12 monthly 260-89Slight decrease in GFR, with other evidence of kidney damage 12 monthly 3a 3b 45-59 30-44 Moderate decrease in GFR, with or without other evidence of kidney damage. 6 monthly 415-29Severe decrease in GFR, with or without other evidence of kidney damage. 3 monthly 5<15Established renal failure6 weekly * Monitor more closely for all patients with CKD during intercurrent illness

15. Read Coding Code as: –CKD 3a, 3b, 4 and 5 Use the QOF guideline to ensure patients are correctly coded and entered on the register. On receipt of ACR results code as CKD disease –with or –without proteinuria.

16. Symptoms Early stages tend to be asymptomatic. As kidney function worsens patients will accumulate uraemic toxins and develop symptoms such as –fatigue, nausea, anorexia, lethargy, weight loss and pruritis In stages 4 and 5 patients are likely to experience –Hyperkalaemia –Uraemia –Anaemia –Impaired Vitamin D metabolism leading to hyperparathyroidism which in turn affects bone turnover.

17. Early intervention 3 key interventions Glycaemic control (for diabetics) Blood pressure control Reducing proteinuria Progression will depend on the cause. Tubulointestinal diseases progress more slowly than glomerular, diabetic, hypertensive and polycystic diseases.

18. Glycaemic control Hyperglycaemia is an independent risk factor for nephropathy Glycaemic control has been shown to reduce the development of microalbuminuria and therefore reduces the progression of diabetic renal disease. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers have been shown to have renoprotective effects in early and late nephropathy caused by type 2 diabetes, by reducing microalbuminuria.

19. Blood Pressure Control Control of blood pressure has been demonstrated to slow the progression of CKD in several trials. Aim to keep blood pressure below 140/90mmHg In Diabetes and CKD or if ACR is > 70mg/mmol aim to keep blood pressure below 130/80mmHg

20. Anti-hypertensives in CKD DiabetesNo diabetes No proteinuria1 st line ACE inhibitorAs per NICE 2 nd line ARB ProteinuriaAs aboveAs diabetes ACR > 70mg/mmolAs aboveAs diabetes ACE inhibitors and ARBs are the preferred treatments because they reduce interglomerular pressure and lower proteinuria. Some patients will experience an initial rise in SrCr and mild increase in potassium levels.

21. Monitoring ACE/ARB Therapy Measure U&Es –before starting treatment with ACE –1-2 weeks after treatment starts and –after each dose increase Titrate to maximum tolerated dose before adding 2 nd agent. If egfr falls by < 25% or creatinine rises by < 30% continue to monitor, do not adjust doses. If egfr falls by > 25% or creatinine rises by > 30% investigate for other causes of decreasing renal function If no other cause stop drug. If potassium rises above 5.6mmol/L – stop

22. Cardiovascular Risk Cardiovascular disease is the most common cause of death in patients with CKD. Risk of CVD and associated mortality increases as GFR decreases. Prophylaxis –Offer statin for primary prevention depending on calculated cardiovascular risk –Offer statin for secondary prevention regardless of baseline lipid –Aspirin should only be offered as secondary prevention.

23. Referral CKD Stage 4 or 5 (with or without diabetes) ACR > 70mg/mmol unless known diabetic and appropriately treated ACR > 30mg/mmol and haematuria Rapidly declining eGFR (> 5ml/min/1.73m 2 in 1 year, or > 10ml within 5 years) Poorly controlled hypertension despite the use of at least 4 antihypertensive drugs at therapeutic doses. People with, or suspected of having, rare or genetic causes of CKD Suspected renal artery stenosis. Refer to urology if CKD and outflow obstruction, unless urgent medical intervention is needed.

24. Other Complications Anaemia Mineral Bone disorder

25. Anaemia In the UK CKD is the most common cause of anaemia. EPO deficiency – produced by the peritubular cells in the kidney. Other factors include: –Blood loss (during dialysis) –Shortened lifespan of red blood cells –Impaired iron haemostasis –Secondary hyperparathyroidism –Inflammation

26. Mineral and bone disorder Begins to appear from stage 3 onwards Manifests as Abnormalities in calcium, phosphate, parathyroid hormone and vitamin d metabolism Abnormalities of bone turnover, mineralisation, volume, linear growth and strength Vascular or soft tissue calcification

27. Mineral and bone disorder Initially phosphate excretion is reduced This triggers an increase in PTH, stimulating the kidney to excrete more phosphate. This ability diminishes with disease progression and phosphate levels rise. Renal hydroxylation of inactive calcidiol to the active form of vitamin D (calcitriol) is reduced. Low levels of calcitriol lead to reduced intestinal absorption of calcium resulting in hypocalcaemia. Net result of hyperphosphataemia, hypocalcaemia and low levels of calcitriol is the stimulation of PTH synthesis and secretion. 2ry hyperparthyroidism and is treated by correcting the imbalance of calcium, phosphate and calictriol.

28. Bone conditions Offer biphosphonates if indicated for prevention and treatment of osteoporosis in CKD stages 1,2,3a,3b If vitamin D supplementation is indicated –cholecalciferol or ergocalciferol for CKD stages 1,2,3a,3b –alfacaldidol or calcitriol for CKD stages 4 and 5 Serum Calcium, phosphate and parathyroid hormone concentrations should be monitored in CKD stages 4 and 5 ( but not routinely in stages 1-3b )

29. Biochemical Targets Biochemistry TestTarget Range Albumin corrected calciumCKD stages 1 to 4 2.2 to 2.5 mmol/litre PhosphateCKD stages 3 to 4 0.9 to 1.5 mmol/litre Calcium x Phosphate product Less than 4.8 mmol/litre and ideally less than 4.2 mmol/litre PTHCKD stages 1 to 3 0.9 to 5.4 pmol/litre

30. Ongoing management Consider discussing management issues with a specialist in cases where it may not be necessary for the patient to be seen. Consider routine follow up at surgery rather than specialist clinic, specifying criteria for re-referral.

31. Drug induced – renal impairment 5 to 20% of cases of acute kidney injury can be attributed to drugs and chemicals. Common nephrotoxic drugs: –ACE inhibitors, ARBs –NSAIDs –Lithium –Tacrolimus, Ciclosporin –Gold, Pencillamine –Mesalazine

32. Drug induced hyperkalaemia Potassium sparing diuretics ACE inhibitors, ARBs Digoxin overdose NSAIDs Ciclosporin Trimethoprim

33. Drug dosing in renal impairment eGFR is only an estimate of renal function Cockgroft and Gault equation is more accurate and provides creatinine clearance which is quoted in all renal dosing references. It should be used for patients with extreme body weight or where egfr is close to the borders between stages. REF sources: BNF, Renal drug handbook www.bnf.org – to calculate creatinine clearancewww.bnf.org www.ukmicentral.nhs.uk/resource/culo.htm -ibwwww.ukmicentral.nhs.uk/resource/culo.htm

34. Useful Websites NICE Guidance no 73. Chronic Kidney Disease – Early identification and management of chronic kidney disease in adults in primary and secondary care. British Renal Society – www.britishrenal.org www.britishrenal.org British Kidney patient association – www.britishkidney-pa.co.uk www.britishkidney-pa.co.uk Quality outcomes framework – www.qof.ic.nhs.ukwww.qof.ic.nhs.uk www.bnf.org

35. Questions