1. Chronic Kidney Disease Jennifer Peebles 16 th Feb 2010

2. Chronic Kidney Disease Long term condition caused by damage to the kidneys. Long term condition caused by damage to the kidneys. Describes abnormal kidney function or structure. Describes abnormal kidney function or structure. Usually asymptomatic and so often unrecognised. Usually asymptomatic and so often unrecognised. Often occurs in the context of other chronic diseases such as cardiovascular disease and diabetes. Often occurs in the context of other chronic diseases such as cardiovascular disease and diabetes. Average prevalence of 6-11% in Europe and USA, rises with age. Average prevalence of 6-11% in Europe and USA, rises with age. Large UK primary care study (NEOERICA project) suggested prevalance of CKD stages 3-5 of 8.5% (5.8% men and 10.6% women). Large UK primary care study (NEOERICA project) suggested prevalance of CKD stages 3-5 of 8.5% (5.8% men and 10.6% women). Prevalence likely to increase with aging population and increase in conditions such as diabetes. Prevalence likely to increase with aging population and increase in conditions such as diabetes.

3. Why is it important? Major UK health burden due to its prevalence Major UK health burden due to its prevalence Can progress to End stage renal disease Can progress to End stage renal disease Where no longer any sufficient function and so dialysis/transplant necessary to maintain life. Where no longer any sufficient function and so dialysis/transplant necessary to maintain life. Renal replacement therapy accounts for over 2% of total NHS budget. Renal replacement therapy accounts for over 2% of total NHS budget. When advanced – there is higher risk of mortality, particularly from cardiovascular disease When advanced – there is higher risk of mortality, particularly from cardiovascular disease 2003 UK retrospective study on incidence and outcomes of new CKD cases showed only 4% developed ESRD by 5.5 yr follow up, but 69% had died (about 50% from cardiovascular cause) 2003 UK retrospective study on incidence and outcomes of new CKD cases showed only 4% developed ESRD by 5.5 yr follow up, but 69% had died (about 50% from cardiovascular cause)

4. Why is it important? Because it is asymptomatic, it is often diagnosed late Because it is asymptomatic, it is often diagnosed late currently 30% of people with advanced kidney disease are referred late causing increased morbidity and mortality currently 30% of people with advanced kidney disease are referred late causing increased morbidity and mortality However, tests for detection are simple and easily available. However, tests for detection are simple and easily available. Treatment can slow the progression of CKD, and reduce cardiovascular mortality. Treatment can slow the progression of CKD, and reduce cardiovascular mortality. (QOF – total of 38 points for CKD indicators) (QOF – total of 38 points for CKD indicators)

5. Detecting kidney damage Direct evidence: Direct evidence: Imaging can show structural abnormalities - (Polycystic kidneys, pyelonephritis, reflux nephropathy, renovascular disease) Imaging can show structural abnormalities - (Polycystic kidneys, pyelonephritis, reflux nephropathy, renovascular disease) Ultrasound Ultrasound MRI MRI Isotope scanning Isotope scanning Renal Biopsy Histopathology – to show underlying glomerular disease (IgA nephropathy, focal glomerulosclerosis) Renal Biopsy Histopathology – to show underlying glomerular disease (IgA nephropathy, focal glomerulosclerosis) Indirect evidence: Indirect evidence: Urinalysis – showing leakage of blood cells or protein into the urine. Urinalysis – showing leakage of blood cells or protein into the urine.

6. Detecting kidney damage Proteinuria Proteinuria Albumin is the principal component in proteinuria in glomerular disease Albumin is the principal component in proteinuria in glomerular disease Albumin Creatinine Ratio has greater sensitivity than Protein Creatinine Ratio for detection of low levels of proteinuria. Albumin Creatinine Ratio has greater sensitivity than Protein Creatinine Ratio for detection of low levels of proteinuria. PCR is cheaper to analyse. PCR is cheaper to analyse. NICE suggest ACR be used in preference to PCR for initial detection/identification in CKD, while PCR can be used later for quantification and monitoring except in diabetics. NICE suggest ACR be used in preference to PCR for initial detection/identification in CKD, while PCR can be used later for quantification and monitoring except in diabetics. SIGN suggest measurement method depends on context. SIGN suggest measurement method depends on context. Urine dipstick – widely available and low cost but not reliable for detection. Urine dipstick – widely available and low cost but not reliable for detection. ACR – for detecting/monitoring diabetic nephropathy. ACR – for detecting/monitoring diabetic nephropathy. PCR – can be used in non-diabetics in populations with high prevalence proteinuria to exclude CKD, PCR – can be used in non-diabetics in populations with high prevalence proteinuria to exclude CKD, - and in non-diabetics with CKD to predict risk of progression. - and in non-diabetics with CKD to predict risk of progression. Indicates higher cardiovascular risk and risk of progression in CVD Indicates higher cardiovascular risk and risk of progression in CVD No evidence that asymptomatic UTI causes proteinuria. No evidence that asymptomatic UTI causes proteinuria.

7. Detecting kidney damage - proteinuria Range for ACR/PCR Range for ACR/PCR Definition Urinary albumin excertion (mg/24hrs) ACR(mg/mmol)PCR(mg/mmol) 24-hr urinary protein excretion (g/24hrs) Normal albumin excertion 10 Microalbuminuria(diabetics)30-300 ≥ 2.5 (men) ≥ 3.5 (women) Proteinuria>300 ≥ 30 ≥ 50 0.5 Higher levels of proteinuria ≥ 70 ≥ 100 1

8. Detecting kidney damage Haematuria Haematuria Frank – exclude infection/malignancy Frank – exclude infection/malignancy Microscopic – single reading a common (2%) finding so rpt. Microscopic – single reading a common (2%) finding so rpt. Risk of CKD low with isolated microscopic haematuia, however renal or urinary pathology often present. Risk of CKD low with isolated microscopic haematuia, however renal or urinary pathology often present. Exclude infection Exclude infection >50yrs urgent referral to urology >50yrs urgent referral to urology <50yrs renal evaluation (especially if proteinuria/reduced eGFR) <50yrs renal evaluation (especially if proteinuria/reduced eGFR)

9. Measuring renal function GFR is the best measure of overall renal function GFR is the best measure of overall renal function Defined as the volume of plasma filtered by the glomeruli per unit time. Defined as the volume of plasma filtered by the glomeruli per unit time. Accurate measurement difficult, and methods such as gold standard inulin clearance too difficult and unsuitable for primary care. Accurate measurement difficult, and methods such as gold standard inulin clearance too difficult and unsuitable for primary care. Urea and Creatinine concentrations Urea and Creatinine concentrations Convenient but insensitive Convenient but insensitive GFR has to fall by half before significant increase in creatinine becomes apparent GFR has to fall by half before significant increase in creatinine becomes apparent Creatinine affected by various factors including age, sex, ethnicity, body habitus (muscle mass), and also diet. Creatinine affected by various factors including age, sex, ethnicity, body habitus (muscle mass), and also diet. Consumption of cooked meat in particular has a rapid but transient effect Consumption of cooked meat in particular has a rapid but transient effect Also significant increase in creatinine if clotted sample not separated for amalysis within 16hrs. Also significant increase in creatinine if clotted sample not separated for amalysis within 16hrs. Prediction equations for estimating GFR Prediction equations for estimating GFR

10. Prediction equations Equations improve correlation between creatinine and GFR by taking into account other variables. Equations improve correlation between creatinine and GFR by taking into account other variables. Cockcroft and Gault: Cockcroft and Gault: age, sex, weight and creatinine age, sex, weight and creatinine MDRD (Modification of Diet in Renal disease): MDRD (Modification of Diet in Renal disease): age, sex, ethnicity and creatinine age, sex, ethnicity and creatinine

11. Prediction equations Limitations: Limitations: Not completely accurate. Not completely accurate. Not valid in children, pregnant women or ARF. Not valid in children, pregnant women or ARF. Perform better at lower eGFR Perform better at lower eGFR At >60ml/min/1.73m 2, tends to underestimate GFR so higher risk of false positive. At >60ml/min/1.73m 2, tends to underestimate GFR so higher risk of false positive. MDRD - validated only in Caucasian and African- American populations. MDRD - validated only in Caucasian and African- American populations. MDRD – tendency to overestimate renal function in malnourished or amputees. MDRD – tendency to overestimate renal function in malnourished or amputees.

12. Measuring renal function Studies have shown that prediction equations are better than creatinine for urinary creatinine clearance. Studies have shown that prediction equations are better than creatinine for urinary creatinine clearance. Studies comparing MDRD and Cockcroft-Gault equations suggest they are either comparable or that MDRD is superior. Studies comparing MDRD and Cockcroft-Gault equations suggest they are either comparable or that MDRD is superior. NICE have concluded that the MDRD equation performs best. NICE have concluded that the MDRD equation performs best. MDRD is used by most labs in their automatic reporting. MDRD is used by most labs in their automatic reporting. Report only eGFR <60ml/min/1.73m 2. Report only eGFR <60ml/min/1.73m 2. Patients should be advised to avoid eating meat for at least 12 hrs before eGFR is tested. Patients should be advised to avoid eating meat for at least 12 hrs before eGFR is tested. Most calculate results assuming Caucasian race, so correction needed for African-Caribbeans. Most calculate results assuming Caucasian race, so correction needed for African-Caribbeans.

13. Classification of CKD Current system based of eGFR. Current system based of eGFR. US National Kidney Foundation Kidney Disease Outcomes Quality Initiative – stratified CKD into 5 stages. US National Kidney Foundation Kidney Disease Outcomes Quality Initiative – stratified CKD into 5 stages. Cut off between stages arbitrary but do have clinical correlates Cut off between stages arbitrary but do have clinical correlates

14. Classification of CKD For CKD - evidence of persisting damage at 90days. For CKD - evidence of persisting damage at 90days. Stages 1 & 2 only diagnosed with proteinuria/albuminuria, haematuria or renal structural abnormalities. Stages 1 & 2 only diagnosed with proteinuria/albuminuria, haematuria or renal structural abnormalities. UK Consensus Conference - divided stage 3 into two parts. UK Consensus Conference - divided stage 3 into two parts. Studies had shown stage 3 encompassed a large number of asymptomatic patients. In those with eGFR <45, complications of CKD were far more common so this was set as lower threshold. Studies had shown stage 3 encompassed a large number of asymptomatic patients. In those with eGFR <45, complications of CKD were far more common so this was set as lower threshold. Stage 3A - eGFR 45-59ml/min/1.73m 2. Stage 3A - eGFR 45-59ml/min/1.73m 2. Stage 3B - eGFR 30-44ml/min/1.73m 2. Stage 3B - eGFR 30-44ml/min/1.73m 2. With proteinuria, the suffix p should be used e.g Stage 3Ap. With proteinuria, the suffix p should be used e.g Stage 3Ap. Patients on dialysis should be have suffix D i.e Stage 5D. Patients on dialysis should be have suffix D i.e Stage 5D. Suffix T indicates functioning transplant (can be any stage). Suffix T indicates functioning transplant (can be any stage).

15. Decline in eGFR with age. Classification takes no account of patient age. Classification takes no account of patient age. Unclear whether decline is ‘normal ageing’ phenomenon, a true increase in prevelance in CKD with age or both. Unclear whether decline is ‘normal ageing’ phenomenon, a true increase in prevelance in CKD with age or both. NICE advise for those >70yrs, with eGFR >45 if stable and no other evidence of kidney damage is unlikely to be associated with complications of CKD. NICE advise for those >70yrs, with eGFR >45 if stable and no other evidence of kidney damage is unlikely to be associated with complications of CKD. SIGN advise that age associated decline in eGFR should be afforded the same significance as decline in other situations. SIGN advise that age associated decline in eGFR should be afforded the same significance as decline in other situations.

16. Identification of patients with CKD Routine surveillance of high risk patients: Routine surveillance of high risk patients: Diabetes Mellitus Diabetes Mellitus Hypertension Hypertension Cardiovascular disease Cardiovascular disease Structural Renal tract disease, calculi & outflow obstuction incl prostatic Structural Renal tract disease, calculi & outflow obstuction incl prostatic Multisystem disease with potential renal involvement e.g. SLE Multisystem disease with potential renal involvement e.g. SLE Family history of CKD stage 5 or hereditary kidney disease Family history of CKD stage 5 or hereditary kidney disease Increased awareness of other risk factors Increased awareness of other risk factors Smokers Smokers Low socioeconomic status. Low socioeconomic status. Obese patients Obese patients Chronic NSAID use? Chronic NSAID use? Incidental finding Incidental finding Urine Dipstick, renal function or structural abnormality on imaging. Urine Dipstick, renal function or structural abnormality on imaging.

17. New eGFR < 60 – what now? Repeat the test Repeat the test If unwell/oliguric – repeat urgently ?AKI If unwell/oliguric – repeat urgently ?AKI Otherwise within 2 weeks to exclude rapid deterioration Otherwise within 2 weeks to exclude rapid deterioration NICE suggest at least 3 measurements over no less than 90 days for diagnosis. NICE suggest at least 3 measurements over no less than 90 days for diagnosis. Clinical assessment of the patient. Clinical assessment of the patient. History History Examination Examination Repeat bloods Repeat bloods Urine examination Urine examination ? Imaging ? Imaging

18. Clinical assessment – History taking Present History Present History Urinary symptoms? (e.g. outflow obstrution/haematuria) Urinary symptoms? (e.g. outflow obstrution/haematuria) Symptoms of systemic disease? Symptoms of systemic disease? Symptoms of CKD? (tiredness, reduced appetite, itch, oedema, muscle cramps) Symptoms of CKD? (tiredness, reduced appetite, itch, oedema, muscle cramps) PMHx PMHx e.g. ?DM, ?CVD, HTN, ?renal stones, BPH e.g. ?DM, ?CVD, HTN, ?renal stones, BPH FMHx FMHx PKD, ESRD PKD, ESRD Medication Medication Any nephrotoxic? E.g Lithium, NSAIDs, diuretics/ACEi Any nephrotoxic? E.g Lithium, NSAIDs, diuretics/ACEi Any meds needing dose adjustment? Any meds needing dose adjustment? NB - recommendations in most publications including BNF are based on creatinine clearance estimation by Cockcroft-Gault. No evidence that this can be used interchangeably with MDRD.

19. Clinical assessment – Examination/Investigation BP BP Pulse Pulse Signs of hypovolaemia/heart failure/sepsis Signs of hypovolaemia/heart failure/sepsis Palpable bladder/Polycystic kidneys Palpable bladder/Polycystic kidneys Prostate examination in men Prostate examination in men Urine examination Urine examination Urinalysis – proteinuria/haematuria Urinalysis – proteinuria/haematuria ACR/PCR on early morning sample ACR/PCR on early morning sample Non-diabetics ACR >30mg/mmol or PCR >50 Non-diabetics ACR >30mg/mmol or PCR >50 Diabetics – microalbuminauria = ACR≥2.5mg/mmol for males (2.5-30) = ACR≥3.5mg/mmol for females (3.5-30) Diabetics – microalbuminauria = ACR≥2.5mg/mmol for males (2.5-30) = ACR≥3.5mg/mmol for females (3.5-30)

20. Clinical assessment – ? Imaging Ultrasound is 1 st line test for imaging in CKD Ultrasound is 1 st line test for imaging in CKD SIGN - “if relevant symptoms” SIGN - “if relevant symptoms” NICE - obstuctive symptoms NICE - obstuctive symptoms - FMHx PKD - progressive CKD (eGFR decline >5 in 1yr, >10 in 5yr), - macroscopic / persistant microscopic haematuria - macroscopic / persistant microscopic haematuria - stage 4 or 5 CKD - being considered for renal biopsy

21. Management of CKD - Aims to minimise progression of CKD to minimise progression of CKD to minimise development of CVD to minimise development of CVD to identify those who with progressive decline in renal function will develop ESRD in their lifetime. to identify those who with progressive decline in renal function will develop ESRD in their lifetime. Identify those needing referral to nephrology: Identify those needing referral to nephrology: Significant proteinuria (ACR>70mg/mmol, PCR>100mg/mmol) Significant proteinuria (ACR>70mg/mmol, PCR>100mg/mmol) Microscopic Haematuria 50yrs to urology) Microscopic Haematuria 50yrs to urology) Advanced CKD – stage 4 or 5 Advanced CKD – stage 4 or 5 Functional consequences – e.g anaemia, bone disease, refractory HTN Functional consequences – e.g anaemia, bone disease, refractory HTN Immediate referral for ARF, malignant HTN, K >7mmol/L, nephritic syndrome. Immediate referral for ARF, malignant HTN, K >7mmol/L, nephritic syndrome.

22. Lifestyle advice in CKD Smoking cessation Smoking cessation Exercise Exercise Weight reduction if high BMI/ abdominal circumference Weight reduction if high BMI/ abdominal circumference Alcohol consumption Alcohol consumption Low salt diet – but beware salt substitutes with high potassium levels. Low salt diet – but beware salt substitutes with high potassium levels. Low protein diet only in advanced CKD (stage 4-5) and after dietician assessment. Low protein diet only in advanced CKD (stage 4-5) and after dietician assessment.

23. Blood pressure and proteinuria reduction BP should be measured at least once a year. BP should be measured at least once a year. BP should be controlled to slow CKD progression and reduce proteinuria. BP should be controlled to slow CKD progression and reduce proteinuria. Usual HTN targets of <140/90 mm/Hg for most patients Usual HTN targets of <140/90 mm/Hg for most patients Target maximum of 130mm/Hg systolic (& 80mm/Hg diastolic) for patients with ACR >70/PCR>100mg/mmol, or for diabetics with microalbuminuria. Target maximum of 130mm/Hg systolic (& 80mm/Hg diastolic) for patients with ACR >70/PCR>100mg/mmol, or for diabetics with microalbuminuria. Any reduction in proteinuria in CKD reduces the relative risk of disease progression Any reduction in proteinuria in CKD reduces the relative risk of disease progression there should be no lower target as the greater the reduction from baseline, the greater the effect on slowing reduction in GFR. there should be no lower target as the greater the reduction from baseline, the greater the effect on slowing reduction in GFR.

24. Blood pressure and proteinuria reduction ACEi and ARBs offer both cardio- and renoprotective effects ACEi and ARBs offer both cardio- and renoprotective effects Dilatation of the efferent renal arteriole reducing intraglomerular pressure and reducing proteinuria independent of systemic blood pressure effects. Dilatation of the efferent renal arteriole reducing intraglomerular pressure and reducing proteinuria independent of systemic blood pressure effects. ACEi can prevent the development of diabetic nephropathy. ACEi can prevent the development of diabetic nephropathy. Both reduce albuminuria and progression from microalbuminuria to macroalbuminuria in diabetics. Both reduce albuminuria and progression from microalbuminuria to macroalbuminuria in diabetics. Both reduce proteinuria in non-diabetics. Both reduce proteinuria in non-diabetics. Diabetics with microalbuminuria should be treated with an ACEi or ARB irrespective of BP. Diabetics with microalbuminuria should be treated with an ACEi or ARB irrespective of BP. In non-diabetics with CKD and protienuria, ACEi or ARB are the agents of choice to reduce proteinuria & progression of CKD. In non-diabetics with CKD and protienuria, ACEi or ARB are the agents of choice to reduce proteinuria & progression of CKD.

25. Blood pressure and proteinuria reduction Some evidence that the beneficial effect of ACEi and ARBs may also apply to people with CKD without diabetes or proteinuria, but NICE conclude not strong enough to recommend these over other antihypertensives. Some evidence that the beneficial effect of ACEi and ARBs may also apply to people with CKD without diabetes or proteinuria, but NICE conclude not strong enough to recommend these over other antihypertensives. Commencing ACEi/ARBs: Commencing ACEi/ARBs: Before starting check creatinine, eGFR and K. Before starting check creatinine, eGFR and K. Check again 1-2 weeks after starting and after each dose change. Check again 1-2 weeks after starting and after each dose change. A fall in eGFR of ≤25% is acceptable/good – suggests they are working. A fall in eGFR of ≤25% is acceptable/good – suggests they are working. A fall in eGFR of >25% from pre-treatment level may indicate renal artery stenosis, also stop if K>6mmol/l. A fall in eGFR of >25% from pre-treatment level may indicate renal artery stenosis, also stop if K>6mmol/l. Some evidence that non-dihydropyridine calcium channel blockers may also reduce proteinuria Some evidence that non-dihydropyridine calcium channel blockers may also reduce proteinuria Should be considered for those intolerant of ACEi/ARBs Should be considered for those intolerant of ACEi/ARBs

26. Cardiovascular prophylaxis Risk assessment as for patients without CKD. Risk assessment as for patients without CKD. Statin for 10yr CVD risk >20%. Statin for 10yr CVD risk >20%. Antiplatelet therapy Antiplatelet therapy NICE: no mention for primary prevention NICE: no mention for primary prevention SIGN: should be considered for stage 1-3 for 10yr CVD risk>20% SIGN: should be considered for stage 1-3 for 10yr CVD risk>20%

27. Other considerations Complications to be aware of: Complications to be aware of: Anaemia – monitor Hb in Stages 3(B) – Stage 5, consideration for EPO. Anaemia – monitor Hb in Stages 3(B) – Stage 5, consideration for EPO. Renal bone disease - stage 4-5, tends to be evaluated in 2dry care. Renal bone disease - stage 4-5, tends to be evaluated in 2dry care. Patient education Patient education Particularly ‘predialysis psychoeducation’ for those with progressive CKD who may eventually need RRT. Particularly ‘predialysis psychoeducation’ for those with progressive CKD who may eventually need RRT.

28. QOF IndicatorPoints CKD1 Practice can produce a register of patients >18yrs with CKD stage 3-5 6 CKD2 % of patients on register with record of BP in last 15months 6 CKD3 % of patients on register with BP in last 15months of 140/85 or less 11 CKD5 % of patients on register with HTN and proteinuria on ACEi or ARB (unless contraindicated or adverse reaction) 9 CKD6 % of patients on register with record of urinary ACR/PCR in last 15months 6

29. Summary CKD is Common, under recognised and under diagnosed CKD is Common, under recognised and under diagnosed Early identification and treatment can slow progression of CKD and also reduce associated increased risk of CVD. Early identification and treatment can slow progression of CKD and also reduce associated increased risk of CVD.Questions?