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Progressive Chronic Kidney Disease. Cherelle Fitzclarence August 2009. Overview. Case studies Discussion Take home messages. Case 1. 50 yo diabetic – 5 yr hx Initial poor control but good last 3 years with combo of insulin and oral hypoglycaemics Monitors own sugars

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progressive chronic kidney disease
Progressive Chronic Kidney Disease
  • Cherelle Fitzclarence
  • August 2009
overview
Overview
  • Case studies
  • Discussion
  • Take home messages
case 1
Case 1
  • 50 yo diabetic – 5 yr hx
  • Initial poor control but good last 3 years with combo of insulin and oral hypoglycaemics
  • Monitors own sugars
  • Post prandial BSL’s <10mmol/L
  • HbA1c – 5-7%
  • No peripheral neuropathy
  • No retinopathy
  • Albuminuria
  • Hypertension
case 1 cont
Case 1 cont.
  • In large epidemiological surveys for diabetes and chronic kidney disease, which of the following are correct?
    • About 1 in 20 people have abnormalities on urinalysis
    • About 8% of the general population have evidence of diabetes mellitus
    • About 1 in 10 type 2 diabetics have evidence of diabetic nephropathy
    • Those with diabetes are at risk of end stage kidney disease
case 1 cont5
Case 1 cont.
  • Question 1
  • In large epidemiological surveys for diabetes and chronic kidney disease, which of the following are correct?
    • About 1 in 20 people have abnormalities on urinalysis
    • About 8% of the general population have evidence of diabetes mellitus
    • About 1 in 10 type 2 diabetics have evidence of diabetic nephropathy
    • Those with diabetes are at risk of end stage kidney disease
discussion case 1
Discussion Case 1
  • AusDiab 1 in 7 pts in Australia have diabetes. This can be as high as 1 in 3 in indigenous Australians
  • CKD was defined by presence of blood or protein on urinalysis and/or serum creatinine >150
  • 8% of the surveyed group had diabetes and half of them were unaware of Dx
  • 30% of those surveyed had hypertension with half being unaware of Dx
  • 1 in 3 type 2 diabetics will develop nephropathy
take home message
Take home message
  • Type 2 Diabetes is now worldwide, the most common cause of end stage kidney disease
  • Indigenous populations have much higher rates of end stage kidney disease (ESKD)
  • Risk factors for ESKD
    • Hypertension
    • Diabetes
    • Family history
    • Ethnicity
    • Smoking
    • Obesity
case 18
Case 1
  • Question 2
  • Which of the following is the most appropriate investigation when screening for CKD?
    • 24 hr urinary protein
    • 24 hr urinary albumin excretion
    • Urinary prot/creat ratio on a spot urine
    • Urinary alb/creat ratio on a spot urine
    • MSU with dipstick, spot ACR, microscopy and culture
case 19
Case 1
  • Question 2
  • Which of the following is the most appropriate investigation when screening for CKD?
    • 24 hr urinary protein
    • 24 hr urinary albumin excretion
    • Urinary prot/creat ratio on a spot urine
    • Urinary alb/creat ratio on a spot urine
    • MSU with dipstick, spot ACR, microscopy and culture
discussion
Discussion
  • CARI/KCAT reviewed evidence
  • Combo screening the best –
    • U/A
    • MSU - m,c,s
    • ACR
    • BP
    • Serum creatinine (GFR)
  • This should be done yearly in high risk groups – eg diabetics, ATSI
  • Further discussion
take home message11
Take home message
  • Single urine dipstick for protein – limitations false positives, false negatives
  • Kidney function should be measured at least yearly in those at increased risk CKD
  • Screening should include measurement of BP, serum creatinine (GFR), MSU
  • Protein creatinine ratio or albumin creatinine ration
case 112
Case 1
  • Question 3
  • Which of the following is/are true statements concerning tests for assessing CKD?
    • Serum creatinine is an accurate measure of renal function and if <120 excludes nephropathy
    • GFR estimated from a formula is an accurate measure of renal function
    • A deterioration in eGFR or more than 15% over a period of months is sign of acute renal failure
    • An eGFR of >20mls/min excludes clinically relevant renal disease
case 113
Case 1
  • Question 3
  • Which of the following is/are true statements concerning tests for assessing CKD?
    • Serum creatinine is an accurate measure of renal function and if <120 excludes nephropathy
    • GFR estimated from a formula is an accurate measure of renal function
    • A deterioration in eGFR or more than 15% over a period of months is sign of acute renal failure
    • An eGFR of >20mls/min excludes clinically relevant renal disease
discussion14
Discussion
  • Serum creatinine can stay in the normal range until more than 50% of GFR is lost
  • Serum creatinine is dependent on age, weight, gender and muscle mass
  • Small people with low muscle mass, elderly, female may have significant renal impairment despite a ‘normal’ creatinine
  • GFR falls over hours, days or weeks in acute renal failure
  • GFR falls over months, years in chronic renal failure
  • eGFR is used to stage kidney disease
take home message16
Take home message
  • eGFR is useful as a screening tool for CKD
  • Should be used in conjunction with BP, U/A, ACR
  • eGFR can be used to stage CKD
case 1 continues
Case 1 continues
  • Over next 12 months, renal disease progresses
  • Creat 312
  • Risk factors for cardiovascular disease poorly controlled
    • BP >150 with 4 drug therapy on board
      • ACEI, CCB, BB, Frusemide
    • Hyperlipidaemia despite statin therapy
    • ACR increasing despite ACEI
case 118
Case 1
  • Question 4
  • In slowing the progression of renal disease and avoiding the development of malnutrition in CKD patients with an eGFR 15-30 mls/min, which of the following statements is/are correct?
    • Nephrotic patients need a high protein diet
    • Reducing proteinuria to <1g/24 hours is associated with a reduction in rate of decline off renal function
    • Proteinuria is a good measure of renal dysfunction
    • Heavy proteinuria (>3g/24hrs) predicts the response to ACEI
case 119
Case 1
  • Question 4
  • In slowing the progression of renal disease and avoiding the development of malnutrition in CKD patients with an eGFR 15-30 mls/min, which of the following statements is/are correct?
    • Nephrotic patients need a high protein diet
    • Reducing proteinuria to <1g/24 hours is associated with a reduction in rate of decline off renal function
    • Proteinuria is a good measure of renal dysfunction
    • Heavy proteinuria (>3g/24hrs) predicts the response to ACEI
discussion20
Discussion
  • CARI guidelines advise against excessive protein restriction for slowing renal function decline
  • High protein diets do little to correct the malnourished state
  • Control of BP can signifcantly reduce proteinuria esp ACEI, AR2B, aldosterone antagonists
take home message21
Take home message
  • Low protein diets may slow progression CKD but only a small impact and may increase risk of malnutrition
  • High protein diets are not effective in treating malnutrition and may accelerate CKD
  • Lowering BP decreases proteinuria
  • Degree of preservation of renal function achieved with AHA directly proportional to decrease in proteinuria
  • ACEI/AR2B’s slow progression CKD more than explained just be AHA
case 122
Case 1
  • Question 5
  • When a pt with T2DM is assessed for diabetic nephropathy, which of the following is correct?
    • The absence of proteinuria excludes diabetic nephropathy
    • Hypertension usually indicates the presence of concomitant macrovascular disease
    • The severity of diabetic nephropathy is related to the severity of hypertension
    • The absence of diabetic retinopathy excludes diabetic nephropathy
    • Kimmelstiel-Wilson lesions must be present to diagnose diabetic nephropathy
case 123
Case 1
  • Question 5
  • When a pt with T2DM is assessed for diabetic nephropathy, which of the following is correct?
    • The absence of proteinuria excludes diabetic nephropathy
    • Hypertension usually indicates the presence of concomitant macrovascular disease
    • The severity of diabetic nephropathy is related to the severity of hypertension
    • The absence of diabetic retinopathy excludes diabetic nephropathy
    • Kimmelstiel-Wilson lesions must be present to diagnose diabetic nephropathy
discussion24
Discussion
  • NHANES 3 study – T2DM with creat > 150 -1/3rd had no evidence of proteinuria
  • Due to more of a Vasculopathy (particularly microvascular) than by classic histological changes of glomerular basement membrane thickening and mesangial expansion
  • Vasculopathy is associated with hypertension and may not be associated with proteinuria
  • Vasculopathy leads to progressive CKD, accelerated by diabetic control, hypertension, proteinuria
take home message25
Take home message
  • Not all T2DM with CKD have proteinuria
  • Hypertension is common and is associated with progressive CKD
  • If hypertension is resistant, think RAS
  • Diabetic retinopathy and nephropathy are commonly but not always bound together
case 126
Case 1
  • Question 6
  • Which of the following is true regarding treatment aimed at slowing the progression of CKD and at preventing cardiovascular events such as AMI and CVA?
    • The target BP is <140/90
    • Only ACEI and AR2B slow progression CKD
    • In large studies, ACEi have been shown to improve overall survival in diabetics with large and small vessel vasculopathy
    • The presence of renovascular diesease is a contraindication to the use of ACEI or AR2B
case 127
Case 1
  • Question 6
  • Which of the following is true regarding treatment aimed at slowing the progression of CKD and at preventing cardiovascular events such as AMI and CVA?
    • The target BP is <140/90
    • Only ACEI and AR2B slow progression CKD
    • In large studies, ACEi have been shown to improve overall survival in diabetics with large and small vessel vasculopathy
    • The presence of renovascular diesease is a contraindication to the use of ACEI or AR2B
discussion28
Discussion
  • Target BP should be <130/80
  • If diabetic with protenuria <1g/24 hours target should be <120/75
  • BP decrease alone contributes to slowing CKD
  • All antihypertensives good for this but AR2B and ACEI have greatest efficacy
  • HOPE and PROGRESS show ACEI in high risk populations decrease cardiovascular events
  • Atherosclerotic renovascular disease with evidence of RAS is not an absolute contraindication to the use of ACEI or AR2B but you need to be very careful
take home message29
Take home message
  • Target BP
    • Proteinuria <1g/24hours 130/80
    • Proteinuria >1g/24hours 120/75
  • For diabetic CKD target BP <120/75
  • AR2B and ACEI preferred but any agent ok as long as BP controlled
  • Atherosclerotic renovascular disease not absolute contraindication to ACEi
case 130
Case 1
  • Question 7
  • In general, which of the following results in 50yo indicate need for referral to Nephrologist?
    • Diabetic with eGFR <60 and poorly controlled hypertension
    • A non diabetic with an eGFR 30-60mls, proteinuria <0.5g/day, controlled BP
    • Proteinuria >1g/day with normal eGFR
    • Unexplained decline in kidney function (>15% drop GFR over 3 months)
case 131
Case 1
  • Question 7
  • In general, which of the following results in 50yo indicate need for referral to Nephrologist?
    • Diabetic with eGFR <60 and poorly controlled hypertension
    • A non diabetic with an eGFR 30-60mls, proteinuria <0.5g/day, controlled BP
    • Proteinuria >1g/day with normal eGFR
    • Unexplained decline in kidney function (>15% drop GFR over 3 months)
discussion32
Discussion
  • Late referral to Nephrologist associated with poorer outcomes, greater morbidity for RRT and pall care groups
  • Guidelines only and controversial – if not sure err on side of caution
  • In general, stable patients with eGFR >30 don’t require referral but a significant number can benefit from referral and progression may be able to be averted
take home message33
Take home message
  • Indications for referral to Nephrologist
    • Proteinuria > 1g/24 hrs
    • eGFR < 30mls in non diabetics
    • eGFR < 60mls in diabetics
    • Unexplained decline in kidney function
    • Glomerular haematuria with proteinuria
    • CKD with difficult to control hypertension
    • Otherwise unexplained anaemia
case 134
Case 1
  • Question 8
  • Pt’s Hb dropped to 90 and treatment with epo commenced. Which of the following are true?
    • Most common cause for anaemia in CKD with GFR<60 is bleeding from the upper GIT
    • If pt on EPO, iron therapy is not required if serum ferritin is >100
    • Treating the anaemia of CKD is not required until HB<100
    • Anaemia occurs earlier in the course of CKD in diabetic than non diabetic patients
case 135
Case 1
  • Question 8
  • Pt’s Hb dropped to 90 and treatment with epo commenced. Which of the following are true?
    • Most common cause for anaemia in CKD with GFR<60 is bleeding from the upper GIT
    • If pt on EPO, iron therapy is not required if serum ferritin is >100
    • Treating the anaemia of CKD is not required until HB<100
    • Anaemia occurs earlier in the course of CKD in diabetic than non diabetic patients
discussion36
Discussion
  • Small increased risk in GIH
  • Anaemia of CKD is due to relative erythropoietin deficiency and show up in stage 3 and is more severe in diabetics
  • Prior to epo, iron deficiency was rare due to blood transfusions
  • Now relative iron deficiency is a problem
  • EPO can only be prescribed once Hb <100
  • Aim Hb 120
  • Worse outcomes if Hb higher than this
  • Renal anaemia is often iron responsive
discussion37
Discussion
  • Aims
  • Prior to starting epo – ferritin >100
  • Once epo started – ferritin 400-600
  • Transferrin saturation >20% prior to epo therapy
  • Transferrin saturation 30-40% post epo starting
  • Adequate iron stores required for epo to work
  • Iron deficiency is most common cause of hyporesponsiveness to epo
take home message38
Take home message
  • Impaired absorption of oral iron and increased utilization of iron with EPO therapy have contributed to the development of iron deficiency
  • Optimize responsiveness to EPO – targets for ferritin 300-600 and saturation 30-40%
case 139
Case 1
  • CKD progresses and he needs dialysis. GP questions whether other therpay may have prevented such a rapid progression to ESKD
  • Question 9
    • For which of the following therapies is there level 1 evidence for efficacy in the CKD population
      • Cholesterol lowering with statins both to slow progressive decline of renal function and to reduce the increased cardiovascular risk associated with CKD
      • Uric acid reduction slows progression
      • Exercise and weight loss improve insulin resistance and slow progression
      • Aldosterone blockade can further slow progression
      • AR2B can further slow progression in pts on ACEI
case 140
Case 1
  • CKD progresses and he needs dialysis. GP questions whether other therpay may have prevented such a rapid progression to ESKD
  • Question 9
    • For which of the following therapies is there level 1 evidence for efficacy in the CKD population
      • Cholesterol lowering with statins both to slow progressive decline of renal function and to reduce the increased cardiovascular risk associated with CKD
      • Uric acid reduction slows progression
      • Exercise and weight loss improve insulin resistance and slow progression
      • Aldosterone blockade can further slow progression
      • AR2B can further slow progression in pts on ACEI
discussion41
Discussion
  • Decrease uric acid, cessation of smoking, weight loss all slow progression but evidence is poor; studies small, non randomised, case studies
  • Statins thought to help but again studies not good – no RCT
  • AR2B and ACEI combo thought to help if patient proteinuric – COOPERATE study
take home message42
Take home message
  • Allopurinol, weight loss, cessation of smoking, exercise may all slow progression of CKD but no level one evidence
  • Beneficial effect of lipid though to be present but still waiting level 1 evidence
  • AR2B and ACEi together can help delay progression in pt with proteinuria
case 143
Case 1
  • Question 10
  • In type 2 DM ACEi and AR2B have been shown to slow the development of progression of nephropathy in pts who are
    • Normoalbuminuric and normotensive
    • Normoalbuminuric and hpertensive
    • Microalbuminuric and hypertensive
    • Macroalbuminuric and hypertensive
case 144
Case 1
  • Question 10
  • In type 2 DM ACEi and AR2B have been shown to slow the development of progression of nephropathy in pts who are
    • Normoalbuminuric and normotensive
    • Normoalbuminuric and hypertensive ***
    • Microalbuminuric and hypertensive
    • Macroalbuminuric and hypertensive
discussion45
Discussion
  • BENEDICT study
    • ACEi decreased albumuria in T2DM with hypertension and normal albumin excretion
    • RENAAL study
    • Similar results with AR2B
take home message46
Take home message
  • ACEi and AR2B have been proven in hypertensive type 2 diabetics to slow progression of CKD, development of microalbuminuria, macroalbuminuria
  • Don’t use combination in patients who are simply hypertensive
conclusion
Conclusion
  • Keep your chronic disease protocols handy
acknowledgements
Acknowledgements
  • Information taken from chapter 11 Clinical Cases in Kidney Disease by David Harris and colleagues