Chronic Renal Failure
Chronic Kidney Disease
BY
PROF. DR M.ABDELAZIZ
Chronic Renal Failure
Chronic Kidney Disease
Defined as either renal injury (proteinuria)
and / or a glomerular filtration rate <60
ml/min/1.73m2 for >3mo
Stages of CKD
Stage
Description
GFR
1
Kidney damage with normal or ↑ GFR
> 90
2
Kidney damage with mild ↓ GFR 60-89
3
Moderate ↓ in GFR
30-59
4
Severe decrease in GFR
5-29
5
Kidney failure
<15
Pathophysiology of Chronic Kidney
disease
Accumulation of nitrogenous waste products
Decrease in glomerular filtration rate
Acidosis
Decrease ammonia synthesis.
Impaired bicarbonate reabsorption
Decrease net acid excretion
Sodium Retention
Excessive renin production, oliguria
Sodium Wasting
Solute diuresis, tubular damage
Hyperkalemia
Decrease in GFR
Metabolic acidosis
Excessive potassium intake
Hyporeninemic hypoaldosteronism
Renal Osteodystrophy
Impaired renal production 1,25Dihydroxycholecalciferol
Hyperphosphatemia
Hypocalcemia
Secondary hyperparathyroidism
Growth Retardation
Inadequate caloric intake
Renal osteodystrophy, Metabolic acidosis
Anemia, Growth hormone resistance
Anemia
Decreased erythropoietin production
Iron deficiency, Vitamin B12 deficiency
Decreased erythrocyte survival
Bleeding tendency
Defective platelet function
Infection
Defective granulocyte functions
Indwelling dialysis catheters
Neurologic symptoms (fatigue, poor
concentration Headache, drowsiness, memory
loss, seizures, peripheral
neuropathy)
Uremic factors, Aluminum toxicity
hypertension
Gastrointestinal symptoms (feeding
intolerance abdominal pain)
Gastroesophageal reflux
Decreased gastrointestinal motility
Hypertension
Volume overload, Excessive renin production
Hyperlipidemia
Decreased plasma lipoprotein lipase activity
Pericarditis / cardiomyopathy
Uremic factors, Hypertension
Fluid overload
Glucose intolerance
Tissue insulin resistance
Clinical Manifestation
Depends upon underlying renal disease
* Lethargy, Anorexia, Vomiting
* Growth failure / short stature
* Failure of thrive
* Pallor
* Edema
* Hypertension
* Hematuria
* Proteinuria
* Polyuria
* UTI
Physical Examination
* Pallor & sallow appearance
* Short stature
* Bony abnormality of renal osteodystrophy
* Edema
* Hypertension
Laboratory Findings
* Elevated BUN and creatinin
* ↓ GFR
* Hyperkalemia
* Hyponatremia
* Acidosis
* Hypocalcemia
* Hyperphosphatemia
* Elevated uric acid
* Hypoproteinemia (if proteinuria)
* Normocytic, normochromic anemia
* Elevated serum cholesterol and triglyceride
* Hematuria & Proteinuria(glomerulonephritis)
GFR
GFR (ml/min /1.73m2) = k x height (cm)
S. Creatinin (mg/dl)
k= 0.33 LBW < 1 yr
0.45 term AGA < 1yr
0.55 children & adolescent female
0.70 adolescent male
ESTABLISHING THE DIAGNOSIS AND ETIOLOGY OF CKD
 The most important initial step in the evaluation of a patient
presenting with renal failure is to distinguish newly diagnosed CKD
from acute renal failure.
 the demonstration of evidence of chronic renal failure
 Hyperphosphatemia
 Hypocalcemia
 elevated PTH levels
 normocytic and normochromic anemia
 bilaterally reduced kidney size(<8.5 cm)
Treatment
Aims
* Replacing absent / diminished renal
function
* Slowing progression of renal
dysfunction
Reversible causes of renal failure
Reversible factors
Diagnostic clues
Infection
Urine culture and sensitivity tests
Obstruction
Bladder catheterization, then renal
ultrasound
Extracellular fluid volume
depletion
Orthostatic blood pressure and
pulse:↓blood pressure and ↑pulse
upon sitting up from a supine
position
Hypokalemia, hypercalcemia, and
hyperuricemia(usually >15 mg/dL)
Serum electrolytes, calcium,
phosphate
uric acid
Nephrotoxic agents
Drug history
Hypertension
Blood pressure, chest X-ray
Congestive heart failure
Physical examination, chest X-ray
TREATMENT
• SLOWING THE PROGRESSION OF CKD
 Protein Restriction
 Reducing Intraglomerular Hypertension And Proteinuria
• MANAGING COMPLICATIONS OF CHRONIC RENAL FAILURE
 Disorders of Mineral Metabolism
 Hypertension
 Cardiovascular Disease
 Uremic Pericarditis
 Congestive Heart Failure
 Anemia
 Abnormal Hemostasis
 Renal replacement therapy
SLOWING THE PROGRESSION OF CKD
Protein Restriction
• A major goal of protein restriction in CKD, is to slow the progression of
nephron injury.
• Protein restriction should be carried out in the context of an overall dietary
program that keeping nutritional status and avoids malnutrition.
• Metabolic and nutritional studies indicate that protein requirements for
patients with CKD are in the range of 0.6-0.8 g/kg per day.
• And we need give patients enough essential amino acids and energy supply
(35 kcal/kg per day).
SLOWING THE PROGRESSION OF CKD Reducing
Intraglomerular Hypertension And Proteinuria
• Progressive renal injury in CKD appears to be most closely related to the
height of intraglomerular pressure and/or the extent of glomerular hypertrophy.
• Antihypertensive therapy in patients with CKD also aims to slow the
progression of nephron injury, by reduce intraglomerular hypertension and
hypertrophy.
• ACE inhibitors(ACEI) and angiotensin receptor blockers (ARB) are now
clearly established as effective, antiproteinuric and anti-intraglomerular
hypertension agents.
• If patients present side effects of the use of ACEI/ARBthese (e.g. cough,
hyperkalemia) . We may choice of calcium channel blockers (CCB) as a second
line medicine.
MANAGING COMPLICATIONS OF CHRONIC RENAL FAILURE
Disorders of Mineral Metabolism
• Treatment should begin with dietary phosphorus restriction to <1000
mg/d. Oral phosphorus binding agents.
• Vitamin D or vitamin D analogs should be given when PTH level is more
than two to three times to normal
• It is particularly important to maintain the calcium-phosphate product in
the normal range to avoid metastatic calcification.
• Volume control with salt restriction is the essential of therapy.
• The choice of antihypertensive agent is similar to that in the general
population, ACE inhibitior, ARB, CCB, or combination.
• In all patients with CKD, blood pressure should be controlled to at
least the level of 130/80 to 85mmHg.
• In CKD patients with diabetes or proteinuria > 1g per 24 h, blood
pressure should be further reduced to 125/75 mmHg.
MANAGING COMPLICATIONS OF CHRONIC RENAL FAILURE
Hypertension
MANAGING COMPLICATIONS OF CHRONIC RENAL FAILURE
Cardiovascular
Disease
Risk factor
Life-style changes
Hyperlipidemia
Hypertension
CKD related risk factor
Congestive Heart Failure
Water and salt intake
Diuretics
Digoxin
ACE inhibitors ARB
Dialysis immediately
Uremic Pericarditis
Dialysis immediately
• As insufficient production of EPO by the diseased kidneys, recombinant
human EPO is most important in treatment of anemia caused by kidney
diseases.
• The iron status of the patient with CKD must be assessed, and adequate
iron stores should be available before treatment with EPO
MANAGING COMPLICATIONS OF CHRONIC RENAL FAILURE Anemia
Management guidelines for correction of anemia of chronic renal
disease
Erythropoietin
Starting dosage:
50-150 units/kg per week IV or SC (once, twice, or three times
per week )
Target hemoglobin(Hb):
11-12 g/dL
Optimal rate of correction
Increase Hb by 1-2 g/dL over 4-week period
Darbepoetin alfa
Starting dosage:
0.45 ug/kg administered as a single IV or SC injection once
weekly
0.75 ug/kg administered as a single IV or SC injection once
every 2 Weeks
Target Hb:
≤12 g/dL
Optimal rate of correction
Increase Hb by 1-2 g/dL over 4-week period
Iron
1. Monitor iron stores by percent transferrin saturation (TSat) and serum ferritin.
2. If patient is iron-deficient (Tsat <20%; serum ferritin<100 ug/L, administer iron, 50-100 mg IV
twice per week for 5 weeks; if iron are still low, repeat the same course.)
3. If iron indices are normal yet Hb is still inadequate, administer IV iron as outlined above;
monitor Hb, Tsat, and ferritin.
4. Withhold iron therapy when TSat >50% and/or ferritin >800 ng/mL(>800 ug/L).
MANAGING COMPLICATIONS OF CHRONIC RENAL FAILURE RENAL
REPLACEMENT THERAPY
• GFR is below 10 ml/min in CRF usually need to require renal
replacement therapy.
• Absolute indications for dialysis include:
 severe volume overload, especially in heart failure
 severe hyperkalemia and/or acidosis
 encephalopathy not otherwise explained
 pericarditis or other serositis
 symptomatic uremia (e.g., anorexia, nausea, vomiting)
 protein energy malnutrition.
MANAGING COMPLICATIONS OF CHRONIC RENAL FAILURE
Hemodialysis
• Hemodialysis requires a constant
flow of blood along one side of a
semipermeable membrane, and
with dialysate solution along the
other side. Diffusion and
convection allow the dialysate to
remove unwanted substances
from the blood while adding back
needed components.
• Most patients undergo dialysis
thrice weekly, usually for 3-4 h.
MANAGING COMPLICATIONS OF CHRONIC RENAL FAILURE
Peritoneal dialysis
Peritoneal dialysis is through a peritoneal
catheter that allows infusion of a dialysate
solution into the abdominal cavity, which
allows transfer of solutes across the peritoneal
membrane.
Patients generally have the choice of
performing their own exchanges (2-3 L of
dialysate, 4-5 times during daytime hours) or
using an automated device at night. The most
common complication of peritoneal dialysis
is peritonitis.
MANAGING COMPLICATIONS OF CHRONIC RENAL FAILURE
kidney transplantation.
Up to 50% of all patients with ESRD are
suitable for kidney transplantation.
The most common method for kidney
transplantantion is put the graft in right side
plevic cavity.
Two-thirds of kidney transplants come from
deceased donors, and the others from living
related or unrelated donors.
Immunosuppressive drugs developed very fast
in these years. (Cyclosporine, MMF,
tacrolimus and rapamycin.)
Acidosis
Sodium bicarbonate tab.( 650mg =8 mEq base)
Bacitra ((1mEq sodium citrate / ml)
Maintain serum bicarbonate > 22 mEq/L
Growth
* Short stature is long term sequela
* Growth hormone resistant state
(GH ↑, IGF ↓)
* Abnormality of IGF binding protein
* Recombinant human GH
(0.05mg/kg/24hrs)
* Continue until 50th percentile for MPH or
achieves a final adult height or undergoes
renal transplantation
Pathophysiology (Renal Osteodystrophy )
* When GFR decline to 50% of normal
* Decline in 1 hydroxylase
* Decreased production of activated Vit. D
* ↓ intestinal absorption of calcium
* Hypocalcaemia
* Secondary hyperparathyroidism(to correct hypocalcemia)
* Increased bone resorption
* When GFR declines to 25% of normal
* Hyperphosphatemia – further promotes
hypocalcemia and increased PTH
Clinical Manifestations of Renal
Osteodydtrophy
* Muscle weakness, Bone pain
Fractures with minor trauma
Rickitic changes, varus or valgus
deformity
* Ca ↓ Ph ↑, alkaline phosphate ↑, PTH normal
* Subperiosteal resorption of bone with
widening of metaphysis
Assessment of GFR
Treatment of Renal Osteodystrophy
* Low phosphorus diet
* Phosphate binders
* Calcium carbonate & calcium acetate
* Sevelamer (Renagel) non calcium binder
* Avoid aluminum based binder
* Vitamin D therapy
* Maintain calcium / phosphorus product (Ca x PO4)
at < 55
Anemia
* Inadequate erythropoitin production
* Iron deficiency
* Folic acid , Vitamin B12 deficiency
* Decreased erythrocyte survival
* Erythropoitin if Hb < 10g/dl
* Dose 50-150 mg/kg/dose S/C 1-3 times/wk
* Keep Hb between 12-13 g/dl
* Darbopoeitin alfa (longer acting)
* Dose 0.45μg/kg/wk
Hypertension
* Salt-restriction
* Diuretic therapy
* Hydrochlorothiazide 2 mg/kg/24hrs
* Furosemide 1-2 mg/kg/dose
* ACE inhibitors - angiotensin II blockers
proteinuric renal disease
(Enalapril, lisiopril, losartin)
* Calcium channel blockers (Amlodipin)
* B-Blockers (propranolol, atenolol)
for
Immunizations
* Immunization according to the schedule
* Avoid live vaccine if on immunosuppressive drugs
* Give live vaccine before renal transplantation
* Yearly influenza vaccine
* Suboptimal response
Adjustment in drug dose
adjust doses as per GFR
Strategy to slow the progression
* Optimal control of hypertension
* Maintain serum phosphorus (Ca x Ph=<55)
* Prompt treatment of infections and episodes of
dehydration
* Correction of anemia
* Control of hyperlipidemia
* Avoidance of smoking
* Prevention of obesity
* Avoid use of NSAID
* Dietary protein restriction helpful but not
recommended in children
Treatment of CRF
 Non-dialysis
 dialysis
CRF
Non-dialysis
• Diet therapy
• Treatment of reversible factors
• Treatment of the underlying disease
• Treatment of complcations of uremia
• Chinese medical herbs
CRF
Diet therapy
• Protein restriction (0.5-0.8mg/kg/d)
• Adequte intake of calories(30-35kcal/kg/d)
• Fluid intake:urine volume +500ml
• Low phosphate diet(600-1000mg/d)
• Supplement of EAA(ketosteril)
CRF
Reversible factors in CRF
• Hypertension
• Reduced renal perfusion (renal artery stenosis,
hypotension , sodium and water depletion, poor
cardiac function)
• Urinary tract obstruction
• Infection
• Nephrotoxic medications
• Metabolic factors(calcium phosphate products )
CRF
Management of complications of uremia
Hyperkalemia
• Identify treatable causes
• Inject 10-20ml 10% calcium gluconate
• 50% gluconate 50-100ml i.v.+insulin 6-12u
• Infusion 250ml 5% sodium bicarbonate
• Use exchage resin
• Hemodialysis or peritoneal dialysis
CRF
Cardiac complications
• Diuretics
• Digitalis
• Treat hypertension
• dialysis
CRF
Antihypertensive therapy
Target blood pressure 130/85mmHg
• ACE inhibitors
• Angiotension II receptor antagonists
• Calcium antagonists
• -blockers
• vesodialators
CRF
Treatment of anemia
• Recombinant human erythropoietin(rhEPO)
• 2000-3000u BIW H
• Target hemoglobin 10-12g/L
• hemotocrit 30-33%
CRF
Side effects of rhEPO
• Hypertension
• Hypercoagulation
• Thrombosis of the AVF
CRF
rhEPO resistant
• Iron deficiency
• Active inflamation
• Malignancy
• Secondary hyperparathyroid
• Aluminum overload
• Pure red cell aplasia
CRF
Treatment of renal osteodystropy
Low phosphate diet
Calcium carbonate (1-6g/d)
Vitamin D (0.25ug/d for prophylactic, 0.5ug/d for symptomatic,
pulse therapy 2-4ug/d for severe cases)
parathyroidectomy
CRF
Renal replacement therapy
• Hemodialysis
• Peritoneal dialysis
• Renal transplantation
CRF
Indications of HD
• GFR<10ml/min
• the uremic syndrome
• hyperkalemia
• acidosis
• fluid overload
CRF
Hemodialysis
Hemodialysis
弥散 Diffussion
渗透 Dialysis
Hemodialysis
超滤 Ultrofiltration
正压
对流 Conduction
负压
Contraindications of HD
•
•
•
•
•
Shoke
Severe caidioc complications
Severe bleeding
malignency , sepsis
poor condition in vascular system
Indications of CAPD
child
old people with cardiovascular disease
dibetic nephropathy
trouble of AVF
CRF
治疗
Choice of HD or CAPD
HD
PD
young
no
eldly
yes
Blood
No bleeding
Bleeding
Vascular condition
good
poor
Ecnomic situation
better
poor
Age
Cardiovascular disease
Indications of RT
• maitenance dialysis patients without contraindications of
RT
• age<60 years
CRF
Prognosis
5-year survival
Home HD 80%
RT 60%
Hospital HD 60%
CAPD 50%
CRF
Drug dosing in CRF
Redused dose and adminstration interval
 Ccr(ml/min)=[(140-years old)×body
weight(kg)]/[72×Scr(mg/dl)]
 for female: ×0.85
CRF
Acute heart failure in uremia
(key treatment?)
•
•
•
•
Diuretics
Digitalis
Treat hypertension
dialysis
Progressive Chronic
Kidney Disease
• Case studies
• Discussion
• Take home messages
Overview
• 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
• 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 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
Case 1 cont.
• 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
Discussion
Case 1
• 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
Take home message
• 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 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 1
• 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
Discussion
• 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
Take home message
• 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 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 1
• 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
Discussion
Stage
GFR
mL/min/1.73
Expected CM’s
1
>90
None or the primary disease
process
2
60-89
None, hyperparathyroidism,
increased risk CVD
3
30-59
Nocturia, anaemia,
increased creat, decreased
vit D, dyslipidaemia, abN
extracellular volume
4
15-29
Uraemic symptoms,
abnomalities electrolytes
<15
Severe uraemic symptoms,
dialysis
Discussion
5
• 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
Take home message
• 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 1 continues
• 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 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 1
• 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
Discussion
• 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
Take home message
• 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 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 1
• 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
Discussion
• 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
Take home message
• 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 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 1
•
•
•
•
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
Discussion
• 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
Take home message
• 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 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 1
• 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
Discussion
• 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
Take home message
• 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 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 1
• 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
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
Discussion
• 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%
Take home message
• 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 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 1
• 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
Discussion
• 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
Take home message
• 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 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
Case 1
• BENEDICT study
• ACEi decreased albumuria in T2DM with hypertension
and normal albumin excretion
• RENAAL study
• Similar results with AR2B
Discussion
• 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
Take home message
• Keep your chronic disease protocols handy
Conclusion
• Information taken from chapter 11 Clinical Cases in
Kidney Disease by David Harris and colleagues
Acknowledgements