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8/6/2019 Chronic Kidney Disease - Dr Ijoma
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05/08/2011 Lecture, Med Students 1
CHRONIC KIDNEY DISEASE
Chinwuba Ijoma FMCP
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05/08/2011 Lecture, Med Students 2
Definition of chronic kidney disease1
1 Kidney damage for � 3 months, as defined bystructural or functional abnormalities of the kidney,with or without decreased GFR, manifest by either:
� Pathological abnormalities
or � Markers of kidney damage, including abnormalities
in the composition of the blood or urine, or abnormalities in imaging tests.
2 GFR <60 ml/min/1.73m2 for � 3 months, with or
without kidney damage
1 National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidneydiseases: evaluation, classification, and stratification. Am J Kid Dis, 2002; 39(Suppl1):S1-S266
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05/08/2011 Lecture, Med Students 3
Classification of chronic kidney diseaseClassification of chronic kidney disease
�� * includes actions from preceding stages* includes actions from preceding stages
�� GFR, glomerular filtration rate; CKD, chronic kidney disease; CVD, cardiovascular diseaseGFR, glomerular filtration rate; CKD, chronic kidney disease; CVD, cardiovascular disease
�� Chronic kidney disease defined as either kidney damage or GFR < 60 ml/min/1.73m2 for � 3Chronic kidney disease defined as either kidney damage or GFR < 60 ml/min/1.73m2 for � 3months. Kidney damage defined as pathologic abnormalities or markers of damage,months. Kidney damage defined as pathologic abnormalities or markers of damage,including abnormalities in blood or urine tests or imaging studiesincluding abnormalities in blood or urine tests or imaging studies
stage description GFR (ml/min/1.73m2) *Action
At increased risk �90 (with CKD riskfactors)
Screening. CKD risk reduction
1 Kidney damage withnormal or GFR
�90 Diagnosis and treatment of comorbid conditions, slowingprogression, CVD risk reduction
2 Kidney damage withmild GFR
60-89 Estimating progression
3 Moderate GFR 30-59 Evaluating and treatingcomplications
4 Severe GFR 15-29 Prepare for kidney replacementtherapy
5 Kidney failure <15 (or dialysis) Replacement (if ureamic)
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05/08/2011 Lecture, Med Students 4
Global picture of CKD1
� 1.5 million patients on dialysis in yr 2000
� Projection for 2010 is 2.5 million
� 7% increase each year
1 Lysaght MJ: Maintenance dialysis population dynamics: current trends andlong term implications. J Am Soc Nephrol. 13: S37-40, 2002
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05/08/2011 Lecture, Med Students 5
Epidemiology� Worldwide increase in incidence of CKD sincethe 1980s
� In the UK incidence of ESRD 45-85 new patientsper million population (pmp)
� In the USA 268 pmp in 1996� Prevalence of pts on RRT in Europe 462 pmp in
1996
� In USA prevalence of pts on RRT 1041 pmp in
1996� In general incidence of ESRD increases with
age, reaching around 1000 pmp per yr in pts>65 yr
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05/08/2011 Lecture, Med Students 6
Common causes of end stage renal disease
Causes
Percentage of patients starting renal replacement therapy
England and
wales 1995
USA
1991-1995
Australia
1996
Japan 1994
Glomerulonephritis 12.4 11.0 34 39.8
Diabetes 13.8 37.4 18 31.2
Cystic disease 5.9 3.5 7 2.6
Hypertension 7.8 28.7 12 6.2
Pyelonephritis 9.1 4.5 4
Analgesic
nephropathy
- - 7
Unknown or 17 4.4 7
Missing 15.7 4.4
Miscellaneous 18.1 6.2 11
- Data not given
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05/08/2011 Lecture, Med Students 7
Less common causes of end stage renal disease
group Causes
metabolic Cystinosis
Oxalosis
Nephrocalcinosis
CystinuriaHyperuricaemia
vascular Ischaemic renal disease
Scleroderma
Haemolytic uraemic syndrome
Post partum renal failuredysproteinaemias Amyloid
Myeloma
Cryoglobulinaemia
Light chain deposition disease
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05/08/2011 Lecture, Med Students 8
Less common causes of end stage renal disease (2)
Group Causes
hereditary Alport syndrome
Fabry¶s disease
Tuberous sclerosis
Sickle cell disease
vasculitis Wegener¶s granulomatosis
Microscopic polyangiitis
Polyarteritis nodosa
Lupus
malignancy Renal cell carcinoma
Lymphoma
structural Cystic kidney disease other than adult onset
Congenital and acquired abnormalities of the urinary btract
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05/08/2011 Lecture, Med Students 9
Causes of chronic kidney disease in Nigeria
� CGN, chronic glomerulonephritis; HTN, hypertension; DM, diabetic nephropathy; obst
uropathy, obstructive uropathy1 Ulasi II, Ijoma CK. Prevalence of end stage renal disease secondary to diabetic
nephropathy, J coll Med.
2 Ojogeu LI. The pathological basis of end stage renal disease in Nigerians
3 Akinsola W, Adesanmi WO, et al. Diseases causing chronic renal failure in Nigeria: Aprospectiv study of 100 cases
Causes. % of
cases
Enugu
19981
Benin
19902
Ile-Ife
19983
Ibadan Lagos
Number of cases
studied
358 1980 100
CGN 22 18
HTN 15 43DM 13.2
Obst uropathy 33
Unknown
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05/08/2011 Lecture, Med Students 10
Mechanisms of progression of chronic kidney disease
Evidence from experimental models� Subtotal nephrectomy in rat leads to progressive renal
insufficiency associated with hypertension, proteinuria,and progressive scarring. Representative of latechanges of CKD
� Exp CGN (anti GBM antibodies) in rats produce acuteproliferative GN followed by chronicmembranoproliferative and sclerotic glom changes
� Models of nephrotic syndrome and glomerulosclerosisare induced in rat by inj of aminonucleoside (puromycin
and adriamycin)� Exp diabetic nephropathy induced in rats by inj of streptozotocin
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05/08/2011 Lecture, Med Students 11
Glomerulosclerosis
� Progression of CKD is associated with progressivesclerosis of glomeruli regardless of underlyingnephropathy
� Numerous hypothesis to explain progressive sclerosisand fibrosis of glomeruli
� Similarity between pathogenesis of glomerulosclerosisand large vessel atherosclerosis
� Resolution of glomerular injury depends on apoptosis of infiltrating inflammatory cells or their efflux from glomeruli
� Apoptosis of glomerular cells may lead to their depletion
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05/08/2011 Lecture, Med Students 12
Pathogenesis of glomerulosclerosis
Hypothesis Authors(s)
Glomerular hyperfiltration/hyperperfusion Hostetter and Brenner 1981
Glomerular hypertension Anderson and Brenner 1985
Nephrotoxicity of lipids Moorhead at al. 1982
Similarities with atherosclerosis El Nahas 1988Diamond and Karnovsky 1988
Glomerular hypertrophy Fogo and Ichikawa 1991
Nephotoxicity of proteinuria Remuzzi and Bertani 1990
Growth factors
platelet derived growth factor
transforming growth factor
Johnson et al 1994
Border et al 1993
Mesangial/myofibroblast differentiation Johnson et al 1994
Podocyte injury Kriz 1996
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05/08/2011 Lecture, Med Students 13
Pathogenesis of tubulointerstitial fibrosis
Hypothesis Author(s)
Adaptive tubular hypermetabolism Harris and Schrier 1988
Adaptive tubular ammoniagenesis Nath and Hostetter 1985
Nephrotoxicity of lipids Moorhead et al 1982
Nephrotoxicity of proteinuria Remuzzi and Bertani 1990
Nephrotoxicity of calcium and phosphate Alfrey 1988
Nephrotoxicity of iron Harris and Alfrey 1994
Nephrotoxicity of oxygen free radicals Nath et al 1994
Tubular cells and fibrosis Kuncio and Neilson 1991
Tubular transdifferentiation Okada, Strutz, and Neilson1994
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05/08/2011 Lecture, Med Students 14
Glomerulosclerosis
Evolves in stages
� Initial stage of glomerular endothelial
injury andinflammation
� Stage of mesangialproliferation
� Stage of glomerular sclerosis
Inflammation
Proliferation
fibrosis
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05/08/2011 Lecture, Med Students 15
Glomerular endothelial injury and
inflammation
Damage to endothelial cells induced by
� Immune insults
� Nonimmune insults1. Haemodynamic (hypertension)
2. metabolic
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05/08/2011 Lecture, Med Students 16
Damaged endothelium:
� Loses its anticoagulant, antiinflammatory,
and antiproliferative properties� Acquires new procoagulant,
proinflammatory, and mitogeniccharacteristics
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05/08/2011 Lecture, Med Students 17
New characteristics mediated through:
� Release of procoagulant factors
1. Platelet activating factor (PAF)2. Thromboxane
3. others
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05/08/2011 Lecture, Med Students 18
� Release of proinflammatory and mitogeniccytokines and growth factors:
1. Platelet derived growth factor (PDGF)
2. Interleukins
3. Tumour necrosis factor alpha
4. Chemokines
5. Monocyte chemoatractant protein 1 (MCP-1)6. Macrophage inflammatory protein-2 (MIP2)
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05/08/2011 Lecture, Med Students 19
� Damaged endothelium also express celladhesion molecules
� Changes lead to attraction of platelets,and inflammatory cells (neutrophils, andmonocytes) to the glomerular capillaries
� Infiltrating monocytes interact with
mesangial cells and stimulate their proliferation (through cell-cell interaction or through release of mitogens eg PDGF)
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05/08/2011 Lecture, Med Students 20
� Proliferating and activated mesangial cellshave capacity to revert to a messenchymalphenotype expressing markers such as -smooth muscle actin (-SMA) andsynthesis of a range of extracellular matrix(ECM) components
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05/08/2011 Lecture, Med Students 21
Resolution of glomerular injury depends on:
1. Apoptosis (programmed cell death) of
infiltrating inflammatory cells2. Efflux of infiltrating inflammatory cells
from glomerular capillaries
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05/08/2011 Lecture, Med Students 22
Epithelial cells involved in glomerulosclerosis1. Unable to replicate in response to injury2. Leeds to stretching along the GBM exposing
areas of denuded GBM3. Exposed GBM attract and interact with parietalepithelial cells leading to formation of adhesion
4. Stretched epithelial cells favour proteinuria andincreased traffic of inflammatory, mitogenic,
and fibrogenic mediators5. Infiltrating cells stimulate glom cells (through
fibrogenic factors (TGF) to produce ECM
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05/08/2011 Lecture, Med Students 23
Clinical features of CKD
� Stages 1 and 2: asymptomatic
� Stages 3 and 4:
anaemiaweakness
anorexia
metabolic bone disease
electrolyte, water and acid-baseabnormality
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05/08/2011 Lecture, Med Students 24
Clinical features of CKD (2)
Stage 5: azotaemia, uraemia
� Fluid, electrolyte, acid-base disorder
� Bone disease and disorders of calcium and
phosphate metabolism� Cardiovascular abnormalities
� Haematological abnormalities
� Neuromuscular abnormalities
� Gastrointestinal and nutritional abnormalities
� Endocrine-metabolic disorders
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05/08/2011 Lecture, Med Students 25
Diagnosis of CKD
1. Symptoms2. Signs3. Laboratory investigation:
� FBC� SEUC, Calcium, phosphate� Urinalysis� Blood glucose
� Imaging� Kidney biopsy� GFR
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05/08/2011 Lecture, Med Students 26
Treatment of CKD (1)
Stage 1 CKD.
� Diagnosis and treatment of co morbid
conditions.
� Slowing progression
� CVD risk reduction
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05/08/2011 Lecture, Med Students 27
Measures to prevent the progression of
chronic kidney disease
� Lifestyle modification
� Blood pressure control
� Glycaemic control
� Reduction of proteinuria� Protein restriction
� Lipid lowering
�
Avoidance of nephrotoxic agents� Early referral to nephrologist
� Other measures (eg., correction of anaemia)
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05/08/2011 Lecture, Med Students 28
Lifestyle modification
Recommended to all patients with CKD
� weight reduction if overweight
�
healthy eating habits� dietary salt restriction
� cessation of smoking
� moderation of alcohol consumption
� increase physical activity
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05/08/2011 Lecture, Med Students 29
Blood pressure control
� Blood pressure goal: <130/80 mm Hg
� ACEI and ARB preferred antihypertensiveagents especially in patients withproteinuria
� Adjunctive dietary salt restriction
� Diuretics and multiple medications in
addition to ACEI/ARB may be needed toachieve BP target
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05/08/2011 Lecture, Med Students 30
Glycaemic control
� Glycaemic control in diabetic patients with CKDoptimizedfasting plasma glucose <7.2 mmol/L
HbA1c < 7%
� Optimal BP <130/80 mm Hg
�Hypertensive diabetics and those withmicroalbuminuria or macroalbuminuria, whether hypertensive or not should be treated with ACEIor ARB
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05/08/2011 Lecture, Med Students 31
Reduction of proteinuria
Patients with CKD and proteinuria (with andwithout hypertension)
1. Treated with ACEI or ARB to reduceproteinuria
2. ? combined ACEI and ARB
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05/08/2011 Lecture, Med Students 32
Dietary restriction
� Manipulation of diet preventscomplications of kidney failure:
metabolic acidosis, abnomalities of calciumand phosphate metabolism, uraemic
symptoms, degree of proteinuria
� Daily allowance of 0.8g protein/kg/day
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05/08/2011 Lecture, Med Students 33
Lipid lowering
� Unclear if lipid lowering per se can slowprogression of CKD
BUT� Patients with CKD at increased risk for
cardiovascular disease
� LDL cholesterol lowered to <2.6 mmol/L(100 mg/dL)
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05/08/2011 Lecture, Med Students 34
Avoidance of nephrotoxic agents
� Nonsteroidal anti-inflamatory drugs
� Aminoglycosides
� Radiocontrast media� Certain herbs
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05/08/2011 Lecture, Med Students 35
Early referral to nephrologists
� Patients should be referred for evaluationwhen creatinine clearance <30ml/min/1.73m2 or earlier in patients at riskof rapid progression
� Identify reversible causes of renal functiondeterioration
� Implement renal protective measures
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05/08/2011 Lecture, Med Students 36
Other measures
� Correction of anaemia with EPO
� Optimization of serum calcium x
phosphate product (below 4.5 mmol2
/L2
or 55 mg2 /dL2 )
� Optimize parathyroid hormone levels (2 to3 times upper limit of normal)
� Maintenance of fluid balance
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05/08/2011 Lecture, Med Students 37
CVD risk reduction
� Screen for risk factors for CVD
Smoking history, BP measurement, body wt,
BMI, fasting plasma glucose, fasting lipid
profile, serum uric acid, 12-lead ECG
� In adults with GFR <60 ml/min/1.73m2 look for evidence of complications of CKD:
Hb, s albumin, calcium, phosphate� Determine rate of GFR decline
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05/08/2011 Lecture, Med Students 38
Treatment of CKD (2)
Stage 2 CKD
Estimating progression
� Determine underlying diagnosis
� Presence of comorbid conditions� Severity of renal impairment (GFR)� Risk for loss of kidney function� Presence of complications related to level of
kidney function� Renal imaging (ultrasound)� Serum electrolytes
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05/08/2011 Lecture, Med Students 39
Treatment of CKD (3)
Stage 3 CKD
� Evaluating and treating complications
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05/08/2011 Lecture, Med Students 40
Treatment of CKD (4)
Stage 4 CKD
Prepare for kidney replacement therapy
� Patient education and adjustment andcounselling
� Decide on mode of RRT
� Establish permanent vascular access
� Peritoneal dialysis catheter placement� Evaluate patient and prospective kidney donor
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Treatment of CKD (5)
Stage 5 CKD
Replacement (if ureamic)
� Dialysis1. Haemodialysis
2. Peritoneal dialysis
� Kidney transplantation
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05/08/2011 Lecture, Med Students 42
Global cost implication of
treating ESRD1
Dialysis cost:
�Decade 1991-2001=US$500 billion
� Decade 2001-2010=US$1.1 trillion
1 Lysaght MJ: Maintenance dialysis population dynamics: current trends and
long term implications. J Am Soc Nephrol. 13: S37-40, 2002