1. Chronic Kidney Disease:
An Update
(Part II)
Yassin Ibrahim El-Shahat
Consultant: Nephrology & Hypertension
Chief Medical Officer
Burjeel Hospital, Abu Dhabi
2. Objectives
Upon completion of this talk the attendant will be able to:
Understand the pathophysiology of Chronic Kidney Disease
Recognize the signs and symptoms of Chronic Kidney Disease
Identify the disease progression and treatment interventions
4. ESRD
&
death
Stages in Progression of Chronic Kidney
Disease and Therapeutic Strategies
Complications
Screening
for CKD
risk factors
CKD risk
reduction;
Screening for
CKD
Diagnosis
& treatment;
Treat
comorbid
conditions;
Slow
progression
Estimate
progression;
Treat
complications;
Prepare for
replacement
Replacement
by dialysis
& transplant
Normal
Increased
risk
CKDDamage GFR
5. Natural History of CKD
Most CKD has a
logarithmic progression
and is predictable
6. Early treatment can make a difference
100
10
0
No Treatment
Current Treatment
Early Treatment
4 7 9 11
Time (years)
Kidney Failure
GFR(mL/min/1.732)
7. CKD is prevalent in CVD
Ix, et al., 2003; Anavekar, et al., 2004; Shlipak, et al., 2004.
0
20
40
60
CAD
GFR ≤60 mL/min
AMI
GFR ≤60 mL/min
CHF
GFR ≤60 mL/min
23%
46%
33%
PatientsWithCKD(%)
8. In addition to ESRD, CKD leads to CVD
Go, et al., 2015
1.0
2.8
3.4
2.0
1.4
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
≥ 60 45-59 30-44 15-29 < 15
AdjustedHazardRatio
eGFR
Adjusted* hazard ratio for CVD events
Leading cause of
morbidity and mortality in
patients with CKD at all
stages
Ischemic CAD
Hypertension and LVH
Congestive heart failure
Uremic pericarditis
11. Intensive glycemic control lessens progression from
microalbuminuria in Type 1 diabetes–goal in Type 2 is less
clear
- DCCT, 1993
- ACCORD, 2008
Antihypertensive therapy with ACE Inhibitors or ARBs
lessens proteinuria and progression
- Giatras, et al., 1997
- Psait, et al., 2000
- Jafar, et al., 2001
Blood pressure below 130/80 is beneficial
- Sarnak, et al., 2005
We can have an impact on progression
of CKD
15. What non-drug therapies should
clinicians recommend?
Quit smoking, and exercise 30 min/d on most days
Limit alcohol intake
Maintain BMI within normal range
Eat a diet high in fruits, vegetables, and whole grains
DASH diet recommended if GFR >60 mL/min per 1.73 m2
and high normal blood pressure or stage 1 hypertension
If hypertension present: restrict salt intake <2.0 g/d
Most patients with CKD should avoid high-protein diets
Stage 4 or 5: consider low-protein diet (0.6 g/kg/d)
16. Therapeutics in CKD
Non Pharmacologic
Risk Factor Modification
Pharmacologic
Treatment of complications
17. Parameter Target Agent used
BP 130/80 mmHg or
125/75 in DM and those with
proteinuria.
Start with ACEI or ARBs if proteinuria or DM
microalbuminuria - caution in the elderly and those with
atherosclerosis. Monitor eGFR within 1-2 weeks of initiation,
review if eGFR decreases by ≥15%, stop at ≥25%.
Proteinuria Lowest achievable ACEI/ ARBs
S. Cholesterol Refer to national guidelines
Lifestyle Standard CV risk reduction measures, including salt restriction
Avoid NSAIDs, COX2s and radiocontrast agents
Anaemia Hb 10.5-12.5 g/dl Replace deficiencies
Erythropoietin in CKD stage 4-5
Renal osteodystrophy
(Stages 4 & 5 only)
Ca: 2.2-2.35 mmol/l
PO4 <1.7 mmol/l
Calcium carbonate / Alfacalcidol
Phosphate binders
Acidosis Venous Bicarbonate > 22
mmol/l
Sodium bicarbonate
Undernutrition Adequate calorie & normal protein intake
Infections Chest infections
Hepatitis B
Immunize: influenza & pneumococcus
vaccination (CKD stages 4-5)
CKD management guidelines
18. Pharmacology in CRF
Pharmacokinetics –
drug absorption, distribution,
metabolism & excretion
Pharmacodynamics –
A drug’s mechanism of action
and effect at the target site
19. Alterations in Drug Responses in CRF
Gastrointestinal impairments affect absorption of
medications
Volume of distribution (Vd) – the availability of a drug
distributed in body tissues is increased or decreased by
alterations in body composition or protein binding
Metabolism of medications altered - the kidneys produce
many enzymes involved in drug metabolism including
cytochrome P-450
Decreased glomerular filtration rate affects drug excretion
Campoy, S, Elwell, R.(2005). Pharmacology & CKD. AJN, 105(9),60-72.
20. Medication Considerations in CKD
Dilantin – increased Vd related to protein binding
changes and low albumin, increasing risk of drug toxicity
Digoxin – increased Vd leading to toxicity due to
decreased renal excretion
Insulin – metabolism of insulin decreases, requiring
dose reduction
Tylenol and procainamide – liver metabolized drugs
with metabolites that are excreted renally, can
accumulate leading to drug toxicity
Campoy, S, Elwell, R.(2005). Pharmacology &
CKD. AJN, 105(9),60-72.
21. Medication Considerations in CKD (Cont.)
Impaired renal excretion leads to toxic drug
accumulations with:
Diamox
Aminoglycoside antibiotics -
(tobramycin & gentamycin)
Atenolol
Captopril
Lithium
Vancomycin
Metformin
Neurontin
Topamax
22. What is the role of Blood Pressure control
in patients with diabetes and CKD?
Identify and treat factors associated with
progression of CKD
HTN
Proteinuria
Glucose control
23. Rodicio JL & Alcazar JM. ESH Newsletter 2011, No. 4
Hypertension in Chronic Kidney Disease
24. Management of Hypertension in CKD
• Investigations into the nature of the patient’s renal disease
• Blood pressure goal
• Non-pharmacological treatment
• Pharmacological treatment
25. What is the role of blood pressure
management?
To reduce CVD risk, treat to <140/90 mm Hg
If proteinuria is significant or urine albumin-to-creatinine ratio
>30mg/g: treat to <130/80 mm Hg
Use ACE inhibitors and ARBs (improve kidney outcomes)
Combination therapy often needed
Diuretics reduce extracellular fluid volume, lower BP, and reduce
risk for CVD
Diuretics also potentiate effects of antihypertensives
Thiazide-type diuretic if GFR ≥30 mL/min per 1.73 m2
Loop diuretic if GFR <30 mL/min per 1.73 m2
26. Clinical Practice Guidelines for
Management of Hypertension in CKD
Type of Kidney Disease Blood
Pressure
Target
(mm Hg)
Preferred Agents
for CKD, with or
without
Hypertension
Other Agents
to Reduce CVD Risk
and Reach Blood
Pressure Target
Diabetic Kidney Disease
<130/80
ACE inhibitor
or ARB
Diuretic preferred, then
BB or CCB
Nondiabetic Kidney
Disease with Urine Total
Protein-to-Creatinine
Ratio 200 mg/g
Nondiabetic Kidney
Disease with Spot Urine
Total Protein-to-Creatinine
ratio <200 mg/g None preferred
Diuretic preferred, then
ACE inhibitor, ARB, BB
or CCB
Kidney Disease in Kidney
Transplant Recipient
CCB, diuretic, BB, ACE
inhibitor, ARB
28. KDIGO Blood Pressure Work Group. Kidney Int Suppl 2012
KDIGO Guidelines
• Non-diabetic adults with CKD:
≤140 mmHg systolic and ≤90 mmHg diastolic if normoalbuminuric
≤130 mmHg systolic and ≤80 mmHg diastolic if micro or macroalbuminuric
• Diabetic adults with non dialysis-dependent CKD:
≤140 mmHg systolic and ≤90 mmHg diastolic if normoalbuminuric
≤130 mmHg systolic and ≤80 mmHg diastolic if micro or macroalbuminuric
• Kidney transplant recipients:
≤130 mmHg systolic and ≤80 mmHg diastolic
• Elderly people with CKD:
probably ≤140 mmHg systolic and ≤90 mmHg diastolic, but set targets after
consideration of co-morbidities
29. Summary
Management of Hypertension in CKD
ESH/ESC 2013
Guidelines
AHA/ACC/CDC
Scientific Advisory
JNC 8 ASH/ISH
Statement
In general <140/90 <140/90 ≥ 60 years:
<150/90
< 60 years:
< 140/90
>140/90
Exception
or
special
comment
Elderly > 80 years
< 150/90
Elderly < 80 years
< 150/90
Fit elderly
< 140/90
Diabetes
< 140/85
CKD+Proteinuria
< 130/90
„lower“ targets for
• elderly
• LVH
• systolic or diastolic
LV dysfunction
• diabetes
• kidney disease Diabetes
< 140/90
CKD
< 140/90
< 80 years
< 150/90
CKD +
Proteinuria
< 130/80
31. KDIGO Blood Pressure Work Group. Kidney Int Suppl 2012
• Generalised arterial vasodilatation:
Reduction of blood pressure
• Vasodilatation particularly of
the efferent glomerular arteriole:
Reduction of glomerular pressure
Reduction of proteinuria
Long-term renoprotection
• Reduction of adrenal aldosterone
secretion: But note aldosterone
breakthrough
ACEIs and ARBs
• Indicated in all hypertensive
patients with CKD,
especially in proteinuric
diabetic and non-diabetic
CKD.
• Will lead to deterioration of
renal function in short term
but then to slower
progression of renal failure
in longer term.
32. IDNT and RENAAL Studies
Brenner BM et al. NEJM 2001Lewis EJ et al. NEJM 2001
Time to primary composite end point (doubling of
serum creatinine, end-stage renal disease, or death)
34. When should clinicians prescribe
ACE inhibitors versus ARBs?
Prescribe either for reducing progression of diabetic
nephropathy
Prescribe either in hypertension or in diabetes when urine
albumin excretion >30mg / 24h
Prescribe either in non-diabetic proteinuria
Do not combine an ACE inhibitor with an ARB in CKD stage
IV and CKD stage V
Monitor patients closely for side effects and adjust dose as
needed
Safe to continue medication if GFR declines < 30% over 4
months and serum potassium <5.5 mEq/L
35. ACEIs and ARBs: Side Effects
Hyperkalaemia
Higher risk of hyperkalaemia in combination with potassium-
sparing diuretics
ACEI: mainly renal excretion (except fosinopril, trandolapril),
ARB mainly hepatic excretion, therefore reduce dose (stop?) at
GFR <15 mL/min
Other treatment strategies in Hyperkalaemia:
• Dietary advice
• Furosemide
• Dose reduction of ACEI/ARB
36. ACEIs and ARBs: Side Effects
Schoolwert AC et al. Circulation 2001
AKI, especially in:
• Bilateral renal stenosis
• Diabetes and sepsis
• Combination with
NSAIDs
• State of volume
depletion (diarrhoea/
vomiting)
37. Diuretics
Thiazide diuretics: e.g. Hydrochlorothiazide, Bendroflumethiazide
Thiazide-like diuretics: e.g. Chlorthalidone, Indapamide
Loop diuretics: e.g. Furosemide, Torasemide
Widely used as patients with CKD are characterised by sodium and water retention
For antihypertensive therapy:
GFR >50 mL/min: Thiazides alone or in combination with distal diuretics (e.g.
spironolactone)
GFR <30 mL/min: Loop diuretics. Avoid distal (potassium sparing) diuretics.
38. Calcium Channel Blockers
• Antihypertensive action
• Oedema and fluid retention
• Dihydropyridines predominantly dilate the afferent arteriole
and thereby increase GFR but also the glomerular
pressure
• Non-DHPs seem not to have this effect.
40. Beta-Blockers
• Beta-blockers reduce increased sympathetic activity in CKD
• Indication in heart failure (but not in acute LVF)
• Often combined with diuretics in RCTs but no reason why
not combine with others
• No robust evidence for superiority of certain beta-blockers
43. What is the role of glycemic control in
patients with diabetes and CKD?
Identify and treat factors associated with
progression of CKD
HTN
Proteinuria
Glucose control
44. What is the role of glycemic control in
patients with diabetes and CKD?
Good glycemic control reduces:
Progression of CKD
Incidence proteinuria
Maybe end-stage renal disease
However, CKD increases risk for hypoglycemia
Current CKD guidelines recommend a goal A1c level ~7%
Avoid using Metformin if GFR <30 mL/min per 1.73 m2
45. Lancet 1998; 352: 837-53
UKPDS
3867 patients with type 2 DM (median age 54 yrs) over
ten years
Intensive tx with sulfonylureas and insulin (HbA1c 7.0%)
vs conventional tx (7.9%)
25% RR in microvascular complications (95% CI 7-40;
p=0.0099)
46. Therapeutics in CKD
Non Pharmacologic
Risk Factor Modification
Pharmacologic
Treatment of complications
49. Acid Base Imbalance
Damaged kidneys are unable to excrete the 1 mEq/kg/day of
acid generated by metabolism of dietary proteins.
NH3 production is limited because of loss of nephron mass
Decreased filtration of titrable acids – sulfates, phosphates
Decreased proximal tubular bicarb reabsorption, decreased
positive H ion secretion
Arterial pH: 7.33 - 7.37; serum HCO3 rarely below 15 –
buffering offered by bone calcium carbonate and phosphate
Should be maintained over 22
Treatment: Sodium bicarbonate, calcium carbonate, sodium
citrate
50. Metabolic acidosis
Seldom significant until GFR <30 mL/min per 1.73 m2
Contributes to CKD progression, insulin resistance,
decreased cardiorespiratory fitness, altered bone
metabolism
Use alkali therapy with serum bicarbonate <22 mmol/L to
maintain serum bicarbonate levels within normal range
How should clinicians manage metabolic
complications?
51. Metabolic acidosis
Muscle catabolism
Metabolic bone disease
Sodium bicarbonate
Maintain serum bicarbonate > 22 meq/L
0.5-1.0 meq/kg per day
Watch for sodium loading
Volume expansion
HTN
52. Hematological Abnormalities
Anemia
Chronic blood loss, hemolysis, marrow suppression by uremic
factors, and reduced renal production of EPO
Normocytic, normochromic
Rx: Iron and Epo as needed
Coagulopathy
Mainly platelet dysfunction – decreased activity of platelet factor
III, abnormal platelet aggregation and adhesiveness and
impaired thrombin consumption
Increased propensity to bleed – post surgical, GI Tract,
pericardial sac, intracranial
Increased thrombotic tendency – nephrotic syndrome
53. Major Minor
Inflammation/infection Hyperparathyroidism
Iron deficiency Aluminium toxicity
Inadequate dialysis B12/folate deficiency
Haemolysis
Bone marrow disorders
Haemoglobinopathies
Anti-EPO antibodies = PRCA
(pure red cell aplasia)
Non-adherence
Causes of ESA Hyporesponsiveness
(Macdougall, 2003)
54. Mechanisms in anemia leading to myocardial damage in chronic kidney
disease: Combination of factors secondary to diminished glomerular
filtration rate (GFR) and low hemoglobin. Consequences of anemia include
the hemodynamic compensatory mechanisms th...
Madhumathi Rao, Brian J.G. Pereira, Kidney International, Volume 68, Issue 4, 2005, 1432–1438
Optimal anemia management reduces CV
morbidity, mortality, and costs in CKD
55. Conclusions:
Treatment of Anemia in CKD
Target Hgb
< 12 g/dL
RCTs in both D-CKD and ND-CKD
CHOIR Post-hoc analysis: Hgb level and Epo dose
Getting to Target
Problem of Hgb cycling
Causes of Hgb cycling multifactorial
Difficult to achieve Hgb in narrow range: broader range or no range
Hyporesponsive patient
30-40% of D-CKD
DRIVE 1 and 2 support greater role for iron therapy
Using iron is cost-effective
56. Causes of Anaemia in CKD
• EPO deficiency
• Chronic blood loss (via GI tract/haemodialyser)
• Iron deficiency
• Vitamin B12 or folate deficiency
• Hypothyroidism
• Chronic infection or inflammation
• Hyperparathyroidism
• Chronic blood loss
• Aluminium toxicity
• Malignancy
• Haemolysis
• Bone marrow infiltration
• Pure red cell aplasia
57. Clinical Effects of Anaemia
Symptoms
Fatigue
Decreased exercise capacity
Exertional dyspnoea
Anorexia
Cognitive impairment
Diminished quality of life
Poor memory
Reduced libido
Pallor
Poor sleep pattern
Reduced immune function
Reduced platelet function
Cardiovascular Effects
Increased cardiac output/stroke volume
Tachycardia
Decreased vascular resistance
Worsening of pre-existing anginal
symptoms/myocardial ischaemia
Left ventricular hypertrophy
Impairment in nitric oxide synthesis
Limited oxygen reserve
Abnormal angiogenesis
58. How should clinicians manage patients
with anemia?
Measure hemoglobin and hematocrit, RBC indices,
reticulocyte count, serum iron, percent transferrin
saturation, vitamin B12 and folate levels, serum ferritin
Identify potential sources of bleeding
Treat with erythropoietin when hemoglobin drops below 9-
10 g/dL
Prescribe oral / IV iron as needed to maintain iron stores
Maintain hemoglobin levels <11.5 g/dL
Use caution with active malignancy or history of stroke
60. NEJM 2000; 342(20): 1478-83
Mineral metabolism
Calcium and phosphate metabolism abnormalities
associated with:
Renal osteodystrophy
Calciphylaxis and vascular calcification
14 of 16 ESRD/HD pts (20-30 yrs) had calcification on CT
scan
3 of 60 in the control group
84. Calcium or Aluminium Containing Non-Calcium, Non-Aluminium Containing
Aluminium Hydroxide Lanthanum Carbonate
Calcium Acetate Magnesium Carbonate
Calcium Carbonate Sevelamar Hydrochloride and Carbonate
Summary of Phosphate Binders
85. Parathyroid sestamibi scan (with
technetium Tc 99m-MIBI) demonstrating
uptake in all 4 glands consistent with 4-
gland hyperplasia
Secondary Parathyroid Adenoma
86. Top Tip: Utilise dietary phosphate restriction, a
phosphate binder and calcitriol in all ESRD patients.
• Secondary hyperparathyroidism occurs as a result of hyperphosphataemia, hypocalcaemia
and impaired synthesis of renal vitamin D with reduction in serum calcitriol levels
• Patients with secondary hyperparathyroidism have a range of symptoms
• The aim of treatment is is to reduce: (1) the occurrence and/or severity of uraemic bone
disease; and, (2) cardiovascular morbidity and mortality caused by elevated serum levels of
PTH and 'calcium x phosphate' product
• Treatment includes control of phosphate retention, maintaining serum calcium
concentration within the normal range and prevention of excess PTH secretion
• The UK Renal Association recommends measuring serum calcium, phosphate and PTH
levels when GFR is < 60ml/min/1.73m 2 (CKD stage 3 and above). Italso recommends, in
dialysis patients:
• Serum calcium, should be maintained within the normal range and be between 2.2 and 2.5
mmol/L, with avoidance of hypercalcaemic episodes
• Serum phosphate should be maintained between 1.1 and 1.7 mmol/L
• The target range for parathyroid hormone (measured using an intact PTH assay) should be
2-9 times the upper limit of normal for the assay used
Tailor dosing to guideline targets
87. JAMA 1993; 269(23): 3015-23
Dyslipidemia
Abnormalities in the lipid profile
Triglycerides
Total cholesterol
NCEP recommends reducing lipid levels in high-risk
populations
Targets for lipid-lowering therapy considered the same as
those for the secondary prevention of CV disease
88. Nutrition
Think about uremia
Catabolic state
Anorexia
Decreased protein intake
Consider assistance with a renal dietician
89.
90.
91.
92.
93.
94.
95.
96.
97. Key Clinical Trials
Normal Hematocrit Study (Besarab, 1998)
• Open-label trial of 1233 HD patients with heart failure/IHD
• Epoetin given either to maintain a normal (42 ±3 %) or low (30 ±3 %) haematocrit
• Primary endpoint – MI/death
• Study was stopped after 29 months due to the higher (albeit non-statistically significant) death rate in the
normal haematocrit group – 183 vs 150 deaths
Note: this study raised concerns regarding the risks of trying to attain a higher level of haemoglobin
CHOIR (Singh, 2006)
• Open-label trial of 1432 CKD patients randomised to either a low-Hb (11.3 g/dl) or high-Hb arm (13.5 g/dl)
• Primary endpoints included death and CV events (and CVA)
• 125 events occurred among the high-Hb group and 97 events among the low-Hb group (HR 1.34; P = 0.03)
• No quality-of-life difference between the two groups
CREATE (Drueke, 2006)
• Multicentre trial of 603 CKD patients randomised to high-Hb (13.0-15.0 g/dl) or low-Hb (10.5-11.5 g/dl)
• No difference between groups in terms of primary endpoints (CV/death)
• Study ended up being underpowered
TREAT (Pfeffer, 2009)
• Multicentre, double-blind, placebo-controlled RCT
• Darbepoetin (Aranesp) (aiming for Hb 13 g/dl) vs placebo* (Hb of 9 g/dl) in 4038 predialysis CKD patients with
type 2 diabetes and anaemia
• No difference in primary CV endpoint/death
• Improved symptoms in treatment arm
• Two-fold increased risk of CVA in treatment arm
98. Treatment
Increase the Adequacy of Dialysis
Increasing the dialysis prescription has been shown to augment the response to ESA therapy.
Iron Management
The causes and diagnosis of iron deficiency in CKD are listed above. If a patient is considered
deficient in iron, then there are a number of iron preparations (both oral and intravenous) that are
available.
Erythropoiesis-Stimulating Agents (ESAs)
EPO is a large glycoprotein (30.4 KDa) that is injected intravenously (HD patients), or
subcutaneously. Current UK guidance recommends starting therapy when the Hb falls below 11
g/dl, but of late there has been a tendency for lower Hb’s to be accepted before intervening with
ESA therapy following data from the TREAT trial (see Key Clinical Trials). ESA therapy is
effective in correcting anaemia in the vast majority of patients, with 5-10% of patients deemed
ESA hyporesponsive.
Correction of Haematinic Deficiency
Folate (and less commonly vitamin B12) is a low molecular weight substance that may be lost
during haemodialysis (especially high-flux. Serum folate is not as accurate as red cell folate level,
as a marker of folate deficiency, but is the most commonly used initial screening test.
99. Top Tips: Consider an ESA in any CKD patient
with Hb <11 g/dL. Keep Ferritin >200 ng/L
• There is no worldwide consensus concerning target ranges for haemoglobin
and iron/ferritin levels. The new KDIGO renal anaemia guidelines are expected
in mid-late 2012
• Functional iron deficiency occurs when stored iron is sufficient but circulating
iron is deficient. It may be detected when serum ferritin levels are decreased
and TSAT levels are <20%, but this is not a hard and fast rule
• TSAT (transferrin saturation) is calculated by the following formula: Serum Fe ÷
TIBC x 100%
• Blood transfusions distort patients’ red cell indices, and it can take 3-4 months
for the normal steady state to be resumed
• Treatment includes Erythropoiesis-Stimulating Agents (ESAs), correcting iron
deficiency, treating infection/inflammation and increasing dialysis dose
• Major causes of ESA hyporesponsiveness are iron deficiency,
inflammation/infection and inadequate dialysis
100. Specific targets and potential therapeutic strategies
to inhibit or slow the progression of CKD
101. Antifibrotic strategies for treating CKD
Agent Setting Primary outcome and/or results
Preclinical studies
Anti-TGF-β antibody Leprdb/db diabetic mice3, 4
Reduction in plasma TGF-β1 levels,
prevention of increases in plasma
creatinine levels and glomerular
mesangial matrix expansion,
associated with decreased renal
mRNAs encoding collagen IV and
fibronectin
Anti-TGF-β antibody
Rats with chronic allograft rejection
nephropathy5
Reduction of proteinuria, attenuation
of mononuclear cell infiltration and
interstitial fibrosis along with
downregulation of mRNA levels of
TGF-β1, TGF-β2, and
proinflammatory cytokines, or with
upregulation of mRNA levels of HGF,
BMP-5, and BMP-7
Anti-TGF-β antibody Mice with STZ-induced diabetes12
Prevention of glomerular
hypertrophy, attenuated gain in
kidney weight, and attenuation of
increased mRNA levels of TGF-β1,
type II TGF-β receptor, collagen IV,
and fibronectin
Reduction of TGF-β isoform mRNA
102. Non-antifibrotic strategies
for treating CKD
Agent Setting Primary outcome and/or results
Vascular calcification
Klotho overexpression Mice with CKD62
Enhanced phosphaturia, improved
renal function, and decreased
calcification
Exogenous Klotho
Mice with UUO67 and mice with
adriamycin-induced CKD67
Inhibition of renal β-catenin
activation, suppression of
myofibroblast activation, reduction in
extracellular matrix protein
expression, and amelioration of renal
fibrosis
Oxidative stress and NADPH oxidases
NOX-2 deficiency
Mice with STZ-induced diabetic
nephropathy74
No beneficial effect on renal
function, and marked increase in
NOX-4 at the protein level in the
kidney
GKT136901* Leprdb/db diabetic mice80,81 Reduction in albuminuria and
oxidative stress
GKT137831* Diabetic Apoe−/− mice83
Reduction in ROS production,
inflammation, vascular
complications, and profibrotic
107. How should clinicians manage metabolic
complications?
Vitamin D and phosphorous metabolism
Derangements occur if GFR <30-40 mL/min per 1.73 m2
Use dietary phosphorous restriction, phosphate binders, and vitamin
D supplementation
Hyperkalemia
Dangerous elevations occur mostly only in stages 4 / 5
Use dietary potassium restriction, and if necessary, sodium
polystyrene sulfonate
Hyperkalemia >6mEq/L or hyperkalemic EKG change requires
emergency treatment with IV calcium gluconate, glucose, insulin,
bicarbonate (if acidosis present), and sodium polystyrene sulfonate
If these measure fail, hemodialysis may be needed
111. C
Syndromes
Acute cardio-
renal (type 1)
Chronic cardio-
renal (type 2)
Acute reno-
cardiac (type 3)
Chronic reno-
cardiac (type 4)
Secondary CRS
(type 5)
Organ failure
sequence
Definition
Acute worsening
of heart function
(AHF–ACS)
leading to kidney
injury and/or
dysfunction
Chronic
abnormalities in
heart function
(CHF-CHD)
leading to kidney
injury or
dysfunction
Acute worsening
of kidney function
(AKI) leading to
heart injury
and/or
dysfunction
Chronic kidney
disease (CKD)
leading to heart
injury, disease
and/or
dysfunction
Systemic
conditions leading
to simultaneous
injury and/or
dysfunction of
heart and kidney
Primary events
Acute heart failure
(AHF) or acute
coronary
syndrome (ACS)
or cardiogenic
shock
Chronic heart
disease (LV
remodelling and
dysfunction,
diastolic
dysfunction,
chronic
abnormalities in
cardiac function,
cardiomyopathy)
AKI CKD
Systemic disease
(sepsis,
amyloidosis, etc.)
115. Trends in the interactions of diabetes,
CHF & CKD: 2002-2003
LVH and dilated CM are
the most ominous risk
factors for excess
mortality and morbidity
High cardiac output
Extracellular fluid overload
AV shunt
Anemia
Medicare: general Medicare CKD patients continuously enrolled in
Medicare Parts A & B for two consecutive years (numbers estimated
from 5 percent sample)
116. Hillege et al, 2002 Arnlov et al, 2005
Microalbuminuria and Survival
117. CKD and CVD Risk
HOORN Study, Henry et al, 2002 Pooled Analysis, Weiner et al, 2004
eGFR<60
eGFR>60
118. Kidney Int 1995; 47(1): 186-92
CV disease I
70% of HD patients have concomitant CV disease
Heart disease leading cause of death in HD patients
LVH can be a risk factor
119. Am J Kidney Dis 2001; 37(6): 1191-200
CV disease II
Patients with CKD (non-HD) have poor prognosis after MI
Prospective CCU registry of 1724 pts with STEMI
Graded increase in RR of post-infarct complications:
arrhythmia, heart block/asystole, acute pulmonary
congestion, acute MR, and cardiogenic shock
Decreased survival over 60 months (RR 8.76; p<0.0001)
120. How should clinicians treat cardiovascular
risk factors?
Aggressively reduce risk factors for atherosclerosis
Encourage a healthy lifestyle regarding smoking, exercise, alcohol
intake, and BMI
Assess for other cardiovascular risk factors
Check BP, and treat hypertension
Screen for diabetes, and treat elevated blood glucose
For people with CKD, ACC/AHA guidelines recommend treatment with
statin or statin/ezetimibe combination regardless of cholesterol level
122. How should clinicians monitor patients
with CKD?
Once a year check BP; GFR; hemoglobin level; and serum
potassium, calcium, phosphorous, PTH, and albumin
More frequent monitoring may be needed if
CKD is moderate to severe
History of rapid decline in kidney function
There are risk factors for faster progression (smoking, poorly
controlled hypertension or diabetes, proteinuria)
Exposure to a cause of acute kidney injury
Active or changing therapeutic interventions to treat CKD,
hypertension, or proteinuria
124. What are the indications for renal
replacement therapy?
Volume overload unresponsive to diuretics
Pericarditis
Uremic encephalopathy
Major bleeding secondary to uremic platelets
Hypertension that does not respond to treatment
Hyperkalemia and metabolic acidosis that cannot be
managed medically
Progressive “uremic” symptoms, which include fatigue;
anorexia, nausea or vomiting; malnutrition; and insomnia
126. When should clinicians consider
consulting a nephrologist for treating
patients with CKD?
To manage complications of advanced CKD
For assistance with a care plan for advanced or complex
renal disease
For therapeutic decision-making about complex acute or
chronic glomerular and tubulointerstitial diseases
When dialysis is anticipated
When GFR first falls below 30 mL/min per 1.73 m2
To discuss treatment for end-stage renal disease
For counseling, psychoeducational interventions, and
referral for fistula placement
127. Should clinicians screen patients for CKD?
If so, how?
Screen individuals at increased risk for CKD
Those older than 55 years
Those with hypertension, diabetes, or obesity
Screening: estimate GFR and test for kidney damage markers
Serum creatinine to estimate GFR
Urinalysis for leukocytes and red blood cells
Qualitative test for urine albumin (or protein) with dipstick; if
positive, measure amount to calculate an albumin-to-creatinine
(or a protein-to-creatinine) ratio
128. Are preventive measures useful for patients at
increased risk for CKD?
Diabetes
Hyperglycemia is associated with development and progression
of diabetic nephropathy
Good glycemic control reduces CKD risk
Maintain hemoglobin A1c ~7% with dietary interventions, oral
hypoglycemic medications, and insulin
Hypertension
Hastens renal function decline
Treatment reduces CV risks but not CKD risk
Maintain blood pressure <140/90 mm Hg with lifestyle
modification and antihypertensive drug therapy
129. People with CKD do progress to kidney
failure–especially those middle-aged
and younger
Levey, et al., 2015
0
10
20
30
40
50
60
70
80
Progressed to Kidney
Failure
Died Before Kidney
Failure
Died After Kidney
Failure
Proportionofpatients
Long term (7 year) follow up of 408 non-diabetic CKD patients
(mean initial GFR=39, mean initial age=52 year old)
130. Primary care providers –
First line of defense against CKD
• Primary care professionals can play a significant role in
early diagnosis, treatment, and patient education
• Therapeutic interventions for diabetic CKD are similar to
those required for optimal diabetes care
• Control of glucose, blood pressure, and lipids
• A greater emphasis on detecting CKD, and managing it
prior to referral, can improve patient outcomes
CKD is Part of Primary Care
132. Should clinicians screen patients for CKD?
If so, how?
Screen individuals at increased risk for CKD
Those older than 55 years
Those with hypertension, diabetes, or obesity
Screening: estimate GFR and test for kidney damage markers
Serum creatinine to estimate GFR
Urinalysis for leukocytes and red blood cells
Qualitative test for urine albumin (or protein) with dipstick;
if positive, measure amount to calculate an albumin-to-
creatinine (or a protein-to-creatinine) ratio
133. Urine albumin & protein to creatinine ratio
Albumin-to-creatinine ratio
Normal to mildly increased <30 mg/g
Moderately increased 30-300 mg/g
Severely increased >300 mg/g
Protein-to-creatinine ratio
Normal to mildly increased <150 mg/g
Moderately increased 150-500 mg/g
Severely increased >500 mg/g
Type 2 diabetes: screen for albuminuria annually
Positive when >30 mg/g creatinine in a spot urine sample
134. Diabetics
Hypertensives
CVD
Relatives of CKD5
Systemic vasculitis
Recurrent UTIs, and urological problems
Chronic NSAIDs
Screening At-risk Population
135. ESRD
&
death
Stages in Progression of Chronic Kidney
Disease and Therapeutic Strategies
Complications
Screening
for CKD
risk factors
CKD risk
reduction;
Screening for
CKD
Diagnosis
& treatment;
Treat
comorbid
conditions;
Slow
progression
Estimate
progression;
Treat
complications;
Prepare for
replacement
Replacement
by dialysis
& transplant
Normal
Increased
risk
CKDDamage GFR
136. Are preventive measures useful for
patients at increased risk for CKD?
Diabetes
Hyperglycemia is associated with development and
progression of diabetic nephropathy
Good glycemic control reduces CKD risk
Maintain hemoglobin A1c ~7% with dietary interventions,
oral hypoglycemic medications, and insulin
Hypertension
Hastens renal function decline
Treatment reduces CV risks but not CKD risk
Maintain blood pressure <140/90 mm Hg with lifestyle
modification and antihypertensive drug therapy
137. Key points
The serum creatinine level is not enough!
Target BP for CKD
<130/80 mm Hg
<125/75 mm Hg in proteinuria
HTN and proteinuria are the two most important
modifiable risk factors for progressive CKD
138. CLINICAL BOTTOM LINE: Screening and
Prevention...
Who to screen
Individuals > 55 years of age
Individuals with hypertension or diabetes
How to screen
Estimate GFR from serum creatinine, and do a urinalysis
In patients with diabetes
• Screen for proteinuria with urine albumin-to-creatinine or protein-to-
creatinine ratio
• Maintain strict glycemic control to prevent CKD
139. CLINICAL BOTTOM LINE: Diagnosis...
o CKD is defined as kidney damage or a GFR <60 mL/min
per 1.73 m2 for > 3 months
o Classify
• Diabetic nephropathy
• Hypertensive nephropathy
• Nondiabetic, nonhypertensive kidney disease
• Then, into groups based on levels of GFR and albuminuria
o History and physical exam often point to a cause
o Definitive diagnosis requires:
• Diagnostic tests
• Renal ultrasound
• Sometimes renal biopsy
140. CLINICAL BOTTOM LINE: Treatment...
The goals are to slow progression of CKD and prevent
complications from cardiovascular disease
Maintain normal blood pressure in patients with hypertension
Include an ACE inhibitor or an ARB when treating hypertension
Control glycemia in patients with diabetes
Manage electrolyte disturbances, anemia, secondary
hyperparathyroidism, and malnutrition
Refer to a nephrologist as CKD progresses
143. Goals of Care in CKD
Slow decline in kidney function
Blood pressure control1
ACR <30 mg/g: ≤140/90 mm Hg
ACR 30-300 mg/g: ≤130/80 mm Hg*
ACR >300 mg/g: ≤130/80 mm Hg
Individualize targets and agents according to age,
coexistent CVD, and other comorbidities
ACE or ARB
*Reasonable to select a goal of 140/90 mm Hg, especially for moderate albuminuria (ACR 30-300
mg/g.)2
1) Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. Kidney Int Suppl.
(2012);2:341-342.
144. Slowing CKD Progression: ACEi or ARB
Risk/benefit should be carefully assessed in the elderly and
medically fragile
Check labs after initiation
If less than 25% SCr increase, continue and monitor
If more than 25% SCr increase, stop ACEi and evaluate
for RAS
Continue until contraindication arises, no absolute eGFR
cutoff
Better proteinuria suppression with low Na diet and diuretics
Avoid volume depletion
Avoid ACEi and ARB in combination1,2
Risk of adverse events (impaired kidney function,
hyperkalemia)
1) Kunz R, et al. Ann Intern Med. 2008;148:30-48.
2) Mann J, et al. ONTARGET study. Lancet. 2008;372:547-553.
145. Goals of Care in CKD: Glucose Control
Target HbA1c ~7.0%
Can be extended above 7.0% with comorbidities or
limited life expectancy, and risk of hypoglycemia
Risk of hypoglycemia increases as kidney function
becomes impaired
Declining kidney function may necessitate changes to
diabetes medications and renally-cleared drugs
NKF KDOQI. Diabetes and CKD: 2012 Update.
Am J Kidney Dis. 2012 60:850-856.
146. Modification of Other CVD Risk
Factors in CKD
Smoking cessation
Exercise
Weight reduction to optimal targets
Lipid lowering therapy
In adults >50 yrs, statin when eGFR ≥ 60
ml/min/1.73m2; statin or statin/ezetimibe combination
when eGFR < 60 ml/min/1.73m2
In adults < 50 yrs, statin if history of known CAD, MI,
DM, stroke
Aspirin is indicated for secondary but not primary
prevention
Kidney Disease: Improving Global Outcomes
(KDIGO) CKD Work Group. Kidney Int Suppls.
2013;3:1-150.
147. Detect and Manage CKD Complications
Anemia
Initiate iron therapy if TSAT ≤ 30% and ferritin ≤ 500 ng/mL
(IV iron for dialysis, Oral for non-dialysis CKD)
Individualize erythropoiesis stimulating agent (ESA) therapy:
Start ESA if Hb <10 g/dl, and maintain Hb <11.5 g/dl. Ensure
adequate Fe stores.
Appropriate iron supplementation is needed for ESA to be
effective
CKD-Mineral and Bone Disorder (CKD-MBD)
Treat with D3 as indicated to achieve normal serum levels
2000 IU po qd is cheaper and better absorbed than 50,000
IU monthly dose.
Limit phosphorus in diet (CKD stage 4/5), with emphasis on
decreasing packaged products - Refer to renal RD
May need phosphate binders
148. Detect and Manage CKD Complications
• Metabolic acidosis
o Usually occurs later in CKD
o Serum bicarb >22mEq/L
o Correction of metabolic acidosis may slow CKD progression and
improve patients functional status1,2
• Hyperkalemia
o Reduce dietary potassium
o Stop NSAIDs, COX-2 inhibitors, potassium sparing diuretics
(aldactone)
o Stop or reduce beta blockers, ACEi/ARBs
o Avoid salt substitutes that contain potassium
1) Mahajan, et al. Kidney Int. 2010;78:303-309.
2) de Brito-Ashurst I, et al. J Am Soc Nephrol.
2009;20:2075-2084.
149. A Balanced Approach to Nutrition in CKD:
Macronutrient Composition and Mineral Content*
Adapted from DASH (dietary approaches to stop hypertension) diet.
*Adjust so total calories from protein, fat, and carbohydrate are 100%. Emphasize such whole-food sources as
fresh vegetables, whole grains, nuts, legumes, low-fat or nonfat dairy products, canola oil, olive oil, cold-water
fish, and poultry.
NKF KDOQI. Am J Kidney Dis. 2007;49(suppl 2):S1-
S179.
*(CKD Stages 1-4)
150. What can primary care providers do? Recognize and test at-risk patients
Educate patients about CKD and treatment
Manage blood pressure and diabetes
Address other CVD risk factors
Monitor eGFR and ACR (encourage labs to report
these tests)
151. What can primary care providers do? Evaluate and manage anemia, malnutrition, CKD-
MBD, and other complications in at-risk patients
Refer to dietitian for nutritional guidance
Consider patient safety issues in CKD
Consult or team with a nephrologist (co-management)
Refer patient to nephrology when appropriate
153. Co-Management Model Collaborative care
Formal
arrangement
Curbside consult
Care coordination
Clinical decision
support
Population health
Development of
treatment protocols
154. Collaborative Care Agreements
Soft Contract between primary care and nephrologist
Defines responsibilities of primary care
Provide pertinent clinical information to inform the consultation
prior to the scheduled visit.
Initiate a phone call if the condition is emergent
Provide timely referrals with adequate number of visits to treat the
condition.
Defines responsibilities of nephrologist
Timely communication of consultation (7 days routine & 48 hours
emergent) – fax if no electronic information sharing
No consultation to other specialist initiated without primary care
input
155. Kidney
damage and
normal or GFR
Kidney
damage and
mild
GFR
Severe
GFR
Kidney
failure
Moderate
GFR
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
NephrologistPrimary Care Practitioner
The Patient (always)
and other subspecialists (as needed)
GFR 90 60 30 15
Who Should be Involved in the
Patient Safety Approach to CKD?
Patient safety
Consult?
156. Impact of primary care CKD detection
with a patient safety approach
Fink et al. Am J Kidney Dis. 2009,53:681-668
Patient Safety
Following
CKD detection
Improved diagnosis creates opportunity for strategic
preservation of kidney function
159. Common Medications Requiring Dose
Reduction in CKD Allopurinol
Gabapentin
CKD 4- Max dose 300mg
qd
CKD 5- Max dose 300mg
qod
Reglan
Reduce 50% for eGFR< 40
Can cause irreversible EPS
with chronic use
Narcotics
Methadone and fentanyl
best for ESRD patients
Lowest risk of toxic
metabolites
• Renally cleared beta blockers
o Atenolol, bisoprolol, nadolol
• Digoxin
• Some Statins
o Lovastatin, pravastatin,
simvastatin. Fluvastatin,
rosuvastatin
• Antimicrobials
o Antifungals, aminoglycosides,
Bactrim, Macrobid
• Enoxaparin
• Methotrexate
• Colchicine
160. Key Points on Medications in CKD
CKD patients at high risk for drug-related adverse events
Several classes of drugs renally eliminated
Consider kidney function and current eGFR (not just SCr)
when prescribing meds
Minimize pill burden as much as possible
Remind CKD patients to avoid NSAIDs
No Dual RAAS blockade
Any med with >30% renal clearance probably needs dose
adjustment for CKD
No bisphosphonates for eGFR <30
Avoid GAD for eGFR <30
161. *Significant albuminuria is defined as ACR ≥300 mg/g (≥30 mg/mmol) or AER ≥300 mg/24 hours, approximately
equivalent to PCR ≥500 mg/g (≥50 mg/mmol) or PER ≥500 mg/24 hours
**Progression of CKD is defined as one or more of the following: 1) A decline in GFR category accompanied by a 25%
or greater drop in eGFR from baseline; and/or 2) rapid progression of CKD defined as a sustained decline in eGFR of
more than 5ml/min/1.73m2/year. KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD
Indications for Referral to Specialist Kidney Care Services
for People with CKD
• Acute kidney injury or abrupt sustained fall in GFR
• GFR <30 ml/min/1.73m
2
(GFR categories G4-G5)
• Persistent albuminuria (ACR > 300 mg/g)*
• Atypical Progression of CKD
**
• Urinary red cell casts, RBC more than 20 per HPF sustained
and not readily explained
• Hypertension refractory to treatment with 4 or more
antihypertensive agents
• Persistent abnormalities of serum potassium
• Recurrent or extensive nephrolithiasis
• Hereditary kidney disease
162. Observational Studies of Early vs. Late
Nephrology Consultation
Chan M, et al. Am J Med. 2007;120:1063-1070.
http://download.journals.elsevierhealth.com/pdfs/journals/0
002-9343/PIIS000293430700664X.pdf
KDIGO CKD Work Group. Kidney Int Suppls. 2013;3:1-
163. Take Home Points PCPs play an important role
Identify risk factors
Know patient’s GFR using appropriate
screening tools
Help your patient adjust medication
Modify diet
Partner and refer to specialist
166. Overview of the CV impact caused by the
interaction of aldosterone and PTH in patients
with chronic HF and aldosterone excess.
Andreas Tomaschitz et al. Cardiovasc Res 2012;94:10-19
167. Advanced glycation end products
and their trafficking
Josephine M. Forbes, and Mark E. Cooper Physiol Rev 2013;93:137-188
168. Schematic overview of the major areas
contributing to diabetic complications
Josephine M. Forbes, and Mark E. Cooper Physiol Rev 2013;93:137-188
172. Screening Tools: eGFR
Considered the best overall index of kidney function.
Normal GFR varies according to age, sex, and body size, and
declines with age.
The NKF recommends using the CKD-EPI Creatinine
Equation (2009) to estimate GFR. Other useful calculators
related to kidney disease include MDRD and Cockroft Gault.
GFR calculators are available online at www.kidney.org/GFR.
Summary of the MDRD Study and CKD-EPI Estimating Equations:
https://www.kidney.org/sites/default/files/docs/mdrd-study-and-ckd-epi-gfr-estimating-equations-summary-ta.pdf
173. Screening Tools: ACR
Urinary albumin-to-creatinine ratio (ACR) is calculated by dividing
albumin concentration in milligrams by creatinine concentration in
grams.
Creatinine assists in adjusting albumin levels for varying urine
concentrations, which allows for more accurate results versus
albumin alone.
Spot urine albumin-to-creatinine ratio for quantification of
proteinuria
New guidelines classify albuminuria as mild, moderately or
severely increased
First morning void preferable
24hr urine test rarely necessary
180. Specific targets and potential therapeutic strategies
to inhibit or slow the progression of CKD
Declèves, A.-E. & Sharma, K. (2014) Novel targets of antifibrotic and anti-inflammatory treatment in CKD, Nat. Rev. Nephrol. doi:10.1038/nrneph.2014.31
181. Specific targets and potential therapeutic strategies
to inhibit or slow the progression of CKD
Declèves, A.-E. & Sharma, K. (2014) Novel targets of antifibrotic and anti-inflammatory treatment in CKD, Nat. Rev. Nephrol. doi:10.1038/nrneph.2014.31
185. Clinical Types of Cardiorenal Syndrome
Syndromes
Acute CRS
(type 1)
Chronic CRS
(type 2)
Acute RCS
(type 3)
Chronic RCS
(type 4)
Secondary CRS
(type 5)
Prevention
strategies
Acutely
decompensated
heart failure, acute
coronary syndromes,
Poorly controlled BP,
and noncompliance
with medication and
dietary sodium
intake.
Randomized trials:
improving
compliance with
heart failure has
reduced rates of
hospitalization and
mortality, and a
reduction in the rates
of acute CRS (type 1)
A common
pathophysiology
(neurohumoral,
inflammatory,
oxidative injury)
could be at work to
create organ
dysfunction. Drugs
that block the renin–
angiotensin system
reduce the
progression of both
CGF and CKD. It is
unknown whether
other classes of
drugs can prevent
chronic CRS (type 2)
Acute sodium and
volume overload are
part of the
pathogenesis. It is
unknown whether
sodium and volume
overload is
prevented with
different forms of
renal replacement
therapy and if this
will result in lower
rates of cardiac
decompensation.
The chronic processes
of cardiac and renal
fibrosis, LVH, vascular
stiffness, chronic Na
and volume overload,
and other factors
(neurohumoral,
inflammatory,
oxidative injury) could
be at work to create
organ dysfunction. A
reduction in the
decline of renal
function and
albuminuria has been
associated with a
reduction in CV
events. The role of
chronic uraemia,
anaemia, and
changes in CKD-
mineral and bone
disorder on the CVS is
known in chronic RCS
Potential systemic
factors negatively
impact function of
both organs acutelyIt
is uncertain if
reduction/elimination
of the key factors
(immune,
inflammatory,
oxidative stress,
thrombosis) will
prevent both cardiac
and renal decline.
186. Clinical Types of Cardiorenal Syndrome
Syndromes
Acute CRS
(type 1)
Chronic cardio-
renal (type 2)
Acute reno-
cardiac (type 3)
Chronic reno-
cardiac (type 4)
Secondary CRS
(type 5)
Management
strategies
Specific—depends on
precipitating
factorsGeneral
supportive—
oxygenate, relieve
pain & pulmonary
congestion, treat
arrhythmias
appropriately,
differentiate left from
right heart failure,
treat low cardiac
output or congestion
according to ESC
guidelines(a); avoid
nephrotoxins, closely
monitor kidney
function.
Treat CHF according
to ESC guidelinesa,
exclude precipitating
pre-renal AKI factors
(hypovolaemia
and/or hypotension),
adjust therapy
accordingly and avoid
nephrotoxins, while
monitoring renal
function and
electrolytesExtracorp
oreal ultrafiltration
Follow ESC guidelines
for acute CHFa
specific management
may depend on
underlying aetiology,
may need to exclude
renovascular disease
and consider early
renal support, if
diuretic resistant
Follow KDOQI
guidelines for CKD
management,
exclude precipitating
causes (cardiac
tamponade). Treat
heart failure
according to ESC
guidelinesa, consider
early renal
replacement support
Specific—according
to etiology. General—
see CRS
management as
advised by ESC
guidelines* 2008
188. Goals of Care in CKD
Slow decline in kidney function
Blood pressure control1
ACR <30 mg/g: ≤140/90 mm Hg
ACR 30-300 mg/g: ≤130/80 mm Hg*
ACR >300 mg/g: ≤130/80 mm Hg
Individualize targets and agents according to age,
coexistent CVD, and other comorbidities
ACE or ARB
*Reasonable to select a goal of 140/90 mm Hg, especially for moderate albuminuria (ACR 30-300 mg/g.)2
1) Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. Kidney Int Suppl. (2012);2:341-342.
2) KDOQI Commentary on KDIGO Blood Pressure Guidelines. Am J Kidney Dis. 2013;62:201-213.
190. direct and indirect
components of the renin –
angiotensin aldosterone
system (RAAS) and their
effects on the progression
of CKD
191. Nephrotic vs. Nephritic Syndromes
Nephrotic Syndromes - glomerular disorders that affect
the glomerular capillary membrane & increases
permeability to plasma proteins
Nephritic Syndromes – glomerular disorders that initiate
the inflammatory response within the glomeruli & initially
decreases permeability of the membrane
192. Nephritic Syndromes
Glomerulonephritis
• An inflammatory response in the endothelial, epithelial &
mesangial cells of the glomeruli
• Inflammatory process damages the capillary wall-
allowing RBCs into the urine
Symptoms:
• 1st oliguria, followed by hematuria, azotemia, low GFR
(d/t hemodynamic changes), hypertension
196. Pathophysiology of CKD
Final Common Pathway is loss of nephron mass
Structural/
Functional
Hypertrophy
of remnant
nephrons
Loss of
Nephron Mass
Sclerosis
of remnant
nephrons
Mediated by
vasoactive
molecules, cytokines
and growth factors,
renin angiotensin
axis
Diabetes
Hypertension
Chronic GN
Cystic Disease
Tubulointerstitia
l disease
199. Old Classification of CKD as Defined by Kidney
Disease Outcomes Quality Initiative (KDOQI)
Modified and Endorsed by KDIGO
Note: GFR is given in mL/min/1.732 m²
National Kidney Foundation. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease:
Evaluation, Classification, and Stratification. Am J Kidney Dis 2002;39(suppl 1):S1-S266
Stage Description Classification
by Severity
Classification
by Treatment
1 Kidney damage with
normal or increased GFR
GFR ≥ 90
2 Kidney damage with
mild decrease in GFR
GFR of 60-89 T if kidney
transplant
3 Moderate decrease in GFR GFR of 30-59 recipient
4 Severe decrease in GFR GFR of 15-29 D if dialysis
5 Kidney failure GFR < 15 D if dialysis
KDIGO, Kidney
Disease: Increasing
Global Outcomes
200. Which patients are at increased risk for CKD?
Risk factors
Diabetes
Hypertension
Autoimmune diseases
Systemic infections
UTI, nephrolithiasis, lower
urinary-tract obstruction
Hyperuricemia
Acute kidney injury
Family history of chronic
kidney disease
Sociodemographic risk
factors
Older age
Black race
Smoking
Heavy alcohol use
Obesity
NSAIDs
201. Diabetes mellitus
Hypertension
Cardiovascular disease
o Note on pediatric patients:
CKD may start with childhood
obesity
No recommendations for routine
testing
The people to test are those at
greatest risk
Age > 60 years
Race or ethnic background
African-American
Hispanic
American Indian
Asian
History of exposure to
chemicals/toxins
Cigarette smoke
Heavy metals
Family history of CKD
National Kidney Foundation, 20012
202. Functional Changes of CRF
The Kidneys are unable to:
Regulate fluids and electrolytes
Balance fluid volume and renin-angiotensin system
Control blood pressure
Eliminate nitrogen and other wastes
Synthesize erythropoietin
Regulate serum phosphate and calcium levels