Chronic Kidney Disease and
Diabetes
Dr Garth Hanson
Talk
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Pathology of Diabetes Mellitus (DM)
DM and Renal Disease
Treatment of Hyperglycemia in DM
DM Treatment CKD Stage III – IV, Stage V HD,
Stage V PD and Renal Transplant
• Special Considerations
Pathology of Diabetes
Hyperglycemia
Hyperglycemia
Reduced insulin
production
Pancreas
muscle
Reduced uptake
glucose
Hyperglycemia
Reduced insulin
production
Pancreas
muscle
liver
Reduced uptake
glucose
Reduced glycogen production
or increased gluconeogenasis
Hyperglycemia
Reduced insulin
production
Pancreas
Hyperglycemia
Non enzymatic glycation of tissues
(AGE products)
Hyperglycemia
Non enzymatic glycation of tissues
(AGE products)
Hyperglycemia
Cytokine production (VGEF,
TGF-beta)
Non enzymatic glycation of tissues
(AGE products)
Hyperglycemia
Cytokine production (VGEF,
TGF-beta)
Tissue ischemia due to
microvascular damage
Non enzymatic glycation of tissues
(AGE products)
Hyperglycemia
Cytokine production (VGEF,
TGF-beta)
Tissue ischemia due to
microvascular damage
?
Basement
membrane
thickening
Glomerular
sclerosis
Mesangial
expansion
Arteriolar
hyalineosis
DM Pathology
DM and Renal Outcomes
DM and Renal Disease
Treatment of Hyperglycemia in DM
intestine
muscle
Reduce Glucose
GLP
liver
DPP4
pancrease
kidney
intestine
muscle
Reduce Glucose
GLP
liver
insulin
DPP4
pancrease
kidney
intestine
muscle
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
insulin
DPP4
pancrease
kidney
intestine
muscle
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
metformin
insulin
DPP4
pancrease
kidney
intestine
muscle
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
metformin
insulin
DPP4
pancrease
kidney
meglithinides
sulfonylureas
intestine
muscle
thioazolinadimediones
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
metformin
insulin
DPP4
pancrease
kidney
meglithinides
sulfonylureas
intestine
muscle
thioazolinadimediones
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
metformin
insulin
GLP 1 agonists
DPP4
pancrease
kidney
DPP4 inhib
meglithinides
sulfonylureas
intestine
muscle
thioazolinadimediones
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
metformin
insulin
GLP 1 agonists
DPP4
SGLT2
pancrease
kidney
DPP4 inhib
meglithinides
sulfonylureas
DM Treatment in CKD
CKD Stage III - IV
• RAS Blockage/HTN
control
• Lipids
• Antiplatelet
/Anticoagulation
• Glucose Control
CKD Stage III - IV
• RAS Blockage/HTN
control
• Each 10 mmHg of systolic
BP 13% reduction in
microvascular complications
(UKPDS)
• After ACCORD, target 140
mmHg and above 120
mmHg.
CKD Stage III - IV
• RAS Blockage/HTN
control
• ACE and ARB reduce
progression by 16% to 30%.
• Dual RAS blockage not
helpful (ONTARGET,
NEHRON-D, ALTITUDE)
• African Americans may not
benefit as much.
• Long acting agents usually
chosen (Ramipril,
Perindopril)
CKD Stage III - IV
• Lipids
• Secondary prevention of
CVD events definitely
beneficial (TNT trail) target
to 1.8 LDL
• Primary prevention of CVD
likely beneficial (CARDS,
SHARP).
• Combination therapy not
likely of benefit (ACCORD,
ENHANCE).
CKD Stage III - IV
• Lipids
• Statin therapy does not
appear to reduce
progression to ESRD (SHARP,
CARDS).
• Watch high dose
rosuvastatin and simvastatin
• atorvastatin safe at all
doses
CKD Stage III - IV
• Antiplatelet
/Anticoagulation
• Secondary prevention
beneficial
• Primary prevention in doubt
except for highest risk.
• Newer agents have little
data
CKD Stage III - IV
• Glucose Control
• DM 1 - 8% HA1C vs 9%-10%
reduced progression of
nephropathy by 50%.
• DM 2 – UKDPS 21%
reduction in progression of
nephropathy, ACCORD 32%
reduction in nephropathy
with lower HA1C (under 7%)
BUT mortality unchanged or
increased.
CKD Stage III - IV
• Glucose Control
• metformin should be
stopped at GFR 30 ml/min
• Insulin has prolonged
halflife
• Thiazolindinediones may
cause volume and bone
issues
• SGLT2 inhibitors less
efficacious under GFR 45
ml/min
CKD V-Hemodialysis
• RAS Blockage/HTN
control
• Lipids
• Antiplatelets
/Anticoagulation
• Glucose Control
High Quality Evidence in HD
DM and Hemodialysis
• DM monitoring
– HA1C may be inaccurate due to RBC turnover, uremic
toxins, acidosis
– Low sugars more common due to prolonged insulin
lifespan
– Tolerate very high glucose levels due to no urine
output
• DM control
– Insulin safest but use reduced dose
– Linagliptin (Trajenta) safe
– Repeglinide (Gluconorm) safe
CKD V-Peritoneal Dialysis
• RAS Blockage/HTN
control
• Lipids
• Antiplatelets
/Anticoagulation
• Glucose Control
High Quality Evidence in PD
DM and PD
• DM monitoring
– HA1C inaccurate with high turnover of RBC with
epo agents
– Icodextran converted to maltose messes up
meters
• DM Treatment
– May need massive insulin doses with glucose load
in PD fluid
CKD V-Transplant
• RAS Blockage/HTN
control
• Lipids
• Antiplatelets
/Anticoagulation
• Glucose Control
DM and Transplants
• Prednisone will increase glucose intolerance
• Calcinurin inhibitors (tac > cyclo) cause DM
due to islet cell toxicity
• No metformin
• Repeglinide, trajenta, insulin ok
Special Considerations
• Hyperglycemia
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–
–
–
Very high levels can be tolerated
High K due to osmotic shift
Low Na due to osmotic shift
Treat with insulin infusion not fluid load
• Hypoglycemia
– Anorexia due to uremia. Watch for malignancy and
infection
– Avoid long acting oral agents and long acting insulin
Special Considerations
• Hypo alternating with Hyper
– Gastroporesis may alter glucose absorption,
gastric emptying study will diagnose. Treat with
promotility agents.
– Watch for non compliance with PD as cause (lower
sugar load).
QUESTIONS?