Post on 21-Dec-2015
transcript
Chronic Kidney Disease and Diabetes
Dr Garth Hanson
Talk
• 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
Pancreas
Hyperglycemia
Reduced insulin production
Pancreas
muscle
Hyperglycemia
Reduced insulin production
Reduced uptake glucose
Pancreas
muscle liver
Hyperglycemia
Reduced insulin production
Reduced glycogen production or increased gluconeogenasis
Reduced uptake glucose
Hyperglycemia
Hyperglycemia
Non enzymatic glycation of tissues (AGE products)
Hyperglycemia
Non enzymatic glycation of tissues (AGE products)
Cytokine production (VGEF, TGF-beta)
Hyperglycemia
Non enzymatic glycation of tissues (AGE products)
Cytokine production (VGEF, TGF-beta)
Tissue ischemia due to microvascular damage
Hyperglycemia
Non enzymatic glycation of tissues (AGE products)
Cytokine production (VGEF, TGF-beta)
Tissue ischemia due to microvascular damage
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Basement membrane thickening
Glomerular sclerosis
Mesangial expansion
Arteriolar hyalineosis
DM Pathology
DM and Renal Outcomes
DM and Renal Disease
Treatment of Hyperglycemia in DM
Reduce Glucose
muscle
liver
pancrease
kidney
intestine
DPP4
GLP
Reduce Glucose
muscle
liver
pancrease
kidney
intestine
DPP4
GLP
insulin
Reduce Glucose
muscle
liver
pancrease
kidney
intestine
DPP4
GLP
Alpha glucosidase inhib
insulin
Reduce Glucose
muscle
liver
pancrease
kidney
intestine
DPP4
GLP
metformin
Alpha glucosidase inhib
insulin
Reduce Glucose
muscle
liver
pancrease
kidney
intestine
DPP4
GLP
metformin
Alpha glucosidase inhib
insulin
meglithinidessulfonylureas
Reduce Glucose
muscle
liver
pancrease
kidney
intestine
DPP4
GLP
metformin
thioazolinadimediones Alpha glucosidase inhib
insulin
meglithinidessulfonylureas
Reduce Glucose
muscle
liver
pancrease
kidney
intestine
DPP4
GLP
metformin
thioazolinadimediones Alpha glucosidase inhib
DPP4 inhib
GLP 1 agonists
insulin
meglithinidessulfonylureas
Reduce Glucose
muscle
liver
pancrease
kidney
intestine
DPP4
GLP
metformin
thioazolinadimediones Alpha glucosidase inhib
DPP4 inhib
GLP 1 agonists
insulin
meglithinidessulfonylureas
SGLT2
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– 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?