Chronic Kidney Disease and Diabetes

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Chronic Kidney Disease and Diabetes

• Dr Garth Hanson

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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

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Pathology of Diabetes
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Hyperglycemia
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Hyperglycemia
Reduced insulin production
Pancreas
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muscle
Reduced uptake glucose
Hyperglycemia
Reduced insulin production
Pancreas
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muscle
liver
Reduced glycogen production or increased
gluconeogenasis
Reduced uptake glucose
Hyperglycemia
Reduced insulin production
Pancreas
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Hyperglycemia
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Non enzymatic glycation of tissues (AGE products)
Hyperglycemia
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Non enzymatic glycation of tissues (AGE products)
Cytokine production (VGEF, TGF-beta)
Hyperglycemia
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Non enzymatic glycation of tissues (AGE products)
Cytokine production (VGEF, TGF-beta)
Hyperglycemia
Tissue ischemia due to microvascular damage
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Non enzymatic glycation of tissues (AGE products)
Cytokine production (VGEF, TGF-beta)
Hyperglycemia
Tissue ischemia due to microvascular damage
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Basement membrane thickening
Glomerular sclerosis
Mesangial expansion
Arteriolar hyalineosis
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DM Pathology
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DM and Renal Outcomes
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DM and Renal Disease
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Treatment of Hyperglycemia in DM
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intestine
muscle
Reduce Glucose
GLP
liver
DPP4
pancrease
kidney
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intestine
muscle
Reduce Glucose
GLP
liver
insulin
DPP4
pancrease
kidney
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intestine
muscle
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
insulin
DPP4
pancrease
kidney
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intestine
muscle
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
insulin
metformin
DPP4
pancrease
kidney
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intestine
muscle
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
insulin
metformin
DPP4
pancrease
kidney
sulfonylureas
meglithinides
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intestine
muscle
thioazolinadimediones
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
insulin
metformin
DPP4
pancrease
kidney
sulfonylureas
meglithinides
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intestine
muscle
thioazolinadimediones
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
insulin
metformin
GLP 1 agonists
DPP4
pancrease
kidney
DPP4 inhib
sulfonylureas
meglithinides
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intestine
muscle
thioazolinadimediones
Alpha glucosidase inhib
Reduce Glucose
GLP
liver
insulin
metformin
GLP 1 agonists
DPP4
SGLT2
pancrease
kidney
DPP4 inhib
sulfonylureas
meglithinides
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DM Treatment in CKD
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CKD Stage III - IV

• RAS Blockage/HTN control
• Lipids
• Antiplatelet /Anticoagulation
• Glucose Control

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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.

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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)

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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).

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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

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CKD Stage III - IV

• Antiplatelet /Anticoagulation
• Secondary prevention beneficial
• Primary prevention in doubt except for highest
  risk.
• Newer agents have little data

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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.

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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

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CKD V-Hemodialysis

• RAS Blockage/HTN control
• Lipids
• Antiplatelets /Anticoagulation
• Glucose Control

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High Quality Evidence in HD
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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

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CKD V-Peritoneal Dialysis

• RAS Blockage/HTN control
• Lipids
• Antiplatelets /Anticoagulation
• Glucose Control

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High Quality Evidence in PD
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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

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CKD V-Transplant

• RAS Blockage/HTN control
• Lipids
• Antiplatelets /Anticoagulation
• Glucose Control

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DM and Transplants

• Prednisone will increase glucose intolerance
• Calcinurin inhibitors (tac gt cyclo) cause DM due
  to islet cell toxicity
• No metformin
• Repeglinide, trajenta, insulin ok

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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

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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).

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QUESTIONS?