DM & CKD Dr. Shahrzad Shahidi Professor of Nephrology Isfahan University of Medical Sciences

CKD  Kidney damage for ≥ 3 months, defined by structural or functional abnormalities of the kidney, ± decreased GFR, manifest by either:  Albuminuria (AER ≥ 30 mg/24 hs; ACR ≥ 30 mg/g Cr )  Urine sediment abnormalities  Electrolyte & other abnormalities due to tubular disorders  Abnormalities detected by histology  Structural abnormalities detected by imaging  Hx of kidney transplantation  GFR < 60 mL/min/1.73 m 2 for ≥ 3 months ± kidney damage 3

If no other markers of kidney disease, no CKD Moderately increased risk High risk Very high risk 4

Diabetic Nephropathy  Over 40% of new cases of end-stage renal disease (ESRD) are attributed to diabetes.  The 5-year mortality rate for a dialysis patient with diabetic nephropathy is 93%.  Dialysis for one patient costs over $50,000 annually.

Diabetic Nephropathy  DN occurs in 35-40% of patients with type I diabetes (IDDM) whereas it occurs only in 15-20% of patients with type II diabetes (NIDDM).  Definition or Criteria for diagnosis of DN  Presence of persistent proteinuria in sterile urine of diabetic patients with concomitant diabetic retinopathy & HTN.

Stages of Diabetic Nephropathy I II III IV V

Nephropathy Risk Factors  DM Type & Duration  Poor diabetic control  HTN  Race (Aboriginal > Indian > Caucasian)  Smokers  Family history

Nephropathy Risk Factors  Modifiable  HbA1c, BP & total cholesterol  Obesity, smoking  Non-modifiable  Age, ethnicity

Screening for Diabetic Nephropathy 1 ADA Diabetes Care 27

Screening  Measurements of urinary ACR in a spot urine sample.  Measurement of serum Cr & estimation of GFR.

How are we doing? Studies show that primary care physicians screen only 20% of their diabetic patients for diabetic nephropathy

Microalbuminuria  Spot AM urine: Alb/Cr ratio mg/g Cr*  Timed urine collection: µg albumin/min  24 hour urine collection: mg albumin in 24 hours *This is the most practical test

Incipient Nephropathy IDDM  2 out of 3 urine tests + for microalbuminuria  Presence of proliferative diabetic retinopathy  80-90% of type 1 patients with microalbuminuria will progress to DN

Incipient Nephropathy NIDDM  2 out of 3 urine tests + for microalbuminuria (start screening at the time of diagnosis of DM)  Presence of diabetic retinopathy  20-30% may have diabetic nephropathy but not diabetic retinopathy  25% may have a diagnosis of nephropathy other than diabetic nephropathy

Q. Which features are typical of diabetic CKD at presentation ?  Haematuria No  Small scarred kidneys No  Progress to ESKD in <2yrs No  Associated retinopathy Yes  β -blockers better than ACE-I Rx No

Other cause(s) of CKD should be considered in the presence of any of the following circumstances:  Absence of diabetic retinopathy  Low or rapidly decreasing GFR  Rapidly increasing Pruria or nephrotic syndrome  Refractory HTN  Presence of active urinary sediment  Signs or symptoms of other systemic disease  >30% reduction in GFR within 2-3 ms after initiation of an ACE I or ARB.

Treatment of Diabetic Nephropathy (cont.)  Glycemic Control  Preprandial plasma glucose mg/dl  A1C ~ 7.0%  Peak postprandial plasma glucose <180 mg/dl  Self-monitoring of blood glucose (SMBG)  Medical Nutrition Therapy  Target dietary Pr intake for people with DM & CKD stages 1-4 should be the RDA of 0.8 g/kg/d.

Management of Hyperglycemia & General Diabetes Care in CKD  Target HbA1c of ~ 7.0% to prevent or delay progression of the microvascular complications of DM, including DKD.  Not treating to an HbA1c target of <7.0% in patients at risk of hypoglycemia.  Target HbA1c be extended above 7.0% in individuals with co-morbidities or limited life expectancy and risk of hypoglycemia.

Metformin in CKD  No hypoglucemia or weight gain  Inexpensive  BUT:  Renally-excreted  Excess doses → anorexia, diarrhea  Dose adjust to GFR: 2g to 250mg/day  Protocol says  eGFR 30 – 45 max 1gm/day  Cease when eGFR <30 but…  Risk of fatal lactic acidosis if unwell

Management of Dyslipidemia in Diabetes & CKD  Using LDL-C lowering medicines, such as statins or statin/ezetimibe combination, to reduce risk of major atherosclerotic events in patients with diabetes & CKD, including those who have received a kidney transplant.  Not initiating statin therapy in patients with diabetes who are treated by dialysis

Management of Albuminuria in Normotensive Patients with Diabetes  Not using an ACE-I or an ARB for the primary prevention of DKD in normotensive normoalbuminuric patients with diabetes.  Using an ACE-I or an ARB in normotensive patients with diabetes & albuminuria levels >30 mg/g Cr who are at high risk of DKD or its progression.

BP management in CKD ND patients with DM  Adults with DM & CKD ND with urine albumin excretion 140 mmHg systolic or > 90 mmHg diastolic be treated with BP lowering drugs to maintain a BP that is consistently ≤140 mmHg systolic & ≤ 90 mmHg diastolic.  Adults with DM & CKD ND with urine albumin excretion > 30 mg/d whose office BP is consistently >130 mmHg systolic or > 80 mmHg diastolic be treated with BP lowering drugs to maintain a BP that is consistently ≤130 mmHg systolic & ≤ 80 mmHg diastolic.  ARB or ACE-I be used in adults with diabetes & CKD ND with urine albumin excretion of ≥ 30 mg/d.

Diabetes & ESRD  Reducing insulin requirements  Difficult vascular access  Accelerated macrovascular disease  Advanced microvascular disease  Frequent sepsis  Silent ischaemia  2-3 x death rate vs non-DM patients

How can DM effect Dialysis?  Autonomic neuropathy – may suffer hypotension increased by large fluid shift in HD  Uncontrolled BS – may absorb some glucose in PD fluid  Severe PVD – difficult to get vascular access for HD  PVD may also affect peritoneum & reduce PD success  Increased risk of infections – problem in both  Transplants – new kidneys develop nephropathy, hence good glycaemic control important

Case #1  Your first pient is a 25 y old young man with a 5 year Hx of type 1 DM.  His urine dipstick is negative for Pr.  Spot AM urine Alb/Cr ratio is 19 mg/g Cr.  His BP is 112/66 mmHg.  His HbA1C is 6.9%.

Which is (are) true? 1. The patient has early or incipient diabetic nephropathy. 2. The patient should maintain a HbA1C of less than 7 to help protect his kidneys. 3. You should start the patient on an ACE inhibitor to protect his kidneys. 4. All of the above are true.

Patient #2  43 y old woman with a 6 year Hx of type 2 DM.  A urine dipstich shows trace Pr  Spot AM urine ACR 390 mg/g Cr  BP is 135/80  HbA1C is 6.7%

Which is (are) not true? 1. You should check the patient’s serum Cr & K. 2. You should start the patient on an ACEI if her K & Cr are okay. 3. You should check a 24 hour urine for total Pr & Cr clearance. 4. The patient has overt diabetic nephropathy & should be referred to a nephrologist.

Case #3  60 y old man with HTN, dyslipidemia & newly diagnosed type 2 DM.  A urine dip shows 2+ Pr  He has a fever & his HbA1C is 10.3%  BP is 140/88  He is taking HCTZ & Glipizide

Which is (are) true? 1. You should get the patient’s diabetes under better control before rechecking his urine. 2. A fever will not cause proteinuria. 3. The patient’s BP is under good control. 4. You should check the patient’s K & Cr.

Case #3  3 months later with exercise, metformin & Enalapril your patient’s HbA1C is now 7.5 & his BP is 135/85.  A urine dip now shows 1+ protein.

Which is (are) true? 1. You should check a 24 hour urine for total Pr & Cr. cl. 2. A spot AM urine ACR correlates well with a 24 hour urine for total Pr 3. The patient likely already has diabetic nephropathy & should be referred to a nephrologist.

Use the Algorithm!  Check all your diabetic patients annually for renal disease.  Help your diabetic patients’ protect their kidneys by helping them keep their diabetes under control.  Help your diabetic patients protect their kidneys by helping them keep their BP under control.