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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 )
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DM & CKD Dr. Shahrzad Shahidi Professor of Nephrology Isfahan University of Medical Sciences
CKD • Kidney damage for ≥ 3months, 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 < 60mL/min/1.73 m2for ≥ 3 months ± kidney damage
If no other markers of kidney disease, no CKD Moderately increased risk High risk Very high risk
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%. • Dialysisfor 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 II III I 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 1ADA 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% oftheir diabetic patients for diabetic nephropathy
Microalbuminuria • Spot AM urine: Alb/Cr ratio 30-300 mg/g Cr* • Timed urine collection: 20-200µg albumin/min • 24 hour urine collection: 30-300 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 90-130 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 inCKD ND patients with DM • Adults with DM & CKD ND with urine albumin excretion < 30 mg/dwhose office BP is consistently > 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/dwhose 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 Hxof 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? • The patient has early or incipient diabetic nephropathy. • The patient should maintain a HbA1C of less than 7 to help protect his kidneys. • You should start the patient on an ACE inhibitor to protect his kidneys. • All of the above are true.
Patient #2 • 43 y old woman with a 6 year Hxof type 2 DM. • A urine dipstichshows trace Pr • Spot AM urine ACR 390 mg/g Cr • BP is 135/80 • HbA1C is 6.7%
Which is (are) not true? • You should check the patient’s serum Cr & K. • You should start the patient on an ACEI if her K & Cr are okay. • You should check a 24 hour urine for total Pr & Cr clearance. • 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? • You should get the patient’s diabetes under better control before rechecking his urine. • A fever will not cause proteinuria. • The patient’s BP is under good control. • 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? • You should check a 24 hour urine for total Pr & Cr. cl. • A spot AM urine ACR correlates well with a 24 hour urine for total Pr • 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.