by

Dr.Sridhar DM (nephrology)

MANAGEMENT OF DIABETES MELLITUS

IN CKD

DIABETES:THE MOST COMMON CAUSE OF ESRD

Primary Diagnosis for Patients Who Start Dialysis

Diabetes50.1%

Hypertension27%

Glomerulonephritis

13%

Other

10% No. of patientsProjection95% CI

1984 1988 1992 1996 2000 2004 20080

100

200

300

400

500

600

700

r2=99.8%243,524

281,355520,240

No.

of d

ialy

sis

patie

nts

(thou

sand

s)

COMORBIDITIES

Non-diabetes Diabetes

Non-CKD

CKD

0

15

30

45

60

Non-diabetes Diabetes

Non-CKD

CKD

0

15

30

45

60

Non-diabetes Diabetes

Non-CKD

CKD

0

15

30

45

60

Non-diabetes Diabetes

Non-CKD

CKD

0

15

30

45

60

%Stroke/TIA

%ASHD %Amputation/PVD

%Heart Failure

CAUSES OF RENAL DISEASE IN DIABETES

• Diabetic nephropathy• Renal artery stenosis• Myeloma, outflow obstruction, polycystic renal disease,

glomerulonephritis, etc• Drugs

• NSAIDS/Cox 2 inhibitors• Fibrates• ACEI, ARBs

DIABETIC NEPHROPATHY

• 30% of all end-stage renal disease

• Increased co-morbidity and mortality – retinopathy, cardiovascular disease, stroke, peripheral vascular disease

• May be prevented/delayed by early screening and treatment

FACTORS AFFECTING PROGRESSION OF NEPHROPATHY

• Blood pressure

• Urinary protein excretion

• (glycaemic control)

MINIMUM SCREENING FOR RENAL DISEASE IN DIABETES

1. Annual EMU for ACR. Repeat within a month if positive, in absence of UTI/renal stones/other renal disease

2. Annual serum creatinine• Creatinine• eGFR (preferred MDRD equation)

MICROALBUMINURIA AND PROTEINURIA

Normal Microalbuminuria Overt proteinuria

F M F M

Albumin/creatinine ratio (mg/mmol)

<3.5 <2.5 >3.5 >2.5 >30

Equivalent Albumen excretion (mg/day)

<30 30-300 300

• Diagnosis of microalbuminuria based on 2 out of 3 positive first passed morning urine samples in absence of urinary tract infection

INITIAL ASSESSMENT OF PATIENT WITH DIABETES AND RENAL IMPAIRMENT

• Is this likely to be diabetic nephropathy?

• Presence of retinopathy

• Microalbuminuria/proteinuria

• Is this likely to be renal artery stenosis?

• Family history, Drug history, GU history etc

• AIP, myeloma screen, PSA

• Ultrasound

METFORMIN

• Metformin has been used in low doses in patients with glomerular filtration rate (GFR) as low as 30 to 60 ml/min. It

• should not be used at a GFR below 30 ml/min -- risk for lactic acidosis.

• As renal function can deteriorate abruptly,

• better to avoid metformin once serum creatinine concentration rises above

1.5 mg/dl (132 μmo/l) in men

1.3 mg/dl (117 μmol/l) in women

ORAL HYPOGLYCEMICS

INSULIN SECRETAGOGUES(SULFONYLUREA AND MEGLITINIDES)

• Sulphonylureas (especially gliblenclamide) may accumulate as renal function deteriorates

• can be associated with hypoglycemia

Glycosidase inhibitors• contraindicated in renal failure

Thiazolidinediones• associated with weight gain, (fluid retention + nonfluid gains)

• patients at risk for congestive heart failure -- should be avoided.

• Concern about increased bone fracture rates in patients using thiazolidinediones,

• could potentiate CKD - related bone disease.

• Insulin regimens are the most commonly used to control glycemia in CKD

• increasing half-life of insulin as CKD progresses, the risk for hypoglycemia increases.

• Insulin requirements decrease further in HD patients, particularly in those with residual diuresis (<500 ml/day),

• Insulin requirement often decreases by 30%

• In peritoneal dialysis (PD) patients,

• intraperitoneal insulin is more physiologic than subcutaneous, as portal absorption of insulin may better mimic the endogenous insulin effect.

• Insulin requirements typically increase by 200% to 300% in this situation

INSULIN

INSULIN IN PT. ON HEMODIALYSIS

• Insulin inhibitors – dialyzable

• Insulin resistance diminishes after the start of dialysis.

• half-life of insulin is prolonged.

• the potential for hypoglycemia with both oral agents and insulin increases in the presence of CKD (with the exception of gliquidone and glimepiride).

• Self-monitoring of blood glucose concentration is imperative.

• Insulin requirement often decreases by ~30%

• Glargine has been shown to reduce hypoglycemia in hemodialysis patients

BLOOD PRESSURE CONTROL

• BP reduction in type 1 & type 2 DM patients reduces rate of CKD progression

• At any given level of GFR, blood pressure tends to be higher in diabetic than in nondiabetic patients with CKD

• recommended blood pressure target 125/75 mm Hg

• Ideally – (typically takes three or four drugs to accomplish)

• start with an ACE inhibitor or ARB

• Add diuretic

• Add calcium channel blocker, β-blocker, or renin inhibitors

(if systolic BP >20 mmHg above goal)START with ACEI or ARB/thiazide diuretic*)

If BP Still Not at Goal (125/705mm Hg)

If BP Still Not at Goal (125/75 mm Hg)

orIf used CCB, Add Other Subgroup of CCB

(ie, amlodipine-like agent if verapamil or diltiazem already being used and the converse)

OR if b blocker used add CCB

Add Vasodilator (hydralazine, minoxidil)

If BP Still Not at Goal (125/75 mm Hg)

Add Long Acting Thiazide Diuretic*

If Blood Pressure >125/75 mm Hg in Diabetes or Chronic Kidney Disease with Any Level of Albuminuria

Recheck within 2-3 weeks

Recheck within 2-3 weeks

Recheck within 4 weeks

(if systolic BP< 20 mmHg above goal)Start ARB or ACE Inhibitor titrate upwards

Add CCB or b blocker** (titrate dose upward)

Consider low dose aldosterone antagonists#

ACEI/ARB begin at a low dose; increase dose at 4-week intervals to reduce microalbuminuriaantiproteinuric effects not necessarily attained at antihypertensive doses increase dose until proteinuria reduced by 30 to 50%

Titrate to maximal suppression of urinary albumin excretion for DM patients with persistent microalbuminuria despite intensive insulin therapy even without HTN

titration limited by adverse effects:• an acute increase in serum creatinine of 50% or more;

• renal artery stenosis;

• hypovolemia; congestive heart failure

• hyperkalemia resistant to corrective maneuvers

• ARB : consider for subjects with documented aldosterone escape

IMPACT OF DIABETES ON DIALYSIS BLOOD PRESSURE MANAGEMENT

• Autonomic Insufficiency

• BP drops and very labile

• Medial Calcificaton

• Wide pulse pressure

• Hypertensive Cardiomyopathy

• Preload

• Cardiac function

• After load

LIPID CONTROL

• Heart Protection Study

• Patients with DM and CKD who received statins had a 23% decrease in cardiovascular risk with an absolute event reduction of 80%

• In HD patients with type 2 DM, the addition of 20 mg of atorvastatin

• 40% decrease in lowdensity lipoprotein cholesterol levels & significant decrease in cardiac events

DOSAGES OF STATINS IN CKD• IN PT.S ON HEMODIALYSIS AND PERITONEAL DIALYSIS

• Atorvastatin - up to 80 mg/day

• Fluvastatin – up to 80 mg/day.

• Pravastatin - limited to 10 mg, as active metabolites can accumulate,

Pravastatin Pooling Project - of up to 40 mg were safely (GFR of 30 ml/min per 1.73 m2)

• Simvastatin – upto 20 mg/day (40-mg/day in stage 3 CKD (Heart Protection Study))

• Rosuvastatin - not more than 10 mg/day when GFR falls below 30 ml/min per 1.73 m2.

• Ezetimibe - safely used (effects absorption mainly bile acid sequestrants)

• Fenofibrate - reduced by one third in CKD stage 2,

reduced by two thirds in CKD stages 3 and 4

avoided in CKD stage 5.

• Gemfibrozil - safely used, although in PD, elevated CPK levels have been reported

• Niacin (Sustained-release) - should be decreased by 50% at CKD stage 5

• DIET IN CKD PT.S WITH DM• Diabetic patients with renal failure are often severely catabolic

and tend to develop malnutrition

• Reduction of dietary protein intake to 0.8 g/kg body weight for CKD Stages 1–4 is recommended

• Increase protien intake >1.2g/kg in HD >2.0g/kg in PD

• ANEMIA

• Anemia occurs at an earlier stage of CKD in DM patients and is often more severe

• Erythropoietin - Anemia associated with CKD

• In DM - higher dosages compared with nonDM pt.s

• Diabetic patients with CKD develop secondary hyperparathyroidism at a slower rate than nondiabetics

• predisposed to low-turnover (adynamic) bone disease - risk factor for cardiovascular calcification

• care should be taken to avoid calcium loading.

• Accumulate aluminum more readily and are more susceptible to aluminum-induced bone disease.

• Aluminum containing phosphate binders should always be avoided in the diabetic patient with advanced CKD

• Target serum phosphorus goal

• < 5.5 mg/dl in patients with Stage 5 CKD

• < 4.6 mg/dl in Stage 3–4 CKD.

• if the i-PTH is abnormal - evaluate for vitamin D deficiency

• measurement of 25-hydroxy vitamin D.

DIABETIC MANAGEMENT IN CKD

Parameter

• Lower BP………………………

• Block RAAS……………………

• Improve glycemia …………….

• Lower LDL cholesterol………..

• Anemia management ………...

• Endothelial protection…………

• Smoking………………………..

Target

< 125/75 mmHg

ACEi or ARB to max tolerated

A1c < 6.5% (Insulin/TZD)

< 100 (70) mg/dl statin + other

Hb 11-12 g/dl (Epo + iron)

Aspirin daily

Cessation

RENAL REPLACEMENT THERAPY IN CKD WITH DM• Start dialysis at eGFR - 15 ml/min per 1.73 m2 (normally - eGFR <7-8)

• they tend to tolerate uremia poorly and frequently have sodium retention and fluid overload.

• Peritoneal dialysis–associated glucose loading • Replace glucose solutions in part by amino acid solutions and polyglucose.

• Loss of solute and water transport often limits long-term use of peritoneal dialysis to 3 to 5 years.

• Switching to hemodialysis should be considered before volume overload or uremic symptoms occur

• Pt.s on PD, Glucose meters based on GLUCOSE OXIDASE TEST should be used • maltose and polyglucose present in PD solution, affect glucose

dehydrogenase–based glucose meters

TRANSPLANTS

• Type 1 DM - pancreas transplant

• Can induce regression of moderate Diabetic Nephropathy lesions in native kidneys

• but only during a period of 10 years after transplantation.

• Pancreas transplantation at the time of renal transplantation

• Prevents / slows the development of Diabetic Nephropathy in the transplanted kidney.

Thank you