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Thug’s MANAGEMENT OF DIABETIC NEPHROPATHY Ian Case 9 Scenario Diabetes at 14 Difficult to control Hyper filtration, microalbuminuria, Proteinuria, CKD RRT: Peritoneal dialysis then combined Introduction Globally, diabetes mellitus is a major reason of chronic kidney disease (CKD) and end-stage renal disease. Diabetes is The Most Common Cause of Renal Failure. Rate of kidney diseases in Egypt is 36.4* with about 5.19% deaths What are the commonest renal problems in diabetic patients? DEFINITION Diabetic nephropathy Renovascular disease Urinary tract infection Glomerulonephritis Contrast induced nephropathy Diabetic nephropathy (DN) is a clinical syndrome in persons with diabetes characterized by: 1. Albuminuria 2. Hypertension . 3. Declining renal function Affects 40% of T1D and T2D patients. Has an exaggerated cardiovascular risk. . Persistent microalbuminuria, predicts early DN DN develops in 20- 30% of Type 1 diabetes after a mean duration of diabetes of 15 years. Both T1D and T2D have equal risk. Natural History of DN Flow Chart for Classifying DN Nephron in DN

MANAGEMENT OF DIABETIC NEPHROPATHY€¦ · nephropathy Diabetic nephropathy (DN) is a clinical syndrome in persons with diabetes characterized by : 1. Albuminuria Type 1 diabetes

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Page 1: MANAGEMENT OF DIABETIC NEPHROPATHY€¦ · nephropathy Diabetic nephropathy (DN) is a clinical syndrome in persons with diabetes characterized by : 1. Albuminuria Type 1 diabetes

Thug’s

MANAGEMENT OF DIABETIC NEPHROPATHY Ian Case 9 Scenario

Diabetes at 14

Difficult to control

Hyper filtration, microalbuminuria, Proteinuria, CKD

RRT: Peritoneal dialysis then combined

Introduction

Globally, diabetes mellitus is a major reason of chronic kidney disease (CKD) and end-stage renal disease.

Diabetes is The Most Common Cause of Renal Failure.

Rate of kidney diseases in Egypt is 36.4* with about 5.19% deaths

What are the commonest renal problems in diabetic

patients?

DEFINITION

Diabetic nephropathy

Renovascular disease

Urinary tract infection

Glomerulonephritis

Contrast induced nephropathy

Diabetic nephropathy (DN) is a clinical syndrome in persons with diabetes characterized by: 1. Albuminuria 2. Hypertension . 3. Declining renal function

Affects ∼40% of T1D and T2D patients.

Has an exaggerated cardiovascular risk.

.Persistent microalbuminuria, predicts early DN

DN develops in 20- 30% of Type 1 diabetes after a mean duration of diabetes of 15 years.

Both T1D and T2D have equal risk.

Natural History of DN

Flow Chart for Classifying DN Nephron in DN

Page 2: MANAGEMENT OF DIABETIC NEPHROPATHY€¦ · nephropathy Diabetic nephropathy (DN) is a clinical syndrome in persons with diabetes characterized by : 1. Albuminuria Type 1 diabetes

Thug’s

PATHOGENESIS RISK FACTORS OF DN

Glomerular hyper perfusion & hyper filtration.

cause leakage from the glomerular capillaries & injury to podocytes

Hyperglycemia induce : - Oxidative stress - Formation of cytokines - Advanced glycation end products.

The process eventually causes fibrosis of the tubule-interstitium & glomeruloscelerosis.

1. Susceptibility

Genetic

Race

Age

2. Induction

Glycaemic control

Glomerular hyperfiltration

3. Progression – Glycaemic control – Blood pressure – Oral contraceptives – Obesity – Dyslipidaemia – Smoking

A Simplified scheme for the pathogenesis of diabetic nephropathy Late Diabetic Nephropathy

SCREENING OF DN

Urinary Albumin creatinine Ratio (uACR) in first- pass morning/ in a spot urine sample .

Measure serum creatinine and estimate the glomerular filtration rate (eGFR)

WHEN TO SCREEN

TYPE 1 DIABETES TYPE 2 DIABETES

5 yrs after diagnosis. Exceptions are in patients: - poor blood glucose

control - poor lipid control - high blood pressure

- Puberty (independent risk factor for microalbuminuria) who have to be screened 1yr after diagnosis.

At diagnosis and yearly follow up.

URINE ACR/ Albumin Values

Category ACR(mg/gms) Correlating

Albumin

values(mg/day)

Normoalbuminuria <30 <30

Microalbuminuria 30-300 30-300

Macroalbuminuria >300 >300

DKD CLASSIFICATION

Stage Description GFR

1 Kidney damage/normal GFR >90ml/min

2 Mild renal insufficiency 89-60

3 Moderate renal insufficiency 59-30

4 Severe renal insufficiency 29-15

5 Kidney Failure/ERF/ESRD <15

EVALUATION & MONITORING OF RENAL FUNCTION - Screen and monitor regularly to reduce the - risk and slow progression.

- Assess patients by history , physical examination, biochemical tests , imaging and renal biopsy .

GFR calculators: http://www.nkdep.nih.gov/lab-evaluation/gfr-calculators.shtml

Page 3: MANAGEMENT OF DIABETIC NEPHROPATHY€¦ · nephropathy Diabetic nephropathy (DN) is a clinical syndrome in persons with diabetes characterized by : 1. Albuminuria Type 1 diabetes

Thug’s

REFER TO NEPHROLOGISTS - Uncertain about the etiology of renal disease

(heavy Proteinuria, active urinary sediments) . - Absence of retinopathy. - Rapid decline in GFR.

- Abnormal ultrasound . - Resistant Hypertension despite treatment. - Advanced kidney disease (Stage 4-5 CKD).

Management of CKD in

Diabetes (1)

All patients Yearly measurement of creatinine, urinary albumin excretion, potassium

45-60

Referral to nephrology if possibility for nondiabetic kidney disease exists

Consider dose adjustment of medications

Monitor eGFR every 6 months

Assure vitamin D sufficiency

Monitor electrolytes, bicarbonate, hemoglobin, calcium, phosphorus, parathyroid hormone at least yearly

Referral for dietary counselling

Consider bone density testing

Management

of CKD in Diabetes (2)

<30 Referral to nephrologist

30-44

Monitor eGFR every 3 months

weight every 3–6 months

Consider need for dose adjustment of medications

Monitor electrolytes, bicarbonate, calcium, phosphorus, parathyroid hormone, hemoglobin, albumin

MANAGEMENT OF DN

TARGETING HEMODYNAMIC FACTORS TARGETING METABOLIC FACTORS

Low Protein Diet

Low Salt Diet

Treatment of hypertension

Angiotensin converting enzyme inhibitors

Angiotensin receptor blockers

Aldosterone Antagonists

- Control of hyperlycemia - Control of dyslipidemia - Control of Proteinuria - Growth Factors & Cytokine

inhibitors

1. GLYCEMIC CONTROL Prevents progression of microalbuminuria to

macroalbuminuria

Prevent deterioration of kidney function in macroalbuminuric patients.

Prevents CVS complications

Glycemic control aims for A1c level <7%. - Adjust the dose of anti-hyperglycemic drugs (If albuminuria and reduced kidney function )

Glycaemic Control in Diabetics with CKD

Glycated hb (%)

Fasting bl glucose 2 hours postprandial bl glucose

mg/dl mmol/l mg/dl mmol/l

Diabetic nephropathy <6.5 80-120 4.4-6.7 <140 <7.8

Predialysis (CrC<10 ml/min) <7.5 100-120 5.6-6.7 <140-160 <7.8

Dialysis <7.5-8.0 100-140 5.6-6.7 <200 <11.1

Renal Transplantation <6.5 80-120 4.4-6.7 <140 <7.8

Antihyperglycemic agents and CKD

Diabetes mellitus (DM) is the leading cause of chronic renal failure (CRF) and dialysis therapy .

Numerous drugs with different action mechanisms may serve to reduce both acute and chronic diabetic complications to improve the quality of life in diabetic patients

In patients with CKD, therapeutic possibilities are limited because of reduction in glomerular filtration rate (GFR) that is accompanied by accumulation of some oral agents and/or their metabolites

Page 4: MANAGEMENT OF DIABETIC NEPHROPATHY€¦ · nephropathy Diabetic nephropathy (DN) is a clinical syndrome in persons with diabetes characterized by : 1. Albuminuria Type 1 diabetes

Thug’s

2. BLOOD PRESSURE (BP) CONTROL 3. DIET MODIFICATION - BP is important in preventing

progression of DN. irrespective of the used agent .

- RAAS blockade is beneficial on DN In a meta analysis : - ACE Inhibitors caused 60% reduction of

macroalbuminuria - ↑ chance of regression of albuminuria.

↓ Salt diet reduces blood pressure.

↑ Fibres improves lipid profile.

↓ Phosphorus .

↓ Protein diet .

Dietary recommendations depend on the stage of CKD

Sodium < 2.4 g/d (< 100 mmol/d)

Protein < 0.8mg /kg /day .

potassium > 4 (g/d)

Calcium & magnesium supplements

Phosphorus < 1.7 (g/d).

4. LIPID CONTROL • Lipid reduction using antilipemic agents might

preserve GFR & ↓ proteinuria in diabetic patients Aim for LDL level < 100mg/dl by statins Adjust dose when using fabric acid derivatives in

patients with Stage 4 or 5 CKD

6. ESRD Renal replacement when eGFR reaches 10-15 mL/min, but preferably earlier

5. ANEMIA Anemia in DN develops from erythropoietin

deficiency. Occurs in both Type 1 and Type 2 diabetes, though it

may occur earlier in the former, Typically severe even with relatively minor deranged

renal function. Hemoglobin to levels of 11-12 g/dl showed benefit

in dialysis patients

Benefits of PD • No need for vascular access • No need for systemic anticoagulation • Continuous therapy • Gradual ultra filtration • Fewer episodes of hypotension • Better blood pressure control • Better control of anemia • More liberal diet • Intraperitoneal administration of insulin • Lifestyle advantages

Conclusion - The best management of diabetic patients is delivered by

an organised multidisciplinary team. - Adoption of preventive measures , targeting the main risk

factors, glycemic control and using agents with a renoprotective effect (ACE and/or ARB) ; decrease the progression of renal disease.

- Early detection of diabetic nephropathy & timely referral of those with advanced kidney disease to nephrologists delays the onset of ESRD

- The role of physicians at 1ry care level is vital