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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
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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
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
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