7.Diabetic Nephropathy.Dr.Thilak Jayalath_Renal Lectures.
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7.Diabetic Nephropathy.Dr.Thilak Jayalath_Renal Lectures.






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    7.Diabetic Nephropathy.Dr.Thilak Jayalath_Renal Lectures. 7.Diabetic Nephropathy.Dr.Thilak Jayalath_Renal Lectures. Document Transcript

    • 1 Diabetic Nephropathy Importance of diabetic nephropathy A major cause of premature deaths in patients with diabetes, principally from cardiovascular disease Becoming the most common cause of chronic kidney disease globally Early stages of diabetic nephropathy could be asymptomatic More prevalent among African Americans, Asians, and Native Americans Definition The appearance of persistent ‘clinical’ albuminuria (albumin excretion rate > 300 mg/24 hours) in an individual who has had diabetes for more than 5 years and who has concomitant retinopathy, in the absence of urinary tract infection (UTI), other renal diseases and heart failure. This process is often associated with rising blood pressure. Early Nephropathy  Microalbuminuria  Rising Blood Pressure 0 2 5 11-23 13-25 15-27 Onset of Onset of Rising ESRD Diabetes Proteinuria Serum Creatinine Dr.Thilak Jayalath MBBS MD FRCP FRCPE FISN Senior Lecturer in Medicine & Consultant Physician Department of Medicine, Peradeniya Functional Changes  GFR  Reversible Albuminuria  Kidney size Structural Changes  Glomerular Basement Membrane Thickness  Mesangial Expansion Hypertension
    • 2 Type l diabetes Nephropathy rare in the first 5 years Peak incidence around 15-20 years After 35 years very rare to develop nephropathy Type ll diabetes Nephropathy may be present at the time of presentation Prevalence of proteinuria is highly variable, ranging from 5-20% Pathophysiology Glycation of the glomerular basement membrane may interfere with its break down and reduce its turnover producing thickening of the membrane. Accumulation of sorbitol could lead to osmotic damage to glomeruli Pathology Glomerular basement membrane thickening Diffuse mesangial sclerosis Hyalinosis Diabetic nephropathy pathological changes in kidney Thickening of capillary wall, Hyaline degeneration Nodular lesions Fibrin Cap, Hyaline degeneration Microaneurysm formation Hyaline arteriosclerosis
    • 3 Increase of mesangial matrix Fibrin Cap Risk factors for diabetic nephropathy Hyperglycaemia Hypertension Familial and genetic factors Dyslipidaemia Stages of diabetic nephropathy Stage GFR Albuminuria BP Time course Renal hyper filtration Elevated < 20µg / min Normal At diagnosis Microalbuminuria (Incipient Nephropathy) Within normal Range 20 - 200µg / min Raising within normal range 5 - 15 Persistent proteinuria Decreasing > 200µg / min High 10 - 15 Renal Failure Diminished Massive High 15 – 30 Proteinuria Smoking Dietary factors
    • 4 Stages of diabetic nephropathy Renal Hyperfiltration Present at the time of dignosis of diabetes Increased glomerular filtration Kidney size may be enlarged Reversible albuminuria Microalbuminuria (Incipient nephropathy) Persistent high excretion of albumin Earliest clinically detectable stage Thickening of glomerular basement membrane Mesangial expansion Blood pressure rises within the normal range Persistent proteinuria Detectable proteins in urine with conventional tests Blood pressure is high Decreased glomerular filtration rate Abnormal renal function tests Renal failure Massive proteinuria Very low glomerular filtration rate Very high serum creatinine level High blood pressure Clinical features of chronic kidney disease Diagnosis of diabetic nephropathy Earliest clinically detectable level is Microalbuminuria stage Microalbuminuria (a misnormer) Presence of albumin in urine in excess of normal level but not detectable with conventional urine tests for albumin Detection of Microalbuminuria 1. Random, spot test Mid stream first urine sample is best Albumin concentration ( > 20mg / L ) Albumin :creatinine ratio> 2.5 mg/mmol in men , > 3.5 mg /mmol in women
    • 5 2. Timed urine collection test overnight Albumin excretion rate > 20 µg / minute 3. Timed urine collection test for 24 hours Albumin excretion rate > 30 mg / 24 hours Diagnosis of Microalbuminuria A rate of more than 20-200 µg / minute or 30-300 mg /day in two of three urine samples tested within 6-12 months Screening for microalbuminuria should not be performed in the presence of Urinary tract infection Haematuria Acute febrile illness Vigorous exercise Heart failure Evaluation of patients with diabetic nephropathy Evaluation should include Work up for other etiologies Assessment of renal function Look for other comorbid associations Work up for other etiologies • Urinary tract obstruction infection and stones • Features for other types of glomerulonephritis • Family history of kidney disease Normal Microalbuminuria Proteinuria Albumin Concentration (mg/l) <20 20 - 200 >200 Albumin Creatinine ratio (mg/mmol) <2.5 (men) <3.5 (Women) 2.5 – 30 3.5 - 30 >30 >30 24 hour urine albumin (mg/24h) <30 30-300 >300 Albumin excretion rate (µg/minute) <20 20-200 >200
    • 6 Assessment of renal function • Urine full report • Serum creatinine • Creatinine clearance Retinopathy  A risk marker  Almost always seen in patients with diabetic nephropathy in type 1 diabetics  About 70% of type 2 diabetic patients have retinopathy with nephropathy  Even at the time of diagnosis of type 2 diabetes, about a quarter of patients have established background retinopathy 4 Stages 1. Background retinopathy 2. Pre- proliferative retinopathy 3. Proliferative retinopathy 4. Advanced eye disease 1. Background retinopathy 2. Pre- proliferative retinopathy • Microaneurysms neovascular proliferation • Haemorrhages cotton wool spots • Hard exudates venous beading and looping • Retinal oedema intraretinal microvascular abnormalities 3. Proliferative retinopathy • New vessel formation may occur at the optic disc • New vessel formation may occur elsewhere on the retina • Vitreous haemorrhages 4. Advanced eye disease • vitreous haemorrhage • retinal detachment • Rubeosis iridis • neovascular glaucoma Other comorbid conditions • Hypertension • Dyslipidemia • Smoking • Anaemia
    • 7 Normal retina Hard exudates Hard and soft exudates New vessel formation New vessel formation Following laser therapy
    • 8 Management of diabetic nephropathy Management of diabetic nephropathy Treatment of microalbuminuria Irrespective of blood pressure ACE inhibitors must be started Angiotensin receptor blockers are alternatives for those who can not tolerate ACE inhibitors Treatment with ACE inhibitors and Angiotensin receptor blockers Renoprotective effect is independent of blood pressure reduction May be due to • Decreased intraglomerular pressure • Decreased passage of proteins into the proximal tubule Treatment of hyperglycemia • Poor glycemic control is associated with faster decline of GFR Early morning urine Test for proteinuria Negative Positive Random test for microalbuminuria Positive Negative Timed urine testing Negative Retest in one year Positive Two other timed urine testing within 3-6 months Positive Start ACE inhibitors or ARB
    • 9 • When clinical albuminuria develops, Insulin is the best treatment • Avoid Metformin and Glibenclamide in advanced nephropathy Treatment of hypertension ACE inhibitors and Angiotensin receptor blockers (ARB s) have additional beneficial effects ACE inhibitors and ARBs can be combined if there is no reduction in albuminuria or if blood pressure target levels are not reached Blood pressure target – 130 / 80 When proteinuria over 1 g / L, blood pressure should be lowered to 125 / 75 Treatment of hyperlipidemia Nephropathy is associated with cardiovascular diseases. Lowering of lipids has beneficial effects Aspirin use is advised for all patients with an increased UAER (unless contraindicated) because of their high risk of cardiovascular disease Dietary restrictions Low-protein diets have been shown to slow the rate of decline of GFR in diabetic patients Current dietary recommendations are for an intake of between 0. 7 and 0 .9 g protein/kg body weight per day Smoking Advice to stop smoking New potential therapeutic stragies Aminoguanidine - Known to interfere with glycation reaction ALT – 711 - significant reduction of urinary albumin excretion Sulodexide – significantly reduced microalbuminuria Pimagedine – reduce urinary protein excretion