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Introduction Globally, • • • • DKD diabetes mellitus is a major reason of chronic kidney disease (CKD) and end -stage renal disease (ESRD). Affects about 40% of T1DM and T2DM patients. Has an exaggerated cardiovascular risk. DN develops in 20- 30% of T1DM after a mean duration of diabetes of 15 years. Both T1DM and T2DM have equal risk. A clinical syndrome in persons with DM characterized by Definition [ Persistent albuminuria >300mg/24h or 200µg/min (confirmed at least 2 out of 3 consecutive urine collection 3-6monthes apart) [ Hypertension . [ Declining renal function ( êê GFR) (With absence of clinical & laboratory evidence of other kidney or urinary system disease) Natural history of DN Pathogenesis Blood pressure control in DN RAAS System Blockers in DN • âBP is important in preventing progression of DN irrespective of the used agent. • Start antihypertensive if BP is >140/90 mmHg aiming for level < 130/80 mm Hg • ACE Inhibitors caused 60% reduction of macroalbuminuria and increased chance of regression of albuminuria @ ACEIs have (Reno-protective effects) Therefore, the indication for ACEIs can be persistent microalbuminuria, regardless of blood pressure (even normotensive patient). @ For T1DM [ ACEI is 1st line management, when not tolerated use ARB. @ For T2DM [ use ARBs or ACEIs (but not combination) (Repeat renal function 1 week after introduction of ACEIs. If hhS.cr >30% rule out renal artery stenosis) When to refer to Nephrologists?? 1. Uncertain about the etiology of renal disease (heavy Proteinuria, 4. Absence of retinopathy. active urinary sediments, hematuria). 5. Rapid decline in GFR. 2. Resistant Hypertension despite treatment. 6. Abnormal ultrasound 3. Advanced kidney disease (Stage 4-5 CKD). Screening for nephropathy in diabetics prevents progression of kidney disease. 1. Urinary Albumin creatinine Ratio (UACR) in 1 st pass morning or in a spot urine sample. 2. Measure serum creatinine and estimate the glomerular filtration rate (eGFR) Screening of DN When to screen? • T2DM à at diagnosis and early follow up • T1DM à 5years after diagnosis , Exception for T1DM are in patient with poor glycemic control, poor lipid control, high BP, puberty (who have to screened 1year after diagnosis) CKD classification Stage 1 2 3 4 5 Description GFR > 90 ml/min 89 – 60 59 - 30 29 - 15 < 15 Kidney damage/normal GFR Mild renal insufficiency Moderate renal insufficiency Severe renal insufficiency Kidney Failure/ ESRD GFR calculators Targeting hemodynamic factors: – Low Protein Diet – Low Salt Diet – Treatment of HTN (ACEIs, ARBs) Glycemic • • • Targeting metabolic factors: – Control of hyperlycemia – Control of dyslipidemia – Control of Proteinuria – Growth Factors & Cytokine inhibitors control prevent progression of microalbuminuria[ macroalbuminuria. prevent deterioration of kidney function in macroalbuminuric patients. prevent cardiovascular complications * Glycemic control aims for [ A1c level <7% (can be >7 with comorbidities, limited life expectancy & h risk of hypoglycemia). Management of DN Anemia Aspirin * Adjust the dose of anti-hyperglycemic drugs (If albuminuria and reduced kidney function) When eGFR is <60 mL/min/1.73 m2, evaluate and manage potential complications of CKD Diet modification: Dietary recommendations depend on the stage of CKD • â Salt diet reduces blood pressure. • Sodium < 2.4 g/d (< 100 mmol/d) • h Fibres improves lipid profile. • Protein < 0.8 mg/kg /day . • â Phosphorus. • potassium > 4 (g/d) • â Protein diet • Calcium and magnesium supplements • Phosphorus < 1.7 (g/d). Exercise and smoking cessation Lipid control • Aim for LDL level < 100mg/dl by statins or statin/ezetimibe combination to reduce risk of major atherosclerotic events in patients with diabetes and CKD • Anemia in DN develops from erythropoietin deficiency. • Occurs in both Type 1 and Type 2 diabetes, though it may occur earlier in the former, • Hemoglobin to levels of 11-12 g/dl showed benefit in dialysis patients • Only moderately effective in reducing cardiovascular risk. • Use it for primary prevention only in diabetic patients at high risk of cardiovascular events Renal Replacement Therapy (RRT) when eGFR reaches10-15 mL/min, but preferably earlier ESRD 1. 55 ys old diabetic patient with Hx. Of cancer bladder and CT urography is planned for further evaluation and you are asked for advice on minimizing risk of contrast induced nephropathy(CIN). His medication was glimipide 3mg/d, metformin 850mg/twice daily 1. 2. 3. 4. 2. What is the precaution to prevent CIN in this patient??? Stop metformin 2days before contrast CT (to avoid lactic acidosis) IV hydration with saline o.9% (hdiuresis) Bicarbonate therapy 150mEq before &after contrast. Oral N-acetyl cysteine 1200mg twice/d for 48 hrs You are consulted by a 52 years old man with T2DM diagnosed for 3 years. On exam: he has puffiness of eye lids, bilateral oedema of LL. His BP is 130/80 mmHg, pulse: regular, HbA1c is 7.9%, • urine analysis: No RBCs, WBCs: 2-5mm/HPF protein +++, S. Creatinine: 1.2 mg/dl • ECG: normal What is the most likely diagnosis of this case? à Diabetic nephropathy The patient was ordered to do fundus examination what do you expect to find ? à Diabetic retinopathy Can we give any hypertensive medication for this patient? Yes, even that he was normotensive What the most suitable antihypertensive for this patient? à ACE-Is or ARBs What if the fundus is normal in previous case? à Search for another cause If the previous patient has RBCs cast in his urine sediment, what is the diagnosis? à Glomerulonephritis 3. A 58-year-old man with a 7-year history of T2DM a walk-in clinic due to increasing swelling in his LL that began about 6m previously and has worsened over the past 6w. The patient’s medical Hx. is significant for HTN, T2DM. His medications include gliclazide 80 mg twice/d, metformin 500 tds, amlodipine 10 mg/d, and ibuprofen occasionally. **Examination: NAD apart from pallor & G2 pitting oedema LL. **Lab: S.cr: 3.7 mg/dl, S.Albumin: 3 gm/dl, Urine analysis: prot. ++++ ,CBC: Hb: 10 (NNA) Is the previous medication suitable for this patient & why??? • NOT suitable • d.t decline of renal function(iGFR) What will happen if the patient continue on this medication??? • Hypoglycemia(iclearance of Sus) • Lactic acidosis(iclearance of metformin)