2. Renal Failure 2 Chronic Renal Failure 1.CRF - irreversible kidney dysfx.with azotemia >3 months. 2.Azotemia - BUN >28mg/dL & Cr>1.5mg/dL 3.ESRD (GFR <5%) - uremia requiring transplantation or dialysis

3. Renal Failure 3 Criteria to Define CRF 1.Kidney damage for 3 months, as defined by structured or fx. Abnormalities of the kidney, with or without GFR, mainfest by either: Pathological abnormalities. Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests. 2.GFR < 60 ml/min/1.73m 2 for 3 months with or without kidney damage.

4. Renal Failure 4 Etiology 1.Episodes of ARF (usually ATN) often lead to CRF 2.Over time, combinations of acute renal insults are additive and lead to CRF 3.The definition of CRF requires that at least 3 months of renal failure have occurred

5. Renal Failure 5 Stages of CRF: A clinical Action Plan StageDescriptionGFR (ml/min/1.73m2) Action 1 Kidney damage with normal or GFR 90 Treatment of comorbid condition, slowing progression. 2 Kidney damage with mild GFR 60-89Estimating progress 3moderate GFR30-59 Evaluating & treat complications 4Severe GFR15-29 Preparation for kidney replacement therapy 5Kidney failure< 15 ( or dialysis) Replacement if uremia present

6. Renal Failure 6 Risk Factor 1.Diabetes: most common cause ESRD. 2.HTN. 3.Medications. 4.Pregnancy. 5.Black men have a 3.5-4 fold increased risk of CRF compared with white men.

7. Renal Failure 7 Treatment Pre-Dialysis Treatment 1.Maintain normal electrolytes a.k, ca, po4 are major electrolytes affected in CRF b.ACEI may be acceptable in many pts with cr >3.0mg/dL c.ACEI may slow the progression of diabetic & non-diabetic pt. d. or D/c other renal toxins (including NSAIDS) e.Diuretics (eg. furosemide) may help maintain k in normal range f.Renal diet including high calcium and low phosphate 2. Protein intake to < 0.6 gm/kg body wt.

9. Equations used to evaluate RF Cockcroft-Gult (suitable in patient with stable kidney function). Jelliffe (GFR in adults). MDRD (evaluate the effect of dietary protein restriction & BP control on the progression of kidney function). Schwartz (GFR in children). Renal Failure 9

10. Limitations of the use of cr Affected by muscle mass. Affected by diet (meat). Affected by liver disease (over estimate). Remain normal in initial stages of kidney disease. Lab differences. So we should use other markers to evaluate kidney function as proteinuria. Renal Failure 10

11. Advantages of MDRD It is derived from Modification of Diet in Renal Disease study. It may provide a better estimate based on the fact that the equation was derived using GFR measured directly in urinary clearance of radio labeled marker (125 I-Iothalamate). Renal Failure 11

12. MDRD Equation Estimated GFR(ml/min/1.72m2)= 70 * (SrCr) -0.999 *(age) -0.176 * (BUN) -0.170 * (Alb) 0.318 * (0.762 F) * (1.18 if African) Abbreviated version: Estimated GFR(ml/min/1.72m2) =186* (SrCr) -1.154 *(age ) -0.203 * (0.742 F) * (1.21 if African) Renal Failure 12

13. Schwartz Equation CL cr (ml/min) = (K * length in cm)/SrCr K= 0.45 (infants 1-52 wks) K= 0.55 (child 1-13 yrs) K= 0.7 (adolescence male) K=0.55 (adolescence female) Renal Failure 13

14. 24-hour urine collection Incomplete urine collection. Diurnal variation in GFR. Variation in Cr excretion. However it is suitable for population with variation in dietary intake of cr source as vegetarians, or pt with poor muscle mass (malnourished, amputees). Renal Failure 14

16. When to use proteinuria? Pt how r at risk of KD should have an additional assessment by prot excretion. Prot is not normally filtered by the glomerulas unless there is damage. It is considered as an early marker for KD since it may proceed elevation in SrCr. Renal Failure 16

17. Classification Microalbuminuria: defined as albumin excretion rate of 20- 200 Mg/min or 30-300 mg/24hr. Proteinuria (or albuminuria): total prot exc rate>200 Mg/min or >300 mg/24hrs. Albumin is better used than total prot since it is an early indicator of G damage. Renal Failure 17

18. Methods for quantification of albumin 24 hr urine collection (can take only over night). Spot urine sample for measurement of albumin/Cr ratio (correct for hydration status, better use early morning sample). Dipstick test (pt with a +ve dipstick test should be further evaluated by quantitative assessment of Alb/Cr ratio to confirm albuminuria). Renal Failure 18

19. Factors associated with proteinuria High protein meal. Vigorous exercise. Renal Failure 19

20. The pt has proteinuria if According to NKF Kidney Disease Quality initiative (K/DOQI) persistent proteinuria at least 2 +ve quantitative tests separated by 1-2wks. ADA microalbuminurea 2 +ve out of three quantitative measurements separated by 3-6 m. Microalbuminuria alb/cr 30 – 300 Mg/mg, any thing over albuminuria. Renal Failure 20

21. Other test to confirm kidney dysfunction Biopsy. Urinalysis. Radiographic procedure. Renal Failure 21

23. Recommendations Assessment of kidney function (SrCr, BUN, urinary protein) should be done annually. Primary prevention is the best treatment goal in patient with diabetes including tight glycemic and blood pressure control. Renal Failure 23

24. Recommendations ADA recommend the use of: ACEI for all patient with type 1 DM, and patient with type 2 without protein urea; ACEI or ARBs in patient with type 2 DM and microalbumin urea; ARBs in patient with type 2 DM and macroalbumin urea. Renal Failure 24

25. Recommendations Some data indicate protein restriction to 0.8-1 g/kg/d can result in stable kidney function. Renal Failure 25

26. Case Study M.R is a 32 years, African American female. (wt=63kg,ht=58) CC: –one week N, V, Malaise. HPI: –Type 1diabetes mellitus since15 years (noncompliant) –Peptic ulcer for the past 6 months Renal Failure 26

27. PE BP=155/102 mmHg Mild pulmonary congestion 2+pedal edema Renal Failure 27

28. Labs Na143 mEq/lH K5.3 mEq/lH Cl106 mEq/lSH SrCr2.9mg/dlH BUN63mg/dlH GLU220mg/dlH ph7.6mg/dlH Mg2.8mg/dlH Uric Acid8.8mg/dlH Hgb8.7g/dlL Albumin700mg/dayH Urineanalysis4+proteinturia Renal Failure 28

29. WHAT IS THE CAUSE ADNANCED KIDNEY DISEASE? WHAT IS THE SIGNIFICANCE ALBUMINURIA? Renal Failure 29

30. Factors affecting progression of kidney disease Male & genetics. Hi Bp. Hi glucose & Hgb A1c. Hi cholesterol. Advanced age. Smoking. Hi protein intake. Insulin deficiency & keton bodies. Advanced glycosylation end products (AGEs) that form in hyperglycemia cause of end organ damage. Renal Failure 30

31. Testing Annual in pt DM I>5yrs. Annual in pt DM II starting from diagnosis. Renal Failure 31

32. Management Intensive glucose control Antihypertensive therapy Dietary protein restriction(0.6-0.8g/kg/day) Renal Failure 32

33. Intensive glucose control DCCT fasting glu 70-120 mg/dl pp glu < 180 mg/dl. DM I, Intensive insulin V conventional, Monitoring after 6.5 yr follow up. <39% in risk of microalbuminuria, < 54% in albuminuria. Risk of hypoglycemia, ADA 90-130 mg/dl, pp <180 mg/dl, Hgb A1C< 7%. DM II insulin or POHG V dietary therapy, over 10yrs, reduce microvascular complications. Renal Failure 33

34. Antihypertensive therapy Systemic HTN occure in pt DM I & MicroAU. 1/3 pt DM II at time of diagnosis. Nephropathy can cause inc vascular resistance or inc plasma volume soooooo HTN DM + HTN------ VC + inc SVR from ATII. So ACEI or ARBs are the preferred agents even with normal BP. Goal BP <130/80 mmHg. Diuretics in DM + edema. Renal Failure 34