1. APPROACH TO AZOTEMIC PATIENTS Florencio J. Pine, M.D.

2. Objective: Aims to assist the students in learning the following: Clinical implication of azotemia Gather and analyze the clinical data base for systemtic and logical assessmemt of azotemic patients Differentiate types and causes of renal failure Differentiate between acute and chronic renal failure Importance of recognizing acute from chronic renal failure Arrive at the diagnosis using the clinical data base and judicious utilization of diagnostic tools

3. Contents 1. Review of the basic renal function, anatomy and physiology 2. Definition and cardinal manifestations of azotemia 3. Diagnostic tools, use and interpretation 4. Types, manifestations and differentiating parameters of renal failure 5. Algorithm

4. Functions of the Kidney 1. Maintains fluid balance 2. Maintains electrolyte balance 3. Maintains acid-base balance 4. Excretes water/ toxic waste products 5. Synthesizes hormones 6. Regulates blood pressure 7. Contributes in glucose metabolism 8. Conserves substrates that can be reused by the body

5. The Nephron

6. The Glomerulus

7. Transport Functions of the Anatomic Segment of the Nephron

8. Patterns of Adaptation

9. Azotemia Definition: Retention of nitrogenous waste products in the blood Implication: Renal dysfunction Phases: Asymptomatic Uremic state

10. Cardinal Manifestations: Renal Dysfunction Oliguria - urine output < 400-500cc/day Anuria - urine output < 100cc/day Polyuria - urine output >3L/day with intake of <3L/day Uremia Other manifestation- determined by underlying disease

11. Basic Screening Diagnostic Tools CBC BUN/Creatinine Urinalysis

12. Diagnostic Tools: Common Complications Na, K, Cl ABG Chest Xray ECG

13. Diagnostic Tools: Causes 1. Uric Acid 2. CPK 3. Urine GS/CS 4. Urine diagnostic indices 5. KUB UTZ 6. Plain KUB Xray 7. CT Stonogram

14. Urine Indices

15. Estimation of Renal Function 1. BUN 2. Serum Creatinine 3. Creatinine Clearance 4. Estimated Creatinine clearance Cockroft-Gault Formula: CrCl (ml/min)=(140-age)(weight) (0.85)if female (72) (creatinine) 5. Nuclear GFR

16. Classification Acute Functional deterioration within hours to days/ weeks Potentially reversible damage Chronic Functional deterioration w/in weeks to months/years Irreversible nephron/s injury

17. Acute renal failure: Classification Pre- renal: Physiologic disturbance Decreased perfusion Increased waste production Intrinsic: Definite anatomic damage Glomerulonephritis Acute tubular necrosis Acute tubulointerstitial nephritis Acute intratubular obstruction Post-renal: Obstruction in the drainage Both ureters Urinary bladder outlet

18. Acute renal failure: Classification Pre-Renal:Most Common Intra-Renal: Most Impact Large Vessel Disease Small Vessel/Glomerulus Ischemic/Toxic ATN Acute TIN Post-renal: Demand Immediate Diagnosis and Treatment

19. Ischemic/Toxic ATN: >90% of intra-renal Vulnerability factors: excretes numerous drugs and solutes ability to concentrate solutes hundred fold large surface area high rates of active transport of solutes and O2 consumption relative hypoperfusion

20. “RIFLE” Criteria for ARF Three severity grades Risk1.5X SCr increase or UO<0.5mL/kg/hr for 6 hrs Injury2.0X SCr increase or UO <0.5mL/kg.hr for 12 hrs Failure3.0X SCr increase or UO<0.5mL/kg/hr for 24hrs or oliguria for 12 hours Two outcome measures Loss (i.e. need for RRT) ESRD (dialysis dependency at three months)

21. “RIFLE” Criteria for ARF These gradings were found to have prognostic value Modified criteria felt to be more useful for patient management Modified R, I, F categories-changed to stages 1-3 L and E remain as outcomes

22. Acute Kidney Injury Network (AKIN) Staging *Stage allocated is highest (worse) of either of the criteria StageCreatinine* change over baseline Oliguria criteria* 1 +27uM or 1.5-2X increase 6 hrs 2 2-3X increase 12 hrs 3 >3X increase or<0.3mL/kg/hr for 24 hours or anuria for 12 hours

23. Laboratory Findings in ARF

24. Chronic Kidney Disease (CKD) Definition presence of either kidney damage OR GFR 3mos Kidney damage refers to the pathological abnormalities OR Markers of damage like abnormalities in blood, urine or imaging tests K/DOQI Practice Guidelines 2002

25. K/DOQI Stages of CKD (Kidney Disese Outcome Quality Initiative) StageDescriptionGFR (ml/min/1.73m 2 ) 012345012345 Increased risk Kidney damage with normal or high GFR Mildly decreased GFR Moderately decreased GFR Severe GFR decline Kidney failure >90 with CKD risk factors >90 60-89 30-59 15-29 <15 dialysis

26. Causes of CKD- REDCOP Registry 1. Diabetes Mellitus (35%) 2. Chronic Glomerulonephritis (25%) 3. Hypertension (20%) 4. Chronic Pyelonephritis (6%) 5. Autosomal Dominant Polycystic Kidney Disease (2%) 6. Unknown (5%)

27. Natural History of Renal Disease DM Nephropathy - usually progress to ESRD within 5 years from detection of overt proteinuria Glomerulonephritis - variable progression to ESRD from few months to 10 years, depending on etiology and histology Nephrosclerosis and Interstitial Diseases - usually slow progression over 10 years

28. End Stage Renal Disease (ESRD) DEFINITION Residual renal function < 15ml/min Irreversible renal damage

29. End Stage Renal Disease (ESRD) CLUES: Permanent Renal Damage 1.History Uremic features >3mos Markedly elevated BUN + creatinine without or minimal symptoms Chronic skin changes of uremia 2. Evidence of renal osteodystrophy 3. Ultrasound changes -small kidneys -hyperechoic kidneys with loss of CMJ

30. End Stage Renal Disease (ESRD) Philippine Estimate (REDCOP 2004) - Incidence = 120 million population - Prevalence= 60 million population Worldwide Incidence: ↑ by 3.2 -7.6% per year

31. Clinical Abnormalities in Uremia Fluid and electrolyte disturbance Endocrine – metabolic disturbances Neuromuscular disturbance Cardiovascular and pulmonary disturbance Dermatologic disturbances Gastrointestinal disturbances Hematologic and immunologic disturbances

32. Cutaneous Manifestations: Uremia 1. Uremic frost- white dust-like material 2. Xerosis 3. Changes in skin pigmentation 4. Changes in skin appendages Onycodermal bands = crescents 5. Half- and –Half Nails Distal brown + normal or white portion 6. Bullous dermatosis 7. Uremic pruritus 8. Vascular renocutaneous syndromes - increased capillary fragility

33. PARAMETERACUTECHRONIC HistoryPreviously normal History of fluid/ blood loss S/Sx of ineffective circulating volume Previously with renal disease/ chronic systemic disease PE VS Skin Appearance (+) signs of reduced circulating volume No change + Acutely ill Hypertension (+)Pallor (+)Chronic uremic skin changes (+)Uremic reath Chronically ill Acute vs Chronic Renal Failure

34. PARAMETERACUTECHRONIC Laboratory Hgb/Hct Ca Phosphorus S. Crea Normal Usually normal Often normal >1mg% per day Usually low Often elevated <0.5mg% per day Ultrasound Kidney Size Echogenicity CMJ Cortical thickness Normal to globularly enlarged Hypoechoic to normal Normal to blurred Normal Normal to small Hyperechoic, heterogenous Indisctinct Thinned out

35. Algorithm Renal Disease GoodPoor Non-dialytic TX Treat Etiology - - Treat AcuteChronic Treat RRT + + Etiology Assess Function Assess for Life Threatening Complications Assess for Nature of Injury Check for Acute Component Treat