1. Patrick Carter MPAS, PA-C Clinical Medicine I February 21, 2011 Approach to the Patient with Renal Disease

2. Objectives Define the following terms: Anuria Oliguria Polyuria Hematuria Proteinuria Pyuria Dysuria Frequency Hesitancy Renal colic Briefly describe the anatomy and physiology of the renal system Review the tools commonly used to detect renal disease including: Significant historical features Significant physical exam findings Lab abnormalities

3. Objectives Define uremic syndrome Review the following organ systems and their manifestations of uremia: GI Neurologic Cardiopulmonary Hematologic Metabolic Differentiate urine findings associated with kidney diseases including: Casts Pyuria Hematuria Proteinuria

4. Objectives Review the role of GFR in ability of the kidney to function Define azotemia Calculate a creatinine clearance on a patient. Differentiate between acute and chronic renal failure including: Causes Laboratory findings Differentiate between nephritic and nephrotic syndrome based upon lab and physical findings.

5. Detection of Renal Disease Patients with renal disease may or may not have symptoms Symptoms of renal disease when they do occur are typically non-specific The patient with renal disease may be presenting with acute or chronic disease A high index of suspicion is required

6. Definitions Anuria – absence of urine production (<50ml/day) Oliguria – decreased urine production (<400ml/day) Polyuria – increased urine production (>2.5L/day) Gross Hematuria – patient able to visualize blood Microscopic Hematuria – blood determined by lab Proteinuria - > 150mg protein / day Pyuria - WBC in the urine Dysuria – Pain or discomfort with urination Frequency – Need to urinate more frequently than usual Hesitancy – difficulty in initiating urination Renal colic – intermittent pain radiating from flack to groin ( in excess of child bearing)

7. Detection of Renal Disease Tools of Detection History and physical Urinalysis Estimates of GFR, Cr Clearance BUN/Creatinine Blood chemistries Renal ultrasonography

8. Tools of Detection: H & P History Changes in urination Abdominal/Flank pain Uremic symptoms Use of NSAIDS Family history of renal disease, stones or dialysis Edema Dyspnea Confusion/Delerium Physical High blood pressure Jugular venous distention Rales Pericardial rub Edema Renal Bruits Prostate Exam Abdominal pain

9. Uremic Syndrome The constellation of findings observed in advanced renal failure Etiology of many manifestations is unknown but some symptoms appear to correlate with the accumulation of nitrogenous waste products Earliest manifestations include anorexia, pruritus, fatigue, difficulty with memory and concentration Advanced stages of renal failure associated with involvement of multiple organ systems

10. Uremic Syndrome GI manifestations of uremia Anorexia, nausea Weight loss Uremic gastritis GI bleeding Arteriovenous malformations (AVMs)

11. Uremic Syndrome Neurologic manifestations of uremia Difficulty with concentration, memory Confusion Drowsiness Myoclonus Tremors Peripheral neuropathy, mononeuropathy Seizures, coma

12. Uremic Syndrome Cardiopulmonary manifestations of uremia Volume overload Hypertension Jugular venous distention Edema Pericarditis Chest pain Pericardial rub Pericardial tamponade

13. Uremic Syndrome Hematologic manifestations of uremia Anemia Fatigue Pallor High output failure Platelet dysfunction Bleeding tendency - GI, CNS, post-operative Prolonged bleeding time

14. Uremic Syndrome Metabolic manifestations of uremia Metabolic acidosis - abdominal pain, weakness, Kussmaul respirations Hyperkalemia - muscle weakness, cardiac arrhythmias Hypocalcemia - tetany, perioral numbness Hyperphosphatemia/hyperparathyroidism - itching, bone pain Hyperuricemia - gout Hypermagnesemia - reduced DTRs, arrhythmias

15. Tools of Detection Urinalysis Important to use mid-stream, clean catch urine that is < 1 hour old Urine dipstick for specific gravity, pH, protein, glucose, hemoglobin Urine sediment after centrifuge evaluated for presence of cells, crystals, casts

16. Tools of Detection Urinalysis for proteinuria Dipstick gives a semi-quantitative analysis Presence of significant proteinuria is highly suggestive of presence of renal disease 24 hour urine collection more accurate <150 mg/24 hours is normal 150 mg-3.5 gm/day non-nephrotic range >3.5 gm/day nephrotic

17. Proteinuria Greater than 150mg/day 3 Classifications Glomerular Increased filtration of albumin across the glomerular capillary wall Diabetic Nephropathy, Preeclampsia, IgA nephropathy Benign exercise or orthostatic proteinuria Tubular Defective reabsorptive capacities in the proximal tubules Hypertensive nephrosclerosis, Fanconia, NSAIDs, Sickle Cell Overflow Overabundance of immunoglobulin light chains secondary to overproduction. Multiple myeloma, Amyloidosis

18. Proteinuria Note of Caution: In order for the dipstick to light up it takes 300-500 mg/day of proteinuria Better to obtain 24 hour urine collection for protein Microalbumin is being utilized as a screening mechanism for diabetic patients with diabetic nephropathy in the office setting

19. Tools of Detection Urinalysis for hematuria Dipstick is semi-quantitative analysis Urine sediment abnormal if >2 RBCs per high power field Presence of hematuria may or may not be secondary to renal disease Dysmorphic RBCs suggest glomerular disease

20. Hematuria Need to determine if Gross Hematuria is actually blood Contaminated (Menstruation, Hemorrhoids, Post-partum) Red Beet consumption in certain genetically disposed pts Medications (rifampin, pyridium) Dipstick cannot differentiate between RBC, Myoglobin, or Hemoglobin Rhabdo, etc. History is the insight to the diagnosis Burning on urination, flank pain, family history, after exercise, asymptomatic elderly or with risk factors for malignancy

21. Tools of Detection Urinalysis for pyuria Implies either infection or inflammation of the kidney or urinary tract Most cases are not related to renal disease but rather represent urinary collecting system disease

22. Tools of Detection Urinalysis for casts WBC casts - inflammation of the kidney RBC casts - glomerular inflammation Granular casts - non-specific but classically associated with acute tubular necrosis Broad/waxy casts - chronic renal disease

23. Casts

24. Estimation of GFR GFR = volume of plasma filtered in a given period of time, typically expressed ml/min GFR is an indirect estimate of functional renal mass Can determine presence of renal insufficiency and follow progression May be normal in many renal diseases eGFR = 186 x Serum Creatinine-1.154 x Age-0.203 x [1.212 if Black] x [0.742 if Female] Or Just use a GFR calculator

25. BUN and Serum Creatinine Indirect estimates of renal function due to the fact they are renally excreted BUN is end-product of protein metabolism Creatinine is breakdown product of muscle creatine Azotemia - abnormal elevation of BUN and creatinine May be influenced by factors other than renal clearance Protein intake for BUN Muscle mass for creatinine BUN/Cr ratio is helpful in determing Pre-renal azotemia

26. Creatinine Clearance The amount of creatinine cleared from the plasma in a given time Creatinine clearance overestimates GFR because it is secreted and freely filtered Urinary Cr (mg/dl) x urine vol (ml/d) Plasma creatinine (mg/dl) x 1440 min/d Normal is 100-140 ml/min (10-15% lower in females) Or just use a Cr Cl calculator

27. The Renal Syndromes Renal Failure Acute Chronic Rapidly Progressive Nephrotic Syndrome Nephritic Syndrome Asymptomatic urinary abnormalities Hematuria Proteinuria Hematuria and proteinuria

28. The Renal Syndromes Allows narrowing of differential diagnosis Can help direct work-up and treatment Each syndrome associated with multiple diseases One disease may be associated with multiple syndromes (Lupus nephritis, IgA nephropathy) Individuals may simultaneously have more than one syndrome

29. The Renal Failure Syndromes Differentiation depends on the rate of progression of renal failure Acute - hours to days Rapidly progressive - weeks to few months Chronic - months to years Uremia may be common to all forms

30. Acute vs. Chronic Renal Failure Acute Baseline Cr normal Baseline UA normal Normal kidney size PTH normal No broad casts Oliguria possible Chronic Baseline Cr abnormal Baseline UA abnormal Reduced kidney size PTH elevated Broad, waxy casts Normal urine output PTH is elevated secondarily due to low calcium levels secondary to chronic renal disease

31. Acute Renal Failure Common Causes Acute Tubular Necrosis (ATN) Prerenal azotemia Acute interstitial nephritis Acute glomerulonephritis Urinary tract obstruction

32. Chronic Renal Failure Common Causes Diabetic nephropathy Hypertensive nephrosclerosis Chronic glomerulonephritis Chronic tubulointerstitial disease Inherited diseases Ischemic nephropathy

33. Rapidly Progressive RenalFailure Most common cause is rapidly progressive glomerulonephritis with the pathologic lesion of necrotizing and crescentic GN. Common causes of rapidly progressive glomerulonephritis include vasculitic disorders (microscopic polyangiitis, Wegener’s disease, cryoglobulinemia), infection associated glomerulonephritis, anti-GBM disease May also be seen in HIV nephropathy, collapsing FSGS, some IgA nephropathy, some lupus nephritis, and others

34. Nephrotic Syndrome Proteinuria > 3.0 to 3.5 gm/day Hypoalbuminemia Edema Hyperlipidemia Lipiduria (oval fat bodies)

35. Nephrotic Syndrome Other manifestations Hypercoagulable state Ascites Pleural effusions Infections secondary to altered immune response

36. Nephrotic Syndrome Common causes Minimal Change Disease Focal Segmental Glomerulonephritis Membranous Nephropathy Membranoproliferative glomerulonephritis Diabetic nephropathy IgA nephropathy Lupus nephritis

37. Acute Nephritic Syndrome Renal failure, acute Intravascular volume expansion Hypertension Edema Active urine sediment Dysmorphic RBCs RBC casts Proteinuria

38. Acute Nephritic Syndrome Common causes Post-strep GN IgA nephropathy Vasculitis Lupus Nephritis Rapidly Progressive Glomerulonephritis

39. Asymptomatic UrinaryAbnormalities Hematuria Gross Microscopic Proteinuria Hematuria and Proteinuria

40. Asymptomatic UrinaryAbnormalities Isolated Hematuria Defined as presence of > 2 RBCs per hpf in the absence of renal insufficiency, proteinuria, or pyuria Most cases are of urinary collecting system origin or extraurinary Dysmorphic RBCs highly suggestive of a renal source and likely glomerular source

41. Asymptomatic UrinaryAbnormalities Common causes of isolated hematuria UTI Vaginal bleeding Tumors Bladder Ureter Kidney Nephrolithiasis Sickle cell disease or trait Glomerular disease

42. Isolated Proteinuria >250 mg/24 hours urinary protein in the absence of hematuria, renal failure, or manifestations of nephrotic syndrome Common Causes Glomerular disease Inherited diseases of the kidney eg. PCKD Tubulointerstitial disease Vascular disease

43. Asymptomatic Hematuria with Proteinuria This combination is more suggestive of a renal disease than hematuria alone Differential diagnosis is similar to that for proteinuria alone

44. Conclusions Detection is relatively easy as long as the index of suspicion is high Once renal disease is detected it should be categorized into one or more renal syndromes Further diagnostic approach and work-up is then guided by the approach to the various syndromes which is determined by the differential diagnosis and treatment potential

45. Any Questions?