Approach to Proteinuria and Hematuria

Transcription

1 Approach to Proteinuria and Hematuria 5 Clinical Scenarios Common to the Boards Ajay K. Singh, MB., FRCP Physician, Renal Division, Brigham and Women s Hospital, Senior Associate Dean for Postgraduate Medical Education, Harvard Medical School

2 GSK - Consultant Disclosures

3 Why Are Proteinuria and Hematuria Important? As markers of kidney disease Insight into causality Prognostic indicator

4 Proteinuria Albuminuria Normal excretion <150 mg/24 h 60% is filtered plasma protein (20-40 mg of albumin) 40% are glycoproteins -- IgA, uromodulin Detected by urine dipsticks (Albustix; Ames or Miles etc) Detects >10-15 mg/dl; almost always (+) if urine alb > 30 mg/dl Read-out is colorimetric; false (+) in highly alkaline urine Microalbuminuria = mg/24h, or µg/min Quantitative assays Sulfosalicylic method Acid precipitation, detects all proteins, sensitivity 5-10 mg/dl Dip for protein Dip scale tr mg/dl mg/dl mg/dl mg/dl mg/dl poor correlation with 24 urine

5 Hematuria Presence of three or more red blood cells per high-power field visible in a properly collected urine specimen without evidence of infection. Microscopic hematuria detected incidentally with a prevalence of 2-31% Occurring along with proteinuria strongly suggests glomerular process

6 Hematuria Major Causes Infection Pyelo, cystitis Malignancy Renal cell Ca Transitional cell Ca Prostatic Ca Metabolic/Other Calculi Hypercalciuria Hyperuricosurua Coagulopathy Cytoxan Glomerular GN eg IgA Hereditary Thin basement membrane Alport s Vaculitis Exercise Interstitial AIN PKD Papillary necrosis Vascular Renal vein thrombosis, Atheroemboli, Malignant HTN

7 #1 Young patient with routine dipstick positivity of protein in urine A 14-year old young girl is noted to have proteinuria on dipstick after a urine is sent for urinalysis and urine c and s. The young girl is asymptomatic, except for some mild frequency, has no past medical history and is completely normal on physical examination. Wt 52 Kg, BSA 1.0 m2, BP 78/62 mmhg, no edema The urine culture is negative. Recheck of UA shows 2+ protein. Spot protein to creatinine 0.8 g prot/gram creat

8 Urine positive for protein Repeat Twice Urine transiently Positive for protein Urine remains positive for protein Routine F/U Abnormal labs Normal labs >1g UPCR Check labs (esp. BUN/Cr, Alb, UPCR UA and sed Normal labs <1g UPCR Refer to Pediatric Nephrologist Check complement ANA, antids DNA Viral serologies, ASLO titer Renal US Neg Check for Orthostatic proteinuria Pos Kidney Biopsy Trial of steroids Annual F/U

9 Orthostatic (Postural) proteinuria May be present normally Proteinuria < 1g / 24 h Commonly seen in adolescents; prevalence 0.6 to 6.3% (Finish study) rare > age 30 In both sexes, proteinuria increases with age. 90% of young men with isolated proteinuria have orthostatic proteinuria; entirely benign Most children who test positive for proteinuria on initial evaluation lose the proteinuria at follow-up. 10 percent of children have persistent proteinuria >6 months Source: MAHMOUD LOGHMAN-ADHAM M., Am Fam Physician Oct 1;58(5): VEHASKARI VM, Archives of Disease in

10 #2 Middle age person, type 1 diabetic (x12 years), noticed to have albuminuria Ms. R is a 39-year old African American woman with T1DM, HTN, atrial fibrillation on Coumadin. Asymptomatic. ROS- patient active, feels energetic Medications: Coumadin, amlodipine, atorvostatin BP 112/65 mmhg, HR 97 bpm, NA 144, K 3.9, CL 110, CO2 24, BUN 17, CRE 0.70, EGFR 128 ml/min/1.73m2, mab 80 mg/g cre; Trace to 1+ prot in UA dip.

11 Natural History

12 Diabetic Nephropathy: KW nodules

13 Diabetic Kidney Disease Commonest cause of ESRD in West 45% of all U.S. patients with ESRD Screen annually for microalbuminuria in: Type 1 diabetic patients who have had diabetes >5 years Type 2 diabetic patients when diagnosis made. Test for urinary albumin excretion Albumin to creatinine ratio (ACR) Timed collection (e.g., 12 or 24 h) of albumin concentration To reduce risk and/or slow progression of nephropathy optimize glucose control. optimize blood pressure control Use ARB or ACEi

14 Screen for MA in Diabetic Patient is positive (repeat twice) Urine transiently Positive for protein >30 mg AB on UACR Routine F/U MAB mg NL Cr 1. Glycemic control HbA1C<7.5% T1DM age<19 or elderly HbA1C<7% for adults 2. Manage BP <140/90 3. ACEi or ARB AB >300 mg Glycemic control Manage BP ACEi/ARB AND REFER TO NEPHROLOGY Typical Work up Manage as High Risk Patient Atypical Kidney Biopsy

15 #3 Patient with hematuria, RBC casts and rapid loss in kidney function A 24-year old hairdresser from Cape Cod is admitted with oliguria. Has a 2 day history of tea colored urine, headaches, and feelling unwell. 1- day history of coughing up blood and dyspnea. Examination 150/95 mmhg, HR 110 bpm, afebrile, O2 sat 91% on air, reduced air entry in lung bases. Labs: BUN 58 mg/dl, creatinine 2.9 mg/dl, Hb 10.2 g/dl, WBC 6.2, plats 286,000. UA 4+ bl 2+ prot, no leuks; sediment dysmporhic RBCs, 1-2 RBC casts, 2-4 WBCs/HPF.

16 Glomerular Syndromes Nephritis: Hypertension, Azotemia, proteinuria, hematuria, RBC casts / dysmorphic RBCs Nephrosis: edema, proteinuria, hypoalbuminemia, lipid abnormalities RPGN: rapid renal failure, crescents on renal biopsy + nephritis Isolated urinary abnormalities: hematuria / proteinuria

17 Pulmonary Renal Syndrome Main Causes Anti GBM Disease: Goodpasture s ANCA associated vasculitis Granulomatosus with polyangiitis (Wegener s) Microscopic polyarteritis (MPA) Churg Strauss Immune complex mediated Lupus nephritis Cryoglobulinemia HSP nephritis

18 Dysmorphic RBCs and Red Cell Cast

19 Anti-GBM Nephritis Goodpasture s Syndrome Uncommon: incidence 0.1 cases/million 1-2% of renal biopsy specimens Slight preponderance in males Age 1st to 9th decade More common in whites over African-American s Year-round presentation,? Spring and summer 50-75% have upper respiratory prodrome, plus fever, rash, myalgias, malaise, headache, weight loss Renal presentation with RPGN - proteinuria but usually not nephrotic, hypertension uncommon US - normal size kidneys

20 Pathologic Features of Anti-GBM Nephritis

21 Goodpasture s Syndrome Treatment Treatment without methylprednisone and plasmaphereis 89% progress to death or dialysis; only 10% improved Treatment with pulse steroids, plasmapheresis, and Cytoxan standard-of-care 50% improve Protocol Pulse methylpred 1 g QD x 3 d, mg/kg prednisone Cyclophosphamide 3 mg/kg/d (reduced dose in older patients, or if GFR < 10) > 2 months Plasma exchange daily 4 L with albumin replacement (or FFP if pulmonary hemorrage present) x 14 d or until ab goes away Patients with serum creat of >7.0 respond to treatment 75% with Scr <7 respond, 8% with Scr > 7 respond Generally no improvement in patients on dialysis

22 #4 19-year old white male and his military physical 19-year white male is evaluated as part of health screening for his military physical. Healthy asymptomatic One prior episode of gross hematuria, resolved spontaneously after 3 or 4 days. Not referred PE normal UA 2+ blood, no protein, 5-10 red cells (dysmorphic) in urine microscopy Biopsy considered done IgA nephropathy

23 Epidemiology IgA nephropathy Most common cause of nephritis in the world (15 to 40% of primary GN in world, 20% of primary GN in USA) Males > Females (2:1) Peak occurrence in 2nd & 3rd decades Asian predominance (up to 40% of biopsies compared with 20% in European/U.S. registries) Clinical Synpharyngitic (24 to 48 hrs after URI or GI infection -- in contrast with post-infectious nephritis 1 to 3 weeks) Low grade fever, loin pain Serum IgA levels elevated in ~50% (Test for elevated serum IgA not diagnostic) Spectrum of microscopic hematuria + albuminuria to RPGN Can be with or w/o Henoch-Schonlein Purpura (HSP) Children: gross hematuria after URI Adults: microscopic hematuria and/or proteinuria

24 IgA: Therapeutic Options No Treatment Treatment ACEi/ARB Glucocorticoids Fish Oils Tonsillectomy Immunosuppressives Azathioprine + steroids Cyclophosphamide + steroids Mycophenolate mofetil

25 #5 Teenager with sudden onset face swelling, LE edema and nephrotic proteinuria 17-year white male high school student develops sudden onset of facial swelling, LE swelling, frothy urine. Otherwise completely asymptomatic. One week before presentation he had a bee sting on his forearm. Examination normal BP. 2 Kg increase in weight, swollen eye-lids, lips, face, anasarca Renal function Bun 14 mg/dl, Creat 0.5 mg/dl,. serum albumin 2.8 g/dl, total cholesterol 315 mg/dl, triglycerides 68 mg/dl, LDL cholesterol 228 mg/dl. UACR - 16 g alb/g cre.

26 Nephrotic Syndrome Proteinuria (> 3.5g/d) (>2 g/d is usually glomerular origin proteinuria) Hypoalbuminemia (< 3 g/dl) Hyperlipidemia Lipiduria Edema Bland urine or fatty casts/ free fat / oval fat bodies

27 Urinalysis: key features

28 NS: Etiology Primary Causes Membranous Focal Segmental GS (FSGS) Minimal Change Disease IgA Secondary Causes Medications Gold, NSAIDs, Interferon - alfa, Heroin, Captopril, Allergens Bee Sting, Pollen Infections Bacterial, Viral, Helminth Cancer Solid: Lung, colon, stomach Leukemia, Hodgkins, ovarian Autoimmune Diseases Metabolic Diseases Pregnancy

29 Normal and Minimal Change Disease A: Normal B: MCD

30 Minimal changes of glomeruli basic characteristics 1. Full blown nephrotic syndrome with selective proteinuria 2. Rarely presence of hematuria, hypertension, or renal insufficiency 3. Absence of glomerular abnormalities on LM an IF. 4. Typical picture of damage of epithelial cells (fusion of foot processes) in EM

31 Swelling/edema/UA pos for protein Check labs esp. BUN/Cr, Alb, UA, UACR Abnormal labs Refer to Nephrology >2 g UACR Abnormal labs Otherwise Normal labs Further W/U Kidney Biopsy Trial of steroids For MCD Partial response or No response Or remission-then-relapse after 16 w therapy Remission Routine F/U

32 Summary/Conclusion 6 clinical scenarios Proteinuria and Hematuria - GN of different causes and different age groups Painting by Sir Luke Fildes.