Diagnosis of kidney disease Linda E. Luther, DVM, DACVIM (SAIM) Small Animal Track November 2012 Learning objectives Review renal physiology. Describe how blood and urine tests, as well as radiographs and ultrasound, can help to define kidney disease. Describe normal and abnormal systemic blood pressure in dogs and cats. Discuss how to interpret Leptospirosis titers. Describe the indications and contraindications for a kidney biopsy. Physiology Functional unit is the nephron. Glomerulus: Filtration (GFR) Tubules: Reabsorption and secretion 1 million nephrons/kidney! Functions of the kidneys Excrete waste products Conserve water Electrolyte and acid/base regulation Produce hormones o Erythropoietin (red blood cell production) o Renin (regulation of blood pressure) o Calcitriol (calcium and phosphorus regulation) Some diseases of the kidneys Acute renal failure Chronic kidney disease (CKD) Pyelonephritis The nephron Diagnosis of kidney disease combines the interpretation of: Clinical signs Blood tests Glomerulonephritis Urine tests Leptospirosis Blood pressure determination Perirenal pseudocyst Function tests Polycystic kidney disease (PKD) Radiographs Calculi Ultrasound Neoplasia Biopsy Renal dysplasia Clinical signs of kidney disease PUPD Anorexia Vomiting Weight loss Abdominal pain Or…nothing Blood tests CBC o Hematocrit, leukogram, platelet count Blood chemistry profile o BUN, creatinine, calcium, phosphorus, sodium, potassium, albumin, HCO3 Azotemia Increased BUN and/or creatinine Azotemia ≠ kidney disease and kidney disease ≠ azotemia Underlying mechanisms o Pre renal: Dehydration o Renal: Renal failure o Post renal: Urethral obstruction, uroabdomen Need Uspgr to differentiate prerenal vs. renal azotemia! Loss of 66% of nephrons: Isosthenuria Loss of 75% of nephrons: Azotemia Leptospirosis testing in dogs o Titers Vaccination vs. disease Acute vs. convalescent 4-fold increase or decrease in 1-3 weeks Vaccination titers often less than 1:800, but up to 1:3200 possible PCR to detect organism Blood in very early infection Urine 10-14 days post infection False positives and false negatives can occur Not affected by vaccination Lyme testing in dogs o Labs and Goldens w/increased risk of Lyme nephritis Other breeds less likely but still may be at risk o Screen for proteinuria if positive for Lyme o Screen for Lyme if proteinuric Urine tests Specific gravity o o o Urine dipstick Normal ‘depends’ 1.003 - >1.080 Isosthenuria 1.008-1.012 if normal hydration 1.012-1.018 if dehydrated >1.030 dog; >1.035-1.040 cat: Can concentrate urine Urine protein o o o o Protein Blood Glucose pH Urine sediment o o Present? Significant? Methods Dipstick/SSA UPC Microalbumin Urine protein o Urein protein/creatinine ratio (UPC) Renal vs. post-renal rbcs wbcs Epithelial cells Casts Crystals Bacteria ✓ sediment first. If active sediment: Post renal proteinuria Repeat 3x q 2 wks if not azotemic. If azotemic (and urine not concentrated), assess proteinuria as significant. Normal < 0.4 in cats < 0.5 in dogs Tubular disease 0.5-1 Glomerular disease ≥ 2.0 Microalbuminuria (albumin ≤ 30 mg/dL) Warning sign of glomerular disease in humans In vet med very sensitive, but not specific Infectious, immune, neoplastic disease increase it well as renal disease Positive predictive value, negative predictive value uncertain o o o o o o o Urine culture with MIC sensitivities Blood pressure > 160 mmHg 65-75% CKD dogs and cats have increased BP Fundic exam may detect retinal changes Check blood pressure when hydration is normal Function tests: GFR Serum creatinine level is used as an approximation/to stage CKD o Low sensitivity, may vary with hydration status, muscle mass, if fasted or not o Serial creatinine levels in an individual animal may indicate early kidney disease. o Other biomarkers of early kidney disease are being investigated, so stay tuned. Clearance studies are more sensitive and specific, but less available/practical o Inulin, creatinine, iohexol o Scintigraphy Kidney imaging Radiographs: Size, mineralization o Large kidneys Acute disease FIP, Lepto, LSA, EG toxicity, PKD o Small kidneys Chronic disease Ultrasound o There are a limited number of ways the kidneys can respond to a variety of disease processes. Several ultrasound changes observed will be nonspecific. o Ultrasound findings further characterize disease. o Ultrasound does not predict renal function. o Ultrasound changes that may be observed include: (Increased/decreased size) (use radiographs to best judge kidney size) Overall echogenicity changes Cortical cysts/polycystic kidney disease Decreased corticomedullary distinction Hyperechoic corticomedullary rim Calculi Renal pelvic dilation Masses Infarcts Subcapsular changes Pseudocysts Fluid/thickening Hematomas/Abscesses Kidney biopsy The value of kidney biopsy will likely increase in the near future as current knowledge/discussion increases. Indicated when it will make a difference in making a specific diagnosis, deterimining prognosis and/or establishing or altering therapy. o Renal dysplasia in a breeding line o Masses o Acute renal failure, specifically acute nephritis not due to Leptospirosis or pyelonephritis o Lyme nephritis suspected o Subcapsular fluid or thickening (FNA) o Protein losing nephropathy* Contraindications o Small patients (< 5 kg), uncontrolled hypertension, coagulopathy, pyelonephritis, cysts, hydronephrosis, severe azotemia Complications o Hemorrhage Processing o Light microscopy (LM) In formalin o Electron microscopy (EM) for glomerular diseases to verify presence of immune complexes and their specific location in the glomerulus In 3% glutaraldehyde in phosphate buffer o Immunofluorescence (IF) to identify type of immune complexes (IgG, IgA, IgM, complement) Frozen or in Michel’s solution Methods o Always with general anesthesia Core biopsy processing o Biopsy cortex only (Lees & Bahr, 2011, p. 214)) Where the diagnosis is (glomeruli) Safer as this avoids the arcuate arteries o Wedge Largest # glomeruli Best for renal dysplasia Surgical o Core or Tru-Cut o 14-18G o Blind, U/S-guided, surgical or laparoscopic? o Laparoscopic best quality, lowest risk o Surgical second best Diagnosis of kidney disease references Greene CE, Sykes JE, Moore GE, Goldstein RE, Schulz RD. Leptospirosis. In Infectious Diseases of the Dog and Cat, 4th ed, Greene CE (ed), 20012, St. Louis, Elsevier Saunders, pp. 431-447. Lees GE, Bahr A. Renal biopsy. In Nephrology and Urology of Small Animals, Bartges J and Polzin DJ (eds), Wiley-Blackwell, Ames, IA, 2011, 209-214.. Lees GE, Berridge BR. Renal biopsy—When & Why. NAVC Clin Brief 2009:26-29. Lyon SD, Sanderson MW, Vaden SL, Lappin MR, Jensen WA, Grauer GF. Comparision of urine dipstick, sulfosalicylic acid, urine protein-to-creatinine ratio, and species-specific ELISA methods for detection of albumin in urine samples of cats and dogs. J Am Vet Med Assoc 2010;236:874-879. Nyland TG, Mattoon JS, Herrgesell EJ, Wisner ER, Urinary tract In Nyland TG, Mattoon JS (eds), Small Animal Diagnostic Ultrasound, 2nd ed., Philadelphia, W.B. Saunders Co., 2002, 158-195. Polzin DJ. Chronic kidney disease. In Textbook of Veterinary Internal Medicine, 7th ed., Ettinger SJ, Feldman EC (eds), Saunders Elsevier, St. Louis, MO, 2010, 1990-2021. 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