JEK Renal I.ppt

Equine Renal Disease Janice Kritchevsky VMD VCS 80800 Examination of the Urinary Tract • Physical examination, collecting UA • Rectal examination • Cytoscopy • Biopsy • Diagnostic Imaging Physical exam and catheterization • General physical- weight loss, gums, edema • Observe micturition • Loo...

Equine Renal Disease Janice Kritchevsky VMD VCS 80800 Examination of the Urinary Tract • Physical examination, collecting UA • Rectal examination • Cytoscopy • Biopsy • Diagnostic Imaging Physical exam and catheterization • General physical- weight loss, gums, edema • Observe micturition • Look for urine on flanks, perineum • Catheterization • ASEPTIC technique • Mare- rigid catheter, place with digital guidance • Miniature and foals, dog speculum • Male- sedate, then pass stallion catheter after aseptically cleaning glans penis Rectal Examination • Left kidney should be palpable and freely movable • Large, painful kidney - acute inflammation • Small, hard kidney - chronic problem • Bladder should be easily palpated, uniform in wall size and nonpainful • Other structures (ureters, right kidney, urethra) not normally palpable Cytoscopy • Visualize bladder wall, ureteral papillae • Can I.D. unilateral or focal disease, stones, tumors • Make sure scope is sterile prior to use Ultrasound and Biopsy • US useful to visualize size, shape, and texture of kidney • Can I.D. calculi (Fat in hilus normal, can be mistaken for calculi) • Use to guide percutaneously guided biopsy • #1- Make sure bleeding parameters normal • Biopsy efficient way to characterize chronic renal disease • NOT helpful in assessing acute renal disease Acute Kidney Injury = Spectrum of abnormal kidney function that results in azotemia • Elevated Blood Urea Nitrogen (BUN) and Creatinine • Must differentiate pre-renal, renal, and postrenal azotemia • Pre-renal most common • Due to dehydration • Post-renal very rare in horses Pre-renal Azotemia vs. Renal • Decreased perfusion of the kidney secondary to volume restriction • May result in renal disease if persists • Need to look at urine indices to differentiate from renal • 3/4 renal mass must be gone before see problems • Creatine better indicator that BUN • With renal disease expect to see fixed urinary sp grav and dehydration Electrolytes • Electrolytes conserved by kidney are lost with renal disease, and electrolytes excreted are elevated. • With renal failure -  K+, Phos., and Na+  Cl• Calcium - unique in horses, increases if horse in renal failure on a high Ca diet Urinalysis • Specific gravity- normal range lower than dog - 1.010 - 1.035 • pH- alkalotic (7.0 - 9.0), if acidotic suspect renal disease • Protein - normally 1+ to 2+, mucus made in renal hilus, false positive on dip stick due to alkaline urine • Sediment - CaCO3 crystals normal • Normal volume - 15 ml/lb/day Urinary Clearance Ratios • These have been developed to identify abnormalities in electrolyte or enzyme excretion prior to alteration in serum values. Because of homeostasis, serum values often preserved until end stage diseases. • Uses creatinine clearance as a surrogate for GFR, Thus timed, volumetric urine collections not required. Urinary Clearance Ratios • The formula is: • % Clearance ratio (X) = • (x) urine X (creat) serum X 100 • (x) serum (creat) urine • Note: This only is useful if creatinine clearance is normal, do not use sedatives with diuretic properties to facilitate collection of urine Urinary Clearance Ratios • Normal % clearance • Na - 0.02 - 1 • K - 15 - 65 • PO3 - 0.0-0.5 • Cl - 0.04 - 1.6 • Increased PO3 = secondary nutritional hyperparathyroidis m • After furosemide • Na - 12 • K - 207 • Cl - 9.5 • Increased Na = hypoaldosteronism or renal tubular disease GGT clearance • GGT is an enzyme contained within the liver and renal tubular cells • It is a large molecule and does not cross the glomerulus, thus all the GGT from the liver is in the blood, and all the GGT in the urine is from the kidney • Increased urinary GGT suggestive of renal tubular disease GGT clearance cont. • Can do clearance ratio of GGT, again using creatinine as a stand in for GFR • Ratio = urinary GGT X (creat) serum X 100 (creat) urine • Greater than 25 suggests tubular disease “Bloody urine” on snow • There are a number of photoactive pigments in horse urine that change color when exposed to sunlight • Makes urine appear red • Can see this effect when horses urinate on snow Acute Renal Failure (ARF) • Any condition which causes marked hypotension and/or release of endogenous pressor agents has the potential of initiating hemodynamically mediated acute renal failure • History- drug administration, volume depletion, SIRS, endotoxemia, myositis or hemolysis ARF -Swollen, hemorrhagic kidney ARF - Diagnosis • History • Chemistry: Increased BUN, creatinine with dilute urine and fixed specific gravity • Cl and Na low, Ca variable • Anorexia and depression • PU/PD “stall always wet” • Tubular casts, hematuria, acidic pH Aminoglycoside toxicity • In order of most to least nephrotoxic: • Neomycin> gentamicin>amikacin>streptomycin • History- acute onset depression and anorexia while being treated with aminoglycoside • Dosing interval more important than total dose, SID safest Peaks and Troughs, Concentration and Time • Aminoglycocides are DOSE dependent antibiotics • Nephrotoxicity avoided when blood concentrations go below a certain trough concentration for a portion of the day • Therefore – Giving one large dose of an aminoglycocide per day both provides • A very high blood concentration for a few hours, which gives maximum bacterial killing and a post-antibiotic effect AND • A long period of time when blood concentrations are low, sparing the kidney Aminoglycocide Toxicity • Clinical history and signs • Foals more common than adult horses • Typical history: • Animal treated for acute bacterial disease (sepsis, pneumonia, other) • Initial response to therapy as expected • Several days into treatment, depression, anorexia, and straining to urinate • Azotemia, casts in urine • Prognosis good if recognized very quickly, aminoglycocide therapy stopped, and treatment of acute renal failure begun. • Prognosis poor if antibiotic use continued Pigmenturia • Hemoglobin or myoglobin. • Myoglobinuria is secondary to severe myositis, hemoglobinuria is secondary to intravascular hemolysis • Serum is clear if Mb, red or pink if Hb. Urine is “port wine urine colored” in both instances and tests positive for blood. • Causes intravascular hemolysis include RBC parasites, wild onion, red maple leaves, phenothiazine toxicosis, giving hypertonic substances Positive for blood in urine • Three things can result in a positive indication of blood on a urine dipstick or urinalysis • Myoglobin • Hemoglobin • Red Blood Cells • RBC’s obvious when urine is spun. • Difficult to differentiate Hb from Myoglobin in urine (need advanced tests) HOWEVER they are very easy to distinguish clinically Intravascular hemolysis Intravascular vs. extravascular hemolysis Hemoglobinuric nephropathy Non-steroidal Antiinflammatory Drugs • Actions and toxicity extremely species dependent • In horses relative toxicity: • Phenylbutazone > Flunixine > Ketoprofin • Toxicity is DOSE dependent, not time dependent • Common manifestations: • Low blood protein due to protein-losing enteropathy, oral ulceration, gastric ulcer, perforating cecal ulcers • Less common – right dorsal colitis NSAID and the kidney • Papillary necrosis • Dehydration is necessary for renal disease • Prostaglandin important for preserving blood supply to hilus of kidney when animal dehydrated. If NSAID’s given, body does not have that protective mechanism. ARF – Less Common Causes • Heavy Metals • • • • Mercury Arsenic Cadmium Lead • Plants • Oxylatecontaining plants • Oak/acorn • Pigweed ARF -Treatment - “Where there’s urine there’s hope” • Remove predisposing factor if one can be identified • Establish diuresis – restore GFR • Fluid therapy • Diuretics - Furosemide, 20% mannitol • Force feed for positive energy balancelow Ca diet Fluid therapy • If animal is polyuric, give fluids at a rate that prevents dehydration • Keep on fluids until BUN/Creatinine in normal range or stabilized • Repeated BUN/Creatinine measures to assess renal function • Once on IV fluids, UA not helpful as it will always be dilute and have an increased Na excretion Treatment, cont. • Diuretics • Furosemide 0.5 -0 1.0 mg/kg q 2-6 hr • 20% Mannitol 0.25 – 1 g/kg over 15 min 1v • If animal is oligouric or anuric, must monitor fluid intake vs. output very carefully • Central venous pressure best way to ensure that animal is not being fluid overloaded • Can do in foals • Very difficult in adult, standing animals Chronic Renal Failure (CRF) • CRF results from continued loss of the nephron function and/or population. • Signalment - usually middle aged or older horse • Clinical signs : weight loss, anorexia, depression, PU/PD, dependent edema, usually TPR normal, may feel hard or small kidney on rectal examination CRF - Clinical Lab data • Anemia - decreased erythropoietin • Hypoproteinemia - primarily albumin • Protein losing nephropathy • Azotemia with fixed urine specific gravity and dehydration • High serum calcium if on alfalfa hay or alfalfa-based diets CRF- Etiology • Proliferative glomerulonephritis antigen/antibody, EIA • Chronic interstitial nephritis and fibrosis - “end stage kidney” • Pyelonephritis - ascending infection, usually Gm - enteric organism (E. coli), often associated with renal or ureteral calculi • Other Chronic pyelonephritis CRF - Diagnostic Plan • Assess hydration status - correct pre-renal component and then reassess renal parameters • Rule out lower urinary tract disease • Renal biopsy - may be necessary for accurate diagnosis and prognosis CRF - Treatment • Antibiotics for pyelonephritis • Supportive therapy • High calorie, low calcium diet (grass hay, corn, beet pulp) • Adequate water at all times • Avoid drugs excreted via kidney Leptospirosis • Widespread but under-reported disease in horses • Very high number of horses have titers, very few have clinical disease • Increased interest with the availability of a vaccine labeled for horses • Research suggests that 400,000 horses in US are affected • Primary concerns are abortion and uveitis Leptospirosis Organism • Leptospires are spirochetes • Spiral-shaped, motile • Multiple serovars and subtypes – little cross protection • Large number of native wildlife species act as hosts • Most common in horses: • Leptospira interrogans serovar Pomona type kennewicki • Leptospira interrogans serovar grippotyphosa • Maintenance host for Leptospira interrogans serovar bratislava (does not cause disease in horses) Pathogenesis • Mucous membranes, eyes, mouth or broken skin contacts organism in infected urine, blood, or aborted tissues • Urine contaminated food and water can also transmit the disease • Motile organisms quickly move throughout body • Generally 1-3 weeks elapse between exposure and clinical disease. Clinical Signs • ASYMPTOMATIC – most horses with titers have had no recognized period of illness • Uveitis • Mid- to late-term abortions • 9 months • Placentitis, lesions in foals • Mares have very high leptospiral load when aborting and may shed in their urine for 3-4 months • Acute renal failure • Hematuria and pyuria ± visible organisms • Swollen, painful kidney on palpation Diagnosis • Fluid samples (urine, blood, ocular fluid) – PCR • Tissues (aborted fetus and membranes) – FAT or IHC • Serology – difficult to assess as most horses have titers • The Microscopic agglutination test is the way titers are measured • Look for increase in titer in acute vs. convalescent samples • For L. Pomona – a 4 fold increase in microscopic agglutination test (MAT) from baseline strongly supports the diagnosis • Titers > 100 that do not change between acute and convalescent samples suggest past exposure Treatment • Specific uveitis treatments • Antibiotics: • Maybe useful in acute infections • Urine may be sterile when horses are on treatment, but organism not eliminated from the body • Enrofloxacin, penicillin, tetracyclines most often used Leptospirosis Prevention • Keeping horses away from standing water • Protect horse feed from wildlife contamination • Good biosecurity • VACCINE • Available since 2015 Vaccine • Will stimulate an immune response with increase in anti-leptospirosis antibodies • Vaccinated horses had prolonged time between attacks of equine recurrent uveitis, but did not changoverall progression of disease unchanged Pyuria – Increased WBC in urine • Diagnostic plan determine location of inflammation - kidney, bladder, or reproductive tract. (Note- horse urine is always cloudy) • Collect urine aseptically. UA plus: • WBC/hpf - more than 5-8 = inflammation • C/S and colony count - more than 105/ml = significant DDx - kidney v.s bladder • Cytoscopy • Rectal exam - may feel ureters (feel like small intestine) • Renal biopsy or aspiration • Other signs renal disease (i.e. azotemia) Cystitis • Clinical signs - frequent attempts to urinate - stranguria, pollakiuria • HORSES WITH Acuter Renal Failure MAY EXHIBIT STRANGURIA • Females more commonly affected than males • Urine grossly hemorrhagic, purulent or normal • Thick walled bladder on rectal examination Cystitis cont. • Predisposing causes periparturient injury in mares • Bladder stones • Previous catheterization • Neurologic disease - inability to empty bladder • Diagnosis - Culture aseptically collected urine, colony counts: 105 bacteria/ml or more Bladder Stone and cystitis Cystitis - Therapy • Antimicrobial - once get sensitivity. Use antibiotic excreted in urine. TMS common first choice • Alter urine pH - 4 - 25 gm ammonium chloride p.o. SID, Vitamin C • If bladder paralysis, may try Urecholine • Prognosis good if no underlying neurologic disease.