Renal & LUTD Notes - EXAM 2 PDF

Renal disease Clinical approach and laboratory evaluation of renal disease Kidney function - regulate volume and composition of extracellular fluid by forming urine - kidney disease: o decreased GFR - azotemia o damaged glomerular filtration barrier - p...

Renal disease Clinical approach and laboratory evaluation of renal disease Kidney function - regulate volume and composition of extracellular fluid by forming urine - kidney disease: o decreased GFR - azotemia o damaged glomerular filtration barrier - proteinuria o tubular defects - altered urine/plasma composition, urolithiasis o endocrine function o blood pressure History - polyuria/polydipsia o PD >100 ml/kg/day in dogs, >50 ml/kg/day in cats o urine more clear/dilute o differentiate PU from pollakiuria, dysuria, urinary incontinence - nonspecific signs: lethargy, anorexia, weight loss - uremia o nausea, vomiting, lethargy, hypothermia, oral mucosal and GI ulceration, melena, encephalopathy, seizures - edema, ascites o nephrotic syndrome o overhydration - ocular signs of hypertension: hyphema (bleeding in anterior chamber of eye), mydriasis, blindness - AKI: acute signs, toxins/medications Physical examination - palpation of the kidneys: size, contour, pain - size of the bladder o large - PU, turgidity - obstruction, empty - oliguria - hydration status o dehydration (PU), hypovolemia o overhydration (oligo-anuria): edema, ascites, pleural effusion, dyspnea - poor body condition (CKD) - fibrous osteodystrophy - video o CKD in young growing animals - pathological fractures o older animals o mineral and bone disorder in CKD - mucous membranes o pale with anemia o uremic ulceration of oral mucosa, tongue tip necrosis - blood pressure, fundic examination Acute/chronic disease? - AKI potentially reversible, CKD irreversible  - CKD ≥3 months - history + PE o longstanding PU/PD, poor appetite, weight loss, poor body condition, poor coat quality – CKD o kidney size and shape: ▪ normal/enlarged, normal shape, turgid, pain - AKI ▪ small, irregular - CKD - diagnostic imaging - renal size and contour - mineralization, loss of internal architecture - CKD - blood testing o nonregenerative anemia - CKD, (AKI) o hyperkalemia - AKI, dogs with CKD fed renal diets - urinalysis o pyuria, bacteriuria, white cell casts - pyelonephritis (acute/chronic) o calcium oxalate crystals - ethylene glycol poisoning o euglycemic glucosuria - proximal tubular dysfunction (acute/chronic) o large numbers of granular casts, renal epithelial tubular cell casts - acute tubular necrosis Prerenal/renal/postrenal azotemia? - renal vs prerenal o USG >1.030 in dogs, >1.035 in cats - prerenal o IV fluid therapy resolves/improves azotemia - prerenal - postrenal o history + PE ▪ lower urinary tract obstruction/rupture signs o diagnostic imaging ▪ partial/unilateral ureteral obstructions o free fluid analysis ▪ creatinine >2x that in blood - urinary tract rupture Assessing disease severity - IRIS grading of AKI, staging of CKD Laboratory diagnostics of kidney function - GFR - glomerular filtration rate o (Direct assessment of GFR) o surrogate plasma/serum markers of GFR: urea, creatinine, SDMA ▪ only valid with steady state renal function ▪ isolated evaluation does not determine whether azotemia is prerenal/renal/postrenal, acute/chronic, reversible/irreversible - USG Proteinuria - pre-renal - postrenal - renal o glomerular o tubular - indications: - CKD - IRIS staging - protein-losing nephropathy Proteinuria - dipstick o sensitivity >80%, poor specificity - UPCR - urine protein to creatinine ratio o proteinuria >0.4 in cats, >0.5 in dogs o glomerular disease >2 o 24 h urine protein quantification o values from in-hospital obtained samples higher o effect of hematuria, pyuria o day-to-day individual variability - more than 1 sample with marked proteinuria Renal biopsy/FNA - indications o persistent substantial proteinuria (UPCR >3.5) o proteinuria unresponsive to anti-proteinuric therapy o progressive decline in renal function despite therapy - contraindications o IRIS stage 4 CKD o primary tubulointerstitial disease o hydronephrosis o pyelonephritis o hemostatic disorders o renal abscessation o little to gain with biopsy: amyloidosis, hereditary nephropathy  - help determine if immunosuppressive therapy is indicated - AKI - prognosis, does not often identify the cause - pre-biopsy o proteinuria is persistent, renal o control of systemic hypertension o discontinue anti-thrombotic therapy o assessment of hemostasis - FNA o low-risk alternative to biopsy with suspected inflammatory/neoplastic disease o rarely rewarding with glomerular disease Coagulation status - protein-losing nephropathy - hypercoagulable state – thrombotic complications - AKI - thrombosis/bleeding disorders - extracorporeal therapy Urinalysis - assessment of renal function, evaluation for renal disease o urine concentrating ability o glomerular and tubular function o bacteria - indication: all patients with known/suspected renal disease o biochemical evaluation (dipstick) o USG o urine culture o UPCR Urinalysis - USG - ratio of weight of volume of liquid to weight of equal volume of distilled water - refractometer o dipsticks are not reliable - isosthenuria 1.008-1.015 - urine has about same solute concentration as glomerular filtrate and plasma - hyposthenuria 0.15 - normal urine concentrating ability from 8 w of age in kittens and 4 w in puppies - normal: o dog: 1.015-1.050 o cat: 1.030-1.060 - dehydration/prerenal azotemia: o dog: >1.030 o cat >1.040 - AKI/CKD: sub-maximally concentrated urine + azotemia - isosthenuria: 1.008-1.012 o healthy/AKI/CKD o kidneys are neither concentrating nor diluting - hyposthenuria o active dilution in tubules  o non-renal causes of PU/PD should be investigated Urinalysis - renal glycosuria o tubular dysfunction - urine pH o renal tubular acidosis Urinalysis - sediment - hematuria o renal: nephrolithiasis, pyelonephritis, idiopathic - pyuria o lower/upper urinary tract infection - transitional epithelial cells o smaller with tapered ends (caudate cells) - renal pelvis o epithelial cellular casts - renal injury - bacteria o lower/upper urinary tract - crystalluria o tubular dysfunction - cylindruria (casts) - kidney damage o hyaline, granular, waxy, fatty, cellular (epithelial, WBC, RBC), contain crystals/microorganisms, mixed - parasites Diagnostic imaging - radiographs o renal size o contour o radiopaque calculi - CT o focus of interest: renal pelvis, ureter o mass Diagnostic imaging - US - significantly diseased kidneys can appear completely normal - diffuse enlargement + normal internal architecture o compensatory hypertrophy, AKI, amyloidosis, lymphoma, portosystemic shunts, acromegaly - small kidneys o congenital renal hypoplasia/dysplasia, CKD, chronic ureteral obstruction - diffuse increase in cortical echogenicity - renal disease (nonspecific) - lack of corticomedullary definition o CKD (nonspecific) - focal lesions o cyst, hematoma, abscess, granuloma, neoplasia, infarct - subcapsular/perirenal fluid  - medullary rim sign - pyelectasia Acute kidney injury - definition - clinical syndrome of varying severity initiated by multitude of causes that can be accompanied by rapid decline in GFR and renal function Phases 1. induction 2. extension 3. maintenance 4. recovery (days or months) kentamycin, monitored renal values → non azotemic AKI progression and recovery for 2 months (crea not in same values as before) Categorization - prerenal (hemodynamic): renal hypoperfusion (no injury to renal parenchyma, e.g. hypovolemia since dehydration, azotemia, if it is there for long time can progress to renal) - intrinsic renal: ischemia/nephrotoxin damages renal parenchyma - postrenal (obstructive): acute obstruction of the urinary tract (acute obstruction to increased hydrostatic pressure injury kidneys, can be reversed) Acute kidney disease - AKI ≤7 days - AKD >7 days - CKD ≥3 months - post-AKI state/early CKD - monitor and treat like AKI - grades (creatinine) - recovery - GFR biomarkers (creatinine, SDMA, BUN) normal following episode of AKI Etiology - prerenal - hypoperfusion → decreased GFR, normal renal parenchyma o rapid correction of GFR following restoration of renal perfusion - drugs/conditions contributing to AKI  o NSAIDs, ACEIs (angiotensin converting enzyme inhibitors), diuretics, cyclosporine, radiocontrast agents, hypercalcemia, bacterial endotoxin Etiology - intrinsic - diseases of large renal vessels o renal artery thrombosis, vasculitis, renal vein compression - diseases of renal microvasculature and glomeruli o glomerulonephritis (common in dogs since borrelia causes), vasculitis, hypertension… - ischemic/nephrotoxic acute tubular necrosis o renal hypoperfusion, endogenous/exogenous toxins - other processes involving tubulointerstitium o neoplastic infiltration, oxidative injury, infectious disease - systemic diseases o infectious diseases: leptospirosis, babesiosis, parvovirosis o sepsis and MODS o hypo-and hyperadrenocorticism o pancreatitis o heatstroke o cutaneous and renal glomerular vasculopathy - nephrotoxins o endogenous/exogenous o different mechanisms of injury ▪ intrarenal vasoconstriction, tubular cell toxic injury, intratubular obstruction o e.g. ▪ contrast agents (not actually known) ▪ myoglobin, hemoglobin ▪ drugs: aminoglycosides, amphotericin B, cyclosporine, tacrolimus, albumin… ▪ grape, raisin, currant (dogs) ▪ lily (cats) ▪ ethylene glycol ▪ melamine (increases protein in petfood but is toxic but finds its way to some feed) ▪ cholecalciferol (vitamin D) - rodenticide - infectious o leptospirosis o pyelonephritis Etiology - postrenal - uroabdomen o trauma o bladder may be palpable o may not be grossly hematuric - ureteral/urethral obstruction o uroliths/debris o urethral/bilateral ureteral obstruction o unilateral ureteral - no biochemical abnormalities if other kidney is normal o unilateral ureteral with CKD - acute on chronic o renal pelvis dilation, blunting of diverticuli, proximal ureteral dilation Diagnosis - clinical signs - uremia: GI, neurologic, cardiovascular - hypothermia - hypertension - hypervolemia o excess IV fluids - ventricular premature complex arrhythmias - nausea, vomiting, diarrhea, anorexia, GI and oral ulceration - obtundation, coma, seizures Diagnosis - laboratory evaluation - CBC oleukocytosis (→ inflammation) ohemoconcentration (→ HCT, RCB high→ dehydration, can be cause (prerenal) or because renal AKI, prerenal and renal azotemia is difficult to differentiate, diagnose with response to treatment (if resolves with 24h fluids → prerenal)) - biochemistry o azotemia - increase in creatinine, BUN ▪ time lag! (treat before azotemia develops) ▪ prerenal: mild to moderate, BUN>creatinine ▪ postrenal: marked, no azotemia with unilateral obstruction o electrolytes: hyperP, hyperK (oligo or anuric), hypoNa - urine o urine volume not helpful o isosthenuria (cannot dilute not concentrate → worse than hyposthenuria that can dilute) o casts o prerenal: UOP decreased, USG >1.030, hyaline casts o urine culture ▪ pyelonephritis o leptospira PCR hematology of 3yo castrated male cat, acute vomiting received treatment for AKI in other clinic, still vomiting, in lateral recumbency ➔ usually maropitant enough but this needed fluids increased erythropoiesis, dehydrated (30% HCT normal, now 60%) biochem: kidney values high → moderate azotemia, hyper chol, hypo Na, hypoK, hypoCl ➔ can be renal or prerenal ➔ fluids 24h ➔ urea okay, crea lower → prerenal azotemia Diagnosis – imaging - radiographs: kidney size, radiopaque calculi - US: cortical thickness, cortical-medullary densities, renal pelvis dilation, calculi - prerenal: kidneys with normal size, shape, and architecture - perirenal effusion - nonspecific - peritoneal/retroperitoneal effusion – uroabdomen - left upper is normal kidney (assess size with length and aorta ratio, in cats only size, regular or irregular, if cortex and medulla look normal, spleen more hyperechoic than cortex) - right up – ethylene glycol toxicity, more cortex echoic than spleen - left down – leptospirosis, hyperechoic, enlarged, homogenous (no difference in cortex, medulla) - right down – pyelonephritis, hyperechoic, pelvis dilation, usually also proximal ureter dilation Diagnosis - fluid analysis - uroabdomen (surgery) o creatinine and K compared to serum o cytology o protein-poor transudate/protein-rich transudate/exudate ▪ hemorrhage, inflammatory cells o urine is chemical irritant - nonseptic neutrophilic inflammation ▪ cell count >5000/mcL ▪ total solids >3.0 g/dL (>30 g/L) Monitoring - hydration (keep fluid status normal is important, difficult to assess) o xerostomia (dry mouth → cannot be said if its due dehydration since kidney injury can cause) o overhydration (body not getting rid of fluids): serous ocular/nasal discharges, SC edema, cavitary effusions, pulmonary edema, hypertension (hypervolemia) - body weight - physical examination - hematocrit, total protein, electrolytes, creatinine, BUN, acid-base status q24h - blood pressure q12h - UOP Treatment - limit further renal damage, enhance cellular recovery - most successful during induction and extension phases - treatment of specific diseases o obstruction, infectious diseases, toxins Treatment: fluid and electrolyte disorders - correct dehydration, hypovolemia, acid-base and electrolyte disturbances, maintain cardiac output, renal perfusion, systemic oxygen delivery, promote diuresis - fluid type: initially isotonic crystalloid, maintenance with lower Na - correction of hypovolemia rapidly, dehydration over 6-24 h, maintenance  - rate: metabolic water demands, insensible losses, sensible losses (increased with PU), correct volume deficits - complications: hypervolemia, hypertension, edema - HyperK: relieving a urethral obstruction, Ca gluconate, IV regular insulin + dextrose, extracorporeal renal support therapy - HypoK: supplementing IV fluids, PO (usually in cats with polyuria, GI losses) - Hyper/hypoNa (do not usually have to treat, usually solved with fluids) - HypoCa: slow bolus IV Ca, followed by a CRI - HyperP: reduced P diets, enteric phosphate binders (use diet with reduced P, or enteric phosphate binders) Treatment: GI complications (caused by uremia) - vomiting, nausea, anorexia, ileus - antiemetics, prokinetics, appetite stimulants o maropitant, ondansetron, metoclopramide, mirtazapine - oral and GI ulcerations (lingual ulcers, abdominal pain, and melena) – gastric acid suppressants o proton pump inhibitor, famotidine - nutrition o feeding tube (if appetite not recovered) Treatment: systemic hypertension - amlodipine o can be given rectally if needed - avoid ACEI/ARB (only in chronic kidney patients that are stable, not in AKI) - try to select drugs that are metabolized in liver → if in kidneys, reduce dose! Oligo/anuria - UOP 1-2 ml/kg/h normal, >2 ml/kg/h PU, 14 µg/dL o abnormal kidney imaging o persistent renal proteinuria ▪ UPC >0.5 in dogs, >0.4 in cats Diagnosis - late stage 2-4 - both of these diagnostic findings: o increased creatinine and SDMA concentrations + o USG 160 mmHg - goal: BP 200 mmHg - dogs (combination): o ACEi o Telmisartan o Amlodipine - later stages/uremic crisis - amlodipine safer - monitoring: o stable mildly hypertensive patient: BP within 7-10 days and the dose adjusted accordingly o unstable, TOD, late stage disease: earlier (1-3 days) o BP, renal values, electrolytes q3-6k ▪ hypotension ▪ worsening azotemia with ACEi/ARB ▪ HyperK with ACEi (dogs) Treatment: proteinuria - UPCR >0.5 in dogs, >0.4 in cats - antiproteinuric drugs o ACEi  o ARB - antithrombotic therapy (glomerular disease) - treatment of systemic hypertension - diet? - kidney biopsy - immune mediated disease? Treatment: anemia - treat underlying conditions o GI hemorrhage ▪ melena, increased BUN to creatinine ratio, iron deficiency, anemia disproportionate to level of azotemia ▪ proton pump inhibitor o infections o chronic inflammation - blood transfusion - darbepoetin alfa o erythrocyte-stimulating agent o based on human EPO - risk of developing antibodies o indication: IRIS CKD III-IV + PCV cats Bacteriuria ≠ UTI - quantitative aerobic culture - LUT is not sterile - sample contamination o aseptic cystocentesis recommended o voided/catheter collected acceptable with quantitative - subclinical bacteriuria o treatment not recommended, assess patient (comorbidities?) and bacteria o untreated - monitor clinical signs, urine (blood, protein, inflammatory cells) Diagnosis - bacteriuria + cystitis - interpret together: clinical signs, urinalysis, urine sediment examination, urine culture - aerobic urine culture Treatment - depends on: o previous UTI history ▪ sporadic: 90% uroliths from dalmatians ▪ neutered males ▪ acidic urine Signalment - age o middle-aged o >7 y: 60% CaOx, 35% struvite, 9% urate, 1% cystine o 90% struvite, CaOx visible o 70-75% urate, cystine visible o contrast radiography - US - video o more sensitive than radiography for uroliths 70%), layers Additional diagnostics based on urolith type - struvite o urine culture at diagnosis o identify underlying causes of UTI - CaOx o aerum total and ionized calcium o genetic testing - cystine o urinary cystine quantification o genetic testing - urate o bile acid test (PSS) o genetic testing Treatment - decision based on estimated probable type o all: promote water intake (USG ≤1.020) o dissolution ▪ diet, medication ▪ struvite, urate, cystine o removal ▪ indications: clinical signs, urethral obstruction, recurrent infection  ▪ radiographs a week or less prior ▪ minimally invasive procedures voiding urohydropropulsion, basket removal, lithotripsy, percutaneous cystolithotomy ▪ cystotomy suture-induced urolith recurrence Treatment - struvite - medical dissolution o diet o UTI: antimicrobial therapy, manage underlying causes - indications: o urease-producing bacteriuria o history of struvite urolithiasis o female dogs that recently received antimicrobial therapy that could confound UTI diagnosis o radiographic urolith appearance supportive of struvite - contraindications: o urethral obstruction o comorbidities that prevent feeding of a therapeutic dissolution diet - success rate 50-60%, dissolution ∼1 month - urolith removal if: o no dissolution by 4-6 weeks o clinical signs fail to resolve within 2 weeks - prevention: prevention and early treatment of UTIs Treatment - CaOx - likely in adult neutered male dogs o exceptions: urease-producing bacteriuria, congenital PSS, urate breeds, intact males (cystine) - cannot be medically dissolved - prevention: 1. diet ▪ low oxalate, moderate calcium, optimal Ca:P, potassium citrate 2. potassium citrate ▪ alkalinizer, crystallization inhibitor ▪ indication: pH persistently