Renal disease Flashcards
What is considered the gold standard for assessment of GFR?
Urine inulin clearance
Why is plasma inulin clearance nor recommended in dogs?
40% inulin is cleared from the plasma by non-renal routes
Which breed of cat is associated with elevated sCr?
Birman
What is cystatin C?
Protease inhibitor
How is cystatin C handled in the kidneys?
Freely filtered
Reabsorbed by megalin-mediated endocytosis
What does increased urinary cystatin C indicate?
Tubular dysfunction
How and where are filtered proteins reabsorbed in the kidney?
Megalin- and cubulin- mediated endocytosis in proximal tubular cells
What can cause false positive/negative results on a urine protein dipstick?
Positive - cats, alkaline/concentrated urine, pyuria/haematuria
Negative - acidic/dilute urine, BJ proteinuria
What stain is used to highlight the basement membrane in renal biopsies?
Jones methenamine silver
Can serum albumin / AT III be used to guide thromboprophylaxis in dogs with PLN?
No - magnitude of hypoalbuminaemia, AT concentration or UPCR are predictive of thromboembolic complications
What is USG?
The weight of a volume of fluid compared to the weight of an equal volume of distilled water
Where is filtered glucose reabsorbed?
Mostly SGLT 2 (SGLT 1 to lesser extent) in proximal tubule
What is the function of different regions of the renal tubule with regards to pH regulation?
PT - main site of H+ and HCO3- reabsorption
DT - regulation of H+ secretion
What are hyaline casts composed of? What is their significance?
Proteinaceous material
Marked proteinuria
What are epithelial casts composed of? What is their significance?
Proteinaceous material and epithelial cells
Direct tubular cellular damage
What are granular casts composed of? What is their significance?
Partial degradation of a cast
Renal tubular insult
What are waxy casts composed of? What is their significance?
Complete cellular degradation
Protracted tubular stasis
What condition should be considered in a cat with a marked increase in renal cortical echogenicity?
EG toxicity
Ddx AKI
Haemodynamic (pre-renal)
Intrinsic renal - vascular
- acute glomerulonephritis
- acute interstitial nephritis
- acute tubular necrosis
Post renal
What GI complication has been reported in dogs with AKI?
Intussusception
What are the 4 stages of AKI?
Initiation
Extension
Maintenance
Polyuric
What test can be used to distinguish haemodynamic from intrinsic renal azotaemia?
FE-Na
<1% expected if haemodynamic
Do a) norepinephrine and b) vasopressin preferentially constrict the afferent or efferent arteriole?
a) Afferent
b) Efferent
What features of aminoglycosides make them associated with AKI?
Not metabolised
LMW
Water soluble
Ionise to cationic complexes which bind to anionic sited on PT epithelium - internalised and concentrate
How do NSAIDs cause AKI?
Renal function more dependent on prostaglandin synthesis in situations of low blood flow
Predominant renal prostaglandin causes afferent arteriolar dilation - maintains RBF during systemic vasoconstriction
MOA fenoldopam
Selective DA-1 agonist
What are the hypothetical benefits of mannitol in AKI?
Inhibits renin => inhibits NA reabsorption
Increases tubular flow
Decreases vascular resistance and cellular swelling
Increases RBF, GFR and solute excretion
Induces intrarenal prostaglandin production and vasodilation
Induces ANP release
May blunt Ca influx into mitochondria
What is the evidence for mannitol in AKI?
No evidence of benefit in people or healthy cats
When is mannitol contraindicated in AKI?
Dehydration
Overhydration
May worsen pulmonary oedema
What are the theoretical benefits of frusemide in AKI?
By inhibiting Na/Cl/K pump, NaK pump becomes unnecessary - medullary oxygen consumption reduces
Renal vasodilatory effects
What is a proven benefit of frusemide in AKI?
Reduced structural damage in thick ascending LOH
What are established indications for frusemide in AKI?
Hyperkalaemia
Overhydration
When is frusemide contraindicated in AKI?
Aminoglycoside-induced AKI
What are potential complications with dialysis?
Dialysis disequilibrium syndrome - rapid decline in osmolality - CNS signs
Hypotension
Haemorrhage
Hypocalcaemia
Catheter thrombosis
What treatment is recommended for Aminoglycoside toxicity?
Ticarcillin and carbenicillin - complex aminoglycosides and prevent uptake
What treatment is recommended for sulphonamide toxicosis?
Urinary alkalisation +/- high-volume fluid therapy/mannitol
What treatment is recommended for pigment nephropathy?
Urinary alkalisation +/- high-volume fluid therapy/mannitol
What ECG findings are reported with hyperkalaemia?
Bradycardia, tall spiked T waves, shortened QT interval, wide QRS complex with small/absent P wave
What ECG findings are associated with SEVERE hyperkalaemia?
Sinoventricular rhythm, VF, ventricular standstill
What effect does metabolic acidosis have on calcium?
Increases ionised fraction
What is the mechanism of hypercalcaemia in AKI?
v GFR = ^P
Ca decreases by law of mass action
When should hypomagnasaemia be suspected in AKI?
Refractory hypokalaemia, normally in PU phase
What are the most common histopathological findings in dogs with CKD?
58% tubulointerstitial nephritis
28% glomerulonephropathy
6% amyloidosis
What are the most common histopathological findings in cats with CKD?
70% tubulointerstitial nephritis
15% glomerulonephropathy
11% lymphoma
2% amyloidosis
In cats with CKD, what 2 baseline parameters are associated with survival?
Creatinine and phosphorus
What are the mechanisms of PUPD in CKD?
Increased solute load per nephron
Impaired renal responsiveness to ADH
Impaired genesis of hypertonic gradient of medulla
What RBC morphological abnormalities are recognised inCKD?
Burr cells or echinocytes
Do CKD patients have relative or absolute EPO deficiency?
Relative (higher than normal but nor proportional for degree of anaemia)
What changes in plasma aldosterone and PRA are seen in azotaemic hypertensive cats?
Elevated aldosterone with reduced renin
What are the 3 layers of the filtration barrier?
Fenestrated endothelium
Glomerular basement membrane
Visceral epithelial cells (podocytes)
What CBC finding is common in dogs with glomerular disease?
Thrombocytosis
What are the hallmarks of nephrotic syndrome?
Hypoalbuminaemia, proteinuria, hypercholesterolaemia, oedema
What stains are used for evaluating renal biopsies and what do the stain?
PAS - glycoprotein, interstitial and glomerular scarring and assessment of GBM
Methenamine silver - GBM
Trichrome - mesangium and immunoglobulin
Congo red - amyloid
What breed is associated with a familial membranoproliferazive glomerulonephritis?
Bernes Mountain dogs
What infectious disease is associated with a rapidly progressive form of membranoproliferazive glomerulonephritis?
Borrelia
What is the pathogenesis of membranoproliferazive glomerulonephritis?
Immune complex deposition - cytokine-mediated complement activation, expansion of the mesangium and inflow of leukocytes
What are the histo findings of membranoproliferazive glomerulonephritis?
Thickened capillary loops and mesangial hypercellularity
What is the recommended treatment of membranoproliferazive glomerulonephritis?
Identification and treatment of underlying disease
Immunosuppression if severe/progressive
Anti-platelet medication
What is the most common glomerular disease in cats?
Membranous nephropathy
What is the pathogenesis of membranous nephropathy?
Antibodies bind to supepithelial (urinary) side of GBM
Primary - ICGN
Secondary - circulating immune complexes
Complement and formation of MAC
What are the histo findings of membranous nephropathy?
Uniform thickening of GBM
Irregular thickening of capillary walls
Immune deposits +/- engulfment by GBM on TEM
What specific treatment is recommended for membranous nephropathy? What is the prognosis?
Identification and treatment of underlying disease
Immunosuppression
Can be slow to progress, spontaneous remission reported
Worse if higher grade
What is the pathogenesis of proliferative glomerulonephritis
ICGN causing endocapillary or mesangial proliferation
What are the histo findings in proliferative glomerulonephritis?
Mesangial or endocapillary hyperplasia with deposits of IgG or IgM
What is the pathogenesis of IgA nephropathy? Why are dogs more prone than people?
IgA non-specifically trapped in GBM
Dog IgA is polymeric, so more likely to be trapped n GBM than monomeric IgA
What are the light microscopy findings in IgA nephropathy?
Mesangial proliferative glomerulonephritis
What diseases are most associated with IgA nephropathy?
Hepatic/GI
What breeds are associated with amyloidosis? In which is there a pattern to amyloid deposition?
Chinese Shar-Pei - medulla
Beagles/English Fox hounds - glomeruli
Abysinninans - medulla
Siamese
How is reactive amyloidosis confirmed on histo?
Stains red with Congo Red
Discoloured by potassium permanganate oxidation
MOA colchicine?
Inhibits release of SAA from hepatocytes by binding microtubules
What breeds are affected by hereditary nephritis and what is the method of inheritance?
English cocker - autosomal recessive
English springer - autosomal recessive
Bull terrier - autosomal dominant
Dalmatian - autosomal dominant
What is the pathogenesis of hereditary nephritis?
Mutation/deletion of type IV collagen - premature deterioration of the GBM
What are the histo findings of minimal change disease?
Light microscopy - minimal
TEM - podocyte foot process effacement
What is the treatment for minimally change disease?
Steroids
Where do defects associated with cystinuria occur?
Proximal tubule
What is the mechanism of inheritance of cystinuria? Give examples of affected breeds
Type 1 - autosomal recessive. Labrador, Newfoundland, Australian Cattle dog
Type 2 - autosomal dominant
What genes are abnormal in cystinuria?
Slc3a1 and Slc7a9
What treatment is recommended to avoid calculi in cystinuria?
Reduced protein
Urine alkalisation
Diuresis
+/- 2-MPG and D-penicillamine
What is a consequence of carnitinuria?
DCM
What condition is carnitinuria commonly associated with?
Cystinuria
How is the purine portion of amino acids metabolised?
To hypoxanthine and xanthine, oxidised to uric acid by xanthine oxidase
Uric acid metabolised to allantoin by hepatic uricase
What diseases increase excretion of xanthine?
HAC, neoplasia, CKD
What breeds are associated with hyperuricosuria?
Dalmatian, English Bulldog, Black Russian Terrier
What are the differences in purine metabolism in Dalmatians? What gene is involved?
Abnormal uric acid transport across hepatic membrane, unable to transport uric acid to uricase
Less proximal reabsorption of uric acid
Increased tubular secretion of uric acid
Slc2a9
How is hyperuricosuria treated? What is the rationale for each treatment?
XO inhibitors - reduce uric acid production
Purine restricted diet - to prevent xanthine calculi
Urine alkalisation - reduced proximal tubular ammonia production - reduces ammonium ions that complex with urate to form calculi
What breed is Fanconi syndrome reported in? What is it’s prevalence?
Basenji’s
10-30%
What medication has been associated with acquired Fanconi syndrome in a) dogs and b) cats
a) Gentamicin
b) Chlorambucil
What acid-base abnormality is associated with Fanconi syndrome?
Hyperchloraemic metabolic acidosis
Which breeds are overrepresented for renal a genesis?
Beagle, Doberman, Shetland Sheepdog
What breed is affected by podocytopathy? What is the typical age of presentation?
Soft coated Wheaten Terrier
6y
What gene is involved in PKD?
Polycystin-1 (PKD-1)
Which dog breeds are affected by PKD?
What is the mechanism of inheritance?
Bull Terrier - autosomal dominant
Cairn Terrier - autosomal recessive
WHWT - autosomal recessive
What is the mechanism of inheritance of PKD in Persian cats?
Autosomal dominant
What is the proposed mechanism for hyperlipidaemina in glomerular disease?
Hypoalbumoinaemia stimulating hepatic protein synthesis leading to production of lipoproteins
Glomerular loss of orosomucoid, leads to reduced hepatic production of heparin - cofactor for normal lipoprotein lipase function
