Urinary Flashcards
What is FGF-23?
a phophotonin that works in concert with a-klotho to regulate phosphate when phosphate is increased.
Where is FGF-25 secreted from?
Why?
Osteoblasts and osteoclasts.
Response to high filtered load of phosphate in the nephron (secondary to increased phosphate absorption from the GIT)
What is the role of FGF-25?
Binds FGF-1 receptror and a-Klotho to down regular 2 Na-Phos transporters in the prox tubule (NPT2a and NPT2c) => reduced reabsorption of filtered phosphate => increased urinary excretion of phosphate . (dependant on GFR and plasma phos conc)
- inhib phosphate absorption from GIT via inhim conversion of 25-OHcholecalciferol to calcitriol via effections on both the calcitrol synthesising (CYP27B1) and catabolising (CYP24A1) enx.
- inhib phosphate absorption from both via inhib PTH secretion.
in regards to renal disease, when does increases in FGF-25 start to occur?
Early renal disease prior to onset of azotaemia (Stage 1) and increases proportionately with the stage of CKD (consistent with reduced GFR given it is renally excreted).
However can be excessively increased compared to plasma phosphate targets for given stage.
What is FGF-25 a marker for in cats?
- the stage of feline CKD
- predictive of progression of the development of azoaemia
- phsophate overload and potentially thus whether phosphate restriction may be beneficial
- all cause mortality.
Is FGF-25 affected by dietary phosphate restriction?
yes - causes reduction.
What is Klotho?
a paracrine and endocrine, transmembrane protein.
Where is it expressed and in what forms?
a-Klotho: transmembrane protein
- distal renal tubules
- PTH gland
- Choroid plexus
- Vascular tissues.
Soluble Klotho: - body fluids inc CSF, blood and urine from the shedding of membrane Klotho
B-Klotho: fibroblast growth factor for bile acid synthesis and lipit metabolism.
- liver
- pancreas
- adipose tissue
What does Klotho do?
- A-Klotho = Obligate co-receptor for FGF-23 => reduce circ phosphorus
- inactivate Na-P cotransporters type 2 (NaPi-2) = > inhib renal phos reabsorption
- reduce 1a-hydroxylase and increase 24-hydroxylase => reduced calcitriol - Soluble Klotho:
- activates TRPV5 and TRPV6 calcium channels in distal tubles => increased renal calcium reabsorption
- down reg NaPi-3 cotransporters to mediate phosphate uptake
- Activates ROMK1 K+ channels => increased K+ excretion in kidneys
- up reg NO production
- Increase Na+’K+ATPase in kidney , PTH gland and choroid plexus => Na and Ca+ homeostasis.
- Inhib insulin and IGF1 => insulin resistance
What decreases Klotho expression?
- ATII
- Oxidative stress/inflam cytokines (TNF-a)
- CKD
- Immune med glomerulopathy
in CKD:
- hyperphosphateamia
- hyper calcaemia
- reduced calcitriol
- inflam cytokines
- dyspilidaemia
- activated RAAS
What increases Klotho?
Age - younger = higher
- healthy = higher
- Calcitrol
- ARBs
What is the prevalence of hypernatraemia in dogs and cats?
does this affect prognosis?
Dogs - 5.7%
Cats 8%
hypernatraemia assocaited with 20-28% risk of death with higher Na associaed with higher case fataily.
Ueda JVIM 2015
What is hyperchloremic metabolic acidosis?
What are the causes?
- decrease pH
- decrease HCo3- or base excess
- increase chloride
- decreased in strong ion difference
- normal anion gap
Causes:
- Excessive sodium loss ralative to chrloide
- excessive gain of chloride relative to sodium (0.9% NaCl, salt poisoning, TPN with AA containing fluids)
- Chloride retention (early CKD, hypoA, spironolactone, corection of DKA, RTA)
Funes VCNA 2017
What are the causes of hyperkalaemia?
only really if kidneys not working to excrete.
- Extra-renal
- increased intake (only wiht concurrent issues kidney/adrenal/drugs)
- GI disease (trichuris, salmonela, perf duodenal ulcer)
- Chylothorax, plerual or peritoenal effusions (thrid space fluid loss) - Translocation from intracellular to extracellular fluid
- DKA/insulin deficiency
- Massive sittue break down/Tumour lysis syndrome/repurfusion injury
- Metabolic acidosis (acute mineral acidosis)
- Hyerkalemic periodic paralysis (NA+/K+ ATPase dysfunction)
- Drug induced/iatrogenic (propanolol - decreases liver/muscle uptake of K+) - Renal:
- AKI (decreased GFR => decreased K+ excretion)
- CKD end stage
- ureteral obstruction
- Ruptured bladder
- HypoA (decreased Na+/K+ ATPase activation due to reduced aldosterone)
- Drug induced - ACEi, ATII RB, Spironolactone, NSAIDs, Heparin, Cyclosporin, Tacrolimus, TMPS
- Hypoerninemic hypoaldosteronism
- Late pregnancy in greyhounds. (GI fluid loss?) - Spurious:
- Leukocytosis (>100,000 leukocytes/uL)
- Severe thrombocytosis
- haemolysis (Akita/Shiba)
- contaimination with IVFT, EDTA, oxalate
What are the causes of hypokalaemia?
GIT or renal loss.
- Extra renal:
- decreased K+ intake - anorexia, diet, K+ free IVFT
- Increased K+ loss via GIT
2.Translocation extracellular to intracellular fluid:
- Glucose cotnaining fluid with or without insulin
- TPR solution
- Caecholamines (phaeo)
- Hypokalaemic periodic parlaysis - burmese, anomolous activation of Na+/K+ ATPase
Other - albuterol overdose, hypothermia
- Renal:
- CKD
- Distal (type I) RTA
- Proximal (type II) RTA
- DIet induced hypoaleamic nepropathy
- post obstructive diuresis
- osmotic diuresis (DKA)
- Drug induced: diuretics (loop, thiazide), amphotericin B
- hyperA
- hyperaldosteron
- hyperT4
- other: peritoneal dialsys, flurocortisone excess, penicillins, high sodium intake
Kogika VNCA 2017
What is the prevalence of proteinuria in healthy geriatric dogs?
11-15%
Meindl JVIm 2018
What is the sensitivity and specificity of Idex sedivue for the detection of:
- RBc/WBC
- CaOx dihydrate
- Struvite
- Squamous epithelial cells
1. RBc/WBC Sens: 85-90% Spec: 87-90% 2. CaOx dihydrate Sens: 75% Spec: 99% 3. Struvite Sens: 85-90% Spec: 84% 4. Squamous epithelial cells Sens: 33% Spec: 99%
Hernandez JVUM 2017
What is the variability of first morning USG in dogs?
mean difference between min and max for individual dogs was 0.015
mean coefficience of variance 15.4%
- inherent intraindividual variability
Rudinsky JVIM 2019
What mutation is associated with renal cystadenomocarcinoma and nodular dermatofibrosis?
- what breed?
- what is the inheritance pattern?
Folliculin - a tumour suppressor gene, mutation
German Shepherds
dominant inheritance.
What can cause renal amyloidosis?
What does it look like cytologically?
What stain is best to see this?
- Inherited: Shar Pei
- reactive (serum amyloid A accumulation) in abyssinians, idiopthic, infectious, chronic inflam or neoplasia
Cytoogically - undulous, glassy swirls of amorpohous eosinophilic materia in close associated with glomeruli or renal tubular epithelial cells.
Stain with congo red, examine under polaized light => apple green stain
VCNA 2017
What are melamed-Worlinska bodies?
large magenta inclusions within epithelial cells associated with TCC.
VCNA 2017
Are UPC usually higher on home or in clinic samples?
50% higher in clinic samples
Duffy JVIM 2015
Is creatinine or SDMA influence by lean body mass?
SDMA - no
Creatinine - yes. lower LBM => reduced creatinine and risk of falsely overestimating gfr.
Hall JVIM 2015
What proportion of dogs presenting to a cademic medical center have evidence of kidney injury?
In what sub groups was the relative risk higher?
11.5%
geriatric dogs
Babyak JVIM 2017
What proportion of geriatric dogs had persistently UPC >0.2?
Is UPC measurement by free catch suitable?
19% had UPC >0.2
strong corrleation betwen free catch and cysto UPC.
Marynissen JVIm 2017
Can SDMA detect AKI?
Can SDMA detect difference between CKD and AKI?
Yes - median SDMA in AKI 39ug/dL
Cannot detect difference between CKD and AKI in dogs
Dahlem JVIM 2017
Does storage medium or time affect UPC values?
Storage emdium - doesn’t affect
time did not have any significant effect, however should be avoided storing at 4C for more than 12h as may increase UPC ratios.
Moyle JVIM 2018
What proportion of cats become azotaemic post I131 therapy?
16%
Peterson JVIM 2018
What is the sensitivity and specificity of SDMA to predict post I131 treatment (masked) CKD?
What does this mean clinically?
SDMA
Sens:33%
Spec 97%
Suggestive that few false positives but likely to fail to predict azotaemia in most hyperhtyroid cats
Peterson JVIm 2018
What is the within dog coefficient of variation for:
- Serum cystatin C
- Urinary retinol binding protein
- Urinary neutrophil gelatinase associated lipocalin
- Urinary IgG
over 1.5years.
- Serum cystatin C: 8%
- Urinary retinol binding protein 33%
- Urinary neutrophil gelatinase associated lipocalin 87%
- Urinary IgG 88%
Liu JVIM 2018
What is the :
- Index of individuality
- critical difference
- number of samples needed for haemostatic set point at 95% CI
for SDMA and creatinine?
Based on this, which is better for population based intervals?
What should be used to assess sequential measurements?
SDMA:
- Index of individuality: 0.87 (intermediate)
- critical difference 1.34 ug/dL
- number of samples needed for haemostatic set point at 95% CI: 45
Creatinin:
- Index of individuality: 0.28 (low)
- critical difference: 0.89 umol/L
- number of samples needed for haemostatic set point at 95% CI: 12
SDMA - better for population based reference intervals due to higher IOI.
Critical difference should be used to evaluate if changes are significant or due to biological variability.
Kopke JVIM 2018
What is the Sensitivity and specificity for: - SDMA at 14ug/dL - creatinine at 115umol/L - Cystatin C at 0.49mg/L for the dectection of decreased GFR? What does this mean clinically?
- SDMA at 14ug/dL
Sens: 90%
Spec: 87% - creatinine at 115umol/L
Sens: 90%
Spec: 90% - Cystatin C at 0.49mg/L
Sens: 90%
Spec:72%
Cystatin C is inferior to SDMA or serum creatining for detection of decreased GFR.
Pelander JVIM 2018
What is the sensitivity, specificity, PPV and NPV of SDMA in cat to detect a 30% decrease from median mGFR?
How much sooner does this increase compared to serum creatinine?
SDMA: Sens - 100% Spec 91% PPV 86% NPV 100%
Increases 9 months sooner than creatinine
Yerramilli VCNA 2017
What is clusterin?
What is its limitation as a biomarker for kidney disease?
Clusterin/Apolipoportein J - extracellular chaperone.
Expressed by lots of tissues.
- increased in urine with renal tubular damage and reduces as damage resolves.
- kidney specific urinary clusterin increases earlier and is more sensitive than creatinine for active kidney injury.
Limitation:
- much higher (nos-pecific) in serum than in urine, thus any blood contamination => false positives.
Thus need to use kidney specific urinary clusterin.
Yerramilli VCNA 2017
What percentage of cats with AKI have normal renal size and architeture on ultrasound?
What are the common renal u/s findings in cats with AKI?
6% have normal kidney size and architecture
Common renal u/s findings in cats with AKI
= renomegaly
- pyelectasia
- increased renal echogenicity
Cole JFMS 2019
What prognostic factors are associated with ultrasound abnormalities in cats with AKI?
- retroperitoneal fluids was associated with oliguria/anuria
- increase number ultrasound abnormalities is associated with poorer long term prognosis
Cole JFMS 2019
In dogs with AKI what changes during hospitalization were associated with markers of renal recovery?
- increased GFR
- increased urine production
- decreased fractional clearance of sodium.
were increased in surviving dogs.
Brown JVIM 2015
