Renal biomarkers Flashcards
What is cystatin C?
Protease inhibitor produced by all cells at a constant rate, responsible for intracellular protein catabolism
What is neutrophil gelatinase associated lipocalin (NGAL)?
Glycoprotein expressed during inflammatory responses and epithelial damage
The urinary NGAL:creatinine ratio is an indicator of what in dogs?
AKI, CKD, and UTI
Higher concentrations of serum and urinary NGAL is associated with what in dogs with CKD?
Shorter survival times
In cats, is NGAL correlated with IRIS stage CKD?
Yes - both urinary NGAL and urine NGAL:creatinine ratios were highly correlated with serum creatinine
What is the sensitivity and specificity of urinary NGAL for predicting CKD progression in cats?
Sensitivity 77%, Specificity 75%
What is kidney injury molecule 1 (KIM1)?
Proximal tubular transmembrane glycoprotein - increases with acute injury to proximal tubule (AKI)
In cats, was urinary KIM1 useful for detecting AKI?
Yes, but increases due to sepsis or UO were transient in the JFMS study.
Not increased on intake, but increased over time in cats with UO in the JSAP study
Can cystatin C be used as a biomarker of CKD in cats?
Not according to the 2016 article evaluating 49 CKD cats
- Serum cystatin C was not a reliable marker of GFR
- Urine cystatin C could only be detected in 35/49 cats - not useful
What form of liver type fatty acid binding protein (L-FABP) was increased in CKD cats compared to healthy cats? In hyperthyroid cats?
CKD: Both serum and urinary were higher - but there was a lot of overlap in ranges
Hyperthyroidism: urinary was higher pre-treatment and dropped post-treatment
Was NGAL useful for predicting the development of CKD after treatment of hyperthyroidism or detecting early CKD?
No
What fecal short chain fatty acid was increased in CKD cats? At what stages?
Fecal isovaleric acid - increased in stages 2, 3, and 4 (could not differentiate them)
In cats with pyelonephritis, what miRNA was increased compared to healthy cats and cats with CKD or other lower urinary tract disease (including subclinical bacteriuria)?
miR16
(4 of the 5 cats had E coli infections)
Could serum cystatin C predict the development of CKD after hyperthyroid treatment?
No - cystatin C was not different between cats that developed azotemia and those that did not. In addition, it was not different between general CKD cats and healthy cats. Why are we still publishing papers on this??
What molecule that plays a role in iron homeostasis was increased in cats with AKI, CKD, and AoCKD and correlated with IRIS staging, creatinine, and phosphorus?
Hemojuvelin
Apart from FGF23, what biomarker is associated with phosphorus concentrations and progression of CKD?
Indoxyl sulfate - actually correlated better with phosphorus than FGF23
Combination of IS and FGF23 predicted renal progression at a AUROC >0.9
Describe the microbiome of cats with CKD vs healthy cats
CKD = reduced diversity and richness, no difference in quantification of E coli (the only species they quantified, eye roll)
In dogs with CKD, what was the area under the curve of creatinine, SDMA, and cystatin C for detecting decreased GFR?
Creatinine: 0.98
SDMA: 0.96
Cystatin C: 0.87
In a prospective study of 97 dogs with CKD, what was the sensitivity and specificity of creatinine and SDMA for diagnosing decreased GFR? Cystatin C?
- Creatinine: sensitivity 90%, specificity 90%
- SDMA: sensitivity 90%, specificity 87%
- Cystatin C: specificity 72% if sensitivity was adjusted to also be 90%
Conclusion: cystatin C was inferior to creatinine and SDMA for predicting decreases in GFR
In a study of non-azotemic dogs that had GFR measured by iohexal clearance, what was the correlation of creatinine and SDMA with GFR?
Creatinine r= 0.52
SDMA r = 0.33
In a study of non-azotemic dogs that had GFR measured by iohexal clearance, using what cutoff for SDMA increased the specifity without compromising sensitivity?
Cutoff >18 (rather than 14)
Sensitivity 90% for both, but a cutoff of 18 increased specificity from 50% to 83%
Consider using a higher cutoff when screening non-azotemic dogs for decreased renal function
In dogs with an AKI induced by gentamicin infusion, the urinary NGAL/creatinine ratio was able to detect AKI how much faster than creatinine?
The urinary NGAL/creatinine ratio increased by 7 fold on day 8, creatinine increased by 50% on day 16
May be an early marker of AKI
In dogs with an AKI induced by gentamicin infusion, how was the urinary NGAL/creatinine ratio correlated with recovery?
The urinary NGAL/creatinine ratio dropped 2 days before creatinine
May be an early marker of recovery from AKI
What was the urinary NGAL/creatinine ratio in dogs with stable CKD vs progressive CKD?
The urinary NGAL/creatinine ratio was higher in dogs with progressive CKD compared to stable CKD - AUC 0.816
May help predict the risk of progression
In a prospective study evaluating 76 dogs with AKI, what was the urinary NGAL concentration and how did it change IRIS grading?
- Urinary NGAL was higher in dogs with AKI compared to controls, regardless of IRIS grade
- Urinary NGAL was not different between dogs with volume responsive AKI and intrinsic AKI, BUT the urinary NGAL/creatinine ratio was higher in dogs with intrinsic AKI
In a prospective study evaluating 76 dogs with AKI, how did inflammation affect urinary NGAL?
Higher in dogs with inflammatory AKI - specificity affected by inflammation
In a simplified protocol for measuring GFR via plasma iohexol clearance, including a sample at what time point gave the strongest diagnostic potential for canine CKD?
180 minutes after injection (compared protocols using 2 or 3 samples at 60, 90, and 180 minutes, rather than traditional 5 sampling time points)
AUC for predicting CKD 0.98
A recurrent neural network was developed to predict CKD in cats using creatinine, BUN, USG, and age. What was the sensitivity 1 year before CKD diagnosis? 2 years before? Near the point of diagnosis?
Near the point of diagnosis: 90% (specificity 99%)
1 year: 63%
2 years: 44%
Does SDMA increase in non-azotemic cats with HCM or DM?
No - SDMA was actually lower in DM cats
What percent of healthy Birman cats had a creatinine higher than the reference interval? SDMA?
40% had a creatinine over the RI
20% had SDMA higher than reference
What should the SDMA reference interval be for Birman cats?
3.4-18.7
Does SDMA increase with AKI in dogs?
Yes - SDMA was significantly higher in dogs with both AKI and CKD (cannot differentiate between them)
Serum SDMA increased how many months before creatinine in cats with CKD?
17 months
Serum SDMA increased how many months before creatinine in dogs with CKD?
9.8 months
What substances can falsely increase creatinine?
Glucose, bilirubin, keto acids, cephalosporins, aminoglycosides, trimethoprim
How can prednisone influence creatinine?
Accelerates muscle metabolism => increase in creatinine
