Renal biomarkers

Question 1

What is cystatin C?

Answer 1

Protease inhibitor produced by all cells at a constant rate, responsible for intracellular protein catabolism

Question 2

What is neutrophil gelatinase associated lipocalin (NGAL)?

Answer 2

Glycoprotein expressed during inflammatory responses and epithelial damage

Question 3

The urinary NGAL:creatinine ratio is an indicator of what in dogs?

Answer 3

AKI, CKD, and UTI

Question 4

Higher concentrations of serum and urinary NGAL is associated with what in dogs with CKD?

Answer 4

Shorter survival times

Question 5

In cats, is NGAL correlated with IRIS stage CKD?

Answer 5

Yes - both urinary NGAL and urine NGAL:creatinine ratios were highly correlated with serum creatinine

Question 6

What is the sensitivity and specificity of urinary NGAL for predicting CKD progression in cats?

Answer 6

Sensitivity 77%, Specificity 75%

Question 7

What is kidney injury molecule 1 (KIM1)?

Answer 7

Proximal tubular transmembrane glycoprotein - increases with acute injury to proximal tubule (AKI)

Question 8

In cats, was urinary KIM1 useful for detecting AKI?

Answer 8

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

Question 9

Can cystatin C be used as a biomarker of CKD in cats?

Answer 9

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

Question 10

What form of liver type fatty acid binding protein (L-FABP) was increased in CKD cats compared to healthy cats? In hyperthyroid cats?

Answer 10

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

Question 11

Was NGAL useful for predicting the development of CKD after treatment of hyperthyroidism or detecting early CKD?

Answer 11

No

Question 12

What fecal short chain fatty acid was increased in CKD cats? At what stages?

Answer 12

Fecal isovaleric acid - increased in stages 2, 3, and 4 (could not differentiate them)

Question 13

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)?

Answer 13

miR16
(4 of the 5 cats had E coli infections)

Question 14

Could serum cystatin C predict the development of CKD after hyperthyroid treatment?

Answer 14

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??

Question 15

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?

Answer 15

Hemojuvelin

Question 16

Apart from FGF23, what biomarker is associated with phosphorus concentrations and progression of CKD?

Answer 16

Indoxyl sulfate - actually correlated better with phosphorus than FGF23

Combination of IS and FGF23 predicted renal progression at a AUROC >0.9

Question 17

Describe the microbiome of cats with CKD vs healthy cats

Answer 17

CKD = reduced diversity and richness, no difference in quantification of E coli (the only species they quantified, eye roll)

Question 18

In dogs with CKD, what was the area under the curve of creatinine, SDMA, and cystatin C for detecting decreased GFR?

Answer 18

Creatinine: 0.98
SDMA: 0.96
Cystatin C: 0.87

Question 19

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?

Answer 19

• 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

Question 20

In a study of non-azotemic dogs that had GFR measured by iohexal clearance, what was the correlation of creatinine and SDMA with GFR?

Answer 20

Creatinine r= 0.52
SDMA r = 0.33

Question 21

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?

Answer 21

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

Question 22

In dogs with an AKI induced by gentamicin infusion, the urinary NGAL/creatinine ratio was able to detect AKI how much faster than creatinine?

Answer 22

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

Question 23

In dogs with an AKI induced by gentamicin infusion, how was the urinary NGAL/creatinine ratio correlated with recovery?

Answer 23

The urinary NGAL/creatinine ratio dropped 2 days before creatinine

May be an early marker of recovery from AKI

Question 24

What was the urinary NGAL/creatinine ratio in dogs with stable CKD vs progressive CKD?

Answer 24

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

Question 25

In a prospective study evaluating 76 dogs with AKI, what was the urinary NGAL concentration and how did it change IRIS grading?

Answer 25

• 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

Question 26

In a prospective study evaluating 76 dogs with AKI, how did inflammation affect urinary NGAL?

Answer 26

Higher in dogs with inflammatory AKI - specificity affected by inflammation

Question 27

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?

Answer 27

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

Question 28

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?

Answer 28

Near the point of diagnosis: 90% (specificity 99%)
1 year: 63%
2 years: 44%

Question 29

Does SDMA increase in non-azotemic cats with HCM or DM?

Answer 29

No - SDMA was actually lower in DM cats

Question 30

What percent of healthy Birman cats had a creatinine higher than the reference interval? SDMA?

Answer 30

40% had a creatinine over the RI
20% had SDMA higher than reference

Question 31

What should the SDMA reference interval be for Birman cats?

Answer 31

3.4-18.7

Question 32

Does SDMA increase with AKI in dogs?

Answer 32

Yes - SDMA was significantly higher in dogs with both AKI and CKD (cannot differentiate between them)

Question 33

Serum SDMA increased how many months before creatinine in cats with CKD?

Answer 33

17 months

Question 34

Serum SDMA increased how many months before creatinine in dogs with CKD?

Answer 34

9.8 months

Question 35

What substances can falsely increase creatinine?

Answer 35

Glucose, bilirubin, keto acids, cephalosporins, aminoglycosides, trimethoprim

Question 36

How can prednisone influence creatinine?

Answer 36

Accelerates muscle metabolism => increase in creatinine