Renal Literature Flashcards
What may • May disrupt the widely held assumption that renal lesions from TKIs are reversible?
Masitinib induced minimal change disease and AKI (oliguria)
When assessing cats that were managed with hemodialysis, how many remained dialysis independent at 30 days?
About 42%
28% died and 30% euthanized
When assessing cats that were managed with hemodialysis, what was the most common etiology?
- 35% = Ureteral obstruction***: Survival rate: 67%
- Pyelonephritis: 57%
- Lily Ingestion: 17%
- Ethylene Glycol: 8%
When assessing cats that were managed with hemodialysis, what is known about the novel clinical scoring system?
Several models that correctly classified outcomes in 75-77% with reevaluation 84-89%
Higher scores were associated with decreased probability of survival
When assessing cats that were managed with hemodialysis, base on the novel clinical scoring system what parameters were associated positively with survival ?
Vomiting and ureteral obstruction
What is an AKI grading system that was established in dogs and cats?
Based on creatinine (need at least 2 values)
Level 0: < 1.6 and change of < 0.3
Level 1: 0.3
Level 2: >1.6 and change of >0.3
Based on the AKI grading system in dogs and cats, what could be concluded about mortality?
Increasing azotemia helps to predict mortality in dogs and cats
Dogs:
Level 1 (2 days): 3X more likely to die within 90 days
Level 2 (2, 3, 7 days): 3X more likely to die within 30 or 90 days
Cats:
Level 2 (3, 7 days): 3X more likely to die at 30 days; 4X more likely to die if within 7 days
○ At 2, 3, 7 days: 3X more likely to die at 90 days
Exception: Cats at Level 2 (day2) did not have decreased survival at 30 days
In a group of cats with AKI nonsurviving cats were noted to have what parameters?
- Lower PVC (lower RBC)
- Lower WBC
- Lower lactate dehydrogenase (LDH)
- Lower albumin
- Lower albumin/globs ratio
- Lower BG
- Reduce body temp
- Older
NOTE: BUN and creatinine were not prognostic factors (but a decrease in 3 days was significant with reduced death)
In a group of cats with AKI, what parameters were used in a prognostic index?
body temp, albumin, and LDH
Predicting death 0.86 (sen 77%/spec 90)
Based on 25 cats after ingestion of lily ingestion within 48 hrs, what showed to result in good outcomes?
GI decontamination
IV diuresis
(within 48 hours)
Based on 25 cats after ingestion of lily ingestion within 48 hrs, what was the incidence of AKI?
LOW incidence of AKI
74% had normal BUN/creat during hospitalization
9% had increased values at d/c
What is the VAKI?
It is a veterinary AKI staging system (JVECC) - Based on baseline creatinine and changes from baseline: stage 0 (S0; <150%) stage 1 (S1; 150-199% or ≥26.5 μmol/L [≥0.3 mg/dL]) stage 2 (S2; 200-299%) stage 3 (S3; ≥300%)
Based on the VAKI staging system used in 164 dogs, mortality was greater in which stages?
Mortality rate was greater for S1-3 (13/24; 54.2%) compared to S0 dogs (22/140; 15.7%)
Dogs meeting VAKI stage 1-3 criteria were less likely to survive to discharge
Based on the VAKI staging system used in 164 dogs, what are associated and NOT associated with mortality?
Associated: Stage and age
Not associated: Length of stay, anesthesia, or # diagnoses
In dogs with AKI, what disease had higher BP?
Lepto AKI
In dogs with AKI, hypertension was a common CS, how did dogs respond to amlodipine?
Amlodipine helped to reduce hypertension within 24 hours, HOWEVER, significantly lower proportion of survivors in treated compared to non-treated dogs 59% versus 83% (overall survival 73%)
Which lillies are associated with AKI in cats?
Lilium genus: Oriental, Easter, and Asiatic lilies; Hemerocallis genu: Daylilies
What is known about E. coli pyometra related nephropathy in dogs?
Results in renal dysfunction (affects glomeruli and proximal tubules) - But it is transient in most dogs (resolved 6 months after sx compared to healthy controls)
Which biomarkers were evaluated in E. coli pyometra related nephropathy in dogs?
Biomarkers that were used in urine (normalized with creatinine in sample):
• IgG (glomerular)
• C-reactive protein (glomerular)
• Albumin (glomerular)
• Retinol Binding Protein (tubular)
• Thromboxane B2 (intrarenal and glomerular filtration)
• NAG (tubular)
What are shown in cats with reduced renal mass (sx) and the effects on GFR with meloxicam and aspirin?
Neither has an effect on GFR (urinary clearance of exogenous creatinine, serum creatinine, or UPC)
Which NSAID may be used in dogs with CKD (IRIS stage 2-3) with OA?
Tepoxalin (Zubrin) - Monitoring is needed
No changes in chemistry, UA, UPC, uNAG, iohexol plasma clearance, or BP
What was noted in healthy dogs that were administered COX-2 selective NSAIDs (carprofen and etodolac) in combination with lasix?
Reduced GFR and transient impaired renal function
What is hyperchloremic metabolic acidosis
with a normal anion gap in the face of an urinary pH of
7 suggestive?
Distal Renal Tubular Acidosis
Which infectious dz in a dog has been noted to result in a distal RTA?
Lepto
hyperchloremic normal anion gap metabolic acidosis with alkaline urine that was consistent with a diagnosis of distal renal tubular acidosis
What are noted in UPC for dogs with pyometra?
Significantly higher UPC with pyometra than healthy age matched controls
27/47: UPC >0.5
12/47: UPC >1
7/47: UPC >2
What are noted in renal bx from dogs with pyometra?
Glomerulosclerosis and tubulointerstitial nephritis were common kidney biopsy findings in proteinuric dogs with pyometra. Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had UPC>1.0 at ovariohysterectomy and afterward.
Which nephron segment is involved with the following biomarker: albumin?
Glomerulus and proximal tubule
Which nephron segment is involved with the following biomarker: IgG and IgA?
Glomerulus
Which nephron segment is involved with the following biomarker: Retinol-binding protein?
Proximal tubule
Which nephron segment is involved with the following biomarker: B2-Microglobulin
?
Proximal tubule
Which nephron segment is involved with the following biomarker: a1-Microglobulin
?
Proximal tubule
Which nephron segment is involved with the following biomarker: Cystatin C
?
Tubular Cells
Which nephron segment is involved with the following biomarker: N-acetyl-b-D-glucosaminidase (NAG)
?
Proximal >distal tubule
Which nephron segment is involved with the following biomarker: Gamma-Glutamyltransferase (GGT)?
Proximal tubule
Which nephron segment is involved with the following biomarker: Lactate dehydrogenase?
Proximal >distal tubule
Which nephron segment is involved with the following biomarker: Tamm-Horsfall protein?
Distal tubule
What are considered Intermediate/High MW proteins as urine biomarkers?
Albumin
IgG
IgA
What are considered Low MW proteins as urine biomarkers?
Retinol-binding protein
B2-Microglobulin
a1-Microglobulin
Cystatin C
What are considered tubular enzymes as urine biomarkers?
N-acetyl-b-D-glucosaminidase (NAG)
Gamma-Glutamyltransferase (GGT)
Lactate dehydrogenase
Alkaline phosphatase
What are considered tubular proteins as urine biomarkers?
Tamm-Horsfall protein
Kidney Injury Molecule-1 (KIM-1)
Liver-type Fatty Acid Binding Protein (LFABP)
What are inflammatory proteins as urine biomarkers?
Interleukin-2, -8, monocyte chemoattractant protein-1, keratinocyte-derived chemokine, granulocyte macrophage colony stimulating factor
What could be used to differentiate AKI from CKD in dogs with renal azotemia?
Plasma NGAL (Neutrophil Gelatinase-Associated Lipocalin)
Plasma NGAL concentration was significantly higher in dogs with AKI compared with dogs with CKD
plasma NGAL concentration >37.4 ng/mL had 65% sensitivity and 82% specificity to differentiate AKI from CKD in dogs with renal azotemia
What is NGAL?
Neutrophil gelatinase-associated lipocalin (NGAL) is released from renal tubular cells after injury and serves in humans as a real-time indicator of active kidney damage
What happens with NGAL in azotemic animals?
Serum and urine NGAL significantly higher in azotemic animals compared to nonazotemic dogs
What has been shown with NGAL in dogs with CKD?
Higher serum and urine NGAL was associated with death compared to survivors
Dogs with higher sNGAL survived a significantly shorter time
What are a better predictor of outcome in CKD dogs than creatinine?
Serum NGAL
sNGAL was 50.6ng/mL
Sen 76.9%, Spec 100%
What may be a useful prognostic marker of CKD in dogs
Serum NGAL
What is a sensitive and specific marker of AKI in the urine in dogs?
NGAL/creatinine ratio
Which urine biomarker was an indicator of AKI in azotemic and nonazotemic dogs?
NGAL/creatinine ratio
What is the IRIS AKI staging system?
Based on creatinine
Grade 1: 10
Substage:
- Non oliguric (NO) or oligoanuric (O)
- Requiring renal replacement therapy (RRT)
Which biomarkers were evaluated in an X-linked hereditary nephropathy (males)?
Urine (compared to creatinine): retinol binding protein β2-microglobulin NGAG NGAL IgG
Which urine biomarker in X-linked hereditary nephropathy correlated most strongly with increasing creatinine, decreased GFR, and interstitial fibrosis?
Urine retinol binding protein/creat
In X-linked hereditary nephropathy, what are considered predictors of GFR?
Age
Serum Creatinine
Urine IgG/creat
Urine β2-microglobulin
NOTE Urine retinol binding protein/creat!
Which urine biomarkers are increased in CKD?
Albumin, Retinol binding protein, and NAG
Is there a difference in urine biomarkers in healthy young vs old dogs?
No there is no significant difference detected with age
What urine biomarker has been predictive of geriatric cats developing azotemia?
Urinary auxin-to-creatinine concentration ratio (higher ratio in cats that later developed azotemia)
BUT no relationship btwn UC/C and plasma creatinine
What urine cytokines have been noted in CKD cats?
Significantly higher IL-8, TGF-B1; lower VEGF
Positive correlation of creatinine with TGFB1 in urine in CKD cats
Despite normal cholesterol levels in dogs with CKD, what is seen?
Dyslipidemia was consistently found in dogs with CKD and Nephrotic syndrome
(Decreased in HDL and variable increased in LDL and VLDV ) - similar to in people
What is different btwn dogs with CKD and nephrocit syndrome in regards to dysplipdemia?
Nephrotic syndrome dogs have proportionately greater increase in VLDL compared to dogs with CKD
In a study in the UK in CKD dogs, what are significantly associated with death and what was the MST?
IRIS stage and BUN significantly associated with hazard of death in CKD dogs
MST: 226 days from dx
In a study in the UNk in CKD dogs, what are the significant risk factors of the dz?
Age
Insurance
Breeds (Cocker, CKSC)
What is the prognosis of azotemic dogs with pulmonary changes?
No association of pulmonary change or dysfunction in azotemic dogs was noted to affect the prognosis
What has been noted to be associated with significantly improved survival in CKD dogs?
Higher BCS!!!
What derangements in Ca-P are noted in CKD?
Hyperparathyroidism and hyperphosphatemia (even in early stages of CKD) noted!!
What range of phosphorus correctly identified presence of hyperparathyroidism in dogs with CKD?
serum phosphorus concentration in the 4.5-5.5 mg/dL
What is true about CKD dogs with CaXPhos product >70?
Negative prognostic factor in CKD dogs
Mortality higher in dogs with CaXPhos>70, risk of death 4.2X as high as risk of death if <70
What is found to be increased in cats with CKD?
SDMA (serum symmetric dimethylarginine) -
Increased SDMA = Decreased GRF (reciprocal), similar relationship of creatinine to GFR
Linear correlation btwn SDMA and creatinine
Which biomarker in CKD cats allows for earlier detection of CKD compared to serum creatinine?
SDMA (serum symmetric dimethylarginine)
Increased before serum creatinine in 17/21 cats
Correlated with creatinine and decreased GFR
What is known about KIM-1 in cats?
KIM-1 (3 variants): Found in urine of cats with AKI (not CKD cats)
Histopath - Revealed KIM-1 in tubular cells
Indicator of tubular injury*
What is the MOA of chinese rhubarb?
Antifibrotic effects dt inhibition of TGF-B (fibrosis with kidney dz)
What did the use of chinese rhubarb show in cats with CKD?
Based on creatinine, BW, HCT, UPC, BP = NO significant difference in progression of CKD bwtn chinese rhubarb, benazepril, or both
What is known about uremic gastropathy in CKD cats?
NO ulcerations!!! Gastric fibrosis (43%) and materialization (38%) most common!!!
Lesions were more likely in CKD cats then controls
What is known about gastrin levels in CKD cats?
Gastrin is significantly higher in CKD cats BUT NOT associated with gastric ulceration
What method can be used in cats to determine ECF volume?
Intercept iohexol clearance
(standard bromide dilution)
Best standardized by body surface area
Explain the ECF volume in normal cats and those with mild CKD (creat about 2).
No difference btwn azotemic and nonazotemic cats in ECF volume
What has been shown to reduce FGF-23 concentrations in CKD cats?
Feeding a renal diet (phosphorus restriction)
Reductions in plasma FGF-23 in hyper- and normophosphatemic cats with stable azotemia CKD - Dietary phos restriction may enable cats to maintain normal phos
This group also had lower phos, PTH, and FGF-23 compared to CKD cats feed normal diet
Is there a single sample method for determining GFR in cats?
Yes! Modified Jacobsson method provides accurate estimation of iohexol clearance in cats, from a single sample collected at 180 minutes postinjection and using a formula based on the body weight to predict ECFV
(compared to iohexol clearance, multisamples)
Doese feeding a high salt diet affect renal function in older cats?
NO! GFR, BP, and other variables were not affected by dietary salt intake over two years
In controls:
Higher aldosterone
Lower Urinary Na/creat ratio
(UNKNOWN IN CKD CATS)
What does FGF-23 do in CKD cats?
FGF-23 plasma concentrations increased with increasing IRIS CKD stage in cats
Higher in cats that have higher phosphorus (based on stage of CKD)
What were predictors of FGF-23 levels in cats with CKD?
Independent predictors: Phosphate Log creatinine Total Calcium Log PTH PCV
In a group of geriatric cats, what was predictive of development of azotemia?
FGF-23 concentrations (significantly increased in cats that developed azotemia compared to cats that did not develop azotemia over the 12 months)
Positive relationship btwn FGF-23 and PTH (suggestive of association with renal secondary hyperPTH)
What is an effective treatment for anemia in CKD cats?
Darbepoetin (1ug/kg/wk, also give iron)
56% responded by reaching target PCV (25%)
MST responders: 238 days compared to MST nonresponders 83 days