Clinical approach and laboratory evaluation of renal disease Flashcards
Purpose of the kidneys broadly.
Regulates volume and composition of extracellular fluid by forming urine.
Kidney disease includes:
- Decreased GFR - azotemia
- Damaged glomerular filtration barrier - proteinuria
- Tubular defects - altered urine/plasma composition, urolithiasis
- Endocrine function
- Blood pressure
Polydipsia has been defined as water intake of how much in dogs and how much in cats?
Polydipsia has been defined as water intake >100 mL/kg/day in dogs and >50 ml/kg/day in cats.
Even if this threshold is not exceeded, observed increase in thirst may be significant.
It is important to differentiate polyuria from pollakiuria, dysuria, or urinary incontinence, which are…
generally problems of the lower urinary tract rather than the kidneys.
polyuria = excessive or an abnormally large production or passage of urine
pollakiuria = abnormally frequent urination (with small volume)
Ocular signs of hypertension, such as (3)
hyphema (blood in anterior chamber)
mydriasis (dilated pupil) &
blindness are more common in cats with CKD than dogs, even though prevalence is comparable.
Dogs and cats with AKI often have a history of recent…
nonspecific signs (lethargy, inappetence).
Occasionally pets with AKI have a history of known toxin ingestion or of being given prescribed, potentially nephrotoxic, medications.
Weight loss can be a sign of more chronic kidney disease.
Signs of uremia: (6+)
Nausea, vomiting,
lethargy, hypothermia,
oral mucosal and GI ulceration,
melena, encephalopathy, seizures.
The collection of clinical signs associated with severe azotemia is termed uremia.
Azotemia =
Elevated concentrations of nitrogenous waste products such as BUN and serum Crea above the reference interval is termed azotemia.
Creatinine is a waste from protein and muscle breakdown.
features of nephrotic syndrome? (2)
Edema and/or ascites are features of nephrotic syndrome but can also develop with overhydration in oligo-anuric dogs and cats.
Main areas to pay especial attention to with a potential kidney disease patient during physical exam? (8)
kidney palpation
bladder size
hydration status
body condition
fibrous osteodystrophy or
pathologic fractures due to mineral & bone disorder from CKD
mm
BP
The kidneys should be assessed for (3)
size, contour, and evidence of pain on palpation.
The kidneys of cats are easily palpated but in dogs they are often difficult to identify conclusively.
The size of the bladder may be…
important:
a large bladder in a pet that urinated recently suggests PU,
bladder turgidity (= swollen or firm) may indicate obstruction, and
an empty bladder in a pet that has not urinated may indicate oliguria.
Cats are particularly vulnerable to developing what? (2) with overhydration.
Cats are particularly vulnerable to developing pleural effusion and dyspnea with overhydration.
Pets with CKD may be (insert non-specific sign)
in poor body condition.
When CKD occurs in young growing animals, what type of sign may be present?
deformity of the maxilla and mandible (“rubber jaw” due to fibrous osteodystrophy) can occur, although this is uncommon.
Older animals occasionally suffer pathological fractures due to CKD-mineral and bone disorder (MBD).
What non-invasive measurement should be taken in all kidney dz patients?
Blood pressure should be measured in all pets with kidney disease.
Fundic examination should also be performed, particularly when systolic pressure is >160 mmHg.
Mucous membranes in CKD. (2)
Mucous membranes may be pale in CKD due to anemia.
Uremic ulceration of the oral mucosa and tongue tip necrosis can be present if azotemia is severe but does not differentiate between acute and chronic disease.
AKI vs CKD
AKI potentially reversible, CKD irreversible (>3months)
Despite permanent loss of functioning nephrons in CKD, remaining nephrons may hypertrophy and hyper-filtrate circulating blood.
Differentiating acute from chronic disease is usually based on history and physical exam.
common features of CKD. (5)
Longstanding history of PU/PD,
weight loss due to poor appetite,
poor body condition, and
poor coat quality are common features of CKD.
Diagnostic imaging can provide further information permitting objective assessment of
renal size and contour, together with evaluation for mineralization and loss of internal architecture, consistent with chronicity.
Kidney size and shape may provide valuable clues to whether
the azotemia is acute (normal or enlarged size, normal shape, occasionally abnormal turgid feeling, evidence of pain)
or chronic (small and/or irregular in shape), especially in cats.
Blood testing in possible kidney disease other than kidney values.
Nonregenerative anemia - CKD, (AKI)
Hyperkalemia - AKI, dogs with CKD that are fed renal diets
Describe hematological changes in kidney disease.
Nonregenerative anemia may be present in CKD but anemia may also occur in pets with AKI, e.g., with overhydration, leptospirosis, or hypoadrenocorticism.
Hemorrhage or hemolysis can cause hypoxia/hypotension, which may serve as an inciting cause for AKI.
Anemia is not always caused by chronic disease, particularly regenerative anemias.
Describe biochemical changes in kidney disease other than classic kidney values.
Hyperkalemia is most often associated with AKI and particularly with postrenal causes of azotemia.
Hyperkalemia may, however, develop in dogs with CKD fed “renal diets” especially if they are concurrently treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (lower blood pressure and thus GFR).
Urinalysis in kidney disease cases. (4)
Possibilities include:
Pyuria, bacteriuria, white cell casts e.g. pyelonephritis (acute/chronic)
Calcium oxalate monohydrate crystals in e.g. ethylene glycol poisoning
Euglycemic glucosuria in e.g. proximal tubular dysfunction (acute/chronic) (impaired reabsorption of GLU)
Large numbers of granular casts, renal epithelial tubular cell casts e.g. acute tubular necrosis
ethylene glycol poisoning can cause the formation of what type of crystals?
how?
Calcium oxalate monohydrate crystals in ethylene glycol poisoning.
due to the metabolic breakdown of ethylene glycol into toxic metabolites, particularly oxalic acid.
Oxalic acid is a dicarboxylic acid that can bind with calcium ions in the body. Oxalic acid binds with calcium ions in the bloodstream to form calcium oxalate. This calcium oxalate can crystallize in two main forms.
These crystals can deposit in various tissues, particularly the kidneys. The formation of calcium oxalate crystals in the kidneys can lead to:
Obstruction of renal tubules
Acute tubular necrosis
Acute kidney injury
These crystals can appear in urine, and their presence is an important diagnostic clue in cases of ethylene glycol poisoning.
high phosphorous to creatinine ratio is more suggestive of AKI, why?
As CKD progresses, phosphorous concentration increases gradually and proportionally to the decrease in kidney function (i.e., to the increase in serum creatinine concentration).
Conversely, in AKI, since compensatory mechanisms are inactive, phosphorus concentration increases substantially compared with the increase in serum creatinine concentration.
Thus, high phosphorous to creatinine ratio is more suggestive of AKI.
Calcium values in AKI vs CKD.
Calcium concentration tends to be normal to low in animals with AKI, while in animals with CKD, calcium concentration tends to be normal to high.
Yet, there are some exceptions to these trends. For example, grapes and raisins intoxication leading to AKI might be associated with hypercalcemia,5 and vitamin D intoxication results in hypercalcemia and AKI (i.e., hypercalcemic nephropathy).
one of the most commonly utilized modalities to differentiate AKI vs. CKD
Ultrasonographic examination
The ultrasonographic appearance of the kidneys is affected by the etiology; however, typical ultrasonographic changes characterizing CKD include small kidneys with irregular margins, hyperechoic cortices and poor corticomedullary differentiation, whereas in AKI, the kidneys maintain normal architecture and often are enlarged with hyperechoic cortices.
However, exceptions occur and in some etiologies of CKD the kidneys may be enlarged (e.g., amyloidosis, lymphoma, polycystic kidney disease, hydronephrosis) whereas in AKI the kidneys may have abnormal appearance (e.g., ethylene glycol intoxication).
A less utilized ultrasonographic method to differentiate AKI from CKD is to
evaluate the parathyroid glands.
Secondary renal hyperparathyroidism is an inevitable and early consequence of CKD, resulting in hypertrophy of the parathyroid glands, therefore should be present, at least in animals with advanced CKD, and absent in AKI.
It has been shown that ultrasonographic examination of the parathyroid glands is helpful in differentiating AKI from CKD, yet identifying the parathyroid glands requires special skills.
Discriminating prerenal from renal causes of azotemia can be aided by measuring
the urine specific gravity. If the USG is >1.030 in dogs or >1.035 in cats, azotemia is usually prerenal in origin, with certain caveats.
Some cats with CKD retain urine concentrating ability (>1.035-1.040) despite azotemia.
Prerenal azotemia is confirmed by
administering intravenous fluids (or reducing the dose of diuretics) and documenting the resolution or improvement in azotemia.
If fluid is present in either the retroperitoneal or peritoneal cavity, a sample should be collected for analysis; if the creatinine concentration is…?
greater than twice that in the blood is consistent with urinary tract rupture.
Since urine is a chemical irritant, nonseptic neutrophilic inflammation is common but the amount of associated hemorrhage and inflammation is variable.
IRIS Grading of Acute Kidney Injury (AKI)
represents a continuum of renal injury from mild, clinically inapparent, nephron loss to severe acute renal failure.
The IRIS AKI Grading scale (I-V) for dogs and cats is based on fasting blood creatinine determination and clinical parameters, such as urinary flow rate.
IRIS Grading of Chronic Kidney Disease (CKD)
Staging of chronic kidney disease (CKD) is undertaken following the diagnosis of CKD in order to facilitate appropriate treatment and monitoring of the patient.
Staging 1-4 is based initially on fasting blood creatinine, assessed on at least two occasions in the stable patient. The patient is then substaged based on proteinuria and systemic blood pressure.
SDMA has also been included in staging criteria.
Surrogate plasma/serum markers of GFR: (3)
urea, creatinine, SDMA.
Only valid with steady state renal function.
Isolated evaluation does not determine whether azotemia is prerenal/renal/postrenal, acute/chronic, reversible/irreversible.
Evaluation of changes in BUN, serumCREA and SDMA:
Proteinuria should be evaluated in all pets with
CKD as part of the IRIS staging scheme. Proteinuria also may be further investigated if a positive result is obtained on a urine dipstick or if protein-losing nephropathy is a concern.
Proteinuria is usually first assessed with a colorimetric biochemical reagent urine dipstick. Dipsticks have reasonable sensitivity (>80%), but poor specificity. If there is concern about proteinuria, further assessment with
a urine protein to creatinine ratio (UPCR) is warranted.
The most common test for quantifying proteinuria is the
Urine Protein to Creatinine Ratio (UPCR)
persistent values >0.4 in cats and >0.5 in dogs are considered abnormal. UPCRs >2.0 are strongly suggestive of underlying glomerular disease although other etiologies cannot be excluded without renal biopsy. Spot UPCR correlates well with 24-hour urine protein quantification.
Considerable day-to-day individual variability in UPCR is reported, particularly in proteinuric pets. UPCR must change by 35% for patients with UPCR ∼12 and by 80% for those with UPCR ∼0.5 for this to reflect a true change in UPCR rather than day-to-day variability.
Whereas 1 sample may be sufficient for dogs with UPCR <4.0, more than 2 samples should be checked when there is marked proteinuria (UPCR >4.0).
They can be averaged to provide a credible assessment of proteinuria.
Pooling an equivolume of urine from 3 samples (e.g., collected in a 48-hour period) is a more cost-effective and comparable way to evaluate proteinuria in pets with UPCR >4.0.
Persistent proteinuria is common, affecting almost ?% of ?
almost 20% of elderly dogs.
Proteinuria can be categorized as (3)
pre-renal/overflow, renal (glomerular or tubular), or post-renal.
Interpretation of proteinuria should be made in the context of the sediment examination, as the presence of RBCs and WBCs is indicative of renal or post-renal issues and their absence may suggest renal origin (glomerulonephritis, amyloidosis).
Pathological pre-renal causes of proteinuria include hemolysis (hemoglobin), rhabdomyolysis (myoglobin) or plasma cell cancers (immunoglobulins).
Renal glucosuria indicates
Tubular dysfunction.
Glucosuria in a euglycemic dog or cat is indicative of altered renal tubular function, called renal glucosuria, and can be either a single or complex renal tubular disorder.
In the latter, increased excretion of other molecules (e.g., amino acids, phosphate, bicarbonate and electrolytes) may occur and the disorder can be either inherited (e.g., Fanconi syndrome) or acquired.
Transitional epithelial cells are derived from
urothelium and are typically smaller with tapered ends (caudate cells) when originating from the renal pelvis or they may form epithelial cellular casts, which are indicative of renal injury.
Cylindruria implies
kidney damage because casts are typically formed within the ascending limb of the loop of Henle and the collecting duct, where tubular flow rates are slowest.
Rare hyaline or granular casts may be normal in dogs and cats, but high numbers of cellular casts are always abnormal.
Casts can be classified as hyaline, granular, waxy, fatty, cellular (epithelial, WBC, RBC), may contain crystals and/or microorganisms, or can be mixed in origin.
Review summary of renal biomarkers.
Biomarkers of GFR typically lag behind
kidney injury biomarkers. Use of biomarkers allows earlier identification of AKI and may lead to earlier diagnosis and treatment.
Describe Urinary Enzymes
Enzymes are located on the brush border and in intracellular locations within tubular cells. Since enzymes are usually medium- to high-molecular-weight proteins (>100 kDa), enzyme activity identified in urine is most likely of renal origin.
Knowledge of the location of urinary enzymes within the nephron and alteration in either urine enzyme concentration or activity can be used to indicate either damage or an alteration in activity of cells from that region of the tubule.
Urine gamma glutamyl transferase (GGT)/creatinine ratio has been used for the monitoring of gentamicin nephrotoxicosis.
