Acute and Chronic Renal Failure Flashcards
What is the difference between acute and chronic kidney disease?
Acute:
- Recovery is possible: can take months for tissue to heal and renal function to come back
Chronic:
- Permanent loss of kidney function
- Requires 2-3 months duration in order to be referred to as chronic kidney disease
You notice an animal has azotemia, what are the 3 main divisions of Azotemia?
- Pre-renal
- Renal
- Post-renal
Therefore, just because azotemia is present, this does NOT mean renal injury is present
You have a patient that is azotemic, how can you tell if it is pre-renal Azotemia?
- Urinalysis is a MUST
- SG: >1.030 (dogs) or >1.035 (cats) then azotaemia pre-renal
- Dehydrated
- Rule out other diseases that can affect urine concentration: e.g. tubular disease, Cushing’s disease and diuretics
You have a patient that is azotemic, how can you tell if it is Post-renal Azotemia?
- Urinalysis
- U/S the bladder to ensure it is still intact and not ruptured
- X-ray to rule out urethral obstructions from urolithiasis
Why are the kidneys at high risk of ischemic and nephrotoxic insults?
- High cardiac output
- High metabolic demand and thus oxygen demand
- Can concentrate certain toxins in the urine and thus end up damaging itself
What is the definition of acute kidney injury?
A creatinine elevation >26.4µmol/L or >25% baseline within 48h
But there is no perfect definition as there are always individuals who don’t have azotemia but are experiencing sudden renal issues
What are the 4 stages of Acute Kidney Injury?
1) Ischemic or Nephrotoxic Insult
2) Structural damages and altered function
3) Maintenance Phase
4) Recovery phase
Describe the 1st stage of Acute Kidney Injury
Ischemic or Nephrotoxic Insult
- No clinical signs, non-azotemic
- Intrinsic parenchymal injury leading to dysfunction
- Rapid changes in hemodynamics, or filtration, or tubulointerstitial or outflow injury, which leads to the accumulation of metabolic toxins, dysregulation of acid-base, electrolytes and extracellular fluid balance
note: duration of this stage is dependent on the nature of the primary insult
Describe the 2nd stage of Acute Kidney Injury
Structural damages and altered function
- Continued hypoxia and inflammation, propagates renal damage
- Cortical structures (loop of Henle and collecting tubules) are predisposed to damage first due to their high metabolism and high blood requirements
- Intervention at this stage may not be successful in repairing 100% of kidney function
Describe the 3rd stage of Acute Kidney Injury
Maintenance Phase
- Critical amount of damage has occurred
- Lasts 1-3 weeks
- Urine output will increase or decrease: owners usually notice a change now
- There is a loss of tubular function
Describe the 4th stage of Acute Kidney Injury
Recovery Phase
- Injury has subsided and the renal tissue is beginning to repair
- Increased urine output
- Volume depletion can lead to the progression of kidney disease
- Repair can take months, and may not go back to 100% functionality. Damage to the basal membrane will mean irreversible loss
What are the Pre-renal causes of Acute Kidney Injury?
Hemodynamic Changes
- Absolute decrease in effective blood volume: blood loss, severe dehydration
- Relative decrease in blood volume: Hypotension
- Arterial occlusion or stenosis of renal artery: aortic thrombus
- Decrease in afferent artery pressure: NSAIDs and ACE inhibitors
What are the Renal causes of Acute Kidney Injury?
1) Ischemia
- Shock (hypovolemic, hemorrhagic, hypotensive, septic)
- Decreased cardiac output (CHF, arrhythmias, tamponade
- Hyperthermia
- Vessel occlusion
2) Nephrotoxin exposure
3) Infectious: pyelonephritis, leptospirosis, borreliosis, FIP, Leishmaniasis
4) Immune-mediated
5) Systemic Inflammation
6) Hypertension
7) Neoplasia (lymphoma)
What are the common Nephrotoxins to be aware of ?
- Ethylene glycol
- Lillies (cats)
- Grapes/ Raisins (dogs)
- Heavy metals
- Myoglobinemia/ Hemoglobinemia
- Hypercalcemia: cholecalciferol (rodenticide)
- Drugs: NSAIDs Aminoglycosides Amphotericin B Radiocontrast media ACE inhibitor Vasodilators
What are the Post-renal causes of Acute Kidney Injury?
- Urinary Tract Rupture (leading to uroabdomen)
- Urinary Tract Obstruction (pelvis, ureter, urethra)
At what Systolic BP will you get damage to organs?
> 180 mmHg
- Retinal hemorrhage
- Retinal detachment
- Intracranial hemorrhage
What is the treatment for Acute Kidney Injury?
- Crystalloid Fluid therapy: maintenance + ongoing losses + dehydration status
Best to replace 1/3 of dehydration within 6 hours, and then the remaining 2/3 is replaced over 24 hours. This will allow for minimal rehydration within the first 6 hours, followed by a SLOW rehydration so not to overwhelm the kidneys
Fluid therapy should be reassessed every 2-4 hours - Norepinephrine for severe hypotension if present
- Furosemide (diuretic) can help convert an oligo-anuric patient to a non-oliguria but must be used carefully with fluid therapy
- Calcium gluconate for the protection against hyperkalemia
You have an in-hospital patient that is suffering from AKI, and showing signs of Hyperkalemia (Bradycardia) due to anuria
You perform an ECG and notice changes reflective of Hyperkalemia (small QRS complexes, prolonged P-QRS intervals, small or absent P waves and tall tented T waves)
What is the treatment of choice?
1) Calcium gluconate (10%)
Protects the myocardium by decreasing the threshold potential and normalizing the conductivity
- It does NOT address the K+ concentration directly
Dose: 0.5 - 1.0ml/kg of Calcium gluconate 10% IV slowly while patient is on an ECG monitor
2) Glucose administration (50% Dextrose)
3) +/- Insulin/Glucose protocol
4) Antibiotics if indicated
You are presented with a patient that is diagnosed with AKI, there are no ECG changes, but serum electrolytes show a hyperkalemia
How can this be managed/ treated?
1) Glucose administration (50% Dextrose)
Dose: 1-2 ml/kg diluted 1:2 in slow IV infusion (15-20mins)
This will increase the endogenous insulin release (within 1 hour) and lead to co-transport of glucose and Na+/K+ into the intracellular space, thus reducing K+ levels
2) +/- Insulin/Glucose protocol
What is the definition of Chronic Kidney Disease?
Chronic Kidney Disease is a syndrome, it is a slow, progressive, irreversible loss of structural or functional nephrons that has been ongoing for at least 3 months
Between Acute and Chronic Kidney Disease, which is more commonly recognized in cats and dogs?
Chronic Kidney Disease
What are the causes of Chronic Kidney Disease in Dogs and Cats?
Chronic Kidney Disease can be considered a Syndrome, with many causes
Dogs:
- 58% chronic tubulointerstitial nephritis
- 28% glomerulonephropathy
- 6% amyloidosis
Cats:
- 70% tubulointerstitial nephritis
- 15% glomerulonephropathy
- 11% lymphoma
- 2% amyloidosis
What are the clinical signs associated with Chronic Kidney Disease?
Clinical signs are associated with the loss of function and thus retention of toxic metabolites and body-fluid imbalance
PUPD (44%) Anorexia (40%), nausea, vomiting (50%) Oral ulceration, stomatitis, necrosis, halitosis (12%) Diarrhoea/melena (37%), haematochesia Weight loss/cachexia (29%) Lethargy/depression (22%) Urinary incontinence (20%) Anemia (4%)
One of the clinical consequences of Chronic Kidney Disease is the disturbed excretion of electrolytes and water, why does this happen and what are the clinical manifestations of this?
- Loss of functional nephrons = decline in GFR = remaining intact nephrons will have to excrete more water and electrolytes to compensate for the loss
- Up to an 80% reduction in GFR does not impair Na, K and water balance, but beyond 80% and you enter end-stage failure leading to the following clinical manifestations:
- Edema: due to water retention
- Hypertension
- HypoNa: loss of Na and unable to reabsorb, or PUPD
- HyperK: oliguric, anuric, loss of filtering capability
- HyperPO: oliguric, anuric, loss of filtering capability
- Metabolic acidosis
What are the clinical pathophysiological consequences of chronic kidney disease?
1) Disturbed excretion of electrolytes and water
2) Reduced excretion of organic solutes (urea and creatinine)
3) Impaired renal hormone synthesis
4) Arterial hypertension and cardiovascular consequences
5) Renal Secondary Hyperparathyroidism
Which organic solutes are retained in the blood system during kidney disease which we use as biomarkers of renal sufficiency?
- Urea and Creatinine
What are the consequences associated with the accumulation of urea and creatinine?
- Na/K ATPase inhibition
- Inhibition of platelet function
- Leukocyte dysfunction
- Insulin resistance
- Increased red cell fragility
What are the hormones produced by the kidney, which can be affected during Chronic Kidney Disease?
- Erythropoietin: stimulates red cell production from the bone marrow
- Calcitriol: Active form of Vitamin D, essential for Ca and skeletal metabolism
- Prostaglandins
- Renin
- Kinins
Vitamin D deficiency and excess retention of Phosphorus in a CKD patient will lead to __________
Renal secondary hyperparathyroidism, leading to the overproduction of PTH and subsequent renal osteodystrophy
Renal osteodystrophy is the result of hyperparathyroidism secondary to hyperphosphatemia combined with hypocalcemia, both of which are due to decreased excretion of phosphate by the damaged kidney.
What is the most common cause of secondary hypertension in dogs and cats, and why?
Chronic Kidney Disease
With a reduction in GFR, water is retained in gradually increasing proportions leading to excess blood volume and hypertension
Hypertension subsequently causes vasodilation of the blood vessels, including the glomerular vessels, leading to leaking of proteins into the urine (proteinuria)
What is the pathophysiology of Renal Secondary Hyperparathyroidism?
- Reduced glomerular filtration → reduced phosphorus excretion → hyperphosphatemia
- Hyperphosphatemia → Calcium-phosphate products + soft tissue mineralization (especially stomach, kidneys, myocardium, lung, and liver) → lowering of [blood calcium]
- PTH secretion → release of calcitriol from remaining nephrons → Osteoclasts release FGF-23 → increase renal excretion of phosphate + decrease phosphate reabsorption
- As the disease progresses GFR reduced further with elevated hyperphosphatemia + Vitamin D metabolism becomes defective, calcitriol levels decrease → reduced intestinal absorption of calcium → hypocalcemia
- Sustained Hypocalcemia → hypertrophy of parathyroid glands → increased PTH secretion.
- Decreased active vitamin D → stimulates PTH secretion further
- PTH → increased osteoclastic activity → bone resorption (particularly in the mandible and skull)
Refer to: https://www.vin.com/apputil/content/defaultadv1.aspx?id=7054902&pid=12886
What is the effect of PTH on the kidneys?
- Stimulates calcitriol activation
- Increases Calcium retention
What is FGF-23 and what is its function/ purpose?
Released from osteoclasts in response to elevated calcitriol levels, when there is an absolute OR relative deficiency in Ca+
How can Chronic Kidney Disease be diagnosed?
- Serum creatinine concentration: but there needs to be a 75% reduction in GFR before the creatinine conc is above the reference range = somewhat insensitive = just because its not above the reference range, doesn’t mean CKD is not present
- Blood Urea Nitrogen Concentration (BUN/ Urea): less specific and less sensitive than creatinine. Can increase with GI ulcers or bleeding, enhanced protein catabolism, dehydration/ pre-renal azotemia or drugs (e.g. corticosteroids)
- SDMA (Symmetric dimethylarginine): ideal biomarker and can detect CKD much earlier than creatinine
- Urine SG: essential to differentiate pre-renal from primary renal disease. In advanced CKD, the kidneys cannot concentrate the urine more than the blood plasma, and therefore they are isosthenuric
- Hyperphosphatemia
- Metabolic Acidosis: excretion of ammonium decreases with GFR reduction = acidosis (remember ammonium is a weak acid) and retention of renal acids
- Cats may be hypocalcemic when measuring iCa, but hypercalcemia when measuring Total calcium levels (likely due to the increased Ca-PO4 complexes)
- Hypokalemia more common in cats with CKD than in dogs
- Full Hematology + Biochemistry
- Urinalysis + Urine culture
- Blood pressure
- Urine protein: creatinine ratio
- Radiographs + U/S
You are presented with a patient who has a Urine SG of <1.006, can this patient have primary renal disease?
No
In order for the kidneys to dilute the urine below the plasma concentration requires proper renal function, and therefore this patient cannot have renal disease
A cat presents with hypokalemia, however hyperaldosteronism is also a disease resulting in hypokalemia, how can the two be differentiated with diagnostics?
- Aldosterone level
- Renin level
- Aldosterone: Renin Ratio (expecting it to be elevated)
+ Imaging (radiographs + U/S)
How can you determine if the patient has Acute Kidney Injury or Chronic Kidney Disease?
- Medical history + physical examination = loss of muscle mass or history of chronic disease will suggest chronicity
- History of changes in renal values on urinalysis will support chronic kidney disease
- Presence of structural changes seen on imaging will also support chronic kidney disease