Introduction
The kidneys play a vital role in maintaining the body's internal environment by performing several essential functions.
Their primary functions include:
1. Filtration of Blood: The kidneys receive blood from the renal arteries. Inside each kidney, there are millions of microscopic units called nephrons. Nephrons are responsible for filtering blood and removing waste products and excess substances, such as toxins, electrolytes, and water.
2. Regulation of Fluid and Electrolyte Balance: The kidneys maintain the balance of fluids and electrolytes in the body. They help regulate the levels of sodium, potassium, calcium, and other ions in the blood. This balance is crucial for various bodily functions, including nerve and muscle activity, fluid distribution, and blood pressure regulation.
3. Blood Acid-Base Balance: The kidneys play a key role in maintaining the body's acid-base balance. They help regulate the levels of hydrogen ions (acidic) and bicarbonate ions (basic) in the blood, which is essential for maintaining the body's pH within a narrow range. The normal pH of blood in both dogs and cats falls within a relatively narrow range, reflecting the body's tightly regulated acid-base balance. The normal blood pH for dogs and cats is typically between 7.35 and 7.45. This range indicates a slightly alkaline or basic condition. The renal system regulates pH by excreting or reabsorbing hydrogen ions (H+) and bicarbonate ions (HCO3-) in the urine.
4. Blood Pressure Regulation: The kidneys contribute to blood pressure regulation by adjusting the amount of sodium and water reabsorbed from the filtered blood. The renin-angiotensin-aldosterone system, which involves hormonal signals, helps control blood volume and systemic blood pressure.
5. Waste Excretion: The kidneys filter waste products from the blood, which are then excreted in the form of urine. These waste products include urea, creatinine, and other nitrogenous compounds produced by metabolism.
6. Red Blood Cell Production: The kidneys produce a hormone called erythropoietin, which stimulates the bone marrow to produce red blood cells. Red blood cells are essential for oxygen transport throughout the body.
7. Vitamin D Activation: The kidneys play a role in converting inactive vitamin D into its active form. This active form of vitamin D helps regulate calcium and phosphorus levels in the body, which is important for bone health.
The process of kidney function involves several steps:
1. Filtration: Blood is filtered in the glomeruli, which are clusters of blood vessels within the nephrons. Small molecules, such as water, electrolytes, and waste products, are forced out of the blood and into the nephron's tubule system.
2. Reabsorption: As the filtrate travels through the nephron's tubules, essential substances like glucose, amino acids, and most of the filtered water are reabsorbed back into the blood.
3. Secretion: Certain substances, such as drugs and excess ions, are actively secreted from the blood into the tubules to be excreted in the urine.
4. Concentration: The tubules adjust the concentration of the filtrate by selectively reabsorbing water. This helps regulate the body's fluid and electrolyte balance.
5. Urine Formation: The remaining fluid, now called urine, flows through the nephron and into the collecting ducts. It eventually drains into the renal pelvis and is then transported to the bladder for storage and eventual elimination from the body.
The kidneys are, therefore, crucial organs responsible for maintaining the body's internal balance, eliminating waste, regulating blood pressure, and supporting various physiological processes. Their intricate structure and function are essential for overall health and homeostasis.
What is kidney failure or Chronic Kidney Disease?
Kidney failure, also known as renal failure, refers to the condition in which the kidneys are unable to adequately perform their essential functions to maintain the body's internal environment. This can lead to a buildup of waste products, electrolyte imbalances, and fluid retention, which can have serious and potentially life-threatening consequences. Kidney failure can be acute or chronic.
Acute Kidney Failure:
Acute kidney failure, also called acute kidney injury (AKI), is a sudden and rapid decline in kidney function. It can occur within a matter of hours or days and is often reversible if the underlying cause is identified and treated promptly. Causes of acute kidney failure include severe dehydration, infections, urinary tract obstructions, medications, toxins, and reduced blood flow to the kidneys. Common symptoms include decreased urine output, fluid retention, electrolyte imbalances, and overall feeling of illness.
Chronic Kidney Disease:
Chronic kidney disease (CKD) is a progressive condition characterized by a gradual loss of kidney function over time. It develops over months or years and is typically irreversible, though its progression can be slowed with appropriate management. CKD can be caused by conditions such as diabetes, hypertension, glomerulonephritis, and polycystic kidney disease. As kidney function declines, waste products and fluids accumulate in the body, leading to symptoms such as fatigue, swelling, changes in urine output, and anemia.
End-Stage Renal Disease (ESRD):
End-stage renal disease is the most advanced form of kidney failure. At this stage, the kidneys have lost almost all of their function, and the patient requires renal replacement therapy, which includes dialysis or kidney transplantation, to survive. ESRD severely impacts the quality of life, and management involves ongoing medical care and lifestyle adjustments for both humans and animals.
Prompt diagnosis and management are critical in preventing the progression of kidney failure and minimizing its impact on overall health and well-being. The age predisposition of kidney failure in young animals is 4 years and below where the disease is mostly congenital or familial (genetic). The acquired form of kidney failure is usually common in older dogs but may affect dogs of any age.
What causes Kidney failure?
Table 1: Causes of acquired chronic kidney disease
Kidney failure can be acquired through any one of the following:-
Tubulointersitial nephritis
Chronic nephrotoxin exposure
Obstructive nephropathy
Nephrolithiasis, ureterolithiasis, spay granuloma, transitional cell carcinoma of bladder affecting ureterovesicular junction
Drug associated
NSAID,
Antibiotics
Immune mediated
Renal ischemia
Proteinuric kidney disease
Amyloidosis
Primary congenital/juvenile glomerulopathy
Secondary glomerulopathy, eg immune complex mediated
Infectious
Bacterial – Leptospirosis, pyelonephritis, Lyme nephritis
Mycotic – Candida albicans, blastomycosis
Leishmaniasis
Metabolic
Hypercalcemia
Hypokalemia
Neoplasia (Cancer)
Renal lymphoma
Renal carcinoma
Nephroblastoma
Table 2: Genetic causes of chronic kidney disease
​Renal (kidney) pathology | Associated breeds |
Renal dysplasia | Shih Tzu, Golden Retriever, Norwegian Elkhound, Lhasa Apso, Chow chow, Standard poodle, Soft Coated Wheaten Terrier, Alaskan malamute, Miniature Schnauzer |
Glomerulopathy | English Cocker Spaniel, Doberman Pinscher, English bull terrier, Soft Coated Wheaten Terrier, Samoyed, Dalmation, Bullmastiff, Newfoundland, Beagle, Bernese Mountain dog, Pembroke Welsh Corgi |
Amyloidosis | Shar-pei, English Foxhound, Beagle |
Polycystic kidney disease | Bull Terrier, West Highland White Terrier, Cairn Terrier |
Reflux nephropathy with segmental hypoplasia | Boxer |
Telangectasia | Pembroke Welsh Corgi |
Fanconi syndrome | Basenji |
How does kidney failure develop?
The total glomerular filtration rate (GFR) is influenced by each nephron in a healthy kidney. Kidney function declines gradually and may at first show no symptoms. This nephron adaptability allows for continued normal clearance of plasma solutes. This adaptive mechanism usually runs its course and eventually causes damage to the glomeruli of the remaining nephrons. Despite early homeostatic mechanisms involving nephron hyperfiltration, the natural course of renal failure is dependent on the etiology of the illness.
Chronic kidney disease or failure arises from a decrease in functional nephrons, which causes a loss of urine concentration and waste product retention. The remaining nephrons eventually perform hyperfiltration, which causes self-replicating damage. Nephron degeneration results in metabolic acidosis, renal ammoniagenesis, and toxic and inflammatory effects on the renal interstitium (tissue). Urea eventually builds up in the bloodstream, creating uremia, which results in a lack of erythropoietin and a shorter RBC lifespan, resulting in normochromic, normocytic, non-regenerative anemia. The inability to excrete phosphate causes hyperphosphatemia, which then causes hyperparathyroidism, which results in renal osteodystrophy and the mineralization of soft tissues (including nephrocalcinosis, which may exacerbate renal impairment).
Plasma levels of substances such as urea and creatinine start to show measurable increases only after total GFR has decreased by 50%. Although hyperfiltration and hypertrophy of residual nephrons are beneficial for maintaining GFR, it is found to be a major cause of progressive renal dysfunction. The increased glomerular capillary pressure may damage the capillaries, leading to focal and segmental glomerulosclerosis (FSGS) and eventually to global glomerulosclerosis.
Hyperparathyroidism is brought on and made worse by a deficiency in active vitamin D3 (calcitriol). It is a possibility for this to promote tubulointerstitial inflammation, which results in proteinuria and the development of tubulointerstitial nephritis, as a result of increased tubular reabsorption of proteins. The progression of glomerular hypertension, glomerular hyperfiltration, and glomerulosclerosis, which perpetuate renal damage, results from the buildup of blood pressure and the systemic hypertension that results in the transfer of high systemic pressure to glomerular capillaries.
How do veterinarians tell a pet has Kidney failure?
Diagnosis of chronic kidney disease or failure is done through a number of presenting problems, client history, clinical signs and laboratory investigations that include haematology, serum biochemistry, urinalysis, radiography (x-rays), ultrasonography (ultrasound) plus other additional tests.
Clinical signs
Polyuria/polydipsia.
Hyporexia/anorexia.
Weight loss.
Lethargy.
Vomiting/nausea.
Constipation.
Low body condition.
Sarcopenia/low muscle condition score.
Pale mucous membranes.
Halitosis (bad breath).
Small irregular kidneys.
Enlargement of parathyroid glands.
Uremic crisis (as above) in addition to:
Weakness.
Collapse.
Muscle tremors.
Uremic stomatitis/oral ulceration/tongue tip necrosis/xerostomia.
Uremic pericarditis.
Uremic pneumonitis.
Uremic enterocolitis (melena, hematochezia, diarrhea).
Altered behavior/uremic or hypertensive encephalopathy.
Hypothermia.
Laboratory investigations
Serum biochemistry
Azotaemia (Uraemia): biochemical abnormalities associated with reduced renal function, eg increased urea, creatinine and other non-protein nitrogenous waste. Azotemic CKD implies that more than 75% functional nephrons have been lost.
Hyperphosphatemia (increased blood phosphate levels).
Hypokalemia (increased blood potassium levels).
Hypercholesterolemia (Increased blood cholesterol levels).
Metabolic acidosis (blood Acid-base imbalance).
Hypo/hypercalcemia (increased or decreased blood total calcium levels).
Hypermagnesemia (increased blood magnesium levels).
Ionized calcium.
Confirmation of diagnosis of azotemic CKD should be made on at least 2 occasions 3-4 weeks apart in order to document persistence and chronicity of disease.
Urinalysis
Specific gravity, dipstick analysis, plus urine sediment examination. A specific gravity less than 1.030 with documented azotemia (ureamia) confirms inadequate urine concentrating ability with a renal origin.
Urine culture preferably from sterile sample, e.g., cystocentesis /catheter.
Urine protein to creatinine ratio (UP/C) Renal function assessment. This is performed only after documentation of inactive sediment and negative urine culture. Pooled urine samples (equivolume of urine collected from 3 morning samples) should be considered for patients with UP/C >2.
Haematology
Complete blood count (CBC).
Non-invasive blood pressure measurement:
Doppler technique ultrasound or oscillometric.
Fundic examination: Indirect ophthalmoscopy.
Radiography (X-ray)
Abdominal radiography is performed to assess the kidneys (size, shape, location, number), presence of uroliths (kidney and bladder stones) or masses affecting kidney ureter, and urinary bladder (size, shape, presence of uroliths).
Common findings are:
Small and irregular kidneys .
Evidence of constipation.
Bone demineralisation consistent with renal secondary hyperparathyroidism. May be most apparent in mandible "rubber jaw".
Soft tissue mineralisation particularly affecting stomach, kidneys, aorta.
2-D Ultrasonography (Ultrasound)
An ultrasound examination is performed to assess renal morphology and architecture.
Common findings may include:
Small and irregular kidneys .
Renal infarct.
Renal cyst Kidney: polycystic disease.
Loss/change in corticomedullary differentiation.
Pyelectasia.
Renal mineralization/nephrolithiasis/uterolithiasis.
Specific conditions identified include:
Hydronephrosis / hydroureter.
Perinephric pseudocyst.
Renal neoplasia.
Further diagnostic tests
These tests may be considered in specific circumstances:
Infectious disease testing (dependent on geographical location):
Borrelia burgdorferi.
Leptospirosis.
Canine leishmaniosis.
Antithrombin.
Coagulation profile (prothrombin time/activated partial thromboplastin time).
Pyelocentesis (pyelonephritis Kidney: pyelonephritis ).
Anterograde pyelogram/intravenous urogram (obstructive nephropathy).
Fractional excretion of electrolytes/amino aciduria.
Microalbuminuria.
Parathyroid hormone concentration.
DNA (genetic tests available for certain familial renal disease)
How is Kidney Failure Classified or Staged?
In veterinary medicine, chronic kidney disease (CKD) is also classified and staged based on similar principles to those used in humans. The classification takes into account both the level of kidney function, as indicated by estimated glomerular filtration rate (eGFR), and the presence of kidney damage. Kidney damage can be assessed through various means, including laboratory tests, imaging studies, and clinical evaluation.
It's important to note that CKD staging helps guide treatment decisions and monitor disease progression. Early detection and appropriate management are crucial in slowing down the progression of CKD and preventing complications. Classification of kidney failure is done only after a diagnosis of chronic kidney failure has been made. The staging is done according to serum/plasma creatinine concentration. This system takes into account the serum creatinine levels and the presence of proteinuria (abnormal levels of protein in the urine) to determine the severity of the disease and guide treatment decisions. Early detection and proper management are key to improving the quality and length of life for cats and dogs affected by CKD.
What is Stage 1 CKD?
In Stage 1 CKD, the damage to the kidneys is mild. The kidneys are still working normally, but there may be signs of kidney damage or physical damage to the kidneys. Stage 1 CKD means the kidneys have a normal estimated glomerular filtration rate (eGFR) equal to or greater than 90 mL/min/1.73 m², creatinine levels are normal, there is protein in the urine, but the urine is normal. The presence of protein alone is evidence of kidney damage and means the kidneys are in Stage 1 CKD.
What is stage 2 CKD?
nIn Stage 2 CKD, the eGFR is slightly reduced, ranging from 60 to 89 mL/min/1.73 m². However, the kidneys are still working normally, filtering blood, with no effects noticed on the health of the patient. While the damage to the kidneys may not be reversible, a lot can be done to slow down the damage to the kidneys. Protein may or may not be be detected in urine.
Stage I and early stage II CKD represents subset of patients which are non-azotemic (non-ureamic) but history, biochemistry, urinalysis, or diagnostic imaging confirms evidence of CKD.
In stage 2 CKD, there is a mild increase in serum creatinine levels, mild proteinuria and the kidney function is slightly reduced. However, the pet may not show significant clinical signs.
What is Stage 3 CKD?
In Stage 3 CKD, the kidneys have mild to moderate damage, and they are less able to filter waste and fluid out of the blood. This waste builds up in the body and begins to harm other areas, such as to cause high blood pressure, anemia and problems with bones. This buildup of waste is called uremia or azotaemia. Stage 3 CKD is split into 2 sub-stages based on the eGFR:
Stage 3a means the eGFR is between 45 and 59mL/min/1.73 m², and
Stage 3b means the eGFR is between 30 and 44mL/min/1.73 m².
Substaging is performed based on two measurements 2 - 4 weeks apart to check on protein levels in urine (proteinuria) and blood pressure or on a single occasion if in conjunction with target organ damage, eg hypertensive retinopathy/choroidopathy. There is also a moderate increase in serum creatinine levels and increasing levels of proteinuria. Pets may start showing clinical signs of kidney disease, such as increased thirst, decreased appetite, and weight loss.
What is Stage 4 CKD?
Stage 4 CKD means that the kidneys are moderately or severely damaged and the kidney function is significantly compromised with an eGFR ranging from 15 to 29 mL/min/1.73 m². Waste products build up in the blood and cause other health problems, such as:
High blood pressure
Anemia (not enough red blood cells in the body)
Bone disease
Heart disease
High potassium
High phosphorus
Metabolic acidosis (a buildup of acid in the body)
Severe increase in serum creatinine levels.
Pronounced proteinuria.
Pets are likely to exhibit noticeable clinical signs and require medical intervention.
What is Stage 5 CKD?
This is the most advanced stage of CKD, where the eGFR is less than 15 mL/min/1.73 m², indicating a severe loss of kidney function. Stage 5 CKD means that the kidneys are severely damaged and have stopped performing their job optimally to filter waste from the blood. Waste products build up in the blood and cause other health problems, such as:
High blood pressure
Anemia (not enough red blood cells in the body)
Bone disease
Heart disease
High potassium
High phosphorus
Metabolic acidosis (a buildup of acid in the body)
Extremely high serum creatinine levels.
Severe proteinuria.
Pets in stage 5 CKDare critically ill, and the disease significantly impacts their quality of life. Dialysis or kidney transplantation is often necessary at this stage to sustain life and is referred to as End-Stage Renal Disease (ESRD).
How is Chronic Kidney Failure Treated?
Treatment options depend on the underlying cause, the severity of the condition, and whether it is acute or chronic. Acute kidney failure may require supportive measures, addressing the underlying cause, and sometimes short-term dialysis. In the case of chronic kidney disease, treatment focuses on managing complications, slowing disease progression, and preserving the remaining kidney function. The acronym NEPHRONS, was developed to assist in treating Chronic Kidney Disease (CKD) based on excesses and deficiencies that occur, and it stands for:
N - Nutrition Management:
Proper dietary management is crucial in addressing excesses and deficiencies related to CKD. A tailored nutritional plan can help control electrolyte imbalances, manage protein intake, and maintain appropriate caloric levels. Restricting sodium, potassium, and phosphorus intake while ensuring adequate protein and energy intake is essential.
E - Electrolyte Balance:
CKD often leads to disturbances in electrolyte balance, including imbalances in sodium, potassium, and calcium levels. Monitoring and managing these electrolyte levels through dietary adjustments and, when necessary, medication can help prevent complications such as cardiac arrhythmias, muscle weakness, and bone disorders.
P - Phosphorus Control:
Elevated phosphorus levels are common in CKD and can contribute to bone and cardiovascular complications. Managing phosphorus intake through diet, phosphate binders, and medications is vital in preventing these adverse effects.
H - Hypertension Management:
Hypertension, or high blood pressure, is a common complication of CKD. Effective management of blood pressure through lifestyle modifications, including dietary sodium restriction, exercise, and potentially antihypertensive medications, is crucial in slowing CKD progression and reducing cardiovascular risks.
R - Renin-Angiotensin System Blockade:
The renin-angiotensin system (RAS) is a hormone system that controls blood pressure and the volume of fluids in the body. Inhibiting the renin-angiotensin system, often achieved through medications like angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), can help manage blood pressure, reduce proteinuria, and slow CKD progression. RAS-acting agents work by blocking different stages of the renin-angiotensin system (RAS).
ACE-inhibitors (benazepril, captopril, cilazapril, delapril, enalapril, fosinopril, imidapril, lisinopril, moexipril, perindopril, quinapril, ramipril, spirapril, trandolapril or zofenopril) and the direct renin inhibitor aliskiren block the actions of specific enzymes involved in the production of angiotensin II in the body (ACE-inhibitors block angiotensin-converting enzyme, while renin inhibitors block an enzyme called renin).
ARBs (containing the active substances azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan or valsartan) block receptors for a hormone called angiotensin II. Blocking the action of this hormone allows blood vessels to widen and helps to reduce the amount of water re-absorbed by the kidneys, thereby reducing blood pressure in the body.
O - Optimal Fluid Balance:
CKD patients may experience fluid retention, leading to edema and hypertension. Monitoring and maintaining optimal fluid balance through dietary sodium restriction and careful fluid intake management are essential to mitigate these complications.
N - Nephrotoxin Avoidance:
CKD patients are particularly susceptible to nephrotoxic substances, which can further damage their compromised kidneys. Avoiding medications, certain dietary supplements, and environmental toxins that could worsen kidney function is crucial.
S - Symptom Management:
CKD can cause a range of symptoms, including fatigue, anemia, and bone pain. Addressing these symptoms through appropriate interventions, such as erythropoiesis-stimulating agents for anemia or medications to manage bone health, can improve the patient's quality of life.
It's important to note that the NEPHRONS acronym provides a comprehensive framework for managing CKD based on specific aspects related to the disease. However, treatment plans should always be tailored to individual patients' needs and should be developed in collaboration with veterinary healthcare professionals.
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