Azotemia

Azotemia – this is an increase in the blood concentration of nitrogenous products of protein metabolism (mainly creatinine and urea). The most frequent cause are diseases causing impairment of the excretory function of the kidneys – glomerulonephritides, interstitial nephritides, nephropathies in systemic diseases. Also, azotemia may be observed in malignant neoplasms. The content of urea and creatinine is determined when performing a biochemical blood analysis. Elimination of azotemia is carried out by hemodialysis sessions and treatment of the underlying disease.

Classification

By the mechanism of origin, azotemia is subdivided into:

Productional

Develops as a consequence of increased entry into the blood of tissue protein breakdown products (high prolonged fever, cachexia in oncological disease).

Retentional

Arises as a consequence of impaired excretion of nitrogen-containing products. In turn, retentional azotemia is divided into:

• Renal ⎼ the cause is a decrease in the excretory function of the kidneys due to direct damage to the renal tissue.
• Extrarenal ⎼ impaired excretion of nitrogenous products as a consequence of reduced renal blood supply or difficulty in urine outflow.

Pathogenesis

When the concentration of urea in the blood increases, it begins to be excreted by the sweat glands, through the mucous membranes of the respiratory organs and the gastrointestinal tract. In the large intestine, under the action of bacterial flora, urea is converted into toxic compounds – ammonium carbonate, ammonium carbamate, indicans, etc. These substances, being absorbed into the systemic circulation, exert a damaging effect on cell membranes, disrupt the function of enzymes.

Azotemia vs Uremia

Intoxication with nitrogenous products affects all organs, especially the central nervous system. Uremia occurs. It is worth clarifying the differences between these two very similar concepts.

Azotemia – is a biochemical (laboratory) syndrome, meaning a high content in the blood of nitrogenous metabolism products.

Uremia, however (a constant companion of chronic renal failure), is a clinical syndrome arising as a result of the accumulation of these very metabolites and including encephalopathy, dystrophic changes of the skin coverings, polyneuropathy, etc. Uremia arises as a consequence of azotemia.

Causes of Azotemia

Kidney diseases

The most frequent cause of azotemia are various nephrological diseases accompanied by damage to the renal tissue. The death of nephrons as a consequence of infectious inflammation of the parenchyma, autoimmune damage of the glomerular apparatus, or deposition of pathological protein leads to impairment of excretory function and azotemia. Listed below are kidney diseases that may be accompanied by azotemia:

• Glomerulonephritides: poststreptococcal, idiopathic, IgA nephropathy (Berger’s disease).
• Tubulointerstitial nephritis: kidney damage caused by taking medicinal preparations (nonsteroidal anti-inflammatory drugs, aminoglycoside antibiotics, cytostatics), poisoning by heavy metals, metabolic disorders, etc.
• Nephropathies in systemic diseases: systemic lupus erythematosus (lupus nephritis), systemic scleroderma (scleroderma kidney), systemic vasculitides.
• Renal infections: pyelonephritis, renal tuberculosis.
• Other kidney lesions: polycystic disease, amyloidosis, kidney cancer.

Obstruction of the urinary tract

Any pathology or anatomical anomaly from the level of the renal pelvis to the urethra, disrupting normal urine outflow, can become a cause of azotemia. Retention of urination increases pressure in the nephron tubules, due to which reverse reabsorption of nitrogenous metabolites occurs. Causes of obstructive uropathy may include:

• urolithiasis;
• compression of the ureter by a tumor of the pelvic organs;
• vesicoureteral reflux;
• hydronephrosis;
• ureteral stricture;
• benign prostatic hyperplasia (adenoma) or prostate cancer.

Impaired renal perfusion

With a significant decrease in pressure in the afferent arterioles of the nephron glomeruli, blood filtration worsens, the formation of primary and secondary urine slows down and, consequently, retention of the excretion of all toxic metabolic products with urine occurs.

At the same time, kidney function in the initial stages remains preserved; the main pathogenetic link in the occurrence of azotemia is a decrease in the effective filtration pressure in the Bowman’s capsules. However, prolonged hypoperfusion leads to the death of nephrons as a consequence of hypoxia. Causes of worsening renal blood supply:

• hemorrhage;
• pronounced dehydration;
• acute heart failure;
• shock: traumatic, anaphylactic, infectious-toxic;
• renal artery stenosis: congenital, atherosclerotic.

Increased tissue catabolism

In certain conditions, azotemia arises as a result of increased formation of nitrogenous metabolites due to increased catabolism of tissue proteins. A distinctive feature of this type of azotemia is that the urea level may remain within the normal range, as the main share is composed of amino acid nitrogen. Conditions accompanied by increased tissue breakdown:

• high fever;
• tumor lysis syndrome;
• leukemias;
• cachectic states;
• excessive intake of glucocorticosteroids;
• extensive burns.

Symptoms of azotemia

Early or mild azotemia

In its early stages, azotemia may produce subtle or no symptoms at all. This is particularly concerning as kidney damage can progress silently. Early indicators may include:

• Mild fatigue or weakness
• Decreased appetite
• Slight changes in urination patterns
• Mild edema (swelling), particularly in the ankles and feet
• Subtle cognitive changes, such as mild difficulty concentrating

Moderate

As azotemia progresses and waste products continue to accumulate, more noticeable symptoms emerge:

• Significant fatigue and general malaise
• Persistent nausea
• Vomiting, particularly in the morning
• Noticeable changes in urine output (either decreased or increased)
• More pronounced edema in the extremities
• Shortness of breath, especially with exertion
• Difficulty sleeping
• Muscle cramps, particularly at night
• Pruritus (itchy skin)
• Metallic taste in the mouth
• Bad breath (uremic fetor)
• Mild confusion or “brain fog”

Severe azotemia and uremic syndrome

When azotemia becomes severe, it can progress to uremic syndrome, a serious condition requiring immediate medical attention. Symptoms include:

• Severe nausea and vomiting
• Significantly decreased urine output (oliguria) or no urine output (anuria)
• Severe edema, which may become generalized (anasarca)
• Dyspnea (difficulty breathing), even at rest
• Chest pain or pressure
• Confusion, disorientation, or altered mental status
• Seizures
• Pericarditis (inflammation of the heart lining)
• Uremic frost (urea crystals on the skin)
• Tremors or muscle twitching
• Hiccups that persist
• Severe pruritus resistant to treatment
• Yellow-brownish skin discoloration

Symptoms by type of azotemia

Prerenal

• Symptoms of dehydration (dry mouth, thirst, reduced skin turgor)
• Orthostatic hypotension (dizziness when standing)
• Tachycardia (rapid heart rate)
• Indicators of the root issue leading to diminished blood supply to the kidneys

Intrarenal (Intrinsic)

• Evidence of kidney inflammation
• Blood in the urine
• Tea-colored urine
• Flank pain (in some cases)
• Symptoms specific to the underlying kidney disease

Postrenal azotemia symptoms

• Pain or discomfort during urination
• Urinary frequency or urgency
• Incomplete bladder emptying
• Visible blood in urine
• Lower abdominal or back pain
• In men, symptoms related to enlarged prostate

How to diagnose azotemia?

Detection of azotemia in analysis results requires clarification of the cause of its occurrence. For this, it is necessary to seek help from a general practitioner or urologist. Knowing the patient’s history (for example, the presence of chronic kidney disease), the specialist may pay attention to symptoms of uremia: pronounced general weakness, skin itching, grayish skin tone. To assess the degree of CKD, calculation of the glomerular filtration rate is mandatory.

During physical examination, an increase in body temperature, facial edema, a positive percussion sign (over the kidneys), etc., can be identified. To confirm one or another disease, additional examination is prescribed:

• Complete Blood Count. In the clinical blood analysis in renal infection, leukocytosis, increased ESR are noted. In CRF, systemic inflammatory diseases, oncological processes, normochromic normocytic anemia is detected.
• Biochemical Blood Analysis. In the biochemical blood analysis, besides increased content of creatinine and urea, often an increased concentration of potassium is detected.
• Urinalysis. In pyelonephritis, leukocyturia, a positive test for nitrites, alkaline reaction of urine are found in the urinalysis. For glomerulonephritis, proteinuria, hematuria are characteristic. In patients with nephrolithiasis, during microscopic examination of urine sediment, various crystals are detected – urates, oxalates, phosphates. For identification of the infectious agent, a bacterial culture of urine is performed (including for mycobacteria tuberculosis) with determination of sensitivity to antibacterial drugs.
• Immunological Studies. For poststreptococcal glomerulonephritis, a high content of ASLO is typical. In rheumatological diseases, analysis for the detection of autoantibodies is performed – antibodies to double-stranded DNA, antineutrophil, anticytoplasmic antibodies.
• Kidney Ultrasound. In pyelonephritis on kidney ultrasound, dilation of the pelvicalyceal system, decreased echogenicity are visualized. In people suffering from urolithiasis, calculi are detected. Renal cysts may be found.
• Kidney X-ray. On X-ray images after contrast administration (excretory urography), various anomalies and defects of the urinary system can be visualized – stones, ureteral strictures, external compression. Voiding cystourethrography is fundamental in the diagnosis of vesicoureteral reflux. In case of suspected renal artery stenosis, renal angiography is mandatory.
• Histological Studies. To confirm kidney cancer, amyloidosis, as well as to establish the exact morphological type of glomerulonephritis (mesangioproliferative, membranous, sclerosing), a kidney biopsy is performed.

Treatment of azotemia

Conservative therapy

To combat azotemia directly, i.e., to remove the excess of toxic nitrogenous metabolites from the body, there are extracorporeal detoxification methods, the main one of which is hemodialysis. However, the mere presence of azotemia is not considered an indication for performing this procedure.

There are certain criteria, for example, the urea concentration must exceed 30 mmol/L, creatinine – 600 µmol/L (Note: units were likely intended as µmol/L for creatinine, adjusted for typical ranges), etc. Also, for the correction of azotemia, treatment of the underlying disease is necessary:

• Antibacterial Therapy.

For elimination of the infectious pathogen, a broad-spectrum antibiotic is used (cephalosporins, penicillin antibiotics). Patients with renal tuberculosis are prescribed long-term treatment with a combination of anti-tuberculosis chemotherapy drugs.

• Anti-inflammatory Therapy.

In glomerulonephritides, with the aim of suppressing autoimmune inflammation, hormonal agents (synthetic glucocorticosteroids) are used; if they are ineffective, cytostatics are added to the treatment.

• Lithokinetic Therapy.

For small sizes of renal calculi, medications are prescribed that relax the smooth muscles of the ureters, which promotes the spontaneous passage of stones. Such drugs include alpha-adrenoreceptor blockers, calcium channel blockers.

• Chemolytic Therapy.

Oral chemolysis (dissolution of calculi) is effective only in the presence of urate stones. Citrate mixtures and sodium bicarbonate solutions are used. In percutaneous chemolysis, irrigation of the PCS (pelvicalyceal system) with solutions through nephrostomy catheters is performed.

• Extracorporeal Shock Wave Lithotripsy.

Destruction of small stones (up to 2 cm) using ultrasound waves (Note: ESWL typically uses shock waves, translating literally as written) is recommended as an alternative to surgical removal.

• Treatment of Amyloidosis.

With the aim of suppressing the processes of amyloidogenesis (formation and deposition of amyloid protein), alkylating type antitumor drugs, antimitotic agents, genetically engineered biological preparations (monoclonal antibodies) are used.

Surgical treatment

In the presence of large-diameter calculi, failure of conservative therapy, surgical treatment of nephrolithiasis is resorted to. The most minimally invasive is percutaneous nephrolitholapaxy (endoscopic fragmentation). Laparoscopic or open surgery is also possible. The choice of surgical method is made by the urologist on an individual basis. In the case of kidney cancer, tuberculosis, or polycystic disease, complete removal of the kidney is considered the most effective.

In hemodynamically significant narrowing of the renal artery lumen, stenting is performed. For ureteral strictures, bougienage, balloon dilation of the narrowed section of the ureter is carried out; for a long segment of stenosis, creation of an anastomosis (ureterocystoanastomosis) or intestinal ureteroplasty is resorted to.

How to prevent azotemia?

Maintain proper hydration

• Consume adequate fluids daily (typically 2-3 liters for adults)
• Boost your fluid consumption when the weather is hot or during physical exertion
• Monitor urine color—pale yellow indicates good hydration

Blood pressure management

• Maintain blood pressure within target range (generally below 130/80 mmHg for those with kidney disease)
• Follow medication regimens as prescribed
• Adopt lifestyle modifications like reducing sodium intake and regular exercise

Blood glucose control

• Monitor blood glucose regularly if diabetic
• Maintain HbA1c levels within target range
• Follow prescribed diabetic management plan

Medication management

• Avoid nephrotoxic medications when possible
• Use NSAIDs cautiously and only as directed
• Follow proper dosing for all medications
• Inform all healthcare providers about your complete medication list

Dietary considerations

• Moderate protein intake based on kidney function
• Limit sodium to help control blood pressure
• Restrict phosphorus and potassium if recommended by healthcare provider
• Consider the DASH diet or Mediterranean diet for kidney health

Lifestyle changes

• Maintain healthy weight
• Exercise regularly (at least 150 minutes of moderate activity weekly)
• Quit smoking
• Limit alcohol consumption

Prevention in clinical settings

During hospitalization

• Ensure adequate hydration before and after procedures
• Use appropriate contrast protocols for imaging studies
• Monitor kidney function during critical illness
• Adjust medication dosages based on kidney function

Perioperative care

• Maintain adequate hydration and blood pressure during surgery
• Avoid prolonged hypotension
• Use kidney-friendly anesthetic agents

Preventing contrast-induced nephropathy

• Hydrate adequately before contrast administration
• Use iso-osmolar or low-osmolar contrast agents
• Consider prophylactic N-acetylcysteine in high-risk patients

Managing chronic conditions

• Treat underlying conditions like heart failure, liver disease, or systemic infections
• Regular follow-up with specialists for complex conditions
• Coordinate care between multiple providers

When to seek medical attention

• Decreased urine output
• Swelling in feet, ankles, or hands
• Shortness of breath
• Fatigue or weakness
• Confusion or difficulty concentrating
• Nausea or vomiting