Acute Kidney Disease Etiology

Acute Kidney Disease

Acute kidney disease also known as acute renal failure is a disease which happens to be associated with high mortality and morbidity. The said disease is caused by ischemia (1). Previous studies have revealed the association between ischemia and loss in NPK cells and cadherin cleavage owing to matrix metalloproteinase (MMP). One such study was conducted to identify MMP that was needed for N-cadherin loss and N-cadherin cleavage. Results showed that cadherin loss was not induced by ischemia when chemical inhibitors were put against soluble MMPs (1). In addition, there was a decrease in (MT) MMP-2 and an increase in (MT) MMP-1 under ischemic conditions. From the said results, it would be prudent to note that cadherin disruption and increased appearance of active MT1-MMP are induced by ischemia (1). In this research paper, I will explain the pathophysiology of acute kidney disease with regard to its incidence, risk factors, differential diagnosis, features, signs and symptoms, molecular basis, normal physiology and homeostasis, types, and etiology.

Epidemiology

Acute kidney disease has conventionally been classed as a nosocomial disease i.e. originating from the hospital (2). The incidence of acute kidney disease was found to be around 7% among patients who had been hospitalized. Research shows that acute kidney disease in urban areas was acquired from hospital while in the rural areas, the said disease was as a result of community acquired diseases such as dehydration and diarrhea (3). The incidence was found to be high among patients in stage III. Stage I and II had lower incidences (2). In addition, patients who are critically ill have a high prevalence of acute kidney disease. Presence of comorbidities and advanced age among patients led to an increase in incidence of acute kidney disease. Obesity, alcoholism, heart failure, heart disease, diabetes mellitus and arterial hypertension were also associated with increased incidence of acute kidney disease (2). Moreover, patients with a history of previous admission in hospital, use of contrast and medium diuretics, use of nephrotoxic drugs, proteinuria and/or hematuria, previous acute kidney disease, lithiasic and/or tumoral pathology had high chances of developing acute kidney disease. Other risk factors associated with acute kidney disease were inclusive of, but they were not limited to; respiratory disease, chronic heart disease, hypovolemia, and age (2). The rate of mortality among acute kidney disease patients was high in patients who were in the third stage of the said disease, those who were critically ill, and those who had undergone surgery.

Etiology

Nitrogenous waste products are excreted and filtrated by the kidney. An increase in the level of creatinine and blood urea nitrogen leads to a decrease in elimination of waste products which indicates a decline in renal function (3). Therefore, it is important to note that acute kidney disease occurs when nitrogenous wastes are retained owing to a decrease in glomerular filtration rate. The said decline may occur over time or in hours. However, the said decline mostly occurs in hours. Renal tissue injury is often caused by renal etiologies. Acute kidney disease may also be caused by other causes. For instance, cellular stress may lead to increased demands in energy and a focal mismatch of nutrient delivery and oxygen owing to an impaired microcirculation (4).

Types and Classification

Acute kidney disease is classed into three categories, i.e. pre-renal acute kidney disease, renal kidney disease, and post-renal kidney disease. As indicated in etiology, a decline in renal perfusion would lead to a decrease in glomerular filtrate rate. Pre-renal acute kidney injury occurs when glomerular filtrate rate has decreased owing to renal hypo perfusion. This happens to be an adaptation owing to extra-renal insults. As a result, intrarenal circulation and general circulation may fail. This happens to be the case given that approximately 25% of cardiac output is received by the kidneys (3). However, it is important to note that the renal parenchyma is not damaged in the said process (4). Post-renal acute kidney diseases occurs when acute urinary flow is obstructed at any point of the urinary track. When obstructed, the acute urinary track leads to inflammatory processes and a decline in renal perfusion. As a result, the glomerular filtration rate is also diminished. Renal failure involves both kidneys and one kidney in patients with one functional kidney if the said obstruction was above the kidney. On the other hand, renal etiologies result from nephrotoxic injury and ischemic injury (3). In order to sustain normal glomerular filtration rate, sufficient renal passage of blood happens to be essential for the said maintenance. Therefore, a decline in renal passage of blood leads to a decrease in glomerular filtrate rate.

Normal Physiology and Homeostasis

To provide the energy required to reclaim the solutes in the blood, the kidney depends on mitochondria found in the renal tubule for generation of ATP (5). Nicotine adenine dinucleotide (NAD+) - a cofactor in reduction - oxidation reactions in the mitochondria and cytosol happens to be useful in gathering energy from substrates and regulating reactions that regulate health of cells. Therefore, it would be prudent to note that a decrease in NAD+ during acute kidney disease impairs the main function of the kidney - essentially selective transportation of solutes. On the other hand, an increase in NAD during acute disease hastens acute kidney disease caused by systemic inflammation, toxic injury, reperfusion or ischemia (5). When NAD+ homeostasis is impaired, some cells are deleted and injured leading to acute kidney disease. In addition, normal homeostasis mechanisms which occur when the flow of blood is normal may be blocked by superoxide owing to oxidative stress in the kidney (3)

Pathophysiology and Molecular Basis of the Disease

The plasma membrane plays an important role in acute kidney disease. This is more so the case given that when the kidney is injured, the primary site of injury happens to be the plasma membrane (6). There are various functions of the plasma membrane in acute kidney disease. For instance, after an acute kidney disease, cholesterol-rich microdomains are altered. In addition, sodium transporters are decreased and caveolin-1 is altered. Third, after acute kidney disease, the expression of zinc-dependent metalloproteinase mepril A is altered and alkaline phosphatase associated with membrane decreases. On the other hand, cell cycle regulatory proteins such as chromatin and DNA are important in describing the manner in which acute kidney disease develops. The said proteins which include microRNAs are important in determining outcomes in acute kidney disease. For instance, endonuclease G and deoxyribonuclease 1 which are found in the kidney may cause damage of DNA and lead to acute tubular injury (3). Tubular injury may result from ischemia which may lead to cell death. As a result, function of tubular cells is shut down.

Signs and Symptoms

Acute kidney disease may only be indicated by a decline in urine output (7). However, the signs and symptoms of acute kidney disease may present differently depending on the type and the stage of the said disease. For instance, in post-renal acute kidney disease, obstruction of the urinary track may present nocturia and/or anuria (4). Prerenal kidney disease may present in form of hypotension or hypovulia. Essentially, hypovulia means vomiting, diarrhea, burns, and hemorrhage (7). On the other hand, hypotension may present as; septic shock, acute coronary syndrome, massive pulmonary embolism, and cardiogenic shock. Acute kidney disease can also lead to a buildup in metabolic products, sodium, and water. In addition, it may lead to disturbances in several electrolytes (7).

Laboratory Features

Assessment of laboratory features of acute kidney disease includes the three types of the said disease. Before checking patient’s labs, the onset of acute kidney disease should be evaluated in hospitalized patients. It would be prudent to check for any radiologic studies, and that entails the use of contrast agents that have been iodinated. This is more so the case given that such agents happens to be common causes of acute kidney disease (7). There would also be need to check for any medications taken by the patient that may lead to renal failure. Lab tests for acute kidney disease involves basic metabolic channel whereby the levels of urine electrolytes are measured (7). Other laboratory tests are inclusive of, but they are not limited to; creatinine to urine albumin ratios, urine osmolality, urine protein, serum and urine protein electrophoresis, renal ultrasound, CT non-contrast, kidney biopsy, and urine sediment examination (7).