What is Acute Kidney Disease & What is its Treatment, Pathophysiology?
Kidneys are bean shaped organs positioned at the back of the abdomen on both sides of the human body. This pair of organs performs the vital task of draining out waste materials from human body, thus keeping balance of chemicals in the body. Besides, draining out wastes from body this vital organ also has many other functions including blood purification, balancing blood pressure, maintaining water level in human body, acid regulation and RBC regulation. Thus, if this organ starts malfunctioning which is called "Kidney failure" many other complications starts surfacing in human body. Acute Kidney Injury or AKI is one such severe medical condition when kidneys fail to perform their normal functions.
What is Acute Kidney Injury or AKI?
Acute Kidney Injury or AKI is not any medical condition due to sudden physical injury, as the name may suggest. It's a typical condition that leads to partial or complete failure of basic functions of the kidney. This kind of problem is observed in older people mostly, which may lead to other complications or irreversible injury to one or both the kidneys if not treated properly at proper time. In many countries including USA, it's a common problem among the patients in hospitals, especially elderly patients and also in patients in "Intensive Care Unit". With time, due to renal failure, waste materials deposits in different body organs and circulate through blood to all over the body causing severe other complications.
Signs and Symptoms of Acute Kidney Injury or AKI
At an early stage, except lesser quantity of urine formation no other symptoms are detectable in this disease. However, in Acute Kidney Injury or AKI, patient's condition deteriorate quickly giving rise to many physical signs and symptoms in different body parts:
- Loss of appetite and apathy for favorite foods
- Fatigue, petulance and regular confusion
- Nausea and vomiting
- High blood pressure
- Regular abdominal pain
- Irregular pulse rate
- Sudden increase in blood sugar level
- Skin rashes
In many patients with Acute Kidney Injury, no signs or symptoms may be detected at the early stages and the problem is only detected while the patient undergoes pathological tests for any other illness. Again, in thousands of other cases the severity of Acute Kidney Injury or AKI may not lead to total kidney failure but it can affect any other organs and can also enhance severity of other existing diseases.
Prognosis of Acute Kidney Injury or AKI
The formation of Acute Kidney Injury or AKI has important implication on both short-term and long-term morbidity and mortality. A long term (10 yrs) observational data has indicated that 4%-5% of critically ill patients develop Acute Kidney Injury or AKI which require Renal Replacement Therapy or RRT. The prognosis of Acute Kidney Injury or AKI is very poor as it indicates almost 60% of mortality rate. The sluggish improvements especially in case of critically ill patients who are already in ICUs prolong their stays in ICUs or hospitals. Very little case studies and statistical interpretations are available on Acute Kidney Injury or AKI leading to very feeble insight into the long-term kidney prognosis for the patients. The risk of formation of acute kidney injury associated with critical illness increases manifold if the patient has already developed chronic kidney disease (CKD). In turn, the development of Acute Kidney Injury or AKI in a patient having CKD may change the history of existing illness and enhance the scope of end-stage kidney disease or ESKD. In such situation, dependence on dialysis or kidney transplantation also increases manifold, which is presently estimated to be 22% approximately.
Epidemiology of Acute Kidney Injury or AKI
Due to lack of enough study and poor reporting habit, the incidence of Acute Kidney Injury around the world is not well known. It is found from the different statistical data available from different countries that the epidemiology disease in developing countries differs from the developed nations in many ways. In developed countries elderly patients predominate, whereas in developing countries, Acute Kidney Injury or AKI is mostly detected in the young adults and children. Recent studies in the United States and Spain found that incidences of Acute Kidney Injury or AKI have increased over 11% yearly between 1992 and 2001. More recent study by Ali T. et. al., in their research paper "Incidence and outcomes in Acute Kidney Injury: A comprehensive population based study", showed that the incidence of Acute Kidney Injury or AKI has become 1811 per million populations during 2003, which is very high in comparison to previous years. In USA approximately 1% of patients admitted to hospitals have Acute Kidney Injury or AKI, while incidence of AKI during hospitalization is found to vary between 2%-5% yearly. In USA, 1% of postoperative general surgery patients, 67% of ICU patients and 21% of solitary kidney transplant patients grow acute kidney injury.
The epidemiological report is very poor for underdeveloped and developing countries where more than 50% of world's population resides.
As per the reports by different group of researchers at different points of time the following data are available for some developing nations-
- In Kuwait 4.1 per 100,000 population is reported to have got Acute Kidney Injury or AKI per year;
- In Nigeria an incidence of 11.7 cases of Acute Kidney Injury or AKI per year was diagnosed in children in a hospital that had already served more than 1 million children;
- In a health care center in north India, the reported incidence was 20 cases per 1000 pediatric admissions in 1990-91.
- In South Africa among adult patients, 20 cases of Acute Kidney Injury or AKI per million population per year has been reported;
- In Brazil, an incidence of 7.9 AKI cases per 1000 hospital admissions has been found per year.
Causes of Acute Kidney Injury or AKI
The causes of acute kidney injury can be broadly categorized into three categories- Prerenal, Intrinsic Renal and Postrenal. Here are descriptions of all these three categories:
- Prerenal Causes for Acute Kidney Injury – Over 70% cases of Acute Kidney Injury or AKI are attributed to Prerenal causes. It's a situation when blood flow into the kidneys decreases abnormally. Low blood flow may be due to any of the following reasons:
- Low Blood Volume as a Cause of Acute Kidney Injury– After profuse bleeding for any other reason, excessive vomiting, diarrhea, or severe dehydration blood volume in the kidneys may reduce drastically.
- Less Heart Pumping as a Cause of Acute Kidney injury– Due to heart failure, liver failure or sepsis etc. heart pumping lessens significantly, thereby reducing blood volume in the kidneys.
- Medicinal Effects as a Cause of Acute Kidney Injury– Several medications may cause Prerenal Acute Kidney Injury. Medicines like Angiotensin to convert enzyme inhibitors and angiotensin receptor blockers can damage renal perfusion. Several Nonsteroidal anti-inflammatory drugs can also reduce the glomerular filtration rate by changing the balance of vasodilatory or vasoconstrictive agents in the renal microcirculation.
- Problematic Blood Vessels as a Cause of Acute Kidney Injury– In case of renal artery stenosis, renal vein thrombosis etc., the circulation of blood into the kidneys gets disrupted thereby creating prerenal causes for acute kidney injury.
- Intrinsic Renal Causes for Acute Kidney Injury – This is also an important source of AKI, where the damage within the Kidney itself is the cause of the disease. Such damage may be tubular, glomerular, interstitial, or vascular. Common causes of intrinsic renal failure are acute tubular necrosis (ATN), Glomerulonephritis, , and acute interstitial nephritis (AIN) etc. Other causes of intrinsic Acute Kidney Injury or AKI are Rhabdomyolysis and tumorlysis syndrome etc.
- Postrenal Causes for Acute Kidney Injury – Postrenal AKI causes typically from obstruction of urinary flow, Urinary urgency or hesitancy, gross hematuria, polyuria, Kidney stones, medications, Kidney cancer etc.
Risk Factors of Acute Kidney Injury or AKI
The primary risk factors of Acute Kidney Injury are given below:
- Elderly people, particularly who have crossed 65 years and having several other complications like heart problems, diabetes, high blood pressure, and other renal complications are at high risk of having AKI.
- Patients already diagnosed with chronic kidney diseases, heart failure, liver diseases and diabetes etc.
- Blockage in urinary tract.
- Patients taking certain medicines regularly such as Nonsteroidal anti-inflammatory drugs, Angiotensin, certain blood pressure drugs, certain antibiotics etc. are always at risk of AKI.
- Severe recurrent dehydration.
What is the Pathophysiology of Acute Kidney Injury or AKI?
The process involved in the etiology of Acute Kidney Injury is as follows:
- Endothelial injury from vascular perturbations
- Ineffectiveness of renal autoregulation
- Development of inflammatory mediators
- Effect of Nephrotoxins
Tubular obstruction is caused by Necrosis and apoptosis of tubular cells, which contributes to the reduction of glomerular filtration rate (GFR). On the other hand, increased intracellular calcium levels from tubular damage cause a series of cellular level modifications that culminate in increased tubuloglomerular reaction, and thus, diminished GFR. Vascular conciliation leads to increased cytosolic calcium, and production of inflammatory mediators and increased endothelial injury markers, which result in reduced GFR. These pathophysiologic processes are continuously affected by a persistent imbalance between the mediators of vasoconstriction and vasodilatation that leads to intrarenal vasoconstriction and, ultimately, ischemia. The vasoconstrictors include adenosine, angiotensin II, endothelin, and thromboxane. The vasodilators include prostacyclin (a kind of lipid molecule) and endothelial-derived nitric oxide.
Higher levels of vasoconstrictors and lower levels of vasodilators result in continued hypoxia and cell damage. Endothelial-derived nitric oxide is under examination as a potential remedial option to break this ischemic cycle.
Diagnosis of Acute Kidney Injury or AKI
Several urinary and serum laboratory values or indices help physicians to distinguish among prerenal, renal, and postrenal causes of Acute Kidney Injury or AKI. Here are some important tests that are conducted to assess AKI:
Serum Creatinine Level- A high serum creatinine level in a patient who had a normal documented level previously suggests an acute development, whereas a rise of the level over weeks or months signifies sub-acute or chronic process.
- Urinalysis - Urinalysis is the most essential noninvasive test in the initial stages of Acute Kidney Injury or AKI. Findings here guide further diagnosis.
- Complete Blood Count - The occurrence of acute hemolytic anemia with schistocytes in the setting of Acute Kidney Injury or AKI should raise the possibility of thrombotic thrombocytopenic purpura (TTP) or Haemolytic-uremic syndrome (HUS).
- Imaging – Renal USG is done to rule out postrenal cause. To diagnose any other extra-renal causes of obstruction like pelvic tumors, other imaging methods like MRI or computed topography is required.
- Renal Biopsy – This is done for the patients in whom prerenal and postrenal AKI are ruled out, but causes of intrinsic renal injury are still unclear.
- Urine Electrolytes – Patients with oliguria (a condition when very small quantity of urine is produced), are given this test to distinguish prerenal from intrinsic renal causes of kidney injury.
What is the Treatment for Acute Kidney Injury or AKI?
Treatment of Acute Kidney Injury requires close collaboration among general physicians, nephrologists, and other subspecialists subsequently participating in the treatment process of a patient. After Acute Kidney Injury or AKI is established, primarily supportive treatment is started.
Patients diagnosed with Acute Kidney Injury or AKI should be hospitalized unless otherwise the condition is treatable at home and clearly developing from any reversible causes. The key to treatment is assuring renal perfusion by achieving and maintaining stable blood flow. If intravascular volume diminution fluid level decreases, isotonic solutions such as normal saline are given for a certain period. Patient with persistent hypertension is given vasopressors to control the blood pressure. Cardiac function is monitored intensively to keep it at optimum level. There remains a keen possibility of electrolytic imbalances like hyperphosphatemia, hypernatremia, hypermagnesemia, hyponatremia, hyperkalemia, metabolic acidosis etc. which is monitored and treated accordingly.
All medications that affect renal functions by toxicity or by hemodynamic mechanisms are either discontinued immediately or adjusted accordingly. The dosages of essential medications are adjusted for the lower level of kidney function.
Supportive medications, nutrition and therapies are applied to treat a patient more effectively. Monitoring of renal functions, regular blood culture, monitoring of urine etc. are done routinely as a part of treatment.
Prevention of Acute Kidney Injury or AKI
Some preventive measures can be adopted to reduce the chance of Acute Kidney Injury. Those at high risk zone include adults older than 65 years, persons with diabetes, pre-existing kidney problems and other risk factors should consult their physicians to take possible preventive steps and also need to monitor certain pathological conditions as preventive measures.
Acute kidney injury is a common medical condition, which is associated with a high mortality rate. Recent advances in medical science are helping medical practitioners in understanding and detecting AKI much faster and earlier than before. Researchers are also looking for newer mechanisms and pathophysiology of Acute Kidney Injury or AKI to reveal the pathways of this disease's different stages. This will help in future to find possible preventive methods to control the disease to a large extent.