Chronic kidney disease

Chronic kidney disease, condition characterized by the progressive loss of the ability of the kidneys to filter waste and fluid from the blood, typically with damage lasting three months or longer before diagnosis. Chronic kidney disease drastically impairs the nephrons, which are the structural and functional units of the kidneys, serving to maintain the body’s balance of fluids, electrolytes, and hormones. This deterioration ultimately leads to life-threatening complications. The condition is a significant cause of illness worldwide, in part because it often progresses considerably before symptoms become apparent.

Risk factors and causes

Risk of chronic kidney disease is linked to lifestyle factors such as alcohol consumption, physical inactivity, and smoking; older age is another risk factor. However, the disease is primarily caused by diabetes and hypertension (high blood pressure). Both conditions are marked by progressive injury to the nephrons, particularly the small arteries, arterioles, and glomeruli (clusters of microscopic blood vessels). Other causes include autoimmune diseases such as systemic lupus erythematosus, inherited disorders such as Fabry disease and polycystic kidney disease, and recurrent urinary tract infections. Previous kidney injury and long-term exposure to certain medications can also increase risk.

Mechanisms of damage

Chronic kidney disease inflicts significant damage on functioning nephrons via nephron hyperfiltration and compensatory hypertrophy. These processes help the kidneys compensate for initially small losses in nephron function but become maladaptive as nephrons are lost over time. Remaining nephrons attempt to compensate by filtering greater-than-normal amounts of blood. However, the elevated pressure and workload ultimately weaken the already overwhelmed filtering structures.

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The ongoing deterioration of nephron function further promotes inflammation and fibrosis, resulting in tissue stiffening. Increased mechanical stiffness in the kidneys perpetuates the cycle, and as damage accumulates, the kidneys become less and less able to eliminate metabolic wastes and excess water. They also become less effective at regulating levels of electrolytes and blood pressure. Advanced disease eventually affects the production of red blood cells, contributing to the development of anemia, as well as the regulation of calcium and phosphorus metabolism, leading to bone disease.

Stages and symptoms

Five stages of chronic kidney disease are recognized, with each being based mainly on the estimated glomerular filtration rate (eGFR), a measure of the effectiveness of the kidneys in removing wastes from the blood. Stage 1 is characterized by normal or high filtration, with an eGFR of 90 or above; the rate drops to about 60–89 in stage 2. Outward symptoms usually are not apparent in stages 1 and 2.

Stage 3 typically is divided into stages 3a and 3b and is marked by a significant decline in eGFR, to 30–59. Symptoms are often noticeable at this stage and include edema (swelling, particularly in the feet, ankles, and hands), fatigue, foamy urine, and increased urination frequency. Early indications of anemia or bone disease may emerge. Kidney function is drastically reduced in stage 4, when eGFR drops to 15–29. The severity of existing symptoms increases, and new symptoms may appear, including loss of appetite, nausea, difficulty sleeping, and difficulty concentrating. Individuals may also be affected by the development of hypertension, bone disease, or heart disease. The further decline of eGFR below 15 indicates stage 5 and the onset of kidney failure. Other symptoms may include extreme fatigue, headache, shortness of breath (caused by a buildup of fluid in the lungs), persistent nausea and vomiting, and muscle cramps.

In addition to eGFR, the progression of chronic kidney disease is tracked by measuring urine levels of the protein albumin; elevated albumin levels in the urine are referred to as albuminuria. In healthy individuals albumin is not normally found in the urine. However, as damage to the nephrons increases, causing them to become more permeable, albumin levels in the urine increase, indicating disease progression.

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Treatment and prognosis

Chronic kidney disease is treated in various ways, depending on the primary objective—such as targeting underlying causes, slowing progression, or preventing complications. Modification of lifestyle factors—particularly dietary changes, incorporation of physical activity, and quitting smoking—is critical. Likewise, medications such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers, which help control blood pressure, and sodium-glucose transport protein 2 (SGLT2) inhibitors, which help control blood glucose levels, typically are employed to address underlying hypertension and diabetes. Complications such as anemia, fluid retention, or mineral imbalances may be treated using specialized supplements or medications. In advanced stages dialysis or kidney transplantation may be needed.