Chronic Kidney Disease (CKD) is a long-term condition where kidneys gradually lose their ability to filter waste products and maintain the body’s balance. The pathophysiology of CKD examines the biological mechanisms behind its development and progression. This article explains how CKD originates, how kidney damage worsens, and its broader impacts on the body.
Understanding Healthy Kidney Function
The kidneys, located below the rib cage, perform several functions. They filter approximately half a cup of blood every minute, removing waste products and excess water to produce urine. This filtration occurs in millions of tiny units called nephrons, each containing a glomerulus and a tubule.
Kidneys also maintain fluid and electrolyte balance, regulating levels of sodium, potassium, calcium, and phosphate. They help maintain the body’s acid-base balance and produce hormones like erythropoietin (for red blood cell production) and renin (for blood pressure regulation). They also activate vitamin D, essential for bone health.
Initial Causes of Kidney Damage
CKD often begins due to other health conditions that strain the kidneys. Diabetes is a leading cause, where persistently high blood glucose levels can damage the tiny filters within the kidneys. High blood pressure, or hypertension, also contributes significantly by putting excessive strain on the small blood vessels in the kidneys, hindering their function.
Other conditions can also cause kidney damage. Autoimmune diseases, such as lupus nephritis, can cause the body’s immune system to attack and damage kidney tissues. Polycystic kidney disease, an inherited disorder, involves the growth of numerous fluid-filled cysts in the kidneys, which progressively reduce kidney function. Recurrent kidney infections, also known as pyelonephritis, can lead to kidney damage if left untreated.
How Kidney Disease Progresses
Once kidney damage occurs, processes within the body accelerate the decline in kidney function. Initially, remaining healthy nephrons compensate for damaged ones by increasing their filtration rate, known as hyperfiltration. While this temporarily maintains kidney function, the increased workload eventually stresses these healthy nephrons, leading to their damage.
Proteinuria, protein leakage into the urine, serves as both a marker and contributor to kidney damage. Protein in the tubules can have toxic effects, injuring kidney cells and promoting inflammation. This chronic inflammation contributes to tubulointerstitial fibrosis, a scarring process where excessive extracellular matrix accumulates within kidney tissue. This scarring alters kidney architecture, impeding blood supply and resulting in irreversible injury.
The Renin-Angiotensin-Aldosterone System (RAAS) also plays a role in CKD progression. While initially helpful in regulating blood pressure, chronic RAAS activation becomes detrimental. Overactivity of this system worsens systemic and glomerular capillary blood pressure, activating pro-inflammatory and pro-fibrotic pathways within the kidney. Angiotensin II, a hormone in this system, promotes scarring and further decline in kidney function.
Widespread Effects on the Body
As kidney function declines, the body’s ability to maintain balance is compromised, leading to various systemic complications. Cardiovascular complications are common, with an increased risk of heart disease and stroke. Hypertension is often exacerbated due to fluid retention and the overactivation of the RAAS.
Anemia, a reduction in red blood cells, frequently occurs because damaged kidneys produce less erythropoietin, a hormone that stimulates red blood cell formation. Impaired iron metabolism and reduced red blood cell survival also contribute to anemia in CKD patients.
Bone and mineral disorders (CKD-MBD) develop due to the kidneys’ inability to activate vitamin D properly. This leads to imbalances in calcium and phosphate levels, often resulting in weakened bones and an increased risk of fractures. These mineral imbalances also contribute to vascular calcification, where calcium deposits accumulate in blood vessels, further increasing cardiovascular risk.
Fluid and electrolyte imbalances are also a hallmark of advancing CKD. The kidneys lose their ability to excrete excess fluid, leading to fluid overload and swelling. The accumulation of waste products and toxins in the blood (uremia) can cause fatigue, nausea, and decreased mental sharpness. High potassium levels (hyperkalemia) and metabolic acidosis can also occur, impacting nerve and muscle function.