Causes and Risk Factors of Chronic Kidney Disease

Chronic kidney disease (CKD) can be a confusing concept to grasp insofar as it is caused by other illnesses or medical conditions. As such, CKD is considered secondary to the primary cause.

Unlike acute kidney injury (AKI), in which the loss of kidney function may be reversible, CKD is "progressive,” which means it gets worse over time. The damage to your kidneys causes scars and is permanent. Among the diseases that can cause CKD are diabetes, hypertension, glomerulonephritis, and polycystic kidney disease.

Risk factors for chronic kidney disease include older age, low birth weight, obesity, smoking, high blood pressure, diabetes, a family history of kidney disease, and being of African-American descent.

Frequent Causes

The kidneys are responsible for filtering waste and regulating water and acid levels in the blood. As part of an interrelated system, the kidneys are prone to damage if any disease alters the flow and/or chemistry of blood entering the kidneys or causes direct injury to the kidneys themselves.

Any damage done to the kidneys will cause harm to other organs as waste, acids, and fluids accumulate to dangerous levels. This can intensify the very condition that triggered CKD in the first place.

Diabetes

Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide. Referred to as diabetic nephritis, the condition affects two of every five people with diabetes and is the most common cause of end-stage renal disease (ESRD).

Diabetes is a disease characterized by abnormally high levels of sugar (glucose) in the blood. Elevated blood glucose can cause harm in many parts of the body, but, with the kidneys, it triggers the excessive production of chemicals known as reactive oxygen species (ROS). These are made up of peroxides and other oxidizing compounds.

Over the course of years, exposure to ROS can damage the filters of the kidneys, called glomeruli. When this happens, larger cells that are meant to be filtered can escape and be eliminated from the body in urine. This is the cause of one of the characteristic symptoms of CKD, called proteinuria, in which abnormally high concentrations of protein are found in the urine.

Hypertension

Hypertension is both a cause and consequence of chronic kidney disease. It causes kidney (renal) disease by directly damaging nephrons of the kidney (the filtration units comprised of glomeruli and tubules).

When this happens, less blood is able to reach the kidneys, resulting in fewer functioning nephrons.

This creates a spiraling effect in which the cycle of hypertension and kidney damage is accelerated, eventually leading to ESRD as more and more blood vessels are damaged and blocked.

Glomerulonephritis

Glomerulonephritis is a group of diseases that cause inflammation of the glomeruli and nephrons. Glomerulonephritis usually affects both kidneys and can occur either on its own or as part of another disease.

While it is often difficult to pinpoint what triggered the inflammatory response, the causes can be broadly broken down as follows:

• Focal segmental glomerulosclerosis, a group of diseases that cause the selective scarring of glomeruli
• Autoimmune disorders, which either damage the kidneys directly (IgA nephropathy or granulomatosis with polyangiitis) or trigger whole-body inflammation that indirectly damages the kidneys (such as with lupus)
• Inherited disorders like polycystic kidney disease, which causes the formation of cysts in the kidneys; Alport syndrome, which damages the blood vessels of the kidneys; or Goodpasture syndrome, which damages kidney membranes

In some cases, the cause of glomerulonephritis is never found.

Less Common Causes

Other, less common causes of CKD in adults and children include:

• Heavy metal poisoning, including lead poisoning
• Hemolytic-uremic syndrome, in which ruptured red blood cells block renal filters (occurs exclusively in children) 
• Hepatitis B and hepatitis C, both of which are associated with glomerulonephritis and renal vascular inflammation
• Interstitial nephritis, inflammation of the kidney tubules often related to the long-term use of analgesics or antibiotics
• Pyelonephritis, a bacterial infection of the kidneys
• Prolonged urinary tract obstruction, including an enlarged prostate, kidney stones, and certain cancers
• Recurrent kidney infections
• Reflux nephropathy, the backing-up of urine into the bladder

In addition to known causes, CKD can often be idiopathic, meaning that the cause cannot be found. This is especially true with children. According to a 2015 study published in the Journal of Clinical Investigation, anywhere from 5% to 25% of pediatric ESRD cases will have known cause.

Risk Factors

There are a number of risk factors that can increase your likelihood of developing CKD. Some are non-modifiable, meaning that you cannot change them, while others are ones you can have influence over.

Among the non-modifiable risk factors associated with CKD:

• Genetics: You may be predisposed to CKD insofar as the risk of ESRD is three to nine times greater if you have a family member with ESRD.
• Race: African-Americans are nearly four times as likely to develop ESRD as Caucasian-Americans. Asian-Americans, Hispanic-Americans, and Native Americans are at risk because they are twice as likely to develop diabetes than their white counterparts.
• Age: CKD is more common in people aged 65 years or older (38%) than in people aged 45 to 64 years (13%) or 18 to 44 years (7%). 
• Low birth weight, which is associated with impaired kidney development, resulting in fewer and smaller nephrons.
• Type 1 diabetes

Among the modifiable risks factors associated with CKD:

• Uncontrolled high blood pressure
  
• Poor blood glucose control in people with type 1 or 2 diabetes
• Cigarette smoking, which further constricts renal blood vessels
• Obesity, which contributes to hypertension, the risk of diabetes, and the production adipokines—inflammatory substances that can cause damage to renal tissue

In 2020, 808,000 Americans had kidney failure and needed dialysis or a kidney transplant to survive. Of these, 69% received dialysis, and 31% were living with a kidney transplant.

In 2018, while roughly 100,000 Americans were waiting for a kidney transplant, only 21,167 received one that year.