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Chronic Kidney Disease (CKD): Signs, Symptoms, and Causes


Permanent kidney injury may result from numerous types of kidney diseases. Chronic kidney disease occurs when the damage progresses over long periods of time.

For a better understanding of CKD causes, symptoms, and treatments) it is helpful to understand the role of the kidneys in essential bodily functions:

  • Filters the blood to maintain the life-sustaining balance of salts, minerals, and water in your body, while also eliminating metabolic waste products and drugs. These substances are eliminated from the body in the urine.
  • Also has a central role in blood pressure (BP) regulation. High BP (hypertension) from kidney disease results from retention of sodium and water in the body, and by activating a hormone system (renin-angiotensin-aldosterone) that narrows arteries and causes sodium retention, thereby causing BP to increase.
  • Converts vitamin D into its active forms that regulate calcium balance and bone metabolism.
  • Produces a hormone called ‘erythropoietin,’ which sustains normal red blood cell synthesis.

Signs and symptoms of CKD

In early stages of CKD, symptoms may be few to none, depending on the patient. Nevertheless, family genetics, sustained high blood pressure, swelling in the legs, and abnormal routine urine testing can raise the suspicion for CKD. As kidney function worsens, more obvious symptoms or signs become more prominent. Many of these are the direct result of the kidney’s inability to perform the functions mentioned above. Examples:

  • Inadequate excretion of sodium and water causing fluid retention (edema) and hypertension.
  • Accumulation of metabolic waste products that can interfere with normal body metabolism and contribute to generally poor health.
  • Diminished elimination of medications usually excreted in the urine can result in unintended and potentially toxic drug levels unless the doses are adjusted for the degree of kidney dysfuntion.
  • Inadequate erythropoietin production results in anemia that can be severe. Anemia may cause symptoms that include a pale appearance, diminished endurance, slowing of mental abilities, and heart strain, among others.
  • Excessive synthesis of a hormone (renin) by the injured kidney that starts a chain of reactions causing elevated blood pressures that ay be severe or life-threatening.
  • Advanced CKD also results in many general symptoms that may include decreased appetite, fatigue, weakness, nausea and vomiting, dry itchy skin, headaches, and failure of normal growth in children, among others.

Causes of CKD

Nephrons are the basic units that perform the kidney’s normal functions. The normal kidney has an average of 500,000 to 1 million nephrons. Each unit has a glomerulus attached to a tubule. The main function of the glomerulus is to separate (filter) out the fluid part of the blood. This fluid then travels through the tubule during which time waste products and excess salts and minerals are filtered out and water retained or eliminated depending on overall fluid balance. Together, these filtered substances and excess water form the urine.

While there are numerous types of kidney diseases, they all share the capacity for chronic and progressive loss of kidney function. The most common method used to measure decreasing kidney function is the glomerular filtration rate. It is a simple test that estimates how the kidney is working, overall.

Systemic illnesses

Diabetes can cause or contribute to CKD. It is the leading cause of late-stage kidney failure. Obesity also is a common cause of direct and secondary (e.g. diabetes, cholesterol disorders, and hypertension) kidney diseases. Sustained elevations of blood lipid levels, and chronic uncontrolled hypertension also independently increase the risk of CKD.

Glomerulonephritis (literally inflammation and injury to the kidney glomerulus) is a general term for this group of diseases. While there are numerous types of glomerulonephritis, almost all are caused by inflammation and injury mediated by the immune system. Glomerulonephritis may be nephritic, nephrotic, or combination of the two.

Nephritic refers to immune inflammation that can decrease the filtration function of the glomeruli, resulting in decreased amount of fluid for processing in the tubules. This type may be acute or chronic and is often accompanied by hypertension, sometimes severe. If the disease remains uncontrolled, the glomeruli and their tubules ultimately become irreversibly damaged.

Nephrotic glomerular diseases are characterized by massive “leaking” of albumin into the filtered fluid. Albumin is one of the major proteins in the blood. Excessive albumin excretion has damaging effects on nephrons. If the loss of albumin is greater than the body’s ability to replace it, massive swelling (edema) can result due to relocation of water from the bloodstream into surrounding body tissue.

Tubulointerstitial Nephritis (TIN) refers to kidney tissue injuries that affect the nephron tubules and surrounding tissue. Like injury to glomeruli, tubular loss can also lead to diminished overall kidney function. While there are numerous infectious and inflammatory disorders that can cause TIN, drugs and medications are common triggers for adverse immune or toxic injuries. Among these, the chronic use of acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs are well known potential causes of severe tubular injury and progressive CKD.

Other Chronic Kidney Diseases

Some inherited metabolic disorders can also cause CKD. The most common of these is what used to be called “adult” polycystic kidney disease, but now is referred to as autosomal ‘dominant polycystic kidney disease.’ This and similar disorders progressively and irreversibly replace normal kidney tissue with a myriad of cysts. Recurrent infections in the kidney (pyelonephritis) can also destroy large portions of normal kidney tissue. When the flow of urine through the urinary system is impaired, such as by obstruction in the urinary tract or severe vesicoureteral reflux. In the latter condition, urine flows backwards from the bladder up to the kidney, especially when the bladder contracts. The pressure of this refluxing urine can cause considerable injury to the kidney, especially when accompanied by infections.

Key take-aways

CKD can be caused by systemic illnesses like Diabetes, nephritic or nephrotic Glomerulonephritis, Tubulointerstitial nephritis (TIN), and other types of chronic kidney diseases.

CKD is a chronic disorder in which there is ongoing kidney injury that often progresses to more severe stages and the emergence of symptoms due to the loss of its critical functional role in a myriad of body processes.

Permanent injury to the kidney’s filtering units (nephrons) places individuals at risk for CKD, even after its cause is removed.

References and further reading

NIDDK/NIH What is chronic kidney disease?

The Kidneys – a Basic Guide. Kidney Research UK

Glomerulonephritis StatPearls, National Institutes of Health

Joyce, E., Ranganathan, S., Swiatecka-Urban, A. (2017). Tubulointerstitial Nephritis: Diagnosis, Treatment and Monitoring. Pediatr Nephrol 32(4):577-587.

Vesicoureteral Reflux (VUR) National Institute of Diabetes and Digestive and Kidney diseases, NIH.

Drug-induced renal disorders National Center for Biotechnology Information/NIH

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