Hidden Causes of Renal Dysfunction: Beyond Diabetes and High Blood Pressure

Medically reviewed by Walead Latif, D.O.
Posted on April 3, 2023

  • One-third of kidney disease cases result from conditions other than diabetes or high blood pressure.
  • Polycystic kidney disease, an inherited kidney disease, is the fourth leading cause of kidney failure.
  • Conditions that damage kidney cells, cause inflammation, or disrupt the fluid and electrolyte balance can cause renal dysfunction.

Renal dysfunction happens when your kidneys have trouble maintaining the balance of water, waste, and other chemicals in your body. Renal dysfunction is sometimes known as kidney failure, renal failure, or kidney injury.

Kidney failure can be chronic (occur over a long period of time) or acute (for a short period). High blood pressure — also known as hypertension — and diabetes mellitus cause two-thirds of chronic kidney disease cases. The remaining one-third of people with kidney disease develop it from various other conditions. More than 150 rare disorders cause renal dysfunction and kidney failure.

This article will highlight some of the causes of renal dysfunction and their prevalence to help you better understand what — beyond diabetes or high blood pressure — may lead to kidney failure.

Inherited Kidney Diseases

Some types of kidney disease can run in families. Most of the rare types of kidney disease are inherited (passed down) from parents or previous generations.

Inherited kidney diseases are caused by a harmful change (also known as a mutation) in your DNA (genetic code). You can inherit a mutation in three ways:

  • Dominant inheritance — The genetic mutation comes from one parent.
  • Recessive inheritance — The genetic mutation comes from both parents.
  • X-linked inheritance — The genetic mutation is linked to the X chromosome, which is passed down from the mother. This type of mutation is more likely in biological males because they have just one X chromosome.

Genetic tests can look for these genetic mutations to help diagnose or rule out certain conditions. People with a family history of inherited kidney disease can also find out their chances of passing on kidney disease to their children.

There are more than 60 types of inherited kidney diseases — we’ll review a few of the most common types.

Polycystic Kidney Disease

Polycystic kidney disease is the fourth leading cause of kidney failure, causing about 5 percent of all cases, according to the National Kidney Foundation.

People with polycystic kidney disease develop fluid-filled cysts in their kidneys. If the cysts are too big or numerous, they can cause impaired renal function.

When polycystic kidney disease develops early in life, it is usually caused by recessive inheritance. This condition has a very aggressive disease progression and is usually fatal in the first few months of life. However, most people with polycystic kidney disease acquire it through dominant inheritance.

Alport Syndrome

People with Alport syndrome have a mutation in a connective tissue protein called collagen. The mutated collagen protein can damage the small blood vessels and glomeruli (filtering unit in the kidney), leading to kidney impairment.

Alport syndrome is rare. It can occur via dominant, recessive, or sex-linked inheritance.

Fabry Disease

Fabry disease is caused by a mutation in a protein called alpha-galactosidase A (alpha GAL), which helps break down certain fats. Without alpha GAL, fats can accumulate throughout the body, including the kidneys. The protein buildup makes it harder for the kidneys to do their job properly.

Fabry disease is rare and has a sex-linked inheritance. It is more common and more severe in biological males.

Cystinosis

People with cystinosis have a mutation in a protein involved with storing the amino acid cysteine. The result is an abnormal cysteine buildup, which can cause damaging crystals to form in the kidney.

Cystinosis is rare and caused by a recessive gene.

Autoimmune Diseases

People with some types of autoimmune diseases can experience kidney damage and renal dysfunction when the immune system mistakenly attacks the kidneys. Kidney damage from autoimmune disease is typically due to inflammation that damages the small blood vessels and glomeruli.

Renal dysfunction can result from several types of autoimmune diseases, such as those discussed below.

Lupus Nephritis

Up to 40 percent of people with lupus will have kidney involvement, also known as lupus nephritis. Lupus is an autoimmune disease that causes the immune system to attack healthy parts of the body such as the kidneys, skin, joints, heart, lungs, or brain.

Immunoglobulin A Nephropathy

Immunoglobulin A (IgA) nephropathy, also known as Berger’s disease, can occur when an immune protein called IgA gets deposited in the kidneys. When IgA builds up, it can cause inflammation. Over time, the inflammation can cause permanent kidney damage.

Complement 3 Glomerulopathy

Complement 3 glomerulopathy (C3G) is a rare disease that occurs when complement proteins from the immune system damage the glomeruli in the kidney. Complement proteins help your immune system fight off infections. If complement proteins are inappropriately activated or can’t be broken down properly, they can get stuck in the kidney and cause inflammation.

Goodpasture’s Syndrome

Goodpasture’s syndrome happens when a person’s immune system mistakenly makes antibodies that attack the lining of the kidney and lungs. The antibodies cause damaging inflammation in these organs.

Medications

Most medications pass through your kidneys, but some drugs can harm these organs when taken in large amounts. Medications that are harmful to your kidneys are known as nephrotoxic.

People with cardiovascular disease, diabetes, sepsis, and previous exposure to contrast dye have an increased risk of kidney damage caused by medications.

Medication side effects can cause kidney damage in different ways, such as by:

  • Directly harming kidney cells
  • Causing inflammation
  • Causing crystals to form in the kidneys
  • Disrupting the body’s fluid or electrolyte balance

Types of medication that can cause renal dysfunction include:

  • Antibiotics, such as vancomycin (Vancocin), aminoglycosides, sulfamethoxazole-trimethoprim (Bactrim), and ciprofloxacin (Cipro)
  • Antifungals, such as amphotericin B (Abelcet)
  • Antivirals, such as acyclovir (Zovirax)
  • Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil)
  • Blood pressure control medications, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)
  • Contrast dyes used in imaging tests
  • Methotrexate
  • Lithium
  • Chemotherapy drugs
  • Proton pump inhibitors

Infections

Repeated or chronic kidney infections — also known as pyelonephritis — can permanently damage kidneys by causing inflammation. Bacteria is the most common cause of pyelonephritis, but many of the antibiotics used to treat kidney infections also have a risk of causing kidney damage.

Viruses such as SARS-CoV-2, which causes COVID-19, can lead to kidney damage through inflammation — causing blood clots — or directly targeting kidney cells. Even mild cases of COVID-19 can increase the risk of kidney damage.

Cancer

Kidney cancer, such as renal cell carcinoma, can lead to kidney failure. Cancer occurs when cells begin to grow out of control. Cancer cells can’t function as well as healthy kidney cells, and as cancer grows in the kidneys, kidney function decreases. Additionally, many chemotherapy drugs used to treat cancer bring a risk of kidney damage.

Risk factors for kidney cancer include:

  • Long-term dialysis
  • Older age
  • Smoking
  • Family history
  • Obesity
  • High blood pressure

Preventing Renal Dysfunction

You can’t always prevent renal dysfunction, but you can lower your risk with healthy steps like these:

  • Maintain a healthy body weight.
  • Eat a nutritious, balanced diet.
  • Quit smoking cigarettes.

If you have diabetes or high blood pressure, work with your health care team to keep these conditions well controlled by attending all follow-up visits. Talk to your nephrology specialist about your risk of renal dysfunction and what you can do to prevent it.

Talk With Others Who Understand

At MyKidneyDiseaseCenter, the site for people with kidney disease and their loved ones, people come together to gain a new understanding of kidney disease and share their stories with others who understand life with kidney disease.

Have you been diagnosed with any of these kidney conditions? Have you discussed your risk of renal dysfunction with your doctor? Share your experience in the comments below.

References
  1. Kidney Failure — Cleveland Clinic
  2. Chronic Kidney Disease (CKD) — National Kidney Foundation
  3. Rare Inherited Kidney Diseases: Challenges, Opportunities, and Perspectives — Lancet
  4. Causes of Chronic Kidney Disease — National Institute of Diabetes and Digestive and Kidney Diseases
  5. Common Elements in Rare Kidney Diseases: Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference — Kidney International
  6. Inherited Kidney Diseases — National Kidney Foundation
  7. Polycystic Kidney Disease — National Kidney Foundation
  8. Alport Syndrome — National Kidney Foundation
  9. Fabry Disease — National Kidney Foundation
  10. Nephropathic Cystinosis — National Kidney Foundation
  11. Autoimmune Diseases — Cleveland Clinic
  12. Disparities in Lupus and Lupus Nephritis Care and Outcomes Among U.S. Medicaid Beneficiaries — Rheumatic Diseases Clinics of North America
  13. Lupus and Kidney Disease (Lupus Nephritis) — National Kidney Foundation
  14. Lupus (Systemic Lupus Erythematosus) — Cleveland Clinic
  15. IgA Nephropathy (Berger’s Disease) — Mayo Clinic
  16. Complement 3 Glomerulopathy (C3G) — National Kidney Foundation
  17. Goodpasture’s Syndrome — National Kidney Foundation
  18. Which Drugs Are Harmful to Your Kidneys? — National Kidney Foundation
  19. Drug-Induced Renal Disorders — Journal of Renal Injury Prevention
  20. Symptoms & Causes of Kidney Infection (Pyelonephritis) — National Institute of Diabetes and Digestive and Kidney Diseases
  21. Acute Pyelonephritis — StatPearls
  22. Mechanisms of COVID-19-Induced Kidney Injury and Current Pharmacotherapies — Inflammation Research
  23. Kidney Outcomes in Long COVID — Journal of the American Society of Nephrology
  24. Kidney Cancer — Mayo Clinic
  25. Kidney Cancer — National Kidney Foundation
  26. CKD Risk Factors and Prevention — Centers for Disease Control and Prevention

Posted on April 3, 2023

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Walead Latif, D.O. is a board-certified nephrologist and an assistant clinical professor at Rutgers New Jersey Medical School. Learn more about him here
Amanda Jacot, PharmD earned a Bachelor of Science in biology from the University of Texas at Austin in 2009 and a Doctor of Pharmacy from the University of Texas College of Pharmacy in 2014. Learn more about her here

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