What Can Help With C3 Glomerulopathy (C3G) Fatigue?

Fatigue is one of the hardest parts of living with C3 glomerulopathy (C3G). It can interfere with work, meals, exercise, relationships, and plans — and sleep may not be enough to make it go away.

There are several aspects of C3G that contribute to fatigue, says Evan Zeitler, MD, a nephrologist and an assistant professor at the UNC School of Medicine in Chapel Hill. “Inflammation, anemia, uremic toxins, protein loss, medication effects, poor sleep, and emotional strain can all overlap,” he says.

Because several causes may be contributing, your doctor may need to run some tests, review your symptoms and medications, and have you track and share how your fatigue impacts your daily life. Together you can find the treatment and lifestyle changes to better manage your energy.

Sources of Fatigue in C3 Glomerulopathy

C3 glomerulopathy causes fatigue both directly and indirectly. Ongoing immune system activity caused by the disease can wear you down, and C3 can contribute to other health issues that zap your energy.

• Chronic Inflammation C3G is driven by overactivity in a part of the immune system called the alternative complement pathway. “Persistent inflammation may affect sleep and motivation,” says Dr. Zeitler.
• Anemia Reduced kidney function can lower production of erythropoietin, the hormone that signals the body to make red blood cells. “The resulting anemia reduces oxygen delivery to the tissues, so people may have less exercise tolerance and feel more fatigued,” he says.
• Uremia and Metabolic Acidosis When the kidneys cannot clear waste and acid effectively, these substances can build up. Zeitler says this may cause poor appetite, nausea, brain fog, weakness, and muscle breakdown.
• Proteinuria Protein in your urine happens when proteins in your blood leak into your urine; kidney disease can cause this.

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  “Heavy protein loss in the urine can lower albumin, allowing fluid to collect in the tissues and worsen swelling. Over time, protein and muscle loss can also make everyday activities more tiring,” Zeitler says.
• Gout Uric acid is another waste product that can build up when kidney function declines. People with C3G who develop gout can have severe joint pain that makes fatigue worse.
• Poor Appetite or Low Nutrient Intake “Inflammation, uremic toxin buildup, and changes in appetite hormones can all make it harder to eat enough,” says Antonette Hardie, RDN, a registered dietitian at the Ohio State University Wexner Medical Center in Columbus. Hardie says low intake of calories, iron, vitamin B12, folate, protein, or other nutrients may add to fatigue.
• Medications Prednisone can cause insomnia, mood changes, and muscle weakness. Mycophenolate mofetil may cause digestive problems or lower blood cell counts, while beta-blockers may worsen fatigue, Zeitler says.
• Mental Health People with chronic kidney disease are more likely to have depression or anxiety; mood disorders can also disrupt sleep and drain energy.

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Medical Help for C3G Fatigue

Your nephrologist will usually consider your symptoms, medication schedule, sleep, mood, daily function, and laboratory results.

Zeitler says testing may include:

• A complete blood count and iron studies for anemia or iron deficiency
• Creatinine, estimated glomerular filtration rate (eGFR), electrolytes, and bicarbonate to assess kidney function and acid balance
• C-reactive protein, complement levels, and other C3G markers to assess inflammation and disease activity
• Thyroid and vitamin D tests
• Screening for depression and questions about sleep apnea, restless legs syndrome, or other sleep problems

Depending on what is contributing to the fatigue, these are some possible treatments.

Treat the C3G Itself

“Effective treatment of C3G can reduce kidney inflammation and proteinuria and slow the decline in kidney function,” Zeitler says. Reducing protein loss may also help ease swelling and loss of muscle mass.

Treat Anemia or Iron Deficiency

Treatment may include iron and, in some cases, an erythropoiesis-stimulating agent (ESA). “Partially correcting anemia can meaningfully improve fatigue and physical function,” Zeitler says. Doctors don’t aim to raise hemoglobin to normal levels with an ESA because higher targets can increase cardiovascular risk, he adds.

Manage Blood Pressure, Protein Loss, and Swelling

Correct Excess Acid in the Blood

Low bicarbonate, which can result from acidosis (too many acids in the blood), may be treated with sodium bicarbonate or sodium citrate, says Zeitler. “However, I have not found this to provide much benefit for my patients with acidosis, and the pill burden can be high,” he says. Talk with your doctor about the pros and cons of treating bicarbonate.

Adjust Medications That May Be Adding to Fatigue

If prednisone is disrupting sleep, your doctor may change when it is taken or gradually lower the dose once C3G is under control.

Another option could be to change the formulation or dose of mycophenolate if digestive symptoms or low blood counts are a problem, or consider another blood pressure medicine if a beta-blocker appears to be worsening fatigue. “Don’t make these changes on your own,” says Zeitler.

Treat Sleep Problems

Work With a Renal Dietitian

A dietitian can assess whether appetite loss, dietary restrictions, digestive symptoms, or inadequate calorie and nutrient intake are contributing. “Small, frequent meals may be easier to manage when appetite is low,” Hardie says.

Protein, sodium, fluid, potassium, and phosphorus recommendations should be tailored to kidney function, laboratory results, other health conditions, and whether you are receiving dialysis. Hardie recommends bringing recent lab results and a food record so the dietitian can estimate calorie and nutrient intake and identify anything that may be interfering with eating.

How to Deal With the Emotional Toll of Living With C3G

“Living with a rare, chronic, and potentially progressive kidney disease carries a substantial psychological burden,” says Zeitler.

Support may include:

• A health psychologist or another therapist who works with chronic illness: Ask your nephrologist for a referral, even if you aren’t sure if your feelings are related to your kidney disease.
• Peer support: Several organizations offer ways to connect to other people who are going through some of the same challenges you are: NKF PEERS offers confidential, one-on-one mentoring over the phone; NephCure offers virtual support groups for patients and parents affected by rare kidney diseases; C3G Warriors is a private Facebook group for patients and caregivers of people with C3G.
• A nephrology social worker: Ask whether your clinic has one available to help with emotional support or practical concerns to help you with the challenges of living with C3G. Insurance issues, employment, transportation, finances, family life, and help communicating with your doctor are a few of the ways that a social worker can help.

Advocate for Yourself

Be specific with your care team about how fatigue is changing your daily routine.

“What has become difficult or impossible — climbing stairs, working, cooking, or socializing — can be just as important as a laboratory number,” Zeitler says.

For two or three weeks before an appointment, Zeitler recommends keeping an energy log that includes:

• Your energy when you wake up, around lunchtime, in the afternoon, and before bed
• Medication timing and whether fatigue changes afterward
• Sleep quality, naps, nighttime awakenings, and whether you awake feeling refreshed
• Food and fluid intake, especially when appetite or nausea is worse
• Brain fog, swelling, shortness of breath, pain, dizziness, and mood changes
• Activities that became difficult, could not be finished, or required help

Bring the log with your medication list and recent laboratory results. Hardie also recommends sharing information about other medical conditions and any history that could affect nutrition, such as gastric bypass surgery.

Use concrete examples, such as “I need to lie down after showering” or “My energy dropped after my medication changed.” Those details can reveal patterns that may not be obvious during a short appointment, Zeitler says.

While the cause is being investigated, schedule important activities during your strongest part of the day, allow time to recover, and accept help with lower-priority tasks so you can save energy for what matters most.