What Causes Hypocomplementemic Glomerulonephritis?

Patient Presentation
A 10-year-old female was admitted to a regional children’s hospital because of headache and hypertension. The headaches had been present intermittently for 1 week but were not increasing in intensity. They were relieved with rest and ibuprofen. She complained of some intermittent leg pains also. About 3 days prior to admission, her mother noted increased puffiness of her face and abdomen. She had no changes in urination. On the day of admission, the headache returned with increased intensity and she had emesis x 3. Her primary care provider noted a blood pressure of 156/108 and periorbital edema. Urine dipstick in his office showed marked protein and blood. She was then referred. The past medical history was negative. The family history was positive for several family members with lupus, but no other autoimmune, nephrology or gastrointestinal problems. The review of systems showed at least a 10 pound weight gain per mother’s estimate, but no fever, chills, rashes, eye changes, or mucous membrane changes. She denied recent illnesses or travel.

The pertinent physical exam showed a child with moderate pain secondary to headache. Blood pressure was 131/85, pulse of 90, and respiratory rate of 32. She had periorbital and peripheral edema. Lungs had mild crackles at the bases. Heart was tachycardic with a flow murmur. Abdomen was soft and slightly tender throughout, but the abdomen was not tense. A fluid wave was inconsistently present. The rest of her examination was negative. The laboratory evaluation included a urinalysis which showed a specific gravity of 1.030, pH = 6, with +1 ketones and bilirubin, and +3 blood and protein. The microanalysis showed numerous red blood cells but no white blood cells. There were some red blood cell casts. Electrolytes showed a sodium of 143 mEq/l, potassium of 4.4 mEq/l, BUN of 44 mg/dl and creatinine of 1.7 mg/dl. Total cholesterol was 126, high density lipoprotein of 36 and low density lipoprotein of 79. C-reactive protein was < 0.5 mg/dl. C3, C4 and CH50 were significantly low. CBC and bleeding profile laboratories were normal. Her antistreptolysin O titer was 738 IU/ml (normal 0-240).

The diagnosis of presumed acute post-infectious glomerulonephritis was made. Additional history revealed treatment for streptococcal pharyngitis 3 weeks before admission. The patient’s clinical course showed that she was treated with fluid restriction, diuretics and anti-hypertensive medications. Within 3 days, the BUN and creatinine began to decrease toward normal. She had no oliguria. Because of the strong lupus family history, additional rheumatological testing was done which was all negative. The patient was discharged on day 4 still on antihypertensive medications. At followup 6 weeks later, she was reported to be back to her normal self including no edema, headache and was her normal weight. She still had slightly high, intermittent blood pressures but her electrolytes and urine were normal with a creatinine of 0.6 mg/dl. She was to stop her anti-hypertensive medication and monitor blood pressures at home with telephone followup in 1 week.

Post-infectious glomerulonephritis (GN) is very common and 80-90% of cases are caused by acute poststreptococcal glomerulonephritis (APSGN) which is an immune-complex mediated problem.

  • Infection precedes the nephritis generally by a few weeks and may be difficult to identify. It can be caused by nephritogenic strains of Group A, Beta-hemolytic Streptococcus from both pharyngitis and dermatological infections, other bacteria, viruses and parasites. Interestingly, usually acute rheumatic fever and APSGN do not occur together.
  • Abrupt onset of edema, hematuria, usually hypertension, with usually mild renal failure.
  • Patients begin recovering usually starting within 1 week for edema and 2-3 weeks for hypertension. Urinalysis may be abnormal for several years though, especially microscopic hematuria.

Lab testing:

  • C3 level low (< 50% normal) and generally returns to normal in 3-6 weeks
  • C4 levels usually are normal (if low, consider other causes)
  • Antistreptolysin O titre is positive in ~80% of children
  • Other tests are often ordered to eliminate other disease causes and to help treatment

Supportive care is the mainstay of treatment with careful fluid management including fluid restriction and diuretics, electrolyte management (including sodium restriction) as necessary, antihypertensive medications to control hypertension, and antibiotics only if an infection is identified.
If the clinical presentation does not support an initial diagnosis or clinical course consistent with the diagnosis of APSGN such as having increasing hematuria or anemia, uncontrollable hypertension, progressive renal insufficiency such as oliguria, azotemia or worsening laboratory tests, then renal biopsy may be necessary to identify other potential causes of GN.

Learning Point
Hypocomplementemic glomerulonephritis is caused by one of 4 diseases:

  • Acute post-infectious GN (usually APSGN)
  • GN associated with chronic infections such as shunt nephritis or bacterial endocarditis
  • Membranoproliferative GN
  • Lupus GN

Questions for Further Discussion
1. What are indications for a renal biopsy?
2. What are indications for renal dialysis? Review a previous case here.
3. What are the components of nephrotic syndrome?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Kidney Diseases and Streptococcal Infections.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1677-1681.

Singh GR. Glomerulonephritis and managing the risks of chronic renal disease. Pediatr Clin North Am. 2009 Dec;56(6):1363-82.

Bhimma R. Acute Poststreptococcal Glomerulonephritis. eMedicine.
Available from the Internet at http://emedicine.medscape.com/article/980685-overview (rev. 1/7/10, cited 10/11/10).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    6. Information technology to support patient care decisions and patient education is used.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Systems Based Practice
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.


    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital