What is HUS?

Atypical HUS Research | Information for Professionals

HEMOLYTIC UREMIC syndrome (HUS) is characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Usually HUS is associated with a preceding diarrheal illness frequently caused by verocytotoxin-producing Escherichia coli (diarrhea-positive HUS). The nondiarrheal form of HUS, diarrhea-negative HUS or atypical HUS, is less frequent, usually leads to end-stage renal failure, and frequently recurs after renal transplantation. 1,2 Atypical HUS can be sporadic and familial; both forms are associated with mutations in complement,  proteins, including the regulators factor H and membrane cofactor protein and the serine protease factor I. 3-12 In contrast to diarrhea-positive HUS, which almost never relapses after kidney transplantation, the risk for recurrence of atypical HUS in allografts ranges from 9% to 64%. 2,7,9,13-17 In cases of HUS associated with a factor H mutation, the chance of recurrence increases to between 41% and 100%. 7,9,14 Treatment of patients with atypical HUS consists of supportive therapy and either plasma exchange (PE) and/or plasma infusions. Although there have been reports of success with both of the latter modalities, it has been difficult to make a direct comparison of their respective efficacy.

The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by the adaptive immune system.

The complement system consists of a number of small proteins found in the blood, generally synthesized by the liver, and normally circulating as inactive precursors (pro-proteins). When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end result of this activation cascade is massive amplification of the response and activation of the cell-killing membrane attack complex. Over 25 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. They account for about 5% of the globulin fraction of blood serum. Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway.

Interpreting Lab Values

Below are lab values that are monitored in those with atypical HUS. Values might differ from lab to lab but in general the values below approximate normal.

Renal Related Lab Values

Atypical HUS Information & Research for Medical Professionals
  • B.U.N. (Blood Urea Nitrogen) - Urea is the end product of protein metabolism. It is what is left over after your body uses the proteins in meat, fish, fowl and dairy products. It is important to your overall health and healing ability to eat enough protein. Increases can be caused by excessive protein intake, kidney damage, certain drugs, low fluid intake, intestinal bleeding, exercise or heart failure. Decreased levels may be due to a poor diet, malabsorption, liver damage or low nitrogen intake.
    • Normal Adult Range: 7 - 25 mg/dl
    • Optimal Adult Reading: 16
    • Pediatric Range: 5-18 mg/dl
  • CREATININE - Creatinine is a waste product of muscle metabolism. Low levels are sometimes seen in kidney damage. Elevated levels are sometimes seen in kidney disease due to the kidney's job of excreting creatinine, muscle degeneration, and some drugs involved in impairment of kidney function.
    • Normal Adult Range: .7 - 1.4 mg/dl
    • Optimal Adult Reading: 1.05
    • Pediatric under .5 mg/dl

Hematology Values

  • HEMATOCRIT (HCT) Red blood cells (RBCs) are produced in the bone marrow, in response to a decrease in their number (thus oxygen carrying capacity). Usually, the decrease is caused by the normal removal of aged RBCs by your spleen but, of course, bleeding will result in the loss of RBCs, too. Special cells that line the smallest renal blood vessels (i.e., renal capillaries) sense any significant loss of oxygen and secrete the hormone, erythropoietin (EPO). EPO travels through the bloodstream and when it reaches the bone marrow, the marrow reacts by producing RBCs. When there are enough RBCs to enable the oxygen level in the blood to return to normal, the secretion of EPO stops. Most renal diseases interfere with the normal secretion of EPO and thus cause severe anemia. Fortunately, human EPO is now available as an injection to prevent the severe form of the anemia, and thus improve the quality of your life. In case you wondered, most doctors are reluctant to administer enough EPO to return the Hct to absolutely normal levels, as there is evidence that the thicker blood could jeopardize your vascular access and perhaps cause other problems.
    • Normal Adult Female Range: 37 - 47%
    • Optimal Adult Female Reading: 42%
    • Normal Adult Male Range 40 - 54%
    • Optimal Adult Male Reading: 47
    • Normal Newborn Range: 50 - 62%
    • Optimal Newborn Reading: 56
    • Pediatric Range 30-40 %
  • HEMOGLOBIN (HGB) Hemoglobin is the iron-containing pigment of red blood cells (RBCs); its function is to carry oxygen from your lungs to all the tissues throughout your body. Hemoglobin is decreased in uremia because the number of RBCs is decreased. Taking erythropoietin (EPO) improves the RBC count and, thus, the Hb level. Improved oxygen-carrying capacity markedly improves your exercise capacity, brain function (clarity of thinking) and overall quality of life.
    • Normal Adult Female Range: 12 - 16 g/dl
    • Optimal Adult Female Reading: 14 g/dl
    • Normal Adult Male Range: 14 - 18 g/dl
    • Optimal Adult Male Reading: 16 g/dl
    • Normal Newborn Range: 14 - 20 g/dl
    • Optimal Newborn Reading: 17 g/dl
    • Pediatric Range 10-13 gm/dl
  • R.B.C. (Red Blood Cell Count) Responsible for carrying oxygen and carbon dioxide throughout the body. Iron deficiency will lower RBC count. In more reduced count, it may indicate hemorrhage or hemolysis. RBC lives for 120 days so an anemia of any kind other than hemorrhage indicates a long standing problem.
    • Normal Adult Female Range: 3.9 - 5.2 mill/mcl
    • Optimal Adult Female Reading: 4.55
    • Normal Adult Male Range: 4.2 - 5.6 mill/mcl
    • Optimal Adult Male Reading: 4.9
    • Lower ranges are found in Children, newborns and infants
  • W.B.C. (White Blood Cell Count) The body's primary means of fighting infection. Decreased levels may indicate overwhelming infections (viruses). Increased levels indicate bacterial infection, emotional upsets and blood disorders.
    • Normal Adult Range: 3.8 - 10.8 thous/mcl
    • Optimal Adult Reading: 7.3
    • Children, newborns and infants. 3,000 – 10,000 cells
  • PLATELET COUNT Platelets (PLT) - Play an important role in blood clotting. Decrease in number occurs in hemolytic anemia and by monitoring them disease activity can be monitored and platelets replaced.
    • Normal Adult Range: 130 - 400 thous/mcl
    • Optimal Adult Reading: 265
    • Children 170-380 thous/mcl
  •  LDH The main use for LDH is as a general indicator of the existence and severity of acute or chronic tissue damage and, sometimes, as a monitor of progressive conditions. LDH isoenzymes, there are 5, may also be used in differential diagnosis to help determine which organs are likely to be involved. LDH-1 is indicative of tissue damage in the renal cortex.
    • Normal Range: 105 to 333 IU/L

Research Papers and Studies

A Comprehensive aHUS Analysis

Ph II Study of Eculizumab (ECU) in Patients (PTS) with Atypical Hemolytic Uremic Syndrome (aHUS) Receiving Chronic Plasma Exchange/Iinfusion (PE/PI)

Continued Improvements in Renal Function with Sustained Eculizumab (ECU) in Patients (PTS) with Atypical Hemolytic Uremic Syndrome (aHUS)

Resistant to Plasma Exchange/Infusion (PE/PI)

Platelets Serve as Source of Complement Factor H (CFH) Activity in a Modified Fluid-Phase Alternative Complement Pathway Cofactor Activity Assay

C4d in Thrombotic Microangiopathy: Cause or Consequence?

Kidney Week 2011 Itinerary

Acute Manifestation and 1-Year Follow-Up of a Big Cohort of Patients with Atypical Hemolytic Uremic Syndrome (aHUS)

Aberrations in Genes Encoding CFHR5 and Terminal Complement Pathway Components in Patients with Atypical Hemolytic Uremic Syndrome