The significant function of releasing the waste products and toxins out from the body is performed by Kidneys. Waste or unwanted material is excreted in the form of urine. When kidneys don’t function effectively, the toxins, for instance, Urea and creatinine remain in blood. This condition is termed as Uremia. Uremia remains a critical condition and can become life-threatening if left untreated. Uremia is an indication of the ultimate stages of kidney disease.
Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by presence of three issues such as reduced count of platelets (thrombocytopenia), decreased number of circulating red blood cells (hemolytic anemia), and incapability of the kidneys to filter out the waste material and excrete it in the urine (renal failure) a condition termed as uremia. It is dissimilar from the more widespread disorder that is a typical hemolytic uremic syndrome in terms that typical uremic syndrome is caused by E. coli producing Shiga toxins. In most cases, aHUS is developed genetically, due to autoantibodies or may be idiopathic.
Individuals affected with typical HUS, usually recover from the respond well to the treatment and recover from the initial life-threatening episodes. Individuals with aHUS may develop chronic serious complications, for instance, elevated blood pressure and kidney failure. Initial symptoms may be, the formation of small blood clots in the blood vessels of the body. The micro blood clots can prevent or reduce the blood supply to vital organs such as kidneys.
Signs and symptoms:
The onset of aHUS ranges from before the birth of the individual until adulthood. In teenagers, the disorder may develop suddenly that routinely follows infection. Particularly, the infection may be upper respiratory tract infection or gastroenteritis. When it follows gastroenteritis, the disease can be confused with the typical hemolytic uremic syndrome. The progression of the disease is different from individual to individual. The triad of thrombocytopenia, hemolytic anemia, and renal failure is the characteristic identification of the disease. Most of the individuals develop with these conditions with few exceptions.
Cause:
Individuals with aHUS generally contain a mutation in one or more genes that are responsible for the encoding of the regulatory protein. Scientists have stated the possibility that the individual carries the gene of the disorder which is is activated later on due to environmental factors or may be due to unknown illness. In some individuals, acute infection or chickenpox or H1N1 can trigger the disease. In women, pregnancy is a common trigger for aHUS.
Treatment:
In 2011, humanized anti-C5 monoclonal antibody eculizumab for the treatment of acute hemolytic uremic syndrome was approved by the United States Food and Drug Administration (USFDA). This drug reduced hemolysis and also stabilized the platelet count and reversed acute kidney injury. Eculizumab is now the first-line therapy in children and adults diagnosed with aHUS.
In 2019, Ultomiris (ravulizumab-cwvz), was approved by the US FDA for adults and pediatric patients with one month of age and older diagnosed with aHUS. This drug is a long-acting C5 complement inhibitor.
Plasma therapy has been the conventional approach in the treatment of aHUS. Fresh frozen plasma (plasma infusion) and plasma exchange (plasmapheresis) were both utilized to serve the purpose. Plasma exchange involves the removal of potentially harmful substances from the blood. Many of the individuals have reported the relapse of the disease when they did not receive long term maintenance therapy. Other individuals experienced an improvement in blood complications but a relatively bad scenario with kidney damage.
Individuals who have failed all other treatment options finally reach the transplant option. Renal transplant in patients with aHUS has remained the controversial treatment option. Almost 50% of the individuals have reported the recurrence of the disease in the newly grafted organ. It is not surprising that the recurrence rate is high in individuals with underlying genetic defects.
Eculizumab has disseminated excellent results in restricting post-transplant aHUS occurrence and as a prophylaxis before the renal transplant in individuals with a known mutation.