Keywords: Atypical hemolytic uremic syndrome; rotavirus. ÖZET Hemolitik üremik sendrom (HÜS) en sık E. coli H7 ve Shigella dysenteriae tip 1’e bağlı. Erişkin Hastada Atipik Hemolitik Üremik Sendrom: Olgu Sunumu.- Atypical Hemolytic Uremic Syndrome in Adult Patient: Case Report. Article (PDF Available ). Hemolytic Uremic Syndrome as a Cause of Adult Acute Renal Failure / Eriskin Akut Bobrek Yetmezliginin Bir Sebebi Olarak Hemolitik Uremik Sendrom.

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Uncontrolled complement activation through the alternative pathway is thought to be the main underlying pathopysiology of aHUS and corresponds to all the deleterious findings of the disease. Today empiric plasma therapy still is recommended by expert opinion to be used as early as possible in any patient with symptoms of aHUS.

The overall treatment goal remains restoration of a physiological balance between activation and control of the alternative complement pathway.

Atypical Hemolytic Uremic Syndrome: Differential Diagnosis from TTP/HUS and Management

So it is a reasonable approach to block the terminal complement complex with eculizumab in order to prevent further organ injury and increase the likelihood organ recovery. Persistence of hemolysis or lack of improvement of renal function after daily plasmaphereses have to be regarded as the major criteria for uncontrolled TMA even if platelet count has normalized and as an indication to switch the treatment to eculizumab. However, there are still some unresolved issues about the follow-up such as the optimal duration of eculizumab treatment and whether it can be stopped or how to stop the therapy.

Hemolytic uremic syndrome HUS is a rare and severe thrombotic microangiopathy TMA characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The disorder occurs most frequently in children under the age of 5 years, with an overall incidence of 1 to 2 cases perThe disease is generally caused by infectious agents and usually has a favorable outcome.

Approximately half of the patients require dialysis during acute episodes, but renal function recovers in most of them [ 12 ]. A history of diarrhea is essential to define the diagnosis of postinfectious HUS and is generally seen 2 weeks before the episode [3]. The enterohemorrhagic Escherichia coli serotypes producing Shiga toxin are the most common infectious agents causing HUS. Shigella is the second important infectious agent that can cause HUS with the deleterious effects of Shiga toxins.

Streptococcus pneumoniae is another important infectious agent that can provoke more aggressive clinical forms [ 4567 ]. Canadian pediatricians compared Streptococcus pneumoniae-related HUS cases with Shiga toxin-associated HUS and found that Streptococcus pneumoniae-related HUS patients were more likely to require dialysis and had a longer duration of hospitalization [ 8 ].

Although there are limited data available in the literature about the incidence and prevalence of this entity, the estimated incidence rate was given as cases per million annually in the United States [7].

Hemolytic-Uremic Syndrome Caused by Rotavirus Infection: Case Report | Article | Türkiye Klinikleri

The age distribution is different and the prevalence in adults is expected to be lower, but clear data are not yet available. The incidence of complement-aHUS is not known precisely.

However, more than aHUS patients investigated for complement abnormalities have been reported [ 12 ].

TMA is a pathological process hmolitik by thickening of arterioles and capillaries, endothelial swelling and detachment, subendothelial accumulation of proteins and cell debris, and fibrin and platelet thrombi obstruction of vessel lumina [ 13 ]. TMA predominantly affects the renal microvasculature, although the brain, heart, lungs, and gastrointestinal tract may also be involved, ultimately leading yemolitik organ dysfunction [ sehdrom15161718 ].

TMA may result from 4 types of lesions: TTP was originally defined pathologically as a systemic disease with widespread VWF-platelet thrombi in the arterioles and capillaries of multiple organs [ 2021 ].

Advances in recent years have demonstrated that VWF-platelet thrombi result from a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 ADAMTS13 deficiency. In Shiga-like toxin-producing E.

Evidence shows that Shiga toxins might directly contribute to complement activation as documented by C3 deposition on microvascular endothelial cell lines exposed to Shiga toxin and then perfused with human serum [ 25 ]. Complement activation products have been detected in the serum and hemolituk of HUS patients, and an in vitro study could show that Shiga toxin not only damages the kidneys directly but also indirectly via a complement, in 2 ways.

First, it activates the complement, and second, it delays the functions of its control protein factor H on the cell surface, both known to damage the kidney [ 2627 ]. Today, TMAs are classified into 4 groups. Group II includes aHUS with defective complement regulation due to genetic mutations or autoantibodies of the activators or regulators of the complement pathway.


Tsai reported that comorbid conditions such as infections, inflammation, surgery, trauma, pregnancy, intravenous contrast agents, and pancreatitis may trigger acute presentation in patients with preexisting TTP or aHUS, either by promoting the VWF-platelet interaction or by activating the complement system [ 28 ]. Tsai further subclassified groups I and II in terms of having one of these comorbidities or not. Sebdrom aHUS, the predominant pathological abnormality is found in the renal arterioles and interlobular arteries.

There is widespread endothelial swelling with retraction leading to exposure of the basement membrane.

The vessel lumens are occluded by red cells and platelet fibrin thrombi. This preglomerular picture differs from Shiga toxin-associated HUS, where the pathology predominantly affects the glomerular capillaries sendron 3031 ]. TTP is characteristically diagnosed when neurological features predominate, although HUS is suspected when renal failure predominates.

Because of these overlapping and changing presentations, some investigators viewed TTP and HUS as one disease with a spectrum of organ involvement. During the last 2 decades, 4 regulatory proteins of the complement alternative pathway were shown to have a role in the pathogenesis of aHUS. Mutations in factor H and membrane cofactor protein MCP were the first mutations that helped to establish that aHUS is a disease of complement dysregulation.

More than 50 different mutations in complement factor Urrmik CFHa plasma protein that inhibits the activation of the alternative pathway of the complement, have been described in aHUS cases.

If patients have defects in MCP or any other complement inhibitory sendro, even if heterozygous, they will probably be at increased risk for hemolitjk tissue damage because they cannot appropriately regulate C3 activation and amplification. The identification of factor H and MCP mutations has substantially enhanced the understanding of the molecular pathogenesis of atypical HUS [ 33 ]. All these findings proved that uncontrolled complement hemolitiik through the alternative pathway is the main underlying pathophysiology of aHUS [ 34353637383940414243444546 ].

It has also been shown that presence of anti-CFH autoantibodies leads to an acquired and transient CFH deficiency [ 4748 ]. Thus, the ultimate diagnosis of aHUS does not require a formal demonstration of its hemolitki genetic cause. The onset of aHUS is generally sudden. Most patients have the complete triad of hemolytic uremic syndrome with anemia, thrombocytopenia, and renal failure, with or without anuria or reduced urine volume, and proteinuria if diuresis hemolitil maintained.

Microangiopathic hemolysis is confirmed by the presence of schistocytes, low haptoglobin, and high lactate dehydrogenase levels. Patients usually complain of fatigue hwmolitik general illness.

If diagnosis is delayed, life-threatening hyperkalemia, acidosis, and volume overload with arterial hypertension and hyponatremia may be observed. Cardiac failure or neurological complications seizures due to hypertension are possible. Distal ischemic gangrene can also occur [ 50 ]. Half of children and the majority of adults need dialysis at admission [ 12 ].

If a patient comes to the clinic with microangiopathic hemolytic anemia, thrombocytopenia, and renal failure preceded by abdominal sendrm and diarrhea, the diagnosis has usually been Shiga toxin-associated HUS.

Bloody diarrhea and abdominal pain are usually manifestations of hemorrhagic enterocolitis caused by Shiga toxin-producing bacteria, most commonly Escherichia coli O Patients with Shiga toxin-associated Hemolitii have been described that do not have obvious diarrhea prodromes.

On the other hand, patients with aHUS commonly present with abdominal pain and diarrhea, which may begin days to weeks before the patients seek medical care, thus giving rise to the impression of diarrhea-associated HUS. For this reason, categorization of HUS according to clinical presentation as diarrhea-positive or diarrhea-negative is inappropriate [ 52 ]. Another infectious form of HUS occurs with T-antigen activation in association with pneumococcal sepsis and this can also easily be differentiated from aHUS.

Clinical presentation is also more confusing snedrom adults and it is difficult to make a differential diagnosis without ADAMTS13 assays.

In contrast, the urenik analysis tests for the diagnosis of aHUS are performed primarily in research laboratories. Furthermore, the molecular defects of aHUS remain unknown in many cases. Plasmapheresis should be started as soon as possible in any patient presenting with microangiopathic hemolytic anemia and thrombocytopenia without waiting for the results of other diagnostic investigations.

It usually takes less than 1 week in Turkey to get the test results. During that time, further investigations should also be done to exclude other possible causes hemllitik TMA, such as Shiga toxin-associated HUS, systemic lupus erythematosus, antiphospholipid syndrome, infections, malignancies, endothelial-insulting drugs, and chemotherapies [53,54].


Therefore, negative inhibitor results do not exclude the diagnosis of acquired TTP. However, there are different test designs developed for the hemoliitik of ADAMTS13 activity and the assays are affected differently by a variety of conditions, such as plasma bilirubin, hemoglobin, or VWF levels.

Therefore, it is better to do these assays in reference laboratories [55]. Anti-CFH autoantibodies represent a significant etiology of aHUS, mainly in preadolescent children, but they may also be present in adults [ 46 ureimk.

Therefore, screening of anti-CFH autoantibodies at the onset of the disease is also recommended, if possible. It is confirmed that progress in intensive care and dialysis opportunity has contributed to the decrease of mortality. For this reason, all patients suspected of having aHUS should be transferred to a specialized center that has dialysis and plasmapheresis facilities.

Until recently, there have been no specific therapies for aHUS; plasma therapy remained the first-line treatment of aHUS in all guidelines published before based on expert opinions zendrom than clinical trials [56,57,58]. Plasmapheresis can replace deficient proteins and remove antibodies against complement regulatory proteins, such sednrom anti-CFH antibodies. It would be especially sufficient in patients with defective complement regulatory proteins such as CFH. However, patient outcomes were still reported as poor with this syndrome if it was treated solely with plasma therapy [ 174959 ].

There are also some observations from case studies, especially in children, that early intensive plasma therapy can reverse aHUS and that long-term plasma therapy can hemloitik relapses and evolution to ESRF in CFH-mutated patients [ 5860 ].

Although most of them had relapses during infections and were treated by intensification of plasma therapy, most patients who received plasma therapy only during acute episodes died or were in ESRF within less than 1 year [ 5860616263 ]. Case studies also showed that plasma therapy responses change with complement mutations. Again, all of the 5 CFI-mutated patients had sedrom or partial remission in the acute phase of the disease, but all had relapses and all except hemolitk developed ESRF within a few weeks or months [ 124464 ].

MCP is a transmembrane protein. Long-term plasma therapy also does not seem to be effective in ugemik patients [ 65 ]. Remission has been achieved in 2 and 3 patients with C3 and CFB mutations, respectively [ 666768 ].

Plasmapheresis and the removal of the antibodies is the first-line treatment in patients with anti-CFH antibodies. Immunosuppressive treatment with steroids, intravenous cyclophosphamide, mycophenolate mofetil, azathioprine, or anti-CD20 should uremk be used during the follow-up period.

However, there is still no standardized protocol for the duration or type of immunosuppressive therapy in patients with anti-CFH antibodies [ 121869707172 ]. However, the clinical outcome of renal transplantation in patients with aHUS is discouraging. Patients with aHUS are more prone to develop acute rejections, which also affects graft survival.

Approximately half of the patient groups with aHUS will develop recurrent disease and graft loss [ 73 ]. Eculizumab therapy is expected to shift the paradigm [ 28 ]. With eculizumab started preoperatively and continued postoperatively, preliminary experience suggests that excessive morbidity, mortality, and kidney graft failure may be prevented [ 7576 ].

Although there are no clinical predictors of outcome, knowledge of the underlying genetic defect is helpful in predicting prognosis [ 77 ]. Recurrences have been seen in patients with CFB and thrombomodulin mutations, as well. On the other hand, patients with a mutation in the gene encoding the membrane-bound MCP have a low risk of developing a disease recurrence in the graft [ 13 ]. MCP is cell membrane-bound and highly expressed in the kidney; kidney transplants, then, would be expected to halt the disease process [ 4 ].

Combined liver-kidney transplantation has been attempted for patients with CFH and CFI mutations to address the abnormal protein synthesis in the liver and its downstream effect on the kidney. Simultaneous liver-kidney transplantation with prophylactic use of plasma therapy has been successful in patients with CFH mutations [ 60 ].

However, liver-kidney transplantation is associated with a higher mortality rate than kidney transplantation alone [ 79 ].