Familial hemolytic uremic syndrome with occurrence in the postpartum period

Myftar Barbullushi; Alma Idrizi; Goce Spasovski

doi:10.4103/1319-2442.220859

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CASE REPORT

Year : 2017 | Volume : 28 | Issue : 6 | Page : 1427-1431

Familial hemolytic uremic syndrome with occurrence in the postpartum period

Myftar Barbullushi¹, Alma Idrizi¹, Goce Spasovski²
¹ Mother Teresa University Hospital Center, Tirana, Albania
² Department of Nephrology, Medical Faculty, University of Skopje, Skopje, Macedonia

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Date of Web Publication

18-Dec-2017

Abstract

The hemolytic uremic syndrome (HUS) is a heterogeneous group of similar entities characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure (ARF) and is an important cause of ARF in childhood. Mutations have been reported in the complement regulatory protein factor H in both sporadic and familial HUS and have been identified in 10–20% of cases. Inherited HUS is unusual. We report the occurrence of HUS in two siblings after delivery, complicated with ARF and with a good outcome.

How to cite this article:
Barbullushi M, Idrizi A, Spasovski G. Familial hemolytic uremic syndrome with occurrence in the postpartum period. Saudi J Kidney Dis Transpl 2017;28:1427-31

How to cite this URL:
Barbullushi M, Idrizi A, Spasovski G. Familial hemolytic uremic syndrome with occurrence in the postpartum period. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2023 Jan 29];28:1427-31. Available from: https://www.sjkdt.org/text.asp?2017/28/6/1427/220859

Introduction

The hemolytic uremic syndrome (HUS) is a heterogeneous group of similar entities characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure (ARF). HUS constitutes an important cause of ARF in childhood.^[1]

The overall incidence of D+ HUS is estimated to be approximately 2.1 cases per 100,000 persons per year, with a peak incidence in children who are younger than five years (6.1 cases per 100,000 per year). The lowest rate is in adults aged 50–59 years (0.5 cases per 100,000 per year).^[2]

Familial occurrence of HUS is reported in siblings^{[3],[4],[5],[6]} in a few families with autosomal dominant inheritance^[7],[8],[9] and rarely with autosomal recessive transmission.^[4] Mutations have been reported in the complement regulatory protein factor H in both sporadic and familial HUS^{[10],[11],[12],[13]} in 10%–20% of cases studied. Post-partum HUS is a rare syndrome and has a poor outcome. We report the occurrence of HUS in two siblings who had postpartum HUS, complicated by ARF with a good outcome. Details about the first case have been published earlier.^[14]

Case Reports

Case 1

A 28-year-old female was diagnosed as having postpartum HUS in August 1990 after pregnancy and delivery,^[14] and her data are showed in [Table 1].

Table 1. Laboratory data at the onset of the two episodes of hemolytic uremic syndrome in the first
patient.

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The diagnosis was confirmed by renal biopsy: the presence of crescent formation with fibrinfibrinogen in the glomeruli in addition to the luminal narrowing of arterioles. Deposits of IgM were observed in the glomeruli on immunofluorescence. Daily treatment was instituted with 100 mg aspirin, 25 mg dipyridamole, 50 mg prednisolone i.v. and fresh plasma exchange (PE). The treatment with PE consisted of exchange of 1.5 L plasma volume (60–75 mL/ kg) per session, through a percutaneous dual lumen central venous femoral catheter with blood flow rate of 80–100 mL/min (four sessions in total); once she became anuric, she was put on dialysis for 19 days and subsequently discharged from the hospital in a good condition, with complete recovery of renal function and normalization of all biochemical parameters.^[14] Three years later, the patient presented again at our department after her second pregnancy [Table 1]. Because of the problems after the first delivery, the patient was kept under strict nephrological control during her second pregnancy, and she had an uneventful antenatal period and full-term normal delivery. She again developed features suggestive of postpartum HUS which was managed in a manner similar to the first episode. In this episode, we did not perform a renal biopsy. She made complete recovery and the blood pressure, renal, liver, and neurological examinations also remained normal.

The workup at our department including clinical examination, laboratory investigations, and the clinical course were consistent with the diagnosis of postpartum HUS. A couple of alternative diagnoses were very carefully excluded in this case by appropriate investigations. She required dialysis again since she became anuric and started slowly recovering thereafter.^[14]

Unfortunately, 10 years after the second episode of HUS, the patient went into terminal renal failure requiring chronic hemodialysis (HD) treatment, with a persistent resistant hypertension that became uncontrollable even on treatment with at least five antihypertensive medicaments. After more than five years on HD, she had a stroke following which she has residual neurologic sequelae.

Case 2

The first patient’s daughter, a 26-year-old woman, presented with severe renal failure to the Nephrology Department immediately after her first delivery. She had anuria, anemia, and moderate thrombocytopenia. A diagnosis of HUS was made. PE was started and substitution performed with fresh frozen plasma; exchange of 1 L plasma (60 mL/kg) per session through a percutaneous dual lumen femoral venous catheter with blood flow rate of 100 mL/min and a total of three sessions were performed. Intravenous hydrocortisone (250 mg) was administered. After about 15 days from the beginning of the illness, signs of active hemolysis disappeared, and renal function had partially improved. The C3 serum level was low. The patient refused to undergo a renal biopsy.

After the episode of the first patient’ s daughter, we performed a genetic study, which became available at our university. It demonstrated the absence of HF1 and MCP mutations but a polymorphic variant of the HF1 gene (C-257T promoter region). Importantly, this polymorphism was found to be strongly associated with the nondiarrhea-HUS, as presented in both cases.

Discussion

These cases present two interesting features. First, two episodes of postpartum HUS have not been previously reported to the best of our knowledge. Second, the mother and her daughter were found to have very low serum levels (5% of normal) of factor H, a regulatory protein of the alternate complement pathway. Both patients had low levels of serum C3, factor B, reflecting persistent alternate pathway activation. Although crescentic glomerular lesions are uncommon in HUS, the histologic findings of our first case revealed the presence of crescentic formation with fibrin-fibrinogen in glomeruli and vessels, associated also with low serum levels of C3.

The first case is also interesting with regard to the good outcome of postpartum HUS with a complete remission and return of renal function toward normal, knowing that postpartum HUS is associated with a poor prognosis in general.^[15] In fact, the two episodes of the first patient showed complete recovery of renal function, i.e., she experienced a complete clinical remission between the two episodes. Moreover, the outcome of the second episode, which we were considering may be fatal, turned out to be even better than the first one.

The apparent improvement in survival in recent years is due to an earlier diagnosis, better management of hypertension, and early institution of dialysis.^{[16],[17],[18]} However, controlled prospective trials with adequate numbers of patients are necessary to evaluate the effects of the proposed therapeutic approaches in the adult patient with severe vascular involvement.^[19] The disease may not manifest until middle age, suggesting that a trigger (such as infection or pregnancy), hypothesized as an endothelial cell insult, is required to initiate the disease in individuals unable to control complement activation.^[20]

Pregnancy is a frequent triggering event in women.^{[21],[22],[23]} About 20% of women with HUS experience the disease mostly in the initial stages of pregnancy and 80% during the postpartum period.^[23] In earlier reports, most women died, or survived with severely impaired renal function, or progressed to ESRD.^[24] Complete recovery of renal function occurred in <10% of the patients.^[25] However, some cases of HUS with a good outcome have been reported.^[26],[27] HUS has been described with increasing frequency by a number of authors as postpartum malignant nephrosclerosis,^[28] irreversible postpartum renal failure,^[24] accelerated postpartum nephrosclerosis^[28], late postpartum intravascular coagulation,^[29] and postpartum renal failure.^[30] In this regard, our first patient developed terminal renal failure 10 years after her second episode of HUS requiring chronic HD treatment.

Conclusion

Within the involved family, factor H deficiency appeared to be associated with HUS, which is transmitted as an autosomal recessive trait. Persistent C3 hypocomplementemia in the setting of familial and/or recurrent HUS should be a clue to a possible inherited complement deficiency. Although postpartum HUS is quite a rare syndrome and has a poor outcome, a prompt diagnosis and efficient therapy with the existing armamentarium could save lives without unfavorable clinical consequences. The excellent outcome of these patients seems to corroborate this concept.

Conflict of interest: None declared.

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