• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of hippokratiaLink to Publisher's site
Hippokratia. 2011 Jan-Mar; 15(1): 90–92.
PMCID: PMC3093155

Atypical hemolytic-uremic syndrome (HUS) with recovery after a long-lasting anuria: a case report

Abstract

We report a case of a seven-year-old girl who suffered from atypical Hemolytic Uremic Syndrome (aHUS) complicated by septicaemia, central nervous system involvement, and cholangiitis. She remained anuric requiring treatment with peritoneal dialysis (PD) for a five-month period. In addition to conventional therapeutic measures including fresh frozen plasma (FFP) and blood cells transfusions she also underwent to plasma exchange (PE) treatment. Following a stormy hospitalization period of 17 weeks, the patient finally regained renal function and three years later she remains well on antihypertensive treatment and free of dialysis.

Keywords: atypical Hemolytic Uremic Syndrome, anuria, cholangitis, seizures

About 10% of overall HUS patients present with the atypical form of the disease. This comprises a heterogeneous group of patients with a rather severe phenotype, usually characterized by oligoanuria, hypertension and central nervous system involvement13. Long term prognosis is poor with high morbidity and mortality.

If these patients survive, they go into chronic replacement therapy or chronic renal failure at a rate of 34.5% and 31% respectively.3,4. Recovery of renal function following long lasting dialysis in children suffering from aHUS has been rarely reported5,6.

We report a case of a seven-year-old girl who suffered from aHUS, complicated by septicaemia, central nervous system involvement, and cholangiitis with recovery, following a five month period on PD.

Case report

A seven-year-old girl was admitted to "Agia Sophia" children's hospital with a two-day history of macroscopic hematuria, abdominal pain, headache and a low grade fever. Two weeks earlier skin eruption attributed to an allergic reaction was reported, and treatment with oral steroids was given for a week. On examination she was pale and icteric with a faded maculopapular eruption on her arms and palms. There was no history of diarrhoea or bloody stools. Laboratory results revealed anaemia (hematocrit 20.9%, hemoglobin 6.7g/dl, leukocytes 9 x103/µl) with fragmented red cells (schistocytes) and reticulocytes (7.5%), thrombocytopenia (platelets 63 x103/µl), hyperbilirubinemia (serum bilirubin 3.2mg/dl), lactate dehydrogenase (LDH) 580U/L(normal 150-450U/ L) and acute renal failure (plasma creatinine 3.8 mg/dl), with estimated GFR (eGFR) 13ml/min/1.73m2. A decrease of serum C3 complement level was found (63.2 mg/dl, normal 90-180 mg/dl). Her urinalysis revealed macroscopic hematuria and four (+) proteinuria. Renal ultrasonography revealed two normal sized kidneys with increased echogenicity. The diagnosis of diarrhea-negative hemolytic uremic syndrome was made and she was treated with fresh frozen plasma (FFP) infusions (20ml/ Kg/day) along with red packed cells. Due to the positive ANA titers (1/320) a percutaneous renal biopsy was performed in order to exclude lupus related HUS. In 5 out of 17 glomeruli examined, thickening and duplication of basement membrane wall with endothelial swelling was found.

Tubules and interstitium revealed areas with ischemic lesions. Extreme luminal narrowing due to intimal proliferation and intraluminal platelet thrombi in vessels, mainly glomerular capillaries and efferent arterioles was identified. A positive deposition of IgM ++ and C3 +++ was found on immunofluoresence. There was no cortical necrosis and the above findings confirmed the diagnosis of non-lupus related HUS.

On the tenth post-admission day the patient became oligoanuric with a plasma creatinine 6.2mg/dl and urea 300mg/dl and treatment with PD were conducted. Six weeks later, while on PD, acute hemolysis and thrombocytopenia remained unchanged ( LDH levels 1073 IU/I and platelets <90 x103/µl respectively, Figure 1). The need for an alternative treatment with PEs was prompt. This treatment was performed on a daily or alternate day basis for two weeks, replacing the patient's plasma with FFP at a rate of 30ml/Kg per session. After a total of seven sessions, the most encouraging results in terms of platelet count rising up to 220 x103/µl and LDH levels dropping down to 326 IU/I were observed. However, PE treatment had to be stopped due to a central venous catheter infection followed by septicemia. Her clinical condition was deteriorated with development of malignant hypertension refractory to a cocktail of antihypertensive regimen including calcium channel blockers, ACE inhibitors, and beta-blockers, while severe headache, confusion and grand mal seizures were added.

Figure 1
LDH-PLTs fluctuations during the course of the disease

Following a stormy period of more than two months, the patients condition improved again but a week later she suffered from a severe episode of cholangitis presented with fever, hyperbilirubinemia (serum bilirubin 4.4mg/dl with direct 3.4 mg/dl), and increased serum levels of SGOT, SGPT and γGT (293U/L, 195U/L, 1976 U/L respectively) confirmed by abnormalities appearing on an abdominal CT scan and ultrasonography. After appropriate medical management she recovered from these complications. Having been an inpatient for sixteen weeks on PD, but with no more signs of hemolysis with normal LDH and platelets she was discharged home on CAPD. On week 19 she started passing urine with gradual improvement of her renal function to the degree that CAPD was no longer necessary. Recent investigation of the complement components including C3 Ag, C4 Ag, factor B Ag, factor H Ag, factor I Ag, Anti-FH Ab and CD46 was performed, showing normal results, although the C3 Ag level was for both, the patient and her father, at the lower normal range thus indicating the role of genetic complement abnormalities. At her last follow-up, three years later, she was in a good clinical condition, attending school on a regular basis, without cognitive or other abnormalities. Her plasma creatinine was 1.2mg/dl and eGFR of 55ml/min/1,73m2. Blood pressure remains well controlled on a ACE inhibitor

(Enalapril tabl 20mg every morning) and Calcium channel blockers (Nifedipine tabl 20mg noon time and Felodipine tabl 5 mg in the evening) and her urinalysis is normal.

Discussion

Our patient represents a sporadic case of aHUS and fulfilled all criteria for a severe form of this disease. During her illness she experienced a number of complications such as septicaemia, refractory hypertension, central nervous system involvement and cholangitis. She was also in an oligoanuric status for almost five months. Under the above described clinical condition this aHUS case fell into the poor prognostic group7. Indeed, it has been suggested, that a long standing period on renal replacing therapy consists of a poor prognostic factor for the recovery of renal function8,9. In contrast to this expectation, this emphasises the fact, already described by others, that children with HUS, who require a longer time for renal function recovery do not necessarily have a worse prognosis10.

Data regarding the HUS affected children who experienced renal function recovery following long period on dialysis, are limited5,6. Included among them there are two cases who remained anuric for 14 and 52 weeks, respectively, and came off dialysis with incomplete recovery of renal function5 and two further cases who also recovered following 8 and 16 months on long lasting dialysis treatment6. PEs consist treatment modality, successfully used in adults with thrombotic thrombopenic purpura-haemolytic uremic and the rationale to extend its use in children with HUS was based on already known beneficial results11. Furthermore, it has been stated that PEs can shorten the duration of acute renal failure and lead to a better long term prognosis. This treatment is especially advantageous for patients suffering from post diarrhoeal syndrome with central nervous system involvement12,13. It remains unclear, whether by this potentially injurious and not established form of treatment, the toxic factor or factors are eliminated, and therefore contributing to a better prognosis. In any case, the fact that we were dealing with a severely ill child, prompted us to continue treatment with PEs, as a proper alternative to FFP infusions. It seems clear from our data that following initiation of PEs, the LDH and platelets levels improved gradually and this steady state situation remained stable for both parameters throughout the course of the disease (fig 1). However, it is difficult to associate patients renal function recovery with PEs, since between these two events there was an interval of three months. The extent to which both FFP and PEs as therapeutic interventions, effectively accelerated renal function recovery remains an unanswered question. The debate regarding the presence of circulating factors or an unidentified deficiency plasma factor, or both, triggering endothelial damage, still exists. Our patient was tested for factor H deficiency and found to be normal. As it is known these genes are coding for proteins involved in regulation or activation of the alternative pathway of complement14,15.

This case seems to belong to a group of patients with aHUS, who although display no factor H mutation, 50% of them exhibit evidence of over activity of the alternative pathway of complement2. The finding of a low level of C3 component of complement in our patient during the acute phase of the disease reflects probably C3 consumption in the renal microvasculature. Indeed, the immunofluoresence test on the renal biopsy specimen was consistent with a positive deposition of C3. It has been reported that among these patients the majority display a decreased C3 plasma level and up to 30% are carriers of mutations in the gene(s) encoding for factor H (HF1) and membrane cofactor protein (MCP), which is highly expressed in the kidney, and probably protecting it. However, the remainder of the aHUS patients, as in our case, do not carry HF1 mutation.The outcome of aHUS affected children is less predictable in comparison to D+ HUS cases and on average fairly unfavourable. However, data from renal pathology findings could be somehow predictive since it has been suggested that renal parenchyma lesions affecting less than 50% of the glomeruli at the initial phase constitutes a favourable prognostic factor16. Indeed, our patients renal biopsy revealed 29% affected glomeruli and this is probably an additional prognostic finding contributing to the good outcome of this severely affected girl. In conclusion, we speculate that PEs contributed to the clinical improvement of this patient and in contrary to expectation regarding severely affected HUS children, a long lasting dialysis period does not exclude a favourable prognosis.

Footnotes

No conflict of interest was declared.

References

1. Siegler RL, Oakes RS. Hemolytic uremic syndrome; pathogenesis, treatment, and outcome. Curr Opin Pediatr. 2005;17:200–204. [PubMed]
2. Noris M, Remuzzi G. Hemolytic uremic syndrome. Am Soc Nephrol. 2005;16:1035–1050. [PubMed]
3. Proesmans W. Typical and atypical hemolytic uremic syndrome. Kidney Blood Press Res. 1996;19:205–08. [PubMed]
4. Fitzpatrick MM, Walters MD, Trompeter RS, Dillon MJ, Barratt TM. Atypical non-diarrhea-associated hemolytic-uremic syndrome in childhood. J Pediatr. 1993;122:532–537. [PubMed]
5. Trompeter RS, Schwartz, ChantlerC, Dillon MJ, Haycock GB, Kay R, Barratt TM. Atypical non-diarrhea-associated Haemolytic- uremic syndrome:an analysis of prognostic futures. Arch Dis Child. 1983;58:101–105. [PMC free article] [PubMed]
6. Brunner K, Bianchetti MG, Neuhaus TJ. Recovery of renal function after long-term dialysis in hemolytic uremic syndrome. Pediatr Nephrol. 2004;19:229–231. [PubMed]
7. Tonshoff B, Sammet A, Sanden I, Mels O, Waldherr R, Scharer K. Outcome and prognostic determinants in the hemolytic uremic syndrome in children. Nephron. 1994;68:63–70. [PubMed]
8. Siegler RL, Milligan MK, Burningham TH, Christofferson R, Chang S, Jorbe L. Long-term outcome and prognostic indicators in the hemolytic-uremic syndrome. J Pediatr. 1991;118:195–200. [PubMed]
9. Oakes, RS, Kirkhamm JK, Nelson RD, Siegler RL. Duration of oliguria and anuria as predictors of chronic renal-related sequele in post-diarrheal hemolytic-uremic syndrome. Pediatr Nephrol. 2008;23:1303–1308. [PubMed]
10. Cobeñas CJ, Alkoncher LF, Spizzirri AP, Rahman RC. Longterm follow-up of Argentinean patients with hemolytic uremic syndrome who had not undergoing dialysis. Pediatr Nephrol. 2007;22:1343–1347. [PubMed]
11. Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Intern. 2001;60:831–846. [PubMed]
12. Gianviti A, Perna A, Caringella A, Edefonti A, Penza R, Remuzzi G, Plasma G. Plasma exchange in children with hemolytic-uremic syndrome at risk of poor outcome. Am J Kidney Dis. 1993;22:264–266. [PubMed]
13. Ruggenenti P, Remuzzi G. Pathophysiology and management of thrombotic microangiopathies. J Nephrol. 1998;11:300–310. [PubMed]
14. Neumann HP, Slazmann M, Bohnert-Iwan B, Mannuelian T, Skerka C, Lenk D, et al. Hemolytic uremic syndrome and mutation for the factor H gene: a registry-based study of German speaking countries. J Med Genet. 2003;40:676–681. [PMC free article] [PubMed]
15. Dragon-Durey MA, Frmeaux-Bacchi V. Atypical haemolytic uraemic syndrome and mutations in complement regulator genes. Springer Semin Immun. 2005;27:359–374. [PubMed]
16. Loirat C, Baudouin V, Sonsino E, Mariani-Kurdjian P, Elion J. Hemolytic uremic syndrome in the child. Adv Nephrol Necker Hosp. 1993;22:141–168. [PubMed]

Articles from Hippokratia are provided here courtesy of Hippokratio General Hospital of Thessaloniki
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...