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. 2013 Jan 1;2(1):85–89. doi: 10.5812/nephropathol.8944

Dose kidney transplant nephrectomy stop disease progression in plasma exchange resistant post transplant hemolytic uremic syndrome? A case report

Farzaneh Sharifipour 1, Abbasali Zeraati 1, Seyed Seifollah Beladi Mousavi 2,*, Fatemeh Hayati 2, Mohsen Tavazoe 2, Marzieh Beladi Mousavi 3
PMCID: PMC3886173  PMID: 24475432

Abstract

Background

Two different case reports, which have been published previously, suggested that bilateral nephrectomy can improve sever and refractory hemolytic uremic syndrome (HUS) in adults without a history of transplantation. At this study, kidney transplant nephrectomy in a patient with sever post transplant HUS was investigated.

Case

Patient was a 55 years old man with a single small size kidney and end-stage renal disease (ESRD). He had received a kidney from an unrelated donor three months before admission. The patient was admitted with fever and acute renal failure. Clinical and laboratory evaluation wereconsistent with sever De novo hemolytic uremic syndrome (HUS). Different therapeutic regimens administered in this patient including intensive plasma exchange, plasma infusion, empirical antibiotics, and high doses of corticosteroid. Although Cyclosporine was changed to Tacrolimus. After 45 days of treatment, patient’s condition did not improve and sever thrombocytopenia (10000-15000/µL) developed. Patient was also suffered from severe hypersensitivity reaction (fever, chills, and itching) following each plasma exchange. Kidney transplant nephrectomy was done. However, sever post operativebleedingoccurred.HUS and thrombocytopenia did not improve and patient died two days after operation.

Conclusions

According to this experience, Kidney transplant nephrectomy may not be an effective treatment and is not recommended in the treatment of severe and refractory post transplant HUS.

Keywords: Hemolytic Uremic Syndrome, Kidney Transplant, Nephrectomy, Transplantation

1. Introduction

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP-HUS) is one of the most important complications in post kidney transplant period (1,2). Similar to non transplant patients, it should be suspected in a recipient who presents with evidence of microangiopathic hemolytic anemia and thrombocytopenia without another clinically apparent cause (1,2). It is occurred in two different conditions; First, as recurrent in patients whose primary cause of end stage renal disease (ESRD) was HUS and Second, as de novo with a different primary renal disease (3-5). Although, the reported recurrence rate of TTP-HUS after renal transplant is between 25-50 percent, De novo HUS is a rare problem among these patients.In some patients with de novo HUS, disease was localized in the kidney, while others may have abnormalities in multiple organs (3-6).

Several modalities have been used for the treatment of TTP-HUS including plasma exchange and plasma infusion. However, in kidney transplant recipients, treatment experiences, especially in severe and refractory cases, are extremely limited.

2. Case report

A 55 years old white man with a single small sized kidney and ESRD underwent kidney transplantation from unrelated living donor. He had been on hemodialysis three times a weekfor around a year prior to the transplantation. The surgery and post surgical course were uneventful.Patient had a good hospital course.Eleven days after transplantation, the patient was discharged with the following vital signs: blood pressure: 130/85mmHg, Creatinine:1.3mg/dL, WBC:13.2x103/µL,Hb:11.6 g/dL,Plt:239,000/µL . Three months after transplantation, patient was admitted because of having fever andrising serum creatinine at our center. Patient’s immunosuppresion regimen was Prednisone15 mg/daily, Mycophenolatemofetile 1 g/BD and Cyclosporine 100mg/BD. In laboratory data creatinine: 3.8mg/dL, WBC:12.8 x 103/µL , Hb: 10.1g/dL, platelets:43, 000/µL and Cyclosporine blood level were in acceptable therapeutic range. Coagulation profile was in normal range as well. An ultrasound evaluation showed an enlarged transplant kidney with an increased resistive index (0.80), without evidence of renal artery stenosis and urinary tract obstruction. Serumlactate dehydrogenase (LDH) level elevated (1300 U/L) and evidences of microangiopathic haemolytic anaemia,fragmented red blood cells in a peripheral smear, was found. Serum cytomegalovirus studies, CMV IgG and IgM antibodies were negative., Since this patient’s thrombocytopenia was associated with a drop in hemoglobinlevel, elevated serum LDH,evidences of microangiopathic haemolytic anaemia in peripheral smear and no evidence of renal artery stenosis orurinary tract obstruction in ultrasound,we considered HUS as the leading cause of acute renal failure (ARF). Daily plasma exchanges with two liters of fresh frozen plasma started immediately, Broad spectrum antibiotics were also administered and Cyclosporine was switched to Tacrolimous. Hemodialysis (4 times/week) was also started due to sever renal failure two weeks after admission, Because of poor response to intensive plasma exchange, high doses of corticosteroid were added four weeks later, Tacrolimous was also discontinued. Intensive plasma exchange and plasma infusion were continued; however, three weeks later, clinical and laboratory courses of HUS did not improve.Patient’s condition was poor and platelets count was between 10000-15000/µL. Patient didn’t tolerate plasma exchangesdue to sever hypersensitivity reaction (fever, chills, and itching) after each plasma infusion. Finally, kidney transplant nephrectomy was done. Sever bleeding after operation was occurred. However, HUS and thrombocytopenia did not improve and patient died two days postoperation.

3. Discussion

In adult patients without a history of transplantation, plasma exchange and plasma infusionare the most effective treatments available for TTP-HUS, if left untreated, it typically follows a progressive course and leading to death is a common outcome. While, prior to the use of plasma exchange, the outcome of thrombotic microangiopathy (TMA)-associated syndromes was poor in the last decades, standard plasma exchange has significantly reduced the mortality rate of TTP/HUS from 94.5% to 13%. Therefore, It is recommended that even if there is some uncertainty about the diagnosis of TTP-HUS, plasma exchange should be initiatedand if an alternative diagnosis is subsequently discovered it should then be stopped (7,8).

In the development of post-transplant de novo HUS, multiple factors have been implicated including systemic viral infections, particularly cytomegalovirus, HIV and some other infections. In addition, the use of some protocols of immunosuppressive strategies have been considered (9-11). Therefore, the mainstay of the management is the removal of the inciting factors, such as treatment of cytomegalovirus, dose reduction or switching from one drug to the another and plasma infusion or exchange.

There is some evidence that calcineurin inhibitors, such as cyclosporine A (CsA) have an important role in the development of post transplant HUS (10). On the other hand, it has been reported that the switch of CsA to other calcineurin inhibitor, tacrolimus is effective in some patients. Zarifian et al (1999), have reported that 13 of 16 renal allograft recipients, who developed TTP-HUS while taking cyclosporine, had a high rate of graft salvage after switching to tacrolimus (6), however, this modality didnot improve our patient’s condition.

Glucocorticoids have a controversial role in the treatment of TTP-HUS. However, it appears that in patients whose platelet counts do not risewithin several days of treatment,plasma exchange, adjunctive immunosuppressive treatment with prednisone or methylprednisoloneshould envisage as a reasonable and appropriate modality (12-15). Unfortunately high doses of corticosteroid were also ineffective in our patient.

It has also been reported that, in patients with primary refractory or relapsing de novo TTP-HUS, administration of intravenous immunoglobulin, anti-CD20 antibody, rituximab, and belatacept in combination with plasma exchange may also had some benefits in terms of improvment (16-19). These drugs were not available in our center and we do not have access to them.

In two different case reports, by Remuzzi, and Feldman et al. (1996)bilateral nephrectomy (native kidneys) has been tried in five women with sever and refractory HUS and without a history of transplantation. They found improvement inclinical courseof the patients and also the disease progression has been ceased (20-21). To our best knowledge, there is no study or case report investigating kidney transplant nephrectomy in refractory post transplant recurrent of de novo TTP-HUS. However, according to above case reports and because of poor response to all available treatments,including intensive plasma exchange and plasma infusion, broad spectrum antibiotics, high dose of corticosteroid followed by discontinuation of calcineurin inhibitors, we had to remove transplanted kidney as a last modality in our patient,. Although it was not accompanied by improvement.

4. Conclusions

Recurrent and de novo TTP-HUS should be suspected in a kidney transplant patients who present with evidence of microangiopathic hemolytic anemia and thrombocytopenia and it typically follows a progressive course. The plasma exchange and plasma infusion is the most effective treatment available for the TTP-HUS.

Treatment of cytomegalovirus, withdrawal of the suspect drugs, dose reduction or discontinuation of CsA, switched from CsA to tacrolimus,adjunctive immunosuppressive treatment with glucocorticoids, rituximab, and belatacept may also have some benefit in de novo TTP-HUS. However according to our experience in this case, Kidney transplant nephrectomy is not recommended as a treatment of severe and refractory post transplant HUS.

Acknowledgments

The authors would like to express their gratitude to the staffs of nephrology ward and department of internal medicine, Ahvaz Jundishapour University of Medical Sciences.

Authors’ contributions

FS, SSBM and FH prepared the primary draft. MT and MBM wrote some parts of the manuscript. MBM AND AZ edited the manuscript. SSBM prepared the final manuscript.

Funding/Support

The author declared no competing interests.

Funding/Support

None declared.

Implication for health policy/practice/research/medical education:

Kidney transplant nephrectomy is not effective and not recommended in the treatment of severe and refractory post transplant hemolytic uremic syndrome.

Please cite this paper as: Sharifipour F, Zeraati A, Beladi Mousavi SS, Hayati F, Tavazoe M, Beladi Mousavi M. Dose kidney transplant nephrectomy stop disease progression in plasma resistant post transplant hemolytic uremic syndrome? A case report. Journal of Nephropathology 2013; 2(1): 85-89. DOI: 10.5812/nephropathol.8944

References

  • 1.Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Kidney Int . 2001;60(3):831–46. doi: 10.1046/j.1523-1755.2001.060003831.x. [DOI] [PubMed] [Google Scholar]
  • 2.Ruggenenti P. Post-transplant hemolytic-uremic syndrome. Kidney Int . 2002;62:1093–1104. doi: 10.1046/j.1523-1755.2002.00543.x. [DOI] [PubMed] [Google Scholar]
  • 3.Schwimmer J, Nadasdy TA, Spitalnik PF, Kaplan KL, Zand MS. Denovo thrombotic microangiopathy in renal transplant recipients: A comparison of hemolytic uremic syndrome with localized renal thrombotic microangiopathy. Am J Kidney Dis . 2003;41(2):471–9. doi: 10.1053/ajkd.2003.50058. [DOI] [PubMed] [Google Scholar]
  • 4.Artz MA, Steenbergen EJ, Hoitsma AJ, Monnens LA, Wetzels JF. Renal transplantation in patients with hemolyticuremicsyndrome: highrate of recurrence and increasedincidence of acuterejections. Transplantation . 2003;76(5):821–6. doi: 10.1097/01.TP.0000085083.74065.1B. [DOI] [PubMed] [Google Scholar]
  • 5.Oyen O, Strøm EH, Midtvedt K, Bentdal O, Hartmann A, Bergan S. et al. Calcineurin inhibitor-free immunosuppression in renal allograft recipients with thrombotic microangiopathy/hemolytic uremic syndrome. Am J Transplant . 2006;6(2):412–8. doi: 10.1111/j.1600-6143.2005.01184.x. [DOI] [PubMed] [Google Scholar]
  • 6.Zarifian A, Meleg-Smith S, O’donovan R, Tesi RJ, Batuman V. Cyclosporine-associated thrombotic microangiopathy in renal allografts. Kidney Int . 1999;55(6):2457–66. doi: 10.1046/j.1523-1755.1999.00492.x. [DOI] [PubMed] [Google Scholar]
  • 7.Von Baeyer H. Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies. Ther Apher . 2002;6(4):320–8. doi: 10.1046/j.1526-0968.2002.00390.x. [DOI] [PubMed] [Google Scholar]
  • 8.Michael M, Elliott EJ, Ridley GF, Hodson EM, Craig JC. Interventions for haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Cochrane Database Syst Rev . 2009;1:CD003595. doi: 10.1002/14651858.CD003595.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Waiser J, Budde K, Rudolph B, Ortner MA, Neumayer HH. De novo hemolytic uremic syndrome post renal transplant after cytomegalovirus infection. Am J Kidney Dis . 1999;34(3):556–9. doi: 10.1016/s0272-6386(99)70085-5. [DOI] [PubMed] [Google Scholar]
  • 10.Pham PT, Peng A, Wilkinson AH, Gritsch HA, Lassman C, Pham PC. et al. Cyclosporine and tacrolimus-associated thrombotic microangiopathy. Am J Kidney Dis . 2000;36(4):844–50. doi: 10.1053/ajkd.2000.17690. [DOI] [PubMed] [Google Scholar]
  • 11.Kiykim AA, Ozer C, Yildiz A, Tiftik N, Senli M, Kelebek E. et al. Development of transplant renal artery thrombosis and signs of haemolytic- uraemic syndrome following the change from cyclosporin to tacrolimus in a renaltransplantpatient. Nephrol Dial Transplant . 2004;19(10):2653–6. doi: 10.1093/ndt/gfh375. [DOI] [PubMed] [Google Scholar]
  • 12.Abramowicz D, Pradier O, Marchant A, Florquin S, De Pauw L, Vereerstraeten P. et al. Induction of thromboses within renalgrafts by high-doseprophylacticOKT3. Lancet . 1992;339(8796):777–8. doi: 10.1016/0140-6736(92)91897-h. [DOI] [PubMed] [Google Scholar]
  • 13.George JN. George JNClinical practiceThrombotic thrombocytopenic purpura. N Engl J Med . 2006;354(18):1927–35. doi: 10.1056/NEJMcp053024. [DOI] [PubMed] [Google Scholar]
  • 14.Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndromeClinicalexperience in 108patients. N Engl J Med . 1991;325(6):398–403. doi: 10.1056/NEJM199108083250605. [DOI] [PubMed] [Google Scholar]
  • 15.Allford SL, Hunt BJ, Rose P, Machin SJ. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol . 2003;120(4):556–73. doi: 10.1046/j.1365-2141.2003.04049.x. [DOI] [PubMed] [Google Scholar]
  • 16.Jasti S, Coyle T, Gentile T, Rosales L, Poiesz B. Rituximab as an adjunct to plasmaexchange in TTP: A report of 12cases and review of literature. J ClinApher . 2008;23(5):151–6. doi: 10.1002/jca.20172. [DOI] [PubMed] [Google Scholar]
  • 17.George JN, Woodson RD, Kiss JE, Kojouri K, Vesely SK. Rituximab therapy for thrombotic thrombocytopenic purpura: A proposedstudy of the TransfusionMedicine/HemostasisClinicalTrialsNetwork with a systematicreview of rituximabtherapy for immune-mediateddisorders. J ClinApher . 2006;21(1):49–56. doi: 10.1002/jca.20091. [DOI] [PubMed] [Google Scholar]
  • 18.Caramazza D, Quintini G, Abbene I, Malato A, Saccullo G, Lo Coco L. et al. Relapsing or refractoryidiopathicthromboticthrombocytopenicpurpura-hemolyticuremicsyndrome: the role of rituximab. Transfusion . 2010;50(12):2753–60. doi: 10.1111/j.1537-2995.2010.02763.x. [DOI] [PubMed] [Google Scholar]
  • 19.Ashman N, Chapagain A, Dobbie H, Raftery MJ, Sheaff MT, Yaqoob MM. Belatacept as maintenance immunosuppression for post renal transplant denovo drug-induced thrombotic microangiopathy. Am J Transplant . 2009;9(2):424–7. doi: 10.1111/j.1600-6143.2008.02482.x. [DOI] [PubMed] [Google Scholar]
  • 20.Remuzzi G, Galbusera M, Salvadori M, Rizzoni G, Paris S, Ruggenenti P. Bilateralnephrectomystoppeddiseaseprogression in plasma-resistanthemolyticuremicsyndrome with neurologicalsigns and coma. Kidney Int . 1996;49(1):282–6. doi: 10.1038/ki.1996.40. [DOI] [PubMed] [Google Scholar]
  • 21.Feldman M, Bruno T, Chong YC, Borstad G, Wild C, Lopez JD. et al. Bilateralnephrectomy for treatmentresistantsystemiclupuserythematosis and thromboticthrombocytopenicpurpura: a casereport. Am J Hematol . 2007;82(6):496–7. doi: 10.1002/ajh.20842. [DOI] [PubMed] [Google Scholar]

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