An audit of CMV disease in renal transplant recipients transplanted at the Queen Elizabeth Hospital Birmingham

Gemma Banham, Shazia Shabir, Richard Borrows

Cytomegalovirus infection

• Direct effects– Viral syndrome– Tissue invasive disease

• Indirect effects– Acute and chronic rejection– Post transplantation diabetes– Opportunistic infections

IMPACT Trial

Humar A et al. American Journal of Transplantation 2010; 10: 1228–1237Humar A et al, Transplantation 2010; 90: 1427–1431

RCT of oral prophylactic ganciclovir vs intravenous pre-emptive therapy

FULL ITT population D+/R- D+/R+ D-/R+

Kliem V et al, American Journal of Transplantation 2008; 8: 975–983

British Transplantation Society Guidelines (2011)

• CMV prophylaxis to seronegative recipients who receive a transplant from a seropositive donor (D+/R-)

• CMV prophylaxis where either the donor or recipient is seropositive if patient is treated with T-cell depleting antibodies

• Choice of prophylaxis strategies

• Audit standards1. Rate of CMV disease in 1st year in D+/R- patients <8%2. Rate of CMV disease in 1st year in D+/R+ patients <8%3. Rate of CMV disease in 1st year in D-/R+ patients <8%

Audit Methods• Patients transplanted at QEHB between 1st August 2007 and 30th June 2011• Patients identified from Surgery Department’s database • Total of 569 patients

CMV status (Donor/Recipient) Number (%)

D-/R- 150 (26.4)D-/R+ 121 (21.3)D+/R+ 178 (31.3)D+/R- 116 (20.4)

Unknown 4 (0.7)

• PICS microbiology tab for CMV PCR results• Electronic clinical notes for those with

CMV viraemia• Heartland’s Hospital Virology Department

results database • Stoke audit• NHS Blood and Transplant

Audit Questions?

1. Should we offer extended prophylaxis (200 days) to D+/R- recipients?

2. Should we offer prophylaxis to D+/R+ recipients?

3. Should we offer prophylaxis to D-/R+ recipients?

£1081.46 for 30 day supply of 900mg once daily dose

CMV Syndrome CMV Disease

Number at risk

0 100 200 300 365

150 137 127 119 111

121 104 96 94 89

116 109 86 75 67

178 128 115 107 105

Number at risk

0 100 200 300 365

150 140 130 121 113

121 110 104 102 97

116 110 98 91 85

178 154 143 136 133

Audit Standards

1. Rate of CMV disease in the first year post transplantation in D+/R- patients <8%

2. Rate of CMV disease in the first year post transplantation in D+/R+ patients <8%

3. Rate of CMV disease in the first year post transplantation in D-/R+ patients <8%

Early CMV in D+/R-

Creatinine clearance (ml/min)Cockcroft-Gault Formula

Recommended valganciclovir prophylaxis

>60 900mg once daily

40 - 59 450mg once daily

25 - 39 450mg alternate days

10 - 24 450mg twice weekly

<10 Not recommended

• 3/23 cases CMV syndrome during 1st 100 days• Subtherapeutic dose of valganciclovir in 2/3

Consequences of CMV Syndrome

Syndrome cases (%)D-/R-

3/150 (2.0)D-/R+

12/122 (9.9)D+/R+

39/178 (21.9)D+/R-

23/116 (19.8)Total

77/569 (13.5)Disease 1 (33.0) 2 (16.7) 5 (12.8) 4 (17.4) 12 (15.6)

Histology 0 (0.0) 2 (16.7) 2 (5.1) 1 (4.3) 5 (6.5)

Death during CMV episode 0 (0.0) 0 (0.0) 1 (2.6) 1 (4.3) 2 (2.6)

Viraemia level(median, range)

2.2x107, 1.6x106 - 3.1x107

1.1x104, 1025-1.9x105

1.3x104, 504- 1.7x108

3.1x105, 571- 7.7x106

2.2x104, 504- 1.7x108

Requiring treatment*- Total- Intravenous

3 (100.0)2 (66.7)

11 (91.7)2 (1.7)

37 (94.9) 12 (30.8)

21 (91.3)8 (34.8)

72 (93.5)24 (31.2)

Patients requiring CMV related hospitalisation - Total- QEHB- Stoke

3 (100.0)3 (100.0)

0 (0.0)

8 (66.7)8 (66.7)0 (0.0)

27 (69.2)23 (59.0)

4 (10.3)

17 (73.9)14 (60.9)

3 (13.0)

55 (71.4)48 (62.3)

7 (9.1)

Days in QEHB (median, range) 8, 6-10 21, 2-42 9, 2-48 10.5, 3-26 9, 2-48Total days in QEHB 24 175 343 168 710

*5 additional patients received treatment with no evidence of CMV Syndrome or Disease

Conclusions

• Meeting targets for CMV ‘Disease’• Large amounts CMV ‘Syndrome’ with significant

morbidity and cost• Highest burden in D+/R+, followed by D+/R- then D-/R+• Majority D+/R- disease is late• Early D+/R- disease may be due to inappropriate dosing

of valganciclovir

Acknowledgments

• Everyone at other transplant units • Kerry Tomlinson• Caroline Clark• Hari Krishnan• Husum Osman

Who should receive prophylaxis?

Number at risk

0 200 400 600 730

150 127 110 97 81

121 96 87 74 59

116 86 62 51 40

178 115 102 90 77