Objectives: Nephropathy from BK virus (BKV) infection is a growing challenge in kidney transplant recipients globally. It is the result of contemporary potent immunosuppressives aimed at reducing acute rejection and improving allograft survival. Untreated BK virus infections lead to kidney allograft dysfunction or loss. Decreased immunosuppression is the principle treatment but predisposes to acute and chronic rejection. Screening for early detection and prevention of symptomatic BK virus nephropathy may improve outcomes. Although no approved antiviral drug is available, leflunomide, cidofovir, quinolones, and intravenous immunoglobulin have been used.
Since the introduction of the new immunosuppressive agents in the transplant regimen at the Royal Hospital, Few cases of BK virus have been detected, and the challenge was to decide upon the best treatment option .
Materials and Methods: The audit was carried out at the Royal Hospital-Oman between January 2010 and December 2012. The nephrology consultant and the clinical pharmacist reviewed all the BK cases and the Royal Hospital. Extensive literature review carried out by the pharmacist to look into the prevalence, prognosis and treatment of BK nephropathy.
A treatment protocol was prepared by the clinical pharmacist through guidance of the consultant and was peer reviewed by team of clinical pharmacists and nephrology doctors and approved by the consultant.
Results: The audit included 19 patients with positive BK virus ployoma nephropathy. The treatment options were applied stepwise in all the patients with BK virus nephropathy with success rate more than 70%.
Conclusions: BK virus nephropathy is emerging at an alarming rate and requires increasing awareness. The uses of current treatment options are still questionable. Our audit confirms that reducing immunosuppression appears to be the criterian standard for the treatment of BK nephropathy.
Key words : BK, Nephropathy, Immunosuppressive, Kidney, Transplantation
BK virus (BKV) was first detected in early 1970s.1 The name was originated from patients initials “BK.” Soon after, there were series of cases where BK virus (BKV) nephropathy (BKVN) was reported in kidney transplant recipients.1,2
BK virus-induced nephritis is increasing in alarming numbers worldwide, which may be the result of newer, more potent immunosuppressive agents in kidney transplant recipients.1 Although these drugs are meant to prevent or reduce the incidence of acute rejections, and prolong the survival of the transplanted graft, the harm these drugs are causing is debatable.2,3
Much research has shown that BKVN is self-limiting in many cases; however, some cases might need strategic interventions to eliminate the virus while preserving the transplanted kidney functions.1,2 Starting with reduction of immunosuppressive agents; which is the criterion standard—to using other agents (eg, quinolone antibiotics, intravenous immunoglobulins, and leflunomide).4-8 Additionally some centers also use cidofovir as an antiviral.3 It is important to consider treating BKVN, as untreated BKV infections lead to graft dysfunction or loss. The challenge that faces most centers with patients having BKVN is that there is no standard antiviral agent, and all the above-mentioned agents are used off-label.
The prevalence of positive BKV in Omani transplant population is approximately 6.3%. Newer immunosuppressive agents in the transplant regimen were introduced almost 10 years back at the Royal Hospital; and since 2008, many cases of BKV have been detected, and the dilemma was to select the best treatment option for eradicating BKV in the transplanted kidney.
A treatment protocol was prepared by the clinical pharmacist through guidance of the nephrology consultant and based on the literature review. The protocol was then peer-reviewed by a team of clinical pharmacists and nephrology doctors.
The main aim of this audit was to monitor the effectiveness of the treatment strategy applied to BKVN patients.
Materials and Methods
An extensive literature review was performed by the team to examine the prevalence, prognosis, and treatment of BK nephropathy worldwide. The protocol was then developed, based on the literature findings.
The audit was carried out at the Royal Hospital, the largest tertiary hospital in Oman between January 2010 and December 2012. From 2008, in our center, we prospectively screened all kidney transplant recipients for BKV. Almost 300 patients were screened for BKV using a polymerase chain reaction to quantify the viral load. Almost 700 tests were performed to quantify the viral load in the 300 patients. All the cases with positive polymerase chain reaction were candidates for kidney biopsy to confirm the diagnosis.
The nephrology team, including the renal clinical pharmacist, reviewed all the BKVN cases from January 2008 until December 2012 at the Royal Hospital. The systematic approaches in the prepared protocol were applied to all patients who were diagnosed with BKVN. The biographic data of all patients were filled in a designed spreadsheet. All the results were filled in the Excel data sheet and simple analytic method was used to generate the results.
Nineteen patients (6.3%) out of 300 kidney transplant recipients were diagnosed with BKV. All 19 patients were transplanted between 2005 and 2012. Of the 19 patients 11 were male and their mean age was 26.7 y (range, 6-52 y). All recipients were on mycophenolate mofetil-based immunosuppressant regimen among which 15, 3, and 1 were on tacrolimus, ciclosporin, and sirolimus (Figure 1). Only 1 patient was on a steroid-free regimen, while all others were on prednisolone as part of their immunosuppressants.
Most patients (90%) were induced by basiliximab, and only a few (10%) were given antithymoglobulin for induction.
Treatment of BKVN was step-wise as per the protocol. All patients were started with immunosuppressive dose reduction (n = 19). Five patients (26.3%) responded well after reducing their doses of tacrolimus and mycophenolate mofetil, and BKV was eradicated successfully without compromising the renal functions. In 9 patients (47.4%), tacrolimus was switched to sirolimus and ciporofloxacin was added to their regimen. Three patients (15.8%) received leflonamide as a substitution for mycophenolate mofetil and 6 patients (31.6%) received intravenous immunoglobulin along with the previous treatment options. Cidofovir was the last treatment given to 4 patients (21%).
Treatment options followed by the nephrologists were in accordance with the protocol, and the success rate of BKV eradication was high. Unfortunately, 2 (10.5%) patients experienced complete graft lost, despite all measures, to save the transplanted kidney from failing. On the other hand, all 17 patients (89.5%) were completely treated from BKVN with good renal function except four patients (21%), who were having their creatinine clearance less than 50 mL/min/1.73m2.
Approximately 60% of renal grafts with BKVN develop progressive graft loss.1 The incidence of BKVN in our patients was more than 6%, which is quiet high; fortunately, the graft survival rate was favorable, only 2 patients (10.5%) lost their graft and went back to renal replacement therapy, and 4 patients had their glomerular filtration rate < 50 mLmin/1.73m2.
Existing treatment of BKVN is scarce as there are no specifically effective antiviral agents currently available.2 The best strategy to eliminate BKV seems to be the prevention of BKVN. Brennan and associates concluded that potential monitoring of urine and blood for BKV and preemptive withdrawal of the antimetabolite upon development of BKV resulted in clearance of viremia and this appeared to decrease the risk of BKVN without increasing the risk of acute rejection.9
In many set-ups, primary approaches include minimizing or stopping the antimetabolite such as mycophenolate mofetil while concurrently keeping the calcineurin inhibitor trough levels at the lower side. Other approaches were to switch from calcineurin to another or switching from a calcineurin to sirolimus. The latter has been reported to decrease risk of BKVN. However, care must be taken because The current strategies of treatment as per the protocol developed appear to be effective, and the outcomes of our patients were satisfactory. Yet further validation of the protocol is warranted.
BK virus nephropathy is an emerging complication of kidney transplant. The prevalence is alarming and requires increasing awareness. The use of cidofovir, leflunomide, ciprofloxacin, and immunoglobulins remain questionable.3-8 Our audit confirms that reducing immunosuppression appears to be the best approach for treating BKVN until a safe antiviral agent becomes available to treat this condition.
Volume : 13
Issue : 1
Pages : 156 - 158
DOI : 10.6002/ect.mesot2014.O139
From the Department of Nephrology, Royal Hospital, Muscat, Oman
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Fatma Al-Raisi, Royal Hospital, Pharmacy Department, PO box 1331 PC 111 Al-Seeb, Oman
Phone: +968 2459 9403
Fax: +968 2459 9864
Figure 1. Immunosuppressive Regimens of Patients