|Year : 2017 | Volume
| Issue : 4 | Page : 328-330
Successful renal transplant in a pediatric patient with HIV-associated nephropathy
Anshuman Sood1, David Hakim1, Abhishek Bose2
1 Department of Medicine and Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland
2 Department of Urology, Narayan Medical College and Hospital, Jamuhar, Sasaram, Bihar, India
|Date of Submission||13-Mar-2016|
|Date of Acceptance||24-Oct-2016|
|Date of Web Publication||27-Sep-2017|
Department of Urology, Narayan Medical College and Hospital, Jamuhar, Sasaram, Bihar
Source of Support: None, Conflict of Interest: None
| Abstract|| |
HIV-associated nephropathy (HIVAN) is a pathological state of the kidneys due to longstanding, uncontrolled HIV infection. With the rapid progression of HIVAN to end-stage kidney failure, there is a significant potential for renal transplantation to improve the quality of life in these patients. Numerous studies have been recently published documenting renal transplantation as a primary treatment for HIVAN. With the use of highly active antiretroviral therapy, allograft and patient survival rates of HIV-infected persons are nearly identical to those who are HIV negative. Our case study documents the successful role of renal transplantation in treating HIVAN in a 9-year-old male child.
|How to cite this article:|
Sood A, Hakim D, Bose A. Successful renal transplant in a pediatric patient with HIV-associated nephropathy. Indian J Urol 2017;33:328-30
| Introduction|| |
HIV-associated nephropathy (HIVAN) in children (≤18) is a rare condition associated with significant morbidity/mortality universally. HIVAN in children has been shown in literature to be significantly more fatal than HIVAN in adults. Survival rates for children with HIVAN at 12, 24, 36, and 48 months after biopsy-proven diagnosis of HIVAN were 58%, 41%, 29%, and 15%, respectively. Survival rates for adults with HIVAN at 12, 24, 36, and 48 months after biopsy-proven diagnosis of HIVAN were 79%, 64%, 49%, and 37%, respectively. The United States Centre for Disease Control and Prevention has recommended renal transplantation as the first-line therapy for HIVAN in both children and adults since 1994.
| Case Report|| |
Our patient is an HIV-positive 9-year-old male child. The patient acquired HIV through vertical transmission from his mother. At the age of 8, the patient presented to the hospital with pulmonary edema and renal impairment with a serum creatinine of 69 μmol/L, an estimated glomerular filtration rate (eGFR) of 44 mL/min, and an HIV viral load of 32,000/mL. HIVAN was diagnosed on kidney biopsy.
Treatment of the patient during his primary admission consisted of continuous hemofiltration and subsequent transfer to hemodialysis. Highly active antiretroviral therapy (HAART) was also initiated, consisting of nelfinavir (50 mg/kg, oral, BID), lamivudine (4 mg/kg, oral, BID), and abacavir (8 mg/kg, oral, BID). Two months after initiation of HAART, the patient's viral load had reached undetectable levels (<50 copies/mL). Eight months after initiation of HAART, the patient underwent renal transplantation.
Based on guidelines set out by the European Association of Urology, the patient was deemed suitable for renal transplantation. he had a CD4 cell count of >200/mm3, undetectable viral load (<50 copies/mL), absence of AIDS-defining illnesses and was currently being administered HAART.
The donor kidney was from the patient's maternal uncle. The donor and the recipient were both blood group O. Both donor and recipient were Cytomegalovirus and Epstein–Barr virus negative.
Before operation, the patient was administered prophylaxis against common opportunistic infections in HIV-positive patients: co-trimoxazole for Pneumocystis jirovecii pneumonia (life-long), fluconazole for prevention against fungal infections (for first 12 weeks postoperatively), and isoniazid and pyrazinamide as prophylaxis against tuberculosis (for first 12 months posttransplantation). The specific regimen of HAART remained the same posttransplantation as it was deemed to be most effective and most suitable for a child of his age (nelfinavir, lamivudine, and abacavir).
Alemtuzumab, a CD-52 monoclonal antibody, was used as induction therapy in our patient. Tacrolimus, corticosteroids, and mycophenolate mofetil were used as maintenance therapy. Alemtuzumab was used as induction therapy due to its low risk of biopsy-proven acute rejection (BPAR) episodes in HIV-positive renal transplant recipients. Tacrolimus was started 8 weeks before transplantation at a dose of 0.15 milligrams, once daily, 5 times per week. The tacrolimus levels we were able to achieve preoperatively were 11.3 mcg/L.
The allograft kidney was successfully transplanted into the patient's right iliac fossa. There were no complications during surgery, and the total time of operation was 2 h 23 min. Due to the relatively tall height of the recipient for his age (147 cm), the allograft renal artery was deemed best fit and anastomosed to the recipient's external iliac artery. Immediate production of urine was seen 25 min after anastomoses. A Doppler flow probe surrounding the anastomosed renal artery confirmed sufficient profusion.
For the first 6 months posttransplantation, the patient's HIV viral load and CD4 cell count were evaluated every week. From the 7th month onward, the HIV viral load and CD4 cell count were evaluated on a monthly basis. For the entire 6 months posttransplantation, the patient's HIV viral load remained at undetectable levels while his CD4 cell count did not dip below 249/mm3. Tacrolimus levels were regularly monitored (once every week, for first six months) due to known drug interactions with the use of tacrolimus and nelfinavir, which is a protease inhibitor.
The patient presented 191 days after his transplant with severe neutropenia. A complete blood count and consultations confirmed that the neutropenia was most likely due to maintenance therapy with mycophenolate mofetil. Azathioprine was immediately substituted as maintenance therapy. On substitution with azathioprine, the patient's neutrophil count returned to normal (absolute neutrophil count = 5500) within 5 days.
Currently, the patient is 13 months posttransplant. He has good allograft function: plasma creatinine 59–62 μmol/L and eGFR 86–91 mL/min. No albuminuria is present (urine albumin: creatinine ratio 2.91 mg/mmol). No signs of rejection were observed. There was no development of donor-specific antibodies. Ultrasound showed no changes in the patient's native kidneys. The patient's current HIV viral load remains undetectable (and has been the entire time posttransplant) while his CD4 cell count currently is 913/mm. Tacrolimus levels are being observed very carefully and being kept within the range of 7.5–9.0 μg/L. Current tacrolimus dosage is 0.15 mg, one dose, 3 days per week.
| Discussion|| |
With highly effective HAART readily available, HIV infection is no longer a contraindication for renal transplantation.
In 2010, two major studies were published documenting the benefits and difficulties of renal transplantation in HIV-positive adults.,
These studies evaluated 323 HIV-positive adults, all of whom underwent renal transplantation as a treatment for their HIVAN. All 323 patients were followed up for at least 3 years. Allograft survival rates at 1 and 3 years posttransplant were 91% and 81%, respectively. Patient survival rates at 1 and 3 years were 94% and 89%, respectively. Despite respectable allograft and patient survival rates, these two studies showed a very high frequency of BPAR episodes in the renal allografts. The incidence of BPAR in the allografts was 39% and 46% at 1 and 3 years, respectively. The two studies concluded that the abnormally high incidence of BPAR episodes in HIV-positive transplant recipients was due to transplantation of deceased organ donor kidneys, use of rabbit anti-thymocyte globulin induction therapy, and use of cyclosporine immunosuppression. Based on the aforementioned results of the two studies, we decided to use a living donor allograft and we decided to use alemtuzumab as the induction therapy of choice.
Our use of tacrolimus as maintenance therapy presented a unique challenge. Tacrolimus has been shown to have a very narrow therapeutic window, a significant amount of variability of trough levels between individuals, and well-documented drug interactions with antiretroviral drugs., We were able to circumvent the side effects of tacrolimus by using a living donor kidney, which allowed us to first titrate tacrolimus to therapeutic levels over an 8-week period before transplantation. Achieving therapeutic tacrolimus levels (9–13 mcg/L) before transplantation allowed us to minimize drug interactions with nelfinavir.
We elected not to remove the patient's native kidneys despite recent studies demonstrating an increased risk of developing renal cell carcinoma in patients' native kidneys after transplantation.
Our case study substantiates that in children with HIV infection and end-stage renal disease, renal transplantation is a very viable treatment option for HIVAN and should be considered in all pediatric patients.
With the advent of today's highly effective antiretroviral therapies, the HIV viral load can remain at undetectable levels despite the lifelong immunosuppression associated with renal transplantation.
Financial support and sponsorship:
Conflicts of interest:
There are no conflicts of interest.
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