Systematic review of ablative therapy for the treatment of renal allograft neoplasms

BACKGROUND To date,there are no guidelines on the treatment of solid neoplasms in the transplanted kidney.Historically,allograft nephrectomy has been considered the only reasonable option.More recently,nephron-sparing surgery (NSS) and ablative therapy (AT) have been proposed as alternative procedures in selected cases.AIM To review outcomes of AT for the treatment of renal allograft tumours.METHODS We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 Checklist.PubMed was searched in March 2019 without time restrictions for all papers reporting on radiofrequency ablation (RFA),cryoablation (CA),microwave ablation (MWA),high-intensity focused ultrasound (HIFU),and irreversible electroporation (IRE) of solid tumours of the kidney allograft.Only original manuscripts describing actual cases and edited in English were considered.All relevant articles were accessed in full text.Additional searches included all pertinent references.Selected studies were also assessed for methodological quality using a tool based on a modification of the Newcastle Ottawa scale.Data on recipient characteristics,transplant characteristics,disease characteristics,treatment protocols,and treatment outcomes were extracted and analysed.Given the nature and the quality of the studies available (mostly retrospective case reports and small retrospective uncontrolled case series),a descriptive summary was provided.RESULTS Twenty-eight relevant studies were selected describing a total of 100 AT procedures in 92 patients.Recipient age at diagnosis ranged from 21 to 71 years whereas time from transplant to diagnosis ranged from 0.1 to 312 mo.Most of the neoplasms were asymptomatic and diagnosed incidentally during imaging carried out for screening purposes or for other clinical reasons.Preferred diagnostic modality was Doppler-ultrasound scan followed by computed tomography scan,and magnetic resonance imaging.Main tumour types were: papillary renal cell carcinoma (RCC) and clear cell RCC.Maximal tumour diameter ranged from 5 to 55 mm.The vast majority of neoplasms were T1a N0 M0 with only 2 lesions staged T1b N0 M0.Neoplasms were managed by RFA (n = 78),CA (n = 15),MWA (n = 3),HIFU (n = 3),and IRE (n = 1).Overall,3 episodes of primary treatment failure were reported.A single case of recurrence was identified.Follow-up ranged from 1 to 81 mo.No cancer-related deaths were observed.Complication rate was extremely low (mostly < 10%).Graft function remained stable in the majority of recipients.Due to the limited sample size,no clear benefit of a single procedure over the other ones could be demonstrated.CONCLUSION AT for renal allograft neoplasms represents a promising alternative to radical nephrectomy and NSS in carefully selected patients.Properly designed clinical trials are needed to validate this therapeutic approach.

Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation

BACKGROUND Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless,long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also unclear.AIM To investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation.METHODS This single-centre observational study with a median follow up of 57(31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasmaquantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment,rejection, renal function, urologic complications, opportunistic infections, newonset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy.RESULTS BK-viremia was detected in 9.5% recipients. Initial viral load was high(≥ 10000 copies/mL) in 66.7% and low(< 10000 copies/mL) in 33.3% of these patients.Polyomavirus-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia(95% vs 25%, P < 0.00001), nephropathy(92.5% vs 15%, P <0.00001), and polyomavirus-related graft loss(27.5% vs 0%, P = 0.0108) than recipients with low initial viral load. Comparison between recipients with or without BK-viremia showed that the proportion of patients with Afro-Caribbean ethnicity(33.3% vs 16.5%, P = 0.0024), panel-reactive antibody ≥ 50%(30% vs14.6%, P = 0.0047), human leukocyte antigen(HLA) mismatching > 4(26.7% vs13.4%, P = 0.0110), and rejection within thirty days of transplant(21.7% vs 9.5%; P= 0.0073) was higher in the viremic group. Five-year patient and overall graft survival rates for patients with or without BK-viremia were similar. However,viremic recipients showed higher 5-year crude cumulative(22.5% vs 12.2%, P =0.0270) and 30-d-event-censored(22.5% vs 7.1%, P = 0.001) incidences of graft failure than control. In the viremic group we also observed higher proportions of recipients with 5-year estimated glomerular filtration rate < 30 mL/min than the group without viremia: 45% vs 27%(P = 0.0064). Urologic complications were comparable between the two groups. Response to treatment was complete in55%, partial in 26.7%, and absent in 18.3% patients. The nephropathy group showed higher 5-year crude cumulative and 30-d-event-censored incidences of graft failure than control: 29.1% vs 12.1%(P = 0.008) and 29.1% vs 7.2%(P <0.001), respectively. Our multivariable model demonstrated that Afro-Caribbean ethnicity, panel-reactive antibody > 50%, HLA mismatching > 4, and rejection were independent risk factors for BK-virus viremia whereas cytomegalovirus prophylaxis was protective.CONCLUSION Current treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panelreactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect.

Treatment options for localised renal cell carcinoma of the transplanted kidney

Currently,there is no consensus among the transplant community about the treatment of renal cell carcinoma(RCC)of the transplanted kidney.Until recently,graftectomy was universally considered the golden standard,regardless of the characteristics of the neoplasm.Due to the encouraging results observed in native kidneys,conservative options such as nephron-sparing surgery(NSS)(enucleation and partial nephrectomy)and ablative therapy(radiofrequency ablation,cryoablation,microwave ablation,high-intensity focused ultrasound,and irreversible electroporation)have been progressively used in carefully selected recipients with early-stage allograft RCC.Available reports show excellent patient survival,optimal oncological outcome,and preserved renal function with acceptable complication rates.Nevertheless,the rarity and the heterogeneity of the disease,the number of options available,and the lack of long-term follow-up data do not allow to adequately define treatment-specific advantages and limitations.The role of active surveillance and immunosuppression management remain also debated.In order to offer a better insight into this difficult topic and to help clinicians choose the best therapy for their patients,we performed and extensive review of the literature.We focused on epidemiology,clinical presentation,diagnostic work up,staging strategies,tumour characteristics,treatment modalities,and follow-up protocols.Our research confirms that both NSS and focal ablation represent a valuable alternative to graftectomy for kidney transplant recipients with American Joint Committee on Cancer stage T1aN0M0 RCC.Data on T1bN0M0 lesions are scarce but suggest extra caution.Properly designed multi-centre prospective clinical trials are warranted.

Allograft artery mycotic aneurysm after kidney transplantation: A case report and review of literature

BACKGROUND Allograft artery mycotic aneurysm(MA)represents a rare but life-threatening complication of kidney transplantation.Graftectomy is widely considered the safest option.Due to the rarity of the disease and the substantial risk of fatal consequences,experience with conservative strategies is limited.To date,only a few reports on surgical repair have been published.We describe a case of true MA successfully managed by aneurysm resection and arterial re-anastomosis.CASE SUMMARY An 18-year-old gentleman,on post-operative day 70 after deceased donor kidney transplantation,presented with malaise,low urinary output,and worsening renal function.Screening organ preservation fluid cultures,collected at the time of surgery,were positive for Candida albicans.Doppler ultrasound and contrastenhanced computer tomography showed a 4-cm-sized,saccular aneurysm of the iuxta-anastomotic segment of the allograft artery,suspicious for MA.The lesion was wide-necked and extended to the distal bifurcation of the main arterial branch,thus preventing endovascular stenting and embolization.After multidisciplinary discussion,the patient underwent surgical exploration,aneurysm excision,and re-anastomosis between the stump of the allograft artery and the internal iliac artery.The procedure was uneventful.Histology and microbiology evaluation of the surgical specimen confirmed the diagnosis of MA caused by Candida infection.Three years after the operation,the patient is doing very well with excellent allograft function and no signs of recurrent disease.CONCLUSION Surgical repair represents a feasible option in carefully selected patients with allograft artery MA.Anti-fungal prophylaxis is advised when preservation fluid cultures are positive.