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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 13  |  Issue : 1  |  Page : 67-72  

Use and outcomes of kidneys from donors with renal angiomyolipoma: A systematic review


1 Department of Internal Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, Mississippi, USA
2 Department of Medicine, Division of Nephrology, Deaconess Health System, Evansville, IN, USA
3 Department of Internal Medicine, University of Arizona, Tucson, AZ, USA
4 Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
5 Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok, Thailand
6 Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, Florida, USA
7 Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York, USA
8 Department of Transplant and Hepatobiliary Surgery, University of Mississippi Medical Center, Jackson, Mississippi, USA

Date of Submission23-Feb-2020
Date of Acceptance25-Aug-2020
Date of Web Publication19-Jan-2021

Correspondence Address:
Wisit Cheungpasitporn
Department of Internal Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, Mississippi 39216
USA
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DOI: 10.4103/UA.UA_14_20

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   Abstract 


Background: Renal angiomyolipoma (AML) is the most frequent mesenchymal tumor of the kidney. Although there is a rare possibility of malignant transformation of AML, this risk has not been studied in immunosuppressed patients. The safety of donors with AML and their kidney transplant recipients has not been well established.
Methods: A literature search was conducted utilizing MEDLINE, EMBASE, and Cochrane databases from inception through May 15, 2018 (updated on October 2019). We included studies that reported the outcomes of kidney donors with AML or recipients of donor with AML. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095157).
Results: Fourteen studies with a total of 16 donors with AML were identified. None of the donors had a diagnosis of tuberous sclerosis complex (TSC), pulmonary lymphangioleiomyomatosis (LAM), or epithelioid variant of AML. Donor age ranged from 35 to 77 years, and recipient age ranged from 27 to 62 years. Ninety-two percent of the donors were female. Only 8% were deceased donor renal transplant. The majority underwent ex vivo resection (65%) before transplantation, followed by no resection (18%), and the remaining had in vivo resection. Tumor size varied from 0.4 cm to 7 cm, and the majority (87%) were localized in the right kidney. Follow-up time ranged from 1 to 107 months. Donor creatinine prenephrectomy ranged 0.89–1.1 mg/dL and postnephrectomy creatinine 1.0–1.17 mg/dL. In those who did not have resection of the AML, tumor size remained stable. None of the donors with AML had end-stage renal disease or died at last follow-up. None of the recipients had malignant transformation of AML.
Conclusion: These findings are reassuring for the safety of donors with AML (without TSC or LAM) as well as their recipients without evidence of malignant transformation of AML. As such, this can also positively impact the donor pool by increasing the number of available kidneys.

Keywords: Donor, kidney transplant, renal angiomyolipoma, renal transplantation, transplantation


How to cite this article:
Anton DG, Kovvuru K, Kanduri SR, Aeddula NR, Bathini T, Thongprayoon C, Kaewput W, Wijarnpreecha K, Watthanasuntorn K, Salim SA, Matemavi P, Vaitla P, Rivera FC, Cheungpasitporn W. Use and outcomes of kidneys from donors with renal angiomyolipoma: A systematic review. Urol Ann 2021;13:67-72

How to cite this URL:
Anton DG, Kovvuru K, Kanduri SR, Aeddula NR, Bathini T, Thongprayoon C, Kaewput W, Wijarnpreecha K, Watthanasuntorn K, Salim SA, Matemavi P, Vaitla P, Rivera FC, Cheungpasitporn W. Use and outcomes of kidneys from donors with renal angiomyolipoma: A systematic review. Urol Ann [serial online] 2021 [cited 2021 Feb 26];13:67-72. Available from: https://www.urologyannals.com/text.asp?2021/13/1/67/307374




   Introduction Top


Kidney transplantation (KTx) is the modality of choice for patients with end-stage renal disease (ESRD) as it improves the quality of life and the survival.[1],[2] Kidney transplant recipients have an increased life expectancy by 3–15 years compared to people on renal replacement therapies.[3] Even though the number of kidney transplants are steadily increasing every year, they are not able to exceed wait-listed ESRD patients. Efforts to expand the donor pool by accepting donors with marginal criteria could help mitigate the shortage. There is still a scarcity of available donors more so in the regions of the world where there is a lack of established living and deceased donor programs.[4] One feasible solution to expand the living donor pool is to include the donors with renal lesions which are amenable for transplant with less potential long-term risk to the immunocompromised recipients.[5]

Renal angiomyolipoma (AML) is the most frequent mesenchymal tumor of the kidney.[6] Although first referenced in 1900,[7] its histopathology was originally described by Fischer in 1911.[8] Renal AML is a heterogeneous, triphasic tumor with varying elements of smooth muscle, adipose tissue, and vascular elements.[9] Renal AML can occur sporadically with an incidence ranging from 55% to 80%[10] or in association with the tuberous sclerosis complex (TSC) in about 20%–30% and very rarely as sporadic lymphangioleiomyomatosis (LAM).[11],[12] The sporadic forms of AML are typically small, solitary, unilateral, and predominantly seen middle-aged women.[13],[14] The diagnosis of the AML is commonly asymptomatic and could be detected incidentally on imaging in more than 80% of the cases. However, in tumors >4 cm in size, they could present with clinical manifestations of left flank pain, tender mass, hematuria, and fatigue.[15],[16],[17] Less than 15% manifests as hemorrhage at the presentation (Wunderlich syndrome), a potential emergency needing immediate intervention, whereas less than 10% of them appear with hypovolemic shock.[18]

Renal AML is usually benign and a true malignant AML is rare.[6] Risk factors for malignant AML include size >7 cm, tumor necrosis, and epithelioid carcinoma-like pattern.[19] The historical criteria for active intervention of renal AML are symptomatic lesions >4 cm with risk of rupture, intolerable pain, hemorrhagic hypovolemic shock, suspected malignancy, especially in renal AML associated with TSC, and females of childbearing age.[20] Although there is a rare possibility of malignant transformation of the AML, the risk is not studied in immunosuppressed patients such as kidney transplant recipients.

The first report of a direct live donor KTx after ex vivo excision of the AML is reported in 1993.[21] Since then, multiple cases and single-center series of successful live and cadaveric donor transplantations were reported after ex vivo and ex vitro incisions.[22],[23],[24] There is still a dearth of knowledge of the safety of donors with AML and their kidney transplant recipients. In this context, we have conducted a systematic review to use and the outcomes of kidneys from donors with renal AML.


   Methods Top


Search strategy

The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095157). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement[25] was followed in conducting this systematic review. Ovid MEDLINE, EMBASE, and the Cochrane databases were systemically searched from database inceptions through May 15, 2018, and updated on October 2019. We conducted a literature search to identify all potential studies that reported the outcomes of kidney donors with AML or recipients of donor with AML. Two investigators (D. G. A. and C. T.) performed an independent literature search using the search terms of“angiomyolipoma” AND (“donor” AND“renal” OR“kidney”). Language restriction was not applied. Potentially related studies are manually reviewed using the references.

Study selection

Observational studies, clinical trials, case series, or case reports providing data on the use of kidneys from donors with renal AML were included in the systematic review. Two investigators (D. G. A. and C. T.) independently reviewed retrieved articles for eligibility. A third reviewer (W. C.) solved inconsistencies by collective agreement.

Data collection

The following data were collected from individual studies: title, name of authors, year of the study, publication year, country where the study was conducted, recipient characteristics, donor characteristics, age and sex of donor and recipient, cause of ESRD, and tumor size and outcomes.


   Results Top


A total of 84 potentially eligible articles were identified with our search approach. After excluding 52 articles based on title and abstract for clearly not fulfilling inclusion criteria on the basis of the type of article, patient population, animal studies, or duplicates, 32 articles remained for full-length article review. Eighteen articles did not report the outcomes of kidney donors with AML or recipients of donor with AML. Therefore, 14 studies[15],[21],[22],[23],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35] with a total of 16 donors with AML were identified. The systematic review of the literature flowchart is demonstrated in [Figure 1].
Figure 1: The flowchart for the systematic review

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None of the donors had a diagnosis of TSC, pulmonary LAM, or epithelioid variant of AML. Donor age ranged from 35 to 77 years, and recipient age ranged from 27 to 62 years. Ninety-two percent of the donors were female. Only 8% were deceased donor renal transplant [Figure 2]. The majority underwent ex vivo resection (65%) before transplantation, followed by no resection (18%), and the remaining had in vivo resection. Donor age ranged from 35 to 77 years, and recipient age ranged from 27 to 62 years. Ninety-two percent of the donors were female. Only 8% were deceased donor renal transplant.
Figure 2: Characteristics of recipients of donor with angiomyolipoma and kidney donors with angiomyolipoma. Abbreviations: ESRD: End-stage renal disease, MPGN: Membranoproliferative glomerulonephritis, PCKD: Polycystic kidney disease, GN: Glomerulonephritis, IgA: Immunoglobulin A, ATN: Acute tubular necrosis, FSGS: Focal segmental glomerulosclerosis, HTN: Hypertension, PVD: Peripheral vascular disease, TXP: Transplant

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The majority underwent ex vivo resection (65%) before transplantation, followed by no resection (18%), and the remaining had in vivo resection. Tumor size varied from 0.4 cm to 7 cm, and the majority (87%) were localized in the right kidney. Follow-up time ranged from 1 to 107 months [Figure 3].
Figure 3: Tumor size and outcomes of recipients of donor with angiomyolipoma. Abbreviations: F/U: Follow-up, Cr: Creatinine, TSC: Tuberous sclerosis complex, IS: Immunosuppression, CNI: Calcineurin inhibitor, m: Month, yr: Year, cm: Centimeters, CrCl: Creatinine clearance

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Donor creatinine prenephrectomy ranged 0.89–1.1 mg/dL and postnephrectomy creatinine 1.0–1.17 mg/dL. In those who did not have resection of the AML, tumor size remained stable. None of the donors with AML had ESRD or died at last follow-up. None of the recipients had malignant transformation of AML.


   Discussion Top


Renal AML and renal cysts are common renal lesions of TSC complex. A two-hit hypothesis has been proposed to explain the pathophysiology. TSC has autosomal dominant inheritance with mutations in TS1 and TS2 genes encoding for hamartin and tuberin proteins, respectively. The second hit could be a superadded viral/bacterial infection, smoking, or other etiologies which could potentiate a plethora of the symptoms. Hamartin and tuberin proteins form a complex which would further downregulate the activity of mammalian target of rapamycin (mTOR) activity. Mutation is these proteins might potentiate further cell growth, proliferation, and increased vascular endothelial growth factor activation leading to renal cyst formation.[36],[37],[38],[39] With tumors >4 cm and potential vascular aneurysm, compression of renal parenchyma further contributes to chronic kidney disease with worsening renal failure, urinary concentration defects, and essential hypertension.

Diagnosis of AML is commonly based on imaging characteristics as clinical features are rarely seen. Ultrasound, computed tomography (CT) abdomen, and magnetic resonance imaging (MRI) are frequent modalities in practice. Ultrasound is simple, most available, affordable modality, however, it is neither sensitive nor specific in diagnosing AML lesions. Hyperechoic lesion with acoustic shadowing is typically seen on a fat-rich lesion on ultrasound.[10] This pattern could be seen with most other renal malignancies, and hence, ultrasound is not very reliable. Unenhanced CT abdomen is a commonly used diagnostic modality of choice. Based on fat quantification, renal AML is classified as fat-rich, fat-poor, and fat-invisible AMLs. Fat poor and fat invisible are not clearly differentiated by abdominal CT. MRI abdomen is very sensitive in diagnosing and distinguishing fat-poor AML lesions from renal malignancies.[40],[41] Renal biopsy can provide an accurate diagnosis of AML, however, it is rarely performed considering the risk of tumor rupture and hemorrhage.[42]

There have been no prospective randomized trials comparing surveillance and treatment for AML. 2012 consensus guidelines recommend mTOR inhibitors (everolimus) as modality of choice treatment for asymptomatic renal AML associated with TSC larger than 3 cm in size.[43],[44] The goal of treatment is to pursue a regression of the size of the tumor. Treatment with mTOR inhibitors is not approved for idiopathic renal AML. There are multiple case reports highlighting the effects of everolimus in reducing the tumor size of hamartomas of greater than 20 cm.[44] Side effect profile, especially after KTx, includes impaired wound healing, proteinuria, renal dysfunction, hyperlipidemia, stomatitis, and acne-like symptoms.[23],[45],[46]

With tumors >4 cm, the risk of vascular complications and retroperitoneal hemorrhage is high. Nephron-sparing techniques are first-line treatment to reduce the risk of chronic kidney disease and eventual ESRD. They include radiofrequency ablation microwave ablation techniques, selective arterial embolization, and partial nephrectomy.[47] However, given an increased risk of recurrence up to 40%, close surveillance and monitoring is recommended.[48] Total nephrectomies are reserved for larger lesions with suspicion for malignancies and as emergent life-saving procedures.[49],[50]

There has been no specific protocol for surveillance for asymptomatic patients with renal AML.[47] However, an expert panel recommends physical examination and imaging studies done at 6 months and annually, especially for patients with high risk of spontaneous rupture and bleeding.[51],[52] Ultrasound can be used for follow-up once the diagnosis is made. Checking glomerular filtration rate, urine analysis, serum creatinine, and blood pressure monitoring are indicated in assessing renal functions periodically. A team approach including urologist, general surgeon, nephrologist, and radiologist might together help navigate the donor with AML and help to increase the organ pool with benign kidney lesions.[22]

There has been a plethora of growing literature with case reports of successful renal transplantation after excision of AML. Postoperative 5-year follow-up did not demonstrate a significant increase in size of the tumor despite immunosuppression. Although it might not solve the global problem of kidney transplant shortage, it could certainly pave the way for the recipients whose only available donors have benign renal AML. Hence, patients with small, sporadic, asymptomatic renal AML can be included in donor pool with favorable donor and recipient outcomes.


   Conclusion Top


In summary, these findings of our systematic review are reassuring for the safety of donors with AML (without TSC or LAM) as well as their recipients without evidence of malignant transformation of AML. As such, this can also positively impact the donor pool by increasing the number of available kidneys.

Authors' contributions

All authors had access to the data and a role in writing the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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