Retroperitoneal fibrosis as a postoperative complication following renal transplantation in cats.

OBJECTIVES: The aim of this report was to describe the clinical signs, diagnostic imaging findings, surgical management, histopathological findings, outcome and possible risk factors for cats that developed retroperitoneal fibrosis (RPF) following renal transplantation. METHODS: Medical records of cats that underwent renal transplantation and developed clinically significant RPF between 1995 and 2019 were reviewed. RESULTS: Eighty-one cats underwent 83 renal transplantations. Of these 81 cats, six developed clinically significant RPF. For all six cats, renal transplantation was performed using cold organ preservation solution and ureteral papilla implantation. Immunosuppression protocol included ciclosporin and prednisolone. All cats had at least one subtherapeutic trough ciclosporin level (<250 ng/ml) in the postoperative period. Cats presented with moderate-to-severe azotemia 39-210 days following renal transplantation. Abdominal ultrasonography and contrast pyelography revealed various degrees of hydroureter and hydronephrosis of the transplanted kidney. Surgical examination revealed a layer of dense fibrous tissue surrounding the transplanted kidney, ureter and bladder resulting in ureteral obstruction. Ureteral obstruction was managed by reimplantation of the proximal ureter or renal pelvis to the bladder. Histopathologic examination of the fibrous tissue and affected portion of the distal ureter revealed fibrous connective tissue with lymphoplasmacytic infiltration and perivascular inflammation suggestive of an autoimmune type reaction. Of the six cats, two died within 5 days after revision surgery, two developed signs consistent with recurrent partial ureteral obstruction (40 and 41 days after revision), one was euthanized 6 years later for an unrelated disease and one was lost to follow-up. CONCLUSIONS AND RELEVANCE: The incidence of RPF in this population of cats was relatively low (7%), but still represents a significant cause of morbidity and mortality. The cause of RPF remains unknown, although investigation into suboptimal immunosuppression as a potential cause for local rejection reaction is warranted.

Retroperitoneal fibrosis in feline renal transplant recipients: 29 cases (1998-2011).

OBJECTIVE: To evaluate features, treatment, and prognosis associated with retroperitoneal fibrosis that developed after renal transplantation in cats. DESIGN: Retrospective case series. ANIMALS: 29 cats. PROCEDURES: Medical records of cats that developed retroperitoneal fibrosis after renal transplantation at the College of Veterinary Medicine, University of Pennsylvania, between 1998 and 2011 were reviewed for signalment, date of transplantation, age, results of urine and blood analyses, blood pressure at the time of diagnosis, infectious disease and medication anamneses, anesthetic protocols, and intraoperative complications. RESULTS: Of 138 transplant recipients, 29 (21%) developed clinically important retroperitoneal fibrosis. Nineteen (66%) were male, and median age at the time of renal transplantation was 8 years (range, 4 to 13 years). Median number of days after transplantation to diagnosis of retroperitoneal fibrosis was 62 (range, 4 to 730 days; mean, 125 days). The most common clinical signs were lethargy and anorexia. All affected cats were azotemic (BUN concentration > 32 mg/dL; creatinine concentration > 2.0 mg/dL) and anemic (PCV < 35%) at the time of retroperitoneal fibrosis diagnosis, although cats were nonazotemic at the time of discharge following transplantation, and anemia was less pronounced. Twenty-five cats successfully underwent surgical ureterolysis in which scar tissue was dissected away from the allograft ureter to relieve extraluminal compression. Retroperitoneal fibrosis recurred in 6 (22%) cats a median of 180 days (range, 8 to 343 days) following the original diagnosis and was treated successfully by repeated ureterolysis. CONCLUSIONS AND CLINICAL RELEVANCE: Retroperitoneal fibrosis occurred in a substantial percentage of feline renal transplant recipients and should be considered a differential diagnosis in any feline renal transplant recipient with clinicopathologic findings, imaging abnormalities, or signs suggestive of obstructive uropathy.

Ureteral obstruction and hydronephrosis in a cat associated with retroperitoneal infarction.

A 9-month-old cat was presented for routine vaccination before rehoming. Physical examination revealed a palpable mass in the cranial abdomen. The right kidney was severely enlarged (6cmx4cm) on plain abdominal radiographs, and failed to opacify normally during intravenous urography. Ultrasonography demonstrated a hydronephrotic right kidney. During exploratory coeliotomy, a retroperitoneal mass was identified, adherent to the caudal edge of the right kidney, enveloping the ureter and blocking urine outflow. The ureter caudal to the mass was of normal size. Right ureteronephrectomy was performed; the mass was subsequently freed from adhesions to the caudal vena cava and sublumbar muscles and excised. Histopathological examination revealed the mass to be composed of both normal and necrotic adipose tissue and fibrous tissue surrounding the ureter and a thrombosed, recanalised vessel. This appearance was consistent with an area of infarction and fibrosis with obstruction of the ureter. The cat was clinically well 3 months postoperatively.

Analysis of 4.3 kilobases of divergent locus B of macaque retroperitoneal fibromatosis-associated herpesvirus reveals a close similarity in gene sequence and genome organization to Kaposi's sarcoma-associated herpesvirus.

We previously identified retroperitoneal fibromatosis-associated herpesvirus (RFHV) as a simian homolog of Kaposi's sarcoma-associated herpesvirus (KSHV) in a fibroproliferative malignancy of macaques that has similarities to Kaposi's sarcoma. In this report, we cloned 4.3 kb of divergent locus B (DL-B) flanking the DNA polymerase gene from two variants of RFHV from different species of macaque with a consensus degenerate hybrid oligonucleotide primer approach. Within the DL-B region of RFHV, viral homologs of the cellular interleukin-6, dihydrofolate reductase, and thymidylate synthase genes were identified, along with a homolog of the gammaherpesvirus open reading frame (ORF) 10. In addition, a homolog of the KSHV ORF K3, the modulator of immune recognition-1, was identified. Our data show a close similarity in sequence conservation, gene content, and genomic structure between RFHV and KSHV which strongly supports the grouping of these viral species within the same RV-1 rhadinovirus lineage and the hypothesis that RFHV is the macaque homolog of KSHV.

Retroperitoneal fibrosis in four cats following renal transplantation.

Four cats developed fibrosis within the retroperitoneal space following renal transplantation. In human transplant patients, retroperitoneal fibrosis is an uncommon complication following surgery and may be secondary to operative trauma, infection, deposition of foreign material in the operative field, urinary extravasation, and perirenal hemorrhage caused by trauma to the allograft. Possible causes of fibrosis in the cats of this report include abdominal inflammation associated with allograft rejection, pyelonephritis, and septic peritoneal effusion. All of the cats of this report were readmitted to the veterinary teaching hospital following renal transplantation because of recurrence of azotemia 1 to 5 months after transplantation. Abdominal ultrasonography revealed a 2- to 4-mm-thick capsule surrounding the allograft in 2 of 4 cats, hydronephrosis in 4 cats, and hydroureter proximally in 2 cats. An exploratory laparotomy was performed in all cats to remove the fibrotic tissue causing the ureteral obstruction. Normal renal function was restored in all cats following surgery. Histologic evaluation of biopsy specimens revealed smooth muscle (3 cats) and fibrous connective tissue (4). All 4 cats, regardless of the cause, responded well to surgical resection of the scar tissue that was causing a ureteral obstruction. None of the cats had recurrence of obstruction following surgery.

Characterization of two divergent lineages of macaque rhadinoviruses related to Kaposi's sarcoma-associated herpesvirus.

We have cloned and characterized the entire DNA polymerase gene and flanking regions from Kaposi's sarcoma-associated herpesvirus (KSHV) and two closely related macaque homologs of KSHV, retroperitoneal fibromatosis-associated herpesvirus-Macaca nemestrina (RFHVMn) and -Macaca mulatta (RFHVMm). We have also identified and partially characterized the corresponding genomic region of another KSHV-like herpesvirus, provisionally named "M. nemestrina rhadinovirus type 2 (MneRV-2)," with close similarity to rhesus rhadinovirus (RRV). A sequence comparison of these four macaque viruses and two KSHV-like gammaherpesviruses recently identified in African green monkeys, Chlorocebus rhadinovirus types 1 and 2 (ChRV-1 and ChRV-2) reveals the presence of two distinct lineages of KSHV-like rhadinoviruses in Old World primates. The first rhadinovirus lineage consists of KSHV and its closely related homologs RFHVMn, RFHVMm, and ChRV-1, while the second more distantly related lineage consists of RRV, MneRV-2, and ChRV-2. Our findings raise the possibility of the existence of another human KSHV-like herpesvirus belonging to the second rhadinovirus lineage.

Two distinct lineages of macaque gamma herpesviruses related to the Kaposi's sarcoma associated herpesvirus.

BACKGROUND: KSHV, Kaposi's sarcoma-associated herpesvirus, is a necessary cofactor for the development of Kaposi's sarcoma (KS). We have previously reported KSHV-related DNA sequences in retroperitoneal fibromatosis (RF) tissue from two species of macaque. The putative herpesvirus was called RFHV for RF-associated herpesvirus. These data suggested that KSHV is a human representative of a larger family of primate herpesviruses. OBJECTIVE: To identify and characterize other members of a putative family of KSHV-related herpesviruses in macaques in order to obtain information on the evolutionary history of KSHV infection in humans. STUDY DESIGN: Lymphoid tissue cells and blood leukocytes from rhesus-, cynomolgus- and pigtailed-macaques were tested for the presence of unknown herpesviruses using degenerate primer-driven PCR amplification. The sequences obtained were compared against known herpesvirus sequences. RESULTS: We have identified new herpesvirus DNA sequences in each of the three macaque species. Sequence comparisons indicate that these new viruses are most related to each other and form a separate phylogenetic lineage within the gamma herpesviruses. Screening of PBMC from Indonesian-origin quarantine animals suggests that these viruses (MGV, macaque gamma virus) are species-specific, and highly prevalent in the wild. They are readily cultured in vivo, and share a common tissue tropism with the previously identified RFHV. CONCLUSIONS: MGV and RFHV represent two independent introductions of an ancestral gamma herpesvirus into macaque precursors.

Localized retroperitoneal fibromatosis causing intestinal obstruction in a cynomolgus monkey (Macaca fascicularis).

Gross examination of a 24-month-old, male cynomolgus monkey (Macaca fascicularis) revealed obstruction of the ileum by a mass that entrapped and compressed the ileocecal junction. The mass was well circumscribed, firm, and white on cut surface. Histologically, the mass consisted of spindle-shaped cells arranged in interweaving bundles or as narrow cords and individual cells widely separated by dense collagen. A diagnosis of localized retroperitoneal fibromatosis was made based on the characteristic gross and microscopic findings and isolation of type D simian retrovirus, serotype-2, from spleen and mesenteric lymph node. Monkeys with localized retroperitoneal fibromatosis generally exhibit signs only of a palpable mass at the ileocecal junction and/or nonspecific diarrhea. This case represents an unusual presentation of localized retroperitoneal fibromatosis in which the lesion produced intestinal obstruction and death.

Distribution of type D retrovirus sequences in tissues of macaques with simian acquired immune deficiency and retroperitoneal fibromatosis.

Horizontally acquired SAIDS retrovirus type 2 (SRV-2), a type D retrovirus related to the Mason-Pfizer monkey virus, has been associated with the simian acquired immunodeficiency syndrome (SAIDS) including retroperitoneal fibromatosis (RF) in several macaque species at two primate research centers. Virus specific gene sequences are present in lymphoid and RF tissues but not in muscle tissue of diseased macaques or in any tissues of uninfected normal monkeys. Serologic and restriction endonuclease mapping techniques have defined unique SRV-2 strains in the Celebes (SRV-2C) and rhesus (SRV-2R) macaques at the Oregon Regional Primate Center, SRV-2 is related to both MPMV and SAIDS type 1 retroviruses and it has no detectable molecular homology with the human AIDS retroviruses.

Retroperitoneal fibromatosis and acquired immunodeficiency syndrome in macaques: epidemiologic studies.

At the University of Washington Regional Primate Research Center, a simian acquired immunodeficiency syndrome (SAIDS) associated with retroperitoneal fibromatosis (RF) has been observed in 82 macaques since 1976, including 77 pigtailed macaques (Macaca nemestrina), two long-tailed macaques (M. fascicularis), one Japanese macaque (M. fuscata) and two rhesus macaques (M. mulatta). The syndrome is characterized by immunodeficiency accompanied by a fibroproliferative lesion, primarily affects young monkeys (1-3 years) and has a high case fatality rate. Based on the occurrence of RF in colony-born and non-colony-born monkeys, the minimum incubation period for natural exposure is believed to be about 9 months. The incidence of RF was 0.9% in M. nemestrina, 0.1% in M. fascicularis, 1.0% in M. fuscata and 0.4% in M. mulatta. There were no significant differences in the incidence of RF by sex or seasonality. Epidemiologic studies were focused on 42 juvenile M. nemestrina that developed RF between January 1980 and June 1983, and the results were compared with 42 age- and sex-matched controls. The incidence of RF was 5.7% in monkeys 12-24 months old and 3.4% in monkeys 24-36 months old, but less than 1.0% in age groups of under 1 year and over 3 years. No significant associations were found for housing history, parentage, generations or ancestral origins. Epidemiologic information and preliminary viral studies suggest a type D retrovirus may be the causative agent in RF and SAIDS. RF associated with SAIDS appears to be an excellent model for Kaposi's sarcoma associated with human AIDS.

Retroperitoneal fibromatosis and acquired immunodeficiency syndrome in macaques. Pathologic observations and transmission studies.

A peculiar fibroproliferative syndrome called retroperitoneal fibromatosis (RF) has been observed in Macaca nemestrina, Macaca mulatta, Macaca fascicularis, and Macaca fuscata at the Washington Regional Primate Research Center. RF is characterized by the aggressive proliferation of highly vascular fibrous tissue subjacent to the peritoneum covering the ileocecal junction and associated mesenteric lymph nodes. In the early, proliferative phase of the disease, most of the fibroblastlike cells contain Factor VIII-related antigen. Two syndromes have been recognized: localized, in which fibroproliferative lesions occur only in solitary nodules; and progressive, in which fibromatosis occurs throughout the abdominal cavity. RF-affected monkeys often develop a simian acquired immunodeficiency syndrome (SAIDS) with severe thymic and lymphoid atrophy, chronic enterocolitis, and wasting. Experimental intraperitoneal inoculation with suspensions of RF tissue in two separate experiments resulted in the development of SAIDS in 5 of 16 and RF-SAIDS in 3 of 16 macaques. RF associated with SAIDS appears to be an excellent model for the Kaposi's sarcoma associated with AIDS.

Isolation of a unique retrovirus, MNV-1, from Macaca nemestrina.

Cell cultures established from the spleen of a Macaca nemestrina with enzootic retroperitoneal fibromatosis (ERF) spontaneously released a unique retrovirus. Throughout 14 serial passages, the spleen cell cultures remained fibroblastic and no cytopathic effect was evident. The virus incorporates [3H]uridine, contains an RNA-dependent DNA polymerase (RDDP), has a buoyant density of 1.15 g/cm3 in sucrose, and was designated MNV-1. Virion-associated reverse transcriptase showed no preference for either Mg2+ or Mn2+ in standard RDDP assays. Complementary DNA (cDNA) transcribed from polyadenylated MNV-1 RNA hybridized to genomic DNA and RNA extracted from diseased tissues but not to nucleic acids from normal tissues of a healthy Macaca nemestrina or a Macaca mulatta. MNV-1 is therefore exogenous to these species. MNV-1 had no detectable homology to the endogenous macaque virus isolates MAC-1 and MMC-1. Liquid hybridization of MNV-1 cDNA to viral RNA derived from exogenous and endogenous subhuman primate retroviruses (SiSV(SSAV), GALV-SF, BaEV-M7, and BILN) did not reveal any significant sequence homologies. In addition, MNV-1 does not share homology with bovine leukemia virus or Mason-Pfizer monkey virus as determined by Southern blot hybridization. We conclude that MNV-1 is a unique retrovirus which has not previously been described. As the ultrastructure of virions in in vitro cell cultures, as well as disease involved tissue, show some particles with type C morphology and others with type D morphology, MNV-1 may be comprised of more than one component.