Outcomes of Renal Transplantation in ANCA-Associated Vasculitis.

BACKGROUND Antineutrophil cytoplasmic antibody-associated vasculitis is characterized by small-vessel inflammation and ANCA-positive serology that often lead to end-stage kidney disease. This study investigated the outcomes of renal transplantation in patients with antineutrophil cytoplasmic antibody-associated vasculitis. MATERIAL AND METHODS A comprehensive search of PubMed, Scopus, and Embase databases was done to retrieve studies that reported on the outcomes of renal transplantation in these patients. Data on mortality, survival, infection, and relapse rates were analyzed. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale for cohort studies. RESULTS Twenty-three retrospective cohort studies were included in this review. Antineutrophil cytoplasmic antibody-associated vasculitis was associated with high post-transplantation mortality rates, with a pooled rate ratio of 11.99 per 100 patient-years, but relatively favorable survival rate (hazard rate of 0.80). After renal transplantation, these patients had elevated infection rates (pooled rate ratio of 52.70 per 100 patient-years), and high risk of relapse (pooled rate ratio of 6.96), emphasizing the importance of vigilant post-transplantation monitoring. CONCLUSIONS End-stage kidney disease patients with vasculitis, undergoing renal transplantation, are at elevated risk of mortality and postoperative infection compared to patients without antineutrophil cytoplasmic antibody-associated vasculitis. The risk of relapse is also high in these patients. However, renal transplantation offers a survival advantage for vasculitis patients who survive the early post-transplantation period.

Renal Transplantation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Center 10-Year Experience.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of rapidly progressive glomerulonephritis resulting in end-stage renal disease. The optimal timing of kidney transplantation for end-stage renal disease due to AAV and the risk of relapse after kidney are poorly defined. Our study aimed to evaluate the clinical outcomes of AAV after kidney transplantation, namely the risk of relapse, rejection, and oncologic disease. METHODS: This retrospective study included all patients with AAV submitted to a kidney transplant between January 2011 and December 2020. RESULTS: Twenty-seven patients (20 males/7 females; mean age 47 years) received a kidney transplant for end-stage renal disease secondary to microscopic polyangiitis (n = 25) or granulomatosis with polyangiitis (n = 2). All patients were in clinical remission at the time of the kidney transplant, but 11 patients were ANCA-positive. A vasculitis relapse after kidney transplantation occurred in only 1 patient (3.7%). Rejection episodes, proven by allograft biopsy, were present in 3 patients (11.1%), with graft losses in 2 (66.7%). The median time until the graft was lost after the initial rejection diagnosis was 27 ± 8 months. Oncologic complications were present in 9 patients (33.3%). Five patients died (18.5%), and the main cause of death was cardiovascular disease (n = 3, 60.0%), followed by oncologic disease (n = 2, 40.0%). CONCLUSIONS: Kidney transplantation is a safe and effective option for treating end-stage renal disease secondary to AAV. Current immunosuppression regimens make relapses and rejection infrequent but place oncologic complications at a higher incidence.

Association of renal transplantation with reduced risk of myocardial infarction and ischemic stroke in ANCA-associated vasculitis: An observational cohort study.

OBJECTIVE: Myocardial infarction and ischemic stroke are leading causes of cardiovascular (CV) morbidity and mortality in ANCA-associated vasculitis (AAV), especially for the 20% with end-stage renal disease (ESRD). We assessed the impact of renal transplantation on the risk of myocardial infarction and stroke among patients with ESRD due to AAV. METHODS: We identified patients from the United States Renal Data System with ESRD due to AAV between 2000 and 2016. We examined the association between renal transplantation and the risk of non-fatal and fatal myocardial infarction or ischemic stroke among waitlisted patients using Medicare claims and death data through 2017. We used time-varying Cox proportional hazards models with age as the time scale to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for myocardial infarction and ischemic stroke events among patients who received a renal transplant compared to those who remained on the waitlist. RESULTS: Of 1029 waitlisted patients, 593 (58%) were transplanted over a mean of 5.7 years. There were 17 events (4.6/1,000 person-years) in the transplanted group and 40 events (13.7/1,000 person-years) in the group that remained waitlisted. A renal transplant was associated with a 78% lower risk of myocardial infarction or ischemic stroke (HR=0.22, 95% CI 0.11 to 0.47). These findings persisted across sex and age groups and when censoring patients after living donor transplantation. CONCLUSIONS: Among AAV patients with ESRD, renal transplantation can substantially reduce the risk of myocardial infarction and ischemic stroke. Improving access to transplantation for this population may further improve outcomes.

Renal Transplantation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Current Perspectives.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is the leading cause of rapidly progressive glomerulonephritis, which may follow an unfavorable disease course. Despite therapeutic advances, a number of patients with AAV will eventually develop end-stage renal disease (ESRD). Renal transplantation (RTx) is associated with a survival benefit and improves quality of life in patients with ESRD. SUMMARY: In recent years, RTx has been increasingly used also in patients with vasculitis. The posttransplant patient- and graft-survival rates in AAV were at least comparable to other diagnoses in most studies. Prior to transplantation, patients should be in stable remission for 12 months. Persistent ANCA positivity does not exclude patients from the waiting list. Even though the recurrence risk is generally low with modern posttransplant immunosuppression, including mycophenolate mofetil and tacrolimus, patients with AAV, particularly those with positive antiproteinase-3 ANCA who may have increased risk of relapse or recurrence of the disease, require constant surveillance. Similar to treatment of relapsing disease in the nontransplant setting, rituximab may become treatment of choice for posttransplant recurrences. Key Messages: RTx is the preferred renal replacement therapy of choice for AAV patients with ESRD. It is recommended that patients should be in remission for about 12 months prior to proceeding with RTx. ANCA positivity alone is not a contraindication for transplantation. The risk of relapse posttransplantation is minimal with currently used posttransplant immunosuppressive regimen.

Long-term outcome of renal transplantation in childhood-onset anti-neutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: There have been a few reports of RTx for AAV in children; however, post-transplant recurrence rate and long-term prognosis remain unclear. Here, we describe the long-term outcomes of RTx in childhood-onset AAV. METHODS: We conducted a retrospective study of children who underwent RTx for AAV between 1999 and 2017 and had a follow-up period of >2 years. RESULTS: Seven patients consisting of three children with MPA and four with RLV were analyzed. Age at Dx was 5.9 (median; range, 4.1-14.5) years. PD was instituted in all patients, and median time on dialysis was 26 (range, 14-63) months. Age at RTx was 12.8 (median; range, 8.7-16.3) years. There were no recurrences of AAV noted during the median follow-up period of 7.0 (range, 2.7-18.8) years after RTx. Graft loss occurred in one patient due to non-adherence. Estimated glomerular filtration rate of the remaining patients at the last follow-up was 73.0 (median; range, 50.7-93.9) mL/min/1.73 m2 . No malignancies and deaths occurred during the observational period. CONCLUSIONS: Our study suggests that RTx for AAV with ESRD is a potentially safe and effective treatment choice for children with AAV.

Kidney transplantation in ANCA-associated vasculitis.

The kidney is commonly affected in patients with ANCA-associated vasculitis (AAV), causing end-stage renal disease (ESRD) in 20-40% of cases. Kidney transplantation is the treatment of choice for eligible patients with ESRD due to AAV. This review provides a summary of patient and graft outcome after kidney transplantation in AAV patients, the risk of relapse and the optimal time of transplantation. We also address the rare event of de novo ANCA-associated vasculitis after kidney transplantation and the treatment options.

The Dutch Transplantation in Vasculitis (DUTRAVAS) Study: Outcome of Renal Transplantation in Antineutrophil Cytoplasmic Antibody-associated Glomerulonephritis.

BACKGROUND: Data on the outcome of renal transplantation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (AAGN) patients are still limited. In particular, how disease recurrence in the renal allograft defines graft outcome is largely unknown. Therefore, we conducted a multicenter observational clinical and histopathological study to establish recurrence rate of AAGN in the allograft and the impact of recurrence on allograft survival. METHODS: Using the nationwide Dutch Pathology Registry (PALGA), we retrospectively collected clinical and histopathological data of consecutive AAGN patients who had developed end-stage renal failure and received a kidney allograft in 1 of 6 Dutch university hospitals between 1984 and 2011. Transplant biopsies were scored using the Banff '09 classification. Renal disease recurrence was scored using the histopathological classification of AAGN. RESULTS: The posttransplantation recurrence rate of AAGN was 2.8% per patient year, accumulating to recurrence in a total of 11 of 110 AAGN patients within the first 5 years after transplantation. Four of these 11 patients lost their graft, with 1-year and 5-year graft survival rates of 94.5% and 82.8%, respectively. By multivariate analysis, AAGN recurrence was independently associated with subsequent graft loss. CONCLUSIONS: In this study in 110 Dutch patients, the recurrence rate of AAGN within 5 years after kidney transplantation appeared slightly higher than in previous reports. Moreover, recurrence of AAGN contributed independently to kidney allograft loss, emphasizing the importance of clinical vigilance, because early treatment might be critical to rescuing the allograft.

Kidney transplantation for a patient with refractory childhood-onset ANCA-associated vasculitis.

A 14-year-old Japanese girl was admitted to our institution for the evaluation of renal dysfunction. Her serum creatinine was 1.1 mg/dL, proteinuria was 1.5 g/day, the urine sediment contained numerous erythrocytes per high-power field, and she was positive for myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). Proteinuria was first noted at the age of 12 years. Renal biopsy showed crescentic glomerulonephritis with slight immunoglobulin A (IgA) deposition. A diagnosis of ANCA-associated vasculitis was made. Immunosuppressive therapy was initiated, including steroid pulse therapy and intravenous cyclophosphamide pulse therapy, but hemodialysis was required after 6 years. Eight months after the patient became anuric and her MPO-ANCA titer became negative, living-related donor kidney transplantation was done from her mother. ANCA became slightly positive 2 years later, but the patient remains stable without proteinuria or hematuria at 4 years after surgery. This case suggests that kidney transplantation can be performed successfully for a patient with refractory childhood-onset ANCA-associated vasculitis, and that remission of vasculitis associated with ANCA negativity at transplantation may contribute to a better renal prognosis in this patient.

Primary disease recurrence­effects on paediatric renal transplantation outcomes.

Primary disease recurrence after renal transplantation is mainly diagnosed by examination of biopsy samples, but can also be associated with clinical symptoms. In some patients, recurrence can lead to graft loss (7-8% of all graft losses). Primary disease recurrence is generally associated with a high risk of graft loss in patients with focal segmental glomerulosclerosis, membranous proliferative glomerulonephritis, primary hyperoxaluria or atypical haemolytic uraemic syndrome. By contrast, disease recurrence is associated with a limited risk of graft loss in patients with IgA nephropathy, renal involvement associated with Henoch-Schönlein purpura, antineutrophil cytoplasmic antibody-associated glomerulonephritis or lupus nephritis. The presence of systemic diseases that affect the kidneys, such as sickle cell anaemia and diabetes mellitus, also increases the risk of delayed graft loss. This Review provides an overview of the epidemiology, pathophysiology and management of primary disease recurrence in paediatric renal graft recipients, and describes the overall effect on graft survival of each of the primary diseases listed above. With appropriate management, few paediatric patients should be excluded from renal transplantation programmes because of an increased risk of recurrence.

Buena respuesta al tratamiento quirúrgico y micofenolato en mujer con pseudotumor inflamatorio secundario a vasculitis ANCA positivo / Good response to surgical treatment and mycophenolate in woman with inflammatory pseudotumor secondary to ANCCA positive vasculitis

Presentamos el caso de una mujer joven con vasculitis ANCA positivo y pseudotumor inflamatorio como manifestación granulomatosa, que cursó con buena repuesta a la exéresis quirúrgica y micofenolato mofetilo (AU)

We present the case of a young woman with ANCA positive vasculitis and inflammatory pseudotumor as a granulomatous manifestation, who had a good response to surgical removal and mycophenolate mofetil (AU)

Early excision and grafting, an alternative approach to the surgical management of large body surface area levamisole-adulterated cocaine induced skin necrosis.

Levamisole-adulterated cocaine as a cause of retiform purpura progressing to full-thickness skin necrosis was first documented in 2003 and currently comprises over 200 reported cases. Whereas, its presentation, pathophysiology, and diagnostic workup have been reasonably well-defined, only one publication has significantly detailed its surgical management. For this reason there exists a relative absence of data in comparison to its reported incidence to suggest a preferred treatment strategy. In the case mentioned, treatment emphasized delayed surgical intervention while awaiting lesion demarcation and the monitoring of autoantibodies. At our institution we offer an alternative approach and present the case of a 34 year old female who presented with 49% TBSA, levamisole-induced skin necrosis managed with early surgical excision and skin grafting. The patient presented three days following cocaine exposure with painful, purpura involving the ears, nose, buttocks, and bilateral lower extremities which quickly progressed to areas of full-thickness necrosis. Lab analysis demonstrated elevated p-ANCA and c-ANCA, as well as leukopenia, decreased C4 complement, and urinalysis positive for levamisole, corroborating the diagnosis. Contrasting the most thoroughly documented case in which the patient underwent first surgical excision on hospital day 36 and underwent 18 total excisions, our patient underwent first excision on hospital day 10 and received only one primary excision prior to definitive autografting. To our knowledge, this is the largest surface area surgically treated that did not result in surgical amputation or autoamputation of limbs or appendages, respectively. We contend that early excision and grafting provides optimal surgical management of this syndrome while avoiding the morbidity seen with delayed intervention.

Heart transplantation in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

BACKGROUND: Heart involvement is the leading cause of death of patients with eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome) and is more frequent in anti-neutrophil cytoplasm antibody (ANCA)-negative patients. Post-transplant outcome has only been reported once. METHODS: We conducted a retrospective international multicenter study. Patients satisfying the criteria of the American College of Rheumatology and/or revised Chapel Hill Consensus Conference Nomenclature were identified by collaborating vasculitis and transplant specialists, and the help of the Churg-Strauss Syndrome Association. RESULTS: Nine ANCA(-) patients who received transplants between October 1987 and December 2009 were identified. The vasculitis and cardiomyopathy diagnoses were concomitant for 5 patients and separated by 12 to 288 months for the remaining 4 patients. Despite ongoing immunosuppression, histologic examination of 7 (78%) patients' explanted hearts showed histologic patterns suggestive of active vasculitis. The overall 5-year survival rate was low (57%), but rose to 80% when considering only the 6 patients transplanted during the last decade. After survival lasting 3 to 60 months, 4 (44%) patients died sudden deaths. CONCLUSIONS: The search for EGPA-related cardiomyopathy is mandatory early in the course of this type of vasculitis. Indeed, prompt treatment with corticosteroids and cyclophosphamide may achieve restore cardiac function. Most patients in this series were undertreated. For patients with refractory EGPA, heart transplantation should be performed, which carries a fair prognosis. No optimal immunosuppressive strategy has yet been identified.

Antineutrophil cytoplasmic antibody-associated renal vasculitis treated with autologous mesenchymal stromal cells: evaluation of the contribution of immune-mediated mechanisms.

We report the first case of renal antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis treated with autologous mesenchymal stromal cells (MSCs). A 73-year-old man was admitted to the hospital for malaise, weight loss, and oliguria. His serum creatinine level was 2.7 mg/dL but it rapidly increased to 7.8 mg/dL; urinalysis showed proteinuria and hematuria, and the ANCA to myeloperoxidase with a perinuclear pattern (pANCA) titer was high (132 IU/mL). Renal biopsy showed necrotizing crescentic glomerulonephritis. Standard immunosuppressive therapy (cyclophosphamide and corticosteroids) was ineffective. Rituximab therapy was started, but it was discontinued after the third dose to minimize the risk of systemic spread of a severe oral Candida infection and to prevent superinfections that were facilitated by leukopenia. The patient received autologous MSCs, 1.5 × 10(6) cells/kg body weight, intravenously. After 7 days, his serum creatinine level decreased to 2.2 mg/dL, pANCA titer decreased to 75 IU/mL, and urinalysis findings normalized. Eight months later, he received a second MSC infusion because his serum creatinine level increased. In 1 week, his creatinine level decreased to 1.9 mg/dL and his pANCA titer decreased to 14 IU/mL. Immunosuppressive therapy was subsequently withdrawn. At the last follow-up visit, 12 months after the second MSC infusion, the patient remained in clinical remission without any therapy. Infusion of MSCs induced expansion of the T-lymphocyte subset expressing a regulatory T-cell phenotype (CD4(+)CD25(+)Foxp3(+)) and a notable reduction in interferon-γ, interleukin 6, and tumor necrosis factor serum levels.

Progression and management of Wegener's granulomatosis in the head and neck.

OBJECTIVES/HYPOTHESIS: To describe the otolaryngologic presentation and natural history of granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis, and to compare otolaryngologic outcomes of patients with systemic GPA to those with a limited form of GPA confined to the head and neck. STUDY DESIGN: Retrospective chart review. METHODS: Review of GPA cases (identified by serology, biopsy, or clinical presentation) seen in the otolaryngology department of an academic medical center. RESULTS: A total of 24 patients were identified; each patient was followed for an average 6.8 years. Sinusitis and subglottic stenosis were the most commonly observed head and neck manifestations at diagnosis, seen in 64% and 36%, respectively. Over time, disease spread to additional sites in more than half the cohort (n = 14), but only two of 13 patients with disease initially limited to the head and neck developed pulmonary disease, and none developed renal disease. Cumulatively, otitis media was more likely to be observed in patients with systemic disease (P = .04). Patients with localized (n = 12) and systemic (n = 12) GPA did not have significantly different rates of surgical interventions (0.55 vs. 0.72 surgical interventions/patient-year of follow-up, respectively, P = .19). CONCLUSIONS: GPA has a variety of head and neck manifestations, most commonly sinusitis, nasal disease, subglottic stenosis, and otitis media. GPA commonly progresses to involve additional sites, regardless of the extent of disease. These patients require frequent surgical intervention, and the clinician should remain vigilant for progression of disease.

[Kidney allograft: a target for systemic disease]. / Le rein transplanté : une cible des maladies systémiques.

Recurrence of disease after transplantation is frequent and represents the third cause of allograft loss. Recurrence of lupus nephritis after transplantation is rare. Kidney transplantation in patients with antiphospholipid syndrome or lupus anticoagulant is challenging due to the high risk of immediate post-transplant thrombosis and bleeding risk associated to the subsequent anticoagulation. Moreover, vascular changes associated to the presence of antiphospholipid antibodies negatively impact allograft rate survival. Recurrence of pauci immune glomerulonephritis or Goodpasture syndrome is exceptional.

[Acute abdomen in a patient with ANCA-associated vasculitis]. / Akutes Abdomen bei ANCA-Assoziierter Vaskulitis.

HISTORY AND FINDINGS: A 49-year-old man complained of increasing pain in the lower left abdomen. Three weeks previously joint pain had developed, and in the last 7 days the patient had noted a cutaneous rash at the lower legs. Within three days after admission a paralytic ileus developed, progressed and culminated in a small bowel perforation. In the 60 cm ileum specimen as well as in the skin lesions there was marked intra- und perivascular infiltration with neutrophil granulocytes and focal necrosis, but no granuloma. DIAGNOSIS, TREATMENT AND COURSE: As the proteinase 3 subtype of antineutrophil cytoplasmic antibodies (ANCA) was positive ANCA-associated vasculitis with gastrointestinal, cutaneous and kidney involvement was diagnosed. After initiation of cytostatic treatment with methylprednisolone boli und cyclophosphamide the patient's condition improved. The post-operative course was uneventful. CONCLUSION: ANCA-associated vasculitis rarely presents with severe gastrointestinal complications. The disease represents an interdisciplinary challenge because of its variable clinical presentation and the possibly lethal outcome if not adequately treated.

Hypertrophic spinal pachymeningitis with thoracic myelopathy: the initial presentation of ANCA-related systemic vasculitis.

STUDY DESIGN: A retrospective case review combined with a review of current literature. OBJECTIVES: We describe a case of antineutrophil cytoplasmic antibodies (ANCA)-related systemic vasculitis, with nearly 4 years of clinical and radiographic follow-up, initially presenting as hypertrophic spinal pachymeningitis (HSP). The diagnosis, surgical, and medical treatment of HSP are discussed in the context of a literature review. SUMMARY OF BACKGROUND DATA: HSP is a rare disease characterized by hypertrophic inflammation of the dura mater and clinical symptoms that progress from local pain to myelopathy. HSP has been associated with infectious, inflammatory, autoimmune, and traumatic conditions. Surgical decompression and/or corticosteroid therapy have been shown effective at managing this disorder, but identifying associated diseases can be essential to a favorable patient outcome. METHODS: The medical, pathologic, and radiographic records of this case were reviewed. A computer-based search of the PubMed database was used to perform a comprehensive literature review of HSP. RESULTS: We report a 66-year-old male with a history of renal cell carcinoma and bladder cancer who presented with upper abdominal pain, thoracic myelopathy (progressive weakness and numbness of the lower extremities, and gait disturbances), and weight loss. A diagnosis of HSP was subsequently shown to be the initial presentation of ANCA-related systemic vasculitis. CONCLUSIONS: The possibility of an ANCA-related systemic vasculitis presenting as HSP without systemic signs is a diagnostic and therapeutic challenge for the spinal surgeon. The diagnosis of HSP should initiate a search for an associated disease process and close follow-up after initial treatment. With interdisciplinary collaboration between medicine, radiology, pathology, and orthopedics, the diagnosis was made and a treatment initiated which halted disease progression and has maintained remission for more than 4 years.