Role Of Immunosuppressive Therapy Research Articles

Risk factors for SARS-CoV-2 infection and severe COVID-19 in unvaccinated solid organ transplant recipients

The role of immunosuppressive therapy on SARS-CoV-2 infection risk and COVID-19 severity remains unclear in unvaccinated solid organ transplant recipients. We included 1957 organ transplant recipients between July 2020 and April 2021 to analyze whether baseline immunosuppressive therapy and other risk factors are associated with SARS-CoV-2 infection and severe COVID-19. In total, 247 (12.6%) had SARS-CoV-2 (defined as positive nasopharyngeal swab and/or positive antibody titer). Of these, 57 (23.1%) had severe COVID-19, defined as oxygen supplementation, intensive care unit admission or death. Multivariable analysis identified diabetes (hazard ratio (HR) 1.39 (95% confidence interval (CI) 1.05–1.83)), chronic lung disease (HR 1.71 (95% CI 1.13–2.60)) and contact with a COVID-19 positive individual (HR 3.61 (95% CI 2.61–4.99) as independent risk factors for SARS-CoV-2 infection. There was no association between immunosuppressive therapy and infection risk. Severe COVID-19 was multivariably associated with hypertension (OR 5.45 (95% CI 1.66–17.84)), chronic kidney disease (OR 3.55 (95% CI 1.75–7.19)), corticosteroid use (OR 2.93 (95% CI 1.03–2.55)) and having a COVID-19 positive housemate (OR 6.77 (95% CI 2.65–17.28)). In conclusion, baseline corticosteroid use, but no other immunosuppressive agent, is independently associated with severe COVID-19 in unvaccinated SOT recipients after correction for hypertension, chronic kidney disease, housemates affected by COVID-19 and transplant type.

Gg4 Pseudo tumors Mimicking Urologic Malignancies: Comprehensive Review and Management of a Rare Infiltrative Upper Tract Lesion

Objectives: Immune-mediated fibroinflammatory conditions are known to affect multiple organ systems, as seen in the IgG-4 related disease. While tubulointerstitial nephritis and membranous glomerulonephritis are the more common intrinsic renal diseases, IgG-4 mediated disease can mimick urologic malignancies and can pose a significant management dilemma. Our goal is to understand how to better diagnose, exclude malignancy, and preserve renal function in a rare Urologic disease. Materials and Methods: A review of current literature was obtained to provide additional insight and understanding on this rarely observed Urologic disease. In discussing the case presented, a pertinent clinical history, physical exam, and review of cross-sectional imaging is presented. Immunohistochemical analysis of the specimen was thoroughly performed with expert analysis by our consulting pathologist. Results: Very rare reports of renal, ureteral, pelvic, or scrotal IgG4 mediated pseudotumors have been published. In the absence of pathologic tissue analysis of biopsy samples, the diagnosis of this rare disease can be significantly challenging. In our presentation, a male patient was noted to have a 7cm mass replacing the left renal sinus and causing moderate left hydronephrosis. Initial concern was for upper tract urothelial cell carcinoma. However, left ureteropyeloscopy demonstrated normal left renal and ureteral architecture and excisional biopsy of a PET avid left cervical lymph node was performed however pathologic diagnosis was not able to be confirmed. This led to a management dilemma due to the progressing mass size, worsening renal drainage, and symptoms. The patient opted for surgical excision. Final pathology from a left radical nephrectomy was significant for an IgG-4 related inflammatory pseudotumor. Conclusions: IgG-4 related diseases are known to represent a systemic disease that leads to lymphoplasmacystic inflammation and fibrosis within the affected tissues. At this time, there is no standardized method for the diagnosis and treatment of patients with retroperitoneal involvement. Additional research is needed to identify improved diagnostic modalities, the role of immunosuppressive therapy, and the surgical management in this disease process.

Role of immunosuppressive therapy in the management refractory postprocedural pericarditis.

To assess the safety and efficacy of a novel immunosuppressive regimen-combination Methotrexate/Prednisone (cMtx/P)-in the management of severe refractory rPPP. In this multicenter, nonrandomized, retrospective, observational study, 408 consecutive patients diagnosed with persistent rPPP between 2017 and 19 were included. Patients with refractory symptoms despite 3 months of conventional therapy were initiated on a 4-week regimen of oral steroids. Persistence of symptoms at this point, that is, rPPP (n = 25; catheter based = 18, open surgical = 7) prompted therapy with Methotrexate (7.5-15 mg weekly) with folate supplementation along with low dose prednisone (5 mg PO) for a further 3 months. Patients were followed for a total of 11.3 ± 1.8 months. Treatment refractory rPPP occurred in 6.1% of the study population prompting immunosuppressive therapy with cMtx/P. All patients demonstrated complete symptom resolution following 3 months of treatment with an 85% decline in clinically significant pericardial effusions. One patient developed recurrent pericarditis during the 11-month follow-up. Therapy was well tolerated with no significant drug related adverse effects. cMtx/P therapy is a safe and effective adjunct in the management of rPPP refractory to standard therapy.

COVID-19 in Autoinflammatory Diseases with Immunosuppressive Treatment.

COVID-19 disease increases interleukin (IL)-1β release. Anti-IL-1-treatment is effective in IL-1-mediated autoinflammatory diseases (AID). This case series presents COVID-19 in patients with IL-1-mediated and unclassified AID with immunosuppressive therapy (IT). Patient 1 is a 34-year-old woman with an unclassified AID and methotrexate. Patients 2 and 3 (14-year-old girl and 12-year-old boy, respectively) have a Cryopyrin-Associated Periodic Syndrome (NLRP3 p.Q703K heterozygous, CAPS) treated with canakinumab 150 mg/month since three and five years, respectively. Patient 4 is a 15-year-old girl who has had familial Mediterranean fever (MEFV p.M694V homozygous) for 3 years treated with canakinumab 150 mg/month and colchicine. All patients had a mild acute COVID-19 course, particularly the adolescent patients. A few weeks after COVID-19 recovery, both CAPS patients developed increased AID activity, necessitating anti-IL-1-treatment intensification in one patient. At day 100, one out of four patients (25%) showed positive antibody response to SARS-CoV-2. This is one of the first reports providing follow-up data about COVID-19 in AID. The risk for severe acute COVID-19 disease was mild/moderate, but increased AID activity post-COVID-19 was detected. Follow-up data and data combination are needed to expand understanding of COVID-19 and SARS-CoV-2 immunity in AID and the role of IT.

Primary CNS lymphoma in scleroderma: a case series.

Many studies have demonstrated an increased risk of cancer in patients with rheumatologic diseases, including systemic sclerosis. Less explored is the role of immunosuppressive therapy as a contributing factor in cancer emergence or detection. This series introduces two cases of patients with systemic sclerosis who demonstrated clinical improvement in their rheumatic disease process with immunosuppression, but both of whom developed neurologic symptoms in the setting of decreasing or discontinuing immunosuppressive therapy, leading to the ultimate diagnosis of Epstein Barr Virus positive (EBV+) diffuse large B cell lymphoma of the CNS. To our knowledge, primary CNS lymphoma has not been previously described in systemic sclerosis patients. Immunosuppressive therapies could promote the development of virus-associated malignancies due to decreased viral clearance. We hypothesize that removing immunosuppression could allow the immune system to generate an inflammatory response to an underlying tumor or viral antigen, contributing to development of neurologic symptoms and detection of underlying disease.

Onychomycosis in Psoriatic Patients with Nail Disorders: Aetiological Agents and Immunosuppressive Therapy.

Psoriasis and psoriatic arthritis are chronic, relapsing, immune-based diseases. Psoriatic patients may have nail involvement in 50 to 80% of cases, and this may reach 85% in patients with joint disease, in spite of the fact that the relationship between psoriasis and onychomycosis is not well established. The aim of this study was to investigate the occurrence of onychomycosis in patients with nail disorders and diagnosis of psoriasis and psoriatic arthritis. This was a cross-sectional study in which 38 patients diagnosed with psoriasis and/or psoriatic arthritis were interviewed and had altered nail samples analysed by mycological and histopathological exams. Twenty-two (57.89%) patients had a confirmed diagnosis for onychomycosis. Seventeen (44.8%) had a positive direct mycological examination, 16 (42.1%) had positive cultures, and 12 (31.6%) were positive for fungi by histopathological examination. Dermatophytes were identified in nine (56.3%) cultures, and of these, eight were Trichophyton rubrum and one T. tonsurans. Yeasts were isolated in seven patients (43.75%), which included four Candida parapsilosis and three C. albicans. Six patients (15.78%) were not using immunosuppressive therapy, and the others were using methotrexate, etanercept, adalimumab, infliximab, secukinumab, or golimumab, in monotherapy or in combination with other drugs. The confirmed onychomycosis rate in patients using methotrexate alone was 92.8% (n = 13). We concluded that it is possible that there is a positive relationship between psoriatic disease and onychomycosis. And we highlight that it is also worth investigating in the future the possible role of immunosuppressive therapy (mainly methotrexate) as a predisposing factor for the development of fungal infections in psoriatic patients.

P4651Biopsy-proven myocarditis: independent predictors of dismal prognosis, relapse and role of immunosuppressive therapy

Abstract Background Biopsy-proven myocarditis may be infectious or autoimmune. Risk stratification in biopsy-proven myocarditis and the role of immunosuppressive therapy in autoimmune forms have not been completely defined. Purpose To identify clinical, instrumental and immunological predictors of death, cardiac transplantation and relapse in a prospective cohort of 314 biopsy-proven myocarditis patients, and describe the effect of immunosuppressive treatment on secondary outcome measures, e.g. left ventricular ejection fraction (LVEF), in a subgroup of 45 consecutive patients with biopsy-proven autoimmune myocarditis diagnosed in our Cardiology Clinic. Methods Univariate and multivariate Cox regression analysis were used to identify predictors of death, heart transplant, and relapse in a cohort of 314 patients with biopsy-proven myocarditis (male 75%, median age 37). Actuarial survival free from death or transplant was calculated by the Kaplan-Meier method. Results Actuarial survival free from death or heart transplantation was 83% at 5 years. Among the clinical, instrumental and immunological features at diagnosis, independent predictors of death or heart transplantation by multivariable analysis were a lower transthoracic echocardiographic biplane LVEF% (p=0.001) and high serum titre for anti-nucler (ANA) and anti-cardiac endothelial cell autoantibodies (AECA). The only independent predictor of relapse was previous history of myocarditis. Immunosuppressive therapy was associated with a significantly favorable effect on LVEF (LVEF pre-therapy 37% (26; 50 interquartile range) vs. LVEF post-therapy 59% (48; 65 interquartile range), respectively, p=0.000). Conclusions In biopsy-proven myocarditis left ventricular dysfunction at diagnosis and autoimmune pathogenesis are associated with dismal prognosis, immunosuppressive therapy with improved LVEF in autoimmune patients.

The Impact of Immunosuppression on Mineral Metabolism One Year after Kidney Transplantation

Introduction After kidney transplantation, a substantial amount of patients still suffer from Mineral Bone Disorder (MBD). However, the role of immunosuppressive therapy on mineral metabolism in transplanted patients is largely unknown. The aim of this study is to compare the effect of two common immunosuppressive schedules on MBD-related biomarkers 1 year after transplantation. Both schedules were tacrolimus- and prednisone-based and patients received either micofenolate or an mTOR inhibitor according to the ongoing protocol. Methods Longitudinal 1-year long retrospective study on patients transplanted from June 2013 to May 2016 at Hospital Clínic, Barcelona, who were treated continuously either with mycophenolate (MP) (n=186) or an mTOR inhibitor (mTORi) (n=122) during the first year after kidney transplantation. These two drugs were always combined with both tacrolimus and prednisone. Patients who died within the first year, lost at the follow-up, with graft failure and those who changed immunosuppression during the first year were discarded from the final analysis (25.7% of original population). Results Patients with the mTORi regimen were older and received more likely a graft from a cadaveric donor. There was no difference in renal function at 1 year between groups (creatinine 1.37 ± 0.52 vs 1.43 ± 0.57 for MP and mTORi group respectively, p=0.273). Patients who were doing mTORi experienced a less significant decrease in PTH values 1 year after transplantation (PTH -211.56 ± 270.22 pg/mL vs -136.75 ± 286.06 pg/mL for difference between 1-year and basal values in the MP and mTORi groups, respectively). Alkaline phosphatase decreased significantly in the MP group, while it did not substantially change in the mTORi group (-32.13 ± 89.51 U/L for MP vs +1.66 ± 104.66U/L for mTORi, p=0.009). There was a trend towards lower phosphate levels in the mTORi group (p=0.078), while total calcium was not affected (p=0.373). Conclusion an mTOR inhibitor-based regimen is associated with higher PTH and alkaline phosphatase values 1 year after kidney transplantation when compared to a mycophenolate-based regimen, along with a standard tacrolimus and prednisone immunosuppression.

Clinicopathological Characteristics, Role of Immunosuppressive Therapy and Progression in IgA Nephropathy with Hyperuricemia

Background/Aims: The aim of the study was to investigate clinicopathological characteristics, the role of immunosuppressive therapy and renal outcome in IgA nephropathy (IgAN) patients with hyperuricemia. Methods: 206 biopsy-proven primary IgAN patients were included between January 2010 and December 2015, and divided into two groups: patients without hyperuricemia (n=122), and patients with hyperuricemia (n=84). The clinicopathological features, response, renal outcome and safety were recorded. In univariate and multivariate models, hyperuricemia-associated pathological factors were analyzed. Results: The patients with hyperuricemia presented higher systolic blood pressure, worse kidney function and more severe time-averaged proteinuria. Proportions of glomerulosclerosis, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, lymphocytes and monocytes infiltration were higher, while the proportion of segmental adhesion was lower in patients with hyperuricemia. By multivariate logistic regression analysis, only tubular atrophy/interstitial fibrosis (T1∼2) (HR=3.969, 95% CI=1.439−10.945, P=0.008) was significantly associated with hyperuricemia. For hyperuricemic patients, the response rate to therapy and renal survival rate were significantly higher in patients that received RAS blockade in combination with immunosuppressive therapy. After RAS blockade treatment, renal survival in the patients with hyperuricemia was worse compared with the patients without hyperuricemia. Conclusion: Hyperuricemic IgAN patients presented more severe clinical features. Tubulointerstitial injury could be a pathological feature closely related to hyperuricemia in IgAN. Immunosuppressive therapy and RAS blockade could reduce proteinuria and improve renal outcome in IgAN patients with hyperuricemia.

Systemic Sclerosis and Malignancy: A Review of Current Data

Systemic sclerosis (SSc) is associated with increased risk of malignancy. The organ systems most commonly affected are the lungs, the breasts and the hematological system. Risk factors predisposing a SSc patient for development of malignancy are not well defined, and the pathogenic basis of the association is yet to be explained. The incidence of malignancies in SSc patients is variable from one report to another, but most importantly, questions regarding the role of immunosuppressive therapies and the effect of autoantibodies have weak or sometimes contradictory answers in most of the currently available literature and physicians have no available guidelines to screen their SSc patients for malignancies. The lack of a concretely defined high-risk profile and the absence of malignancy screening guidelines tailored for SSc patients raise the importance of the need for more studies on the association of SSc and cancer and should incite rheumatology colleges to develop specific recommendations for the clinician to follow while approaching patients with SSc.

Nodular Hyperplasia of the Gastrointestinal Tract After Liver Transplantation: Role of Immunosuppressive Therapy? A Case Report

Nodular lymphoid hyperplasia (NLH) of the gastrointestinal tract is a rare disease usually reported in patients with congenital or acquired immunodeficiency and chronic gastrointestinal infections. However, no case of NLH in a patient receiving immunosuppressive therapy has been reported to date. We describe the case of a woman who developed chronic diarrhea related to NLH 9 years after liver transplantation. Other causes of diarrhea and NLH were excluded. Her immunosuppressive regimen consisted on mycophenolate mofetil (MMF) and tacrolimus. Reduction of MMF dose improved symptoms but led to a rising aminotransferase level. Given the risk of graft rejection, MMF at full dose was resumed and she was started on symptomatic treatment for diarrhea. The role of immunosuppressive drugs in the pathogenesis of NLH may be related to the reduction of T- and B-lymphocyte proliferation and decreasing antibody production. NLH will further develop to compensate functionally inadequate lymphoid tissue, as reported in congenital immunodeficiency states.

Pulmonary hypertension in rheumatic diseases: epidemiology and pathogenesis

The focus of this review is to increase awareness of pulmonary arterial hypertension (PAH) in patients with rheumatic diseases. Epidemiology and pathogenesis of PAH in rheumatic diseases is reviewed, with recommendations for early screening and diagnosis and suggestion of possible role of immunosuppressive therapy in treatment for PAH in rheumatic diseases. A MEDLINE search for articles published between January 1970 and June 2012 was conducted using the following keywords: pulmonary hypertension, scleroderma, systemic sclerosis, pulmonary arterial hypertension, connective tissues disease, systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, Sjogren's syndrome, vasculitis, sarcoidosis, inflammatory myopathies, dermatomyositis, ankylosing spondylitis, spondyloarthropathies, diagnosis and treatment. Pathogenesis and disease burden of PAH in rheumatic diseases was highlighted, with emphasis on early consideration and workup of PAH. Screening recommendations and treatment were touched upon. PAH is most commonly seen in systemic sclerosis and may be seen in isolation or in association with interstitial lung disease. Several pathophysiologic processes have been identified including an obliterative vasculopathy, veno-occlusive disease, formation of microthrombi and pulmonary fibrosis. PAH in systemic lupus erythematosus is associated with higher prevalence of antiphospholipid and anticardiolipin antibodies and the presence of Raynaud's phenomenon. Endothelial proliferation with vascular remodeling, abnormal coagulation with thrombus formation and immune-mediated vasculopathy are the postulated mechanisms. Improvement with immunosuppressive medications has been reported. Pulmonary fibrosis, extrinsic compression of pulmonary arteries and granulomatous vasculitis have been reported in patients with sarcoidosis. Intimal and medial hyperplasia with luminal narrowing has been observed in Sjogren's syndrome, mixed connective tissue disease and inflammatory myopathies. Pulmonary arterial hypertension (PAH) associated with rheumatic diseases carries a particularly grim prognosis with faster progression of disease and poor response to therapy. Though largely associated with systemic sclerosis, it is being increasingly recognized in other rheumatic diseases. An underlying inflammatory component may explain the poor response to therapy in patients with rheumatic diseases and is a rationale for consideration of immunosuppressive therapy in conjunction with vasodilator therapy in treatment for PAH. Further studies identifying pathogenetic pathways and possible targets of therapy, especially the role of immunomodulatory medications, are warranted.

Pulmonary langerhans cell histiocytosis

Pulmonary Langerhans Cell Histiocytosis (PLCH) is a relatively uncommon lung disease that generally, but not invariably, occurs in cigarette smokers. The pathologic hallmark of PLCH is the accumulation of Langerhans and other inflammatory cells in small airways, resulting in the formation of nodular inflammatory lesions. While the overwhelming majority of patients are smokers, mechanisms by which smoking induces this disease are not known, but likely involve a combination of events resulting in enhanced recruitment and activation of Langerhans cells in small airways. Bronchiolar inflammation may be accompanied by variable lung interstitial and vascular involvement. While cellular inflammation is prominent in early disease, more advanced stages are characterized by cystic lung destruction, cicatricial scarring of airways, and pulmonary vascular remodeling. Pulmonary function is frequently abnormal at presentation. Imaging of the chest with high resolution chest CT scanning may show characteristic nodular and cystic abnormalities. Lung biopsy is necessary for a definitive diagnosis, although may not be required in instances were imaging findings are highly characteristic. There is no general consensus regarding the role of immunosuppressive therapy in smokers with PLCH. All smokers must be counseled on the importance of smoking cessation, which may result in regression of disease and obviate the need for systemic immunosuppressive therapy. The prognosis for most patients is relatively good, particularly if longitudinal lung function testing shows stability. Complications like pneumothoraces and secondary pulmonary hypertension may shorten life expectancy. Patients with progressive disease may require lung transplantation.

Early use of mammalian target of rapamycin inhibitors is an independent risk factor for incisional hernia development after liver transplantation

Incisional hernias (IHs) are common complications after liver transplantation (LT) with a reported incidence of 1.7% to 34.3%. The purpose of this retrospective study was to evaluate the risk factors for IH development after LT with a focus on the role of immunosuppressive therapy during the first month after LT. We analyzed 373 patients who underwent LT and divided them into 2 groups according to their postoperative course: an IH group (121 patients or 32.4%) and a no-IH group (252 patients or 67.6%). A univariate analysis demonstrated that the following were risk factors related to IH development: male sex (P = 0.03), a body mass index ≥ 29 kg/m(2) (P = 0.005), LT after 2004 (P = 0.02), a Model for End-Stage Liver Disease (MELD) score ≥ 22 (P = 0.01), and hepatitis B virus infection (P = 0.01). The highest incidence of IHs was found in patients treated with mammalian target of rapamycin (mTOR) inhibitors (54.5%, P = 0.004). A multivariate analysis revealed male sex (P = 0.03), a pretransplant MELD score ≥ 22 (P = 0.04), and the use of mTOR inhibitors (P = 0.001) to be independent risk factors for IHs after LT. In conclusion, immunosuppressive therapy with mTOR inhibitors is an important independent risk factor for IH development after LT. To reduce the incidence of IHs, mTOR inhibitors should be avoided until the fourth month after LT unless their use is deemed to be strictly necessary.

Response to Immunosuppressive Therapy with Antithymocyte Globulin (ATG) In Older Patients with Aplastic Anemia

Abstract 4374Immunosuppressive therapy (IST) with antithymocyte globulin in combination with prednisolone and cyclosporine is the treatment of choice for patients with aplastic anemia who are ineligible for transplant either because of age or because of absence of a HLA identical donor. Limited data that exists on the role of immunosuppressive therapy in older patients with aplastic anemia suggest that responses were poorer. This retrospective analysis was aimed at determining whether older patients with aplastic anemia had an inferior response to IST compared with younger patients.Between October 1985 to December 2010, 322 adult patients (>12 years) were treated at our centre with antithymocyte globulin (ATG) in combination with prednisolone and with/without cyclosporine. Either ATGAM (Pharmacia Upjohn, USA) at 40 mg/kg/day × 4 days or Lymphoglobulin (Pasteur Merieux, France) at 15 mg/kg/day × 5 days was used. Prednisolone at 1 mg/kg in 3 divided doses were started one day after completion of ATG and tapered from Day +14 if there was no evidence of serum sickness. Cyclosporine at the dose of 6 mg/kg/day in 2 divided doses was started once steroids were tapered and then continued for 12 months and then tapered depending upon response. Patients were divided into 3 age groups - Ages 12 – 29 [n=116], ages 30 – 49 [n = 116] and > 50 years [n = 90]. The baseline characteristics are detailed in the table below – Thirty one patients were above the age of 60 years. The older age group had significantly higher % of males, more use of ATGAM compared with Lymphogloblin and a higher number was given Cyclosporine (CSA) post ATG. The severity of aplastic anemia (severe vs non-severe) and the median time from diagnosis to administration of ATG was not significantly different between the 3 groups. The number of patients who developed serum sickness was significantly lower in the older age group (21.1%) compared to the age group of 30 – 49 (35.3%) and 12 – 29 years (48.3%) [p = 0.000]. The overall response to ATG was similar in all 3 groups (63.8% in age 12 –29, 64.7% in ages 30 – 49 and 54.4% in age > 50 yrs) [p = 0.233]. The response in patients above the age of 60 years was 51.6%. Six patients received a second course of ATG while 3 patients underwent HLA identical sibling donor transplantation. At a median follow up of 32 months (range: 1 –145), 221 patients (68.6%) are alive. The overall survival is similar for the older age group compared with the younger age groups (66.7% with age>50 years, 68.1% with age 30–49 and 70.7% with age 12 –29) [p= 0.817]. In conclusion, immunosuppressive therapy with ATG has a reasonable outcome in older patients (> 50 years) with aplastic anemia.Table 1:Demographic characteristics and outcome of IST among the 3 age groupsVariables12 – 29 yrs (n = 116)30 – 49 yrs (n = 116)>50 yrs (n = 90)p valueMale84 (72.4%)87 (75%)52 (57.8%)Female32 (27.6%)29 (25%)38 (42.2%)0.019Severity of AA86 (74.1%)77 (66.4%)63 (70%)0.581VSAA + SAA30 (25.9%)39 (33.6%)27 (30%)NSAAType of ATG45 (38.8%)33 (28.4%)53 (58.9%)0.000ATGAM71 (61.2%)83 (71.6%)37 (41.1%)LymphoglobulinCSA used92 (79.3%)103 (88.8%)85 (94.4%)0.005Yes24 (20.7%)13 (11.2%)5 (5.6%)NoResponse74 (63.8%)75 (64.6%)49 (54.4%)0.233Overall response34 (29.3%)28 (24.1%)15 (16.7%)Complete response (CR)40 (34.5%)47 (40.5%)34 (37.8%)Partial response (PR)42 (36.2%)41 (35.3%)41 (45.6%)No response (NR)Overall survival82 (70.7%)79 (68.1%)60 (66.7%)0.817Alive34 (29.3%)37 (31.9%)30 (33.3%)Dead Disclosures:No relevant conflicts of interest to declare.

Have We Changed the Outcome in Membranous Nephropathy? A Propensity Study on the Role of Immunosuppressive Therapy

The long-term effect of immunosuppressive therapy (IS) on kidney survival in idiopathic membranous nephropathy (MGN) is debated. The introduction of renin angiotensin blockade, rigorous BP control, and the increasing age at presentation of patients with MGN adds further uncertainty. Given these important changes, we sought to determine whether implementation of IS has altered outcome. We prospectively evaluated 280 incident MGN patients from three distinct 10-year periods starting from 1975. We found expected changes in treatment regimens but also variations in age, renal function, severity of proteinuria, and BP at presentation over this time. Outcomes did not differ over time if these significant variations in clinical characteristics were not accounted for across the eras. The effect of IS in the 57 patients treated with currently recommended regimens was assessed using propensity adjustment to address selection bias and the effect of newer, conservative therapies. A propensity score estimating the probability of receiving IS permitted the pairing of 39 treated patients with controls with similar high risk of progression of clinical features. Using this approach, IS was associated not only with remissions in proteinuria but also with substantially improved renal survival. The study confirms that patient presenting characteristics and management regimens have changed significantly over time and the natural history of MGN has been altered. A study of propensity-matched patients confirms that current recommendations for IS have improved outcomes in MGN patients at high risk of progression.

Outcome of idiopathic membranous nephropathy using targeted stepwise immunosuppressive treatment strategy

The natural course of idiopathic membranous nephropathy (IMN) is variable and the role of immunosuppressive therapy is controversial. In our centre, the strategy has been conservative: the immunomodulating treatment (glucocorticoids and/or cyclosporine A) has been targeted to patients at high risk of developing progressive renal disease and the cytotoxic drugs have been used cautiously. The aim of this retrospective observational study was to evaluate the efficacy of this strategy. We evaluated the clinical course and outcome of IMN patients diagnosed between 1993 and 2003. Risk assessment was done during an observation period of ≥6 months after the initial renal biopsy. Patients were followed up until death, the development of end-stage renal disease (ESRD) or the last clinical visit (before December 2006). Treatments and their side effects were recorded. One hundred and forty-two patients with membranous nephropathy were diagnosed of which 81 were idiopathic. The clinical course of 76 IMN patients (38 high risk and 38 low risk) were followed up [mean duration 66 ± 40 (median 59) months]. Thirty-five patients were treated with immunosuppressive drugs, and at last follow-up, 71% of them were in complete or partial remission. The overall response rate of this therapy was 83%. 11% of the high-risk patients had reached ESRD. For the high-risk patients, 10-year survival (alive with glomerular filtration rate >10 mL/min/1.73 m(2)) was 79%. No major side effects were observed. This study suggests that targeted, stepwise, cytotoxic drug-sparing immunosuppressive treatment in IMN was associated with favourable renal, as well as overall survival among patient at risk of developing ESRD.

New onset diabetes and liver transplantation: the case for screening

Over recent years, liver transplantation has transformed the lives of many people with liver disease; however, with the need for immunosuppression therapy following transplantation comes the significantly increased risk of the individual developing diabetes. This article aims to identify ′best practice′ in relation to screening pre-transplant patients for diabetes and cardiovascular risk factors to ensure metabolic stability is achieved pre-operatively to avoid potential post−operative complications. Consideration is given to the role of immunosuppressive therapy in the development of diabetes, as well as to the identification of key markers for those who are at increased risk of developing diabetes post transplant. Suggestions for practice are offered relating to the choice of immunosuppressive therapy and the need for post−transplant surveillance for diabetes to help ensure the best possible long−term patient outcomes.

Aortic Root Aneurysm Due to Donor Cystic Medial Degeneration After Heart–Lung Transplantation

A patient presented with symptomatic aortic root enlargement 5 years after combined heart and double-lung transplantation for cystic fibrosis, requiring homograft aortic root replacement. Histologic examination of the resected aneurysm showed cystic medial degeneration with no evidence of infectious or atherosclerotic process. Surgical options and potential role of immunosuppressive therapy after homograft implantation are discussed.

Para-testicular cellular angiofibroma: a rare tumour in a male renal transplant patient

Cellular angiofibroma is a rare, benign, mesenchymal neoplasm that should be distinguished from other more aggressive mesenchymal lesions. A 32-year-old male presented with a painless para-testicular mass. Pathological examination showed features characteristic of cellular angiofibroma. He had a history of renal transplantation and was on immunosuppressive drugs. The pathogenesis of cellular angiofibroma is largely undetermined. The role of immunosuppressive therapy in the genesis of this tumour awaits further analysis.