Napat Leeaphorn

Clinical features of inflammatory myopathies and their association with malignancy: a systematic review in asian population.

Introduction. Idiopathic inflammatory myopathies (IIMs) are a group of chronic systemic autoimmune diseases that mainly affect the skeletal muscle. The common subtypes include adult dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM). Most of the earlier studies that described the clinical characteristics of IIM as well as their association with cancer were conducted in Western population. Our study is the first systematic review that summarizes the clinical data of DM/PM in Asian population. Methods. We identified 14 case series of DM/PM that met our eligibility criteria. We then compared this data with that from previous reports from Europe and North America. Results. Our systematic review included 2518 patients. Dermatomyositis is more common, with the ratio of dermatomyositis to polymyositis being 1.36 : 1. 69% of them were females with mean age of 45.5 years. Extramuscular manifestations, including arthritis/arthralgia, dysphagia, and interstitial lung disease, are found in one-third of the patients. Malignancy was found in 10% of patients, with lung and nasopharyngeal carcinomas being the most common malignancies associated with these myopathies. Conclusion. Clinical presentation of PM/DM appears to be similar in both Western and Asian populations. However, the type of associated malignancies in Asians differs from that in Caucasians. Ethnic background should be one of the factors that clinicians should consider while screening for malignancy.

Prevalence of Cancer in Membranous Nephropathy: A Systematic Review and Meta-Analysis of Observational Studies

Background: The association between membranous nephropathy (MN) and cancer has been well documented. However, the true prevalence and characteristics of cancer associated with MN have not been well described. Methods: A systematic review and meta-analysis of cohort studies was conducted to summarize the prevalence of cancer-associated MN as well as patient characteristics and types of cancer in this population. We used a random-effects meta-analysis model to estimate the prevalence of cancer. Results: We included 6 studies (n = 785). The estimated prevalence of cancer was 10.0% (95% CI, 6.1-14.6). The mean age of MN patients with cancer was 67 ± 7 years. The diagnosis of cancer preceded the diagnosis of MN in 20 ± 6.8%. Lung cancer was the most common type of tumor, accounting for 22 cases (26%), followed by prostate cancer (13 cases, 15%), hematologic malignancies (12 cases, 14%), colorectal cancer (9 cases, 11%), breast cancer (6 cases, 7%), and stomach and esophageal cancer (5 cases, 6%). Conclusion: The estimated prevalence of cancer in patients with MN is 10% (95% CI, 6.1-14.6). The vast majority of tumors associated with MN are lung and prostate cancer. Hematologic malignancies should also be considered as one of the potential cancers associated with MN. Our study was based on a largely Caucasian population; therefore, the findings might not be applicable to other populations.

Protease inhibitors and avascular necrosis: A systematic review and meta-analysis

Avascular necrosis (AVN) is a pathological process associated with many medical conditions, including human immunodeficiency virus (HIV) infection. Whether or not the use of protease inhibitors (PIs) confers additional risk for AVN to HIV-infected patients is controversial. Previous epidemiological studies showed an increased risk of AVN among PI users, but these studies did not have enough power to achieve statistical significance. A meta-analysis of case-control studies reporting the odds ratios (ORs) of AVN among HIV-infected patients who were exposed to PIs compared with non-exposed patients was conducted. Pooled ORs and 95% confidence intervals (CIs) were calculated using a fixed-effect Mantel-Haenszel analysis. Four case-control studies were identified and included for data analysis. The meta-analysis demonstrated an increased odds of AVN in participants exposed to PIs, with an OR of 2.09 (95% CI 1.01-4.31; P=0.05). The statistical heterogeneity of this meta-analysis was determined not to be important, with an I(2) of 0%. The meta-analysis revealed a statistically significant increased odds of AVN among PI-exposed, HIV-infected patients. Physician should be aware of this association as it may help guide potential therapeutic options, particularly for patients with other classic risk factors for AVN.

Recurrence of IgA nephropathy after kidney transplantation in steroid continuation versus early steroid-withdrawal regimens: a retrospective analysis of the UNOS/OPTN database

In the past 20 years, there has been an increase in use of steroid‐withdrawal regimens in kidney transplantation. However, steroid withdrawal may be associated with an increased risk of recurrent IgA nephropathy (IgAN). Using United Network of (Organ Sharing/Organ Procurement and Transplantation Network) UNOS/OPTN data, we analyzed adult patients with end‐stage renal disease (ESRD) due to IgAN who received their first kidney transplant between 2000 and 2014. For the primary outcome, we used a competing risk analysis to compare the cumulative incidence of graft loss due to IgAN recurrence between early steroid‐withdrawal (ESW) and steroid continuation groups. The secondary outcomes were patient survival and death‐censored graft survival (DCGS). A total of 9690 recipients were included (2831 in ESW group and 6859 in steroid continuation group). In total, 1238 recipients experienced graft loss, of which 191 (15.43%) were due to IgAN recurrence. In multivariable analysis, steroid use was associated with a decreased risk of recurrence (subdistribution hazard ratio 0.666, 95% CI 0.482–0.921; P = 0.014). Patient survival and DCGS were not different between the two groups. In the USA, ESW in transplant for ESRD due to IgAN is associated with a higher risk of graft loss due to disease recurrence. Future prospective studies are warranted to further address which patients with IgAN would benefit from steroid continuation.

Rituximab-induced serum sickness in overlapping syndrome between sjögren syndrome and systemic lupus erythematosus.

To the Editor: W e read the article by Finger and Scheinberg with great interest, which described a rare adverse effect of rituximab as well as subsequent reports. We similarly observed a case of a patient who developed serum sickness after receiving rituximab as a treatment for her Sjögren syndrome. We emphasize that the literature suggests that this reaction to rituximab appears to be more common in autoimmune disease than after use in malignancies. A 50-year-old woman with overlapping syndrome between Sjögren syndrome and systemic lupus erythematosus (SLE) presented to our institute with 2 days’ history of low-grade fever, diffuse joint pain, and pruritic rash over her torso. She received rituximab 1 week before the onset of symptoms for her painful bilateral parotid gland swelling from her Sjögren syndrome. She had also previously received rituximab for central nervous system vasculitis, lymphocytic interstitial lung disease, and inflammatory arthritis from her SLE 5 years ago. She had not been taking any immunosuppressive agent for 3 years since her SLE had been inactive. Physical examination revealed temperature of 38.6-C, blood pressure of 102/67 mm Hg, and heart rate of 130 beats/min. Head, eyes, ears, nose, and throat examination was remarkable for bilateral and painful parotid gland enlargement without any associated lymphadenopathy. Her musculoskeletal examination revealed mild warmth, tenderness, erythema, and swelling in her wrists, all metacarpalphalangeal joints, and all proximal interphalangeal joints. She had urticarial rash over her torso and her back. Her cardiovascular, respiratory, neurological, and abdominal examinations were unremarkable. Laboratory tests showed hemoglobin of 10.2 g/dL, white blood cell count of 3800/KL (neutrophil of 82% and lymphocyte of 12%), and platelet count of 72,000/KL. Blood chemistry and liver function tests were within reference range. Complements were suppressed with C3 level of 97 mg/dL (90Y207 mg/dL), C4 level of less than 6 mg/dL (17.4Y52.2 mg/dL), and CH50 of 12 U/mL (30Y75 U/mL. Microbiologic investigations, including blood culture, urine culture, and viral serology, did not reveal any evidence of infection. The diagnosis of rituximab-induced serum sickness was made in the view of classic presentation of fever, arthralgia, and rash following rituximab exposure. She was treated with intravenous methylprednisolone. She responded well to the corticosteroids, and all of her symptoms were completely resolved within 48 hours. She was discharged home with oral prednisone for 7 days. Rituximab is a chimeric monoclonal anti-CD20 antibody, containing both human and murine portion in its protein structure. It has been approved for use in a variety of autoimmune diseases as well as lymphoproliferative disorders. Rituximab is relatively safe, although mild and self-limited infusion reaction can be found in 30% to 45% of patients. Serum sickness is an immune complexY mediated or type III hypersensitivity reaction characterized by clinical triad of fever, rash, and polyarthralgia/polyarthritis after exposure to triggering agents. It is a relatively uncommon adverse effect of rituximab with approximately 40 cases reported thus far. Interestingly, it has been reported more frequently in patients with autoimmune diseases than hematologic malignancies. The reasons why serum sickness occurs more frequently in patients with autoimmune disorders remains unclear. Suppression of humoral immune response in patients with cancer who often receive concurrent chemotherapy with rituximab may be an explanation of the lower incidence of the adverse reaction in this group. Another explanation is related to the nature of autoimmune disorders that usually create pools of polyclonal immunoglobulin with high affinity to self-epitopes capable of binding to infused monoclonal protein. This could also explain why in some cases this reaction occurred after first infusion but not in subsequent ones. Serum sickness is generally self-limited, and patients usually improve rapidly after withdrawal of the culprit agent. Glucocorticoid may be indicated in patients with more severe reaction. Rapid resolution of serum sickness associated with rituximab after administration of glucocorticoid has been documented in several case reports. Our patient also responded well to glucocorticoid and had complete resolution within 48 hours. As the utility of this monoclonal antibody in autoimmune disorders expands, rheumatologists should be alert for serum sickness as a possible adverse reaction to this treatment. Prompt withdrawal of rituximab and timely administration of glucocorticoid can result in rapid improvement of symptoms and excellent clinical outcome.

Metabolic acidosis may increase fibroblast growth factor-23 and cardiovascular mortality in the community

To the Editor: Thank you for the excellent study on fibroblast growth factor-23 (FGF23) and cardiovascular mortality by Ärnlöv et al.1 The authors demonstrated an interesting association between higher FGF23 and increased risk of all-cause and cardiovascular mortality in the community. However, an interesting topic that the authors did not mention about was the degree of metabolic acidosis in the study population. The authors stated that FGF23 becomes elevated in chronic kidney disease (CKD) because of the yet unknown pathological factor(s). We are wondering whether metabolic acidosis has a key role behind this effect. Recently, Krieger et al.2 found that metabolic acidosis directly increased FGF23 mRNA and protein in neonatal mouse bone. If we can confirm these results in humans with CKD, we might be able to decrease FGF23 and cardiovascular mortality by therapeutic interventions for metabolic acidosis.

Zero-mismatch deceased-donor kidney versus simultaneous pancreas-kidney transplantation.

Background Patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease may receive a simultaneous pancreas-kidney (SPK), living-donor kidney (LDK), or deceased-donor kidney (DDK) with possible pancreas after kidney transplantation. SPK is associated with superior patient and kidney graft survival compared with DDK, whereas SPK and LDK have comparable outcomes. It is unclear whether SPK and LDK offer a survival benefit over zero-mismatch (0MM) DDK. In this study, we compared the outcomes of T1DM recipients using data from the Organ Procurement and Transplant Network/United Network for Organ Sharing. Methods Adult (≥18 years) first-time transplant recipients with T1DM waitlisted for SPK and transplanted from 1995 to 2010 were included in this study. Patient and death-censored kidney graft survival were compared between 0MMDDK (n=228), mismatched (MM) DDK (n=964), 0MMSPK (n=215), MMSPK (n=11951), 2 haplotype identical (2hap) LDK (n=205), and non-2hapLDK (n=1719) recipients. Multivariate analysis was performed using stepwise Cox proportional hazards models. Results At 7 years, patient and death-censored graft survival of 0MMDDK recipients (85% and 81%, respectively) were not statistically different from that of 0MMSPK (81% and 85%; log-rank P value vs. 0MMDDK, 0.17 and 0.48, respectively) and 2hapLDK recipients (89% and 86%; log-rank P value vs. 0MMDDK, 0.34 and 0.18, respectively). Among all groups, MMDDK showed the worst patient survival (71%; log-rank P value vs. 0MMDDK, 0.001) Conclusion Patient and kidney graft survival of 0MMDDK recipients were comparable to both SPK and LDK recipients. These findings suggest that T1DM patients awaiting SPK may consider accepting a 0MMDDK if an offer is available.

Outcomes of kidney transplantation in patients with hepatitis B virus infection: A systematic review and meta-analysis

AIM To assess outcomes of kidney transplantation including patient and allograft outcomes in recipients with hepatitis B virus (HBV) infection, and the trends of patient’s outcomes overtime. METHODS A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through October 2017. Studies that reported odds ratios (OR) of mortality or renal allograft failure after kidney transplantation in patients with HBV [defined as hepatitis B surface antigen (HBsAg) positive] were included. The comparison group consisted of HBsAg-negative kidney transplant recipients. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017080657). RESULTS Ten observational studies with a total of 87623 kidney transplant patients were enrolled. Compared to HBsAg-negative recipients, HBsAg-positive status was significantly associated with increased risk of mortality after kidney transplantation (pooled OR = 2.48; 95%CI: 1.61-3.83). Meta-regression showed significant negative correlations between mortality risk after kidney transplantation in HBsAg-positive recipients and year of study (slopes = -0.062, P = 0.001). HBsAg-positive status was also associated with increased risk of renal allograft failure with pooled OR of 1.46 (95%CI: 1.08-1.96). There was also a significant negative correlation between year of study and risk of allograft failure (slopes = -0.018, P = 0.002). These associations existed in overall analysis as well as in limited cohort of hepatitis C virus-negative patients. We found no publication bias as assessed by the funnel plots and Egger’s regression asymmetry test with P = 0.18 and 0.13 for the risks of mortality and allograft failure after kidney transplantation in HBsAg-positive recipients, respectively. CONCLUSION Among kidney transplant patients, there are significant associations between HBsAg-positive status and poor outcomes including mortality and allograft failure. However, there are potential improvements in patient and graft survivals in HBsAg-positive recipients overtime.

HLA-DQ Mismatching and Kidney Transplant Outcomes

BACKGROUND AND OBJECTIVES Recent evidence suggests that HLA epitope-mismatching at HLA-DQ loci is associated with the development of anti-DQ donor-specific antibodies and adverse graft outcomes. However, the clinical significance of broad antigen HLA-DQ mismatching for graft outcomes is not well examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Using the United Network Organ Sharing/the Organ Procurement and Transplantation Network (UNOS/OPTN) data, patients with primary kidney transplants performed between 2005 and 2014 were included. Patients were classified as having either zero HLA-DQ mismatches, or one or two HLA-DQ mismatches. Primary outcomes were death-censored graft survival and incidence of acute rejection. RESULTS A total of 93,782 patients were included. Of these, 22,730 (24%) and 71,052 (76%) received zero and one or two HLA-DQ mismatched kidneys, respectively. After adjusting for variables including HLA-ABDR, HLA-DQ mismatching was associated with a higher risk of graft loss in living kidney donor recipients with an adjusted hazard ratio (HR) of 1.18 (95% confidence interval [95% CI], 1.07 to 1.30; P<0.01), but not in deceased kidney donor recipients (HR, 1.05; 95% CI, 0.98 to 1.12; P=0.18) (P value for interaction <0.01). When taking cold ischemic time into account, HLA-DQ mismatching was associated with a higher risk of graft loss in deceased kidney donor recipients with cold ischemic time ≤17 hours (HR, 1.12; 95% CI, 1.02 to 1.27; P=0.002), but not in deceased kidney donor recipients with cold ischemic time >17 hours (HR, 0.97; 95% CI, 0.88 to 1.06; P=0.49) (P value for interaction <0.01). Recipients with one or two HLA-DQ mismatched kidneys had a higher incidence of acute rejection at 1 year, with adjusted odds ratios of 1.13 (95% CI, 1.03 to 1.23; P<0.01) in deceased donor and 1.14 (95% CI, 1.03 to 1.27; P=0.02) in living donor kidney transplant recipients. Specific donor-DQ mismatches seemed to be associated with the risk of acute rejection and graft failure, whereas others did not. CONCLUSIONS HLA-DQ mismatching is associated with lower graft survival independent of HLA-ABDR in living donor kidney transplants and deceased donor kidney transplants with cold ischemia time ≤17 hours, and a higher 1-year risk of acute rejection in living and deceased donor kidney transplants.

Idiopathic Granulomatous Interstitial Nephritis Responsive to Mycophenolate Mofetil Therapy

Granulomatous interstitial nephritis (GIN) is a rare histologic disease. Various causes have been reported in the literature, including drugs, sarcoidosis, and infections. Other incidents have no discernible cause and are identified as idiopathic. We report a 68-year-old white man who presented with acute kidney injury and was given a diagnosis of idiopathic GIN. Mycophenolate mofetil treatment was elected because of steroid toxicity. He responded well to mycophenolate mofetil and has been in remission for more than 3 years. To our knowledge, this is the first report of successful treatment with mycophenolate mofetil of an adult patient with idiopathic GIN.