Association of HLA class II alleles and haplotypes with bullous and mucus membrane pemphigoid risk: A systematic review, a meta-analysis and a meta-regression.

Although, several studies have assessed the association of HLA Class II and genes with bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP), results were inconsistent and between-studies heterogeneity needs to be investigated. An electronic literature search for eligible studies among all papers published prior to May 31, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the three following HLA genes: DRB1, DQA1 and DQB1. Combined analyses revealed a significant increase in pemphigoid risk conferred by the following alleles: DQB1*0301, DRB1*11, DRB1*1101 subtype and DQA1*0505, all p-values <.001. However, there was a moderate to high level of between-studies heterogeneity. Subgroup analyses revealed that the risk conferred by the aforementioned alleles was significantly higher in case of dipeptidyl peptidase-4 inhibitors induced BP (DBP) comparatively to idiopathic BP and MMP. In addition, the risk conferred by the DQB1*0301 was significantly higher in MMP (OR [95% CI] = 5.25 [4.03-6.84]) than in BP (OR [95% CI] = 2.22 [1.87-2.65]), p = .007. Besides, the DRB1*1101-DQB1*0301 and DRB1*11-DQA1*05-DQB1*0301 haplotypes were significantly associated with an increased pemphigoid risk, both p-values <.001. Conversely, the DQA1*0201 allele was significantly associated with reduced pemphigoid risk (OR [95% CI] = 0.3 [0.17-0.52]), with no between-studies heterogeneity (I2 = 0%, p = .76). This meta-analysis demonstrated that the DRB1*1101, DQA1*0505 and DQB1*0301 were significantly associated with increased pemphigoid risk. These associations were found to be significantly stronger in case of DBP comparatively to idiopathic pemphigoid. The DQA1*0201 allele seems to play a protective role against pemphigoid. Registration: This review has been registered on PROSPERO: CRD42024552821, Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024552821.

Association of four CTLA-4 gene polymorphisms with pemphigus risk: a systematic review, meta-analysis, and meta-regression.

OBJECTIVES: This review aimed to summarize the existing data on the contribution of four single nucleotide polymorphisms (SNPs) in the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) genes to pemphigus susceptibility. METHODS: An electronic literature search for eligible studies among those published prior to 30 April 2024 was conducted through the PubMed, EMBASE, Web of Science, and Scopus databases. To minimize publication bias, an additional search was performed via the Google Scholar and Semantic Scholar search engines. Meta-analyses, together with subgroup analyses and meta-regressions, were performed for the following four CTLA-4 SNPs: rs231775, rs5742909, rs3087243, and rs733618. RESULTS: Combined analyses revealed a significant increase in pemphigus risk conferred by the CTLA-4 rs5742909*C and rs733618*C alleles. Conversely, there was no evidence of any significant association between the rs231775*G and rs3087243*G alleles and susceptibility to pemphigus. Subgroup analyses by ethnicity and pemphigus type (vulgaris or foliaceus) and meta-regressions did not reveal any significant difference. CONCLUSION: This meta-analysis suggested that two of the four investigated CTLA-4 SNPs were significantly associated with increased pemphigus risk.Registration: This review has been registered on PROSPERO: CRD42024550668; available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024550668.

A regression predictive model for QuantiFERON-TB Gold Plus® indeterminate results in immunosuppressed patients.

Background: Screening for latent tuberculosis infection using Interferon-Gamma Release Assays is a routine procedure prior to the initiation of anti-tumor necrosis factor (TNF) biotherapy or immunosuppressive therapy. However, indeterminate results are relatively frequent and are an obstacle to treatment initiation. Aim: The aim of this cross-sectional study was to estimate the frequency of indeterminate QuantiFERON-TB Gold Plus® test results in Tunisian patients, and to analyze the potential clinico-biological risk factors associated with these indeterminate results. Methods: Whole blood samples from 712 patients being monitored for autoimmune diseases and candidates for anti-TNF biotherapy or switch of immunosuppressive therapy were used to screen for latent tuberculosis infection using the QuantiFERON-TB Gold Plus® test. Based on literature background, the following variables were tested for the association with indeterminate results: gender, age, diabetes, immunosuppressive drugs, lymphocyte count, Neutrophil-to-lymphocyte ratio, serum albumin, and estimated glomerular filtration rate. Results: The QuantiFERON-TB Gold Plus® test was negative in 572 (80.3%) patients, positive in 106 (14.9%), and indeterminate in 34 (4.8%) cases. Positive results were significantly associated with a family history of confirmed and treated tuberculosis, OR (95% CI) = 52 (20.2-134.3). The use of immunosuppressive drugs and duration of treatment were significantly associated with the occurrence of indeterminate results: OR (95% CI) = 24.5 (5.8-103) and OR (95% CI) = 1.004 (1.002-1.007), respectively. Biologically, lymphopenia, hypoalbuminemia, and decreased estimated glomerular filtration rate were significant risk factors for indeterminate results: p = 5 E-6, p = 4.3 E-4, and p = 0.002, respectively. Thus, a multiple logistic regression model based on these three biological parameters enabled us to develop a predictive score for indeterminate results with a sensitivity of 91.2% and a specificity of 99.9%, AUC = 0.9964 (0.9917-1), p = 2.8 E-52. Conclusion: Immunosuppressive therapy, lymphopenia, hypoalbuminemia, and kidney failure appeared to be risk factors for indeterminate QuantiFERON-TB Gold Plus® results.

Impact of IL-10 gene promoter polymorphisms on treatment response in HCV patients: A systematic review, a meta-analysis, and a meta-regression.

The impact of interleukin-10 (IL-10) gene promoter polymorphisms (SNPs) on treatment response in HCV patients was dissimilarly estimated. Hence, the aim of this meta-analysis was to robustly assess the effect of IL-10 SNPs on treatment response in HCV patients. An electronic literature search was carried out through PubMed, EMBASE, Web of science, and Scopus databases. Studies assessing the association between IL-10 polymorphisms and treatment response in HCV patients were included. Studies were excluded if genotype frequencies are not consistent with the Hardy-Weinberg Equilibrium (HWE) or in case of including patients with hepatitis B virus coinfection. Risk of bias in included studies was assessed using the Newcastle-Ottawa Scale. Meta-analyses were performed for the influence of IL-10 gene promoter SNPs (rs1800896 (-1082 A/G), rs1800871 (-819 C/T), and rs1800872 (-592 C/T)) and haplotypes on treatment response in HCV patients. Subgroup analyses, meta-regressions, publication bias assessment, and sensitivity analyses were also conducted. Overall, 32 studies with a total of 5943 HCV cases and 2697 controls were included in the present study. The -1082*G allele was significantly associated with increased risk of non-response (NR) to treatment, OR [95% CI] = 1.29 [1.1-1.51], p = .002. Besides, the rs1800872 -592*C allele was significantly associated with increased NR risk, OR [95% CI] = 1.22 [1.02-1.46], p = .03. Subgroup analysis showed that this association remained significant only in patients treated with PEG-IFN alone, p = .01. The -1082*G/-819*C/-592*C (GCC) haplotype was significantly associated with increased NR risk, OR [95% CI] = 1.62 [1.13-2.23], p = .009. Our results suggest that the IL-10 rs1800896 was associated with NR risk especially in North-African and Asian populations. Moreover, the IL-10 gene promoter -1082*G/-819*C/-592*C (GCC) haplotype which has been associated with higher production of IL-10, was significantly associated with increased NR risk.

Access to kidney transplantation for patients with end-stage renal failure in Maghreb countries: state of art and recommendations / Accès à la transplantation rénale des patients en insuffisance rénale chronique terminale dans les pays du Maghreb : état des lieux et recommandations

We present an overview of kidney transplantation activity in the Maghreb countries, based on data from the 9th Colloque France-Maghreb (Paris, May 20 and 21, 2022). For Algeria, Morocco and Tunisia, the incidence of end stage renal failure is respectively 120, 130 and 130 per million inhabitants, its prevalence 626, 900 and 833 per million inhabitants and the part of patients with a functional graft of 10.3, 1.8 et 8.5% with an annual number of transplants of 6.5, 0.8 and 8.7 per million inhabitants. Living donor transplants account for 99% of transplants in Algeria, 93% in Morocco and 80% in Tunisia. In conclusion, access to transplantation remains low in the Maghreb countries. All the modalities (living donor with enlargement of the circle of donors, deceased donors) must be further developed. Recommendations were issued to support activity.

Nous présentons un état des lieux de l'activité de transplantation rénale dans les pays du Maghreb à partir des données du 9e Colloque France-Maghreb (Paris, 20 et 21 mai 2022). Pour l'Algérie, le Maroc et la Tunisie, l'incidence de l'insuffisance rénale chronique terminale est respectivement de 120, 130 et 130 par million d'habitants, sa prévalence de 626, 900 et 833 par million d'habitants et la part des patients porteurs d'un greffon fonctionnel est de 10,3, 1,8 et 8,5 % avec un nombre annuel de transplantations de 6,5, 0,9 et 7,7 par million d'habitants. La transplantation avec donneur vivant représente 99 % des transplantations en Algérie, 93 % au Maroc et 80 % en Tunisie. En conclusion, l'accès à la transplantation reste faible dans les pays du Maghreb. Toutes les modalités (donneur vivant avec élargissement du cercle des donneurs, donneurs décédés) doivent être développées. Des recommandations ont été émises pour soutenir cette activité.

Knowledge and Attitudes Toward Organ Donation Among Tunisian Adults: Results of a National Survey.

OBJECTIVES: Attitudes and knowledge toward organ donation can influence a person's willingness to donate. The aim of this study was to assess attitudes and knowledge regarding organ donation among Tunisian adults. MATERIALS AND METHODS: We conducted a crosssectional survey at the national level from January 23 to February 15, 2017, among 1026 Tunisian adults. We used a standardized questionnaire to collect data by phone call. We performed statistical analyses with Stata software (version 11). RESULTS: The study included 495 male and 531 female participants. Forty-one percent of participants were 18 to 30 years old. In total, 81.7% had heard about organ donation. Fewer than half of respondents (47.8%) were aware that organ donation is regulated. In total, 80.7% accepted to donate their organs after death, and 32.2% had mentioned their opinion to relatives or friends. Only 1% had added their donor status on their national identity cards. CONCLUSIONS: Tunisian adults seem to have positive attitudes regarding organ donation. However, the proportion of respondents who included their donor status on their national identity cards was low. It is important to enhance information and education on organ donation in an effort to mitigate the shortage of organs.

Predicting long-term outcomes of kidney transplantation in the era of artificial intelligence.

The ability to accurately predict long-term kidney transplant survival can assist nephrologists in making therapeutic decisions. However, predicting kidney transplantation (KT) outcomes is challenging due to the complexity of the factors involved. Artificial intelligence (AI) has become an increasingly important tool in the prediction of medical outcomes. Our goal was to utilize both conventional and AI-based methods to predict long-term kidney transplant survival. Our study included 407 KTs divided into two groups (group A: with a graft lifespan greater than 5 years and group B: with poor graft survival). We first performed a traditional statistical analysis and then developed predictive models using machine learning (ML) techniques. Donors in group A were significantly younger. The use of Mycophenolate Mofetil (MMF) was the only immunosuppressive drug that was significantly associated with improved graft survival. The average estimated glomerular filtration rate (eGFR) in the 3rd month post-KT was significantly higher in group A. The number of hospital readmissions during the 1st year post-KT was a predictor of graft survival. In terms of early post-transplant complications, delayed graft function (DGF), acute kidney injury (AKI), and acute rejection (AR) were significantly associated with poor graft survival. Among the 35 AI models developed, the best model had an AUC of 89.7% (Se: 91.9%; Sp: 87.5%). It was based on ten variables selected by an ML algorithm, with the most important being hypertension and a history of red-blood-cell transfusion. The use of AI provided us with a robust model enabling fast and precise prediction of 5-year graft survival using early and easily collectible variables. Our model can be used as a decision-support tool to early detect graft status.

Pre- and Post-treatment Serum BAFF Levels and BAFF Gene Polymorphisms in Patients with Graves' Disease.

BACKGROUND: B cell activating factor (BAFF), a crucial factor for B cell survival and differentiation, has been linked to several autoimmune conditions. The aim of this study was to evaluate the association of BAFF gene's polymorphisms with its serum levels and to assess their effect on Graves' disease (GD) susceptibility and presentation. METHODS: Sixty-two GD patients and 152 healthy controls have been enrolled to investigate BAFF rs9514827 (-2841 T/C), rs1041569 (-2701 T/A) and rs9514828 (-871 C/T) gene's polymorphism by PCR-RFLP and serum BAFF level's kinetics under medical treatment by ELISA. RESULTS: Median serum BAFF level at baseline was significantly higher in GD patients (841.7 pg/ml [685.23-1058.32]) comparatively to controls (495.75 pg/ml [383.17-595.7]), p = 7.29 E-25. A ROC curve was used to assess BAFF performances in GD diagnosis and revealed an AUC of 94.9% [0.919-0.979], p = 7.29 E-25. At a cutoff value of 654.9 pg/ml of BAFF at baseline, the sensitivity and the specificity were, respectively, 83.9% and 90.8%. BAFF level was significantly increased in smoking patients (1079.55 pg/ml [875.35-1203]) comparatively to nonsmokers (746.95 pg/ml [643.2-915.7]), p = 3.1 E-5. While -2841 T/C and -2701 T/A genotypes and alleles frequencies were similar between patients and controls, the -871*T allele was significantly more prevalent in patients (0.613) than in controls (0.477); p = .01, OR [95% CI] = 1.73 [1.13-2.65]. The three studied polymorphisms were not associated with serum BAFF level at baseline. CONCLUSION: Serum BAFF level is significantly increased in GD especially in smoking patients. rs9514828 - 871*T allele might be a susceptibility variant for GD.

Toward generalizing the use of artificial intelligence in nephrology and kidney transplantation.

With its robust ability to integrate and learn from large sets of clinical data, artificial intelligence (AI) can now play a role in diagnosis, clinical decision making, and personalized medicine. It is probably the natural progression of traditional statistical techniques. Currently, there are many unmet needs in nephrology and, more particularly, in the kidney transplantation (KT) field. The complexity and increase in the amount of data, and the multitude of nephrology registries worldwide have enabled the explosive use of AI within the field. Nephrologists in many countries are already at the center of experiments and advances in this cutting-edge technology and our aim is to generalize the use of AI among nephrologists worldwide. In this paper, we provide an overview of AI from a medical perspective. We cover the core concepts of AI relevant to the practicing nephrologist in a consistent and simple way to help them get started, and we discuss the technical challenges. Finally, we focus on the KT field: the unmet needs and the potential role that AI can play to fill these gaps, then we summarize the published KT-related studies, including predictive factors used in each study, which will allow researchers to quickly focus on the most relevant issues.

The effects of the CYP3A5*3 variant on tacrolimus pharmacokinetics and outcomes in Tunisian kidney transplant recipients.

INTRODUCTION: Tacrolimus, exhibits interindividual pharmacokinetic variability and a narrow therapeutic index. The influence of the CYP3A5 6986A>G single nucleotide polymorphism (SNP) on this variability remains a topic of debate. AIM: To assess the impact of the aforementioned SNP on tacrolimus area under curve (AUC0-12h), adverse drug reactions (ADRs), and kidney graft outcomes. METHODS: Blood samples were collected from Tunisian kidney transplants over a five-year period during either the early (<3 months) or late (>3 months) post-transplant phases. Through blood concentration (C0) and AUC0-12h of tacrolimus were measured. Patients were prospectively followed to assess graft outcomes. Polymerase chain reaction of restriction fragment length polymorphism was used for CYP3A5 6986A>G genotyping. RESULTS: Fifty Tunisian kidney recipients receiving tacrolimus were enrolled in the study. Acute and chronic graft rejections were observed in eight and three patients, respectively. Twenty-one patients (42%) reported ADRs. C0 and AUC0-12h, showed a significant difference between CYP3A5*1 carriers (mean C0=4 ng.mL-1 and AUC0-12h=94.37 ng.h.mL-1) and CYP3A5*3/3 or poor metabolizers carriers (mean C0=7.45 ng.mL-1; AUC0-12h=151.27 ng.h.mL-1) (p=0.0001; p=0.003, respectively). Supratherapeutic tacrolimus levels were significantly more common in poor metabolizers (p=0.046; Odds-ratio =1.3; confidence interval 95% [1.12-1.66]). The impact of SNP was significant on C0, AUC0-12h, C0/Dose and AUC0-12h/Dose, only in the late phase (p=0.01, 0.002, 0.012, 0.003 respectively). CONCLUSION: CYP3A5*3 variant was significantly associated with tacrolimus pharmacokinetics but had no impact on graft outcomes.

Peritoneal dialysis in the era of COVID-19: experience of a Tunisian center.

The COVID-19 pandemic has transformed the health landscape by hampering the management of patients with chronic diseases. Providing optimal healthcare has become a critical issue, especially for patients with end-stage renal disease (ESRD) receiving in-center dialysis. Peritoneal Dialysis (PD) has the advantage of being a home-based therapy. Several papers about COVID-19 in the chronic kidney disease (CKD) population have been published, but few studies focused on the PD population, with limited case series. In this paper, we share our strategy for managing PD patients during the pandemic and describe the characteristics of 24 episodes of COVID-19 that occurred in our PD patients. Also, we report the impact of the pandemic on different outcomes and discuss the challenges of renal replacement therapy (RRT) in the time of COVID-19 and the advantages of PD. During the period from December 2019 to September 2021, 127 patients received PD in our center. Among them, we recorded 24 episodes of COVID-19 that occurred in 20 patients, corresponding to an incidence of 8.4 per 1000 patient-months. None of the 20 patients with COVID-19 were vaccinated and there was a significant male gender predominance in the COVID-19 group compared to the non-COVID-19 group. The prevalence of diabetic nephropathy and primary glomerulonephritis were also significantly higher in the COVID-19 group. The revealing symptoms were asthenia, dry cough, and the deterioration of general conditions in 100%, 75%, and 63% of the patients, respectively. A biological inflammatory syndrome was found in 30% of the patients. Chest computed tomography (CT) scan, performed in 5 patients, showed features of COVID pneumonia with an average extent of damage of 55%. The rate of patients starting PD during the study period was comparable to that before the pandemic. Furthermore, we did not find a significant difference between the infected and the non-infected groups regarding the incidence of peritonitis, PD technique failure, and mortality (6.1 [0-1.46] vs 3.9 [0.15-0.64] deaths per 1000 patient-months. COVID-19 does not seem to have influenced the outcomes of our patients treated with PD even before the launch of mass immunization in our country. Thus, PD can be a great option for RRT in the era of the COVID-19 pandemic since many issues could be managed remotely to avoid regular hospital visits and contribute to maintaining social distancing, which is the cornerstone of breaking the chain of transmission of the novel virus.

Comparative study of six SARS-CoV-2 serology assays: Diagnostic performance and antibody dynamics in a cohort of hospitalized patients for moderate to critical COVID-19.

BACKGROUND: To overcome the COVID-19 pandemic, serology assays are needed to identify past and ongoing infections. In this context, we evaluated the diagnostic performance of 6 immunoassays on samples from hospitalized patients for moderate to critical COVID-19. METHODS: 701 serum samples obtained from 443 COVID-19 patients (G1: 356 positive RT-PCR patients and G2: 87 negative RT-PCR cases) and 108 pre-pandemic sera from blood donors were tested with 6 commercial immunoassays: (1) Elecsys Anti-SARS-CoV-2, Roche (Nucleocapsid, N), (2) Elecsys Anti-SARS-CoV-2 S, Roche (Spike, S), (3) Vidas SARS-COV-2 IgM/IgG, BioMérieux (S), (4) SARS-CoV-2 IgG, Abbott (N), (5) Access SARS-CoV-2 IgG, Beckman Coulter (Receptor Binding Domain), and (6) Standard F COVID-19 IgM/IgG Combo FIA, SD Biosensor (N). RESULTS: Global sensitivities of the evaluated assays were as follows: (1) Roche anti-N = 74.5% [69.6-79.3], (2) Roche anti-S = 92.7% [84.7-100], (3) Vidas IgM = 74.9% [68.6-81.2], (4) Vidas IgG = 73.9% [67.6-80.1], (5) Abbott = 78.6% [63.4-93.8], (6) Beckman Coulter = 74.5% [62-86.9], (7) SD Biosensor IgM = 73.1% [61-85.1], and (8) SD Biosensor IgG = 76.9% [65.4-88.4]. Sensitivities increased gradually from week 1 to week 3 as follow: (1) Roche anti-N: 63.3%, 81% and 82.1%; (2) Vidas IgM: 68.2%, 83.2% and 85.9%; and (3) Vidas IgG: 66.7%, 79.1% and 86.6%. All immunoassays showed a specificity of 100%. Seropositivity was significantly associated with a higher frequency of critical COVID-19 (50.8% vs. 38.2%), p = 0.018, OR [95% CI] = 1.668 [1.09-2.553]. Inversely, death occurred more frequently in seronegative patients (28.7% vs. 13.6%), p=3.02 E-4, OR [95% CI] = 0.392 [0.233-0.658]. CONCLUSION: Evaluated serology assays exhibited good sensitivities and excellent specificities. Sensitivities increased gradually after symptoms onset. Even if seropositivity is more frequent in patients with critical COVID-19, it may predict a recovery outcome.

[Renal involvement in sarcoidosis: Prognostic and predictive factors]. / Atteinte rénale au cours de la sarcoïdose : facteurs pronostiques et prédictifs.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease that primarily affects the respiratory system and lymphatic vessels. Renal involvement is rare, poorly studied and found in less than 10% of cases. The objective of our study was to identify factors of poor renal prognosis and predictive factors of renal involvement during sarcoidosis. METHODS: It's a retrospective study including patients hospitalized in our department for sarcoidosis with renal involvement over a period of 40 years. To study renal survival, we identified two groups of patients with renal manifestations of sarcoidosis by following their evolution: group A (n=26) represents those with renal remission or deterioration of renal function but without progression to end-stage renal disease and group B (n=8) those with progression to end-stage renal disease. To detect the predictive factors of end-stage renal disease in patients with sarcoidosis, we compared the clinical and paraclinical characteristics of our patients (group 1) to those of 44 patients with sarcoidosis without renal impairment followed in our department during the same period (group 2). RESULTS: Renal involvement was observed in 34 patients hospitalized for sarcoidosis (43.6%). There were 28 women and 6 men with a sex ratio of 0,21. The mean age at diagnosis of sarcoidosis was 47.1 years. The median time from sarcoidosis diagnosis to renal disease was 2 months (range 1-72). Tubulointerstitial nephropathy was the most frequent renal manifestation observed in 24 patients (70.6%). Hypercalcemia and hypercalciuria were found in 52.9% and 46.4% respectively. Renal failure was noted in 25 patients (73.5%). Corticosteroid therapy was initiated in 33 patients (97%) associated with immunosuppressive therapy in 3 cases. Predictive factors of end-stage renal disease were advanced age at diagnosis of nephropathy (P=0.007), comorbidities (P=0.002), multi-organ involvement (P=0.041), initial renal failure (P=0.013), interstitial fibrosis (P=0.006) and renal granulomas (P=0.007). Predictive factors of renal impairment during sarcoidosis were multi-organ involvement, inflammatory syndrome and hypercalcemia. CONCLUSION: Renal envolvement, although rare during sarcoidosis, can influence the prognosis hence the great interest of its early detection to prevent progression to end-stage renal failure.

[Emphysematous pyelonephritis and cystitis: An exceptional complication in a kidney transplant recipient]. / Pyélonéphrite et cystite emphysémateuses : une complication exceptionnelle chez un transplanté du rein.

Emphysematous pyelonephritis is a rare and severe infectious complication characterized by the presence of gas in the renal parenchyma, excretory cavities and surrounded tissues. It is due to the development of non-anaerobic gasifier bacteria. We report a new rare case of emphysematous pyelonephritis in a kidney transplant recipient, particular by its occurrence in a non-functional graft and its exceptional association with emphysematous cystitis.

[Successful treatment with paclitaxel of a visceral relapse of post-transplant Kaposi's sarcoma]. / Succès du traitement par paclitaxel d'une rechute viscérale d'un sarcome de Kaposi après transplantation rénale.

We report the observation of a patient who presented with post-transplant Kaposi's sarcoma after a delay of eight months with a dual cutaneous and palatal localisation. The reduction in immunosuppressive treatment and the introduction of Rapamune® allowed good clinical progress initially with regression of the skin lesions. He subsequently presented later a skin relapse with visceral localisation. Chemotherapy was conducted based on weekly paclitaxel infusions allowing partial remission and maintenance of renal graft function with good clinical tolerance.

Deep vein thrombosis: An unusual way of revealing microscopic polyangiitis. Deep vein thrombosis in microscopic polyangiitis.

Unexplained deep vein thrombosis may justify screening for antineutrophil cytoplasmic antibody-associated vasculitis as it can be an unusual presentation of this disease.

[Etiologies and prognostic factors of acute interstitial nephritis]. / Étiologies et facteurs pronostiques des néphropathies interstitielles aiguës.

INTRODUCTION: Acute interstitial nephritis represents a clinically and etiologically heterogeneous group of kidney diseases. The aim of our study was to explore the main causes of biopsy-proven acute interstitial nephritis and to identify predictive factors of renal outcome. METHODS: We conducted a retrospective monocentric study which included patients with biopsy proven AIN, followed in our department during the period between 1980 and 2018. The non-recovery of kidney function or an estimated glomerular filtration rate˂60 mL/min/1.73 m2 were considered as a worse renal outcome. RESULTS: A total of 65 acute interstitial nephritis patients were enrolled. The mean age of patients was 41.3±16 years with a female predominance (78%). Drug-induced etiology was the most common (29%). The most frequent culprit drugs in our study were NSAID followed by antibiotics. The renal prognosis was unfavorable in 21 cases (32%). The independent predictive factors for renal outcome were : a percentage of sclerotic glomeruli greater than 15% (P=0.004), absence of interstitial edema (P˂0.001), non-use to corticosteroid therapy (P=0.02) and a delay in initiating corticosteroid therapy greater than 21 days (P=0.02). CONCLUSION: Drugs currently represent the most common cause of acute interstitial nephritis. The renal prognosis is often favorable, but the progression can be towards chronic renal failure in the event of diagnostic and therapeutic delay. Our data suggest a beneficial influence of steroids on the outcome of acute interstitial nephritis.

PLA2R antibody, PLA2R rs4664308 polymorphism and PLA2R mRNA levels in Tunisian patients with primary membranous nephritis.

BACKGROUND: Primary membranous nephritis (PMN) is an autoimmune disease induced by the deposit of antibodies (Ab) to the phospholipase receptor A2 receptor (PLA2R) on podocytes. In this context, we aimed to assess the relationships between anti-PLA2R Ab, PLA2R rs4664308 SNP, PLA2R mRNA levels and PMN susceptibility and outcome. METHODS: Sixty-eight PMN patients, 30 systemic lupus erythematosus (SLE) patients with secondary MN and 30 healthy control subjects served for anti-PLA2R Ab measurement by ELISA and PLA2R rs4664308 SNP genotyping by a commercial real-time PCR. Twenty patients with tubulo-interstitial nephritis (TIN) were used as controls for renal PLA2R mRNA quantification in PMN patients from kidney biopsies. PLA2R mRNA quantification was carried-out by real-time PCR after RNA extraction. RESULTS: Forty-three (63.2%) PMN patients received initial therapy consisting of alternating monthly cycles of corticosteroids and cyclophosphamide. Twelve (17.6%) patients had resistant PMN to initial therapy and were consecutively treated by cyclosporine or tacrolimus. Anti-PLA2R Ab were positive in 54 (79.4%) PMN patients, while all SLE patients and controls were negative, p<0.0001. Moreover, anti-PLA2R Ab levels were significantly higher in PMN patients (134.85 [41.25-256.97] RU/ml) than in SLE patients (3.35 [2.3-4.35] RU/ml) and controls (2 [2-2.3]), p<0.0001. Consequently, a ROC curve showed for 100% specificity a sensitivity of 94.1% at a threshold of 2.6 RU/ml. Besides, Anti-PLA2R antibodies levels were significantly associated to non-remission; p = 0.002. The rs4664308*A wild-type allele was significantly more frequent in PMN patients (0.809) than in controls (0.633) and SLE patients (0.65); p = 0.008, OR [95% CI] = 2.44 [1.24-4.82] and p = 0.016, OR [95% CI] = 2.27 [1.15-4.5], respectively. Renal PLA2R mRNA levels were significantly higher in PMN patients (218.29 [66.05-486.07]) than in TIN patients (22.09 [13.62-43.34]), p<0.0001. Moreover, PLA2R mRNA levels were significantly higher in non-remission patients (fold-factor vs. partial remission = 2.46 and fold-factor vs. complete remission = 12.25); p = 1.56 10E-8. In addition, PLA2R mRNA and anti-PLA2R Ab levels were significantly correlated, Spearman Rho = 0.958, p<0.0001. CONCLUSION: Anti-PLA2R Ab and renal PLA2R mRNA could be useful markers for PMN outcome predicting. The PLA2R rs6446308 SNP is associated with PMN susceptibility in Tunisians.

Prevalence and risk factors of hypogonadism in men with chronic renal failure.

AIM: To determine the prevalence and the risk factors of hypogonadism in men with chronic renal failure (CRF). METHODS: We conducted a cross sectional analysis in 48 men with CRF. Total testosterone, prolactin, and gonadotropins were measured in all patients. Hypogonadism was defined by a low level (<10 nmol/l) or a low normal level (10-14 nmol/l) of total testosterone. RESULTS: The mean age was 53.31±10.22 years. Renal impairment was mild, moderate, severe and at end stage in 9,14,4 and 21 patients, respectively. Nineteen patients had been undergoing extra-renal purification. The average of total testosterone was 13.44±6.17 nmol/L. It was lower in patients with diabetic nephropathy (p=0.004). Hypogonadism was diagnosed in 22 patients (46 %). In this group, gonadotropins were normal in 21 cases and elevated in only one case. Hyperprolactinemia was retained in six patients. Type 2 diabetes (OR: 3.96; p=0.02) and diabetic nephropathy (OR=4.26; p=0.01) were the only risk factors of hypogonadism in our patients. CONCLUSION: Our results had demonstrated a high prevalence of hypogonadism in males with chronic renal failure. This hormone disorder was associated with type 2 diabetes and diabetic nephropathy.

Early interaction between tacrolimus and rifampin.

Drug interactions are unavoidable and need to be proactively identified and managed, in particular, the inductive effect of rifampin on tacrolimus whose potency and duration data are limited. We report the case of a renal transplant patient who was prescribed tacrolimus with preserved tough blood levels (C0) of 7.9 +/- 2 ng/mL. He presented ganglionic tuberculosis and started rifampin. One day later, C0 was 2.6 ng/mL with 5 mg/day. The serum creatinin was normal. Nine days later, C0 was 1.6 ng/mL with 7 mg/day. In this case-report, the tacrolimus-rifampin interaction occurred just one day after rifampin introduction necessitating early C0 monitoring.