Therapeutic drug monitoring of mycophenolic acid and azole antifungals on two distinct LC-MS/MS instruments.

Background: As an active metabolite of a commonly prescribed immunosuppressant, mycophenolic acid (MPA) levels are often monitored to prevent organ rejection following a transplant. Triazoles are often prescribed for treatment of invasive fungal infections in immunocompromised patients. Due to the variability in individual pharmacokinetics and drug-drug interactions, therapeutic drug monitoring is recommended for triazole antifungals. A multiplex LC-MS/MS assay has been developed that can quantify both MPA and triazole drugs in serum. Methods: A sample preparation procedure was established to spike in internal standard compounds and precipitate proteins. Reversed-phase chromatographic separation was performed on a C18 column with an analysis time of five minutes per sample. The mass spectrometer was operated in multiple reaction monitoring mode. The method was validated on two HPLC systems interfaced with either a Triple Quad 6500 or an API 4000 instrument. Results: The multiplex assay was linear over a wide dynamic range with analyte measurable ranges of 0.4-48 µg/mL for MPA, 0.1-12 µg/mL for posaconazole, and 0.2-24 µg/mL for voriconazole, itraconazole, hydroxyitraconazole, and isavuconazole. The between-day and intraday imprecisions were less than 10 %. Limits of detection were below 0.04 ug/mL with limits of quantitation below 0.2 µg/mL. Method comparison studies against the current in-house method met acceptance criteria. The instrument comparison study demonstrated a strong correlation between data collected from the two systems. Conclusion: A robust multiplex LC-MS/MS assay was developed and validated for monitoring MPA and triazoles drug levels in a clinical laboratory. The assay performance on two distinct instruments was acceptable and comparable.

Tailored Polymersomes for Enhanced Oral Drug Delivery: pH-Sensitive Systems for Intestinal Delivery of Immunosuppressants.

Ensuring precise drug release at target sites is crucial for effective treatment. Here, pH-responsive nanoparticles for oral administration of mycophenolate mofetil, an alternative therapy for patients with inflammatory bowel disease unresponsive to conventional treatments is developed. However, its oral administration presents challenges due to its low solubility in the small intestine and high solubility and absorption in the stomach. Therefore, this aim is to design a drug delivery system capable of maintaining drug solubility compared to the free drug while delaying absorption from the stomach to the intestine. Successful synthesis and assembly of a block copolymer incorporating a pH-responsive functional group is achieved. Dynamic light scattering indicated a significant change in hydrodynamic size when the pH exceeded 6.5, confirming successful incorporation of the pH-responsive group. Encapsulation and controlled release of mycophenolate mofetil are efficiently demonstrated, with 90% release observed at intestinal pH. In vitro cell culture studies confirmed biocompatibility, showing no toxicity or adverse effects on Caco-2 cells. In vivo oral rat studies indicated reduced drug absorption in the stomach and enhanced absorption in the small intestine with the developed formulation. This research presents a promising drug delivery system with potential applications in the treatment of inflammatory bowel disease.

Breaking Out of the Hive: A Case Report on Hypocomplementemic Urticarial Vasculitis Syndrome.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disorder characterized by chronic urticaria, systemic vasculitis, and hypocomplementemia, posing significant diagnostic challenges due to its overlap with common conditions and varied systemic manifestations. We report the case of a 36-year-old female with a history of post-birth cerebral hemorrhage and seizure disorder, who presented with abdominal pain, diarrhea, and subtle urticarial lesions. Initial investigations by gastroenterology suggested inflammatory bowel disease (IBD), but persistent symptoms and evolving cutaneous signs prompted further evaluation. A skin biopsy demonstrated leukocytoclastic vasculitis, while serological tests showed hypocomplementemia and positive antineutrophil cytoplasmic antibodies (ANCA), confirming HUVS. The patient's management included high-dose corticosteroids and mycophenolate mofetil, with partial symptom relief. Subsequent introduction of rituximab markedly improved her gastrointestinal and dermatological symptoms, highlighting its effectiveness in treating refractory HUVS. This case emphasizes the necessity for vigilance, interdisciplinary collaboration, and personalized treatment adaptations in managing HUVS.

Outcomes in Patients with Vogt-Koyanagi-Harada Disease from the First-line Antimetabolites for Steroid-sparing Treatment Uveitis Trial.

PURPOSE: To compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: A subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX versus MMF) and disease stage (acute versus chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25mg weekly oral MTX or 1.5g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). RESULTS: Ninety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P=.12) or in BSCVA improvement (P=.78). Methotrexate was superior to MMF in reducing CST (P=.003) and resolving SRD (P=.02). There was no significant difference in treatment success by disease stage (P=.25), but patients with acute VKH had greater improvement in BSCVA (P<.001) and reduction of CST (P=.02) than chronic VKH patients. CONCLUSIONS: MTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182929.

Influence of interruption of oral mycophenolate mofetil for graft-versus-host disease prophylaxis on outcomes after single cord blood transplantation.

Mycophenolate mofetil (MMF), in combination with a calcineurin inhibitor, is used as the prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Compared to intravenous methotrexate (MTX), MMF is associated with a lower incidence of mucositis and shorter time for hematopoietic engraftment but comparable incidence of acute GVHD, resulting in the preferred use of MMF for GVHD prophylaxis in elderly patients or those undergoing cord blood transplantation (CBT). Although several studies have evaluated the clinical impact of MTX omission due to toxicity after allogeneic HCT, the impact of oral MMF interruption for GVHD prophylaxis on transplant outcomes remains unclear. Therefore, in this study, we retrospectively analyzed the consecutive data of adult patients who underwent single-unit unrelated CBT and received oral MMF in combination with cyclosporine for GVHD prophylaxis at our hospital. Among the 53 patients, the planned dose of MMF was interrupted in 14 with a median of 19.5 d (range, 3-27 d) of CBT. In multivariate analysis, MMF interruption, which was treated as a time-dependent covariate, was significantly associated with poorer overall survival (hazard ratio [HR], 5.41; 95% confidence interval [CI], 2.03-14.43; P < 0.001) and higher non-relapse mortality (HR, 7.56; 95% CI, 1.99-28.79; P = 0.002). Further studies with larger cohorts are necessary to confirm the clinical significance of oral MMF interruption in GVHD prophylaxis.

Mechanisms of gastrointestinal toxicity in neuromyelitis optica spectrum disorder patients treated with mycophenolate mofetil: insights from a mouse model and human study.

Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial ß-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The ß-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF. IMPORTANCE: Neuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.

Pancytopenia as a first presentation of late-onset systemic lupus erythematosus: a case report.

Introduction: Systemic lupus erythematosus (SLE) is a systemic immune disease that classically occurs in young to middle-aged women and may present with cutaneous, renal, haematologic, neurological, and/or other symptoms at the time of diagnosis. Late-onset SLE or SLE in the elderly is a subtype that differs from classic SLE in terms of age group, clinical symptoms, organ involvement and severity. Case presentation: A 63-year-old female noted to have pancytopenia. The patient was diagnosed with lupus upon obtaining clinical presentations and serological marker, along with high titres of the antinuclear antibody and/or anti-double-stranded DNA antibody. The patient was managed with glucocorticoids and mycophenolate mofetil therapy, which led to a rapid response. Discussion: Late-onset SLE accounts for 2-12% of SLE patients with a minimum age of onset of 50 years and older, leading to significant delays in diagnosis. Late-onset SLE differs from early-onset SLE in terms of sex and ethnicity prevalence, clinical symptoms and signs, development of organ damage, disease activity and severity, and prognosis. Some studies have also shown that late-stage SLE patients have higher rates of RF and anti-Ro/anti-La antibody positivity, lower complement titre, and higher incidence of elevated creatinine and decreased creatinine clearance. First-line treatment of pancytopenia is glucocorticoid. In refractory cases, rituximab and immunosuppressants can be used. Conclusion: It is important to assess any unusual presentation of SLEs when clinical suspicion remains high and conducting further laboratory and imaging investigation.

Successful Treatment with Mycophenolate Mofetil in a Patieint with Anti-MDA 5 Antibody-positive Interstitial Lung Disease and Posterior Reversible Encephalopathy syndrome: A Case Report.

A 59-year-old woman presented with a rash on the top part of her hands and pain in the wrist joint and was diagnosed with dermatomyositis complicated by interstitial pneumonia positive for anti-melanoma differentiation-associated gene 5 (MDA-5) antibody. However, the patient reported a severe headache following treatment with oral prednisolone and tacrolimus. Posterior reversible encephalopathy syndrome (PRES) was diagnosed based on the brain magnetic resonance imaging findings. Tacrolimus was discontinued, and mycophenolate mofetil was instead administered with a favorable outcome. Mycophenolate mofetil should therefore be considered as an alternative treatment for anti-MDA-5-positive interstitial lung disease in cases where calcineurin inhibitors cannot be used.

A Case of Immunomodulator-Responsive Hypersensitivity Pneumonitis Secondary to Chronic Passive Smoke Inhalation.

Hypersensitivity pneumonitis (HP) is a pulmonary disease characterized by inflammation and fibrosis of the lung parenchyma following chronic exposure to immunogenic antigens. The pathophysiology of HP involves type 3 and type 4 hypersensitivity reactions leading to acute and chronic manifestations, respectively. Clinically, it manifests as exertional dyspnea and wheezing. Pulmonary function tests display a pattern of restrictive lung disease, and high-resolution CT scans display a pattern of ground glass opacities, centrilobular nodules, and mosaic attenuation. Antigen avoidance remains the only method for primary prevention. Alternative therapy may be needed due to either the inability to avoid antigens or the lack of antigen identification. Prednisone 0.5 mg/kg per day is the first-line treatment for acute non-fibrotic forms of HP. In chronic or fibrotic HP, the immunomodulator mycophenolate mofetil (MMF) was shown to be an effective treatment in improving the diffusing capacity of the lungs for carbon monoxide and forced vital capacity, but not overall survival. The following study aims to bring to attention the need for additional prospective multicenter clinical trials to clarify the role of MMF as an immunomodulator in fibrosing HP.

Successful long-term systemic sclerosis treatment by high-frequent low-dose B cell-depleting therapy.

OBJECTIVES: Systemic sclerosis (SSc) is a multiorgan disease with a 10-year mortality rate of up to 50 %. B cell-depleting therapy with rituximab (RTX) appears effective in SSc treatment, but data from randomized controlled trials (RCTs) are lacking, and the frequency and dosage of RTX in SSc have no consensus. We aimed to evaluate the long-term efficacy and safety of quarterly RTX administration in SSc. METHODS: This study retrospectively analyzed 40 patients with SSC treated with RTX twice within 14 days every 3 months from 2010 to 2020. The patients fulfilled the LeRoy and the American College of Rheumatology/European League Against Rheumatism Criteria for SSc. Modified Rodnan skin score (mRSS), lung function test results, and serum immunoglobulin (IgG, IgA, and IgM) concentrations were analyzed. RESULTS: A total of 40 patients with SSc received RTX over a median time of 3.9 years (range: 1-10 years). The median mRSS (baseline: 19, 24 months: 16, p < 0.001) demonstrated a significant improvement, and the predicted forced vital capacity was stable. No new or unexpected safety signals, especially regarding treatment-related infectious adverse events, were observed. Immunoglobulin concentrations were within normal range, and specific antibodies to pneumococcal polysaccharides were preserved despite long-term B cell-depleting therapy. None of the patients died during the observation period of up to 10 years. CONCLUSION: SSc was effectively and safely treated with low-dose RTX quarterly. RCTs are warranted to validate the advantage of continuous B cell depletion by quarterly low-dose RTX administration compared to other treatment intervals.

Orbital Kimura disease: maintenance therapy using mycophenolate mofetil.

Kimura disease (KD) is a rare, chronic, inflammatory condition, predominantly found in male patients of Asian ethnicity. It typically presents between 50-60 years of age and usually with bilateral disease. Angiolymphoid hyperplasia with eosinophilia (ALHE) remains the main differential diagnosis, although histological analysis is essential in differentiating from other similarly presenting pathologies. In this case, we present an atypical case of unilateral orbital KD in a middle-aged, Caucasian, male gentleman and no evidence of regional lymphadenopathy along with a literature review of orbital KD and the differential diagnoses, histological features and management modalities available, adding to the sparse literature on the topic. At present, no recognised diagnostic criteria for KD are available, with histopathological analysis through incisional or excisional biopsy being the primary diagnostic method. Complete surgical excision with or without corticosteroid management remains the most common treatment modality although management is shifting to steroid-sparing immunomodulatory therapy. To the best of our knowledge, this is the first case to describe maintenance therapy of KD using mycophenolate mofetil.

Mycophenolate mofetil vs. cyclophosphamide-based induction regimens for lupus nephritis: Outcomes at a tertiary care centre in Lahore, Pakistan.

Objectives: To compare the efficacy of mycophenolate mofetil with intravenous cyclophosphamideas induction therapy in lupus nephritis. METHODS: The observational, prospecrive, cohort study was conducted at the Rheumatology Department of Fatima Memorial Hospital, Lahore, Pakistan, from July 2016 to June 2019, and comprised lupus nephritis patients. For induction therapy, the patients were assigned at the discretion of the treating rheumatologist to mycophenolate mofetil group MMF, and intravenous cyclophosphamide group CYC. The latter group was further divided into NIH subgroup that received the therapy as per the protocol of the National Institutes of Health, and ELNT subgroup which recived the therapy as per the Euro Lupus Nephritis Trial protocol. Maintenance therapy in all groups was mycophenolate mofetil. Tacrolimus was added in case of non-response. The outcome was the achievement of complete renal response at 6, 12 and 24 months. Data was analysed using SPSS 26. RESULTS: Of the 131 patients, 126(96.2%) were females. The overall mean age was 27±7.7 years. There were 58(44.2%) patients in group MMF and 73(55.7%) in group CYC, which had subgroup NIH 46(63%) and subgrpup ELNT 27(37%). The complete renal response rates at 6, 12, and 24 months were 22 (43.1%), 35 (71.4%), and 40(83.3%) for group MMF; 5(12.5%), 9(22%) and 24 (58.5%) for subgroup NIH, and 6(26.1%), 8(36.4%) and 14(63.6%) for subgroup ELNT. Group MMF outcomes were significantly better than the rest (p<0.05). CONCLUSIONS: Mycophenolate mofetil induction therapy was more effective than intraveenous cyclophosphamide in terms of achieving remission at 6, 12 and 24 months.

Oral Prescription Management.

The treatment of atopic dermatitis (AD) with oral treatments has been limited in the past due to the increased risk of adverse effects associated with oral agents. However, in recent years, a shift toward the minimization of adverse effects has been explored. Although existing treatment options like oral corticosteroids and Immunosuppressive therapies have been utilized for acute flare-ups of AD, their long-term use is limited by adverse effects and the need for lab monitoring. New systemic treatment options such as Janus kinase (JAK) inhibitors are emerging as a promising therapy, due to their quick onset and antipruritic features. However, the black box warning associated with this medication class requires careful selection of appropriate candidates and patient education despite early favorable safety profiles seen in AD trials. Discussion of other oral agents, like antibiotics and antihistamines, and their role in AD management are also clarified.

Clinical Characteristics and Outcomes of Interstitial Lung Disease in Primary Sjögren's Syndrome: A Retrospective Cohort Study.

Objectives: To describe the characteristics of primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD) and to assess treatment response. Methods: All patients of pSS from 2010 to 2019 were retrospectively identified. Lung function tests, high resolution computed tomography (HRCT) findings, and treatment outcomes were analysed. Results: Out of 550 patients with pSS, ILD was detected in 33 patients (frequency of 6 %). The mean(±SD) age at the diagnosis of pSS was 50 (± 9.3) years. 28/33(84.8%) were females. ILD onset preceded pSS diagnosis in 2 (6%) patients, simultaneously diagnosed in 21 (63.6%) patients and developed after pSS onset in 10 (30.3%) patients. 5 patients (15.15 %) were asymptomatic for ILD. Non-specific interstitial pneumonia (NSIP) accounted for the most frequent ILD subtype, in 15 patients (45.5%). Mycophenolate mofetil (MMF) was the most frequently used steroid sparing agent, in 25 patients (75.7%). 7 patients were lost to follow up. Response was seen in 22 patients, whereas 3 patients were non responders. There was one mortality due to lower respiratory tract infection-related sepsis. Presence of sicca symptoms [91.5% vs 8.7% (p<0.001)], NSIP pattern of ILD [90% vs 10% (p = 0.002)], and absence of Raynaud's phenomenon [91.7% vs 8.3% (p<0.001)] were significantly associated with responder status when compared to non-responders. Conclusion: ILD in primary Sjögren's syndrome is not an uncommon entity, and immunosuppression with steroids along with steroid-sparing agents led to good clinical outcomes of ILD in a majority of the patients in our cohort.

Development of a nomogram to predict the risk of secondary failure of platelet recovery in patients with ß-thalassemia major after hematopoietic stem cell transplantation: a retrospective study.

Background: Secondary failure of platelet recovery (SFPR) is a common complication that influences survival and quality of life of patients with ß-thalassemia major (ß-TM) after hematopoietic stem cell transplantation (HSCT). Objectives: A model to predict the risk of SFPR in ß-TM patients after HSCT was developed. Design: A retrospective study was used to develop the prediction model. Methods: The clinical data for 218 ß-TM patients who received HSCT comprised the training set, and those for another 89 patients represented the validation set. The least absolute shrinkage and selection operator regression algorithm was used to identify the critical clinical factors with nonzero coefficients for constructing the nomogram. Calibration curve, C-index, and receiver operating characteristic curve assessments and decision curve analysis (DCA) were used to evaluate the calibration, discrimination, accuracy, and clinical usefulness of the nomogram. Internal and external validation were used to test and verify the predictive model. Results: The nomogram based on pretransplant serum ferritin, hepatomegaly, mycophenolate mofetil use, and posttransplant serum albumin could be conveniently used to predict the SFPR risk of thalassemia patients after HSCT. The calibration curve of the nomogram revealed good concordance between the training and validation sets. The nomogram showed good discrimination with a C-index of 0.780 (95% CI: 70.3-85.7) and 0.868 (95% CI: 78.5-95.1) and AUCs of 0.780 and 0.868 in the training and validation sets, respectively. A high C-index value of 0.766 was reached in the interval validation assessment. DCA confirmed that the nomogram was clinically useful when intervention was decided at the possibility threshold ranging from 3% to 83%. Conclusion: We constructed a nomogram model to predict the risk of SFPR in patients with ß-TM after HSCT. The nomogram has a good predictive ability and may be used by clinicians to identify SFPR patients early and recommend effective preventive measures.

Navigating Treatment Dilemmas: Recalcitrant Pemphigus and the Burden of Multiple Comorbidities.

Pemphigus vulgaris is a chronic autoimmune disease of the skin caused by the production of autoantibodies targeting desmogleins 1 and 3 usually presenting in individuals with an average age of onset of approximately 40 years. A 35-year-old obese, diabetic woman presented with fluid-filled lesions over her body for three months along with erosions and painful ulcers in her mouth and genital area for two months. Based on clinical and histopathological studies, the patient was diagnosed as a case of pemphigus vulgaris. She was started on conventional treatment with oral corticosteroids followed by pulse therapy and mycophenolate mofetil. Rituximab infusion was scheduled but could not be administered due to elevated D-dimer values. The patient underwent screening for deep vein thrombosis (DVT) and received subcutaneous enoxaparin and oral rivaroxaban. She developed severe sepsis for which she was treated with systemic antibiotics. She subsequently developed acute renal failure and underwent hemodialysis. The patient's clinical condition further deteriorated, which necessitated therapeutic plasma exchange (TPE). Collagen, colloidal silver, and silicone foam dressings were done to hasten wound healing. Two distinct approaches were employed to eliminate the pseudomembrane on the wounds. One portion was treated with hydrogen peroxide (H2O2), while the other was with hyaluronidase. The hyaluronidase treatment resulted in considerable improvement of the lesions. Intravenous immunoglobulin (IVIG) infusion was scheduled. However, the treatment could not be administered as the patient succumbed to death due to pulmonary thromboembolism (PTE) secondary to DVT.

Immunoglobulin A glomerulonephropathy: A review.

In this editorial, we comment on the article by Meng et al published in the World Journal of Clinical Cases. We comprehensively review immunoglobulin A nephropathy (IgAN), including epidemiology, clinical presentation, diagnosis, and management. IgAN, also known as Berger's disease, is the most frequent type of primary glomerulonephritis (GN) globally. It is mostly found among the Asian population. The presentation can be variable, from microscopic hematuria to a rapidly progressive GN. Around 50% of patients present with single or recurring episodes of gross hematuria. An upper respiratory infection and tonsillitis often precede these episodes. Around 30% of patients present microscopic hematuria with or without proteinuria, usually detected on routine examination. The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy. We focus on risk stratification and management of IgAN. We provide a review of all the landmark studies to date. According to the 2021 KDIGO (kidney disease: Improving Global Outcomes) guidelines, patients with non-variant form IgAN are first treated conservatively for three to six months. This approach consists of adequate blood pressure control, reduction of proteinuria with renin-angiotensin system blockade, treatment of dyslipidemia, and lifestyle modifications (weight loss, exercise, smoking cessation, and dietary sodium restrictions). Following three to six months of conservative therapy, patients are further classified as high or low risk for disease progression. High-risk patients have proteinuria ≥ 1 g/d or < 1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy. Some experts consider proteinuria ≥ 2 g/d to be very high risk. Patients with high and very high-risk profiles are treated with immunosuppressive therapy. A proteinuria level of < 1 g/d and stable/improved renal function indicates a good treatment response for patients on immunosuppressive therapy.

Anti-CFH-associated hemolytic uremic syndrome: do we still need plasma exchange?

BACKGROUND: Between 5 and 50% of atypical hemolytic uremic syndrome (aHUS) cases in children are caused by autoantibodies against complement factor H (CFH). Given the acquired autoimmune nature of the disease, plasma exchange (PE) and various immunosuppressive treatments have been used. More recently, eculizumab has been proposed. METHODS: In this multicenter, retrospective study, we report outcomes of 12 children with anti-FH antibody-associated HUS treated with eculizumab associated with various immunosuppressive regimens. RESULTS: Patients were treated with eculizumab for 15.5 [9.5;23.0] months and 3 received PE or IgG adsorption. Three patients received mycophenolate mofetil (MMF) alone, 1 patient received MMF and steroids, 1 patient received MMF and rituximab, 3 patients received MMF/steroids and rituximab, and 4 patients did not receive any immunosuppression. Anti-FH antibody levels significantly decreased but no difference was observed based on the immunosuppressive regimen. Eculizumab was discontinued in 7/10 patients after 11 [7.5;15.5] months and MMF in 6/8 patients after 36 [35;40] months. Anti-FH titers at MMF discontinuation ranged from 257 to 3425 UI/L. None of these patients relapsed and eGFR at last follow-up was above 70 mL/min/1.73 m2 in all patients. CONCLUSIONS: Eculizumab is effective and safe in inducing and maintaining remission in aHUS secondary to anti-FH antibodies and renders reduction of anti-FH titers less urgent. Anti-FH antibody titers decreased in most patients irrespective of the immunosuppressive treatment chosen, so that a strategy consisting of combining eculizumab with MMF monotherapy seems sufficient at least in non-Indian or less severe forms of anti-FH antibody-associated HUS.

Do we really need cyclophosphamide for lupus nephritis?

A 14-year-old patient presents with hematuria and proteinuria. Clinical evaluation reveals a positive anti-nuclear antibody titer, positive anti-double stranded DNA antibody and hypocomplementemia. Systemic lupus erythematosus (SLE) is diagnosed based on the 2019 EULAR/ACR (European League Against Rheumatism/American College of Rheumatology) classification criteria (Aringer et al. Arthritis Rheumatol 71:1400-1412, 2019). A kidney biopsy is performed that confirms the presence of immune complex glomerulonephritis, ISN-RPS (International Society of Nephrology/Renal Pathology Society) class IV (Bajema et al. Kidney Int 93:789-796, 2018). According to the latest clinical practice guidelines (Rovin et al. Kidney Int 100:753-779, 2021; Fanouriakis et al. Ann Rheum Dis 83:15-29, 2023), there are alternatives to treating this patient with cyclophosphamide. But what if this patient also presented with oliguria and volume overload requiring intensive care and dialysis? What if this patient also presented with altered mental status and seizures, and was diagnosed with neuropsychiatric lupus? What if this patient was also diagnosed with a pulmonary hemorrhage and respiratory failure? The clinical practice guidelines do not address these scenarios that are not uncommon in patients with SLE. Moreover, in some countries worldwide, patients do not have the privilege of access to biologics or more expensive alternatives. The purpose of this review is to evaluate the contemporary options for initial treatment of nephritis in patients with SLE.