Developments in the Immunotherapy of Glomerular Disease

2002 ◽  
Vol 15 (6) ◽  
pp. 472-489
Author(s):  
Patrick H. Nachman ◽  
Jeffrey Martin
Keyword(s):  
Alkylating Agents ◽  
Clinical Manifestations ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Glomerular Disease ◽  
Drug Induced ◽  
Glomerular Diseases ◽  
Care Givers ◽  
Clinical Syndromes ◽  
History Of

Glomerular diseases span a broad spectrum of clinical syndromes, with varied clinical manifestations, underlying etiologies, and pathogenic mechanisms. They can be secondary to underlying infectious, toxic, environmental, or drug exposures, or present as “primary entities.” In the latter case, most glomerular diseases are thought to be due to autoimmune dysregulation, and their treatment is primarily immunosuppressive. The armamentarium for immunomodulation includes corticosteroids, alkylating agents, anti-metabolites, calcineurin inhibitors, and new biological agents designed to block specific inflammatory pathways. The choice of therapy for an individual patient must be based on the specific character of the glomerular disease and its acuity and severity, as well as the patient’s comorbidities, history of prior exposure to immunosuppressive drugs, and risk factors for developing complications of the disease or its treatment. The complexities of such therapy can best be addressed by an experienced team of care givers in which the clinical pharmacist can help minimize, if not eliminate, potential sources of drug induced toxicities and adverse effects. This article will describe the major agents and modalities used in the management of the most common glomerular diseases.

scholarly journals Creutzfeldt–Jakob disease-like syndrome induced by gabapentin toxicity

2010 ◽  
Vol 1 (1) ◽  
pp. 3 ◽  
Author(s):  
Vicky Chau ◽  
Sadhana Prasad ◽  
Dwight Stewart ◽  
George Heckman
Keyword(s):  
Cognitive Impairment ◽  
Drug Toxicity ◽  
Clinical Manifestations ◽  
Drug Induced ◽  
Eeg Abnormalities ◽  
Negative Myoclonus ◽  
History Of ◽  
Jakob Disease ◽  
Neurological Effects ◽  
Gait Abnormalities

Patients with Creutzfeldt–Jakob disease (CJD) may exhibit characteristic abnormalities on the electroencephalogram (EEG). However, these abnormalities have been associated with a number of cases of drug toxicity. We report a case of CJD-like syndrome associated with gabapentin. A 78-year-old man was hospitalized for recurrent falls. Three months prior to admission, gabapentin was prescribed to treat symptoms of trigeminal neuralgia. The patient subsequently presented with a two-month history of worsening gait abnormalities, negative myoclonus, and cognitive impairment. The EEG showed diffuse background slowing with larger amplitude delta discharges, which at times appeared triphasic, raising the possibility of CJD. The gait abnormalities and myoclonus resolved and the EEG normalized after the gabapentin was discontinued. Several cases of drug-induced CJD-like syndrome have been reported, mainly presenting with cognitive impairment, myoclonus, Parkinsonism, and EEG abnormalities. This patient may have been predisposed to adverse neurological effects from gabapentin owing to age, concurrent renal insufficiency, and cardiac disease. We concluded that it is imperative to include drug toxicity in the differential diagnosis of patients presenting with clinical manifestations and EEG findings suggestive of CJD, particularly in the setting of advanced age and comorbidities.

scholarly journals Biologics in the Treatment of Lupus Erythematosus: A Critical Literature Review

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Dominik Samotij ◽  
Adam Reich
Keyword(s):  
Clinical Trials ◽  
Lupus Erythematosus ◽  
Unmet Need ◽  
Clinical Manifestations ◽  
Immunosuppressive Drugs ◽  
Multiple Organ ◽  
Biologic Agents ◽  
Drug Induced ◽  
Treatment Regimes ◽  
Organ Systems

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease affecting multiple organ systems that runs an unpredictable course and may present with a wide variety of clinical manifestations. Advances in treatment over the last decades, such as use of corticosteroids and conventional immunosuppressive drugs, have improved life expectancy of SLE sufferers. Unfortunately, in many cases effective management of SLE is still related to severe drug-induced toxicity and contributes to organ function deterioration and infective complications, particularly among patients with refractory disease and/or lupus nephritis. Consequently, there is an unmet need for drugs with a better efficacy and safety profile. A range of different biologic agents have been proposed and subjected to clinical trials, particularly dedicated to this subset of patients whose disease is inadequately controlled by conventional treatment regimes. Unfortunately, most of these trials have given unsatisfactory results, with belimumab being the only targeted therapy approved for the treatment of SLE so far. Despite these pitfalls, several novel biologic agents targeting B cells, T cells, or cytokines are constantly being evaluated in clinical trials. It seems that they may enhance the therapeutic efficacy when combined with standard therapies. These efforts raise the hope that novel drugs for patients with refractory SLE may be available in the near future. This article reviews the current biological therapies being tested in the treatment of SLE.

The glomerulus and the concept of glomerulonephritis

2015 ◽  
Author(s):  
Alexander Woywodt ◽  
Diana Chiu
Keyword(s):  
Filtration Rate ◽  
Hybrid Approach ◽  
Glomerular Disease ◽  
Multisystem Disease ◽  
Glomerular Diseases ◽  
Clinical Syndromes ◽  
Different Types ◽  
Key Features ◽  
The 1960S

The key features of glomerular diseases—haematuria, proteinuria, loss of glomerular filtration rate, and hypertension—were recognized in the nineteenth century, and some earlier, but Richard Bright is usually given credit for synthesizing the concepts of renal disease, and glomerulonephritis came under the heading of Bright’s disease for almost a century. Separation into different types was based on first clinical syndromes, but in the early twentieth century, pathological description was improving and with the introduction of percutaneous renal biopsies in the 1950s, in the 1960s histopathological definitions assumed the ascendancy. A unifying classification of glomerular disease remains work in progress. Current classifications are pathologically based but increasingly include the results of other investigations (including genotype and a variety of immunological and other tests). This chapter follows this pragmatic, hybrid approach, categorizing glomerular disease by pattern on renal biopsy except where aetiological factors are clearly identified (e.g. HIV nephropathy), or associated multisystem disease is defined (e.g. lupus nephritis), or the immunopathogenesis is well characterized (e.g. antiglomerular basement membrane disease).

scholarly journals A Case of Essential Thrombocythemia and IgA Nephropathy with Literature Review of the Concurrence

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Shoja Rahimian ◽  
Timothy Johnson ◽  
Ronald Herb
Keyword(s):  
Renal Function ◽  
Literature Review ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Immunoglobulin A ◽  
Glomerular Disease ◽  
Common Finding ◽  
Glomerular Diseases ◽  
Pathological Review ◽  
History Of

Myeloproliferative neoplasms such as essential thrombocythemia (ET) have been associated with glomerular disease on rare instances. A case of ET associated with immunoglobulin A nephropathy (IgAN) is described in a 57-year-old man with a history of hypertension. Progressively worsening renal function was noted in the patient along with unexplained mild thrombocytosis. Pathological review of renal biopsy identified IgAN concurrently with newly diagnosed JAK2-mutated ET. The patient was started on aspirin therapy and closely monitored for his renal function. A literature review of the association of ET and renal disease revealed nine cases of ET associated with IgAN, focal segmental glomerulosclerosis, and fibrillary glomerulonephritis. Comparison of the pathological features of the renal biopsies within the cases noted mesangial proliferation as a common finding, which has been described to be potentiated by platelet-derived growth factor (PDGF). This commonality may represent a link between ET and glomerular disease which deserves further attention in future cases. Improved management of such cases depends on the recognition of the combined occurrence of ET and glomerular diseases and uncovering the shared pathogenesis between platelets and glomeruli.

Symptomatic therapy

2019 ◽  
pp. 17-70
Author(s):  
Richard J Glassock
Keyword(s):  
Glomerular Filtration Rate ◽  
Renal Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Clinical Manifestations ◽  
Glomerular Disease ◽  
Symptomatic Therapy ◽  
Glomerular Diseases ◽  
Progression Of Renal Disease ◽  
Disease Specific

Patients with glomerular diseases develop a wide variety of biochemical disturbances and pathophysiologic alterations leading to overt clinical manifestations. Collectively, these abnormalities give rise to the classical syndromes of glomerular disease. The clinical abnormalities resulting from these disturbances in renal pathophysiology require management in order to minimize or avoid disabling symptoms, often referred to as symptomatic therapy. This chapter provides an introduction to and overview of these abnormalities. It then covers therapies for a variety of manifestations of primary glomerular diseases, including haematuria, oedema, hypertension, hyperlipidaemia (e.g. hypercholesterolaemia), the ‘hypercoagulable’ or ‘thrombophilic’ state, non-disease-specific strategies designed to retard the progression of renal disease (loss of glomerular filtration rate, GFR), and more.

scholarly journals The Rationale and Evidence for SGLT2 Inhibitors as a Treatment for Nondiabetic Glomerular Disease

2021 ◽  
Vol 1 (1) ◽  
pp. 21-33
Author(s):  
Kana N. Miyata ◽  
Shao-Ling Zhang ◽  
John S.D. Chan
Keyword(s):  
Glucose Transporter ◽  
Mesangial Cells ◽  
Systemic Blood Pressure ◽  
Glomerular Disease ◽  
Renal Tubules ◽  
Protective Effects ◽  
Glomerular Diseases ◽  
Urinary Glucose ◽  
Proximal Tubular ◽  
History Of

Background: Recent studies show that sodium-glucose cotransporter 2 inhibitors (SGLT2i), originally approved for glycemic control in patients with type 2 diabetes, also exert renoprotective effects independently from effects on dysglycemia. Moreover, recent work indicates that SGLT2i treatment may be effective in patients with nondiabetic chronic kidney disease, including primary and secondary glomerular diseases. Summary: SGLT2i lower blood glucose by blocking glucose resorption in the early renal proximal tubule through the glucose transporter, SGLT2, leading to enhanced urinary glucose excretion. Recent studies indicate that SGLT2i may have pleiotropic effects on cells other than proximal tubular cells. SGLT2i reduce the glomerular workload by decreasing the intraglomerular pressure, thus ameliorating hyperfiltration, if present, and may also decrease systemic blood pressure. SGLT2i may also act directly on endothelial cells, possibly via modulating the effects of adhesion molecules and reducing inflammatory cytokines and reactive oxygen species. SGLT2i may have direct anti-inflammatory and antifibrotic effects on renal tubules. Some reports suggest direct protective effects on podocytes and mesangial cells as well. Here, we provide a review of the potential mechanisms of renoprotection, therapeutic utility, and potential side effects of SGLT2i in patients with nondiabetic glomerular diseases, based on data from studies carried out in cells, experimental animals, and humans. Key Messages: SGLT2i may be a promising addition to the glomerular disease treatment armamentarium. However, it is unclear at what point of the natural history of specific glomerular diseases (whether this is immune or nonimmune mediated) SGLT2i can be beneficial. Additionally, further studies are needed to assess the long-term efficacy and safety of SGLT2i in patients with nondiabetic glomerular diseases.

scholarly journals Use of Belatacept as Alternative Immunosuppression in Three Renal Transplant Patients withDe NovoDrug-Induced Thrombotic Microangiopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Federico Cicora ◽  
Marta Paz ◽  
Fernando Mos ◽  
Javier Roberti
Keyword(s):  
Renal Transplant ◽  
Thrombotic Microangiopathy ◽  
De Novo ◽  
Parvovirus B19 ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Drug Induced ◽  
Transplant Patients ◽  
Proliferation Signal Inhibitors ◽  
Renal Transplant Patients

Thrombotic microangiopathy (TMA), a severe complication of renal transplantation, is a pathological process involving microvascular occlusion, thrombocytopenia, and microangiopathic hemolytic anemia. It generally appears within the first weeks after transplantation, when immunosuppressive drugs are used at high doses.De novoTMA may also be drug-induced when calcineurin inhibitors or proliferation signal inhibitors are used. We report three cases ofde novodrug-induced TMA in renal transplant patients who were managed by replacing calcineurin inhibitors or proliferation signal inhibitors with belatacept, a primary maintenance immunosuppressive drug, which blocks the CD28 costimulation pathway, preventing the activation of T lymphocytes. To identify the cause of TMA, we ruled out HUS, hepatitis C serology, HIV serology, parvovirus B19, cytomegalovirus, anti-HLA antibodies, and prolonged activated partial thromboplastin time. We suspect that the TMA was caused by the calcineurin inhibitors or proliferation signal inhibitors. Belatacept treatment was initiated at a dose of 10 mg/kg on days 1, 5, 14, 28, 60, and 90; maintenance treatment was 5 mg/kg once a month for 1 year. Belatacept, in combination with other agents, prevented graft rejection in three patients.

scholarly journals ENGLISH VERSION: PERSONALIZED DESENSITIZATION WITH ACETYLSALICYLIC ACID IN PATIENTS WITH HYPERSENSITIVITY TO NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

2020 ◽  
Vol 24 (1-2) ◽  
pp. 40-43
Author(s):  
A.V. Lavrenko ◽  
Ya.M. Avramenko ◽  
O.A. Borzykh ◽  
I.P. Kaidashev
Keyword(s):  
Adverse Reactions ◽  
Initial Dosage ◽  
Clinical Manifestations ◽  
Aspirin Therapy ◽  
English Version ◽  
Drug Induced ◽  
Clinical Syndromes ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Aims: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) has various mechanisms and represents different clinical syndromes from anaphylaxis to severe bronchospasm. The prevalence of aspirin hypersensitivity among patients with asthma and nasal polyps reaches 25.6%. Respiratory reactions associated with aspirin or other NSAIDs are not immunological. The basis of these reactions is non-allergic hypersensitivity of the cross-reactive type. Desensitization followed by long-term aspirin therapy is an effective method of treating hypersensitivity to aspirin or other NSAIDs. Using aspirin 600-1200 mg/day can significantly alleviate the symptoms of asthma, allergic rhinitis. Methods: We successfully applied aspirin desensitization for method of patients with hypersensitivity to NSAIDs. According to the method, an hour before the desensitization, daily montelukast 10 mg was taken orally, then aspirin every 3 hours. Results: Three patients underwent desensitization of aspirin. The dose was selected individualy depending on the clinical manifestations of drug-induced adverse reactions (AR). ARs during desensitization were treated by iv dexamethasone administration. Subsequent doses did not cause AR. Doses of aspirin were increased to a maximum of 1250 mg daily, and were continued for the long-term use. Conclusion: It is possible to conclude that the initial dose of aspirin should be 16-40mg; it is possible to increase the dose if the initial dosage is well tolerated; symptoms of moderate intolerance are treated by 4-8 mg iv dexamethasone; prior to desensitization, we recommended to use montelukast 10 mg, it is safe to practice desensitization of aspirin according to a personalized technique by a specialist in an intensive care unit.

scholarly journals Insidious-onset, non-wheezing carteolol-induced asthma in an atopic patient without asthma history

2019 ◽  
Vol 12 (4) ◽  
pp. e229343 ◽  
Author(s):  
Jo-Hsuan Wu ◽  
Jih-Shuin Jerng ◽  
Chien-Chia Su
Keyword(s):  
Pulmonary Function ◽  
Pulmonary Function Test ◽  
Clinical Manifestations ◽  
Eye Drops ◽  
Drug Induced ◽  
Previous Diagnosis ◽  
Insidious Onset ◽  
Function Test ◽  
History Of ◽  
Associated Risk Factors

Carteolol, a non-selective beta-antagonist with a potential risk of severe bronchial constriction in patients with asthma, is one of the most commonly prescribed medication for managing ocular pressure in glaucoma. We present a case of a 24-year-old woman with a history of atopy but no known asthma who presented an insidious onset of clinical manifestations compatible with drug-induced asthma after the initiation of carteolol for ocular hypertension control. The patient developed progressive chest tightness and dyspnoea for 2 months before the pulmonary function test revealed a positive bronchoprovocation response. She reported significant improvement of respiratory symptoms within 2 weeks after the discontinuation of carteolol, and a negative provocation response was later confirmed by repeat pulmonary function test. In conclusion, eye drops with non-selective beta-antagonising effect can induce asthmatic symptoms in patients without a previous diagnosis of asthma and should be administered with caution in patients with associated risk factors.

Antineoplastic drugs and drug-induced liver damage with cholestasis

2020 ◽  
Vol 1 (19) ◽  
pp. 47-54 ◽  
Author(s):  
A. P. Pereverzev ◽  
O. D. Ostroumova
Keyword(s):  
Alkylating Agents ◽  
Interleukin 1 ◽  
Clinical Manifestations ◽  
Antineoplastic Drugs ◽  
Targeted Drugs ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Treatment And Prevention ◽  
The Russian Federation ◽  
Novel Drug

The number of cases of drug-induced liver injury (DILI) has been increasing since the 1990s. DILIs cause up to 40,000 deaths each year. One of the leaders in the number of DILIs are antineoplastic drugs ms, such as alkylating agents, antimetabolites, targeted drugs, monoclonal antibodies, etc. One of the most effective and safe strategies for the treatment and prevention of DILI is to use hepatoprotective drugs. Currently, on the market of the Russian Federation, is available novel drug Heptrong® (does not have an International Non-proprietary Name), which has anti-inflammatory, antioxidant activity and the ability to stabilize and reduce the permeability of hepatocyte membranes, suppress the activity 5-lipoxygenase, a decrease in the synthesis of leukotriene B4, interleukin-1, interleukin-6, which are pro-inflammatory cytokines. The drug activates the antitoxic function of the liver, improves its protein- and lipid-synthesizing functions. Heptrong® neutralizes the processes of inflammation in the liver, thereby reducing the severity of the clinical manifestations of drug-induced lesions.

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