scholarly journals Case Report: Cyclophosphamide in COVID-19 – when an absolute contraindication is an absolute necessity

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 829
Author(s):  
Kamila Bołtuć ◽  
Ada Bielejewska ◽  
Alejandro Coloma-Millar ◽  
Robert Dziugieł ◽  
Arkadiusz Bociek ◽  
...  

Background: Despite many studies on COVID-19, our knowledge of it remains incomplete. In some cases, treating SARS-CoV-2 infection concomitant with other diseases can be particularly challenging, as finding an appropriate treatment may involve some risks. Case presentation: A 34-year-old SARS-CoV-2 positive patient admitted due to fever, dyspnoea, haemoptysis and pneumonia, developed alveolar haemorrhage and acute kidney injury. Due to his severe state, abnormalities in laboratory tests and rapidly progressing loss of kidney function, kidney biopsy, as well as antibody panel were carried out, in which perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were found with a high titer (>200; N: <1:20). The results of kidney biopsy, combined with clinical manifestation and laboratory findings prompted the diagnosis of rapidly progressing glomerulonephritis (RPGN) in the course of p-ANCA vasculitis. Initial treatment consisted of heamodialyses, remdesivir, plasmaphereses, intravenous immunoglobulins, antibiotics, corticosteroids and fraxiparine. Once the haemorrhage had subsided, kidney function had been partially retrieved and heamodialyses had no longer been necessary, cyclophosphamide treatment was initiated, despite being contraindicated in COVID-19 according to its summary of product characteristics. Immunotherapy is still continued. The patient has already received a total of 2.4g of cyclophosphamide (4 cycles of 600mg each every three weeks). Pulmonary and radiological regression, as well as improvement of renal parameters have been achieved.        Conclusions: We suspect that cyclophosphamide, the drug of choice in p-ANCA vasculitis, could be a potential factor providing regression of the radiological changes in the lungs and it could have prevented the patient from developing acute respiratory distress syndrome. COVID-19 diagnosis should not exclude searching for other diseases which can have a similar course. When treating a patient in a life-threatening condition, a departure from trying to find the perfect timing of cyclophosphamide delivery should be considered, as delaying it could cause potentially greater harm.

Author(s):  
Joana Eugénio Santos ◽  
Rita Vicente ◽  
Beatriz Malvar ◽  
Iolanda Santos ◽  
Miguel Coimbra ◽  
...  

Abstract Antineutrophil cytoplasmic antibodies (ANCAs) are associated with small vessel vasculitis but their prevalence is not rare in other immune diseases. In lupus nephritis (LN), their pathological role and clinical relevance have been the target of controversial views. We present a case of acute kidney injury and nephrotic syndrome in a young woman with diffuse global proliferative and membranous nephritis on her kidney biopsy, showing a full-house immunofluorescence pattern, very allusive of class IV + V LN, but lacking associated clinical criteria and laboratory findings to support the diagnosis of systemic lupus erythematosus (SLE). Furthermore, the patient presented with high titers of ANCA, steadily decreasing alongside the renal function and proteinuria improvements, with mycophenolate mofetil (MMF) and steroid treatment. The authors believe this is a case of lupus-like nephritis, in which ANCAs are immunological markers, although they are not directly involved in the pathogenesis.


2013 ◽  
Vol 35 ◽  
pp. 567-572 ◽  
Author(s):  
Sanja Simic Ogrizovic ◽  
Suzana Bojic ◽  
Gordana Basta-Jovanovic ◽  
Sanja Radojevic ◽  
Jelena Pavlovic ◽  
...  

Objectives. Retrospective study was designed to examine the importance of tissue kidney injury molecule-1 (KIM-1) expression in predicting kidney function in sixty patients (27 males) aged 34.15 ± 12.23 years with different kidney diseases over three years after kidney biopsy.Materials and Methods. Tissue KIM-1 expression was determined immunohistochemically and KIM-1 staining was scored semiquantitatively, as well as tubulointerstitialis (TIN), inflammation, atrophy, and fibrosis. Kidney function (MDRD formula) and proteinuria/day were evaluated at the time of biopsy (GFR0) and 6, 12, 24, and 36 months later.Results. Significantly positive correlations between tissue KIM-1 expression and age (r=0.313), TIN inflammation (r=0.456), fibrosis (r=0.317), and proteinuria at 6 months (r=0.394) as well as negative correlations with GFR0 (r=−0.572), GFR6 (r=−0.442), GFR24 (r=−0.398), and GFR36 (r=−0.412) were found. Meanwhile, TIN inflammation was the best predictor of all measured kidney functions during three years, while tissue KIM-1 expression (P=0.016) was a predictor only at 6 months after biopsy.Conclusion. Tissue KIM-1 expression significantly predicts kidney function solely at 6 months after biopsy, when the effects of immune and nonimmune treatments are the strongest.


2021 ◽  
Vol 35 (1) ◽  
pp. 55-58
Author(s):  
Mariana Sousa ◽  
◽  
Cristina Santos ◽  
Rita Gouveia ◽  
Fernando Pereira ◽  
...  

Introduction: Antineutrophil cytoplasmic autoantibodies (ANCAs) are crucial in the pathogenesis of ANCA-associated glomerulonephritis. Although highly specific for this disease, these antibodies can appear in healthy individuals or occur in other settings such as malignance, other inflammatory disease, or drugs. Renal biopsy remains essential for diagnosis and as a prognostic tool. Failing to perform a biopsy risks an incomplete evaluation or misdiagnosis. Clinical case: A 60-year-old male known to have had previous normal kidney function was admitted with generalized pitting edema, nonpruritic erythematous rash, and decreased urine output. He had been recently started on clozapine for depression. Laboratory tests revealed nephrotic syndrome with massive proteinuria (11g/day), hematuria and elevated serum creatinine that reached a maximum of 4.9 mg/dl. The only positive finding was a high titer of myeloperoxidase (MPO) ANCA antibody (111 UI/ml). Clozapine was discontinued, and he was started on conservative management of the nephrotic syndrome. The rash disappeared within one week. Kidney biopsy showed cellular variant focal segmental glomerulosclerosis (FSGS) with mild acute tubular injury. The patient was treated with oral prednisolone with complete remission. Repeat MPO-ANCA was negative after one month. Discussion: We present a challenging case that highlights the importance of kidney biopsy for accurate diagnosis with major impact on treatment and prognosis. This case also underlines the presentation and evolution of FSGS cellular variant, a rare and poorly understood disease. The relationship between skin rash with high MPO titer and the administration of clozapine with clinical remission after its discontinuation favors the hypothesis of drug associated ANCA-vasculitis.


2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Gaurav Agarwal ◽  
Ghayyath Sultan ◽  
Sherry L. Werner ◽  
Claudia Hura

We report a case of hydralazine-induced ANCA-associated glomerulonephritis with pulmonary hemorrhage. A 62-year-old Hispanic man with hypertension, who was being treated with hydralazine 100 mg three times a day for four and half years, presented to the hospital with severe anemia. He had acute kidney injury and urinalysis showed proteinuria, dysmorphic RBCs, and rare RBC cast. CT scan of the chest revealed bilateral pulmonary ground-glass infiltrates. Transbronchial biopsy was consistent with pulmonary hemorrhage. Serologic tests showed high titer PR3 ANCA and, to a lesser extent, MPO ANCA. Kidney biopsy revealed focal segmental necrotizing glomerulonephritis with crescents, without evidence of immune complex deposits. Hydralazine was discontinued and the patient was treated with corticosteroids and intravenous cyclophosphamide. At one-year follow-up, he had no symptoms and anemia had resolved. Kidney function improved dramatically. Serology showed undetectable PR3 ANCA and minimally elevated MPO ANCA. To our knowledge, hydralazine-associated PR3 ANCA has not been previously reported. The possibility of ANCA systemic vasculitis should be included in the differential diagnosis of any patient with hydralazine use and pulmonary renal syndrome. This is a potentially life threatening condition requiring prompt cessation of the drug and treatment with glucocorticoids and immunosuppression.


2004 ◽  
Vol 57 (7-8) ◽  
pp. 391-395
Author(s):  
Biljana Vuckovic ◽  
Tatjana Ilic ◽  
Igor Mitic ◽  
Violeta Knezevic ◽  
Slavenka Vodopivec ◽  
...  

Introduction Goodpasture's syndrome is a rare, autoimmune disease characterized by pulmonary hemorrhage, glomerulonephritis and production of anti-GBM (glomerular basement membrane) antibodies. The etiology of this syndrome is still unknown. Goodpasture's syndrome usually starts with pulmonary hemorrhage, which is followed by symptoms of kidney disease. Laboratory findings often include: anemia, microhematuria, proteinuria, increased levels of urea and creatinine and anti-GBM antibodies. Diagnosis of this syndrome can be established by presence of pulmonary hemorrhage, pulmonary radiography, kidney biopsy and positive result of circulating anti-GBM antibodies. Treatment of this syndrome should be initiated as soon as possible using a combination of cortocosteroids, cytostatics and plasmapheresis. Case report The first symptoms in a nineteen-year-old female patient were caused by anemia. Two months later she reported symptoms of pulmonary hemorrhage. At that point of time she already had renal insufficiency and was immediately hospitalized. The same day we started therapy with cortocosteroids, endoxan and plasmapheresis was initiated. Recovery of pulmonary function was obtained, but kidney function was lost. Discussion and Conclusions The most important thing in regard to Goodpasture's syndrome is quick diagnosis. Because of that, if patients report any kind of pulmonary hemorrhage, this syndrome must be considered. At that point of time, kidney function is usually not irreversibly damaged. The second important thing in Goodpasture's syndrome is that treatment must be very aggressive using a combination of immunosuppressives and plasmapheresis. This is the only chance for these patients to avoid hemodialysis or death.


2020 ◽  
Vol 8 ◽  
pp. 2050313X2091002 ◽  
Author(s):  
Umut Selamet ◽  
Ramy M Hanna ◽  
Anthony Sisk ◽  
Lama Abdelnour ◽  
Lena Ghobry ◽  
...  

Drug-induced lupus erythematosus has features distinct from primary systemic lupus erythematosus. It can occur with a wide variety of agents that result in the generation of anti-histone or other types of antibodies. Systemic manifestations of drug-induced systemic lupus erythematosus may include renal dysfunction due to circulating immune complexes or due to other immune reactions to the culprit medication(s). Acute interstitial nephritis occurs due to DNA–drug or protein–drug complexes that trigger an allergic immune response. We report a patient who developed acute kidney injury, rash, and drug-induced systemic lupus diagnosed by serologies after starting chlorthalidone and amiodarone. A renal biopsy showed acute interstitial nephritis and not lupus-induced glomerulonephritis. It is important to note that systemic lupus erythematosus and acute interstitial nephritis can occur together, and this report highlights the role of the kidney biopsy in ascertaining the pathological diagnosis and outlining therapy in drug-induced lupus erythematosus.


2021 ◽  
Vol 14 (1) ◽  
pp. e236695 ◽  
Author(s):  
Rasmi Ranjan Sahoo ◽  
Sourav Pradhan ◽  
Akhil Pawan Goel ◽  
Anupam Wakhlu

Staphylococcus-associated glomerulonephritis (SAGN) occurs as a complication of staphylococcal infection elsewhere in the body. Dermatomyositis (DM) can be associated with glomerulonephritis due to the disease per se. We report a case of a 40-year-old male patient with DM who presented with acute kidney injury, and was initially pulsed with methylprednisolone for 3 days, followed by dexamethasone equivalent to 1 mg/kg/day prednisolone. He was subsequently found to have SAGN on kidney biopsy along with staphylococcus bacteraemia and left knee septic arthritis. With proof of definitive infection, intravenous immunoglobulin 2 g/kg over 2 days was given and steroids were reduced. He was treated with intravenous vancomycin. With treatment, the general condition of the patient improved. On day 38, he developed infective endocarditis and died of congestive heart failure subsequently. Undiagnosed staphylococcal sepsis complicating a rheumatological disease course can lead to complications like SAGN, infective endocarditis and contribute to increased morbidity and mortality, as is exemplified by our case.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Katarzyna Szajek ◽  
Marie-Elisabeth Kajdi ◽  
Valerie A. Luyckx ◽  
Thomas Hans Fehr ◽  
Ariana Gaspert ◽  
...  

Abstract Background Acute kidney injury (AKI) associated with severe coronavirus disease 19 (COVID-19) is common and is a significant predictor of morbidity and mortality, especially when dialysis is required. Case reports and autopsy series have revealed that most patients with COVID-19 – associated acute kidney injury have evidence of acute tubular injury and necrosis - not unexpected in critically ill patients. Others have been found to have collapsing glomerulopathy, thrombotic microangiopathy and diverse underlying kidney diseases. A primary kidney pathology related to COVID-19 has not yet emerged. Thus far direct infection of the kidney, or its impact on clinical disease remains controversial. The management of AKI is currently supportive. Case Presentation The patient presented here was positive for SARS-CoV-2, had severe acute respiratory distress syndrome and multi-organ failure. Within days of admission to the intensive care unit he developed oliguric acute kidney failure requiring dialysis. Acute kidney injury developed in the setting of hemodynamic instability, sepsis and a maculopapular rash. Over the ensuing days the patient also developed transfusion-requiring severe hemolysis which was Coombs negative. Schistocytes were present on the peripheral smear. Given the broad differential diagnoses for acute kidney injury, a kidney biopsy was performed and revealed granulomatous tubulo-interstitial nephritis with some acute tubular injury. Based on the biopsy findings, a decision was taken to adjust medications and initiate corticosteroids for presumed medication-induced interstitial nephritis, hemolysis and maculo-papular rash. The kidney function and hemolysis improved over the subsequent days and the patient was discharged to a rehabilitation facility, no-longer required dialysis. Conclusions Acute kidney injury in patients with severe COVID-19 may have multiple causes. We present the first case of granulomatous interstitial nephritis in a patient with COVID-19. Drug-reactions may be more frequent than currently recognized in COVID-19 and are potentially reversible. The kidney biopsy findings in this case led to a change in therapy, which was associated with subsequent patient improvement. Kidney biopsy may therefore have significant value in pulling together a clinical diagnosis, and may impact outcome if a treatable cause is identified.


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