Eculizumab therapy in a patient with dense-deposit disease associated with partial lipodystropy

Özkaya, Ozan; Nalçacıoğlu, Hülya; Tekcan, Demet; Genç, Gürkan; Meydan, Bilge Can; Ozdemır, B. Handan; Baysal, Mehmet; Keçeligil, Hasan Tahsin

doi:10.1007/s00467-013-2748-5

Cited by 38 publications

(28 citation statements)

References 13 publications

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“…Eculizumab is registered for use in paroxysmal nocturnal hematuria (11) and atypical hemolytic uremic syndrome (HUS) (12). Recent reports have described the use of eculizumab in DDD, with varying results (13)(14)(15)(16)(17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Eculizumab in Pediatric Dense Deposit Disease

Oosterveld¹,

Garrelfs²,

Höppe

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children.Design, setting, participants, & measurements The authors analyzed clinical and histologic data of five pediatric patients with a native kidney biopsy diagnosis of DDD. Patients received eculizumab as therapy of last resort for severe nephritic or nephrotic syndrome with alternative pathway complement activation; this therapy was given only when the patients had not or only marginally responded to immunosuppressive therapy. Outcome measures were kidney function, proteinuria, and urine analysis.Results In all, seven disease episodes were treated with eculizumab (six episodes of severe nephritic syndrome [two of which required dialysis] and one nephrotic syndrome episode). Median age at treatment start was 8.4 (range, 5.9-13) years. For three treatment episodes, eculizumab was the sole immunosuppressive treatment. In all patients, both proteinuria and renal function improved significantly within 12 weeks of treatment (median urinary protein-to-creatinine ratio of 8.5 [range, 2.2-17] versus 1.1 [range, 0.2-2.0] g/g, P,0.005, and eGFR of 58 [range, 17-114] versus 77 [range, 50-129] ml/min per 1.73 m 2 , P,0.01). A striking finding was the disappearance of leukocyturia within 1 week after the first eculizumab dose in all five episodes with leukocyturia at treatment initiation.Conclusions In this case series of pediatric patients with DDD, eculizumab treatment was associated with reduction in proteinuria and increase in eGFR. Leukocyturia resolved within 1 week of initiation of eculizumab treatment. These results underscore the need for a randomized trial of eculizumab in DDD.

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Section: Introductionmentioning

confidence: 99%

Eculizumab in Pediatric Dense Deposit Disease

Oosterveld¹,

Garrelfs²,

Höppe

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…A growing number of case reports have detailed the use of anti-complement C5 therapy, specifically eculizumab, as treatment for DDD both before and after transplantation (44,(47)(48)(49)(50).…”

Section: Treatment Today and Into The Futurementioning

confidence: 99%

American Society of Nephrology Clinical Pathological Conference

Meyers

Liapis

Atta

2014

Clinical Journal of the American Society of Nephrology

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A 13-year-old girl presented with proteinuria and acute kidney failure. She was born at full term via cesarean delivery (due to nuchal cord), but there were no other prenatal or perinatal complications. In early childhood the patient had two hospitalizations at ages 4.5 and 9 years, respectively, the latter for pneumonia. She had no history of symptoms of kidney disease. She came to the hospital at age 12 years for routine bilateral molar extractions. She was treated with oral antibiotics and discharged after the procedure without complications. At age 13 years, 10 months after the molar extraction, she was seen by a pediatrician because of puffiness and increased BP. She had had respiratory symptoms 2 weeks before presentation. The pediatrician prescribed furosemide and amlodipine. A few days later, the patient returned to the pediatrician's office because of hand, ankle, and facial swelling and malaise. The pediatrician recommended hospitalization and the patient was admitted at this time.

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“…Eight individual patients were reported, [73][74][75][109][110][111][112][113] showing success in seven patients. These optimistic results may be influenced by publication bias and contrast with the more modest effects obtained in an open-label proof-of-concept study in six patients.…”

Section: Inhibit Complement Activationmentioning

confidence: 99%

“…The phenotypic expression (DDD or C3 GN) does not seem to predict the response to treatment, 68,[73][74][75][109][110][111][112][113] although biomarker studies have suggested a greater terminal pathway activity in C3 GN compared with DDD. 115 In contrast, elevated soluble membrane attack complex was found to be a marker of response 68 in accordance with the mechanism of action of eculizumab on terminal pathway activation.…”

Section: Inhibit Complement Activationmentioning

confidence: 99%

Kidney Disease Caused by Dysregulation of the Complement Alternative Pathway

Vriese

Sethi²,

Praet

et al. 2015

Journal of the American Society of Nephrology

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Kidney diseases caused by genetic or acquired dysregulation of the complement alternative pathway (AP) are traditionally classified on the basis of clinical presentation (atypical hemolytic uremic syndrome as thrombotic microangiopathy), biopsy appearance (dense deposit disease and C3 GN), or clinical course (atypical postinfectious GN). Each is characterized by an inappropriate activation of the AP, eventuating in renal damage. The clinical diversity of these disorders highlights important differences in the triggers, the sites and intensity of involvement, and the outcome of the AP dysregulation. Nevertheless, we contend that these diseases should be grouped as disorders of the AP and classified on an etiologic basis. In this review, we define different pathophysiologic categories of AP dysfunction. The precise identification of the underlying abnormality is the key to predict the response to immune suppression, plasma infusion, and complement-inhibitory drugs and the outcome after transplantation. In a patient with presumed dysregulation of the AP, the collaboration of the clinician, the renal pathologist, and the biochemical and genetic laboratory is very much encouraged, because this enables the elucidation of both the underlying pathogenesis and the optimal therapeutic approach.

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Eculizumab therapy in a patient with dense-deposit disease associated with partial lipodystropy

Cited by 38 publications

References 13 publications

Eculizumab in Pediatric Dense Deposit Disease

Eculizumab in Pediatric Dense Deposit Disease

American Society of Nephrology Clinical Pathological Conference

Kidney Disease Caused by Dysregulation of the Complement Alternative Pathway

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