Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children

Pravitsitthikul, Nanthiya; Willis, Narelle S; Hodson, Elisabeth M; Craig, Jonathan C.

doi:10.1002/14651858.cd002290.pub4

Cited by 67 publications

(77 citation statements)

References 80 publications

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“…Several Cochrane reviews are available covering treatment of FSGS in adults (104) and children using not only glucocorticoids (105) but also, other therapies, including cyclophosphamide, azathioprine, levamisole, mizorbine, and rituximab (106,107). Many other agents have been tested in small trials or reported as case series, and they have been the subject of recent reviews (13,(108)(109)(110)(111).…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Focal Segmental Glomerulosclerosis

Rosenberg

Kopp

2017

CJASN

392

366

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Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies arenow recognized asdrivers of FSGS: high-penetrance geneticFSGSdue to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele-associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g., glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g., to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

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Section: Therapeutic Approachesmentioning

confidence: 99%

Focal Segmental Glomerulosclerosis

Rosenberg

Kopp

2017

CJASN

392

366

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“…It inhibits calcineurin (like tacrolimus; TAC) and thus blocks the activation of T cells, modifying the immune response. The first comparative studies published on this drug involved alkylating agents, showing no superiority of CsA versus chlorambucil (46) or versus cyclophosphamide (46). The fact that CsA is easier to handle (no need for frequent check of the blood count and no gonadal toxicity) and that alkylating agents seemed to be more effective in frequently relapsing NS than steroid-dependent NS, led to a preference for CsA, especially in steroid-dependent NS.…”

Section: Nonsteroidal Immunosuppressive Drugsmentioning

confidence: 99%

Minimal Change Disease

Vivarelli

Massella

Ruggiero

et al. 2016

CJASN

374

383

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Minimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS), characterized by intense proteinuria leading to edema and intravascular volume depletion. In adults, it accounts for approximately 15% of patients with idiopathic NS, reaching a much higher percentage at younger ages, up to 70%-90% in children >1 year of age. In the pediatric setting, a renal biopsy is usually not performed if presentation is typical and the patient responds to therapy with oral prednisone at conventional doses. Therefore, in this setting steroid-sensitive NS can be considered synonymous with MCD. The pathologic hallmark of disease is absence of visible alterations by light microscopy and effacement of foot processes by electron microscopy. Although the cause is unknown and it is likely that different subgroups of disease recognize a different pathogenesis, immunologic dysregulation and modifications of the podocyte are thought to synergize in altering the integrity of the glomerular basement membrane and therefore determining proteinuria. The mainstay of therapy is prednisone, but steroid-sensitive forms frequently relapse and this leads to a percentage of patients requiring second-line steroid-sparing immunosuppression. The outcome is variable, but forms of MCD that respond to steroids usually do not lead to chronic renal damage, whereas forms that are unresponsive to steroids may subsequently reveal themselves as FSGS. However, in a substantial number of patients the disease is recurrent and requires long-term immunosuppression, with significant morbidity because of side effects. Recent therapeutic advances, such as the use of anti-CD20 antibodies, have provided long-term remission off-therapy and suggest new hypotheses for disease pathogenesis.

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“…Bone marrow suppression with leucopenia, anemia, and thrombocytopenia, alopecia, nausea, abdominal pain, and hemorrhagic cystitis (for CYC), constitute the most important short-term side effects. Arterial hypertension, hypertrichosis, gingival hyperplasia, hypomagnesaemia, hyperuricemia, and nephrotoxicity may be encountered during CYA therapy [41][42][43][44]. Infection is a universal concern in patients receiving cytotoxic or immunosuppressive therapy.…”

Section: Toxicity Of Cytotoxic and Immunosuppressive Drugs: A Pediatrmentioning

confidence: 99%

Treatment of Steroid-Resistant Nephrotic Syndrome

Abeyagunawardena¹

2017

UNOAJ

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Nephrotic syndrome is the most common glomerular disorder in children, and corticosteroids are the first choice of treatment. While the majority of children respond to corticosteroid therapy, a few do not enter remission after daily therapy for 1-2 months, hence showing steroid-resistance. Most of these children show focal and segmental glomerulosclerosis (FSGS) upon renal biopsy. Steroid resistance and associated complications make management of these patients very challenging, with their higher chance of progression to end-stage renal failure. Various immunosuppressive drugs have been used to induce remission with different success rates, though most of them have shown weak effectiveness. However, careful weighing of their toxic effects and effective dose should be done, especially when treating children with a non-malignant disease like nephrotic syndrome, thus obtaining optimum results. This review discusses steroid-resistant nephrotic syndrome and treatment strategies that have been attempted.

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Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children

Cited by 67 publications

References 80 publications

Focal Segmental Glomerulosclerosis

Focal Segmental Glomerulosclerosis

Minimal Change Disease

Treatment of Steroid-Resistant Nephrotic Syndrome

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