The Evidence-Based Approach to Adult-Onset Idiopathic Nephrotic Syndrome

Canetta, Pietro A.; Radhakrishnan, Jai

doi:10.3389/fped.2015.00078

Cited by 24 publications

(21 citation statements)

References 57 publications

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“…For example, among patients with focal segmental glomerulosclerosis, the absence of genetic mutations in structural components of the glomerular basement membrane would indicate an acquired, immunologic cause of the condition and would support the use of immunosuppression. 31 We detected known or expected pathogenic variants in the 59 ACMG medically actionable genes in 34 of the 2187 patients (1.6%) assessed, a finding consistent with previous studies involving unselected adults. 32,33 Although classically viewed as secondary findings, the findings for these genes had implications for nephrologic care in all cases.…”

Section: Discussionsupporting

confidence: 89%

Faculty Opinions recommendation of Diagnostic utility of exome sequencing for kidney disease.

Böckenhauer

2019

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

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BACKGROUND-Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally. METHODS-We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings. RESULTS-In all, 3037 patients (91.6%) were over 21 years of age, and 1179 (35.6%) were of self-identified non-European ancestry. We detected diagnostic variants in 307 of the 3315 patients (9.3%), encompassing 66 different monogenic disorders. Of the disorders detected, 39 (59%) were found in only a single patient. Diagnostic variants were detected across all clinically defined categories, including congenital or cystic renal disease (127 of 531 patients [23.9%]) and nephropathy of unknown origin (48 of 281 patients [17.1%]). Of the 2187 patients assessed, 34 (1.6%) had genetic findings for medically actionable disorders that, although unrelated to their nephropathy, would also lead to subspecialty referral and inform renal management. CONCLUSIONS-Exome sequencing in a combined cohort of more than 3000 patients with chronic kidney disease yielded a genetic diagnosis in just under 10% of cases. (Funded by the National Institutes of Health and others.) Targeted capture and sequencing of the protein-coding regions of the genome through exome sequencing is increasingly applied as a first-line diagnostic tool in clinical medicine, particularly for the diagnosis of metabolic and neurodevelopmental disorders in children, 1,2 as well as for the detection of causal mutations in cancer. 3-5 In those contexts, exome sequencing can inform medical management, including the choice of therapy. 1,6-9 However, the usefulness of this approach has not been systematically studied for most constitutional disorders in adults. Because the diagnostic yield of exome sequencing can vary according to the clinical disorder and the population studied, 9 thorough investigations across different constitutional disorders are needed to inform its use in clinical practice. Chronic kidney disease affects more than 10% of people worldwide, with substantial associated morbidity and mortality and a high burden in health care spending. 10 Yet the

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Section: Discussionsupporting

confidence: 89%

Faculty Opinions recommendation of Diagnostic utility of exome sequencing for kidney disease.

Böckenhauer

2019

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

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Section: Discussionmentioning

confidence: 99%

Diagnostic Utility of Exome Sequencing for Kidney Disease

Groopman¹,

Marasà²,

et al. 2019

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BACKGROUND Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally. METHODS We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings. RESULTS In all, 3037 patients (91.6%) were over 21 years of age, and 1179 (35.6%) were of self-identified non-European ancestry. We detected diagnostic variants in 307 of the 3315 patients (9.3%), encompassing 66 different monogenic disorders. Of the disorders detected, 39 (59%) were found in only a single patient. Diagnostic variants were detected across all clinically defined categories, including congenital or cystic renal disease (127 of 531 patients [23.9%]) and nephropathy of unknown origin (48 of 281 patients [17.1%]). Of the 2187 patients assessed, 34 (1.6%) had genetic findings for medically actionable disorders that, although unrelated to their nephropathy, would also lead to subspecialty referral and inform renal management. CONCLUSIONS Exome sequencing in a combined cohort of more than 3000 patients with chronic kidney disease yielded a genetic diagnosis in just under 10% of cases. (Funded by the National Institutes of Health and others.)

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“…Also, rituximab has proven to be effective in adults (73), and data from another frequent cause of nephrotic syndrome in adults, membranous nephropathy, in which rituximab is used as single agent, are encouraging even considering the long-term safety (74). A current evidence-based approach to MCD therapy in adults is shown in Table 3 and reviewed in Hogan and Radhakrishnan (65) and Canetta and Radhakrishnan (75).…”

Section: Adultsmentioning

confidence: 99%

Minimal Change Disease

Vivarelli

Massella

Ruggiero

et al. 2016

CJASN

395

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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The Evidence-Based Approach to Adult-Onset Idiopathic Nephrotic Syndrome

Cited by 24 publications

References 57 publications

Faculty Opinions recommendation of Diagnostic utility of exome sequencing for kidney disease.

Faculty Opinions recommendation of Diagnostic utility of exome sequencing for kidney disease.

Diagnostic Utility of Exome Sequencing for Kidney Disease

Minimal Change Disease

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