What are we missing in the clinical trials of focal segmental glomerulosclerosis?

Ladan Zand, Richard J. Glassock, An S. De Vriese, Sanjeev M Sethi, Fernando Custodio Fervenza

Research output: Contribution to journalReview article

6 Citations (Scopus)

Abstract

Focal segmental glomerulosclerosis (FSGS) is a lesion and not a disease. This conundrum is the crux of controversies regarding interventions to alter its natural history. In the broadest sense, the lesion can be primary (idiopathic), or secondary to a process originating outside the kidneys or to a genetic mutation. The organ-based target is the podocyte, and the mechanisms responsible for the podocytopathy are numerous and diverse. Recurrence of primary FSGS in renal allografts provides the best evidence for the existence of a circulating factor or factors, the nature of which remains uncertain. The separation of primary from secondary FSGS clinically and pathologically is challenging, but full-blown nephrotic syndrome and diffuse (universal) foot process effacement are strong signals for a primary form of FSGS. It is imperative that clinical trials designed to investigate therapeutic strategies for patients with a lesion of FSGS pay careful attention to the separation of primary from secondary forms of FSGS. This critical review provides a rationale and a process for helping to ensure that this is accomplished, such that clinical trials provide useful information and treatment responsiveness applicable to the primary forms of FSGS.

Fingerprint

Focal Segmental Glomerulosclerosis
Clinical Trials
Kidney
Podocytes
Nephrotic Syndrome
Natural History
Allografts
Foot
Recurrence
Mutation
Therapeutics

Keywords

  • clinical trials
  • electron microscopy
  • focal segmental glomerulosclerosis
  • nephrotic syndrome
  • secondary FSGS

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

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title = "What are we missing in the clinical trials of focal segmental glomerulosclerosis?",
abstract = "Focal segmental glomerulosclerosis (FSGS) is a lesion and not a disease. This conundrum is the crux of controversies regarding interventions to alter its natural history. In the broadest sense, the lesion can be primary (idiopathic), or secondary to a process originating outside the kidneys or to a genetic mutation. The organ-based target is the podocyte, and the mechanisms responsible for the podocytopathy are numerous and diverse. Recurrence of primary FSGS in renal allografts provides the best evidence for the existence of a circulating factor or factors, the nature of which remains uncertain. The separation of primary from secondary FSGS clinically and pathologically is challenging, but full-blown nephrotic syndrome and diffuse (universal) foot process effacement are strong signals for a primary form of FSGS. It is imperative that clinical trials designed to investigate therapeutic strategies for patients with a lesion of FSGS pay careful attention to the separation of primary from secondary forms of FSGS. This critical review provides a rationale and a process for helping to ensure that this is accomplished, such that clinical trials provide useful information and treatment responsiveness applicable to the primary forms of FSGS.",
keywords = "clinical trials, electron microscopy, focal segmental glomerulosclerosis, nephrotic syndrome, secondary FSGS",
author = "Ladan Zand and Glassock, {Richard J.} and {De Vriese}, {An S.} and Sethi, {Sanjeev M} and Fervenza, {Fernando Custodio}",
year = "2017",
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doi = "10.1093/ndt/gfw324",
language = "English (US)",
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T1 - What are we missing in the clinical trials of focal segmental glomerulosclerosis?

AU - Zand, Ladan

AU - Glassock, Richard J.

AU - De Vriese, An S.

AU - Sethi, Sanjeev M

AU - Fervenza, Fernando Custodio

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Focal segmental glomerulosclerosis (FSGS) is a lesion and not a disease. This conundrum is the crux of controversies regarding interventions to alter its natural history. In the broadest sense, the lesion can be primary (idiopathic), or secondary to a process originating outside the kidneys or to a genetic mutation. The organ-based target is the podocyte, and the mechanisms responsible for the podocytopathy are numerous and diverse. Recurrence of primary FSGS in renal allografts provides the best evidence for the existence of a circulating factor or factors, the nature of which remains uncertain. The separation of primary from secondary FSGS clinically and pathologically is challenging, but full-blown nephrotic syndrome and diffuse (universal) foot process effacement are strong signals for a primary form of FSGS. It is imperative that clinical trials designed to investigate therapeutic strategies for patients with a lesion of FSGS pay careful attention to the separation of primary from secondary forms of FSGS. This critical review provides a rationale and a process for helping to ensure that this is accomplished, such that clinical trials provide useful information and treatment responsiveness applicable to the primary forms of FSGS.

AB - Focal segmental glomerulosclerosis (FSGS) is a lesion and not a disease. This conundrum is the crux of controversies regarding interventions to alter its natural history. In the broadest sense, the lesion can be primary (idiopathic), or secondary to a process originating outside the kidneys or to a genetic mutation. The organ-based target is the podocyte, and the mechanisms responsible for the podocytopathy are numerous and diverse. Recurrence of primary FSGS in renal allografts provides the best evidence for the existence of a circulating factor or factors, the nature of which remains uncertain. The separation of primary from secondary FSGS clinically and pathologically is challenging, but full-blown nephrotic syndrome and diffuse (universal) foot process effacement are strong signals for a primary form of FSGS. It is imperative that clinical trials designed to investigate therapeutic strategies for patients with a lesion of FSGS pay careful attention to the separation of primary from secondary forms of FSGS. This critical review provides a rationale and a process for helping to ensure that this is accomplished, such that clinical trials provide useful information and treatment responsiveness applicable to the primary forms of FSGS.

KW - clinical trials

KW - electron microscopy

KW - focal segmental glomerulosclerosis

KW - nephrotic syndrome

KW - secondary FSGS

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