This is the fsgs (focal segmental glomerulosclerosis) editorial that I wrote in 
May 1999 for Kidney International, the journal of the International Society of 
Nephrology.  Multiple people have asked for it lately, and it occurred to me 
that I had it on disk and could just paste to here.
     Dr. Sue Conely
The child whose idiopathic nephrotic syndrome defies treatment presents the greatest
of challenges to the skills of the pediatric nephrologist.  The majority of such patients,
on renal biopsy, are found to have the lesion called focal segmental glomerulosclerosis
(FSGS), where segments of one or more glomeruli are sclerotic.  The glomeruli in the
juxtamedullary region are the most likely to be affected with this lesion.  With time, renal
failure may develop and progress to end stage renal disease.  Some of the patients will 
have recurrence of the nephrotic syndrome and eventually show this typical sclerotic
lesion on biopsy of the transplant kidney, though early in the evolution of the recurrence,
the biopsy is more typical of minimal change disease.
It has seemed to many of us over the past few years that we are seeing more such
children, and the paper by Bonilla-Felix, et al.1 confirms that feeling.  When one asks
why we are seeing more such children, a pandora's box of questions is opened.  First,
what is this condition called focal segmental glomerulosclerosis?  Is it a unique disease,
or is it the same disease as minimal change nephrotic syndrome (MCNS)?   If MCNS
and FSGS are the same disease and signify different ends of the severity spectrum of this
disease, why has the disease become more severe?   The more one reads, the muddier
the whole picture becomes.
The lesion of focal segmental glomerulosclerosis is eventually present on biopsy in the 
majority of children with  primary nephrotic syndrome who are resistant to steroid therapy
and in many of those who respond to steroids with remission of the nephrotic syndrome
but become steroid-dependant to stay in remission.   Does prolonged proteinuria cause 
glomerular injury, resulting in the FSGS lesion, or is the lesion a specific indicator  of a
unique and more severe disease  in which proteinuria continues unabated by therapeutic
attempts?     McAdams3 et al argue that the lesion of segmental glomerulosclerosis is 
not a specific marker for a subtype of idiopathic nephrotic syndrome but reflects instead
the progressive nature of the disease process.  If this is true, we are left with the question,
why is the disease progressing in a larger percentage of children?  Is it, as Bonilla-Felix et al.
1 suggest, secondary to an environmental factor?  At this point, we have no idea why this
may be happening.
Genetic factors appear to play a role, as there is a higher and increasing incidence of the
FSGS lesion in African American children, shown not only in the Bonilla-Felix study1 but
in several other studies4,5, as well as a lower incidence in Hispanic children.
In spite of the predilection of children with the FSGS lesion to respond poorly to therapy,
those who do respond tend to have a prognosis more similar to that of the child with MCNS.
The achievement of  long-term remission is a stronger correlate of a favorable prognosis
than is the presence or absence of a specific finding on biopsy3,6.
So, where do we go from here?  It is clear that we have a very poor understanding of the
disease process in children with idiopathic nephrotic syndrome.  We know that the
condition is associated with multiple abnormalities of the immune system, some likely 
etiologic and others secondary to the disease process7,  and we know that immunosuppressive
therapies are effective in many patients8,9,  but we cannot predict which therapy will help
which patient, or if any therapy will be helpful in a given patient.   As a result, we expose
some patients to very toxic therapies with no benefit.  We don't know the basic cause or 
causes of idiopathic nephrotic syndrome, and we don't understand the role of the FSGS
lesion in the steroid-dependent or in the steroid-resistant patient.   In order to advance our
knowledge and better correlate pathological lesion, course and response to therapy, we need
to do renal biopsies on all children with nephrotic syndrome who are steroid-dependent or
steroid-resistant. With modern techniques the risk of percutaneous biopsy is minimal, and
the procedure can be done with little pain for the patient.  We pediatric nephrologists, along 
with our pathology colleagues, need to work together in multicenter  studies to look closer
at these patients for clues to the etiology of  their disease and to compare potential therapies