Klin Wochenschr (1988) 66:1126-1137
Klinische
Wochen-
schdft
© Springer-Verlag 1988
Cyclosporin A Treatment in Children
with Minimal Change Nephrotic Syndrome
and Focal Segmental Glomerulosclerosis
J. Brodehl 1, M. Brandis 2, U. Helmchen 3, P.F. Hoyer 1, R. Burghard 2, J.H.H. Ehrich 1,
R.B. Zimmerhackl 2, W. Klein 2, and K. Wonigeit 4
1 KinderklinikMedizinische ttochschuIe,Hannover
z Universit/its-Kinderklinik, Marburg
3 PathologischesInstitut der Universit/it,G6ttingen
4 Klinik fiir Abdominal-und Transplantationschirurgie, Medizinische Hochschule,Hannover
Summary. In a pilot study 23 children with neph-
rotic syndrome were treated with cyclosporin A
(Cs) for 6-45 months. 8 children suffered from
steroid dependent minimal change nephrotic syn-
drome (MCNS) and had experienced at least one
course with cytotoxic drugs, but had relapsed
thereafter. 2 children had diabetes mellitus type I
with nephrotic syndrome and 13 children had ster-
oid resistant focal segmental glomerulosclerosis
(FSGS). Cs was started with 100 mg/m2/day in
two doses and increased stepwise to obtain a Cs
whole blood trough level of 200400 ng/ml. In ster-
oid dependent MCNS treatment with Cs reduced
relapse rate significantly, and prednisone therapy
could be stopped completely. After discontinua-
tion of Cs, relapses reoccurred as frequently as be-
fore. Renal function remained unimpaired despite
repeated Cs treatment courses up to 38 months.
In cases of nephrotic syndrome with diabetes type I
Cs treatment led to complete remission without
changing the insulin requirement. However, after
discontinuation of Cs relapses reoccurred. In ster-
oid resistant FSGS 6 children benefited from Cs
treatment: 4 went into complete remission, 2 into
partial remission. The 2 children with complete re-
mission relapsed but remained Cs responsive. The
remaining 7 children with FSGS did not respond
to Cs but continued the course of their disease,
with two patients rapidly progressing to terminal
renal failure. Side-effects of Cs treatment were
mild. It is concluded that Cs is an effective agent
in steroid dependent MCNS and can be used as
an alternative drug in specific cases like steroid
toxicity or diabetes mellitus. In steroid resistant
FSGS a trial with Cs seems to be warranted since
Abbreviations: MCNS=minimal change nephrotic syndrome;
FSGS = focal segmental glomerulosclerosis; Cs = Cyclosporin
A
some cases do respond favorably. To avoid neph-
rotoxicity treatment with Cs should always be
monitored closely by determination of blood levels
and renal function.
Key words: Cyclosporin - minimal change neph-
rotic syndrome - focal segmental glomerulosclero-
sis - children
Cyclosporin A (Cs) is a novel and potent immuno-
suppressive drug, that has found widespread appli-
cation in organ transplantation. It has an unique
action on T helper/inducer lymphocytes without
exhibiting any myelosuppressive side effects. Its
mechanism of action is primarily by blocking the
production of interleukin 2, a T-lymphocyte de-
rived lymphokine, which plays an important role
in the immune respone to foreign antigens [7, 8,
51]. Because of this specific action, it has been sug-
gested to extend the indications for Cs treatment
to therapy of autoimmunological diseases,
especially to those which are thought to be T-cell
mediated. Minimal change nephrotic syndrome
(MCNS) and focal segmental glomerulosclerosis
(FSGS) belong to this category [17, 18, 39, 43].
In 1983 we, therefore, initiated a pilot study to
treat children with MCNS and FSGS with Cs.
After a 4 years' experience we now assess prelimi-
nary results [9-11, 23] and compare them to those
reported by other investigators [15, 33, 34, 37, 44,
45, 49].
Patients and Methods
The efficacy and tolerance of Cs treatment was
assessed in children with steroid-dependent MCNS