Untitled - Roche Trasplantes

EARLY DIAGNOSIS OF CHRONIC ALLOGRAFT NEPHROPATHY
BY MEANS OF PROTOCOL BIOPSIES
long term cyclosporine dosage with a cut off point at a maintenance dose of about 5 mg/
kg/day. The histological appearance that is classically described is of a nodular hyaline
change in the wall of renal arterioles (14). In our data, however, this classical change often
gave way to more diffuse change with narrowing of the lumen and evidence of glomerular
ischaemia. The question thus arises as to whether the arteriolar change may be
associated with hypertension or with diabetes in our series. We were able to dispel these
two possibilities since treated hypertension succeeded the appearance of arteriolar hyalinosis
and did not preceed it as would be expected if it had a role in aetiology, also 60%
of hypertensive and 68% of normotensive patients had arteriolar changes. With respect
to the possibility of an effect from diabetes, the simultaneous glucose tolerance test performed
with each protocol biopsy showed identical glucose handling in those with and
those without arteriolar changes (38).
Glomerular disease
The final pathway for damage to the nephron is exhibited through glomerulosclerosis,
with which irreversible loss of glomerular and nephron function occurs. Glomerular filtration
rate is also closely linked to the glomerular sclerosis, especially as the number of
functioning nephrons falls and glomerular hyperfiltration capacity is exceeded. There are
at least three different mechanisms of destruction and pathologies that can be discerned
in transplant glomeruli.
Recurrent glomerulonephritis
Occurs at different frequencies in different diseases and may account for a significant
number of graft failures, such as in focal and segmental glomerular sclerosis (FSGS), or
be essentially irrelevant such as in systemic lupus erythematosus (SLE) (15). No more
will be said here about recurrent disease except to note that an increase in proteinuria
by >500 mg/day or an absolute excretion rate of >1,500 mg/day are a reliable guide to the
need for a diagnosis of the glomerular pathology (39), except possibly in patients treated
with sirolimus or everolimus.
Chronic transplant glomerulopathy
In which the earliest signs, seen on electron microscopy include splitting of the basement
membrane. This may be associated with the deposition of C4d and chronic antibody
mediated damage to the glomerulus (40). It has been well accepted since the 1960’s
that antibody to HLA mediates hyperacute and forms of acute rejection. Transplant glomerulopathy
was recognised as early as 1963 with enlarged glomeruli, mesangial matrix
expansion, changes in mesangial cells and splitting of both the glomerular and peritubular
basement membranes (41). Perhaps lulled into a false sense of security by the improvement
in crossmatching techniques, or perhaps by the confounding factors sur-
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