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