Manchester Royal Infirmary Nephrology Manchester, UK Email: yingseow{at}aol.com
Sir,
Icodextrin-associated sterile peritonitis is well-recognized. An incidence of 1030% amongst CAPD Extraneal® (Baxter, UK) users has been estimated [1]. A higher incidence of nearly 50% was found by Foggensteiner et al. [2], which has been attributed to prolonged contact with the polymer since it was used in an early start single overnight exchange regime.
Between 1 December 2001 and 31 May 2002, we noticed an increase in sterile peritonitis in our CAPD/APD population (52/110 = 47.2%) compared with the preceding 6 months (10/55 = 18%) with comparable infective episodes. Thirteen of these sterile peritonitis patients were part of a study using biocompatible fluids in CAPD that was being conducted at the time.
There were 14 patients in the study, all were new end-stage renal failure within 1 month of being on peritoneal dialysis. Each patient had an overnight Extraneal® exchange and three daytime exchanges of Physioneal® (two exchanges) and Nutrineal® (one exchange). Thirteen of the 14 (92.9%) experienced at least one episode of hazy dialysate within the first 6 months. Eleven of the 13 also had a peritoneal fluid white cell count >100/mm3. Nine of the 13 (69.2%) were incidentally picked up during protocol follow-up sessions when the dialysate was brought in for biochemical analyses. Out of five who were treated empirically with intra-peritoneal antibiotics, three had a transient or partial response. All cases responded fully to withdrawal of Extraneal®.
Baxter has reported that the culprit may be batches of fluid with peptidoglycan levels >10 ng/ml coming from one of its manufacturing plants [3]. Peptidoglycan is a major irritant cell wall component of Gram-positive organisms. Normal sera contain antibodies to peptidoglycan. Peptidoglycan excites only low pro-inflammatory response but strongly activates macrophages. This corresponds with the high percentage of macrophages found in the dialysate. The concentration required to activate macrophages is 10100ng/ml. Some of these sterile peritonitis cases appear to have a transient or partial response to antibiotics [1,2], while others appear to follow on from a bacterial peritonitis [4,5]. For the latter cases, streptococci have been identified (viridans and agalactiae). Peptidoglycan being the cause of icodextrin-associated peritonitis could explain these observations. Possible hypotheses will be that some of the antibodies raised to Gram-positive microbes react to the peptidoglycan in the dialysate hence triggering a sterile component to the inflammation; alternatively, the low load of dialysate peptidoglycan and microbe, whilst clinically insignificant individually, together could excite inflammation to give rise to obvious peritonitis. In either case, antibiotics itself would decrease but not completely resolve the inflammation. Patients will also become sensitized, and this accounts for the recurrence of cloudy dialysate when re-challenged with dialysate containing <10 ng/ml peptidoglycan.
Our study reflects the true incidence of sterile peritonitis amongst CAPD Extraneal® users as we relied on organized check-ups rather than reporting by patients. Baxter has since had a voluntary recall of batches with known high peptidoglycan levels. This has resulted in a dramatic decline in incidence of Extraneal®-associated sterile peritonitis. This makes peptidoglycan the likely cause of the icodextrin-associated sterile peritonitis observed recently. It would seem logical that only a <10 ng/ml peptidoglycan level fluid should be used. However, the concern is that presence of any peptidoglycan, even low levels <10 ng/ml, may lower the bacterial load required to trigger off peritonitis. Likewise, previously sensitized patients may only be able to tolerate fluid containing no peptidoglycan. This, however, may not be technically feasible.
Conflict of interest statement. None declared.
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