[Standardized histomorphological processing of peritoneal biopsies as part of the German Peritoneal Biopsy Registry (GRIP, German registry in PD)]. / Standardisierte histomorphologische Aufarbeitung von Peritonealbiopsien im Rahmen des Deutschen Peritonealbiopsieregisters (GRIP, German Registry In PD).

The peritoneal lining of the abdominal cavity consists of a parietal and visceral sheet. The serosa is an interesting organ, which in medical practice is particularly important in the context of chronic peritoneal dialysis (PD). This method of renal replacement therapy utilizes the semipermeability of the peritoneal surface by applying PD solutions of differing osmolarity to eliminate toxic substances and regulate fluid and electrolyte equilibrium. This method is an ideal approach especially for younger patients and is very effective at least for some time. Pre-existing injury to the peritoneum, for example as a consequence of chronic renal insufficiency or associated comorbidities and inflammatory changes that develop during PD, results in a structural remodelling of the serosa. As a consequence, the filtering function of the serosa is lost and PD has to be replaced by another renal replacement therapy. Thorough knowledge of the morphology of peritoneal changes as well as of the risk factors is of paramount importance for therapeutic management and prognosis of PD patients. In order to take this into account, the German Registry In Peritoneal Dialysis (Deutsches Peritonealbiopsieregister, GRIP) was founded a few years ago, which now includes roughly 1700 biopsies, of which detailed clinical and histomorphological information was systematically acquired and collected.

Effect of different hemodialysis regimens on genomic damage in end-stage renal failure.

Patients with end-stage renal disease display enhanced genomic damage that may have pathophysiologic relevance for cancer development and cardiovascular complications. We investigated to what extent the genomic damage in peripheral blood lymphocytes can be modulated #1: by initiation of standard hemodialysis (SHD) in formerly conservatively treated end-stage renal disease patients, #2: by a switch from SHD to hemodiafiltration, and #3: daily dialysis (DHD). Genomic damage was evaluated by the micronuclei (MN) frequency test and the comet assay (CA). In a prospective study we found that initiation of SHD did not induce significant changes of genomic damage in peripheral blood lymphocytes whereas the change to hemodiafiltration improved the percentage of DNA in the tail as measured by CA without modulating the MN frequency. In a cross-sectional investigation the degree of genomic damage as evaluated by MN frequency was significantly lower in a patient group treated by DHD as compared with a group treated by SHD. In the DHD patients there also was a significant decrease of the plasma concentrations of urea and the advanced glycation end products imidazolone A, carboxymethyllysine, and of advanced glycation end product-associated fluorescence.

Genomic damage and circulating AGE levels in patients undergoing daily versus standard haemodialysis.

BACKGROUND: Patients with end-stage renal failure, whether on conservative or haemodialysis therapy, have a high incidence of DNA damage. It is not known if improved control of the uraemic state by daily haemodialysis (DHD) reduces DNA lesions. METHODS: DNA damage in peripheral blood lymphocytes (PBLs) was evaluated in a cross-sectional study of 13 patients on DHD (2-3 h, 6 times/week), 12 patients on standard haemodialysis (SHD) therapy (4-5 h, 3 times/week) and 12 healthy age-matched volunteer controls. The biomarker of DNA damage used was micronucleus frequency. The assessed plasma parameters of microinflammation and oxidative stress were C-reactive protein (CRP), interleukin-6 (IL-6), neopterin, advanced oxidation protein products (AOPP), and homocysteine. We also measured plasma concentrations of the circulating advanced glycation end products (AGEs) MGI (methylglyoxal-derived imidazolinone), CML (carboxymethyllysine), imidazolone A (3-deoxyglucosone-derived imidazolinone) and AGE-associated fluorescence. RESULTS: Compared to SHD, DHD was associated with significantly lower DNA damage, approaching the normal range. Micronuclei (MN) frequency averaged 29.1 MN+/-5.9/1000 binucleated (BN) cells in the SHD group, which is significantly elevated (P<0.01), 14.8 MN+/-4.0/1000 BN cells in the DHD group, and 13.2 MN+/-3.04/1000 BN cells in the controls. CRP and AOPP were in the normal range (and similar between the dialysis groups). In contrast, IL-6 and neopterin were significantly elevated, with lower values associated with DHD as compared with SHD. The increased levels of AGEs tended to be lower in the DHD group, reaching significance for CML and imidazolone A. CONCLUSIONS: Overall, it was found that genomic damage in PBLs is lower in patients on DHD than in those on SHD. Lower plasma concentrations of uraemic toxins, including circulating AGEs, may account for the differences. To confirm these data, prospective clinical trials need to be performed.