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In kidney disease renal proximal tubular epithelial cells (RPTEC) actively contribute to the progression of tubulointerstitial fibrosis by mediating both an inflammatory response and via epithelial-to-mesenchymal transition. Using laser capture microdissection we specifically isolated RPTEC from cryosections of the healthy parts of kidneys removed owing to renal cell carcinoma and from kidney biopsies from patients with proteinuric nephropathies. RNA was extracted and hybridized to complementary DNA microarrays after linear RNA amplification. Statistical analysis identified 168 unique genes with known gene ontology association, which separated patients from controls. Besides distinct alterations in signal-transduction pathways (e.g. Wnt signalling), functional annotation revealed a significant upregulation of genes involved in cell proliferation and cell cycle control (like insulin-like growth factor 1 or cell division cycle 34), cell differentiation (e.g. bone morphogenetic protein 7), immune response, intracellular transport and metabolism in RPTEC from patients. On the contrary we found differential expression of a number of genes responsible for cell adhesion (like BH-protocadherin) with a marked downregulation of most of these transcripts. In summary, our results obtained from RPTEC revealed a differential regulation of genes, which are likely to be involved in either pro-fibrotic or tubulo-protective mechanisms in proteinuric patients at an early stage of kidney disease.

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Abstract. The demographic data on the use of continuous peritoneal dialysis in Europe for children starting renal replacement therapy under the age of 15 years was obtained from data collected by the Registry of the European Dialysis and Transplant Association-European Renal Association (EDTA Registry) on individual patient questionnaires 1980-1986. Continuous ambulatory peritoneal dialysis (CAPD) and its variants appeared to be increasingly utilised as treatment for children with end-stage renal failure (ESRF) and accounted for approximately 25% of all renal replacement therapy (RRT). Important differences in its use in various European countries are demonstrated. The proportional contribution of CAPD to treatment was higher during the first year of RRT and gradually decreased thereafter. No significant sex differences existed in the use of this treatment. Approximately 70% of all patients on CAPD were older than 6 years of age, but it is in those under 6 years that the highest proportion are put on CAPD as first method of treatment for end-stage renal failure. The most common cause of abandonment of this treatment was peritonitis, which contributed 50% of the drop-out rate.Correspondence and offprint requests to: Professor F. P. Brunner, EDTA Registry, St Thomas' Hospital, London SE1 7EH, UK.

Background Human polymorphonuclear neutrophils (PMN) are activated and undergo apoptosis if brought into contact with cuprophane haemodialysis membranes, a phenomenon not observed if more 'biocompatible' polysulfone dialysers are used. It remains yet to be defined if this differential response is due to mechanisms regulated on a transcriptional or protein level. Furthermore, it is not clear if the contact of PMN with membranes ('frustrated' phagocytosis) activates the same response as phagocytosis of bacteria (complete phagocytosis). Materials and methods We performed a genome-wide differential gene expression study using cDNA microarrays to analyse the impact of different dialysis fibres on the transcriptional response of PMN of human healthy volunteers. These results were compared to transcriptional response of PMN during phagocytosis of Escherichia coli. Results We did not detect significant differences in gene expression between PMN stimulated with cuprophane or pulysulfone. Compared to unstimulated PMN the 'frustrated' phagocytosis of either dialysis membrane resulted in increased expression of 50 genes, with a marked up-regulation of FOS - and JUN - transcripts, but with only little activation of immune response genes, and virtually no activation of apoptosis related RNA transcripts. In contrast, phagocytosis of E.coli was associated with a striking up-regulation of 88 genes, most of them involved in pro- and antiapoptotic pathways, immune response and activation of nuclear factor kappa B and inhibitor of NF-kappa B. Conclusions Our results suggest that the response of PMN to artificial surfaces is not controlled on transcriptional level. Complete and 'frustrated' phagocytosis activate markedly distinct transcriptional regulatory pathways in PMN.