Background: Calcitriol (C) improves anemia in chronic renal failure. This effect may be related to the suppression of iPTH release, or to a direct effect on erythropoiesis. Methods: Thirty-three patients with chronic renal failure were enrolled; among them, 24 were on chronic hemodialysis and 9 on conservative management. None had other chronic or hematological disease, aluminum levels were below 20 µg/l and DFO testing was negative. The iPTH range was 250–480 pg/l. None were treated with C or r-HuEpo. In vitro study: Samples were drawn for a basal erythroid precursor (burst forming unit-erythroid BFU-E) study: Mononuclear cells were incubated for 14 days with r-HuEpo 3U/ml (A), r-HuEpo 3U/l + C 30 pg (B), r-HuEpo 3U/ml + C 300 pg (C), or r-HuEpo 30 U/ml + C 300 pg (D). In vivo study: After the basal evaluation, 10 patients on chronic dialysis were treated with C (Calcijex-Abbott) 1 µg three times a week, and 4 patients served as controls. BFU-E studies were performed after 1, 2 and 4 months. Results: In vitro, culture B showed increased BFU-E proliferation vs. A (41 ± 23 vs. 27 ± 15, p < 0.02); in cultures C and D, proliferation was 61 ± 31 and 78 ± 42, respectively, p < 0.01 vs. A. There was no difference among patients with predialysis renal failure and those on dialysis. BFU-E proliferation was inversely related to basal Hb (p < 0.04) and CRP levels (p < 0.05). During the in vivo study, all cultures showed a progressive increase in proliferation without a plateau level (basal, after 1, 2 and 4 months, respectively) In A: 17 ± 8, 22 ± 13, 30.9 ± 14.9, 41.4 ± 20; in B: 27.3 ± 15, 35.6 ± 20, 45.5 ± 21, 57 ± 26; in C: 48.2 ± 20.6, 63.7 ± 32, 75.7 ± 37, 83 ± 40; in D: 72 ± 24, 91 ± 42, 106 ± 42, 110 ± 42.3 (all p < 0.001). Hb and Hct showed a significant increase (p < 0.03) in the treatment group. The decrease in iPTH was not related to BFU-E proliferation. Conclusions: In chronic uremia, C has a direct effect on erythroid precursors proliferation, as demonstrated both in vitro and in vivo, with a synergistic effect with r-HuEpo. C may be a useful adjuvant therapy to r-HuEpo treatment.

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These findings support the hypothesis that a PMMA dialyser may improve renal itching in ESRD patients. This effect is not mediated by increased dialysis efficiency or an improvement in other biochemical parameters, but we can speculate that ionic substances may be directly or indirectly adsorbed into the polymer composition of BG-U series (PMMA membrane dialyser). We are currently undergoing further studies using a proteomic approach.

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Background: Mutations in the NPHS2 gene, encoding podocin, and in the ACTN4 gene, encoding α-actinin-4, have been identified in familial childhood-onset forms of focal and segmental glomerulosclerosis (FSGS). NPHS2 may be also responsible for some sporadic cases. The role of NPHS2 and ACTN4 in the adult sporadic form of the disease is being clarifying. Methods: Thirty-three adult subjects affected by sporadic FSGS were studied at molecular level. At biopsy, 12 patients had nephrotic syndrome, 5 patients had isolated proteinuria and 16 patients showed proteinuria and hematuria. Glomerular filtration rate (GFR) was in the normal range in 19 subjects and 14 patients had a variable degree of renal failure. Multiplex families presenting with a clear familial inheritance for proteinuria or other congenital nephrotic syndrome were excluded. The whole coding region, all intron/exon boundaries and flanking intronic regions of NPHS2 gene and the exon 8, i.e. hot-spot mutations of the ACTN4 gene, were analyzed in all patients by denaturing high-performance liquid chromatography (DHPLC) to search disease-causing defects. Results: The analysis identified four already described and two new polymorphisms, IVS3–21C>T and IVS3–46C>T, on the NPHS2 gene. Moreover, the R229Q allele was identified in 3/33 patients and in 7/124 controls, accounting for an allelic frequency of 0.045 and 0.028, respectively. The new intronic polymorphism IVS7–54C>T was also found in the exon 8 of the ACTN4 gene. Conclusions: In this study, we exhaustively analyzed the NPHS2 and the exon 8 of the ACTN4 genes in a series of sporadic ‘adult-onset’ FSGS patients. No causative mutations were found while the R229Q allele was identified in 3 patients confirming its possible role as a ‘disease-associated NPHS2 allele’ although its pathogenetic involvement needs to be further clarified. Moreover, the description of new intronic polymorphisms in both genes is reported.