A focus on CKD reporting and inappropriate prescribing among older patients discharged from geriatric and nephrology units throughout Italy: A nationwide multicenter retrospective cross-sectional study.

Older hospitalized patients with chronic kidney disease (CKD) are part of the geriatric population with a substantial risk of potentially inappropriate medication (PIM) use. The high rates of multimorbidity and polypharmacy, along with the progressive decline of eGFR, contribute to increasing the risk of drug-drug and drug-disease interactions, overdosing, and adverse drug reactions (ADRs). In this multicenter cross-sectional study, we aimed to evaluate the prevalence of CKD under-reporting and PIMs among older patients discharged from acute geriatric and nephrology units throughout Italy. Renal function was determined by estimated glomerular filtration rate (eGFR) through the Berlin Initiative Study (BIS) equation; the prevalence of PIMs was calculated by revising drug prescriptions at discharge according to STOPP criteria, Beers criteria, and summaries of product characteristics (smPCs). A descriptive analysis was performed to compare the clinical and pharmacological characteristics of patients in the two distinct settings; univariate and multivariate logistic regression models were performed to explore factors associated with CKD under-reporting in the discharge report forms and PIM prevalence. Overall, the study population consisted of 2,057 patients, aged 83 (77-89) years, more commonly women, with a median of seven (5-10) drugs prescribed at discharge. CKD under-reporting was present in 50.8% of the study population, with higher rates in geriatric vs. nephrology units (71.1% vs. 10.2%, p < 0.001). 18.5% of the study population was discharged with at least one renally inappropriate medication; factors associated with at least one contraindicated drug at discharge were the number of drugs (PR 1.09, 95% CI 1.14-1.19); atrial fibrillation (PR 1.35, 95% CI 1.01-1.81); diabetes (PR 1.61, 95% CI 1.21-2.13); being hospitalized in nephrology units (PR 1.62, 95% CI 1.14-2.31), CKD stage 3b (PR 2.35, 95% CI 1.34-4.13), and stage 4-5 (PR 14.01, 95% CI 7.36-26.72). Conversely, CKD under-reporting was not associated with the outcome. In summary, CKD under-reporting and inappropriate medication use were common in older patients discharged from hospital; the relatively high number of PIMs in both nephrology and geriatric settings underlines the need to improve appropriate prescribing during hospital stay and to decrease the risk of ADRs and side effects in this highly vulnerable population.

Molecular analysis of NPHS2 and ACTN4 genes in a series of 33 Italian patients affected by adult-onset nonfamilial focal segmental glomerulosclerosis.

BACKGROUND: Mutations in the NPHS2 gene, encoding podocin, and in the ACTN4 gene, encoding alpha-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.

Effects of ethylene oxide and steam sterilization on dialysis-induced cytokine release by cuprophan membrane.

The effects of sterilization modalities on dialysis-induced cytokine release are still unknown. To investigate these effects, 8 patients on chronic hemodialysis were enrolled for evaluating at different intervals interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) production (pg/ml/106). They were using a 1.3 m2 ethylene oxide (E3) or steam (E3S) sterilized Cuprophan membrane. The patients underwent a basal test with E3 (A1) and 2 following tests after 1 (B1) and 2 (B2) months of E3S treatment, respectively. Finally, the last test was performed 1 month after the switch to E3 (A2). Il-1beta predialysis release by mononuclear cells was 162 +/- 114 pg/ml/106 in A1, 185 +/- 129 pg/ml/106 in B1, and 226 +/- 138 pg/ml/106 in B2, then decreased to 123 +/- 134 in A2 (p < 0.07). Il-1beta postdialysis levels were 234 +/- 238 pg/ml/106 in A1, 429 +/- 285 pg/ml/106 (B1), and 438 +/- 473 pg/ml/106 (B2) with the steam membrane, decreasing to 204 +/- 134 pg/ml/106 in A2 (p < 0.01). TNF-alpha predialysis basal release (A1) was 826 +/- 817 pg/ml/106, 720 +/- 496 in B1, and 1079 +/- 515 pg/ml/106 in B2, and finally 680 +/- 588 pg/ml/106 in A2 (p < 0.03). In postdialysis TNF-alpha levels were 963 +/- 542 pg/ml/106 in A1, 1,226 +/- 541 pg/ml/106, and 1,183 +/- 776 in B1 and B2 respectively, and 388 +/- 297 pg/ml/106 in A2 (p < 0.003). Steam sterilization seems to induce a higher cytokine release by mononuclear cells when a Cuprophan membrane is used. This finding may be related to a less physiologic action of the steam in the case of Cuprophan membranes. Further studies are needed to clarify this hypothesis.