1. Improved protective effect of umbilical cord stem cell transplantation on cisplatin-induced kidney injury in mice pretreated with antithymocyte globulinŽeljka Večerić-Haler, Andreja Erman, Anton Cerar, Helena Motaln, Katja Kološa, Tamara Lah Turnšek, Snežna Sodin-Šemrl, Katja Lakota, Katjuša Mrak Poljšak, Špela Škrajnar, Simona Kranjc Brezar, Miha Arnol, Martina Perše, 2016, original scientific article Abstract: Mesenchymal stem cells (MSCs) are recognised as a promising tool to improve renal recovery in experimental models of cisplatin-induced acute kidney injury. However, these preclinical studies were performed on severely immunodeficient animals. Here, we investigated whether human umbilical cord derived MSC treatment could equally ameliorate acute kidney injury induced by cisplatin and prolong survival in mice with a normal immune system and those with a suppressed immune system by polyclonal antithymocyte globulin (ATG). We demonstrated that ATG pretreatment, when followed by MSC transplantation, significantly improved injured renal function parameters, as evidenced by decreased blood urea nitrogen and serum creatinine concentration, as well as improved renal morphology. This tissue restoration was also supported by increased survival of mice. The beneficial effects of ATG were associated with reduced level of inflammatory protein serum amyloid A3 and induced antioxidative expression of superoxide dismutase-1 (SOD-1), glutathione peroxidase (GPx), and hem oxygenase-1 (HO-1). Infused MSCs became localised predominantly in peritubular areas and acted to reduce renal cell death. In conclusion, these results show that ATG diminished in situ inflammation and oxidative stress associated with cisplatin-induced acute kidney injury, the effects that may provide more favourable microenvironment for MSC action, with consequential synergistic improvements in renal injury and animal survival as compared to MSC treatment alone.
Keywords: mesenchymal stem cells, nephrotoxicity
Published in DiRROS: 25.07.2024; Views: 117; Downloads: 115
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2. Feasibility of droplet digital PCR analysis of plasma cell-free DNA from kidney transplant patientsBarbara Jerič Kokelj, Maja Štalekar, Sebastian Vencken, David Dobnik, Polona Kogovšek, Matjaž Stanonik, Miha Arnol, Maja Ravnikar, 2021, original scientific article Abstract: Increasing research demonstrates the potential of donor-derived cell-free DNA (dd-cfDNA) as a biomarker for monitoring the health of various solid organ transplants. Several methods have been proposed for cfDNA analysis, including real-time PCR, digital PCR, and next generation sequencing-based approaches. We sought to revise the droplet digital PCR (ddPCR)-based approach to quantify relative dd-cfDNA in plasma from kidney transplant (KTx) patients using a novel pilot set of assays targeting single nucleotide polymorphisms that have a very high potential to distinguish cfDNA from two individuals. The assays are capable of accurate quantification of down to 0.1% minor allele content when analyzing 165 ng of human DNA. We found no significant differences in the yield of extracted cfDNA using the three different commercial kits tested. More cfDNA was extracted from the plasma of KTx patients than from healthy volunteers, especially early after transplantation. The median level of donor-derived minor alleles in KTx samples was 0.35%. We found that ddPCR using the evaluated assays within specific range is suitable for analysis of KTx patientsʼ plasma but recommend prior genotyping of donor DNA and performing reliable preamplification of cfDNA.
Keywords: kidney transplantation, droplet digital PCR, plasma cell-free DNA, minor allele quantification, assay evaluation, graft health monitoring
Published in DiRROS: 19.07.2024; Views: 121; Downloads: 61
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5. Onko-nefrologija - pristop k obravnavi bolnikovTomaž Milanez, Janja Ocvirk, Miha Arnol, 2021, professional article Abstract: Onko-nefrologija je novo, multidisciplinarno področje, ki povezuje predvsem področji onkologije in nefrologije. Število bolnikov z rakom, ki imajo različno stopnjo ledvične okvare, narašča. Cilj celostne obravnave onko-nefrološkega bolnika je večja učinkovitost in varnost zdravljenja. Bolniki z ledvično okvaro višje stopnje so bili izključeni iz prospektivnih randomiziranih raziskav, tako da za njih ni na voljo podatkov z visoko dokazi visoke stopnje o učinkovitosti in varnosti zdravil ter mejnih vrednostih biooznačevalcev, ki so v pomoč pri vodenju zdravljenja. V klinični praksi se zato pri zdravljenju onko-nefrološkega bolnika opiramo na klinične izkušnje, podatke iz retrospektivnih analiz in posameznih objavljenih primerov ter priporočila, ki temeljijo na soglasju strokovnjakov. Pri zdravljenju onko-nefrološkega bolnika je ključno tesno sodelovanje med onkologom in nefrologom, mnogokrat je nujen multidisciplinarni posvet. Zdravnik, ki je odgovoren za načrt zdravljenja, potrebuje osnovno znanje nefrologije in dobro poznavanje omejitev onkološkega zdravljenja. Zaradi vedno večjega števila onko-nefroloških bolnikov in novih možnosti protirakavega zdravljenja je pred desetimi leti na Onkološkem inštitutu Ljubljana začela delovati onko-nefrološka ambulanta, za zahtevnejše bolnike, ki potrebujejo dodatno multidisciplinarno obravnavo, pa deluje onko-nefrološki konzilij. Delovna skupina za onko-nefrologijo v okviru Sekcije za internistično onkologijo vsako leto pripravi onko-nefrološko šolo, kjer svoj pogled na isti klinični problem predstavijo različni strokovnjaki. Ena izmed prioritet onko-nefrologije so raziskave. V prispevku so opisane pomembnejše teme s področja onko-nefrologije skupaj z izzivi iz klinične prakse.
Keywords: onko-nefrologija, ocena ledvičnega delovanja, nefrotoksičnost
Published in DiRROS: 10.06.2021; Views: 1536; Downloads: 374
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