The efficacy of interleukin-1 antagonist drugs in combination with colchicine in patients with FMF-AA with colchicine resistance after kidney transplantation: A study with histopathologic evidence.

BACKGROUND: The efficacy of anti-interleukin-1 (IL-1) drugs in kidney transplant patients with FMF-AA who developed colchicine resistance has not been clearly demonstrated. METHOD: Thirty nine kidney transplant recipients with FMF-AA were evaluated. Group 1 consisted of patients who were in remission after transplantation with colchine and Group 2 included those who developed colchicine resistance. RESULTS: The mean follow-up of the patients was 88.5 ± 61.9 months. Following the treatment with IL-1 antagonists; serum Amyloid A (SAA) averages (79.4 ± 35.3 mg/L) as well as the average number of hospitalizations per month due to FMF episodes (1.4 ± 0.5 times/month) decreased significantly (26.6 ± 25.9 mg/L and 0.1 ± 0.3 times/month) (p < .001). Rates of death with a functional graft were 30% and 0% in group 1 and 2 (p = .086). Biopsy-proven AA amyloidosis recurrence in the allograft was observed in 11 of 19 (58%) and seven of nine (78%) patients in group 1 and 2, respectively. Interestingly, glomerular amyloid deposition was not present in the vast majority of biopsies. De novo vasculer amyloid deposition was observed during treatment. CONCLUSION: IL-1 antagonist drug and colchicine combination almost completely prevented acute FMF attacks in kidney transplant patients with colchicine resistance. However, amyloid accumulation did not cease during IL-1 antagonist drug treatment.

Response to treatment in kidney transplant recipients with acute antibody-mediated rejection: A follow-up biopsy study
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BACKGROUND: The aim of this study is to evaluate the efficacy of a treatment protocol for the management of acute antibody-mediated rejection (AAMR) and mixed-type rejection (MTR), both histopathologically and clinically. MATERIALS AND METHODS: Of the 362 cases undergoing kidney transplantation from January 2010 to January 2018, patients with AAMR or MTR in the first 3 months after transplantation were included. All patients had follow-up biopsy (Bx) after treatment. RESULTS: 33 (9.1%) patients had diagnosis of AMR. Mean follow-up was 35 ± 20 months. 28.5% of patients had poor clinical progression at the last follow-up. Of the 25 patients with functional grafts, the mean serum creatinine was 1.6 ± 0.6 mg/dL for live and 2.1 ± 1.0 mg/dL for deceased transplant recipients. In diagnostic biopsies, there were 61% MTR. In follow-up Bx, after treatment, both C4d positivity and the severity of rejection had decreased while the mean chronic allograft damage index (CADI) score and transplant glomerulopathy showed an increase. CONCLUSION: With effective antibody mediated rejection (AMR) therapy, renal function parameters were significantly improved. Histologically, improvement in tubulointerstitial inflammation may be responsible for this process. However, progressive chronic changes, particularly in the glomeruli, are noteworthy.

3-Hydroxyhexanoate-based polycationic nanoparticle system for delivering reprogramming factors.

Aim: In this study, we aimed to develop a polycationic non-viral carrier for the delivery of the reprogramming factors to the L929 fibroblast cell.Methods: We have prepared (3-hydroxybutyrate-co-3-hydroxyhexanoate) PHBHHx-based nanoparticles with the solvent diffusion method. Cytotoxicity of PXNs was determined via MTT assay. Transfection efficiency was evaluated via screening GFP expression by fluorescence microscopy. The expression of reprogramming factors (Oct4, Klf4, and Sox2) was determined by RT-qPCR.Results: PXNs with 32.9 ± 0.41 mV zeta potential and 177.6 ± 0.80 nm size were used for transfection of L929 Fbroblast cells. The percentage of cell viability of PXN were between 91.8%(±2.9) and 42.1%(±1.3). The transfection efficiency was found as 71.6%(±3,5). According to RT-qPCR data, the rate of transfection factors was significantly increased after the 11th cycle compared to non-transfected cells. Based on these results, it can be concluded that newly developed PXN is thought to be an effective tool for reprogramming cells.

Efficacy of mTOR Inhibitors and Intravenous Immunoglobulin for Treatment of Polyoma BK Nephropathy in Kidney Transplant Recipients: A Biopsy-Proven Study.

OBJECTIVES: We investigated the efficacy of a predetermined protocol that consisted of immunosuppressive drug reduction/withdrawal and intravenous immunoglobulin administration for the treatment of polyoma BK virus nephropathy. MATERIALS AND METHODS: Patients with biopsy-proven polyoma BK virus nephropathy received a treatment regimen based on discontinuation of both calcineurin inhibitors and antiproliferative agents and switching to mTOR inhibitors accompanied by intravenous immunoglobulin administration. RESULTS: Our study included 508 patients, with polyoma BK viremia detected in 80 patients. The mean age was 45.3 ± 9.5 years (range, 18-71 y), 64% were male, and mean follow-up was 37 ± 21 months (6-94 mo). All 16 patients who developed polyoma BK virus nephropathy and 9 patients who had highgrade polyoma BK viremia without nephropathy received intravenous immunoglobulin treatment. Compared with patients with viremia, patients with polyoma BK virus nephropathy had significantly higher rates of graft loss due to rejection (18.8% vs 1.6%; P = .024) and all-cause graft loss (31.2% vs 6.3%; P = .014). Histopathologically, viral inclusion bodies disappeared and SV40 became negative after treatment in all 13 patients who underwent protocol biopsies. Unfortunately, histopathologically complete recovery without chronic tubular and interstitial tissue damage was achieved in only 4 patients after treatment. In addition, 3 patients lost their grafts due to acute antibody-mediated or mixed-type rejection (18.8%). CONCLUSIONS: In patients with polyoma BK virus nephropathy, clearance of viremia and SV40 should not be the sole outcomes to obtain. Aggressive reductions in maintenance immunosuppression and switching to double-drug therapy combined with high-dose intravenous immunoglobulin leads to high rates of graft loss/rejection and sequalae of chronic histological changes.

Kidney Transplantation From Infected Donors With Particular Emphasis on Multidrug-Resistant Organisms: A Single-Center Cohort Study.

OBJECTIVES: Prevention of sepsis-related organ dysfunction in septic donors is crucial. In this study, septic donors were followed-up based on donor Sequential Organ Failure Assessment criteria. MATERIALS AND METHODS: Between January 2014 and 2020 at our center, 29 primary kidney transplant recipients received organs from 20 septic donors. All donors received either pathogen-specific or broad-spectrum antibiotics at least 48 hours before procurement, and all recipients received similar treatment posttransplant for an average of 7 to 14 days. Donor eligibility was determined according to the sum of donor-Sequential Organ Failure Assessment scores obtained from 6 parameters: Pao2/Fio2 ratio; platelet count; serum bilirubin, creatinine, and lactate levels; and presence of hypotension. The cut-off value for bacteremic donor acceptance was below 12 points. RESULTS: Fever (≥38 °C) persisted in 5 donors in the last 24 hours before organ removal. However, in these 5 donors, the mean donor-Sequential Organ Failure Assessment score was 6.5 ± 1.1, mean arterial pressure was >70 mm Hg, and serum lactate levels were <2 mmol/L. Fifteen donors had systemic inflammatory response syndrome scores of ≤2 with corresponding donor-Sequential Organ Failure Assessment scores of 7.9 ± 1.2; none had systemic inflammatory response syndrome scores >3, which would have indicated severe organ failure. In 28 recipients (97%), no donor-related infections were observed in the perioperative first month and afterwards. CONCLUSIONS: Treatment of donors and recipients with a common protocol greatly reduced the risk of donor-induced infection transmission. In addition, we found the donor-Sequential Organ Failure Assessment criteria to be a helpful tool in predicting organ failure in infected donors.

Acute Allograft Pyelonephritis: Vague Symptoms, Indeterminate Laboratory Results, and the Necessity of Indication Biopsy.

OBJECTIVES: In this study, we examined the clinical and biochemical features of biopsy-proven acute pyelonephritis among 769 kidney transplant recipients. MATERIALS AND METHODS: This cohort study was performed between January 2003 and December 2019 at the University of Health Sciences (Izmir, Turkey). Acute pyelonephritis refers to urinary tract infection with acute graft dysfunction. All patients with suspected acute pyelonephritis underwent diagnostic biopsy and received antibiotic treatment for an average of 14 to 21 days. Patients with acute pyelonephritis (18/769, 2.3%) were categorized into groups of 9 patients each: group 1 developed acute pyelonephritis in the first 6 months, and group 2 developed acute pyelonephritis >6 months posttransplant. RESULTS: All patients in group 1 had acute graft dysfunction; only 2 (22%) were symptomatic. All patients recovered baseline graft function after treatment. Patients in group 2 had at least 2 laboratory findings that included leukocytosis, neutrophilia, and high C-reactive protein values. Six patients had urine culture positivity. Recurrent pyelonephritis occurred in 3 patients. Four patients had graft loss. Over the mean follow-up of 48.0 ± 28.4 months, 14 patients (78%) were alive with a functioning graft. CONCLUSIONS: Diagnostic biopsy is of great importance in patients with urinary tract infection accompanied by acute graft dysfunction in the first 6 months after transplant.

Genitourinary Cancers Following Kidney Transplant: Our 20 Years of Experience With Mechanistic Target of Rapamycin Inhibitors.

OBJECTIVES: We investigated patients with genitourinary cancer after kidney transplant and the effects of immunosuppression reduction and switching to mechanistic target of rapamycin inhibitors. MATERIALS AND METHODS: We retrospectively evaluated kidney transplant recipients seen at our center between January 2000 and January 2020. Patients with <1 year of follow-up were excluded. RESULTS: Of 827 patients, genitourinary cancer was detected in 11 (1.3%): prostate cancer in 5 patients (45%), renal cell carcinoma in native kidney in 3 (27%), renal cell carcinoma in allograft kidney in 2 (18%), and transitional cell carcinoma of the bladder in 1 (9%). All patients had surgery. Two patients had bone metastasis due to prostate cancer at diagnosis. Two patients had allograft nephrectomy due to de novo renal cell carcinoma. Mean follow-up and age were 97 ± 45 months (range, 26-189) and 50 ± 10.2 years (19% female). After cancer diagnosis, excluding the 2 patients with allograft nephrectomy, immunosuppression was changed in 8 patients (88.8%) (1 patient received the same treatment before and after cancer diagnosis). Six patients received double-drug and 3 received triple-drug protocols. Of 9 patients, 2 were already using mechanistic target of rapamycin inhibitors before cancer diagnosis and 7 were switched: 4 to double-based and 3 to triple-based regimens. Six were switched from tacrolimus. With new treatments, patients showed no progressive kidney failure or rejection (38 ± 40 mo average follow-up). At last follow-up, mean glomerular filtration rate was 62.8 ± 34 mL/min/1.72 m2, which was similar to rate at cancer diagnosis (58.9 ± 24 mL/ min/1.72 m2; P = .78). During follow-up, no patients developed local recurrence of primary tumor or new metastasis, and none showed adverse effects after switch to mechanistic target of rapamycin inhibitors. Three patients died of malignancy-unrelated reasons (ileus, urinary sepsis, heart failure). CONCLUSIONS: Mechanistic target of rapamycin inhibitor-based drugs can be an important maintenance immunosuppressive treatment option for kidney transplant recipients with genitourinary cancers.

A Cationic Stearamide-based Solid Lipid Nanoparticle for Delivering Yamanaka Factors: Evaluation of the Transfection Efficiency.

Induced pluripotent stem cells (IPSC) are preferred as an alternative source for regenerative medicine, disease modeling, and drug screening due to their unique properties. As seen from the previous studies in the literature, most of the vector systems to transfer reprogramming factors are viral-based and have some well-known limitations. This study aims to develop a non-viral vector system for the transfection of reprogramming factors. Cationic stearamide lipid nanoparticles (CSLN) were prepared via the solvent diffusion method. The obtained CSLNs were used for the delivery of plasmid DNA (pDNA) encoding Oct3/4, Sox2, Klf4, and GFP to fibroblast cell lines. The optimization studies, for zeta potential and particle size of the conjugate, was performed to achieve high cell viability. CSLN63 with 36.5±0.06 mV zeta potential and 173.6±13.91 nm size was used for the transfection of Fibroblast cells. The transfection efficiency was observed by following GFP expression and was found as 70 %±0.11. The expression of the Oct4, Sox2, Klf4 was determined by RT-qPCR; an increase was observed after the 12th cycle in Klf4 (Ct averages: 13,41), Sox2 (Ct averages; 12,4), Oct4 (Ct average; 13,77). The tendency of colonization was observed. The upregulation efficiency of Oct4 and SSEA-1 with CSLN and another non-viral vector designed for the transportation of Yamanaka factors developed in our lab previously were compared with flow cytometer analysis.

A study on bone tissue engineering: Injectable chitosan-g-stearic acid putty.

BACKGROUND: Bioengineering products can help bone tissue regeneration. OBJECTIVE: There is an ongoing research for more effective biomaterials in bone regeneration. Chitosan (Ch) grafted stearic acid (Ch-g-Sa) polymer was synthesized and its usability as a putty was evaluated in this study. METHODS: The chemical structure of Ch-g-Sa polymer was investigated using Proton nuclear magnetic resonance (H-NMR) and Fourier-transformed infrared spectroscopy-attenuated total reflectance (FTIR-ATR). Thermal properties of Ch-g-Sa polymer were determined by thermal gravimetric analysis (TGA). Putties containing nano-hydroxyapatite were prepared and in-vitro degradation properties and viscosity of the putties were determined. RESULTS: The cytotoxicity, oxidation effect and osteogenic potential of the putties were investigated on MC3T3 cells while the inflammatory effect of the putties was studied on THP-1 cells. For the determination of the osteogenic effect of the putties, ALP and RUNX2 gene expression of MC3T3 cells were studied. CONCLUSION: Ch-g-Sa/HA putties are promising biomaterials for bone tissue regeneration.