Dyslipidemia in children with chronic kidney disease-findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study.

BACKGROUND: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. METHODS: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3-5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. RESULTS: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. CONCLUSIONS: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.

Is a non-cytotoxic and non-genotoxic novel bioinspired dipeptide structure synthesis possible for theragnostic applications?

The diagnosis and treatment of the diseases in a certain coordination is a subject that has been emphasized in recent years. Theragnostics approaches allow simultaneous diagnosis and treatment of chronic diseases such as cancer. An ideal theragnostic should be biocompatible and can be used safely in humans. Although several types of theragnostics have been developed, none of yet satisfied these criteria. Bioinspired materials with noble metal centers encapsulating therapeutic and imaging agents were shown to possess theragnostic activities. In this study, it was aimed to synthesize, characterize, and evaluate the cytotoxic and genotoxic effects of self-assembly of diphenylalanine (Phe-Phe) dipeptides presence of mercury (Hg2+) ions to be used for theragnostic. Cytotoxicity and genotoxicity studies were done in mouse fibroblast (NIH/3T3) cells by 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) and single cell gel electrophoresis (Comet) assays, respectively. It was found that cell viability decreased in a dose-dependent manner in 24-, 48-, and 72-h treatment. Also, Phe-Phe dipeptides did not cause any significant changes in DNA damage at the concentrations of 1, 2, and 5 mg/mL in 4- and 24-h exposures. In the 48-h exposure, Phe-Phe peptide exposure at concentrations of 2 and 5 mg/mL caused a significant increase in DNA damage and in the 72-h of exposure, a significant increase in DNA damage was observed at all studied concentrations. According to the results of the study, it can be said that Phe-Phe dipeptides presence of Hg2+ ions are biocompatible and can be used safely for theragnostic purposes.

Clinical features of pediatric renal glucosuria cases due to SLC5A2 gene variants.

BACKGROUND: Familial renal glycosuria (FRG) is a rare renal tubular disorder characterized by a variable loss of glucose in the urine despite normal blood glucose levels, which is seen in a condition in which other tubular functions are preserved. In this study, the molecular and clinical characteristics of pediatric FRG cases due to SLC5A2 gene variants were defined. METHODS: Demographic features, diagnostic tests, and molecular analyses of patients with a diagnosis of FRG cases due to SLC5A2 gene variants were retrospectively analyzed between 2016 and 2019. RESULTS: The data of 16 patients who were clinically and genetically diagnosed with FRG in a 4-year period were analyzed. Seven (44%) of the cases were female and 9 (56%) were male. The median age at diagnosis was 6 years old (2 months old to 17 years old). Neuromotor development was found to be appropriate for the age in each case. Systemic blood pressure was evaluated as normal. A homozygous pathogenic variant in the SLC5A2 gene was detected in 14 patients in the genetic examination. A heterozygous variant was detected in one patient. In the other patient, two different heterozygous pathological variants were found in the SLC5A2 gene. CONCLUSIONS: It was revealed that growth and development were normal in children with glucosuria due to variations in the SCL5A2 gene. Renal function tests and urinary amino acid excretion were also within normal values. In our case series, the most common genetic variation in the SCL5A2 gene was the A219T (c.655G>A) variant.

Cation-based approach to morphological diversity of diphenylalanine dipeptide structures.

Different approaches are taken in order to examine the spontaneous arrangement processes of dipeptide structures. One of these approaches is to examine the effects of common cations on dipeptide structures' self-assembly processes. In this study, the effects of Al3+, Cu2+, Pb2+, Hg2+, Mg2+, Zn2+, Cd2+, Fe2+ and Ni2+ cations on the self-assembly processes of diphenylalanine (FF) dipeptide molecules were investigated. A detailed examination was made of the self-assembly of FF dipeptides in the presence of Hg2+, and a spherical architecture structure was shown. The morphological diversity resulting from the effects of Hg2+ cations at different concentrations on FF dipeptides was explained using Scanning Electron Microscopy (SEM), X-ray Diffraction, (XRD), and Fourier Transform Infrared Spectroscopy (FTIR) techniques. It is thought that this work will contribute to the indexing of the effects of toxic species such as Hg2+ on dipeptides, which are the smallest peptide units obtained. We think that the examination of FF dipeptides in the structures of amyloid plaques, which are thought to affect neurological disorders such as Alzheimer's and Parkinson's, will prompt further studies.

Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children.

Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6-17 years with baseline estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m2. uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m2, and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m2, or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69-0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD.

Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease.

Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m2 and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression.

Fabrication of Plasmonic Nanorod-Embedded Dipeptide Microspheres via the Freeze-Quenching Method for Near-Infrared Laser-Triggered Drug-Delivery Applications.

Control of drug release by an external stimulus may provide remote controllability, low toxicity, and reduced side effects. In this context, varying physical external stimuli, including magnetic and electric fields, ultrasound, light, and pharmacological stimuli, have been employed to control the release rate of drug molecules in a diseased region. However, the design and development of alternative on-demand drug-delivery systems that permit control of the dosage of drug released via an external stimulus are still required. Here, we developed near-infrared laser-activatable microspheres based on Fmoc-diphenylalanine (Phe-Phe) dipeptides and plasmonic gold nanorods (AuNRs) via a simple freeze-quenching approach. These plasmonic nanoparticle-embedded microspheres were then employed as a smart drug-delivery platform for native, continuous, and pulsatile doxorubicin (DOX) release. Remarkable sustained, burst, and on-demand DOX release from the fabricated microspheres were achieved by manipulating the laser exposure time. Our results demonstrate that AuNR-embedded dipeptide microspheres have great potential for controlled drug-delivery systems.

Pentoxifylline Inhibits Epidural Fibrosis in Post-Laminectomy Rats.

BACKGROUND: The aim of this experimental study was to investigate the effectiveness of intramuscular pentoxifylline in the prevention of postoperative fibrosis. MATERIAL/METHODS: We divided 16 adult Wistar albino rats into 2 equal groups: treatment and control. Both groups underwent L1 vertebral total laminectomy to expose the dura. The intramuscular treatment group received pentoxifylline. Four weeks later, epidural fibrosis was studied in both groups using electron microscopy, light microscopy, histology, biochemistry, and macroscopy. RESULTS: The evaluation of epidural fibrosis in the 2 groups according to macroscopic (p<0.01) assessment and light microscopy revealed that epidural scar tissue formation was lower in the treatment group compared to the control group (p<0.001) and the number of fibroblasts was also decreased significantly in the pentoxifylline-treated group (p<0.05). More immature fibers were demonstrated in the treatment group by electron microscopy in comparison with the control group. In biochemical analysis, a statistically significant decrease was detected in hydroxyproline, which indicates fibrosis and myeloperoxidase activity, and shows an inflammatory response (P<0.001). CONCLUSIONS: Systemic pentoxifylline application prevents postoperative epidural fibrosis and adhesions with various mechanisms. Our study is the first to present evidence of experimental epidural fibrosis prevention with pentoxifylline.

Hemostasis vs. epidural fibrosis?: A comparative study on an experimental rat model of laminectomy.

AIM: The aim of this study was to evaluate the histopathological and biochemical impact and effectiveness of two hemostatic agents, Ankaferd blood stopper (ABS) and Microporous Polysaccharide Hemospheres (MPH), on epidural fibrosis in an experimental rat laminectomy model. MATERIAL AND METHODS: Twenty adult Wistar albino rats were divided into MPH-treated (n=6), ABS-treated (n=6) and control (n=8) groups. Laminectomy of the lumbar spine was performed in all animals and treatment groups were exposed to MPH and ABS while closure was applied in control group as per usual. Epidural fibrosis was evaluated in all groups macroscopically, histopathologically, biochemically and with electron microscopy four weeks later. RESULTS: Statistically, it was found that MPH-treated group had significantly less epidural fibrosis compared to ABS-treated and control groups. CONCLUSION: We compared two hemostatic agents for their propensity to cause adhesions in the present study. Our results show that MPH significantly reduces epidural scar formation and dural adhesion in a rat model of laminectomy while ABS increases postoperative fibrosis.

Morphological Versatility in the Self-Assembly of Val-Ala and Ala-Val Dipeptides.

Since the discovery of dipeptide self-assembly, diphenylalanine (Phe-Phe)-based dipeptides have been widely investigated in a variety of fields. Although various supramolecular Phe-Phe-based structures including tubes, vesicles, fibrils, sheets, necklaces, flakes, ribbons, and wires have been demonstrated by manipulating the external physical or chemical conditions applied, studies of the morphological diversity of dipeptides other than Phe-Phe are still required to understand both how these small molecules respond to external conditions such as the type of solvent and how the peptide sequence affects self-assembly and the corresponding molecular structures. In this work, we investigated the self-assembly of valine-alanine (Val-Ala) and alanine-valine (Ala-Val) dipeptides by varying the solvent medium. It was observed that Val-Ala dipeptide molecules may generate unique self-assembly-based morphologies in response to the solvent medium used. Interestingly, when Ala-Val dipeptides were utilized as a peptide source instead of Val-Ala, we observed distinct differences in the final dipeptide structures. We believe that such manipulation may not only provide us with a better understanding of the fundamentals of the dipeptide self-assembly process but also may enable us to generate novel peptide-based materials for various applications.

A single-center experience on percutaneously performed partial omentectomy in pediatric peritoneal dialysis patients.

OBJECTIVE: This study describes a single-center experience on percutaneously performed partial omentectomy procedure in pediatric peritoneal dialysis (PD) patients who showed early catheter dysfunction and required catheter replacement due to catheter flow obstruction. MATERIALS AND METHODS: We performed a retrospective review of clinical outcomes from pediatric PD patients who underwent percutaneous catheter replacement by pediatric nephrologists between November 1995 and December 2012. Partial omentectomy was performed in those patients in whom omental or adhesion trapping to the catheter tip was seen. RESULTS: During the study period, catheter dysfunction that eventually required percutaneous catheter replacement occurred in 32 (23.7%) children. Of these, 9 patients were performed partial omentectomy. Mean age at initiation of PD and time of omentectomy was 97.48 ± 46.06 and 98.53 ± 45.55 months, respectively. Catheter dysfunction appeared after a mean 1.20 ± 1.0 months. The causes of catheter dysfunction were omental wrapping and malposition. No peritonitis occurred before omentectomy. Mean total operation time was 60 ± 8.83 min. No complications were encountered during the procedure. After omentectomy, mean catheter survival period was 5.92 ± 6.88 months. A total of five peritonitis episodes occurred. Three patients were transferred to hemodialysis. Six patients were on PD treatment without any problem at the end of the first year of their follow-up. Two patients underwent kidney transplantation. Four patients were still on chronic PD treatment at the end of the study period. CONCLUSION: When performed by an experienced nephrologist, the performance of partial omentectomy by percutaneous route, when required, is an easy, safe and efficient therapeutic procedure in children on chronic PD treatment.

Can large language models provide accurate and quality information to parents regarding chronic kidney diseases?

RATIONALE: Artificial Intelligence (AI) large language models (LLM) are tools capable of generating human-like text responses to user queries across topics. The use of these language models in various medical contexts is currently being studied. However, the performance and content quality of these language models have not been evaluated in specific medical fields. AIMS AND OBJECTIVES: This study aimed to compare the performance of AI LLMs ChatGPT, Gemini and Copilot in providing information to parents about chronic kidney diseases (CKD) and compare the information accuracy and quality with that of a reference source. METHODS: In this study, 40 frequently asked questions about CKD were identified. The accuracy and quality of the answers were evaluated with reference to the Kidney Disease: Improving Global Outcomes guidelines. The accuracy of the responses generated by LLMs was assessed using F1, precision and recall scores. The quality of the responses was evaluated using a five-point global quality score (GQS). RESULTS: ChatGPT and Gemini achieved high F1 scores of 0.89 and 1, respectively, in the diagnosis and lifestyle categories, demonstrating significant success in generating accurate responses. Furthermore, ChatGPT and Gemini were successful in generating accurate responses with high precision values in the diagnosis and lifestyle categories. In terms of recall values, all LLMs exhibited strong performance in the diagnosis, treatment and lifestyle categories. Average GQ scores for the responses generated were 3.46 ± 0.55, 1.93 ± 0.63 and 2.02 ± 0.69 for Gemini, ChatGPT 3.5 and Copilot, respectively. In all categories, Gemini performed better than ChatGPT and Copilot. CONCLUSION: Although LLMs provide parents with high-accuracy information about CKD, their use is limited compared with that of a reference source. The limitations in the performance of LLMs can lead to misinformation and potential misinterpretations. Therefore, patients and parents should exercise caution when using these models.

ON/OFF based synergetic plasmonic photothermal drug release approach through core-satellite like mussel-inspired polydopamine nanoparticles.

One of the studies on new drug delivery and release systems that has increased in recent years is the study using plasmonic nanoparticles. In this study, polydopamine nanoparticles (PDOP NPs), which contribute to photothermal drug release by near infrared radiation (NIR), were decorated with gold nanoparticles (AuNPs) to utilize their plasmonic properties, and a core-satellite-like system was formed. With this approach, epirubicin (EPI)-loaded PDOP NPs were prepared by utilizing the plasmonic properties of AuNPs. Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) methods were used to evaluate the structural properties of these particles. The release behavior of the prepared structures in acidic (pH 5.0) and neutral (pH 7.4) environments based on the ON/OFF approach was also examined. The biocompatibility properties of the particles were evaluated on mouse fibroblast (L929) and anticancer activities on neuroblastoma (SH-SY5Y) cells. The effects of prepared EPI-loaded particles and laser-controlled drug release on ROS production, genotoxicity, and apoptosis were also investigated in SH-SY5Y cells. With the calculated combination index (CI) value, it was shown that the activity of EPI-loaded AuNP@PDOP NPs increased synergistically with the ON/OFF-based approach. The developed combination approach is considered to be remarkable and promising for further evaluation before clinical use.

Laser-triggered degelation control of gold nanoparticle embedded peptide organogels.

Further understanding of the interactions between nanoparticles (NPs) and biological molecules offers new possibilities in the applications of nanomedicine and nanodiagnostics. The properties of NPs, including size, shape, and surface functionality, play a decisive role in these interactions. Herein, we evaluated the influences of gold NPs (AuNPs) with different sizes (5-60 nm) and shapes (i.e., spherical, rod, and cage) on the self-assembly of diphenylalanine (Phe-Phe) dipeptides. We found that the size of AuNPs smaller than 10 nm did not affect the self-assembly process of Phe-Phe, while bigger AuNPs (>10 nm) caused the formation of starlike peptide morphologies connected to one center. In the case of shape differences, nanorod and nanocage morphologies acted differently than spherical ones and caused the formation of densely packed, networklike dipeptide morphologies. In addition to these experiments, by combining photothermal properties of AuNPs with a Phe-Phe-based organogel having a thermo-responsive property, we demonstrated that the degelation process of AuNPs embedded organogels may be controlled by laser illumination. Complete degelation was achieved in about 10 min. We believe that such control may open the door to new opportunities for a number of applications, such as controlled release of drugs and tissue engineering.

Alpha-lipoic acid reduces peridural fibrosis after laminectomy of lumbar vertebrae in rabbits.

BACKGROUND: Peridural fibrosis is an inevitable healing process causing failed back surgery syndrome after lumbar spinal operations. In this study, alpha-lipoic acid (ALA), reported to reduce fibrosis in liver, oral mucosa, and peritoneum, investigated as a potential candidate for prevention of peridural fibrosis. METHOD: Twelve adult New Zealand white male rabbits were divided into control (n = 5) and ALA groups (n = 7). Laminectomy of lumbar spine was performed and ALA was applied on the exposed dura mater topically in ALA group. RESULTS: According to histological peridural grading, the ALA group (median grade 1) showed significantly less peridural fibrosis than the control group (median grade 3, p = 0.005). CONCLUSIONS: ALA is a promising substance in the prevention of peridural fibrosis, especially in early preoperative and postoperative period.

Antioxidative, cytotoxic, and antibacterial properties of self-assembled glycine-histidine-based dipeptides with or without silver nanoparticles in bio-inspired film.

Recent years have seen much attention being given to self-assembly of dipeptide-based structures, especially to self-regulation of dipeptide structures with different amino acid sequences. In this study we investigated the effects of varying solvent environments on the self-assembly of glycine-histidine (Gly-His) dipeptide structures. First we determined the morphological properties of Gly-His films formed in different solvent environments with scanning electron microscopy and then structural properties with Fourier-transform infrared (FTIR) spectroscopy. In addition, we studied the effects of Gly-His films on silver nanoparticle (AgNP) formation and the antioxidant and cytotoxic properties of AgNPs obtained in this way. We also, assessed antibacterial activities of Gly-His films against Gram-negative Escherichia coli and Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus. Silver nanoparticle-decorated Gly-His films were not significantly cytotoxic at concentrations below 2 mg/mL but had antibacterial activity. We therefore believe that AgNP-decorated Gly-His films at concentrations below 2 mg/mL can be used safely against bacteria.

Evaluation of cytotoxic and genotoxic effects of paclitaxel-loaded PLGA nanoparticles in neuroblastoma cells.

Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy. Paclitaxel (taxol), a diterpenoid pseudoalkaloid isolated from the shells of Taxus brevifolia, is the first taxane derivative used in the clinic for cancer treatment. Poly (lactic-co-glycolic acid) (PLGA) is one of the most successfully used biodegradable polymers for drug delivery which has a minimum systemic toxicity. This study aimed to evaluate the cytotoxicity and genotoxicity of paclitaxel nanoencapsulated with PLGA. Cytotoxic effects were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and genotoxic effects were determined by single cell gel electrophoresis (Comet) method in human neuroblastoma cells (SH-SY5Y). According to our results, the viability of cells treated with concentrations higher than 10 nM of free paclitaxel and paclitaxel loaded PLGA nanoparticles for 48 and 72 h was found lower than 50%. Additionally, DNA damage increased with the increase of nanoparticle dose when the cells exposed to paclitaxel loaded PLGA nanoparticles for 24, 48 and 72 h. It can be concluded that PLGA nanoparticles can be considered as a biocompatible carrier system for drug delivery and might be promising agent against neuroblastoma.

Microalbuminuria and Serum Cystatin C in Prediction of Early-Renal Insufficiency in Children with Obesity.

OBJECTIVE: Serum cystatin-C (SCysC) and microalbuminuria are well-recognized early markers of renal damage. This study aims to assess whether these early markers are elevated in children with obesity and normal serum creatinine (SCr). METHODS: Pediatric patients diagnosed with obesity were included (n = 105, ages 4-18 y) in this study. The patients were divided into three groups as follows: solely obese, metabolic syndrome and type 2 diabetes. Serum cystatin-C, 24-h microalbuminuria, SCr and glomerular filtration rate (GFR) were evaluated in all patients. All patients were examined with history, physical examination, laboratory analysis and ultrasonography evaluation. RESULTS: The findings showed that renal function, GFR and SCr levels were normal in all patients. There was microalbuminuria in six patients and SCysC was elevated in eight patients. There were also both elevated SCysC and microalbuminuria in eight patients. Significant elevations of both microalbuminuria and SCysC were detected in cases with type 2 diabetes (p < 0.05). CONCLUSIONS: The findings suggest that SCysC may have a diagnostic value in early-renal insufficiency. Although there was not any statistically significant difference between groups in GFR, significant elevations for both microalbuminuria and SCysC in patients with type 2 diabetes were detected. This suggests that the risk factors of diabetes may have a direct relation with renal damage. Regarding renal function in type 2 diabetic and obese pediatric patients, microalbuminuria and SCysC may be screened to observe early-renal damage, even in cases with normal GFR and SCr levels.

The Number of Patients Diagnosed with Brain Death and Organ Donation Rates at the Baskent University Konya Hospital: 6-Year Experience.

OBJECTIVES: Kidney transplant started at Baskent University Konya Hospital in July 2016. In this study, we compared the causes of brain death and the organ donation rates in our center between 2013 and 2016 versus between 2016 and 2019. MATERIALS AND METHODS: Patient files and records were analyzed retrospectively. Age, biologic sex, cause of brain death, and organ donation rates of patients diagnosed with brain death were examined and compared. RESULTS: The number of patients who were diagnosed with brain death and became deceased donors at our center increased 4-fold during the period from 2016 to 2019 compared with that shown from 2013 to 2016. In addition, organ donation rates increased to 71.4%, which is much higher than the average in Turkey (24%-28%). Between 2013 and 2016, trauma was the leading cause of brain death (42.8%), whereas between 2016 and 2019 cerebral hemorrhages rose to first place with a rate of 89.3%. In 2018 and 2019, there were 199 and 62 brain deaths, respectively, reported in our organ donation coordination region with an approximate organ donation rate of 25%. In our center, 12 patients were diagnosed with brain death in 2018 and 8 of these patients (66.7%) became donors; 6 brain deaths were diagnosed in 2019, and 4 patients (66.7%) became donors. Since we started kidney transplant at our center in 2016, the number of patients diagnosed with brain death has increased significantly. CONCLUSIONS: Establishing a healthy communication with relatives of patients and having a dedicated organ transplant center are important reasons for our much higher organ donation rates compared with the general rate in Turkey. A healthy communication is the most effective way to establish trust with next-of-kin and the general public.

Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children.

The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3-0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD.