Brown Tumour in Chronic Kidney Disease: Revisiting an Old Disease with a New Perspective.

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation, may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions, placing them in the spectrum of RAS-MAPK-driven neoplasms, which were until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumours, such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumours includes clinical symptoms involving chronic bone pain and laboratory findings of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically, both lesions are characterized by clustered osteoclasts in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumours.

Selectively mixed matrix hemodialysis membrane for adequate clearance of p-cresol by the incorporation of imprinted zeolite.

The adequacy in uremic toxin removal upon hemodialysis treatment is essential in patients with kidney failure diseases as poor removal leads to heart failure, hypertension, and stroke. The combination of adsorption and diffusion processes has become very advantageous for hemodialysis membranes. By this mechanism, water-soluble uremic toxins (WSUTs) and protein-bounded uremic toxins (PBUTs) could be removed at one time. Therefore, this study aimed to develop a novel imprinted zeolite by p-cresol (IZC) and then incorporated it into polyethersulfone (PES) and poly(vinyl pyrrolidone) (PVP) to produce hollow fiber mixed matrix membrane (HF-MMM). The IZC proved to be sensitive in attracting the adsorbate, classifying it as having a strong adsorption behavior. Accordingly, IZC is very promising to be applied as an adsorbent in the hemodialysis treatment. In this study, IZC as p-cresol's adsorbent was incorporated into a PES-based polymeric membrane with a small addition of PVP to produce HF-MMM using a dry/wet spinning process. The effect of air gap distance between the spinneret and coagulant bath and percentage loading for PES, PVP, and IZC were studied and optimized to obtain the best performance of HF-MMM. The 40 cm of air gap distance, 16 wt% of PES, 2 wt% of PVP, and 1 wt% of IZC loading were able to produce a superior hemodialysis membrane. These optimized parameters showed sufficient uremic toxin removal, i.e., 60.74% of urea, 52.35% of p-cresol in the phosphate buffer saline solution, and 66.29% of p-cresol in bovine serum albumin solution for 4 h permeation using the dialysis system. These HF-MMMs also achieved pure water flux of 67.57 L m-2 h-1 bar-1 and bovine serum albumin rejection of 95.05%. Therefore, this membrane has proven to be able to clean up WSUT and PBUT through a one-step process. Moreover, as compared to the neat PES membrane, MMM was able to remove p-cresol at 186.22 times higher capability.

Osteoblastogenesis of adipose-derived mesenchymal stem cells in chronic kidney disease patient with regular hemodialysis.

Background: Chronic kidney disease (CKD) is a health problem associated with high morbidity and mortality. Mineral and bone disorders are complications of CKD with a risk of fractures and cardiovascular disease. Mesenchymal stem cells can differentiate into osteoblasts and regulate their regulation by a network of cytokines and transcription factors. Objective: Analyzing differences in osteoblastogenesis of adipose mesenchymal stem cells in CKD patients and healthy people. Methods: The study sample was adipose mesenchymal stem cells from CKD patient undergoing hemodialysis and healthy people. Osteoblastogenesis was assessed by measuring the concentrations of transforming growth factor-ß1 (TGF-ß1), bone morphogenetic protein-2 (BMP-2), and (DKK-1) in culture media. The Elisa method measured the concentration of these parameters on days 4, 7, 14, and 21. Data were analyzed using an independent t-test and post hoc test with p-value <0.05. Result: There was a significant difference in CKD patients with increasing TGF-ß1 on day 4 (t = 2.821; 95% CI = 30,498-199,727; p = 0.010) and decreased on day 14. In the BMP-2 parameter, there was an increase on day 7 (t = 4.291; 95% CI = 0.289-0.831; p <0.001). Similar conditions were also found in the DKK-1 parameter, increasing on the 7th day, but there was no significant difference (p = 0.583). Conclusion: Osteoblastogenesis in adipose mesenchymal stem cells in CKD patients differs from that in healthy individuals. Osteoblasts fail in maturation and cause failure in matrix mineralization.

Dialysis Membranes for Acute Kidney Injury.

Mortality and morbidity rates among critically ill septic patients having acute kidney injury (AKI) are very high, considering the total number of deaths after their admission. Inappropriate selection of the type of continuous renal replacement therapy and inadequate therapy become the immediate causes of these issues. Dialysis is a commonly used treatment intended to prolong the life of AKI patients. Dialysis membranes, which are the core of dialysis treatment, must be properly selected to ensure fair treatment to the patients. The accumulation of certain types of molecules must be dealt with using the right membrane. Whether it is low-flux, high-flux, or adsorptive type, the dialysis membrane should be chosen depending on the condition of the patients. The selection of dialysis membranes should also be based on their effect on the treatment outcomes and well-being. All these options are needed to serve the patients of different clinical settings. The use of dialysis membranes is not restricted to conventional haemodialysis, but rather they can be employed in haemoperfusion, haemofiltration, haemodiafiltration, or a combination of any two of them. This review focuses in-depth on different types of dialysis membranes, their characteristics, and approaches in addressing the issues encountered in patients having AKI with sepsis and/or multiorgan failure in intensive care units.

A rare case: Vesicoureteral reflux in Indonesian young adult with neurogenic bladder and chronic kidney disease stage 4.

BACKGROUND: Vesicoureteral reflux (VUR) is one of the main causes of chronic kidney disease (CKD) in adolescence and young adult. It can be a congenital or an acquired anomaly and its uncommon in adult life. CASE PRESENTATION: A 19th years old male with neurogenic bladder, VUR grade 4, CKD stage 4, malnutrition, and short stature. Radiological examinations show a spastic neurogenic bladder, cystitis, right VUR grade 4. Abdominal ultrasonography (USG) results were bilateral severe hydronephrosis due to post-renal causes. This patient had a history of myelocele excision at the age of 1.5 years. He had recurrent urinary tract infection with CKD stage 4. DISCUSSION: The diagnosis of VUR and neurogenic bladder in CKD stage 4 is a rare case in nephrology. CONCLUSION: Indonesian male confirms of diagnosis VUR grade 4, neurogenic bladder, and CKD stage 4.

Antimicrobial activities of fungus comb extracts isolated from Indomalayan termite (Macrotermes gilvus Hagen) mound.

Incorporating antimicrobial components into food packaging materials can prevent microbial contamination. Fungus combs could be an alternative source of natural antimicrobial agents. In this study, n-hexane, ethyl acetate, methanol, and water extracts were obtained from fungus combs isolated from Indomalayan termite (Macrotermes gilvus Hagen) mound. Their antibacterial and antifungal activities against food spoilage microorganisms including Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Aspergillus flavus, and Aspergillus niger were evaluated by Kirby-Bauer disc diffusion and microdilution. Results showed that ethyl acetate extract formed the largest diameter inhibition zone for all tested bacteria and fungi, exhibited antibacterial activity against all tested bacteria with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.39 and 0.78 mg/mL, respectively, and suppressed A. flavus and A. niger with an MIC value of 0.78 mg/mL. This extract contained guaiacol and syringol, which were predicted as the main antimicrobial components in fungus comb. n-Hexane extract only inhibited Gram-positive bacteria. S. aureus ATCC 25923 was the most sensitive to all the extracts, and A. flavus was more sensitive than A. niger. All these fungus comb extracts exhibited antimicrobial activity against E. coli ATCC 25922, P. aeruginosa ATCC 27853, S. aureus ATCC 25923, A. flavus, and A. niger. This study revealed that fungus comb extracts, especially ethyl acetate, could be considered as a new antimicrobial agent.

Severe COVID-19 infection in a kidney transplant recipient treated with lopinavir/ritonavir, hydroxychloroquine and dexamethasone.

Severe COVID-19 infection management for a recipient of kidney transplant has debatable prognosis and treatment. We described the case of a COVID-19 infected 70 year old female, previously had renal transplantation in 2017. The patient took immunosuppressive agents as routine drugs for transplant recipient status and received lopinavir/ritonavir, hydroxychloroquine, and dexamethasone daily at the hospitalization. Specific question arises about renal transplant recipients being infected by COVID-19 - whether the infection will get worse compared to those without immunosuppresive agent. In this case, author decided to stop the immunosuppressive agent followed administration of combination lopinavir/ritonavir, hydroxychloroquine, and dexamethasone that gives a good clinical impact change to patient's condition after once getting worsened and mechanically ventilated. Nevertheless, the assessment of risk and benefit in continuing immunosuppressive drugs is concurrently essential due to the prevention of transplant rejection.

Case Report: Asymptomatic COVID-19 patient with a subtle hypercoagulable state and fluctuating D-dimer level.

Background: COVID-19 can infect an asymptomatic person silently without any overt symptoms despite diffuse blood clots throughout the body. Clot formation is induced by COVID-19 associated coagulopathy that can cause a high mortality rate. D-dimer, a fairly decisive marker for the coagulopathy event, is physiologically a marker of the fibrinolysis process. The increase of D-dimers in COVID-19 cases must be followed up because it relates to the initiation of a cytokine storm. Case presentation: We report an asymptomatic patient with sudden D-dimer elevation who received anticoagulant therapy. After three days of heparin administration, D-dimer results became normal and anticoagulant therapy was stopped. However, on the 12th day, the D-dimer level rebounded back and was followed by an increase of hs-C-reactive protein, erythrocyte sedimentation rate, IL-6, although SARS-CoV-2 PCR result became negative. A hyperglycaemic reaction and a sudden increase of HbA1C was observed in the patient. After three weeks D-dimer had returned to normal levels, and so did the other markers. The patient recovered fully and still no symptoms were obvious. Conclusion: COVID-19 patients without symptoms may be at risk of an asymptomatic coagulopathy process. The decreasing level of D-dimer erroneously cannot ensure that the coagulopathy process stops.

Mesenchymal Stem Cell Senescence and Osteogenesis.

Mesenchymal stem cells (MSCs) are stem cells with the potential ability to differentiate into various cells and the ability to self-renew and resemble fibroblasts. These cells can adhere to plastic to facilitate the culture process. MSCs can be used in research into tissue biotechnology and rejuvenation medicine. MSCs are also beneficial in recipient tissue and differentiate as a breakthrough strategy through paracrine activity. Many databases have shown MSC-based treatment can be beneficial in the reduction of osteogenesis induced by senescence. In this article, we will discuss the potential effect of MSCs in senescence cells related to osteogenesis.

Petrology and geochemistry dataset of lava from the Ijen Crater and Mount Blau, Banyuwangi, East Java, Indonesia.

This article presents rock texture and mineralogy, as well as major and trace elements of lava from Ijen Crater and Mount Blau, Ijen Volcanic Complex (IVC), East Java, Indonesia related to article entitled "Rock Magnetic, Petrography, and Geochemistry Studies of Lava at the Ijen Volcanic Complex (IVC), Banyuwangi, East Java, Indonesia" [1]. Six lava samples were taken from three lava flows that are the product of the eruption of the Ijen Crater and three lava samples from a lava flow that is the product of the eruption of Mount Blau. The samples were crushed and used for measuring major and trace elements using XRF method. Meanwhile, the thin sections of all samples were used to analyze rock texture and mineralogy. These data are invaluable in identifying the lithology, tectonic setting, and magmatism process through the analysis of total silica alkaline and Harker diagram. Other researchers can analyze the other diagrams and graphs to know in more detailed information as intended. On the other hand, the data can be used as a comparison for other lava products from different eruption sources.

Preparation and characterization of imprinted zeolite-Y for p-cresol removal in haemodialysis.

In this work, the novel imprinted zeolite (IZ) was synthesized, and its properties and performance in terms of adsorption of p-Cresol, which represent the protein-bounded uremic toxins in aqueous phase under phosphate buffer saline, were studied and compared with the synthesized zeolite-Y (ZeoY-S) and commercial CBV 100 zeolite-Y (ZeoY-C). The ZeoY-S was synthesized from sodium aluminate, NaOH, H2O and SiO2 under aging for 24 h at room temperature and hydrothermal condition for 24 h at 100 °C, with an initial composition of 10SiO2:Al2O3:4Na2O:180H2O. The ZeoY-S has been modified by using the imprinting technology to produce the IZ via the use of p-Cresol as a template. The p-Cresol successfully imprinted on the zeolite-Y was proved through the multipoint Brunauer-Emmett-Teller (BET) and the performance of IZ that was compared to ZeoY-S and ZeoY-C. Based on the BET results, it proves that the pore size of IZ is in accordance with the target compound, which is p-Cresol at 0.79 nm. This modification was able to adsorb p-Cresol 2.5 and 3.5 times higher than ZeoY-S and ZeoY-C can, respectively. Langmuir and Freundlich adsorption isotherm models, together with the pseudo-first and -second order and intra-particle diffusion kinetics models, were used to investigate the adsorption behavior of p-Cresol on the zeolites. The IZ has 4.30 times greater competitive molecules than ZeoY-S and the properties of IZ were not influenced by the content of other phenolic group uremic toxins as competitive molecules. It can be concluded that the micropores of zeolite as adsorbent can be modified using the imprinting technology in order to increase its sensitivity and selectivity towards p-Cresol.

Comparison of Asymmetric Dimethylarginine Levels Between Stages Three, Four, and Five Non-dialysis of Chronic Kidney Disease.

AIM: to determine the differences of ADMA level between stages 3, 4, and 5 non-dialysis of chronic kidney disease (CKD) patients at Outpatient Nephrology Clinic, Dr. Soetomo Hospital. METHODS: a cross-sectional study was conducted on stage 3, 4, and 5 non-dialysis CKD patients at Outpatient Nephrology Clinic, Dr. Soetomo Hospital, Surabaya from January to February 2015. Stages of CKD were determined based on GFR estimation according to 4-variable MDRD formula. Statistical analysis of differences in the levels of ADMA in three subject groups use one-way ANOVA test. RESULTS: seventy-five patients were included in the study. Each group consisted of 25 patients stage 3, 4, and, 5 non-dialysis patients. Mean age of stage 3, stage 4, and stage 5 non-dialysis CKD patients were respectively 57.12 years, 54.80 years and 53.68 years. The mean levels of ADMA in stage 3, stage 4, and 5 were 0.62 (0.11) IU/mL, 0.72 (0.16) IU/mL, and 0.73 (0.18) IU/mL respectively. Analysis of the differences between the groups showed significant differences in ADMA levels (p=0.04), with the highest difference between stage 3 and stage 5. CONCLUSION: comparison of ADMA levels showed significant differences between CKD stages and the level tends to be higher along with increase severity of CKD stages.

Activity of Bacillus thuringiensis toxins against cocoa pod borer larvae.

Twelve Cry proteins from Bacillus thuringiensis Berliner were tested in bioassays on cacao plantations in Indonesia for activity against the larvae of cocoa pod borer (Conopomorpha cramerella (Snellen)), an insect pest of the cacao tree. Through the damage caused by their feeding, the larvae of cocoa pod borer cause the pods of the cocoa tree to ripen prematurely. They are difficult to control with conventional measures. Preliminary assays identified five toxins that were more active than others. In two subsequent bioassays the activity of selected toxins was determined more accurately. Three Cryl proteins with relatively little homology were all found to be toxic, opening perspectives for controlling cocoa pod borer by expression of Cry proteins in transgenic plants.

Regulation of pyrimidine metabolism in plants.

Pyrimidine nucleotides represent one of the most fundamental of cellular components. They are the building blocks for the direct synthesis of DNA and RNA that function in information storage and retrieval within the cell, but they also participate in the metabolism of a large number of other cellular components from sugar interconversion to cellular polysaccharides to glycoproteins and phospholipids. Thus, the metabolism of pyrimidine nucleotides and their intracellular pool sizes influence vast areas of normal cellular metabolism. The first pyrimidine, UMP, is synthesized by a de novo pathway that appears to be mechanistically invariant in all organisms. UMP is then further modified to form other pyrimidines. Breakdown of deoxyribo- and ribonucleic acids, the main sink for pyrimidine nucleotides, allows pyrimidines to be reutilized for resynthesis of these important cellular components. Pyrimidines are salvaged by converting the modified components into the free base, uracil for reutilization. Finally, pyrimidines are degraded into simple cellular metabolites permitting reutilization of nitrogen and carbon from pyrimidine ring systems into cellular metabolic pools. The regulation of pyrimidine metabolism is tightly controlled in plants. Additionally, plants produce toxic secondary metabolites derived from pyrimidines for use as defense compounds.

Osteodystrophy in Indonesian haemodialysis patients.

A preliminary study of the intact-parathyroid hormone (i-PTH) measurements from haemodialysis patients was conducted to determine the prevalence of renal bone diseases at the Dr Soetomo Hospital. The objective of this study is to evaluate the osteodystrophy renal pattern in haemodialysis patients using i-PTH and radiological parameters. The selected populations of 48 (32 males and 16 females), the mean age 48 +/- 10.3 years, was evaluated to conduct a cross-sectional study. The calorimetric method was applied to measure serum P and Ca, while a radioimmunoassay was used to assay the i-PTH level. Of those 48 patients receiving haemodialysis, with a duration ranging from 4 to 432 weeks, 61% had hypocalcaemia and 10% had hypercalcaemia. The i-PTH levels below 100 pg/mL (normal, 10-65 pg/mL) suggested 'aplastic' bone, and values of 100-200 pg/mL most commonly indicated 'normal' bone turnover. The i-PTH levels over 200 pg/mL suggested hyperparathyroidism. The results of this study demonstrated that 42% of those patients had <100 pg/mL (low turnover bone presumed, no biopsy), 23% had 100 - <200 pg/mL ('normal' bone turnover) and 35% of them had >200 pg/mL ('hyperparathyroidism'). In addition, the radiological study showed that 10% of those patients were positive for renal bone diseases. In conclusion, this study shows that the common type of renal osteodystrophy was of a low turnover type, which was different from the findings in other previous studies. It is postulated that this difference is likely to be caused by some factors such as the general health condition of the population those patients belong to and, in particular, the nutritional status of those patients.