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Introduction: The burden of chronic kidney disease (CKD) is increasing in Kenya and is a significant cause of morbidity and mortality. While definitive treatment is renal transplantation, many patients require kidney replacement therapy with haemodialysis (HD) or peritoneal dialysis (PD). The predominant modality utilized in Kenya is currently HD. There is a need to explore why PD remains underutilized and whether patient factors may be contributory to barriers that limit the uptake of PD.Methods: This was a descriptive cross-sectional study where patients with advanced CKD were assessed by a multidisciplinary team for PD eligibility using a standardized tool. Contraindications and barriers to the modality were recorded as was the presence or absence of support for the provision of PD. Demographic and clinical data were recorded using a standardized questionnaire. The impact of support on PD eligibility was determined.Results: We found that 68.9% patients were eligible for PD. Surgery-related abdominal scarring was the most common contraindication. Barriers to PD were identified in 45.9% and physical barriers were more common than cognitive barriers. Presence of support was associated with a significant increase in PD eligibility (p< 0.001).Conclusion: The rate of eligibility for PD in this study was similar to that found in other populations. Surgical-related factors were the most commonly identified contraindication. Physical and cognitive barriers were commonly identified and may be overcome by the presence of support for PD.

The syntheses, crystal structures, and catalytic radical scavenging activity are reported for four new molecular clusters that have resulted from a bottom-up molecular approach to nanoscale CeO2. They are [Ce6O4(OH)4(dmb)12(H2O)4] (dmb–= 2,6-dimethoxybenzoate), [Ce16O17(OH)6(O2CPh)24(HO2CPh)4], [Ce19O18(OH)9(O2CPh)27(H2O)(py)3], and [Ce24O27(OH)9(O2CPh)30(py)4]. They represent a major expansion of our family of so-called “molecular nanoparticles” of this metal oxide to seven members, and their crystal structures confirm that their cores all possess the fluorite structure of bulk CeO2. In addition, they have allowed the identification of surface features such as the close location of multiple Ce3+ions and organic ligand binding modes not seen previously. The ability of all seven members to catalytically scavenge reactive oxygen species has been investigated using HO•radicals, an important test reaction in the ceria nanoparticle biomedical literature, and most have been found to exhibit excellent antioxidant activities compared to traditional ceria nanoparticles, with their activity correlating inversely with their surface Ce3+content.

CblC is a chaperone that catalyzes removal of the β-axial ligand of cobalamin (or B12), generating cob(II)alamin in an early step in the cofactor trafficking pathway. Cob(II)alamin is subsequently partitioned to support cellular needs for the synthesis of active cobalamin cofactor derivatives. In addition to the β-ligand transferase activity, the Caenorhabdiitis elegansCblC (ceCblC) and clinical R161G/Q variants of the human protein exhibit robust thiol oxidase activity, converting glutathione to glutathione disulfide while concomitantly reducing O2to H2O2. The chemical efficiency of the thiol oxidase side reaction during ceCblC-catalyzed dealkylation of alkylcobalamins is noteworthy in that it effectively scrubs ambient oxygen from the reaction mixture, leading to air stabilization of the highly reactive cob(I)alamin product. In this study, we report that the enhanced thiol oxidase activity of ceCblC requires the presence of KCl, which explains how the wasteful thiol oxidase activity is potentially curtailed inside cells where the chloride concentration is low. We have captured an unusual chlorocob(II)alamin intermediate that is formed in the presence of potassium chloride, a common component of the reaction buffer, and have characterized it by electron paramagnetic resonance, magnetic circular dichroism, and computational analyses. The ability to form a chlorocob(II)alamin intermediate could represent an evolutionary vestige in ceCblC, which is structurally related to bacterial B12-dependent reductive dehalogenases that have been proposed to form halogen cob(II)alamin intermediates in their catalytic cycle.

There is a huge gap between the number of patients worldwide requiring versus those actually receiving safe, sustainable, and equitable care for kidney failure. To address this, the International Society of Nephrology coordinated the development of a Strategic Plan for Integrated Care of Patients with Kidney Failure. Implementation of the plan will require engagement of the whole kidney community over the next 5–10 years.

The CblC and CblD chaperones are involved in early steps in the cobalamin trafficking pathway. Cobalamin derivatives entering the cytoplasm are converted by CblC to a common cob(II)alamin intermediate via glutathione-dependent alkyltransferase or reductive elimination activities. Cob(II)alamin is subsequently converted to one of two biologically active alkylcobalamins by downstream chaperones. The function of CblD has been elusive although it is known to form a complex with CblC under certain conditions. Here, we report that CblD provides a sulfur ligand to cob(II)alamin bound to CblC, forming an interprotein coordination complex that rapidly oxidizes to thiolato-cob(III)alamin. Cysteine scanning mutagenesis and EPR spectroscopy identified Cys-261 on CblD as the sulfur donor. The unusual interprotein Co–S bond was characterized by X-ray absorption spectroscopy and visualized in the crystal structure of the human CblD thiolato-cob(III)alamin complex. Our study provides insights into how cobalamin coordination chemistry could be utilized for cofactor translocation in the trafficking pathway.

The prevalence of chronic kidney disease and its risk factors is increasing worldwide, and the rapid rise in global need for end-stage kidney disease care is a major challenge for health systems, particularly in low- and middle-income countries. Countries are responding to the challenge of end-stage kidney disease in different ways, with variable provision of the components of a kidney care strategy, including effective prevention, detection, conservative care, kidney transplantation, and an appropriate mix of dialysis modalities. This collection of case studies is from 15 countries from around the world and offers valuable learning examples from a variety of contexts. The variability in approaches may be explained by country differences in burden of disease, available human or financial resources, income status, and cost structures. In addition, cultural considerations, political context, and competing interests from other stakeholders must be considered. Although the approaches taken have often varied substantially, a common theme is the potential benefits of multistakeholder engagement aimed at improving the availability and scope of integrated kidney care.

Substantial heterogeneity in practice patterns around the world has resulted in wide variations in the quality and type of dialysis care delivered. This is particularly so in countries without universal standards of care and governmental (or other organizational) oversight. Most high-income countries have developed such oversight based on documentation of adherence to standardized, evidence-based guidelines. Many low- and lower-middle-income countries have no or only limited organized oversight systems to ensure that care is safe and effective. The implementation and oversight of basic standards of care requires sufficient infrastructure and appropriate workforce and financial resources to support the basic levels of care and safety practices. It is important to understand how these standards then can be reasonably adapted and applied in low- and lower-middle-income countries.

Kidney transplant provides superior outcomes to dialysis as a treatment for end-stage kidney disease. Therefore, it is essential that kidney transplantation be part of an integrated treatment and management plan for chronic kidney disease (CKD). Developing an effective national program of transplantation is challenging because of the requirement for kidney donors and the need for a multidisciplinary team to provide expert care for both donors and recipients. This article outlines the steps necessary to establish a national kidney transplant program, starting with the requirement for effective legislation that provides the legal framework for transplantation whilst protecting organ donors, their families, recipients, and staff and is an essential requirement to combat organ trafficking. The next steps involve capacity building with the development of a multiskilled workforce, the credentialing of transplant centers, and the reporting of outcomes through national or regional registries. Although it is accepted that most transplant programs will begin with living related kidney donation, it is essential to aspire to and develop a deceased donor program. This requires engagement with multiple stakeholders, especially the patients, the general community, intensivists, and health departments. Development of transplant centers should be undertaken in concert with the development of a dialysis program. Both are essential components of integrated care for CKD and both should be viewed as part of the World Health Organization’s initiative for universal health coverage. Provisions to cover the costs of treatment for patients need to be developed taking into account the state of development of the overall health framework in each country.

A sophisticated intracellular trafficking pathway in humans is used to tailor vitamin B12into its active cofactor forms, and to deliver it to two known B12-dependent enzymes. Herein, we report an unexpected strategy for cellular retention of B12, an essential and reactive cofactor. If methylmalonyl-CoA mutase is unavailable to accept the coenzyme B12product of adenosyltransferase, the latter catalyzes homolytic scission of the cobalt–carbon bond in an unconventional reversal of the nucleophilic displacement reaction that was used to make it. The resulting homolysis product binds more tightly to adenosyltransferase than does coenzyme B12, facilitating cofactor retention. We have trapped, and characterized spectroscopically, an intermediate in which the cobalt–carbon bond is weakened prior to being broken. The physiological relevance of this sacrificial catalytic activity for cofactor retention is supported by the significantly lower coenzyme B12concentration in patients with dysfunctional methylmalonyl-CoA mutase but normal adenosyltransferase activity.

Mast cells (MC) are ubiquitous in the body and are critical for allergic diseases, but also in immunity and inflammation, as well as potential involvement in the pathophysiology of dysautonomias and neuroinflammatory disorders. MC are located perivascularly close to nerve endings and sites such as the carotid bodies, heart, hypothalamus, the pineal and the adrenal glands that would allow them to regulate, but also be affected by the autonomic nervous system (ANS). MC are stimulated not only by allergens, but also many other triggers including some from the ANS that can affect MC release of neurosensitizing, proinflammatory and vasoactive mediators. Hence MC may be able to regulate homeostatic functions that appear to be dysfunctional in many conditions, such as postural orthostatic hypertension syndrome (POTS), autism spectrum disorder (ASD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long-COVID syndrome. The evidence indicates that there is a possible association between these conditions and diseases associated with mast cell activation, There is no effective treatment for any form of these conditions other than minimizing symptoms. Given the many ways MC could be activated and the numerous mediators released, it would be important to develop ways to inhibit stimulation of MC and the release of ANS-relevant mediators.

The energetic and geometric features enabling redox chemistry across the copper cupredoxin fold contain key components of electron transfer chains (ETC), which have been extended here by templating the cross-β bilayer assembly of a synthetic nonapeptide, HHQALVFFA-NH2(K16A), with copper ions. Similar to ETC cupredoxin plastocyanin, these assemblies contain copper sites with blue-shifted (λmax573 nm) electronic transitions and strongly oxidizing reduction potentials. Electron spin echo envelope modulation and X-ray absorption spectroscopies define square planar Cu(II) sites containing a single His ligand. Restrained molecular dynamics of the cross-β peptide bilayer architecture support metal ion coordination stabilizing the leaflet interface and indicate that the relatively high reduction potential is not simply the result of distorted coordination geometry (entasis). Cyclic voltammetry (CV) supports a charge-hopping mechanism across multiple copper centers placed 10–12 Å apart within the assembled peptide leaflet interface. This metal-templated scaffold accordingly captures the electron shuttle and cupredoxin functionality in a peptide membrane-localized electron transport chain.

This contribution describes electron paramagnetic resonance (EPR) experiments on Mn(III) in oxalate decarboxylase of Bacillus subtilis, an interesting enzyme that catalyzes the redox-neutral dissociation of oxalate into formate and carbon dioxide. Chemical redox cycling provides strong evidence that both Mn centers can be oxidized, although the N-terminal Mn(II) appears to have the lower reduction potential and is most likely the carrier of the +3 oxidation state under moderate oxidative conditions, in agreement with the general view that it represents the active site. Significantly, Mn(III) was observed in untreated OxDC in succinate and acetate buffers, while it could not be directly observed in citrate buffer. Quantitative analysis showed that up to 16% of the EPR-visible Mn is in the +3 oxidation state at low pH in the presence of succinate buffer. The fine structure and hyperfine structure parameters of Mn(III) are affected by small carboxylate ligands that can enter the active site and have been recorded for formate, acetate, and succinate. The results from a previous report [Zhu, W., et al. (2016) Biochemistry55, 429–434] could therefore be reinterpreted as evidence of formate-bound Mn(III) after the enzyme is allowed to turn over oxalate. The pH dependence of the Mn(III) EPR signal compares very well with that of enzymatic activity, providing strong evidence that the catalytic reaction of oxalate decarboxylase is driven by Mn(III), which is generated in the presence of dioxygen.

Oxalate decarboxylase, a bicupin enzyme coordinating two essential manganese ions per subunit, catalyzes the decomposition of oxalate into carbon dioxide and formate in the presence of oxygen. Current efforts to elucidate its catalytic mechanism are focused on EPR studies of the Mn. We report on a new immobilization strategy linking the enzyme's N-terminal His6-tag to a Zn-loaded immobilized metal affinity resin. Activity is lowered somewhat due to the expected crowding effect. High-field EPR spectra of free and immobilized enzyme show that the resin affects the coordination environment of the active site Mn ions only minimally. The immobilized preparation was used to study the effect of varying pH on the same sample. Repeated freeze-thaw cycles lead to break down of the resin beads and some enzyme loss from the sample. However, the EPR signal increases due to higher packing efficiency on the sample column.

The electrophoretic mobility of low molecular mass oligoglycines is examined in this study using a “coarse‐grained” bead modeling methodology [Pei, H., Allison, S. A., J. Chromatogr. A2009, 1216, 1908–1916]. The advantage of focusing on these peptides is that their charge state is well known [Plasson, R., Cottet, H., Anal. Chem.2006, 78, 5394–5402] and extensive electrophoretic mobility data are also available in different buffers [Survay, M. A., Goodall, D. M., Wren, S. A. C., Rowe, R. C., J. Chromatogr. A1996, 741, 99–113] and over a broad range of temperatures [Plasson, R., Cottet, H., Anal Chem. 2005, 77, 6047–6054]. Except for assumptions about peptide secondary structure, the B model has no adjustable parameters. It is concluded that the oligoglycines adopt a random configuration at high temperature (50°C and higher), but more compact conformations at lower temperature. It is proposed that triglycine through pentaglycine adopt compact cyclic structures at low temperature (up to about 25°C) in aqueous solution. At 25°C, buffer interactions are also examined and may or may not influence peptide conformation depending on the buffer species. In a borate buffer at high pH, the mobility data are consistent with complex formation between the oligoglycine and borate anion.