Opportunistic infections saw a rise during the COVID-19 pandemic. We report rhinocerebral mucormycosis following COVID infection in six patients with kidney disease. Though there was a variable outcome with 50% mortality, it is prudent to assess the risk factors for development of life-threatening infection.

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are often complicated by high-turnover renal osteodystrophy (HTRO) and secondary hyperparathyroidism (SHPT), characterized by disturbances in mineral metabolism and skeletal abnormalities. Genetic variations within the vitamin D receptor (VDR) gene, known as VDR gene polymorphisms, have been implicated in modulating the susceptibility to HTRO and SHPT. This systematic review aims to evaluate the existing literature on the association between VDR gene polymorphisms and the development of these complications in ESRD and hemodialysis patients. A comprehensive literature search across multiple databases was conducted, and studies investigating VDR gene polymorphisms and HTRO or SHPT in ESRD or hemodialysis patients were included. The included studies examined various VDR gene polymorphisms, such as BsmI, ApaI, TaqI, and FokI, and their associations with clinical outcomes like parathyroid hormone (PTH) levels, bone mineral density, and the development of SHPT or HTRO. The findings suggest that certain VDR gene polymorphisms, notably the ApaI \"aa\" genotype, BsmI \"bb\" genotype, TaqI \"tt\" genotype, and FokI variant, may contribute to the pathogenesis of SHPT and HTRO by affecting PTH levels, bone turnover markers, and vitamin D sensitivity. However, the studies had relatively small sample sizes and were conducted in different populations, limiting generalizability. Further larger-scale studies, functional investigations, and exploration of gene-environment interactions are warranted to elucidate the underlying mechanisms and facilitate personalized treatment approaches for CKD and ESRD patients with mineral and bone disorders.

UNASSIGNED: We tested the feasibility of adding a potassium binder to enable increased renin angiotensin aldosterone system inhibition (RAASi) and reduce albuminuria in patients with chronic kidney disease (CKD). In a controlled trial design, a potassium binder was introduced exclusively in patients developing hyperkalemia after intensified RAASi, thereby mirroring clinical decision-making.
UNASSIGNED: We planned to include 140 patients aged 18 to 80 years with estimated glomerular filtration rate (eGFR) 25 to 60 ml/min per 1.73 m2, albuminuria, and a history of hyperkalemia to an open-label, randomized trial comparing treatment with or without patiromer alongside maximally tolerated RAASi. Patients were randomized only if developing a documented P-potassium >5.5 mmol/l during run-in with intensified RAASi (losartan/spironolactone). The primary end point was change in urine albumin-creatinine ratio (UACR).
UNASSIGNED: Screening among 800,000 individuals with available laboratory results yielded just 317 candidates meeting major selection criteria during 18⅔ months, with 75 ultimately included. Among them, only 23 developed P-potassium >5.5 mmol/l, qualifying for randomization. Consequently, only 20 participants completed the study, falling short of the planned 98, precluding a significant effect on the primary outcome. Inclusion and randomization challenges stemmed from a limited pool of eligible patients for intensified RAASi at risk of hyperkalemia, along with a lower than expected incidence of hyperkalemia during run-in.
UNASSIGNED: Despite extensive screening efforts, few eligible patients were identified, and fewer developed hyperkalemia during run-in. Hence, a trial design limited to CKD patients at high hyperkalemia risk and including a run-in phase appears unlikely to provide evidence for a potential renal benefit from additional use of potassium binders.

UNASSIGNED: The importance of albuminuria as opposed to proteinuria in predicting kidney outcomes in primary immunoglobulin A nephropathy (IgAN) is not well established.
UNASSIGNED: From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the German Chronic Kidney Disease (GCKD) cohort, a prospective observational cohort study (N = 5217). Adjudicated endpoints include a composite kidney endpoint (CKE) consisting of eGFR decline >40%, eGFR <15 ml/min/1.73 m2 and initiation of kidney replacement therapy; the individual components of the CKE; and combined major adverse cardiac events (MACE), including non-fatal myocardial infarction, non-fatal stroke and all-cause mortality. The associations between the incidence of CKE and baseline factors, including demographics, laboratory values and comorbidities were analysed using the Cox proportional hazards regression model.
UNASSIGNED: The mean age of IgAN patients at baseline was 51.6 years (± 13.6) and 67% were male. The patient-reported duration of disease at baseline was 5.9 ± 8.1 years. Baseline median urine albumin:creatinine ratio (UACR) was 0.4 g/g [interquartile range (IQR) 0.1-0.8] and mean eGFR was 52.5 ± 22.4 ml/min/1.73 m2. Over a follow-up of 6.5 years, 64 (15.2%) patients experienced a >40% eGFR decline, 3 (0.7%) reached eGFR <15 ml/min/1.73 m2, 53 (12.6%) initiated kidney replacement therapy and 28% of the patients experienced the CKE. Albuminuria, with reference to <0.1 g/g, was most associated with CKE. Hazard ratios (HRs) at UACRs of 0.1-0.6 g/g, 0.6-1.4 g/g, 1.4-2.2 g/g and >2.2 g/g were 2.03 [95% confidence interval (CI) 1.02-4.05], 3.8 (95% CI 1.92-7.5), 5.64 (95% CI 2.58-12.33) and 5.02 (95% CI 2.29-11-03), respectively. Regarding MACE, the presence of diabetes [HR 2.53 (95% CI 1.11-5.78)] was the most strongly associated factor, whereas UACR and eGFR did not show significant associations.
UNASSIGNED: In the GCKD IgAN subcohort, more than every fourth patient experienced a CKE event within 6.5 years. Our findings support the use of albuminuria as a surrogate to assess the risk of poor kidney outcomes.

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Renal fibrosis is the common outcome of practically all progressive forms of chronic kidney disease (CKD), a significant societal health concern. Glutamate dehydrogenase (GDH) 1 is one of key enzymes in glutamine metabolism to catalyze the reversible conversion of glutamate to α-ketoglutarate and ammonia. However, its function in renal fibrosis has not yet been proven. In this study, GDH1 expression was significantly downregulated in kidney tissues of both children with kidney disease and animal models of CKD. In vivo, the use of R162 (a GDH1 inhibitor) significantly improved renal fibrosis, as indicated by Sirius red and Masson trichrome staining. These findings are consistent with the impaired expression of fibrosis indicators in kidneys from both the unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (5/6 Nx) models. In vitro, silencing GDH1 or pretreatment with R162 inhibited the induction of fibrosis indicators in tissue kidney proximal tubular cells (TKPTS) treated with Transforming growth factor Beta 1 (TGF-β1), whereas activating GDH1 worsened TGF-β1\'s induction impact. Using RNA-sequence, luciferase reporter assays and Biacore analysis, we demonstrated that GDH1 interacts with Peroxisome proliferator-activated receptor gamma (PPARγ) and blocks its transcriptional activity, independent of the protein\'s expression. Additionally, R162 treatment boosted PPARγ transcriptional activity, and blocking of this signaling pathway reversed R162\'s protective effect. Finally, we discovered that R162 treatment or silencing GDH1 greatly lowered reactive oxygen species (ROS) and lipid accumulation. These findings concluded that suppressing GDH1 or R162 treatment could prevent renal fibrosis by augmenting PPARγ transcriptional activity to control lipid accumulation and redox balance.

Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events. Despite therapeutic advances, several challenges and unmet needs remain in the current management of anaemia of CKD. In particular, clinical practice does not include an assessment of QoL, which prompted a group of European nephrologists and representatives of patient advocacy groups to revisit the current approach. In this consensus document, the authors propose a move towards a more holistic, personalised and long-term approach, based on existing evidence. The focus of treatment should be on improving QoL without increasing the risk of adverse cardiovascular events, and tailoring management strategies to the needs of the individual. In addition, the authors discuss the suitability of a currently available anaemia of CKD-specific health-related QoL measure for inclusion in the routine clinical management of anaemia of CKD. The authors also outline the logistics and challenges of incorporating such a measure into electronic health records and how it may be used to improve QoL for people with anaemia of CKD.

BACKGROUND: Currently, kidney disease is an increasing major health problem worldwide. It is expected to be the 5th ranked cause of death by 2040. If it is early detected, further complication caused by kidney disease will be minimized. An assessment of impaired glomerular filtration rate (eGFR) has potential aids in early identification and treatment of kidney disease. However, in hospital practice instead of using eGFR, direct measurement of serum creatinine level is used for assessing renal function. Hence, this study is aimed to assess the magnitude and associated factors of impaired glomerular filtration rate among admitted patients in Wolkite University Specialized Teaching Hospital (WKUSTH).
OBJECTIVE: To assess the magnitude and associated factors of impaired glomerular filtration rate in WKUSTH, Ethiopia 2023.
METHODS: Institutional based cross-sectional study with secondary data was conducted. 338 participants were selected by a convenient sampling technique. Epidata 3.1 version for data entry and SPSS version 20 for data analysis was used. Bivariate analysis was used to screen candidate variables for multivariate analysis. In the multivariate analysis a P-value < 0.05 were considered statistically significant.
RESULTS: The study enrolled 338 patients admitted to WUSTH. Seventy (20.7%) (95% CI: 16.6-25.4%) of them had impaired eGFR according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and Modification of Diet in Renal Disease (MDRD-4). older age (AOR 3.38, 95% CI; 1.31, 8.71), hypertension (AOR 17.8, 95% CI; 7.75, 41.22), anemia (AOR 2.51, 95% CI; 1.11, 5.83) DM (AOR 11.2, 95% CI; 4.11, 30.73), and high BMI (AOR 7.56, 95% CI; 3.16, 18.08), were independently associated with impaired eGFR.
CONCLUSIONS: The magnitude of impaired eGFR was prevalent among adult patients admitted to WKUSTH medical ward with different medical conditions. Old age, Hypertension, Diabetes, high body mass index, and Anemia were significantly associated with impaired eGFR both in CKD-EPI and MDRD-4 equation. Estimation of GFR for all hospitalized adults with known CKD risk factors might help in early detection of CKD and prevent complications.

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a critical clinical issue. Although previous studies have suggested macrophages as a key player in promoting inflammation and fibrosis during this transition, the heterogeneity and dynamic characterization of macrophages are still poorly understood. Here, we used integrated single-cell RNA sequencing and spatial transcriptomic to characterize the spatiotemporal heterogeneity of macrophages in murine AKI-to-CKD model of unilateral ischemia-reperfusion injury. A marked increase in macrophage infiltration at day 1 was followed by a second peak at day 14 post AKI. Spatiotemporal profiling revealed that injured tubules and macrophages co-localized early after AKI, whereas in late chronic stages had spatial proximity to fibroblasts. Further pseudotime analysis revealed two distinct lineages of macrophages in this transition: renal resident macrophages differentiated into the pro-repair subsets, whereas infiltrating monocyte-derived macrophages contributed to chronic inflammation and fibrosis. A novel macrophage subset, extracellular matrix remodeling-associated macrophages (EAMs) originating from monocytes, linked to renal fibrogenesis and communicated with fibroblasts via insulin-like growth factors (IGF) signalling. In sum, our study identified the spatiotemporal dynamics of macrophage heterogeneity with a unique subset of EAMs in AKI-to-CKD transition, which could be a potential therapeutic target for preventing CKD development.

Studies in animal models suggest a linkage between inflammatory response to injury and subsequent nephron loss during acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Failure of normal repair during CKD transition correlates with de novo expression of vascular cell adhesion protein-1 (VCAM-1) by a subset of injured proximal tubule cells. This study identifies the role of VCAM-1 expression in promoting the failed repair state. Single-cell transcriptome analysis of patients with AKI and CKD, and whole kidney RNA and protein analyses of mouse models of CKD, confirmed a marked increase of VCAM-1 expression in the proximal tubules of injured kidneys. In immortalized mouse proximal tubular (MPT) cells and primary cultured renal cells (PCRCs), VCAM-1 expression was induced by proinflammatory cytokines including TNFα and IL-1β. Analyses of bulk RNA sequencing of TNFα-treated PCRCs or pseudo-bulk RNA sequencing of biopsies from the Kidney Precision Medicine Project (KPMP) datasets indicated activation of NF-κB and an enrichment of inflammatory response and cell adhesion pathways in VCAM-1-positive cells. Pharmacologic inhibition of NF-κB signaling or genetic deletion of myeloid differentiation factor 88 (Myd88) and TIR-domain-containing adapter-inducing interferon-β (Trif) suppressed TNFα- and IL-1β-induced VCAM-1 expression in vitro. TNFα stimulation or overexpression of VCAM-1 significantly increased splenocyte adhesion to the MPT monolayer in culture. These results demonstrate that persistence of proinflammatory cytokines after AKI can induce NF-κB-dependent VCAM-1 expression by proximal tubule cells, mediating increased immune cell adhesion to the tubule and thus promoting further tubule injury and greater risk of progression from AKI to CKD.