Asymptomatic hyperuricemia and chronic kidney disease: Narrative review of a treatment controversial.
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ABSTRACT:
SUBMITTER: Eleftheriadis T
PROVIDER: S-EPMC5512148 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
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Asymptomatic hyperuricemia and chronic kidney disease: Narrative review of a treatment controversial.
Eleftheriadis Theodoros T Golphinopoulos Spyridon S Pissas Georgios G Stefanidis Ioannis I
Journal of advanced research 20170505 5
Today there is plausible evidence both on experimental and epidemiological basis, that hyperuricemia represents a risk factor for the development and progression of chronic kidney disease (CKD). Nevertheless, the role of serum uric acid lowering treatment in CKD is still a matter of serious controversy. Review of randomised controlled trials, suggests that there may be an improvement of renal function with allopurinol treatment in CKD stage 3-5. However, these studies have included a relatively ...[more]
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Project description:Because the serum uric acid level increases as the glomerular filtration rate (GFR) decreases, hyperuricemia is associated with chronic kidney disease (CKD). Although hyperuricemia is a risk factor for CKD progression, the causal role of uric acid remains controversial in patients with CKD and asymptomatic hyperuricemia. This study included 588 patients with stage 3-4 CKD and asymptomatic hyperuricemia. Using propensity score matching, 165 pairs treated and untreated with pharmacologic urate-lowering therapy were matched. Kaplan-Meier curves were constructed to determine the effect of urate-lowering agents on kidney survival. The prognostic value for kidney survival was ascertained using Cox regression analysis. The GFR changes over time between the patients treated and untreated with urate-lowering agents were assessed using a linear mixed model analysis. The mean age of the matched patients was 63.2 ± 12.7 years, and 52 (15.8%) patients had diabetic nephropathy. The mean estimated GFR (eGFR) and serum uric acid level were 36.7 mL/min/1.73 m2 and 7.8 mg/dL, respectively. During a mean follow-up period of 41.9 months, 87 developed end-stage kidney disease (ESKD). The incidence rates of ESKD were comparable between the patients treated and untreated with urate-lowering agents. The Kaplan-Meier analysis indicated that kidney survival was also comparable between them. In the multivariate analysis, heart failure and low eGFR were the significant prognostic factors for kidney survival. However, pharmacologic urate-lowering therapy was not predictive of kidney survival. The overall GFR decline rate was also comparable between the groups (P = 0.13). The efficacy of pharmacologic urate-lowering therapy in delaying CKD progression remains controversial. Therefore, further randomized controlled trials are needed to confirm its efficacy in attenuating kidney function deterioration in patients with stage 3-4 CKD.
| S-EPMC6576756 | biostudies-literature
Project description:BackgroundThe roles of asymptomatic hyperuricemia or uric acid (UA) crystals in CKD progression are unknown. Hypotheses to explain links between UA deposition and progression of CKD include that (1) asymptomatic hyperuricemia does not promote CKD progression unless UA crystallizes in the kidney; (2) UA crystal granulomas may form due to pre-existing CKD; and (3) proinflammatory granuloma-related M1-like macrophages may drive UA crystal-induced CKD progression.MethodsMALDI-FTICR mass spectrometry, immunohistochemistry, 3D confocal microscopy, and flow cytometry were used to characterize a novel mouse model of hyperuricemia and chronic UA crystal nephropathy with granulomatous nephritis. Interventional studies probed the role of crystal-induced inflammation and macrophages in the pathology of progressive CKD.ResultsAsymptomatic hyperuricemia alone did not cause CKD or drive the progression of aristolochic acid I-induced CKD. Only hyperuricemia with UA crystalluria due to urinary acidification caused tubular obstruction, inflammation, and interstitial fibrosis. UA crystal granulomas surrounded by proinflammatory M1-like macrophages developed late in this process of chronic UA crystal nephropathy and contributed to the progression of pre-existing CKD. Suppressing M1-like macrophages with adenosine attenuated granulomatous nephritis and the progressive decline in GFR. In contrast, inhibiting the JAK/STAT inflammatory pathway with tofacitinib was not renoprotective.ConclusionsAsymptomatic hyperuricemia does not affect CKD progression unless UA crystallizes in the kidney. UA crystal granulomas develop late in chronic UA crystal nephropathy and contribute to CKD progression because UA crystals trigger M1-like macrophage-related interstitial inflammation and fibrosis. Targeting proinflammatory macrophages, but not JAK/STAT signaling, can attenuate granulomatous interstitial nephritis.
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Project description:Background:Hyperuricemia is associated with the development and progression of chronic kidney disease (CKD) as well as cardiovascular diseases. However, there is no consistent recommendation regarding the treatment of asymptomatic hyperuricemia (AHU) in CKD patients. Here, we surveyed Korean physicians' perceptions regarding the diagnosis and management of AHU in CKD patients. Methods:Questionnaires on the management of AHU in CKD patients were emailed to regular members registered with the Korean Society of Nephrology. Results:A total of 158 members answered the questionnaire. Among the respondents, 49.4%/41.1% were considered hyperuricemic in male CKD patients whereas 36.7%/20.9% were considered hyperuricemic in female CKD patients when defined by serum uric acid level over 7.0/8.0 mg/dL, respectively. A total of 80.4% reported treating AHU in CKD patients. The most important reasons to treat AHU in CKD patients were renal function preservation followed by cerebro-cardiac protection. Majority of respondents (59.5%) thought that uric acid-lowering agents (ULAs) were the most effective method for controlling serum uric acid levels. Approximately 80% chose febuxostat as the preferred medication. A total of 32.3% and 31.0%, respectively, initiated ULA treatment if the serum uric acid level was more than 8.0 or 9.0 mg/dL, respectively. In addition, 39.2% and 30.4% answered that target serum uric acid levels of less than 6.0 or 7.0 mg/dL, respectively, were appropriate. The two major hurdles to prescribing ULAs were concerns of adverse reactions and the existing lack of evidence (i.e., the absence of Korean guidelines). Conclusion:Most Korean physicians treat AHU in CKD patients to prevent CKD progression and cerebro-cardiovascular complications.
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Project description:The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has posed a huge threat to global health because of its rapid spread and various mutant variants. Critical illness occurs in the elderly and vulnerable individuals, such as those with chronic kidney disease. The severity of SARS-CoV-2 infection is associated with the severity of chronic kidney disease (CKD)and even kidney transplantation (KT) because of the chronic use of immunosuppressive agents. To develop adaptive immunity against SARS-CoV-2, vaccination against the spike protein is important. Current phase III trials of vaccines against SARS-CoV-2 have not focused on a specific group of individuals, such as patients with CKD or those undergoing dialysis or kidney transplantation. Chronic use of immunosuppressive agents might disturb the immune response to the SARS-CoV-2 spike protein. On the basis of limited evidence, the immune compromised status of CKD patients might decrease neutralizing antibody development after a single dose of a specific vaccine. Boosting dosage more than the protocol might increase the titer of the neutralizing antibody in CKD patients. Further evidence is needed to understand the factors disturbing the immunogenicity of the SARS-CoV-2 vaccine, and CKD patients should receive the recommended dose of the SARS-CoV-2 vaccine due to their relatively immune compromised status.
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Project description:Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate-lowering therapy to prevent or delay CKD is controversial. Alternatively activated macrophages in response to local microenvironment play diverse roles in kidney diseases. Here, we aim to investigate whether and how macrophage integrin αM (ITGAM) contributes to hyperuricemia-related CKD. In vivo, we explored dynamic characteristics of renal tissue in C57BL/6J mice with hyperuricemia-related CKD. By incorporating transcriptomics and phosphoproteomics data, we analyzed gene expression profile, hub genes and potential pathways. In vitro, we validated bioinformatic findings under different conditions with interventions corresponding to core nodes. We found that hyperuricemia-related CKD was characterized by elevated serum uric acid levels, impaired renal function, activation of macrophage alternative (M2) polarization, and kidney fibrosis. Integrated bioinformatic analyses revealed Itgam as the potential core gene and was associated with focal adhesion signaling. Notably, we confirmed the upregulated expression of macrophage ITGAM, activated pathway, and macrophage M2 polarization in injured kidneys. In vitro, through silencing Itgam, inhibiting p-FAK or p-AKT1 phosphorylation, and concurrent inhibiting of p-FAK while activating p-AKT1 all contributed to the modulation of macrophage M2 polarization. Our results indicated targeting macrophage ITGAM might be a promising therapeutic approach for preventing CKD.
2024-06-26 | GSE262687 | GEO
Project description:Purpose of review:Provision of education to inform decision making for renal replacement therapy (RRT) is a key component in the management of chronic kidney disease (CKD), yet patients report suboptimal satisfaction with the process of selecting a dialysis modality. Our purpose is to review the influencers of RRT decision making in the CKD population, which will better inform the process of shared decision making between clinicians and patients. Sources of information:PubMed and Google Scholar. Methods:A narrative review was performed using the main terms "chronic kidney disease," "CKD," "dialysis," "review," "decision-making," "decision aids," "education," and "barriers." Only articles in English were accessed. The existing literature was critically analyzed from a theoretical and contextual perspective and thematic analysis was performed. Key findings:Eight common themes were identified as influencers for decision making. "Patient-focused" themes including social influence, values and beliefs, comprehension, autonomy and sociodemographics, and "clinician-focused" themes including screening, communication, and engagement. Early predialysis education and decision aids can effectively improve decision making. Patient-valued outcomes need to be more fully integrated into clinical guidelines. Limitations:This is not a systematic review; therefore, no formal tool was utilized to evaluate the rigor and quality of studies included and findings may not be generalizable. Implications:Standardized comprehensive RRT education programs through multidisciplinary health teams can help optimize CKD patient education and shared decision making. Involving patients in the research process itself and implementing patient values and preferences into clinical guidelines can help to achieve a patient-centered model of care.
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| S-EPMC9290151 | biostudies-literature
Project description:BackgroundPyuria seems to be common in chronic kidney disease (CKD), irrespective of urinary tract infection (UTI). It has been hypothesized that sterile pyuria occurs in CKD because of chronic renal parenchymal inflammation. However, there are limited data on whether CKD increases the rate of pyuria or how pyuria in CKD should be interpreted. We investigated the prevalence and characteristics of asymptomatic pyuria (ASP) in CKD via urinary white blood cell (WBC) analysis.MethodsUrine examination was performed for all stable hemodialysis (HD) and non-dialysis CKD patients of the outpatient clinic (total N=298). Patients with infection symptoms or recent history of antibiotic use were excluded. Urine culture and WBC analysis were performed when urinalysis revealed pyuria.ResultsThe prevalence of ASP was 30.5% (24.1% in non-dialysis CKD and 51.4% in HD patients). Over 70% of the pyuria cases were sterile. The majority of urinary WBCs were neutrophils, even in sterile pyuria. However, the percentage of neutrophils was significantly lower in sterile pyuria. In multivariate logistic regression analysis, the degree of pyuria, percentage of neutrophils, and presence of urinary nitrites remained independently associated with sterile pyuria.ConclusionsThe prevalence of ASP was higher in CKD patients and increased according to CKD stage. Most ASP in CKD was sterile. Ascertaining the number and distribution of urinary WBCs may be helpful for interpreting ASP in CKD.
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