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1.
Korean J Intern Med ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39135524

RESUMO

Background/Aims: Obesity has known to be a modifiable risk factor associated with worse outcomes in chronic kidney disease (CKD), but few studies have examined the impact of obesity on CKD incidence in the general population. The purpose of this study was to investigate the role of body mass index (BMI) and waist-to-hip ratio (WHR) as predictors of incident CKD and to evaluate the impact of weight reduction on CKD prevention. Methods: A total of 2,711 participants from a community-based cohort with normal renal function were prospectively analyzed. Among participants with obesity, we analyzed the change in WHR to evaluate the association of obesity reduction with CKD development. Results: During a mean follow-up of 11.03 ± 4.22 years, incident CKD occurred in 190 (7.0%) participants. In the fully adjusted multivariable Cox proportional hazard models, the risk of incident CKD increased with higher BMI (hazard ratio, 1.06; 95% confidence interval, 1.00-1.11; p = 0.033) and higher WHR (hazard ratio, 1.33; 95% confidence interval, 1.07-1.66; p = 0.009). In the Kaplan-Meier analysis, cumulative adverse renal events were significantly more common in the maintained obesity group than in the reduced obesity group (p = 0.001). Conclusions: Both higher BMI and WHR were associated with development of CKD, but the magnitude of the effect of WHR was higher than that of BMI. Moreover, reducing obesity would be beneficial for renal prognosis.

2.
Electrolyte Blood Press ; 22(1): 16-20, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38957546

RESUMO

Although renal infarction (RI) is not a rare disease, its outcomes have not been well-documented. Furthermore, transient resolution and recurrence of RI have not been captured through imaging. We report a case of idiopathic RI that recurred within a short period following transient resolution, as demonstrated by serial computed tomography (CT). A 53-year-old man diagnosed with RI was transferred to the emergency room. An abdominal CT scan at the local hospital revealed a segmental wedge-shaped perfusion defect in the left kidney and a focal thrombotic filling defect in the anterior segmental branch of the left renal artery. Since his left flank pain improved, another CT scan was performed again 6 hours after the initial CT scan. A repeat CT scan showed that the thrombus in the renal artery remained, but the perfusion defect had spontaneously resolved. We initiated anticoagulant therapy using unfractionated heparin. On the sixth day of hospitalization, the left flank pain recurred, prompting another CT scan. The follow-up CT scan confirmed that RI had recurred in the same area as before. We continued anticoagulant therapy and switched to warfarin. After treatment, his symptoms improved, and he was discharged. RI can recur at any time, even after it has spontaneously resolved, as evidenced by our case. Therefore, it is crucial to closely monitor patients who experience resolution of RI for any recurrence of symptoms, and repeat radiological evaluation should be performed even within a short period.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39034862

RESUMO

Background: Fabry disease (FD) is an X-linked lysosomal disorder caused by α-galactosidase A enzyme activity deficiency. Although glycosphingolipid analogs have been identified in the plasma or urine of patients with FD, there is a limited understanding of altered metabolomics profiles beyond the globotriaosylceramide accumulation in FD. Methods: Metabolomics study was performed for monitoring of biomarker and altered metabolism related with disease progression in serum and urine from male α-galactosidase A knockout mice and age-matched wild-type mice at 20 and 40 weeks. Profiling analysis for metabolites, including organic acids, amino acids, fatty acids, kynurenine pathway metabolites, and nucleosides in the serum and urine was performed using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry combined with star symbol patterns and partial least squares discriminant analysis (PLS-DA). Results: A total of 27 and 23 metabolites from the serum and urine of Fabry mice were distinguished from those of wild-type mice, respectively, based on p-value (<0.05) and variable importance in projection scores (>1.0) of PLS-DA. In the serum, metabolites of the glutathione, glutathione disulfide, citrulline, and kynurenine pathways that are related to oxidative stress, nitric oxide biosynthesis, and inflammation were increased, whereas those involved in pyruvate and tyrosine metabolism and the tricarboxylic acid cycle were altered in the 20- and 40-week-old urine of FD model mice. Conclusion: Altered metabolic signatures associated with disease progression by oxidative stress, inflammation, nitric oxide biosynthesis, and immune regulation in the early and late stages of FD.

4.
Sci Rep ; 14(1): 4136, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374135

RESUMO

While the relationship between circulating osteoprotegerin (OPG) and cardiovascular events is well-established in the general population, its association with cardiovascular risks in chronic kidney disease (CKD) patients remains less robust. This study hypothesized that elevated circulating OPG levels might be associated with an increased risk of major adverse cardiac events (MACE) in CKD patients, a total of 2,109 patients with CKD stages 1 through pre-dialysis 5 from the KNOW-CKD cohort were categorized into quartiles based on serum OPG levels. The primary outcome of the study was 3-point MACE, defined as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiac death. The median follow-up duration was 7.9 years. The cumulative incidence of 3-point MACE significantly varied across serum OPG levels in Kaplan-Meier curve analysis (P < 0.001, log-rank test), with the highest incidence observed in the 4th quartile. Cox regression analysis indicated that, relative to the 1st quartile, the risk of 3-point MACE was significantly higher in the 3rd (adjusted hazard ratio 2.901, 95% confidence interval 1.009 to 8.341) and the 4th quartiles (adjusted hazard ratio 4.347, 95% confidence interval 1.410 to 13.395). In conclusion, elevated circulating OPG levels are associated with adverse cardiovascular outcomes in pre-dialysis CKD patients.


Assuntos
Doenças Cardiovasculares , Infarto do Miocárdio , Insuficiência Renal Crônica , Humanos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular , Diálise , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/complicações , Osteoprotegerina/sangue , Osteoprotegerina/química , Insuficiência Renal Crônica/complicações , Fatores de Risco
5.
Clin Res Cardiol ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319325

RESUMO

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major cause of mortality in patients with chronic kidney disease (CKD), and diagnosis is challenging. Moreover, no specific biomarker for HFpEF has been validated in patients with CKD. The present study aimed to investigate the association between serum osteoprotegerin (OPG) levels and the risk of left ventricular diastolic dysfunction (LVDD), a surrogate of HFpEF, in patients with pre-dialysis CKD. METHODS: A total of 2039 patients with CKD at stage 1 to pre-dialysis 5 were categorized into quartiles (Q1 to Q4) by serum OPG levels, and were cross-sectionally analyzed. The study outcome was LVDD, which was operationally defined as the ratio of early transmitral blood flow velocity to early diastolic velocity of the mitral annulus (E/e') > 14. RESULTS: In the analysis of baseline characteristics, higher serum OPG levels were clearly related to the risk factors of HFpEF. A scatter plot analysis revealed a moderate correlation between serum OPG levels and E/e' (R = 0.351, P < 0.001). Logistic regression analysis demonstrated that the risk of LVDD in Q3 (adjusted odds ratio 2.576, 95% confidence interval 1.279 to 5.188) and Q4 (adjusted odds ratio 3.536, 95% confidence interval 1.657 to 7.544) was significantly higher than that in Q1. CONCLUSIONS: Elevated serum OPG levels are associated with the risk of LVDD in patients with pre-dialysis CKD. The measurement of serum OPG levels may help the diagnosis of LVDD, which is an important echocardiographic feature of HFpEF.

6.
Redox Biol ; 70: 103042, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38244399

RESUMO

Hypoxia is the key pathobiological trigger of tubular oxidative stress and cell death that drives the transition of acute kidney injury (AKI) to chronic kidney disease (CKD). The mitochondrial-rich proximal tubular epithelial cells (PTEC) are uniquely sensitive to hypoxia and thus, are pivotal in propagating the sustained tubular loss of AKI-to-CKD transition. Here, we examined the role of PTEC-derived small extracellular vesicles (sEV) in propagating the 'wave of tubular death'. Ex vivo patient-derived PTEC were cultured under normoxia (21 % O2) and hypoxia (1 % O2) on Transwell inserts for isolation and analysis of sEV secreted from apical versus basolateral PTEC surfaces. Increased numbers of sEV were secreted from the apical surface of hypoxic PTEC compared with normoxic PTEC. No differences in basolateral sEV numbers were observed between culture conditions. Biological pathway analysis of hypoxic-apical sEV cargo identified distinct miRNAs linked with cellular injury pathways. In functional assays, hypoxic-apical sEV selectively induced ferroptotic cell death (↓glutathione peroxidase-4, ↑lipid peroxidation) in autologous PTEC compared with normoxic-apical sEV. The addition of ferroptosis inhibitors, ferrostatin-1 and baicalein, attenuated PTEC ferroptosis. RNAse A pretreatment of hypoxic-apical sEV also abrogated PTEC ferroptosis, demonstrating a role for sEV RNA in ferroptotic 'wave of death' signalling. In line with these in vitro findings, in situ immunolabelling of diagnostic kidney biopsies from AKI patients with clinical progression to CKD (AKI-to-CKD transition) showed evidence of ferroptosis propagation (increased numbers of ACSL4+ PTEC), while urine-derived sEV (usEV) from these 'AKI-to-CKD transition' patients triggered PTEC ferroptosis (↑lipid peroxidation) in functional studies. Our data establish PTEC-derived apical sEV and their intravesicular RNA as mediators of tubular lipid peroxidation and ferroptosis in hypoxic kidney injury. This concept of how tubular pathology is propagated from the initiating insult into a 'wave of death' provides novel therapeutic check-points for targeting AKI-to-CKD transition.


Assuntos
Injúria Renal Aguda , Ferroptose , Insuficiência Renal Crônica , Humanos , Túbulos Renais Proximais , Rim/metabolismo , Células Epiteliais/metabolismo , Hipóxia/metabolismo , Injúria Renal Aguda/metabolismo , Insuficiência Renal Crônica/metabolismo , RNA
7.
Artigo em Inglês | MEDLINE | ID: mdl-38148129

RESUMO

Background: Insulin resistance is prevalent in chronic kidney disease and may accelerate the progression of chronic kidney disease. This study aimed to investigate whether insulin resistance is associated with the development of incident chronic kidney disease in a population with normal renal function. Methods: A total of 3,331 participants from a community-based cohort with normal renal function were prospectively analyzed. We determined the relationship of insulin resistance indices with the incident chronic kidney disease using the Cox proportional hazard model and Kaplan-Meier survival analysis. Results: During a mean follow-up of 11.03 ± 4.22 years, incident chronic kidney disease occurred in 414 participants (12.4%). The high homeostasis model assessment-insulin resistance level group had an increased risk of incident chronic kidney disease (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.13-1.74; p = 0.002) compared to the normal group after adjustment for age, sex, history of hypertension, body mass index, total cholesterol, alcohol drinking status, smoking status, and baseline estimated glomerular filtration rate. The risk of incident chronic kidney disease also increased with the lower quantitative insulin sensitivity check index level (HR, 0.62; 95% CI, 0.41-0.92; p = 0.02) and higher leptin-adiponectin ratio level (HR, 1.23; 95% CI, 1.06-1.42; p = 0.006). Conclusion: Higher insulin resistance indices are associated with the incidence of chronic kidney disease. Our data suggest that increased insulin resistance may be involved in the development of incident chronic kidney disease in a population with normal renal function.

8.
Electrolyte Blood Press ; 21(2): 66-71, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38152602

RESUMO

Hypermagnesemia is a rare but potentially fatal electrolyte disorder often overlooked because of its unfamiliarity. Magnesium is regulated through a balance of bone, intestinal absorption, and renal excretion. Hypermagnesemia typically arises from excessive magnesium intake or reduced renal excretion; however, it also occurs in patients with normal kidney function. Herein, we report two cases of hypermagnesemia in patients taking magnesium hydroxide for constipation. The first case involved an 82-year-old woman with end-stage renal disease who developed metabolic encephalopathy due to hypermagnesemia, after taking 3,000 mg of magnesium hydroxide daily for constipation. Her magnesium level was 9.9 mg/dL. Her treatment involved discontinuing magnesium hydroxide and continuing hemodialysis, which led to her recovery. In the second case, a 50-year-old woman with a history of cerebral hemorrhage and mental retardation developed hypermagnesemia despite having normal renal function. She was also taking magnesium hydroxide for constipation, and her magnesium level was 11.0 mg/dL. She experienced cardiac arrest while preparing for continuous renal replacement therapy (CRRT). After achieving return of spontaneous circulation, CRRT was initiated, and her magnesium level showed a decreasing trend. However, vital signs and lactate levels did not recover, leading to death. These cases highlight the importance of prompt diagnosis and intervention for hypermagnesemia and the need to regularly monitor magnesium levels in individuals receiving magnesium-containing preparations, especially those with impaired kidney function.

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