scholarly journals Endogenous Fructose Metabolism Could Explain the Warburg Effect and the Protection of SGLT2 Inhibitors in Chronic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Takahiko Nakagawa ◽  
Laura G. Sanchez-Lozada ◽  
Ana Andres-Hernando ◽  
Hideto Kojima ◽  
Masato Kasahara ◽  
...  

Chronic low-grade inflammation underlies the pathogenesis of non-communicable diseases, including chronic kidney diseases (CKD). Inflammation is a biologically active process accompanied with biochemical changes involving energy, amino acid, lipid and nucleotides. Recently, glycolysis has been observed to be increased in several inflammatory disorders, including several types of kidney disease. However, the factors initiating glycolysis remains unclear. Added sugars containing fructose are present in nearly 70 percent of processed foods and have been implicated in the etiology of many non-communicable diseases. In the kidney, fructose is transported into the proximal tubules via several transporters to mediate pathophysiological processes. Fructose can be generated in the kidney during glucose reabsorption (such as in diabetes) as well as from intra-renal hypoxia that occurs in CKD. Fructose metabolism also provides biosynthetic precursors for inflammation by switching the intracellular metabolic profile from mitochondrial oxidative phosphorylation to glycolysis despite the availability of oxygen, which is similar to the Warburg effect in cancer. Importantly, uric acid, a byproduct of fructose metabolism, likely plays a key role in favoring glycolysis by stimulating inflammation and suppressing aconitase in the tricarboxylic acid cycle. A consequent accumulation of glycolytic intermediates connects to the production of biosynthetic precursors, proteins, lipids, and nucleic acids, to meet the increased energy demand for the local inflammation. Here, we discuss the possibility of fructose and uric acid may mediate a metabolic switch toward glycolysis in CKD. We also suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors may slow the progression of CKD by reducing intrarenal glucose, and subsequently fructose levels.

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ernawati Ernawati ◽  
Rebekah Malik ◽  
Yoanita Widjaja

Increased life expectancy is an advantage but at the same time becomes a condition that can be a source of problems in the health sector, especially non-communicable diseases. Currently non-communicable diseases that are often found are cardiovascular diseases such as high blood pressure, coronary heart disease, metabolic disorders such as diabetes, dyslipidemia, muscle and joint diseases such as arthritis, gout, osteoarthritis, nutritional disorders: obesity or malnutrition. The prevalence of various non-communicable diseases from 2013-2016 strokes increased from 7% to 10.9%; and chronic kidney disease rose from 2% to 3.8%. Based on blood sugar tests, diabetes mellitus rose from 6.9% to 8.5%; and blood pressure measurement results, hypertension rose from 25.8% to 34.1%. The increase in the prevalence of non-communicable diseases is related to lifestyle, including smoking, consumption of alcoholic beverages, physical activity, and consumption of fruits and vegetables. Problems require comprehensive handling and reach as broad as possible. One form of expansion of service coverage is posbindu. Posbindu in Kelurahan Kembangan Selatan is one of the posbindu that aims to provide comprehensive services to the age group> 15 years to make efforts to prevent non-communicable diseases and prevent complications for participants who have experienced interference so that no further complications occur. Activities are carried out routinely every month on Saturdays in the form of weighing, height, blood pressure, blood sugar levels, cholesterol and gout for every visitor of Posbindu. In addition to health checks, counseling activities are also carried out both individuals and groups and health consultations for visitors posbindu both experiencing health problems or not. This activity was carried out for 1 year from August 2018 to July 2019 (June Eid holidays) with the number of Posbindu visitors between 28-45 people with an average visitor 38. The average cases of high blood pressure were 33.45% (12), high cholesterol 27.24% (10), high blood sugar 24.74 (9), and high uric acid 19.87 (8). The results obtained for 1 year showed that the control of blood pressure, blood sugar, cholesterol and uric acid was still fluctuating even though counseling and consultation had been given based on the results of the examination. The conclusion from this activity shows that blood pressure, blood sugar, cholesterol and gout are not only influenced by regularity of control and knowledge but also diet, activity and environment. The advantage of this postbindu activity is that the health condition of visitors is monitored and health information can be conveyed on an ongoing basis. Suggestions for the future harmonious cooperation between health workers, patients and families / closest people of the patient must always be maintained through this posbindu activityABSTRAK:Peningkatan usia harapan hidup merupakan suatu keuntungan tetapi sekaligus menjadi suatu kondisi yang dapat menjadi sumber permasalahan di bidang kesehatan terutama penyakit tidak menular. Saat ini penyakit tidak menular yang banyak dijumpai adalah penyakit kardiovaskular seperti darah tinggi, jantung koroner, penyakit kelainan metabolik seperti kencing manis, dislipidemia, penyakit otot dan persendian seperti radang sendi, gout, osteoartritis, gangguan gizi: obesitas atau gizi kurang. Prevalensi berbagai penyakit tidak menular dari tahun 2013-2016 stroke naik dari 7% menjadi 10,9%; dan penyakit ginjal kronik naik dari 2% menjadi 3,8%. Berdasarkan pemeriksaan gula darah, diabetes melitus naik dari 6,9% menjadi 8,5%; dan hasil pengukuran tekanan darah, hipertensi naik dari 25,8% menjadi 34,1%. Kenaikan prevalensi penyakit tidak menular ini berhubungan dengan pola hidup, antara lain merokok, konsumsi minuman beralkohol, aktivitas fisik, serta konsumsi buah dan sayur. Permasalahan membutuhkan penanganan yang bersifat menyeluruh dan menjangkau seluas mungkin. Salah satu bentuk perluasan jangkauan pelayanan adalah posbindu. Posbindu di Kelurahan Kembangan Selatan merupakan salah satu posbindu yang bertujuan memberikan pelayanan yang secara menyeluruh pada kelompok usia > 15 tahun untuk melakukan upaya pencegahan penyakit tidak menular dan mencegah komplikasi bagi peserta yang sudah mengalami gangguan agar tidak terjadi komplikasi lebih lanjut. Kegiatan dilakukan rutin setiap bulan pada hari Sabtu berupa penimbangan berat badan, tinggi badan, tekanan darah, kadar gula darah, kolesterol dan asam urat bagi setiap pengunjung posbindu. Selain pemeriksaan kesehatan, juga dilakukan kegiatan penyuluhan baik perorangan maupun kelompok dan konsultasi kesehatan bagi pengunjung posbindu baik yang mengalami gangguan kesehatan maupun tidak. Kegiatan ini dilakukan selama 1 tahun dari Agustus 2018 sampai Juli 2019 (Juni libur lebaran) dengan jumlah pengunjung posbindu antara 28-45 orang dengan rata-rata pengunjung 38. Rata-rata kasus tekanan darah tinggi 33,45% (12), kolesterol tinggi 27.24% (10), gula darah tinggi 24,74 (9), dan asam urat tinggi 19,87 (8). Hasil yang didapat selama 1 tahun ini menunjukkan bahwa pengendalian tekanan darah, gula darah, kolesterol dan asam urat masih naik turun walaupun sudah diberikan penyuluhan maupun konsultasi berdasarkan hasil pemeriksaan. Simpulan dari kegiatan ini menunjukkan bahwa tekanan darah, gula darah, kolesterol dan asam urat tidak hanya dipengaruhi oleh keteraturan kontrol dan pengetahuan tetapi juga pola makan, aktivitas dan lingkungan. Keuntungan dari kegiatan posbindu ini adalah termonitornya kondisi kesehatan pengunjung dan informasi kesehatan dapat tersampaikan secara berkelanjutan. Saran ke depannya kerjasama yang harmonis antara petugas kesehatan, pasien dan keluarga/orang terdekat pasien harus selalu dijaga lewat kegiatan posbindu ini


Kidney360 ◽  
2020 ◽  
Vol 1 (4) ◽  
pp. 292-299
Author(s):  
David J. Leehey

Diabetic kidney disease (DKD) is the most common cause of ESKD in the United States and worldwide. Current treatment for DKD includes strict glycemic control and normalization of BP with renin-angiotensin-aldosterone system (RAAS) blockade. Although RAAS blockers slow progression of disease, they do not generally prevent ESKD and none of the studies with these agents in DKD included patients who were nonproteinuric, which make up an increasingly large percentage of patients with diabetes now seen in clinical practice. Recent studies with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown beneficial renal effects, and the benefits of SGLT2 inhibitors likely extend to patients who are nonproteinuric. However, there remains a need to develop new therapies for DKD, particularly in those patients with advanced disease. A role of chronic low-grade inflammation in microvascular complications in patients with diabetes has now been widely accepted. Large clinical trials are being carried out with experimental agents such as bardoxolone and selonsertib that target inflammation and oxidative stress. The Food and Drug Administration–approved, nonspecific phosphodiesterase inhibitor pentoxifylline (PTX) has been shown to have anti-inflammatory effects in both animal and human studies by inhibiting the production of proinflammatory cytokines. Small randomized clinical trials and meta-analyses indicate that PTX may have therapeutic benefits in DKD, raising the possibility that a clinically available drug may be able to be repurposed to treat this disease. A large, multicenter, randomized clinical trial to determine whether this agent can decrease time to ESKD or death is currently being conducted, but results will not be available for several years. At this time, the combination of RAAS blockade plus SGLT2 inhibition is considered standard of care for DKD, but it may be reasonable for clinicians to consider addition of PTX in patients whose disease continues to progress despite optimization of current standard-of-care therapies.


2018 ◽  
Vol 38 (2) ◽  
pp. 111-120 ◽  
Author(s):  
Guanshi Zhang ◽  
Manjula Darshi ◽  
Kumar Sharma

2021 ◽  
pp. 1-8
Author(s):  
Tingjing Zhang ◽  
Yawen Wang ◽  
Yeqing Gu ◽  
Ge Meng ◽  
Qing Zhang ◽  
...  

Abstract Seaweeds have numerous biologically active ingredients, such as polysaccharides, polyphenols and carotenoids, that are beneficial to human health. Although these benefits might be related to the synthesis, secretion or reabsorption of uric acid, no studies have explored the relationship between seaweeds consumption and hyperuricaemia (HUA) in the general population. The aim of this study was to investigate whether seaweeds consumption is related to HUA in a large-scale adult population. A cross-sectional study was conducted with 32 365 adults (17 328 men and 15 037 women) in Tianjin, People’s Republic of China. Frequency of seaweeds consumption was assessed by a validated self-administered FFQ. HUA was defined as serum uric acid levels >420 μmol/L in men and >350 μmol/L in women. The association between seaweeds consumption and HUA was assessed by multiple logistic regression analysis. Restricted cubic spline functions were used for non-linearity tests. The prevalence of HUA in men and women was 21·17 % and 5·93 %, respectively. After adjustments for potential confounding factors, the OR (95 % CI) for HUA across seaweed consumption (g/1000 kcal per d) were 1·00 (reference) for level 1, 0·91 (95 % CI 0·81, 1·02) for level 2; 0·90 (95 % CI 0·81, 1·01) for level 3; 0·86 (95 % CI 0·78, 0·97) for level 4 in men and 0·90 (95 % CI 0·73, 1·10) for level 2; 0·82 (95 % CI 0·67, 1·00) for level 3; 0·84 (95 % CI 0·68, 1·03) for level 4 in women, respectively. A negative correlation between seaweeds consumption and HUA in males but not in females was observed. Further studies are needed to explore the causal relationship.


Author(s):  
Diah Lestari ◽  
Fatwa Imelda ◽  
Febrina Oktavinola Kaban

Non-communicable diseases are quite serious public health problems and require more comprehensive and multidisciplinary care. The high mortality rate caused by heart disease, stroke, gout and diabetes mellitus is caused by unhealthy eating patterns, unhealthy habits, lack of physical activity and stress. Indonesia is the 4th country with people with diabetes mellitus after China, India and the USA. Hypertension or high blood pressure is a cause of increased risk of stroke, heart and kidney. The number of Majelis Taklim assemblies and Pengajian can be used maximally by health workers to socialize health programs in improving community health status. Perwiritan An-Nur, Marindal Village 1 Kec. Patumbak Kab. Deli Serdang is thought to have a high risk of non-communicable diseases such as hypertension, stroke, gout and diabetes mellitus. Observation of the habits of the community has an unhealthy lifestyle. This community service carried out 2 activities namely promotion and prevention with 30 samples. Educational activities are education about hypertension, stroke, gout and diabetes mellitus as well as activities. Preventive activities include checking cholesterol, uric acid and blood sugar levels. From the results of the implementation of community service found the majority of respondents aged> 50 years as many as 22 people (27%), the majority of low levels of education 17 people (57%), the majority do not work 27 people (90%), the majority of Javanese 20 people (67% ), the majority of married women 28 people (93%) and the majority with a history of passive smoking as many as 20 people (67%), the majority of normal blood pressure as many as 21 people (70%), the majority of normal cholesterol levels as many as 27 people 27 (90%) , the majority of normal uric acid levels were 26 people (87%), the majority of normal blood sugar levels were 28 people (93%). To improve health status and reduce the incidence of non-communicable diseases by conducting counseling and health checks.


2020 ◽  
Author(s):  
Bing Han ◽  
Lu Wang ◽  
Meilin Wei ◽  
Cynthia Rajani ◽  
Runming Wei ◽  
...  

AbstractFructose metabolism is increasingly recognized as a preferred energy source for cancer cell proliferation. However, dietary fructose rarely enters the bloodstream. Therefore, it remains unclear how cancer cells acquire a sufficient amount of fructose to supplement their energy needs. Here we report that the cancer cells can convert glucose into fructose through intra- and extracellular polyol pathways. The fructose metabolism bypasses normal aerobic respiration’s self-control to supply excessive metabolites to glycolysis and causes the Warburg effect. Inhibition of fructose production drastically suppressed glycolysis and ATP production in cancers. Furthermore, we determined that a glucose transporter, SLC2A8/GLUT8, exports intracellular fructose to other cells in the tumor microenvironment. Taken together, our study identified overlooked fructose resources for cancer cells as an essential part of their metabolic reprogramming and caused the Warburg effect.Statement of SignificanceOur findings in this study suggest that the Warburg effect is actually achieved by means of fructose metabolism, instead of glucose metabolism alone. Fructose metabolism results in accelerated glycolysis and an increased amount of ATP and key intermediates for anabolic metabolism.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria Marques Vidas ◽  
Alba Maroto ◽  
Ignacio Sanz ◽  
Paula López ◽  
Jose' M Portoles

Abstract Background and Aims The use of sodium glucose co-transporter 2 inhibitors (SGLT2i) is consistently associated with decrease of serum uric acid levels due to increase uricosuria coupled to glucosuria by mechanisms that are still incompletely understood. In diabetic kidney disease these drugs had shown only modest effects on HbA1c control allegedly due insufficient glucosuric effect. However, renal patients also benefit from hypouricemic effect of SGLT2 inhibitors. The aim of this study was to evaluate glucosuria and uricosuria in DKD patients treated with SGLT2i Method We prospectively analyzed glucose and urate fractional excretions of patients that were to initiate treatment with an SGLT2i, using fractional excretion classical formulas. Patients on GLP1ar or any uricosuric agent including losartan were excluded. All participants gave written consent. Results 37 patients (75.7% male) diagnosed from DKD were included, median age 69.6 years IQR [65.6-73.4], median CKD-EPI eGFR 54,10 ml/min/1,72 m2 [ 41,12- 69,68 IQR] and UACR 137 [49-443] mg/g. SGLT2i used was 53.3% dapagliflozin, 24.4% empagliflozin or 22.2% canagliflozin and mean follow- up was 1.5 years.Serum uric acid levels didn’t show any significative difference along time in this group of patients (6.8 vs 6.3; p 0.4) and %HbA1C was only slightly decreased by month 12 (7.1 vs 6.7; p0.03). Urinary uric acid fractional excretion increased by month 3 and was stabilized till month 12 when this effect seemed to decrease (figure and table) Glucosuria exhibit a similar effect: Urinary glucose fractional excretion increased immediately after the addition of the drug and stabilized over time decreasing at the end of the observation period. Spearman rank correlation test indicated dependency glucosuria and uricosuria (Spearman´s rho 0,24, p 0,03). GFR estimated by CKD-EPI kept stable along the study indicating that loss of uricosuric and glucosuric effect are independent of GFR Conclusion We conclude that uric acid renal excretion is significantly increased in patients treated with SGLT2i even in the presence of DKD but tends to diminish over time, feature that was also observed on urinary glucose excretion and that showed no correlation with GFR. Over-expression of SGLT1 after SGLT2 inhibition has been described in animal models of DKD. Whether this extends to human tubule and explains these results need to be further investigated


Author(s):  
IK Ndu ◽  
SR Ohayi ◽  
BO Edelu

Abstract: Chronic kidney disease (CKD) is described as a complex and progressive condition that arises from both non-communicable diseases (NCD) and communicable diseases (CD). Approximately a tenth of adults are affected worldwide, but the global prevalence of paediatric CKD remains unknown. Unfortunately, advanced diagnostic techniques and interventions are not readily available in most developing countries. This review seeks to create more awareness about paediatric CKD in a developing country like Nigeria and the need to intensify efforts to make new technologies for its diagnosis available and more affordable.


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