Kidney Damage Caused by Obesity and Its Feasible Treatment Drugs

The rapid growth of obesity worldwide has made it a major health problem, while the dramatic increase in the prevalence of obesity has had a significant impact on the magnitude of chronic kidney disease (CKD), especially in developing countries. A vast amount of researchers have reported a strong relationship between obesity and chronic kidney disease, and obesity can serve as an independent risk factor for kidney disease. The histological changes of kidneys in obesity-induced renal injury include glomerular or tubular hypertrophy, focal segmental glomerulosclerosis or bulbous sclerosis. Furthermore, inflammation, renal hemodynamic changes, insulin resistance and lipid metabolism disorders are all involved in the development and progression of obesity-induced nephropathy. However, there is no targeted treatment for obesity-related kidney disease. In this review, RAS inhibitors, SGLT2 inhibitors and melatonin would be presented to treat obesity-induced kidney injury. Furthermore, we concluded that melatonin can protect the kidney damage caused by obesity by inhibiting inflammation and oxidative stress, revealing its therapeutic potential.

Determinants of Kidney Function and Accuracy of Kidney Microcysts Detection in Patients Treated With Lithium Salts for Bipolar Disorder

Objectives: Early kidney damage during lithium treatment in bipolar disorder is still hypothetical. We aimed at identifying the determinants of a decreased measured glomerular filtration rate (mGFR) and the accuracy of kidney MRI imaging in its detection.Methods: In this cross-sectional cohort study, 217 consecutive lithium-treated patients underwent mGFR and kidney MRI with half-Fourier turbo spin-echo and Single-shot with long echo time sequences.Results: Median age was 51 [27–62] years, and median lithium treatment duration was 5 [2–14] years. 52% of patients had a stage 2 CKD. In multivariable analysis, the determinants of a lower mGFR were a longer lithium treatment duration (β −0.8 [−1; −0.6] ml/min/1.73 m2 GFR decrease for each year of treatment), a higher age (β −0.4 [−0.6; −0.3] ml/min/1.73 m2 for each year of age, p < 0.001), albuminuria (β −3.97 [−6.6; −1.3], p = 0.003), hypertension (β −6.85 [−12.6; −1.1], p = 0.02) and hypothyroidism (β −7.1 [−11.7; −2.5], p = 0.003). Serum lithium concentration was not associated with mGFR. Renal MRI displayed renal microcyst(s) in 51% of patients, detected as early as 1 year after lithium treatment initiation. mGFR and lithium treatment duration were strongly correlated in patients with microcyst(s) (r = −0.64, p < 0.001), but not in patients with no microcysts (r = −0.24, p = 0.09). The presence of microcysts was associated with the detection of an mGFR <45 ml/min/1.73 m2 (AUC 0.893, p < 0.001, sensitivity 80%, specificity 81% for a cut-off value of five microcysts).Conclusion: Lithium treatment duration and hypothyroidism strongly impacted mGFR independently of age, especially in patients with microcysts. MRI might help detect early lithium-induced kidney damage and inform preventive strategies.

The Effect of Broccoli Extract in Arsenic-Induced Experimental Poisoning on the Hematological, Biochemical, and Electrophoretic Parameters of the Liver and Kidney of Rats

Heavy metals such as arsenic contribute to environmental pollution that can lead to systemic effects in various body organs. Some medicinal plants such as broccoli have been shown to reduce the harmful effects of these heavy metals. The main aim of the present study is to evaluate the effects of broccoli extract on liver and kidney toxicity, considering hematological and biochemical changes. The experimental study was performed in 28 days on 32 male Wistar rats classified into four groups: the control group (C), a group receiving 5 mg/kg oral arsenic (AS), a group receiving 300 mg/kg broccoli (B), and a group receiving arsenic and broccoli combination (AS + B). Finally, blood samples were taken to evaluate the hematological and biochemical parameters of the liver and kidney, as well as serum proteins’ concentration. Liver and kidney tissue were fixed and stained by H&E and used for histopathological diagnosis. The results demonstrated a significant decrease in white blood cells (WBC), red blood cells (RBC), and hemoglobin (Hb) in the AS group compared to other groups. However, in the B group, a significant increase in RBC and WBC was observed compared to the AS and C groups ( P < 0.05). Moreover, RBC and WBC levels increased significantly in the AS + B group compared to the AS group ( P = 0.046). However, in the AS group, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine levels increased, while total protein, albumin, and globulin decreased. This can be a result of liver and kidney damage, which was observed in the AS group. Furthermore, the increase in the concentration of albumin and globulin in the AS + B group was higher than that in the AS group. Infiltration of inflammatory cells and necrosis of the liver and kidney tissue in the pathological evaluation of the AS group were significantly higher than other groups. There was an increase in superoxide dismutases (SOD), glutathione peroxidase (GPx), and total antioxidant capacity (TAC); however, a decrease in malondialdehyde (MDA) concentration was seen in the AS + B group compared to the AS group. It seems that broccoli is highly effective at reducing liver and kidney damage and improving the hematological and biochemical factors in arsenic poisoning conditions.

Associations of a healthy lifestyle score from childhood to adulthood with subclinical kidney damage in midlife: a population-based cohort study

Background The relationships of healthy lifestyle scores (HLS) of various kinds in adulthood with the risk of chronic kidney disease (CKD) have been reported, but little is known about the association of childhood lifestyle with later life CKD. This study examined the relationship of HLS from childhood to adulthood with subclinical kidney damage (SKD) in midlife, a surrogate measure for CKD. Methods Data were collected in an Australian population-based cohort study with 33 years follow-up. 750 participants with lifestyle information collected in childhood (ages 10–15 years) and midlife (ages 40–50 years), and measures of kidney function in midlife were included. The HLS was generated from the sum scores of five lifestyle factors (body mass index, smoking, alcohol consumption, physical activity, and diet). Each factor was scored as poor (0 point), intermediate (1 point), or ideal (2 points). Log-binomial regression was used to investigate the relationship of HLS in childhood and from childhood to adulthood with SKD defined as either 1) estimated glomerular filtration rate (eGFR) 30–60 mL/min/1.73m2 or 2) eGFR> 60 mL/min/1.73m2 with urine albumin-creatinine ratio ≥ 2.5 mg/mmol (males) or 3.5 mg/mmol (females), adjusting for socio-demographic factors and the duration of follow-up. Results The average HLS was 6.6 in childhood and 6.5 in midlife, and the prevalence of SKD was 4.9% (n = 36). Neither HLS in childhood nor HLS from childhood to adulthood were significantly associated with the risk of SKD in midlife. Conclusions A HLS from childhood to adulthood did not predict SKD in this middle-aged, population-based Australian cohort.

Rutin Protects from Destruction by Interrupting the Pathways Playing a Role in the Possible Damage Mechanism of Sodium Valproate in the Liver and Kidney Tissues of Rats

Background: The present study investigated the effects of rutin (RUT), which has various biological and pharmacological properties, on liver and kidney damage caused by histone deacetylase inhibitor valproic acid (VLP), which is used in the treatment of many psychiatric disorders.Methods and Results: In the study, 50 or 100 mg/kg RUT treatment was administered 30 minutes after 500 mg/kg VLP was given to rats for 14 days. Then, some pathways that may be involved in the damage mechanism of VLP in liver and kidney tissues were investigated using biochemical, RT-PCR and Western blotting techniques. The results show that the levels of MDA induced by VLP in liver and kidney tissues decreased after RUT treatment, and the levels of SOD, CAT, GPx and GSH suppressed by VLP increased after RUT administration. It was observed that ER stress induced by oxidative stress was alleviated by suppressing the expressions of ATF-6, PERK, IRE1 and GRP78 after RUT treatment. It was observed that the expressions of NF-kB, TNF-a, IL-6, JAK2 and STAT3 in the inflammatory pathway increased after VLP administration, while RUT treatment decreased the levels of these markers. It is also among the data obtained that the levels of markers that play a role in the regulation of apoptosis (Bax, Bcl-2, kaspaz-3, pERK, pJNK) or autophagy (Beclin-1, LC3A, LC3B) approach the control group after RUT treatment.Conclusions: Taken together, it was determined that RUT treatment protected against liver and kidney damage by attenuating VLP-induced oxidative stress, ER stress, inflammation, apoptosis and autophagy.

Resveratrol Butyrate Ester Protects Adenine-Treated Rats against Hypertension and Kidney Disease by Regulating the Gut–Kidney Axis

Despite recent advances in pharma-nutritional management, chronic kidney disease (CKD) remains an increasingly prevalent disorder. Resveratrol, a pleiotropic phytochemical, has been found to reduce the risk for several chronic diseases. Considering the low bioavailability of resveratrol, we recently synthesized resveratrol butyrate ester (RBE) via the esterification of resveratrol with butyrate. The aim of this study was to examine the effectiveness of RBE as regards protection from hypertension and kidney damage and explore the underlying mechanisms using a young rat adenine-induced CKD model. Three-week-old male Sprague Dawley rats received regular or 0.5% adenine chow for three weeks. Three groups of adenine-fed CKD rats (N = 8/group) received resveratrol (50 mg/L), or a low dose (25 mg/L) or high dose (50 mg/L) of RBE in drinking water from week 6 to week 12. As compared with the controls, adenine-treated rats had markedly increased creatinine levels and blood pressure, which was associated with renal hypertrophy and decreased creatinine clearance. Treatment with resveratrol or a low or high dose of RBE, similarly protected adenine-fed rats against hypertension and kidney damage. CKD-induced hypertension is associated with an altered gut microbiota profile, dysregulated renal short chain fatty acid (SCFA) receptor expression, activation of the aryl hydrocarbon receptor (AhR) signaling pathway, and reduced nitric oxide bioavailability. We found gut microbiota compositions were shaped differentially by resveratrol and RBE treatment in adenine-treated CKD rats. The beneficial effect of high-dose RBE was associated with reduced renal expression of SCFA G protein-coupled receptor 41 (GPR41) and olfactory receptor 78 (Olfr78), antagonizing the AhR signaling pathway, and increased abundance of beneficial bacteria such as genera Akkermansia, Blautia, and Enterococcus. Our study provided the first evidence documenting RBE as a novel phytochemical supplement targeting the gut–kidney axis to protect against adenine-induced kidney damage and hypertension.

Effect of aqueous extract of Irvengia gabonensis on acetaminophen induced Nephrototoxicity in rats

The use of medicinal plant to prevent and/or cure liver problems is a practice not peculiar to developing countries. This research work evaluated the nephrocurative ability of aqueous seed extract of Irvengia gabonensis on Acetaminophen Induced Nephrotoxicity. A total of thirty albino rats were grouped into six groups (GI – GVI) of five rats each. GI served as normal control, GII served as positive control, GIII, GIV and GV were administered with the extract at a dose of 50mg/Kg, 100mg/Kg and 150mg/Kg respectively while GVI rats were administered with standard drug (Vit E) at a dose of 10mg/Kg. Kidney damage was induced in groups (II-VI) using 800mg/Kg of acetaminophen administered orally, rats from group I and II were euthanized24 hours after acetaminophen administration to confirm inducement of kidney damage. Groups III, IV, V and VI were administered with the respective doses for two weeks. A significant decrease (p<0.05) in mean serum level of Urea, Potassium (K+), Chloride (Clˉ) and Creatinine with a significant increase (p<0.05) in the level of serum Sodium (Na+) and Bicarbonate (HCO3ˉ) was observed when compared with positive control. The nephrocurative effect of the plant could be due to its reported secondary metabolites contents.