Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Effect of Long-Term Systolic Blood Pressure Trajectory on Kidney Damage in the Diabetic Population： A Prospective Study in a Community-Based Chinese Cohort

Background：Previous studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage.However,the relationship between the patterns of blood pressure （BP） trajectory and kidney damage in the diabetic population remains unclear.This prospective study investigated the effect of long-term systolic BP （SBP） trajectory on kidney damage in the diabetic population based on an 8-year follow-up community-based cohort.Methods：This study included 4556 diabetic participants among 101,510 participants.BP,estimated glomerular filtration rate （eGFR）,and urinary protein were measured every 2 years from 2006 to 2014.SBP trajectory was identified by the censored normal modeling.Five discrete SBP trajectories were identified according to SBP range and the changing pattern over time.Kidney damage was evaluated through eGFR and urinary protein value.A multivariate logistic regression model was used to analyze the influence of different SBP trajectory groups on kidney damage.Results：We identified five discrete SBP trajectories：low-stable group （n =864）,moderate-stable group （n =1980）,moderate increasing group （n =609）,elevated decreasing group,（n =679）,and elevated stable group （n =424）.The detection rate of kidney damage in the low-stable group （SBP：118-124 mmHg） was the lowest among the five groups.The detection rate of each kidney damage index was higher in the elevated stable group （SBP：159-172 mmHg） compared with the low-stable group.For details,the gap was 4.14 （11.6% vs.2.8%） in eGFR 〈60 ml.min-1.1.73 m 2 and 3.66 （17.2% vs.4.7%）,3.38 （25.0% vs.7.4%）,and 1.8 （10.6% vs.5.9%） times in positive urinary protein,eGFR 〈60 ml.min-1.1.73 m 2 and/or positive urinary protein,and eGFR decline ≥30%,respectively （P 〈 0.01）.Conclusion：An elevated stable SBP trajectory is an independent risk factor for kidney damage in the diabetic population.

A STUDY ON LIMITATION OF HIGH-ENERGY SHOCK WAVE-INDUCED RENAL DAMAGE BY SALVIA MILTIORRHIZAE INJECTION IN RABBIT MODEL

Objective To study the protective function of Salvia Miltiorrhizae on high-energy shockwaves (HESW) induced renal damage. Methods Thirty healthy New Zealand adult male white rabbits were randomly divided into Salvia Miltiorrhizae group and control group with 15 in each. Three days before extracorpeal shock wave lithotripsy (ESWL) the two groups were injected Salvia Miltiorrhizae and physiological saline respectively. Plasma endothelin-1 (ET-1), Superoxide dismutase (SOD) and malondialdehyde (MDA) were determined and renal morphology was observed. Results After ESWL, levels of ET-1 and MDA increased significantly, the activity of SOD decreased significantly compared with those before ESWL in control group (P< 0.05, respectively); the Salvia Miltiorrhizae treated group showed a much increase in ET-1 and MDA (P< 0.05, respectively), which kept no more than a week. And MDA in Salvia Miltiorrhizae group was not statistically significant as compared with the pre-shocking's (P> 0.05). After shocking, SOD, related to renal protection, in Salvia Miltiorrhizae group was significantly higher than that of controls (P< 0.05). Renal morphological injury was slight in Salvia Miltiorrhizae group. Conclusion Salvia Miltiorrhizae injection has protective function on renal toxicity induced by high-energy shock waves.

Combined Effects of Cd and Hg on Liver and Kidney Histology and Function in Wistar Rats

The present study was performed in order to discern the effects of combined exposure to cadmium and mercury on liver function and histopathological alterations in male adult Wistar rats. In the present investigation, cadmium (100 mg/l) and mercury (25 mg/l) were administered orally for 10 weeks separately or in combination. The rational for studying cadmium and mercury is that both of these metals are encountered frequently in the same contaminated areas. In liver, the activities of serum alanine aminotransferase (ALT) and aspartate amino tranferase (AST) increased significantly in the cadmium (Cd) and mercury (Hg) alone or in combination (Cd + Hg) compared to the control suggesting that both cadmium and mercury cause hepatotoxicity spatially when co-administrated. We noted an increase in serum lactate dehydrogenase (LDH) activity in Cd and combined Cd + Hg treated groups while it decreased in Hg treated group. There was no statistically significant change in the level of total bilirubilin. Serum urea concentration showed a significant increase in the Cd and Hg groups compared to the control group. However an increase in serum creatinine concentration was noted only in the combined treated rats showing that renal insufficiency is more serious in the co-exposed group. Light microscopic examination indicated severe histological changes in the two organs under Cd and mercury influence. Results of the present investigation clearly showed that mercury has profound effects of hepatic handling of cadmium (synergistic effect) as shown by histological and biochemical results. Moreover, we observed a antagonist effect between these two toxic metals on kidney markers such as urea.

F-Actin Distribution Changes Provoked by Acetaminophen in the Proximal Tubule in Kidney of Adult Male Rat

Acetaminophen is a drug used to treat many conditions as headache, muscle aches, arthritis, backache, toothache, and fever between others, but collateral effects of this drug are not well known yet. Here is tested its effect on proximal tubule epithelium. Acetaminophen (APAP) at doses of 200, 500, 1000 and 1500 mg/Kg i.p. caused cell damage and changes in F-actin distribution in the proximal tubule of male Wistar rats. After 48 hours of treatment, the proximal tubule epithelium showed tumefaction and necrosis. Dose of 200 mg/kg decreased the F-actin and was observed a structure in patches in the basal cytoplasm of epithelial cells of the proximal tubule. This effect was increased depending on the administered dose. Dose of 1000 mg/kg produced the highest histological damage and changes in the actin cytoskeleton. Results of this study suggested that nephrotoxic damage produced by high doses of APAP included breakdown of cytoskeleton in proximal tubule epithelium.

Potential role of microRNA-503 in Icariin-mediated prevention of high glucose-induced endoplasmic reticulum stress

BACKGROUND Dysregulated microRNA(miRNA)is crucial in the progression of diabetic nephropathy(DN).AIM To investigate the potential molecular mechanism of Icariin(ICA)in regulating endoplasmic reticulum(ER)stress-mediated apoptosis in high glucose(HG)-induced primary rat kidney cells(PRKs),with emphasis on the role of miR-503 and sirtuin 4(SIRT4)in this process.METHODS Single intraperitoneal injection of streptozotocin(65 mg/kg)in Sprague-Dawley rats induce DN in the in vivo hyperglycemic model.Glucose-treated PRKs were used as an in vitro HG model.An immunofluorescence assay identified isolated PRKs.Cell Counting Kit-8 and flow cytometry analyzed the effect of ICA treatment on cell viability and apoptosis,respectively.Real-time quantitative polymerase chain reaction and western blot analyzed the levels of ER stressrelated proteins.Dual luciferase analysis of miR-503 binding to downstream SIRT4 was performed.RESULTS ICA treatment alleviated the upregulated miR-503 expression in vivo(DN)and in vitro(HG).Mechanistically,ICA reduced HG-induced miR-503 overexpression,thereby counteracting its function in downregulating SIRT4 levels.ICA regulated the miR-503/SIRT4 axis and subsequent ER stress to alleviate HG-induced PRKs injury.CONCLUSION ICA reduced HG-mediated inhibition of cell viability,promotion of apoptosis,and ER stress in PRKs.These effects involved regulation of the miR-503/SIRT4 axis.These findings indicate the potential of ICA to treat DN,and implicate miR-503 as a viable target for therapeutic interventions in DN.

Tangled relationship between insulin resistance and microalbuminuria in children with obesity

Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver,type 2 diabetes,metabolic syndrome,and cardiovascular disease.From a pathogenic point of view,insulin resistance(IR)represents the key factor underlying the spectrum of these obesity consequences.As observed in adults,recent data supported the occurrence of microalbuminuria(MA)as marker of early kidney dysfunction and its potential link with cardiometabolic factors also in children with obesity.In fact,a well-documented pathophysiological hypothesis both in adults and children supported an intimate correlation with the major feature of obesity such as IR through the influence of insulin on renal hemodynamics.Based on the clinical and prognostic relevance of this relationship in daily practice(including an increased risk of chronic kidney disease development overtime),more scientific attention needs to be paid to the evaluation of early kidney damage in children with obesity.In this paper,we attempt to address three debated questions regarding the intriguing liaison between IR and MA in children with obesity:(1)What is the prevalence of pediatric MA?(2)What is the state of art of MA in children with obesity?and(3)Is there a link between IR and MA in children with obesity?

Toxicological and histopathological effects of Dennettia tripetala seed used as grain protectant,food,and medicine

The study revealed the safety of Dennettia tripetala seed on man and the environment.Adult male rats weighing 0.158-0.168 kg housed in standard cages with free access to food and water were used for the experiments.The median lethal dose(LD50)was estimated using revised up and down procedure.The LD50 for D.tripetala seed extract was 5785 mg/kg and this evoked paralysis in rats for 4 days coupled with discharge from the eyes and eventual death.The least weight gain by the animals administered 75%seed powder of D.tripetala(4338.75 mg/kg)was an index of high powder concentration,whereas the weight loss experienced by group V animals is strongly attributed to chemical assault by permethrin designated as a standard insecticide.The high values of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and urea in the groups administered 75%permethrin powder(4338.75 mg/kg)and 75%D.tripetala seed powder is an index of liver and kidney injury and dysfunction.The presence of normal serum levels of ALT,AST,alkaline phosphatase,and creatinine;normal liver and kidney structures;and normal weight gains in the animal groups fed basal diet(control)and basal diet plus 25%D.tripetala is a strong indication that 25%D.tripetala seed powder(1446.25 mg/kg)supplementation is not toxic to the liver and kidney and therefore supports normal organ functions.The LD50 recorded strongly indicates that D.tripetala has a moderately high safety margin.Supplementation of less than 50%(2892.5 mg/kg)is recommended in the safe use of the plant material as grain protectant,food,and medicine.The botanical insecticide,D.tripetala,is safer than the conventional synthetic insecticide,permethrin,on account of the latter showing evidence of kidney damage.

COVID-19 induced renal injury differs from that in other viral-infections

Background:Kidney injuries caused by several viral diseases have been reported worldwide among all age groups,races,and genders.Of particular importance is coronavirus disease 2019(COVID-19),and its prevalence in communities infecting all patient populations with symptoms ranging from asymptomatic to severe,including complications and mortality.Methods:Data were acquired from PubMed,Scopus,Google Scholar,Centers for Disease Prevention and Control(CDC),and Lexi-Comp using the following search terms:“COVID-19 and renal pathology,”“COVID-19 induced kidney disease,”“Viral infection induced kidney disease,”and“Viral infection induced renal damage.”Titles and abstracts were manually analyzed as per the exclusion and inclusion criteria of relevant articles;relevance of articles included studies on the pathology of a specific viral infection and the impact of the virus on the adult renal system.Results:The mechanisms for renal disease due to COVID-19 include direct renal tubular injury,cytokine storm,inflammation,thrombosis vs.acute tubular necrosis,thrombotic events,and direct renal injury.Although some mechanisms behind renal dysfunction among the studied viral infections are similar,the prevalence rates of kidney injury or damage differ.This might be described by recommended prophylactic and therapeutic approaches that can alter the viral infection characteristics and possibly the impact a particular organ system.Conclusion:The patient population at risk was old in age and had a high body mass index.The mechanisms associated with renal dysfunction are similar,including direct renal injury through angiotensin converting enzyme 2(ACE2)entry,inflammation,and thrombosis.The renal pathology of coronaviruses that differs from that of other prevalent viral infections is the activation of cytokine storm,which causes elevations of a greater number and different kinds of cytokines than other viral infections.