Evaluation of COX-2 Inhibitor Injurious Effects on Proximal Convoluted Tubular Diameter of Kidney with Favorable Impact of Lycopene in Albino Rats on the Basis of Microscopic Features

Objective: To analyze the harmful effect of COX-2 inhibitor on proximal convoluted tubular diameter of kidney, amendment by lycopene. Research Design: Experimental Research. Abode of Research: Animal House, JPMC, Karachi. Materials and Methods: 90-120 days old, forty healthy adult male Albino rats of 200-220gm weight were taken for this study and distributed into 4 cliques, set 1was chosen as control, in Set 2 Celecoxib was given 0.05g/1000g by gavage, in set 3 Celecoxib was given0.05g/1000g by gavage with lycopene 0.05g/1000g by gavage and set4 lycopene was given0.05g/1000g by gavage for 30 days. At accomplishment of study, animals were sacrifice and tissues were preserved for staining. Results: Inset 2 proximal convoluted tubular diameter became distended due to apoptosis of lining epithelial cells. They turn into low cuboidal from simple cuboidal cells along with ill-defined brush border at the luminal surface due to scarce microvilli and had disrupted basement membrane, however renal structure were amended in set3 which were given celecoxib with lycopene. Conclusion: This study reveals that lycopene amended the apoptotic changes of set2.

Correlation and Diagnostic Value of Serum RBP4 and sRAGE and the Condition of Patients with Chronic Kidney Disease

Chronic kidney disease (CKD) is a progressive damage of renal structure and function caused by various reasons. Its course is long and irreversible. CKD can be divided into 5 stages according to the glomerular filtration rate (GFR). Early detection and early intervention of CKD can reduce the complications of patients and improve the survival rate. Retinol-binding protein 4 (RBP4) is a small molecule transporter. Receptor for advanced glycation end products (RAGE) is a multi-ligand transmembrane signal transduction receptor discovered in recent years. Soluble RAGE (sRAGE) is a new splicing heterogeneity of RAGE. Our results show that serum RBP4 is increased while sRAGE is decreased in CKD patients, both of which are closely related to the severity of CKD. The combined use of serum RBP4 and sRAGE has a high diagnostic value for CKD and can provide a reliable diagnostic basis for the clinic.

The mutual repression between Pax2 and Snail factors regulates the epithelial/mesenchymal state during intermediate mesoderm differentiation

The pronephros is the first renal structure in the embryo, arising after mesenchymal to epithelial transition (MET) of the intermediate mesoderm, where Pax2 induces epithelialization of the mesenchyme. Here we show that, in the early embryo, Snail1 directly represses Pax2 transcription maintaining the intermediate mesoderm in an undifferentiated state. Reciprocally, Pax2 directly represses Snail1 expression to induce MET upon receiving differentiation signals. We also show that BMP7 acts as one such signal by downregulating Snail1 and upregulating Pax2 expression. This, together with the Snail1/Pax2 reciprocal repression, establish a regulatory loop in a defined region along the anteroposterior axis, the bi-stability domain within the transition zone, where differentiation of the neural tube and the somites is known to occur. Thus, we show that the antagonism between Snail1 and Pax2 determines the epithelial/mesenchymal state during the differentiation of the intermediate mesoderm and propose that the bi-stability zone extends to the intermediate mesoderm, synchronizing the differentiation of tissues aligned along the mediolateral embryonic axis.

The Goto Kakizaki rat: Impact of age upon changes in cardiac and renal structure, function

Background Patients with diabetes are at a high risk for developing cardiac dysfunction in the absence of coronary artery disease or hypertension, a condition known as diabetic cardiomyopathy. Contributing to heart failure is the presence of diabetic kidney disease. The Goto-Kakizaki (GK) rat is a non-obese, non-hypertensive model of type 2 diabetes that, like humans, shares a susceptibility locus on chromosome 10. Herein, we perform a detailed analysis of cardio-renal remodeling and response to renin angiotensin system blockade in GK rats to ascertain the validity of this model for further insights into disease pathogenesis. Methods Study 1: Male GK rats along with age matched Wistar control animals underwent longitudinal assessment of cardiac and renal function for 32 weeks (total age 48 weeks). Animals underwent regular echocardiography every 4 weeks and at sacrifice, early (~24 weeks) and late (~48 weeks) timepoints, along with pressure volume loop analysis. Histological and molecular characteristics were determined using standard techniques. Study 2: the effect of renin angiotensin system (RAS) blockade upon cardiac and renal function was assessed in GK rats. Finally, proteomic studies were conducted in vivo and in vitro to identify novel pathways involved in remodeling responses. Results GK rats developed hyperglycaemia by 12 weeks of age (p<0.01 c/w Wistar controls). Echocardiographic assessment of cardiac function demonstrated preserved systolic function by 48 weeks of age. Invasive studies demonstrated left ventricular hypertrophy, pulmonary congestion and impaired diastolic function. Renal function was preserved with evidence of hyperfiltration. Cardiac histological analysis demonstrated myocyte hypertrophy (p<0.05) with evidence of significant interstitial fibrosis (p<0.05). RT qPCR demonstrated activation of the fetal gene program, consistent with cellular hypertrophy. RAS blockade resulted in a reduction blood pressure(P<0.05) cardiac interstitial fibrosis (p<0.05) and activation of fetal gene program. No significant change on either systolic or diastolic function was observed, along with minimal impact upon renal structure or function. Proteomic studies demonstrated significant changes in proteins involved in oxidative phosp4horylation, mitochondrial dysfunction, beta-oxidation, and PI3K/Akt signalling (all p<0.05). Further, similar changes were observed in both LV samples from GK rats and H9C2 cells incubated in high glucose media. Conclusion By 48 weeks of age, the diabetic GK rat demonstrates evidence of preserved systolic function and impaired relaxation, along with cardiac hypertrophy, in the presence of hyperfiltration and elevated protein excretion. These findings suggest the GK rat demonstrates some, but not all features of diabetes induced “cardiorenal” syndrome. This has implications for the use of this model to assess preclinical strategies to treat cardiorenal disease.

Endothelial-Specific Deletion of CD146 Protects Against Experimental Glomerulonephritis in Mice

CD146 is an endothelial junctional adhesion molecule, which expression is increased in human glomerular diseases. However, the pathological significance of this overexpression remains unknown. Induction of glomerulonephritis in mice, by using nephrotoxic serum, showed that CD146 expression was highly induced within damaged glomeruli and was associated with renal inflammation and fibrosis. Interestingly, 2 weeks after glomerulonephritis induction, CD146 knockout mice showed preserved renal function as proteinuria and blood urea nitrogen levels were significantly lower compared with wild-type littermates. Furthermore, renal structure was considerably conserved, since crescents formation, tubular dilation, monocyte and lymphocyte infiltration, and interstitial renal fibrosis were highly reduced. Colocalization with markers for different types of glomerular cells showed that CD146 expression was mainly increased within the injured endothelium of the glomerular tuft. Consequently, we generated a new transgenic strain in which CD146 was specifically deleted in the vascular endothelium. Similarly to CD146 knockout, these mice showed preservation of renal structure and function after the induction of glomerulonephritis compared with wild-type animals. These data show that endothelial CD146 plays a major role in glomerulonephritis and may represent a novel therapeutic target to reduce glomerular damage and the progression of renal disease.

Analysis and Detection of Nephrolithiasis using Imaging Techniques

Nephrolithiasis (kidney stone) is a disease which affects 7% of females and 11% of males at some stage in their life. Early identification of Nephrolithiasis is necessary to avoid complications. Imaging techniques form the basis for the detection of kidney stones and aid in locating the position, size, and the number of stones present in the renal structure. This paper reports an extensive analysis of recent trends in the detection of Nephrolithiasis using Imaging techniques. Since Computed Tomography (CT) and ultrasound imaging are commonly used in the medical field, analysis of both the methods is considered in this paper. The detailed study on various methodologies and algorithms that have been adopted on CT and ultrasound images in recent years in locating kidney stones, finding the exact size of the stones based on pixel count, enhancing image quality, obtaining better de-speckling, faster segmentation, and pre-processing of the renal images has been carried out. Based on the analysis, an artificial intelligence-based approach is proposed that will aid the medical practitioner for faster, accurate detection of Nephrolithiasis and a technique to reduce the exposure of radiation in Computed Tomography Imaging. Further, it is concluded that ultrasound techniques can be employed subsequently for preliminary diagnosis through CT if the medical practitioner recommends.

Sex Differences in Renal Ammonia Metabolism

Sexual dimorphic variations are present in many aspects of biology and involve the structure and/or function of nearly every organ system. Acid-base homeostasis is critical for optimal health, and renal ammonia metabolism has a major role in the maintenance of acid-base homeostasis. Recent studies have shown sex-dependent differences in renal ammonia metabolism with regards to both basal ammonia excretion and the response to an exogenous acid load. These sexual dimorphisms are associated with structural changes in the proximal tubule and the collecting duct and variations in the expression of multiple proteins involved in ammonia metabolism and transport. Studies using orchiectomy (ORCH)-induced testosterone deficiency and physiological testosterone replacement show testosterone underlies much of the sex-dependent differences in the proximal tubule. This parallels the finding that the canonical testosterone target receptor, androgen receptor (AR), is present exclusively in the proximal tubule. Thus, testosterone, possibly acting through AR activation, regulates multiple coponents of renal structure and ammonia metabolism. The lack of detectable AR in the remainder of the nephron and the collecting duct suggests that some dimorphisms in renal structure and ammonia transporter expression are mediated through mechanisms other than direct testosterone-dependent AR activation. A better understanding of the mechanism and biological implications of sex's effect on renal structure and ammonia metabolism is critical for optimizing our ability to care for both men and women with acid-base disturbances.

Radix Rehmanniae and Corni Fructus against Diabetic Nephropathy via AGE-RAGE Signaling Pathway

Background and Aims. Radix Rehmanniae and Corni Fructus (RC) have been widely applied to treat diabetic nephropathy (DN) for centuries. But the mechanism of how RC plays the therapeutic role against DN is unclear as yet. Methods. The information about RC was obtained from a public database. The active compounds of RC were screened by oral bioavailability (OB) and drug-likeness (DL). Gene ontology (GO) analysis was performed to realize the key targets of RC, and an active compound-potential target network was created. The therapeutic effects of RC active compounds and their key signal pathways were preliminarily probed via network pharmacology analysis and animal experiments. Results. In this study, 29 active compounds from RC and 64 key targets related to DN were collected using the network pharmacology method. The pathway enrichment analysis showed that RC regulated advanced glycosylation end product (AGE-) RAGE and IL-17 signaling pathways to treat DN. The animal experiments revealed that RC significantly improved metabolic parameters, inflammation renal structure, and function to protect the kidney against DN. Conclusions. The results revealed the relationship between multicomponents and multitargets of RC. The administratiom of RC might remit the DM-induced renal damage through the AGE-RAGE signaling pathway to improve metabolic parameters and protect renal structure and function.

DOES PROTEIN SUPPLEMENTATION AND EXERCISE INTERFERE WITH RENAL FUNCTION AND STRUCTURE?

ABSTRACT Introduction: During physical activity, the body diverts blood to essential areas such as skeletal muscle, reducing the supply to non-essential areas such as the kidney. Whey protein is one of the most widely used supplements in gyms. Objectives: To evaluate renal function and renal structure in rats submitted to physical exercise with and without the use of protein supplementation. Methods: The protein used was Whey Hydro PRO 2 - Probiotica®. It was administered orally (by gavage), diluted in mineral water (1.8 g/kg of body weight, shortly after swimming training). The rats were divided into four groups: rats with exercise (Exc), rats without exercise (ñExc), rats with exercise and with protein supplementation (Prot/Exc) and rats without exercise and with protein supplementation (Prot/ñExc). The training consisted of swimming for 30 minutes, using load equivalent to 2% of body weight, five times a week for a total of 10 weeks. The protein was administered by gavage, once daily, immediately after the training. Results: A reduced glomerular filtration rate was observed in the animals of the Exc group compared to those of the Prot/Exc group. Plasma creatinine values were similar between the groups submitted to exercise and those not submitted to exercise. Plasma sodium and the sodium excretion fraction were lower in the Prot/Exc group compared to the Exc group. Urinary excretion was similar between groups. Histological analysis: Significant hydropic degeneration was observed in the animals that received protein supplementation and submitted to exercise. Conclusion: These results show that exercise associated with protein supplementation (2g/day/kg) leads to changes in the tubular mechanisms of sodium adjustments and structural changes in the renal parenchyma. Level of evidence II; Therapeutic studies - Investigation the results of treatment.

Testosterone modulates renal ammonia metabolism

There are substantial sex differences in renal structure and ammonia metabolism that correlate with differences in expression of proteins involved in ammonia generation and transport. This study determined the role of testis-derived testosterone in these differences. We studied 4-mo-old male C57BL/6 mice 4 and 8 wk after either bilateral orchiectomy (ORCH) or sham-operated control surgery and determined the effect of testosterone replacement to reverse the effects of ORCH. Finally, we determined the cellular expression of androgen receptor (AR), testosterone’s canonical target receptor. ORCH decreased kidney and proximal tubule size, and testosterone replacement reversed this effect. ORCH increased ammonia excretion in a testosterone-dependent fashion; this occurred despite similar food intake, which is the primary component of endogenous acid production. ORCH increased expression of both phospho enolpyruvate, a major ammonia-generating protein, and Na+-K+-2Cl− cotransporter, which mediates thick ascending limb ammonia reabsorption; these changes were reversed with testosterone replacement. Orchiectomy also decreased expression of Na+/H+ exchanger isoform 3, which mediates proximal tubule ammonia secretion, in a testosterone-dependent pattern. Finally, ARs are expressed throughout the proximal tubule in both the male and female kidney. Testosterone, possibly acting through ARs, has dramatic effects on kidney and proximal tubule size and decreases ammonia excretion through its effects on several key proteins involved in ammonia metabolism.