Effects of GABA on Oxidative Stress and Metabolism in High-Glucose Cultured Mongolian Sheep Kidney Cells.

The Mongolian sheep, emblematic of the Inner Mongolian grasslands, is renowned for its exceptional stress resistance and adaptability to harsh environments, drawing considerable attention. Recent research has unveiled the novel role of γ-aminobutyric acid (GABA) in combating oxidative stress. This investigation examined how GABA impacts renal-cortex and medulla cells from Mongolian sheep exposed to high-glucose stress conditions, utilizing gene expression analysis and non-targeted metabolomics. Elevated glucose levels significantly reduced the viability of Mongolian sheep renal cells and increased reactive oxygen species (ROS) levels. Conversely, the introduction of GABA notably enhanced cell viability, reduced ROS production, and stimulated the expression of antioxidant genes (e.g., Gpx, SOD, CAT) in the renal cortex. In the renal medulla, CAT expression increased, while Gpx gene expression showed mixed responses. Metabolomics analysis indicated that high-glucose exposure altered various metabolites, whereas GABA alleviated the metabolic stress induced by high glucose through modulating glycolysis and the tricarboxylic acid cycle. In Mongolian sheep renal cells, GABA effectively mitigated oxidative damage triggered by high-glucose stress by upregulating antioxidant genes and regulating metabolic pathways, revealing insights into its potential mechanism for adapting to extreme environments. This finding offers a fresh perspective on understanding the stress resilience of Mongolian sheep and may provide valuable insights for research across diverse disciplines.

Renal medullary perfusion differs from that in renal cortex in patients with sepsis associated acute kidney injury and correlates with renal function prognosis: A prospective cohort study.

BACKGROUND: Renal perfusion status remains poorly studied at the bedside during sepsis associated acute kidney injury (AKI). The aim of the study is to examine renal cortical and medullary perfusion using renal contrast enhanced ultrasound (CEUS) in septic patients. METHODS: In this single-center, prospective longitudinal study, septic patients were enrolled. Renal ultrasonography was performed within 24 hours of ICU admission (D1), then repeated at D3, D5 and D7. Each measurement consisted of three destruction replenishment sequences that were recorded for delayed analysis with dedicated software (Vuebox). Renal cortex and medulla perfusion were quantified by measuring time to peak (TTP). Receiver operating characteristic (ROC) analysis was used to evaluate 28-day renal prognosis. RESULTS: The study included 149 septic patients, including 70 non-AKI patients and 79 AKI patients. Both renal cortical and medullary TTP was longer in the AKI group than in the non-AKI group. The difference of TTP between renal cortex and medulla in AKI group was higher than that in the non-AKI group (p = 0.000). Medullary TTP on day 3 had the best performance in predicting the prognosis of 28-day renal function (AUC 0.673, 95% confidence interval 0.528-0.818, p = 0.024), and its cut-off value was 45 s with a sensitivity 52.2% and a specificity of 82.1%. Cortical TTP on day 3 also had the performance in predicting the prognosis of 28-day renal function (AUC 0.657, 95% confidence interval 0.514-0.800, p = 0.039), and its cut-off value was 33 s with a sensitivity 78.3% and a specificity of 55.0%. CONCLUSION: Renal medullary perfusion alterations differ from those in cortex, with the medulla is worse. Simultaneous and dynamic assessment of cortical and medullary microcirculatory flow alterations necessary. TTP on day 3, especially medullary TTP, seems to be a relatively stable and useful indicator, which correlates with 28-day renal function prognosis in septic patients. Early correction of renal cortical and medullary perfusion alterations reduces the incidence of adverse renal events.

The protective effect of 1400W against ischaemia and reperfusion injury is countered by transient medullary kidney endothelial dysregulation.

Renal ischaemia and reperfusion (I/R) is caused by a sudden temporary impairment of the blood flow. I/R is a prevalent cause of acute kidney injury. As nitric oxide generated by inducible nitric oxide synthase (iNOS) has detrimental effects during I/R, the pharmacological blockade of iNOS has been proposed as a potential strategy to prevent I/R injury. The aim of this study was to improve the understanding of 1400W (an iNOS inhibitor) on renal I/R as a pharmacological strategy against kidney disease. BALB/c mice received 30 min of bilateral ischaemia, followed by 48 h or 28 days of reperfusion. Vehicle or 1400W (10 mg/kg) was administered 30 min before inducing ischaemia. We found that after 48 h of reperfusion 1400W decreased the serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin and proliferating cell nuclear antigen 3 in the I/R animals. Unexpectedly, we observed mRNA upregulation of genes involved in kidney injury, cell-cycle arrest, inflammation, mesenchymal transition and endothelial activation in the renal medulla of sham animals treated with 1400W. We also explored if 1400W promoted chronic kidney dysfunction 28 days after I/R and did not find significant alterations in renal function, fibrosis, blood pressure or mortality. The results provide evidence that 1400W may have adverse effects in the renal medulla. Importantly, our data point to 1400W-induced endothelial dysfunction, establishing therapeutic limitations for its use. KEY POINTS: Acute kidney injury is a global health problem associated with high morbidity and mortality. The pharmacological blockade of inducible nitric oxide synthase (iNOS) has been proposed as a potential strategy to prevent AKI induced by ischaemia and reperfusion (I/R). Our main finding is that 1400W, a selective and irreversible iNOS inhibitor with low toxicity that is proposed as a therapeutic strategy to prevent kidney I/R injury, produces aberrant gene expression in the medulla associated to tissue injury, cell cycle arrest, inflammation, mesenchymal transition and endothelial activation. The negative effect of 1400W observed in the renal medulla at 48 h from drug administration, is transient as it did not translate into a chronic kidney disease condition.

Contribution of Serial Focused High-Resolution Renal Ultrasound in the Management of a Neonate in Acute Renal Failure.

Most newborns begin urinating within 24hours of life, and almost always by 48hours. Rarely, some of them are anuric beyond 24hours, thereby causing concern to parents and treating doctors. We report the case of a newborn who presented with anuria till 48hours after birth. High-resolution ultrasound examination, focusing on the renal medulla, demonstrated increased echogenicity at the tip of the pyramids. This was attributed to slow clearance of urinary sediment deposited there, which was causing obstruction to the urinary outflow. On monitoring serially over the next few days, the echogenic sludge was observed being slowly eliminated leading thereby to improvement in the urinary output. High-resolution ultrasound focusing on the renal pyramids played an important role in the observation and management of this transient event unfolding, in the urinary tract.

Animal models of hypertension: The status of nitric oxide and oxidative stress and the role of the renal medulla.

Hypertension significantly contributes to overall morbidity and mortality worldwide, and animal models of hypertension provide important tools to verify the physiological and molecular mechanisms underlying the development of the disease. A review of the most important models available would provide an insight into the appropriate targets to be addressed in the treatment of different forms of human hypertension. In the animal models discussed a special attention is given to the status and pathophysiological role of nitric oxide and its interaction with reactive oxygen species and oxidative stress. Another focus of the review are the processes running in the renal medulla which are still insufficiently explored. Deficient nitric oxide synthesis and its reduced bioavailability are important determinants of hypertension since NO is recognized as a major control factor of vascular tone homeostasis. For decades perfusion of the renal medulla has also been regarded as one of the blood pressure control factors and, noteworthily, the renal medulla belongs to the tissues with the highest NO content. The list of most often applied animal hypertension models reviewed here includes variants of salt-induced hypertension, the models with genetic background: such as spontaneously hypertensive rats (SHR) and Dahl salt sensitive (SS/SR) rats, Goldblatt 2K-1C hypertensive rats, and also the pharmacologically-plus-dietary salt-induced model known as DOCA-salt hypertension.

Identification of Structural and Molecular Signatures Mediating Adaptive Changes in the Mouse Kidney in Response to Pregnancy.

Pregnancy is characterized by adaptations in the function of several maternal body systems that ensure the development of the fetus whilst maintaining health of the mother. The renal system is responsible for water and electrolyte balance, as well as waste removal. Thus, it is imperative that structural and functional changes occur in the kidney during pregnancy. However, our knowledge of the precise morphological and molecular mechanisms occurring in the kidney during pregnancy is still very limited. Here, we investigated the changes occurring in the mouse kidney during pregnancy by performing an integrated analysis involving histology, gene and protein expression assays, mass spectrometry profiling and bioinformatics. Data from non-pregnant and pregnant mice were used to identify critical signalling pathways mediating changes in the maternal kidneys. We observed an expansion of renal medulla due to proliferation and infiltration of interstitial cellular constituents, as well as alterations in the activity of key cellular signalling pathways (e.g., AKT, AMPK and MAPKs) and genes involved in cell growth/metabolism (e.g., Cdc6, Foxm1 and Rb1) in the kidneys during pregnancy. We also generated plasma and urine proteomic profiles, identifying unique proteins in pregnancy. These proteins could be used to monitor and study potential mechanisms of renal adaptations during pregnancy and disease.

Role of perioperative hypotension in postoperative acute kidney injury: a narrative review.

Perioperative hypotension is common and associated with poor outcomes, including acute kidney injury (AKI). The mechanistic link between perioperative hypotension and AKI is at least partly a consequence of the susceptibility of the kidney, and particularly the renal medulla, to ischaemia and hypoxia. Several critical gaps in our knowledge lead to uncertainty about when and how to intervene to prevent AKI attributable to perioperative hypotension. First, although we know that the risk of AKI varies with both the severity and duration of hypotensive episodes, 'safe' levels of arterial pressure have not been identified. Second, there have been few adequately powered clinical trials of interventions to avoid perioperative hypotension. Thus, most evidence surrounding perioperative hypotension is observational rather than based on randomised clinical trials. This means that the link between perioperative hypotension and AKI may represent association (where both phenomena reflect illness severity) rather than causation. Third, there is little information regarding the relative risks and benefits of various clinically available therapies (e.g. vasoconstrictors, i.v. fluids, or both) to treat and prevent perioperative hypotension, particularly with regard to renal medullary perfusion and oxygenation. Fourth, there are currently no validated, clinically feasible methods for real-time clinical monitoring of renal perfusion or oxygenation. Thus, future developments in perioperative kidney-protective strategies must rely on the development of methods to better monitor renal perfusion and oxygenation in the perioperative period, and thereby guide timing, intensity, type, and duration of interventions.

The hypoxia-inducible factor prolyl hydroxylase inhibitor FG4592 promotes natriuresis through upregulation of COX2 in the renal medulla.

The renal medulla is a key site for the regulation of renal sodium excretion. However, the molecular mechanism remains unclear. Cyclooxygenase 2 (COX2) is specifically expressed in the renal medulla and contributes to the maintenance of the electrolyte/water balance in the body. Hypoxia-inducible factors (HIFs) have also been found to be expressed in the renal medulla, probably owing to the hypoxic conditions in the renal medulla. This study was designed to test the effects of HIF activation on renal sodium handling and renal medullary COX2 expression. Our data showed that HIF activation by the prolyl hydroxylase inhibitor (PHI) FG4592 enhanced natriuresis in mice challenged with a high-salt diet. In addition, FG4592 upregulated the expression of COX2 in the renal medulla. An in vitro study further supported the finding that HIF can induce the expression of COX2 and that this induction is mediated through direct binding to the promoter region of the Cox2 gene, facilitating its transcription. In addition, the COX2 inhibitor celecoxib diminished the natriuretic effect of FG4592. Together, these results suggest that HIF activation promotes sodium excretion through upregulation of COX2 in the renal medulla and therefore maintains sodium homeostasis in the body.

Identification of sodium homeostasis genes in Camelus bactrianus by whole transcriptome sequencing.

Salt dietary intake is tightly coupled to human health, and excessive sodium can cause strokes and cardiovascular diseases. Research into the renal medulla of camels exhibiting high salt resistance may aid identification of the mechanisms governing resistance to high salinity. In this study, we used RNA sequencing (RNA-seq) to show that in the renal medulla of camels under salt stress, 22 mRNAs, 2 long noncoding RNAs (lncRNAs), and 31 microRNAs (miRNAs) exhibited differential expression compared with the free salt-intake diet group. Using fluorescence in situ hybridization and dual-luciferase reporter assays, we demonstrated that the lncRNA LNC003834 can bind miRNA-34a and thereby relieve suppression of the salt-absorption-inhibiting SLC14A1 mRNA from miRNA-34a, suggesting that the above lncRNA-miRNA-mRNA act as competing endogenous RNAs (ceRNAs). We subsequently performed short hairpin RNA and small RNA interference and reactive oxygen species (ROS) detection assays to show that SLC6A1, PCBP2, and PEX5L can improve the antioxidation capacity of renal medulla cells of camel by decreasing ROS levels. Our data suggest that camels achieve sodium homeostasis through regulating the expression of salt-reabsorption-related genes in the renal medulla, and this involves ceRNAs (SLC14A1 mRNA, LNC003834, and miRNA-34a) and antioxidant genes (SLC6A1, PCBP2, and PEX5L). These data may assist in the development of treatments for diseases induced by high salt diets.

Intra-operative and early post-operative prediction of cardiac surgery-associated acute kidney injury: Urinary oxygen tension compared with plasma and urinary biomarkers.

Acute kidney injury (AKI) is a common and serious post-operative complication of cardiac surgery. The value of a predictive biomarker is determined not only by its predictive efficacy, but also by how early this prediction can be made. For a biomarker of cardiac surgery-associated AKI, this is ideally during the intra-operative period. Therefore, in 82 adult patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB), we prospectively compared the predictive efficacy of various blood and urinary biomarkers with that of continuous measurement of urinary oxygen tension (UPO2 ) at pre-determined intra- and post-operative time-points. None of the blood or urine biomarkers we studied showed predictive efficacy for post-operative AKI when measured intra-operatively. When treated as a binary variable (≤ or > median for the whole cohort), the earliest excess risk of AKI was predicted by an increase in urinary neutrophil gelatinase-associated lipocalin (NGAL) at 3 h after entry into the intensive care unit (odds ratio [95% confidence limits], 2.86 [1.14-7.21], p = 0.03). Corresponding time-points were 6 h for serum creatinine (3.59 [1.40-9.20], p = 0.008), and 24 h for plasma NGAL (4.54 [1.73-11.90], p = 0.002) and serum cystatin C (6.38 [2.35-17.27], p = 0.001). In contrast, indices of intra-operative urinary hypoxia predicted AKI after weaning from CPB, and in the case of a fall in UPO2 to ≤10 mmHg, during the rewarming phase of CPB (3.00 [1.19-7.56], p = 0.02). We conclude that continuous measurement of UPO2 predicts AKI earlier than plasma or urinary NGAL, serum cystatin C, or early post-operative changes in serum creatinine.

Analysis of Risk Factors for Changes in the Renal Two-Dimensional Image in Gout Patients.

OBJECTIVE: To explore the effects of different blood uric acid levels in gout patients on the two-dimensional image of the kidney and the risk factors for gout-related kidney damage for providing clinical evidence to enable early prevention and treatment of gout-related kidney damage. METHODS: We obtained information of 227 patients with primary gout and estimated the association between two-dimensional kidney images and clinical indicators using binary logistic regression. RESULTS: Our study showed that different uric acid levels, age, disease course, cystatin C (CysC) level, and γ-glutamyl transpeptidase level were correlated with echo of the renal medulla (P < 0.05). CysC level was correlated with the renal cortex thickness and kidney stones in different uric acid-level groups (P < 0.05). Disease course, aspartate transaminase (AST) level, creatinine (CREA) level, and tophi were risk factors for renal cortex thinning in gout patients (P = 0.045, 0.026, 0.004, 0.006, respectively). The disease course, platelet (PLT) count, and high-density lipoprotein (HDL-C) level were risk factors for kidney stone formation in gout patients (P = 0.037, 0.022, 0.023, respectively), while CysC level and C-reactive protein (CRP) level were risk factors for increased renal medulla echo in these patients (P = 0.022, 0.028, respectively). CONCLUSION: Our study revealed disease course, AST level, CREA level, tophi, PLT count, HDL-C level, CysC level and CRP level may be important predictors of renal image changes.

Pathophysiological Relevance of Renal Medullary Conditions on the Behaviour of Red Cells From Patients With Sickle Cell Anaemia.

Red cells from patients with sickle cell anaemia (SCA) contain the abnormal haemoglobin HbS. Under hypoxic conditions, HbS polymerises and causes red cell sickling, a rise in intracellular Ca2+ and exposure of phosphatidylserine (PS). These changes make sickle cells sticky and liable to lodge in the microvasculature, and so reduce their lifespan. The aim of the present work was to investigate how the peculiar conditions found in the renal medulla - hypoxia, acidosis, lactate, hypertonicity and high levels of urea - affect red cell behaviour. Results show that the first four conditions all increased sickling and PS exposure. The presence of urea at levels found in a healthy medulla during antidiuresis, however, markedly reduced sickling and PS exposure and would therefore protect against red cell adherence. Loss of the ability to concentrate urine, which occurs in sickle cell nephropathy would obviate this protective effect and may therefore contribute to pathogenesis.

A mathematical model of the rat kidney. III. Ammonia transport.

Ammonia generated within the kidney is partitioned into a urinary fraction (the key buffer for net acid excretion) and an aliquot delivered to the systemic circulation. The physiology of this partitioning has yet to be examined in a kidney model, and that was undertaken in this work. This involves explicit representation of the cortical labyrinth, so that cortical interstitial solute concentrations are computed rather than assigned. A detailed representation of cortical vasculature has been avoided by making the assumption that solute concentrations within the interstitium and peritubular capillaries are likely to be identical and that there is little to no modification of venous composition as blood flows to the renal vein. The model medullary ray has also been revised to include a segment of proximal straight tubule, which supplies ammonia to this region. The principal finding of this work is that cortical labyrinth interstitial ammonia concentration is likely to be several fold higher than systemic arterial ammonia. This elevation of interstitial ammonia enhances ammonia secretion in both the proximal convoluted tubule and distal convoluted tubule, with uptake by Na+-K+-ATPases of both segments. Model prediction of urinary ammonia excretion was concordant with measured values, but at the expense of greater ammoniagenesis, with high rates of renal venous ammonia flux. This derives from a limited capability of the model medulla to replicate the high interstitial ammonia concentrations that are required to drive collecting duct ammonia secretion. Thus, renal medullary ammonia trapping appears key to diverting ammonia from the renal vein to urine, but capturing the underlying physiology remains a challenge.NEW & NOTEWORTHY This is the first mathematical model to estimate solute concentrations within the kidney cortex. The model predicts cortical ammonia to be several fold greater than in the systemic circulation. This higher concentration drives ammonia secretion in proximal and distal tubules. The model reveals a gap in our understanding of how ammonia generated within the cortex is channeled efficiently into the final urine.

High salt diet contributes to hypertension by weakening the medullary tricarboxylic acid cycle and antioxidant system in Dahl salt-sensitive rats.

High salt diet (HSD, 8% NaCl) contributes to salt-sensitive hypertension, this study aimed to determine the effect of HSD on salt-sensitive hypertension by combining proteomic with metabolomics methods. Salt-sensitive rats were fed on HSD and normal salt diet (NSD, 0.4% NaCl) for two weeks before further analysis. Proteomic analysis showed the differential expression proteins (DEPs) were primarily mapped in the tricarboxylic acid (TCA)-cycle, glycolysis/gluconeogenesis, and other pathways associated with multiple amino acids. HSD decreased the medullary activities and protein expression level of two key enzymes of TCA-cycle, MDH and NADP+-IDH. Metabolomics showed three serous TCA-cycle-associated compounds, including decreased malic acid, decreased citric acid, and increased fumaric acid were differentially detected, which resulted in a decrease in NO content and an increase in H2O2 content in serum. The content of GSH, GSH/GSSG ratio, and synthesis substrates of GSH-cysteine and glycine, were significantly decreased by HSD, thus attenuated the antioxidant system in the renal medulla. HSD enhanced the medullary pentose phosphate pathway, which finally increased the concentration of NADPH and NADP+, NADPH/NADP+, and the activity of NADPH oxidase in the renal medulla. Additionally, HSD enhanced the glycolysis pathway in the renal medulla. In summary, HSD significantly weakened the TCA cycle, and attenuated the antioxidant system in the renal medulla, which finally contributed to salt-sensitive hypertension.

Role for ovarian hormones in purinoceptor-dependent natriuresis.

BACKGROUND: Premenopausal women have a lower risk of hypertension compared to age-matched men and postmenopausal women. P2Y2 and P2Y4 purinoceptor can be considered potential contributors to hypertension due to their emerging roles in regulating renal tubular Na+ transport. Activation of these receptors inhibits epithelial Na+ channel activity (ENaC) via a phospholipase C (PLC)-dependent pathway resulting in natriuresis. We recently reported that activation of P2Y2 and P2Y4 receptors in the renal medulla by UTP promotes natriuresis in male and ovariectomized (OVX) rats, but not in ovary-intact females. This led us to hypothesize that ovary-intact females have greater basal renal medullary activity of P2 (P2Y2 and P2Y4) receptors regulating Na+ excretion compared to male and OVX rats. METHODS: To test our hypothesis, we determined (i) the effect of inhibiting medullary P2 receptors by suramin (750 µg/kg/min) on urinary Na+ excretion in anesthetized male, ovary-intact female, and OVX Sprague Dawley rats, (ii) mRNA expression and protein abundance of P2Y2 and P2Y4 receptors, and (iii) mRNA expression of their downstream effectors (PLC-1δ and ENaCα) in renal inner medullary tissues obtained from these three groups. We also subjected cultured mouse inner medullary collecting duct cells (segment 3, mIMCD3) to different concentrations of 17ß-estradiol (E2, 0, 10, 100, and 1000 nM) to test whether E2 increases mRNA expression of P2Y2 and P2Y4 receptors. RESULTS: Acute P2 inhibition attenuated urinary Na+ excretion in ovary-intact females, but not in male or OVX rats. We found that P2Y2 and P2Y4 mRNA expression was higher in the inner medulla from females compared to males or OVX. Inner medullary lysates showed that ovary-intact females have higher P2Y2 receptor protein abundance, compared to males; however, OVX did not eliminate this sex difference. We also found that E2 dose-dependently upregulated P2Y2 and P2Y4 mRNA expression in mIMCD3. CONCLUSION: These data suggest that ovary-intact females have enhanced P2Y2 and P2Y4-dependent regulation of Na+ handling in the renal medulla, compared to male and OVX rats. We speculate that the P2 pathway contributes to facilitated renal Na+ handling in premenopausal females.

Altered renal medullary blood flow: A key factor or a parallel event in control of sodium excretion and blood pressure?

In the context of the ongoing debate on the mechanism of blood pressure (BP) regulation and pathophysiology of arterial hypertension ("renocentric" vs "neural" concepts), attention is focused on the putative regulatory role of changes in renal medullary blood flow (MBF). Experimental evidence is analysed with regard to the question whether an elevation of BP and renal perfusion pressure (RPP) is likely to increase MBF due to its impaired autoregulation. It is concluded that such increases have been clearly documented only in rats with extracellular fluid volume expansion. A possible translation of this finding to BP regulation in health and hypertension in humans may only be a matter of speculation. Within the "renocentric" theory, the key event leading to restoration of initial BP level is pressure natriuresis. Its relation to elevation of renal interstitial hydrostatic pressure and to the phenomenon of "wash-out" of renal medullary solutes by increasing MBF is discussed. We also assessed the validity of data supporting the putative mechanism of short-term restoration of elevated BP owing to the release of a vasodilator lipid (medullipin) by the medulla. The structure of the proposed medullary lipid is still undefined, and there is no sound evidence on its mediatory role in lowering elevated BP level. In conclusion, MBF change can hardly be regarded as a crucial event in the regulation of BP: it can be involved in the control of sodium excretion and BP only in some circumstances, although its contributory role cannot be excluded.

Renal oxygenation: From data to insight.

Computational models have made a major contribution to the field of physiology. As the complexity of our understanding of biological systems expands, the need for computational methods only increases. But collaboration between experimental physiologists and computational modellers (ie theoretical physiologists) is not easy. One of the major challenges is to break down the barriers created by differences in vocabulary and approach between the two disciplines. In this review, we have two major aims. Firstly, we wish to contribute to the effort to break down these barriers and so encourage more interdisciplinary collaboration. So, we begin with a "primer" on the ways in which computational models can help us understand physiology and pathophysiology. Second, we aim to provide an update of recent efforts in one specific area of physiology, renal oxygenation. This work is shedding new light on the causes and consequences of renal hypoxia. But as importantly, computational modelling is providing direction for experimental physiologists working in the field of renal oxygenation by: (a) generating new hypotheses that can be tested in experimental studies, (b) allowing experiments that are technically unfeasible to be simulated in silico, or variables that cannot be measured experimentally to be estimated, and (c) providing a means by which the quality of experimental data can be assessed. Critically, based on our experience, we strongly believe that experimental and theoretical physiology should not be seen as separate exercises. Rather, they should be integrated to permit an iterative process between modelling and experimentation.

Screening of drought-resistance related genes and analysis of promising regulatory pathway in camel renal medulla.

Camels as a sort of animal long living in desert have evolved stress-resistance characteristics to adapt to environment with high temperature and water shortage environment. However, the research of non-coding RNA (ncRNA)-mediated molecular regulation about how camel responds to arid condition in post-transcriptional regulation level is deficient. Under water-deprivation stress, by RNA-sequencing of camel renal medulla associated with regulating water metabolism, we detected significantly differential 575 alternative splicing events (ASEs) and 17 mRNAs, 26 miRNAs and 0 lncRNA. The down-regulated ACLY and LOC105061856, up-regulated PCBP2 and miR-195 potentially targeting LOC105061856 and PCBP2 mRNA were selected as candidate resistance-related genes. In quantitative experiment, the expression level of above four genes was consistent with RNA-seq data by qRT-PCR. The suppressive cell dehydration with down-regulated ACLY, inhibitive aerobic respiration with down-regulated LOC105061856 targeted by miR-195 and strong anti-oxidative capability with PCBP2 aimed by miR-195 may be regulatory modes of camel renal medulla adapting to water-deprivation condition.

The impact of prematurity on postnatal growth of different renal compartments.

AIM: In humans, nephrogenesis ceases before birth, but the renal medulla compartment continues to develop after birth. We aim to evaluate the relative growth of different renal compartments in preterm babies compared with age-matched term babies, and explore the impact of premature birth on postnatal renal maturation, remodelling and possible long-term implications. METHODS: This retrospective study compared the renal ultrasonographic images between preterm babies and term infants. Ultrasound images were obtained at 32 weeks (preterm), 37 weeks and at 6 months of age. Kidney volume, length, renal cortex and medulla thickness were measured and compared between preterm and term babies. RESULTS: Preterm babies were lighter in body weight and shorter for crown-heel length at age-matched 37 weeks. All kidney growth parameters were also smaller compared with term babies. However, by 6 months of age kidney volume and length measurements were no longer significantly different between the two groups though preterm babies were still significantly lighter and shorter. The catch-up of the overall kidney growth in preterm babies was mainly attributed to the hypertrophic growth of the renal cortex while the postnatal renal medulla growth was disrupted. This trend continued as the renal cortical thickness became significantly larger while the medulla became smaller in preterm babies at 6 months of age, compared with age-matched term baby. CONCLUSIONS: In preterm babies, the renal cortical region undergoes accelerated growth after birth while the renal medulla growth lags behind. Further investigations will be necessary to determine whether this has a negative impact on renal function later in life.

What Makes the Kidney Susceptible to Hypoxia?

Per gram of tissue, the kidneys are among our most highly perfused organs. Yet the renal cortex and, in particular, the renal medulla are susceptible to hypoxia. In turn, hypoxia is a major pathophysiological feature of both acute kidney injury and chronic kidney disease. We identify seven factors that render the kidney susceptible to hypoxia: (1) the large metabolic demand imposed by active reabsorption of sodium; (2) limitations on oxygen delivery to cortical tissue imposed by the density of peritubular capillaries; (3) the poor capacity for angiogenesis in the adult kidney; (4) the limited ability of the renal vasculature to dilate in response to hypoxia; (5) diffusive oxygen shunting between arteries and veins in the cortex and descending and ascending vasa recta in the medulla; (6) the physiological requirement for low medullary blood flow to facilitate urinary concentration; and (7) the topography of vascular-tubular arrangements in the outer medulla that limit oxygen delivery to the thick ascending limb of Henle's loop. Recent collaborative efforts between anatomists, physiologists, and mathematicians have improved our understanding of the roles of these factors in both physiological regulation of intrarenal oxygenation and development of renal hypoxia under pathophysiological conditions. We are also better able to understand these apparent maladaptations in the context of evolution. That is, they can be explained by the combined effects of historical contingency (our ancestral life in the sea) and selection pressures imposed by the multiple functions of the kidney to regulate extracellular fluid volume, retain water, and control erythrocyte production.