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The aim of this study was to evaluate the production performance and the occurrence of histomorphometric changes in the digestive, hepatic and renal systems of goats fed with a diet containing different contents of 25 and 55% spineless cactus (Nopalea cochenillifera (L.)) and with partial or total restriction of drinking water. A total of 35 castrated male goats were used, with an average initial body weight of 19 + 1.4 kg, an average age of 8 months and distributed into five treatments: control (CON): 0.8 Tifton-85 hay and 0.2 concentrate with access to drinking water; 0.25 spineless cactus with access to drinking water (25ADW); 0.25 spineless cactus without access to drinking water (25NDW); 0.55 spineless cactus with access to drinking water (55ADW) and 0.55 spineless cactus without access to drinking water (55NDW). Ruminal and intestinal morphometry, liver glycogen reserve index, duodenal goblet cell index and liver and kidney histopathology were carried out. In the treatment with 0.25 spineless cactus and 0.55 Tifton-85 hay, dry matter intake increased by 26%. The papilla absorption area showed that the 0.55 spineless cactus content provided a larger area (P < 0.05) compared to the 0.25 content and the control. It can be concluded that spineless cactus (N. cochenillifera (L.)) can be used in the diet of goats at a concentration of up to 0.55, associated with Tifton-85, with or without access to drinking water, without causing losses in animal performance or at ruminal, intestinal, hepatic or renal level.
Enhanced dietary Ca intake linearly increases intestinal Ca absorption in pigs, but not in broilers, suggesting potential differences in whole body Ca homeostasis. To determine the role of kidney in Ca homeostasis in these species, we varied in growing pigs in experiment (Exp) 1, the dietary Ca content 2·0 v. 9·6 g/kg and phytase 0 v. 500 FTU/kg, in broilers, in Exp 2 the dietary Ca/retainable P from 1·3 to 2·8 and phytase 0 v. 1000 FTU/kg, and in Exp 3 dietary Ca/P from 0·50 to 1·75. Increasing dietary Ca reduced renal mRNA expression of Ca-related transporters (TRPV5, TRPV6, CaBP-D28k and NCX1) and tight junctions (CLDN-12 and −16) in pigs, indicating Ca reabsorption was reduced to maintain Ca homeostasis. In broilers (Exp 2), high dietary Ca increased renal TRPV6, CaBP-D28k and CLDN-2 mRNA, indicating an increased capacity for Ca reabsorption. Moreover, the effect of dietary Ca was enhanced by inclusion of dietary phytase in pigs but reduced in broilers. Furthermore, increasing dietary Ca upregulated inorganic phosphate transporter 1 (PiT-1), while phytase downregulated xenotropic and polytropic retrovirus receptor 1 (XPR1) mRNA expression in pigs; in broilers, dietary Ca downregulated renal mRNA expression of Na-dependent phosphate transporter IIa (NaPi-IIa), PiT-1, PiT-2 and XPR1, while phytase downregulated NaPi-IIa but upregulated PiT-2 and XPR1 mRNA expression. In Exp 3, Ca/P effect on transporter mRNA expression was largely consistent with Exp 2. In conclusion of this study, together with previously measured data about Ca and P homeostasis, in pigs the kidneys play a more regulatory role in Ca homeostasis than in broilers where the intestine is more important for regulation.
The scientific literature provides little evidence-based guidance in amount (quantitative fluid intervention) or type (qualitative fluid intervention) of fluid to optimize outcomes during liver and renal transplantation. Fluid intervention and vasoactive pharmacological support for transplantation depend on clinician preference, institutional resources and practice culture. Patients undergoing liver and renal transplantation should be managed on an individualized basis. No single approach will be effective. This chapter provides a contemporary overview of the fundamental principles underpinning fluid intervention for adult liver and renal transplantation. The overarching principles of fluid intervention for transplantation are to normalize the microcirculation by maintaining intravascular volume, tissue perfusion and tissue oxygenation, thereby protecting the new graft and other organs. The chapter also summarizes contemporary recommendations from expert panels for the perioperative fluid management and outcomes for adults undergoing liver and kidney transplantation.
Acute kidney injury is a common postoperative complication of paediatric cardiac surgery associated with increased morbidity and mortality. The purpose of this study is to characterise associations between haemodynamic parameters, clinical parameters, and medical interventions, on acute kidney injury.
Methods:
Nine patients with univentricular physiology undergoing the Norwood procedure from a single-centre tertiary care paediatric cardiac ICU were included (September 2022 to March 2023). Patients were monitored with the T3 software. Data were analysed using a Fisher exact test, Mann–Whitney-U test, LASSO-based machine learning techniques, and receiver operator curve analyses.
Results:
Over 27,000 datapoints were included. Acute kidney injury occurred in 2 patients (22%) during this period. Net fluid balance and renal oxygen extraction were independently associated with acute kidney injury, while commonly used metrics of pressure (systolic, diastolic, or mean arterial blood pressure) were not. The resulting acute kidney injury risk score was (4.1 × fluid balance) + (1.9 × renal oxygen extraction). The risk score was significantly higher in acute kidney injury with a score of 32.9 compared to 7.9 (p < 0.01). Optimal cut-offs for fluid balance (7 mL/hr) and renal oxygen extraction (29%) were identified. Higher serum creatinine:baseline creatinine ratio was associated with a higher mean airway pressure, higher renal oxygen extraction, higher mean arterial blood pressure, higher vasoactive inotropic score, and fluid balance.
Conclusion:
Among patients with univentricular physiology undergoing the Norwood procedure, renal oxygen extraction and a higher net fluid balance are independently associated with increased risk of acute kidney injury. Renal perfusion pressure is not significantly associated with acute kidney injury.
Kidney failure is a major killer. Many lives could be saved through organ donation if people were less reluctant to part with their spare kidney. Should we incentive donation by paying people to do it?
Zearalenone (ZEA), a common contaminant in food and feedstuffs, threatens human and animal health. The present study aimed to investigate the protective effects of modified palygorskite (MPal), a ZEA-targeted adsorbent, on broilers (young chickens) fed a ZEA-contaminated diet. Broilers were subjected to one of three treatments for a period of 42 days: a basal diet (control group), a ZEA- contaminated diet, and a ZEA-contaminated diet supplemented with 1 g/kg of MPal. Blood was collected for serum metabolite assay, and liver and kidney were sampled to determine ZEA residue and antioxidant-related parameters, using commercial spectrophotometric kits. Compared with the basal diet, the ZEA- contaminated diet resulted in compromised growth performance (reduced daily gain and feed intake during finisher period), disordered relative liver weight (decreased at 21 days but increased at 42 days), increased ZEA residue in liver and kidney, abnormal serum metabolites (decreased total protein content but increased alanine aminotransferase activity at 21 and 42 days, reduced albumin content at 21 days, and elevated aspartate aminotransferase activity at 42 days), and disrupted antioxidant capacities of broilers (increased total superoxide dismutase (T-SOD) activity in liver at 21 and 42 days, decreased T-SOD activity in kidney at 21 and 42 days, and in serum at 42 days, greater malondialdehyde accumulation in liver and kidney at 42 days, and lower glutathione content in kidney at 21 days). The adverse consequences resulting from the ZEA-contaminated diet were relieved by the supplementation of MPal (except albumin concentration in serum and T-SOD activity in liver at 21 days), with the values of growth-performance parameters, liver weight, renal ZEA accumulation, total protein content, transaminase activity at 42 days, and antioxidant indexes being similar to those in the control group. These results suggested that MPal supplementation could promote growth performance, attenuate liver damage, and improve the antioxidant abilities of broilers fed ZEA-contaminated diet by reducing ZEA accumulation.
Methotrexate (MTX) is a cytotoxic immunosuppressant that is widely used in the treatment of tumours, rheumatoid arthritis and psoriasis. This study aims to evaluate the effects of whey proteins on MTX-induced liver and kidney damage by focusing on oxidant–antioxidant systems and eating habits. The study was conducted in four groups of thirty Sprague–Dawley rats (control, control + whey protein concentrate (WPC), MTX, MTX + WPC). A single dose of 20 mg/kg MTX was administered intraperitoneally to the MTX groups. Control and MTX groups were given 2 g/kg WPC by oral gavage every day for 10 d. At the end of day 10, blood samples were drawn and liver and kidney tissues were removed. MTX administration increased the lipid peroxidation level and decreased glutathione level, superoxide dismutase and glutathione-S-transferase activities in the liver and kidney. Administration of WPC significantly reduced the damage caused by MTX in the liver and kidney. While a decrease in serum urea level and an increase in serum creatinine level were detected in the MTX group, WPC administration reversed these results up to control group levels. Administration of WPC to the MTX group significantly reversed the histopathological damage scores of the liver and kidney. WPC administration ameliorated the MTX-induced oxidative damage in the liver and kidney tissues due to its antioxidant properties. Liver and kidney damage can be prevented by using whey proteins as a nutraceutical in MTX therapy. In conclusion, whey proteins demonstrated a protective effect against MTX-induced liver and kidney damage.
Here we uncover the mysteries of the baby as it develops in the womb, discussing how fetal development is controlled. We give insights into aspects of pregnancy not widely known, from the fetus starting to breathe months before it is born, to the question of whether it sleeps – and dreams. We discuss the ways in which information about the mother’s life and her environment affect the baby’s development. Although birth may seem the first major milestone for a baby, we emphasise that many other milestones have been passed before that, inside the womb, out of sight but over which parents can have substantial influence. We give insights into new discoveries about how the organs of the fetal body develop in prediction of the world in which that individual ‘expects’ to live, and what happens when the prediction turns out to be wrong. The idea that the fetus is preparing for life after birth will get the reader thinking about the long-term consequences of the way a fetus develops. Each of us is unique as a result of our development – and nobody is perfect. Our unique development starts from the moment of conception, which introduces the next chapter on sex.
A critical component of the theory of the multiple reserves is that the health of the body is good for the health of the brain. The brain is dependent on all other body parts for maintenance of its functions. This dependence upon other bodily functions is especially prominent in older persons, because of their lower reserve capacities. Research has shown that intensive blood pressure control is more effective than standard blood pressure control in reducing the risk of cognitive impairment. It is certainly true that "what is good for the heart is good for the brain.” It is valuable to have the best possible heart, lung, kidney, liver, and endocrine function. Diabetes increases the risk of Alzheimer’s disease as well as small and large strokes. Avoidance of obesity and physical exercise can lower the risk of diabetes. A high-fiber diet can improve insulin responsiveness and diminish the severity of diabetes. The recommendations in this book are good for the health of the heart, lungs and other organs as well as directly beneficial to the nervous system. Good systemic health means good physical reserve. Good physical reserve helps to maintain healthy brain function throughout life.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the novel global coronavirus disease 2019 (COVID-19) disease outbreak. Its pathogenesis is mostly located in the respiratory tract. However, other organs are also affected. Hence, realising how such a complex disturbance affects patients after recovery is crucial. Regarding the significance of control of COVID-19-related complications after recovery, the current study was designed to review the cellular and molecular mechanisms linking COVID-19 to significant long-term signs including renal and cardiac complications, cutaneous and neurological manifestations, as well as blood coagulation disorders. This virus can directly influence on the cells through Angiotensin converting enzyme 2 (ACE-2) to induce cytokine storm. Acute release of Interleukin-1 (IL1), IL6 and plasminogen activator inhibitor 1 (PAI-1) have been related to elevating risk of heart failure. Also, inflammatory cytokines like IL-8 and Tumour necrosis factor-α cause the secretion of von Willebrand factor (VWF) from human endothelial cells and then VWF binds to Neutrophil extracellular traps to induce thrombosis. On the other hand, the virus can damage the blood–brain barrier by increasing its permeability and subsequently enters into the central nervous system and the systemic circulation. Furthermore, SARS-induced ACE2-deficiency decreases [des-Arg9]-bradykinin (desArg9-BK) degradation in kidneys to induce inflammation, thrombotic problems, fibrosis and necrosis. Notably, the angiotensin II-angiotensin II type 1 receptor binding causes an increase in aldosterone and mineralocorticoid receptors on the surface of dendritic cells cells, leading to recalling macrophage and monocyte into inflammatory sites of skin. In conclusions, all the pathways play a key role in the pathogenesis of these disturbances. Nevertheless, more investigations are necessary to determine more pathogenetic mechanisms of the virus.
In the following interview, philosophers Leonard Fleck and Arthur Ward discuss the latter’s recent experience of being a nondirected kidney donor. The interview took place in the Center for Bioethics and Social Justice at Michigan State University.
Injection of solutes such as Na+ or mannitol, which initially elevate ECF osmotic pressure and then draw water from cells to dilute the load to near isotonicity, causes reliable drinking in all species studied. This osmoregulatory drinking is accompanied by report of thirst in humans and secretion of AVP. The threshold elevation of systemic osmolality to initiate these changes is in the range 1–3%. Regardless of whether drinking is allowed, the osmotic load is excreted by the kidney over the course of2–4 hours. From sham drinking and other studies, osmoregulatory drinking is satiated when osmotic pressure is normalized and cellular water is restored. Many studies have shown that osmoreceptors for drinking and AVP secretion are located in or near the CVOs of the lamina terminalis. In addition, peripheral osmoreceptors in the gut or splanchnic regions monitor the osmolality of fluids absorbed from the gut and are sufficient to stimulate drinking in the absence of systemic hyperosmolality.
Despite the apparent beneficial effects of probiotics/synbiotics on glucose haemostasis, lipid profile and inflammatory responses, it is not clear whether these beneficial effects also impact renal and hepatic function in diabetes. Therefore, we sought to assess the effect of probiotics/synbiotics supplementation on renal and liver biomarkers in adults with type 2 diabetes mellitus (T2DM) using a systematic review and meta-analysis of randomised controlled trials (RCT). PubMed, Scopus, Web of Science and Cochrane Library were systematically searched, up to February 2021. The pooled weighted mean difference (WMD) was estimated using a random-effects model. The methodological quality of studies, as well as certainty of evidence, was assessed using standard scales. Fifteen related trials were identified. Meta-analysis of six trials, involving 426 participants, indicated that probiotics/synbiotics supplementation reduced serum levels of creatinine (WMD = −0·10 mg/dl, 95 % CI −0·20, −0·00; P = 0·01; I2 = 87·7 %; P-heterogeneity < 0·001), without any significant effect on blood urea nitrogen (BUN), glomerular filtration rate or microalbuminuria. No significant improvement was found on liver biomarkers following probiotics/synbiotics supplementation. The subgroup analysis showed a significant improvement in BUN when follow-up duration lasted for 12 weeks or more (WMD = −1·215 mg/dl, 95 % CI −1·933, −0·496; P = 0·001) and in creatinine levels in patients with renal dysfunction (WMD = −0·209 mg/dl, 95 % CI −0·322, −0·096; P < 0·001). Our results are insufficient to advocate the use of probiotics/synbiotics for improving renal or liver function in patients with T2DM. Indeed, due to the low certainty of evidence, these findings need to be affirmed in further high-quality RCT.
Tramadol is used worldwide and is listed in many medical guidelines to treat both acute and chronic pains. There is a growing evidence of abuse of tramadol in some African and West Asian countries. Tramadol has some side effects. The present study designed to follow up the treatment of the cellular responses which might be induced in the kidney of tramadol mice. Treated mice received daily injection of tramadol dose (125 μg/100 g b.wt) for 20 and 40 days. Other mice received tramadol for 40 days and then were divided into three groups: the first received distilled water, the second received Lagenaria siceraria, and the third received melatonin daily for 40 days. Both the daily injection of tramadol for 20 and 40 days resulted in radical, extensive, and severe alterations in the normal histological architecture of the kidney. Treatment with Lagenaria siceraria or melatonin after tramadol administration for a long-term, markedly changed the collagen content and other chemical components, that may reach nearly normal levels. Such findings propose that although tramadol has many cytological and histopathological side effects on the kidneys of male mice, the treatments via Lagenaria siceraria and melatonin have effective therapeutic impacts on the tramadol side effects.
Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6–13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.
Concurrent three-dimensional imaging of the renal vascular and tubular systems on the whole-kidney scale with capillary level resolution is labor-intensive and technically difficult. Approaches based on vascular corrosion casting and X-ray micro computed tomography (μCT), for example, suffer from vascular filling artifacts and necessitate imaging with an additional modality to acquire tubules. In this work, we report on a new sample preparation, image acquisition, and quantification protocol for simultaneous vascular and tubular μCT imaging of whole, uncorroded mouse kidneys. The protocol consists of vascular perfusion with the water-soluble, aldehyde-fixable, polymeric X-ray contrast agent XlinCA, followed by laboratory-source μCT imaging and structural analysis using the freely available Fiji/ImageJ software. We achieved consistent filling of the entire capillary bed and staining of the tubules in the cortex and outer medulla. After imaging at isotropic voxel sizes of 3.3 and 4.4 μm, we segmented vascular and tubular systems and quantified luminal volumes, surface areas, diffusion distances, and vessel path lengths. This protocol permits the analysis of vascular and tubular parameters with higher reliability than vascular corrosion casting, less labor than serial sectioning and leaves tissue intact for subsequent histological examination with light and electron microscopy.
Kidneys are sensitive to damage by drugs, with up to 20% of episodes of drug-induced acute renal failure. New prescribers must be able to identify these patients and eliminate these risks when possible; avoid potentially nephrotoxic drugs; and adjust drug doses in patients, where necessary, in those with pre-existing renal impairment to avoid drug accumulation and toxicity. This chapter identifies high-risk drug classes to avoid in renal failure, top tips to avoid drug toxicity, how to treat patients in chronic renal failure and provides a quick reference guide for drug dose reduction in those with renal impairment.
Children with CHD who undergo cardiopulmonary bypass are at an increased risk of acute kidney injury. This study evaluated the association of end-organ specific injury plasma biomarkers for brain: glial fibrillary acidic protein and heart: Galectin 3, soluble suppression of tumorgenicity 2, and N-terminal pro b-type natriuretic peptide with acute kidney injury in children undergoing cardiopulmonary bypass.
Materials and Methods:
We enrolled consecutive children undergoing cardiac surgery with cardiopulmonary bypass. Blood samples were collected pre-bypass in the operating room and in the immediate post-operative period. Acute kidney injury was defined as a rise of serum creatinine ≥50% from pre-operative baseline within 7 days after surgery.
Results:
Overall, 162 children (mean age 4.05 years, sd 5.28 years) were enrolled. Post-operative acute kidney injury developed in 55 (34%) children. Post-operative plasma glial fibrillary acidic protein levels were significantly higher in patients with acute kidney injury (median 0.154 (inter-quartile range 0.059–0.31) ng/ml) compared to those without acute kidney injury (median 0.056 (inter-quartile range 0.001–0.125) ng/ml) (p = 0.043). After adjustment for age, weight, and The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category, each natural log increase in post-operative glial fibrillary acidic protein was significantly associated with a higher risk for subsequent acute kidney injury (adjusted odds ratio glial fibrillary acidic protein 1.25; 95% confidence interval 1.01–1.59). Pre/post-operative levels of galectin 3, soluble suppression of tumorgenicity 2, and N-terminal pro b-type natriuretic peptide did not significantly differ between patients with and without acute kidney injury.
Conclusions:
Higher plasma glial fibrillary acidic protein levels measured in the immediate post-operative period were independently associated with subsequent acute kidney injury in children after cardiopulmonary bypass. Elevated glial fibrillary acidic protein likely reflects intraoperative brain injury which may occur in the context of acute kidney injury-associated end-organ dysfunction.
The management of fluid overload after congenital heart surgery has been limited to diuretics, fluid restriction, and dialysis. This study was conducted to determine the association between peritoneal dialysis and important clinical outcomes in children undergoing congenital heart surgery.
Methods:
A retrospective review was conducted to identify patients under 18 years of age who underwent congenital heart surgery. The data were obtained over a 16-year period (1997–2012) from the Kids’ Inpatient Database. Data analysed consisted of demographics, diagnoses, type of congenital heart surgery, length of stay, cost of hospitalisation, and mortality. Logistic regression was performed to determine factors associated with peritoneal dialysis.
Results:
A total of 46,176 admissions after congenital heart surgery were included in the study. Of those, 181 (0.4%) utilised peritoneal dialysis. The mean age of the peritoneal dialysis group was 7.6 months compared to 39.6 months in those without peritoneal dialysis. The most common CHDs were atrial septal defect (37%), ventricular septal defect (32.6%), and hypoplastic left heart syndrome (18.8%). Univariate analyses demonstrated significantly greater length of stay, cost of admission, and mortality in those with peritoneal dialysis. Regression analyses demonstrated that peritoneal dialysis was independently associated with significant decrease in cost of admission (−$57,500) and significant increase in mortality (odds ratio 1.5).
Conclusions:
Peritoneal dialysis appears to be used in specific patient subsets and is independently associated with decreased cost of stay, although it is associated with increased mortality. Further studies are needed to describe risks and benefit of peritoneal dialysis in this population.