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ABSTRACT Arthropods have integrated digestive and renal systems, which function to acquire and maintain homeostatically the substances they require for survival. The cryptonephridial complex (CNC) is an evolutionary novelty in which the renal organs and gut have been dramatically reorganised. Parts of the renal or Malpighian tubules (MpTs) form a close association with the surface of the rectum, and are surrounded by a novel tissue, the perinephric membrane, which acts to insulate the system from the haemolymph and thus allows tight regulation of ions and water into and out of the CNC. The CNC can reclaim water and solutes from the rectal contents and recycle these back into the haemolymph. Fluid flow in the MpTs runs counter to flow within the rectum. It is this countercurrent arrangement that underpins its powerful recycling capabilities, and represents one of the most efficient water conservation mechanisms in nature. CNCs appear to have evolved multiple times, and are present in some of the largest and most evolutionarily successful insect groups including the larvae of most Lepidoptera and in a major beetle lineage (Cucujiformia + Bostrichoidea), suggesting that the CNC is an important adaptation. Here we review the knowledge of this remarkable organ system gained over the past 200 years. We first focus on the CNCs of tenebrionid beetles, for which we have an in‐depth understanding from physiological, structural and ultrastructural studies (primarily in Tenebrio molitor), which are now being extended by studies in Tribolium castaneum enabled by advances in molecular and microscopy approaches established for this species. These recent studies are beginning to illuminate CNC development, physiology and endocrine control. We then take a broader view of arthropod CNCs, phylogenetically mapping their reported occurrence to assess their distribution and likely evolutionary origins. We explore CNCs from an ecological viewpoint, put forward evidence that CNCs may primarily be adaptations for facing the challenges of larval life, and argue that their loss in many aquatic species could point to a primary function in conserving water in terrestrial species. Finally, by considering the functions of renal and digestive epithelia in insects lacking CNCs, as well as the typical architecture of these organs in relation to one another, we propose that ancestral features of these organs predispose them for the evolution of CNCs. [ABSTRACT FROM AUTHOR]

COVID-19 is primarily a respiratory disease, but numerous studies have indicated the involvement of various organ systems during the course of illness. We conducted a comprehensive review of atypical complications of COVID-19 with their incidence range (IR) and their impact on hospitalization and mortality rates. We identified 97 studies, including 55 research articles and 42 case studies. We reviewed four major body organ systems for various types of atypical complications: (i) Gastro-intestinal (GI) and hepatobiliary system, e.g., bowel ischemia/infarction (IR: 1.49–83.87%), GI bleeding/hemorrhage (IR: 0.47–10.6%), hepatic ischemia (IR: 1.0–7.4%); (ii) Neurological system, e.g., acute ischemic stroke/cerebral venous sinus thrombosis/cerebral hemorrhage (IR: 0.5–90.9%), anosmia (IR: 4.9–79.6%), dysgeusia (IR: 2.8–83.38%), encephalopathy/encephalitis with or without fever and hypoxia (IR: 0.19–35.2%); (iii) Renal system, e.g., acute kidney injury (AKI)/acute renal failure (IR: 0.5–68.8%); (iv) Cardiovascular system, e.g., acute cardiac injury/non-coronary myocardial injury (IR: 7.2–55.56%), arrhythmia/ventricular tachycardia/ventricular fibrillation (IR: 5.9–16.7%), and coagulopathy/venous thromboembolism (IR: 19–34.4%). This review encourages and informs healthcare practitioners to keenly monitor COVID-19 survivors for these atypical complications in all major organ systems and not only treat the respiratory symptoms of patients. Post-COVID effects should be monitored, and follow-up of patients should be performed on a regular basis to check for long-term complications. [ABSTRACT FROM AUTHOR]

The angiotensin-converting enzyme (ACE) gene (ACE) insertion/deletion (I/D) polymorphism raises the possibility of personalising ACE inhibitor therapy to optimise its efficiency and reduce side effects in genetically distinct subgroups. However, the extent of its influence among these subgroups is unknown. Therefore, we extended our computational model of blood pressure regulation to investigate the effect of the ACE I/D polymorphism on haemodynamic parameters in humans undergoing antihypertensive therapy. The model showed that the dependence of blood pressure on serum ACE activity is a function of saturation and therefore, the lack of association between ACE I/D and blood pressure levels may be due to high ACE activity in specific populations. Additionally, in an extended model simulating the effects of different classes of antihypertensive drugs, we explored the relationship between ACE I/D and the efficacy of inhibitors of the renin–angiotensin–aldosterone system. The model predicted that the response of cardiovascular and renal parameters to treatment directly depends on ACE activity. However, significant differences in parameter changes were observed only between groups with high and low ACE levels, while different ACE I/D genotypes within the same group had similar changes in absolute values. We conclude that a single genetic variant is responsible for only a small fraction of heredity in treatment success and its predictive value is limited.

COVID-19 is primarily a respiratory disease, but numerous studies have indicated the involvement of various organ systems during the course of illness. We conducted a comprehensive review of atypical complications of COVID-19 with their incidence range (IR) and their impact on hospitalization and mortality rates. We identified 97 studies, including 55 research articles and 42 case studies. We reviewed four major body organ systems for various types of atypical complications: (i) Gastro-intestinal (GI) and hepatobiliary system, e.g., bowel ischemia/infarction (IR: 1.49–83.87%), GI bleeding/hemorrhage (IR: 0.47–10.6%), hepatic ischemia (IR: 1.0–7.4%); (ii) Neurological system, e.g., acute ischemic stroke/cerebral venous sinus thrombosis/cerebral hemorrhage (IR: 0.5–90.9%), anosmia (IR: 4.9–79.6%), dysgeusia (IR: 2.8–83.38%), encephalopathy/encephalitis with or without fever and hypoxia (IR: 0.19–35.2%); (iii) Renal system, e.g., acute kidney injury (AKI)/acute renal failure (IR: 0.5–68.8%); (iv) Cardiovascular system, e.g., acute cardiac injury/non-coronary myocardial injury (IR: 7.2–55.56%), arrhythmia/ventricular tachycardia/ventricular fibrillation (IR: 5.9–16.7%), and coagulopathy/venous thromboembolism (IR: 19–34.4%). This review encourages and informs healthcare practitioners to keenly monitor COVID-19 survivors for these atypical complications in all major organ systems and not only treat the respiratory symptoms of patients. Post-COVID effects should be monitored, and follow-up of patients should be performed on a regular basis to check for long-term complications.

The use of a circularly polarized patch antenna array to detect kidney cancer by microwave techniques is proposed in this paper. A four-element linear antenna array is designed and fabricated at the ISM frequency of 2.4 GHz. The dimensions of the antenna array are 200 mm $\times78$ mm. The single element is a square patch with side length of 30 mm. The distance between patches is chosen to be 20 mm which ensures that mutual coupling between any two adjacent patches is less than 20 dBs. The substrate is a FR-4 material of relative permittivity 4.3 and thickness 1.6 mm. The circular polarization has an axial ratio of 0.8 dB at 2.4 GHz. The bandwidth at S11 = −10 dB is 7.23 %. Renal system phantom consisting of kidney cortex, renal capsule, ureter, adrenal gland, muscle, fat, and skin is used. Four stages of renal cancer tumors are considered depending upon the tumor size in each stage. The presence of a tumor causes an increase in the reflection coefficient (S11) and a shift in resonance frequency, which can be used to identify cancer. The increase in reflection coefficient and the shift in resonance frequency are calculated for each stage of the cancer tumors. The shift in resonance frequency for the early stages is too small. Therefore, detection depends mainly on the increase in S11. The shift in resonance frequency and increase in S11 are large for advanced stages of the tumor, which makes detection easier. Computed specific absorption rate (SAR) is found to be less than the safety levels, which means this technique is safe to use. Overall, this work suggests a new simple detection technique of kidney cancer. The advantages of this technique are: safe, compact, fast, inexpensive, comfortable examination, non-invasive, and finally non- ionizing radiation during measurement.

Hypertension is a multifactorial disease arising from complex pathophysiological pathways. Individual characteristics of patients result in different responses to various classes of antihypertensive medications. Therefore, evaluating the efficacy of therapy based on in silico predictions is an important task. This study is a continuation of research on the modular agent-based model of the cardiovascular and renal systems (presented in the previously published article). In the current work, we included in the model equations simulating the response to antihypertensive therapies with different mechanisms of action. For this, we used the pharmacodynamic effects of the angiotensin II receptor blocker losartan, the calcium channel blocker amlodipine, the angiotensin-converting enzyme inhibitor enalapril, the direct renin inhibitor aliskiren, the thiazide diuretic hydrochlorothiazide, and the β-blocker bisoprolol. We fitted therapy parameters based on known clinical trials for all considered medications, and then tested the model’s ability to show reasonable dynamics (expected by clinical observations) after treatment with individual drugs and their dual combinations in a group of virtual patients with hypertension. The extended model paves the way for the next step in personalized medicine that is adapting the model parameters to a real patient and predicting his response to antihypertensive therapy. The model is implemented in the BioUML software and is available at https://gitlab.sirius-web.org/virtual-patient/antihypertensive-treatment-modeling.

The coexistence of empyema, nephropleural fistula and perinephric abscess is rare and presents diagnostic challenges, especially when patients exhibit atypical or mild symptoms. This case report details a female in her early 90s who presented with 3 weeks of chest pain and was found to have a left-sided pleural effusion. Further imaging revealed additional findings of a left-sided nephropleural fistula and left perinephric collection. The patient underwent thoracentesis and video-assisted thoracoscopic surgery, with cultures growing Streptococcus Anginosus Subsequently, she underwent a left nephrectomy, with pathology findings consistent with chronic pyelonephritis and a fistulous tract. The patient was discharged on intravenous antibiotics. Follow-up imaging showed improvement. The patient completed the antibiotic course and reported symptom resolution 2 weeks after discharge., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Granulomatosis polyangiitis (GPA) is an autoimmune condition causing inflammation of small blood vessels. It is a rare disorder that may affect various parts of the body. The diagnosis is often based on clinical examination, laboratory investigations and tissue biopsy. In about 10-20% of patients, the anti-neutrophilic cytoplasmic antibody (ANCA) can be negative, and histology maybe inconclusive, which can lead to diagnostic uncertainty. Failure to treat vasculitis can lead to morbidity and even mortality. We present a case report of a gentleman who was presented with an airway emergency with inflammation of the nasal cavity and subglottic involvement amounting to airway stenosis. His ANCA was negative and tissue biopsy from the subglottis was inconclusive. He underwent urgent dilatation of his airway, local therapies to the nose and was commenced on 10 cycles of cyclophosphamide. A follow-up of over 4 years has not shown any relapse of his disease clinically or biochemically. We discuss the clinical findings, diagnostic dilemma and multidisciplinary management of this life-threatening condition., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Osmoregulation is influenced by a wide variety of biotic and abiotic variables, and maintenance of systemic osmoregulatory homeostasis is critical to insect fitness. Because insects are so small, accurately quantifying renal organ function is technically challenging, and often requires specialized equipment. On top of this, nearly a century of toiling in the laboratory has led to a wide and still growing variety of methods that can be difficult for novice researchers to disentangle. Here, we provide a reference guide for the most used in vitro approaches in the study of insect osmoregulation, including the Ramsay assay, Ussing chamber, epithelial potential measurement, scanning ion-selective electrode technique, and hindgut assays. Along the way, we highlight the history of each methodological innovation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Mycobacterium chelonae ( M. chelonae ) is a member of the rapidly growing non-tuberous mycobacteria and can cause disseminated tissue infection, particularly, in the limbs. We reviewed medical records of two kidney transplant patients. We describe their background disease and transplantation details, with the use of immunosuppressive medication. We also discuss the presentation of M. chelonae infection and treatment. Both patients received deceased brain-dead donor kidney transplants for end-stage kidney disease. Both developed cutaneous manifestations of M. chelonae , progressing to disseminated infections. Case 1 was on low-dose prednisolone (2 mg) and tacrolimus, whereas, case 2 received varying doses of prednisolone (5-40 mg) and sirolimus. Antibiotics advised by infectious disease specialists were initiated within a month of skin lesion appearance. Effective treatment involved a combination of antibiotics such as clarithromycin, azithromycin, linezolid and tigecycline. These cases underline the efficacy of clarithromycin and azithromycin as long-term antibiotic treatment, with linezolid and tigecycline for management of acute dissemination., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

It is highly uncommon for solid tumours to metastasise to the testis. Here, we report a case of metachronous testicular metastasis from clear cell renal cell cancer (RCC) in a male patient 3 years after left radical nephrectomy. Ultrasound of the scrotum showed a 3.5 cm × 4 cm left testicular mass with normal serum tumour markers. The patient underwent left high inguinal orchidectomy, which revealed metastatic renal cell carcinoma. CT of the chest, abdomen and pelvis showed multiple liver secondaries. Cabozantinib was started for metastatic RCC, and the patient showed no evidence of disease progression in a follow-up of 1 year., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Drug abuse has become a public health concern. The misuse of ketamine, a psychedelic substance, has increased worldwide. In addition, the co-abuse with alcohol is frequently identified among misusers. Considering that ketamine and alcohol share several pharmacological targets, we hypothesize that the consumption of both psychoactive substances may synergically intensify the toxicological consequences, both under the effect of drugs available in body systems and during withdrawal. The aim of this review is to examine the toxicological mechanisms related to ketamine plus ethanol co-abuse, as well the consequences on cardiorespiratory, digestive, urinary, and central nervous systems. Furthermore, we provide a comprehensive discussion about the probable sites of shared molecular mechanisms that may elicit additional hazardous effects. Finally, we highlight the gaps of knowledge in this area, which deserves further research. [ABSTRACT FROM AUTHOR]

Introduction: Each kidney has a single renal artery. The kidney receives about 20% of the cardiac output. Renal artery variations are a common entity that becomes an important consideration while performing renal surgeries. Aim: To study the variability of the renal arteries concerning emergence, diameter, and length. Materials and Methods: This cross-sectional study was conducted in the Department of Anatomy of VMGMC, Solapur, Maharashtra, India for three years, from August 2012 to September 2015. The pattern of the renal artery in humans were studied for emergence, length, and it’s branching by dissection method in 75 human cadavers. A thorough dissection of these specimens were done by routine dissection instruments. Statistical analysis of specimens of both sides were carried out by Epi info 7.2.5.0. Unpaired t-test was applied and p-value was derived for the length and diameter of the artery. Results: Right renal artery 37 (49.4%) had proximal origin in relation to the left renal artery in a greater number of specimens. Average distance between the superior mesenteric and the left renal artery was 11.03±4.8 mm. The average diameter of right renal artery was 6.65±1.6 mm. The average length of the Right Renal Artery (RRA) 39.5±11.8 mm was significantly greater than Left Renal Artery (LRA) 30.7±12.6 mm, p-value

Aquaporins (AQP) are transmembrane proteins that function as channels for water molecules' movement. It is conserved across bacteria, plants and animals. It helps in thermoregulation during extreme climatic conditions. So, this study focuses on the expression of AQP1, AQP2 and AQP3 in the ureter and bladder tissues of goat (Capra hircus) during winter, spring and summer seasons. The study was conducted on goats (n=30) to investigate the expression of AQP (water channels) in ureter and urinary bladder and metabolic and hormonal influence by aquaporins. mRNAs were isolated from ureter and urinary bladder tissues and cDNA were synthesized for RT-PCR expression studies. Biochemical parameters were studied in the blood samples. AQP1 mRNA expression was non-significant in goat ureters but considerably greater (p<0.05) in the urine bladder during summer compared to winter. During the summer, both ureter and urinary bladder tissue samples showed increased expression of AQP2 and AQP3. Aquaporins 3 had significantly greater (p<0.05) mRNA expression in the ureter and urine bladder than Aquaporins 1 and 2 throughout the summer season. The significant (p<0.05) increase in physiological responses, haematological counts and blood biochemical components seen in goats throughout the summer season. Finally, it concludes that AQP and their role in thermotolerance and direct association with effective water balance mechanisms in the body via expression of AQP in different extreme climatic conditions. • AQP1 mRNA expression was greater in urine bladder during summer. • During summer, ureter & urinary bladder showed increased expression of AQP2 and AQP3. • AQP3 had greater (p<0.05) mRNA expression in ureter & urine bladder than AQP1 & AQP2 throughout summer. • The (p<0.05) increase in physiological responses, haematological counts & biochemical components throughout summer. • It demonstrates thermotolerance & direct association with water balance in body. [ABSTRACT FROM AUTHOR]

A 17-year-old African American male high school athlete was diagnosed with an acute kidney injury secondary to severe dehydration following a football game. After administering intravenous fluids and obtaining multiple blood tests, the athlete was released from the emergency department. Following the care in the emergency department, the athlete was restricted from all physical exertion for 2 weeks. Furthermore, after a gradual, monitored return-to-play protocol, he returned back to sport without complications. This case is unique in its presentation because acute kidney injury is often found, in sports medicine literature, to occur in older endurance athletes; it is rarer to encounter it in the adolescent population within a team sport. This case also highlights the need for interprofessional collaboration in order to enhance and facilitate a safe return to play for all athletes. [ABSTRACT FROM AUTHOR]

Background: Cells trigger caspase‐mediated apoptosis to eliminate themselves from the system when tissue needs to be sculptured, or they detect any abnormality within them, thus preventing irreparable damage to the host. However, nonapoptotic activities of caspases are also involved in many cellular functions. Interestingly, Drosophila Malpighian tubules (MTs) express apoptotic proteins, without succumbing to cell death. Results: We show apoptosis‐independent role of executioner caspase‐3, Drice, in MT morphogenesis. Drice is required for precise cytoskeleton organization and convergent extension, failing which morphology, size, cell number, and arrangement get affected. Furthermore, characteristic stellate cell shape transformation in MTs is also governed by Drice. Genetic interaction study shows that Drice mediates its action by regulating Rho1GTPase functionally, and localization of polarity protein Disc large. Subsequently, downregulation of Rho1GTPase in Drice mutants significantly rescues the cystic MTs phenotype. The study shows a mechanism by which Drice governs tubulogenesis via Rho1GTPase‐mediated coordinated organization of actin cytoskeleton and membrane stabilization. Conclusion: Collectively our findings suggest a nonapoptotic function of caspase‐3 in fine‐tuning of cellular rearrangement during tubule development, and these results will add to the growing understanding of diverse roles of caspases during its evolution in metazoans. Key Findings: Collectively our findings suggest a non‐apoptotic function of caspase‐3 in the fine tuning of cellular rearrangement during tubule development, and these results will add to the growing understanding of diverse roles of caspases during its evolution in metazoans. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: None declared.

We present a case of a man in his 40s with pulmonary-renal syndrome due to myeloperoxidase-positive antineutrophil cytoplasmic antibodies-associated vasculitis and concurrent cold agglutinin disease, a combination that has not yet been described in the literature. The fulminant course of the disease, including the need for kidney replacement therapy and mechanical ventilation posed a significant treatment challenge due to haemolytic complications., Competing Interests: Competing interests: JL received consulting/lecture fees from Vifor Pharma., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A man in his 40s with end-stage kidney disease due to IgA nephropathy and receiving peritoneal dialysis presented with a 1-week history of breathlessness, cough and nosebleeds. CT scan of the chest revealed ground glass changes while blood tests indicated elevated inflammatory markers and a negative vasculitis screen. This included negative ANCA and anti-GBM antibodies. Initial treatment for suspected atypical pneumonia with antibiotics yielded no clinical improvement.Over the course of the admission, his symptoms progressively worsened, leading to oxygen dependency with a FiO2 of 40% and episodes of haemoptysis. Suspicions of pulmonary vasculitis arose due to clinical deterioration, prompting consultation with a tertiary vasculitis centre. It was subsequently concluded that the clinical and radiological findings correlated with ANCA-negative pulmonary vasculitis or a rare case of IgA-associated pulmonary capillaritis. Treatment with methylprednisolone and rituximab led to significant improvement, allowing rapid oxygen withdrawal. The patient was discharged with a tapering prednisolone regimen., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Here we present a modular agent-based mathematical model of the human cardiovascular and renal systems. It integrates the previous models primarily developed by A. C. Guyton, F. Karaaslan, K. M. Hallow, and Y. V. Solodyannikov. We performed the model calibration to find an equilibrium state within the normal vital sign ranges for a healthy adult. We verified the model's abilities to reproduce equilibrium states with abnormal physiological values related to different combinations of cardiovascular diseases (such as systemic hypertension, chronic heart failure, pulmonary hypertension, etc.). For the model creation and validation, we involved over 200 scientific studies covering known models of the human cardiovascular and renal functions, biosimulation platforms, and clinical measurements of physiological quantities in normal and pathological conditions. We compiled detailed documentation describing all equations, parameters and variables of the model with justification of all formulas and values. The model is implemented in BioUML and available in the web-version of the software. [ABSTRACT FROM AUTHOR]

Here we present a modular agent-based mathematical model of the human cardiovascular and renal systems. It integrates the previous models primarily developed by A. C. Guyton, F. Karaaslan, K. M. Hallow, and Y. V. Solodyannikov. We performed the model calibration to find an equilibrium state within the normal vital sign ranges for a healthy adult. We verified the model’s abilities to reproduce equilibrium states with abnormal physiological values related to different combinations of cardiovascular diseases (such as systemic hypertension, chronic heart failure, pulmonary hypertension, etc.). For the model creation and validation, we involved over 200 scientific studies covering known models of the human cardiovascular and renal functions, biosimulation platforms, and clinical measurements of physiological quantities in normal and pathological conditions. We compiled detailed documentation describing all equations, parameters and variables of the model with justification of all formulas and values. The model is implemented in BioUML and available in the web-version of the software.

Vitamin D regulates the calcium and phosphorus balance in the body. The activated form of vitamin D (1 α,25-dihydroxyvitamin D) binds to vitamin D receptor which regulates genes that control cell proliferation, differentiation and apoptosis. In the cardiovascular system, the vitamin D receptor is present in cardiomyocytes and the arterial wall. A clear correlation between vitamin D level and cardiovascular diseases is established. Vitamin D deficiency affects the renin-angiotensin system leading to ventricular hypertrophy and eventually to stroke. While clinical trials highlighted the positive effects of vitamin D supplements on cardiovascular disease these still need to be confirmed. This review outlines the association between vitamin D and cardiovascular and renal disease summarising the experimental data of selective cardiovascular disorders. [ABSTRACT FROM AUTHOR]

Even though scientific literature shows numerous heath complications and performance decrements associated with rapid weight loss (RWL), its prevalence remains exceedingly high across various combat sports. The aim of this study was to thoroughly search the existing literature to explore the influence of RWL on kidney function in Olympic and non-Olympic combat sport athletes. PubMed and Web of Science were searched for the relevant studies. Only original articles published from 2005 onwards, written in English, that included healthy males and females who prompted ~5% weight loss within a week or less, were included in the study. Retrieved studies showed that creatinine, blood urea nitrogen and urine specific gravity values were significantly increased after RWL in the majority of the included studies. This observation indicates that RWL caused dehydration and subsequent acute kidney damage despite various degrees of weight lost during the RWL phase, which can lead to adverse events in other body systems. Alternative methods of weight reduction that prioritize athletes’ health should be considered. [ABSTRACT FROM AUTHOR]

Body tissues are frequently exposed to stress, from toxic byproducts generated during cellular metabolism through to infection or wounding. Although it is well-established that tissues respond to exogenous injury by rapidly upregulating cytoprotective machinery, how energetically demanding tissues -- vulnerable to persistent endogenous insult -- withstand stress is poorly understood. Here, we show that the cytoprotective factors Nrf2 and Gadd45 act within a specific renal cell subtype, the energetically and biosynthetically active 'principal' cells, to drive stress resilience during Drosophila renal development and homeostasis. Renal tubules lacking Gadd45 exhibit striking morphogenetic defects (with cell death, inflammatory infiltration and reduced ploidy) and accumulate significant DNA damage in post-embryonic life. In parallel, the transcription factor Nrf2 is active during periods of intense renal physiological activity, where it protects metabolically active renal cells from oxidative damage. Despite its constitutive nature, renal cytoprotective activity must be precisely balanced and sustained atmodest sub-injury levels; indeed, further experimental elevation dramatically perturbs renal development and function. We suggest that tissues requiring long-term protection must employ restrained cytoprotective activity, whereas higher levels might only be beneficial if activated transiently pre-emptive to exogenous insult. [ABSTRACT FROM AUTHOR]

Background: Achieving target blood glucose in type 2 diabetes patients with hypertension remains a challenge despite the availability of different classes of drugs to treat these conditions. Objective: to assess the level of glycemic control and identify associated factors among ambulatory type 2 diabetes patients with hypertension co-morbidity. Methods: We conducted a hospital based cross-sectional study from April 4 to May 11, 2016 among ambulatory type 2 diabetes patients with hypertension comorbidity at Jimma University Medical Center. We collected data on patient demographics, diabetes complications, and treatments using pretested questionnaire and data extraction format from a total of 300 eligible patients. We included consecutive patients that visited the hospital during the study period. We performed statistical analysis using SPSS version 21. Logistic regression analyses were done to identify the factors associated with poor glycemic control. P-value

Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of renal dysfunction. It is the most common genetic disorder leading to end-stage kidney disease requiring dialysis. ADPKD is a multisystem disease and is linked to several extra renal abnormalities. Splenic artery aneurysms are rare in the general population. ADPKD is associated with cerebral artery aneurysms. However, splenic artery aneurysms are not a well-recognised complication of ADPKD. We report an unusual case of a splenic artery aneurysm found incidentally on abdominal CT imaging of a woman with known ADPKD., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Renal artery stenosis can complicate the management of heart failure with reduced ejection fraction, as it is a conventional contraindication to the use of ACE inhibitors. We report a case in which bilateral renal artery revascularisation allowed the safe reintroduction of enalapril (and subsequently sacubitril valsartan) in a patient with severe left ventricular systolic dysfunction. There is a role for renal artery angioplasty in selected patients to allow optimal medical therapy for patients with heart failure due to impaired systolic function., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The angiotensin-converting enzyme (ACE) gene ( ACE ) insertion/deletion ( I/D ) polymorphism raises the possibility of personalising ACE inhibitor therapy to optimise its efficiency and reduce side effects in genetically distinct subgroups. However, the extent of its influence among these subgroups is unknown. Therefore, we extended our computational model of blood pressure regulation to investigate the effect of the ACE I/D polymorphism on haemodynamic parameters in humans undergoing antihypertensive therapy. The model showed that the dependence of blood pressure on serum ACE activity is a function of saturation and therefore, the lack of association between ACE I/D and blood pressure levels may be due to high ACE activity in specific populations. Additionally, in an extended model simulating the effects of different classes of antihypertensive drugs, we explored the relationship between ACE I/D and the efficacy of inhibitors of the renin-angiotensin-aldosterone system. The model predicted that the response of cardiovascular and renal parameters to treatment directly depends on ACE activity. However, significant differences in parameter changes were observed only between groups with high and low ACE levels, while different ACE I/D genotypes within the same group had similar changes in absolute values. We conclude that a single genetic variant is responsible for only a small fraction of heredity in treatment success and its predictive value is limited., Competing Interests: Authors Elena Kutumova, Ruslan Sharipov, and Fedor Kolpakov were employed by Biosoft.Ru, Ltd. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 The Authors.)

We present a case involving a male patient in his 30s who was admitted to hospital due to recurrent episodes of hypokalaemia over the past 5 years. His medical history revealed hypertension, attention deficit hyperactivity disorder (ADHD), autism, and paranoia. He was taking citalopram, ramipril, amlodipine, and pramipexole. Tests indicated normal levels of aldosterone/renin ratio and plasma metanephrines. On reviewing his dietary history, it was noted that he consumed 3 to 3.5 L of cola-flavoured drinks on a daily basis. Normal potassium levels were achieved after a significant reduction in cola-flavoured drinks intake and potassium replacement. Subsequent outpatient clinic follow-up revealed that normal potassium levels were maintained even after the patient ceased taking potassium replacement tablets. Given the rarity of hypokalaemia associated with fizzy drinks, the underlying mechanism for this association remains unclear. In this case report, we attempt to provide a possible explanation for the involved mechanisms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Genetic focal segmental glomerulosclerosis (FSGS) is an important but underestimated cause of inherited proteinuric chronic kidney disease (CKD) in adults. We discuss a case of familial CKD due to inverted formin 2 ( INF2 ) gene mutation, where three siblings had disparate phenotypic presentations ranging from CKD with subnephrotic proteinuria to nephrotic-range proteinuria with collapsing FSGS on kidney biopsy over a period of 8 years. The youngest sibling was the index case. The family agreed to undergo genetic testing only after two more siblings were diagnosed with kidney disease. This case highlights how clinical heterogeneity, absence of family history in the index case, initial lack of specific biopsy-proven diagnosis and reluctance to undergo genetic testing can delay the diagnosis of genetic kidney disease in adults., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Flexible ureteroscopy involves expensive equipment that is expensive to repair. This study aimed to investigate the effects of cleavage by various tools on the laser fiber tip and to determine the extent of damage incurred to the laser passing through the working channel and firing at different degrees of deflection. Materials and methods: We investigated the effect of cleavage on Lumenis Slimline reusable fibers (272 and 365 μm) as performed by four cleavage tools: a scribe pen, a surgical blade, suture scissors, and ceramic scissors. Following cleavage, we recorded the pattern of light dispersion and power output. The laser fibers passed through the working channel at various. Results: The ceramic scissors provided the best pattern of light dispersion and the highest power output. The suture scissors provided unacceptable levels of light dispersion. The 272 μm fiber was able to pass through the working channel at 30 and 45 degrees of deflection. The 365 μm laser fiber was only able to pass through the working channel at 30 degrees of deflection. There was no breakage of the laser fiber at any of the degrees of deflection evaluated. Conclusions: Analysis showed that the ceramic scissors were the best tool for cleaving Lumenis Slimline reusable fibers and that suture scissors were unacceptable. We also found that the deflection angle that causes damage to the working channel by laser insertion is dependent on both the size of the laser fiber and the degree of bending. Firing the laser during scope deflection could be performed safely at any degree of deflection, even with a high laser power of 40 W for a duration of 30 s

Doping tests for the illegal use of erythropoiesis-stimulating agents (ESAs) have been developed. We developed a new Western blotting method to detect and distinguish endogenous erythropoietin (Epo, 35-38 kDa) and exogenous ESAs (epoetin α and β, 38-42 kDa; darbepoetin α, 47-50 kDa; epoetin β pegol, 93-110 kDa). Epo and ESAs are glycoproteins and deglycosylation using peptide-N-glycosidase F shifted all Epo and ESA bands except epoetin β pegol to 22 kDa. We cut the bands of Epo and ESAs from SDS-PAGE gels and analyzed them by Liquid Chromatography/Mass Spectrometry (LC/MS). LC/MS detected all endogenous Epo and exogenous ESAs as deglycosylated 22 kDa Epo, indicating that LC/MS analysis could confirm the presence of Epo or ESA, but could not distinguish between endogenous Epo and exogenous ESAs. We propose the following Epo doping tests: 1) detect Epo or ESAs by Western blotting of the glycosylated form; 2) increase the reliability by the band shift following deglycosylation; and 3) complete confirmation of Epo or ESA by LC/MS analysis using cut gels. One of the advantages of our method is that pre-purification of samples for Epo is not required in our Western blotting.

Background: Paediatric sepsis remains a major public health problem with significant morbidity and mortality especially in developing countries. Clinical symptoms associated with sepsis are unreliable and laboratory parameters unspecific, making an early diagnosis of paediatric sepsis difficult. The lack of definitive biomarker(s) for early diagnosis of sepsis further leads to the misuse of antibiotics. Diagnosis based on a single biomarker does not provide adequate accuracy. Subsequently, combining multiple biomarkers into a single score will help clinicians make a better diagnostic judgment. Aims: This study for the first time evaluated the individual and combined diagnostic accuracy of procalcitonin (PCT), presepsin (sCD14-ST) and high sensitive C-reactive protein (hs-CRP) using a Bioscore model. Materials and methods: In a case control study conducted at the Paediatric Emergency Unit (PEU) and the Mother and Baby Unit (MBU) of Komfo Anokye Teaching Hospital (KATH), sixty (60) paediatric subjects aged zero to six (0–6) years, were diagnosed with sepsis using case-definition by the national neonatal bloodstream infection surveillance and Pediatric Sepsis Consensus Congress. Thirty (30) other paediatric subjects, aged and sex matched without sepsis or inflammatory conditions were used as controls. One-time blood sample was taken at the time of admission for blood culture and measurement of PCT, hs-CRP, and presepsin by ELISA. The Statistical Package for Social Sciences (SPSS release 20.0, Copyright ©SPSS Inc.) was used for analysis. Results: Out of the sixty septic paediatric subjects, 14 patients (23.3%) had positive blood cultures (LCS) and 46 (76%) had negative for blood cultures (CS). Klebsiella spp. recorded the highest median levels of PCT, and hs-CRP while Pseudo. Aeruginasa recorded the highest of sCD14-ST levels. Significant elevations in PCT, sCD14-ST and hs-CRP levels were observed among septic cases in comparison to controls (p < 0.0001). Individually, PCT showed better accuracy (AUC = 78.7%) followed by hs-CRP (AUC = 78.4%) and sCD14-ST (AUC = 74.8%). Combination of PCT + hs-CRP had the highest accuracy (AUC = 80.1%) followed by hs-CRP + sCD14-ST (AUC = 77.2%), PCT + sCD14-ST + hs-CRP (AUC = 77.0%) and PCT + sCD14-ST (AUC = 75.9%).Conclusion: hs-CRP, PCT, and sCD14-ST are independent predictors of paediatric sepsis due to their high prognostic values. Moreover, Bioscore combination of these biomarkers was significantly associated with increased odds for sepsis. The incorporation of these biomarkers into routine diagnostic tests will aid in prompt diagnosis of paediatric sepsis.

Objective: To identify the correlation between demographic factors and upper urinary tract stone composition in the Thai population. Method: A retrospective observational study of first-time upper urinary tract stone former patients aged over 18 years who underwent stone surgery was performed in a tertiary referral university hospital from January 2013 to May 2018. Collected data included demographic information and stone composition information, which were analysed by the Fourier Transform-Infrared Spectroscopy (FTIR) method. The correlation between the demographic factors and major upper urinary tract stone composition was analysed using Fisher's exact test. Results: A total of 480 patients were included in this study. The stones were 319 (66.5%) renal calculi and 161 (33.5%) ureteric calculi. There were 248 (51.7%) single composition stones and 232 (48.3%) mixed composition stones. The major stone compositions were 288 (60.0%) calcium oxalate (CaOx), 125 (26.0%) calcium phosphate (CaP), 40 (8.3%) uric acid (UA), 19 (4.0%) magnesium ammonium phosphate (MAP), five (1.0%) cystine, and three (0.6%) ammonium hydrogen urate (AHU). Gender was correlated with the major stone composition. In females, a correlation was found between the major stone composition and age, diabetes mellitus (DM), and glomerular filtration rate (GFR). The study showed no significant correlation between the major stone composition and dyslipidemia (DLP), hypertension (HT), gout, and body mass index (BMI) in both genders. Conclusion: Gender, age, DM, and GFR were the factors affecting the stone composition.

Aim: To study the relationship between melatonin levels and Melatonin membrane receptor 1A (MTNR1A) SNP (rs13140012) in end-stage renal disease patients (ESRD) in Alexandria, Egypt on maintenance hemodialysis with or without atherosclerosis. Materials and methods: 40 end-stage renal disease patients on regular hemodialysis were divided into 2 subgroups, one with (n = 20) and one without atherosclerosis (n = 20) and normal subjects (n = 40). Serum melatonin, carotid intimal medial thickness (CIMT) were measured. Melatonin membrane receptor 1A (MTNR1A) SNP (rs13140012) genotyping was done using 5'nuclease Allelic discrimination. Results: Serum melatonin was significantly lower in ESRD patients [1.6 to 11.30 (pg/mL) with a median of 2.5] than the control group [20.50 to 56.40 (pg/mL) with a median of 35.20]. Serum melatonin was significantly lower in atherosclerotic patients subgroup [1.6–2.50 (pg/mL) with a median value of 2.30] than non-atherosclerotic patients subgroup [2.0–11.30 (pg/mL) with a median of 4.9]. No significant association was found between serum melatonin and (MTNR1A) SNP (rs13140012) (p = 0.633). Conclusion: These results lead us to suggest that melatonin production is impaired in ESRD patients (included in this pilot study), and this impairment is more evident in atherosclerotic ESRD patients.

Macrotyloma uniflorum Linn. (Fabaceae) seeds are widely used for their diuretic and urolithiatic effects in India. The present study investigated the effect of aqueous extract of Macrotyloma uniflorum seeds (AEMU) on ethylene glycol induced urolithiasis in rats. To induce urolithiasis, 0.75% v/v ethylene glycol was administered orally for 14 days. The curative doses of 400 and 800 mg/kg were administered from 15th to 28th day. On the 28th day, 24 h urine, serum was collected and various biochemical parameters were estimated in urine, serum and kidney homogenate along with histology of kidney. Co-administration of AEMU with ethylene glycol has significantly (p < 0.001) increased the urine volume and the level of calculus inhibitors like magnesium, citrate and decreased the level of calculus promoters like calcium, oxalate, uric acid and urea also decreased in crystalluria in urine. AEMU supplement also prevented the pathological changes in the kidney and increased the glomerulus activity of the kidney. These results indicate that AEMU showed significant activity in urolithiasis which might be due to its diuretic, calcium oxalate crystal formation inhibitory effects and its ability to increase the levels of inhibitors and decrease the level of promoters of urolithiasis.

Objectives: The vascular amplifier in hypertension is a result of structural changes in resistance arteries. We estimated the vascular amplifier hypertensive:normotensive (H:N) ratio in the renal bed compared with the total peripheral bed in conscious rabbits during infusion of vasoconstrictor and vasodilator stimuli. Methods: Rabbits were subjected to bilateral renal cellophane wrap or sham operation. A perivascular ultrasonic flow probe was implanted on the left renal artery to measure renal blood flow. A catheter was inserted into the thoracic aorta for agonist administration. Blood pressure, heart rate and renal blood flow were measured on three separate days in conscious rabbits with intact effectors, ganglionic block or neurohumoral block. Dose-response curves were constructed to intra-arterial infusion of noradrenaline, angiotensin II, adenosine and acetylcholine. Results: Resting renal vascular resistance in hypertensive rabbits was markedly decreased by ganglionic block and further by neurohumoral block. With effectors intact, ganglionic block or neurohumoral block, the H:N ratio for renal vascular resistance was 2.32, 1.72 or 1.72, respectively. The ratio was generally maintained during the infusion of constrictor and dilator drugs although distortions occurred at higher concentrations of constrictor or dilator drugs. Conclusions: Estimation of the renal resistance amplifier in renal wrap hypertension with neurohumoral block accords with our earlier estimates of the total peripheral resistance amplifier (1.79). This vascular resistance amplifier is consistent with a decrease in internal radius through structural remodelling in the renal vascular bed as is reflected in the total arterial circulation in hypertension.

Polyuria is a hallmark symptom and the first clinical manifestation of diabetes mellitus (DM). The glucose that remains in renal tubules was proposed to produce an osmotic effect resulting in polyuria. Although water is reabsorbed in proximal tubules through an aquaporin-1 (AQP1) dependent mechanism, AQP1 role in the genesis of polyuria is unknown. AQP1 expression was studied in a rat model of Type-1 DM at 15-days and 5-months of evolution. A different AQP1 expression pattern was found in both experimental groups, with no changes in AQP1 localization, suggesting that changes in AQP1 may be involved in the development of polyuria.

Aims: The renin-angiotensin system (RAS) is a dual system with two opposite arms: i) the classical one formed by the angiotensin converting enzyme (ACE), angiotensin (Ang) II and angiotensin type 1 (AT1) receptors; ii) the counter-regulatory arm consisting of ACE2, Ang-(1–7) and Mas receptor. Physical exercise can modulate this system, however, only animal studies have compared the effects of different intensity protocols on the RAS. No data with humans were provided. Therefore, we investigated the acute effect of two protocols of isowork aerobic exercise [High-Intensity Interval Exercise (HIIE) and Moderate-Intensity Continuous Exercise (MICE)] in plasma and urinary levels of RAS components in physically active men. Main methods: The HIIE protocol included a 5-minute warm-up cycling at 60–70% of heart rate peak (HRp) intensity followed by 10 sets of 30 s above 90% with 1 min of recovery and 3 min of cool down. The MICE protocol was performed at a constant power corresponding to 60–70% of HRp and finalized at the same total work of HIIE. Blood and urine samples were collected before and after the protocols. Plasma and urinary levels of ACE, ACE2, Ang-(1–7) and Ang II were analyzed by enzyme-linked immunoassay. Key findings: While the HIIE protocol significantly increased urinary levels of ACE and plasma levels of ACE2, the MICE protocol elevated urinary concentrations of ACE2 and of Ang-(1–7). A greater increase of urine concentrations of Ang-(1–7) occurred in the MICE if compared with the HIIE protocol. Significance: Aerobic physical exercise acutely increases the activity of the counter-regulatory RAS axis, mostly the MICE protocol.

Imatinib is a tyrosine kinase inhibitor widely administered against chronic myeloid leukemia. On the other hand, drug-induced kidney proximal tubular injury, electrolytes disturbances, and renal failure is a clinical complication associated with imatinib therapy. There is no precise cellular mechanism(s) for imatinib-induced renal injury. The current investigation aimed to evaluate the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of imatinib nephrotoxicity. Rats received imatinib (50 and 100 mg/kg, oral, 14 consecutive days). Serum and urine biomarkers of renal injury and markers of oxidative stress in the kidney tissue were assessed. Moreover, kidney mitochondria were isolated, and mitochondrial indices, including mitochondrial depolarization, dehydrogenases activity, mitochondrial permeabilization, lipid peroxidation (LPO), mitochondrial glutathione levels, and ATP content were determined. A significant increase in serum (Creatinine; Cr and blood urea nitrogen; BUN) and urine (Glucose, protein, gamma-glutamyl transferase; γ-GT, and alkaline phosphatase; ALP) biomarkers of renal injury, as well as serum electrolytes disturbances (hypokalemia and hypophosphatemia), were evident in imatinib-treated animals. On the other hand, imatinib (100 mg/kg) caused an increase in kidney ROS and LPO. Renal tubular interstitial nephritis, tissue necrosis, and atrophy were evident as tissue histopathological changes in imatinib-treated rats. Mitochondrial parameters were also adversely affected by imatinib administration. These data represent mitochondrial impairment, renal tissue energy crisis, and oxidative stress as possible mechanisms involved in the pathogenesis of imatinib-induced renal injury and serum electrolytes disturbances.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.