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Endocrinology, Diabetes & Metabolism... Aug 2022Vasoactive intestinal peptide-secreting tumours (VIPomas) are an extremely rare form of functional pancreatic neuroendocrine tumour with an estimated annual incidence of...
SUMMARY
Vasoactive intestinal peptide-secreting tumours (VIPomas) are an extremely rare form of functional pancreatic neuroendocrine tumour with an estimated annual incidence of 1 in 10 million. Associated tumour hypersecretion of other peptides, including pancreatic polypeptide (PPomas), may also be seen. These malignancies classically present with a defined triad of refractory diarrhoea, hypokalaemia and metabolic acidosis known as Verner-Morrison syndrome. Diagnosis is frequently delayed, and the majority of patients will have metastatic disease at presentation. Symptoms are usually well controlled with somatostatin analogue administration. Here we report a case of metastatic mixed VIPoma/PPoma-induced diarrhoea causing renal failure so severe that ultrafiltration was required to recover adequate renal function.
LEARNING POINTS
Profuse, watery diarrhoea is a common presenting complaint with a multitude of aetiologies. This, combined with the rarity of these tumours, makes diagnosis difficult and frequently delayed. A functional neuroendocrine tumour should be suspected when diarrhoea is unusually extreme, prolonged and common causes have been promptly excluded. These patients are likely to be profoundly unwell on presentation. They are extremely hypovolaemic with dangerous electrolyte and metabolic abnormalities. Aggressive initial rehydration and electrolyte replacement are imperative. A somatostatin analogue should be commenced as soon as the diagnosis is suspected. This is an extreme example of Verner-Morrison syndrome. We are unaware of another case where renal failure secondary to diarrhoea and dehydration was so severe that renal replacement therapy was required to restore adequate renal function, further emphasising how critically unwell these patients can be. Both the primary tumour and metastases showed a remarkably good and rapid response to somatostatin analogue administration. Cystic change and involution were noted on repeat imaging within days. Prior to his illness, this patient was extremely high functioning with no medical history. His diagnosis was an enormous psychological shock, and the consideration and care for his psychological well-being were a crucial part of his overall management. It highlights the importance of a holistic approach to cancer care and the role of the clinical nurse specialist within the cancer multidisciplinary team.
PubMed: 36001009
DOI: 10.1530/EDM-22-0231 -
PloS One 2023Renal involvement is a common occurrence in subjects with systemic autoimmune diseases. The renal manifestation and its severity depend on the underlying condition and...
Renal involvement is a common occurrence in subjects with systemic autoimmune diseases. The renal manifestation and its severity depend on the underlying condition and may reversely complicate the clinical course of autoimmune diseases. Renal function markers have been widely used in the assessment of normal functioning of kidneys including glomerular filtration rate and concentrating and diluting capacity of the kidney. An increase or decrease in the values of these markers may indicate kidney dysfunction. In this study, a number of critical renal markers were examined in seropositive autoimmune diseases including systemic lupus erythematosus (SLE), connective tissue disorder (CTD), and rheumatoid arthritis (RA). The data from three cohorts of subjects enrolled in renal markers and autoimmune antibody testing between January 2015 to August 2019 were retrospectively studied. The prevalence of renal markers that were out of the reference range and their average levels in female and male subgroups across SLE, CTD, and RA cohorts were compared and analyzed. The levels of renal markers are significantly affected by the presence of autoantibodies, in particular eGFR, cystatin C, and albumin. Autoantibodies were also more frequent in subjects with severe renal function damage. Close follow-up of both renal markers and autoantibodies may potentially assist in the early diagnosis of kidney diseases and improve the survival and life expectancy of autoimmune patients.
Topics: Humans; Male; Female; Retrospective Studies; Lupus Erythematosus, Systemic; Kidney; Autoimmune Diseases; Autoantibodies; Connective Tissue Diseases; Arthritis, Rheumatoid
PubMed: 37352246
DOI: 10.1371/journal.pone.0278441 -
Nutrition Reviews Apr 2023Optimal hydration is required for all physiologic functions and cognition. Children, especially younger ones, are particularly susceptible to dehydration, given their... (Review)
Review
Optimal hydration is required for all physiologic functions and cognition. Children, especially younger ones, are particularly susceptible to dehydration, given their physiological specificities, in particular, their renal immaturity and relatively large skin surface in early life, but also their dependence on adults and their greater propensity to develop digestive diseases leading to fluid losses. Mild dehydration consequences are dominated by their impact on cognitive functions, whereas more severe dehydration may endanger the health outcome. Studies on this subject in children are scarce; in particular, the long-term consequence on renal function remains questionable. This review considers how children's water intake including fluid intake and water content of food, are worrying. The findings show that, worldwide, most children do not meet adequate water intake recommendations. The main problems likely to explain insufficient water intake are access to safe water, availability of drinking water at school, and healthy-hydration education, which are all points that need to be improved within health policy.
Topics: Adult; Humans; Child; Drinking; Dehydration; Public Health; Water; Water-Electrolyte Balance
PubMed: 36228121
DOI: 10.1093/nutrit/nuac073 -
International Journal of Molecular... Dec 2022The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the... (Review)
Review
The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6. TRPC3 plays a key role in Ca homeostasis and is involved in transcellular Ca reabsorption in the proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to better understand certain renal disorders and ultimately create new therapeutic targets to improve patient care.
Topics: Humans; TRPC6 Cation Channel; TRPC Cation Channels; Polycystic Kidney, Autosomal Dominant; Transient Receptor Potential Channels; Homeostasis
PubMed: 36613622
DOI: 10.3390/ijms24010181 -
Current Opinion in Insect Science Oct 2021The insect renal (Malpighian) tubules are functionally homologous to the mammalian kidney. Accumulating evidence indicates that renal tubule crystals form in a manner... (Review)
Review
The insect renal (Malpighian) tubules are functionally homologous to the mammalian kidney. Accumulating evidence indicates that renal tubule crystals form in a manner similar to mammalian kidney stones. In Drosophila melanogaster, crystals can be induced by diet, toxic substances, or genetic mutations that reflect circumstances influencing or eliciting kidney stones in mammals. Incredibly, many mammalian proteins have distinct homologs in Drosophila, and the function of most homologs have been demonstrated to recapitulate their mammalian and human counterparts. Here, we discuss the present literature establishing Drosophila as a nephrolithiasis model. This insect model may be used to investigate and understand the etiology of kidney stone diseases, especially with regard to calcium oxalate, calcium phosphate and xanthine or urate crystallization.
Topics: Animals; Calcium Oxalate; Disease Models, Animal; Drosophila melanogaster; Malpighian Tubules; Nephrolithiasis
PubMed: 34044181
DOI: 10.1016/j.cois.2021.05.003 -
High Blood Pressure & Cardiovascular... Jan 2024In patients with end-stage renal disease (ESRD) undergoing haemodialysis, hypertension is of common detection and frequently inadequately controlled. Multiple... (Review)
Review
In patients with end-stage renal disease (ESRD) undergoing haemodialysis, hypertension is of common detection and frequently inadequately controlled. Multiple pathophysiological mechanisms are involved in the development and progression of the ESRD-related high blood pressure state, which has been implicated in the increased cardiovascular risk reported in this hypertensive clinical phenotype. Renal sympathetic efferent and afferent nerves play a relevant role in the development and progression of elevated blood pressure values in patients with ESRD, often leading to resistant hypertension. Catheter-based bilateral renal nerves ablation has been shown to exert blood pressure lowering effects in resistant hypertensive patients with normal kidney function. Promising data on the procedure in ESRD patients with resistant hypertension have been reported in small scale pilot studies. Denervation of the native non-functioning kidney's neural excitatory influences on central sympathetic drive could reduce the elevated cardiovascular morbidity and mortality seen in ESRD patients. The present review article will focus on the promising results obtained with renal denervation in patients with ESRD, its mechanisms of action and future perspectives in these high risk patients.
Topics: Humans; Sympathetic Nervous System; Sympathectomy; Kidney; Kidney Failure, Chronic; Hypertension; Blood Pressure; Denervation
PubMed: 38267652
DOI: 10.1007/s40292-023-00621-1 -
JCI Insight Nov 2023BACKGROUNDCardiorenal syndrome (CRS) - renal injury during heart failure (HF) - is linked to high morbidity. Whether circulating extracellular vesicles (EVs) and their...
BACKGROUNDCardiorenal syndrome (CRS) - renal injury during heart failure (HF) - is linked to high morbidity. Whether circulating extracellular vesicles (EVs) and their RNA cargo directly impact its pathogenesis remains unclear.METHODSWe investigated the role of circulating EVs from patients with CRS on renal epithelial/endothelial cells using a microfluidic kidney-on-chip (KOC) model. The small RNA cargo of circulating EVs was regressed against serum creatinine to prioritize subsets of functionally relevant EV-miRNAs and their mRNA targets investigated using in silico pathway analysis, human genetics, and interrogation of expression in the KOC model and in renal tissue. The functional effects of EV-RNAs on kidney epithelial cells were experimentally validated.RESULTSRenal epithelial and endothelial cells in the KOC model exhibited uptake of EVs from patients with HF. HF-CRS EVs led to higher expression of renal injury markers (IL18, LCN2, HAVCR1) relative to non-CRS EVs. A total of 15 EV-miRNAs were associated with creatinine, targeting 1,143 gene targets specifying pathways relevant to renal injury, including TGF-β and AMPK signaling. We observed directionally consistent changes in the expression of TGF-β pathway members (BMP6, FST, TIMP3) in the KOC model exposed to CRS EVs, which were validated in epithelial cells treated with corresponding inhibitors and mimics of miRNAs. A similar trend was observed in renal tissue with kidney injury. Mendelian randomization suggested a role for FST in renal function.CONCLUSIONPlasma EVs in patients with CRS elicit adverse transcriptional and phenotypic responses in a KOC model by regulating biologically relevant pathways, suggesting a role for EVs in CRS.TRIAL REGISTRATIONClinicalTrials.gov NCT03345446.FUNDINGAmerican Heart Association (AHA) (SFRN16SFRN31280008); National Heart, Lung, and Blood Institute (1R35HL150807-01); National Center for Advancing Translational Sciences (UH3 TR002878); and AHA (23CDA1045944).
Topics: Humans; Endothelial Cells; Cardio-Renal Syndrome; Kidney; MicroRNAs; Extracellular Vesicles; Heart Failure; Transforming Growth Factor beta
PubMed: 37707956
DOI: 10.1172/jci.insight.165172 -
Life Sciences Aug 2021Diabetes promotes renal sympathetic hyperactivity, autonomic imbalance, and cardiovascular and renal dysfunction. Bilateral renal denervation (BRD) has emerged as a...
UNLABELLED
Diabetes promotes renal sympathetic hyperactivity, autonomic imbalance, and cardiovascular and renal dysfunction. Bilateral renal denervation (BRD) has emerged as a treatment for diabetes; however, the mechanisms that underlie the beneficial effects of BRD are unknown.
AIMS
The present study evaluated the effects of BRD on autonomic, cardiovascular, metabolic, and renal function in streptozotocin-diabetic rats.
MAIN METHODS
Wistar rats were separated into three experimental groups: control (CTR), diabetic (DM), and diabetic that underwent BRD (DM BRD). BRD was performed two weeks after STZ-diabetes induction, the experiments were performed four weeks after DM induction. This study evaluated sympathetic vasomotor nerve activity in different territories (renal, lumbar and splanchnic), arterial baroreceptor reflex, metabolic and renal function.
KEY FINDINGS
BRD significantly reduced glycemia, glycosuria, albuminuria, and SGLT2 gene expression in the kidney in DM rats. Renal sympathetic nerve activity (rSNA) was significantly increased and splanchnic sympathetic nerve activity (sSNA) was significantly decreased in DM rats, without changes in lumbar sympathetic nerve activity (lSNA). BRD was able to normalize sSNA and significantly increase lSNA in DM rats compared to control rats. Additionally, cardiac baroreceptor sensitivity was impaired in DM rats, and BRD significantly improved baroreflex sensitivity.
SIGNIFICANCE
Our data suggest that renal nerves play an important role in autonomic, cardiovascular, and renal dysfunction in STZ-DM rats. Thus, sympathetic renal hyperactivity should be considered a possible therapeutic target in diabetic patients.
Topics: Animals; Baroreflex; Blood Pressure; Cardiovascular System; Catheterization; Denervation; Diabetes Mellitus, Experimental; Heart; Heart Rate; Hematocrit; Kidney; Male; Pressoreceptors; Rats; Rats, Wistar; Sodium-Glucose Transporter 2; Streptozocin; Sympathetic Nervous System
PubMed: 33933461
DOI: 10.1016/j.lfs.2021.119534 -
Expression, localization, and functional properties of inwardly rectifying K channels in the kidney.American Journal of Physiology. Renal... Feb 2020Inwardly rectifying K (K) channels are expressed in multiple organs and cell types and play critical roles in cellular function. Most notably, K channels are major... (Review)
Review
Inwardly rectifying K (K) channels are expressed in multiple organs and cell types and play critical roles in cellular function. Most notably, K channels are major determinants of the resting membrane potential and K homeostasis. The renal outer medullary K channel (K1.1) was the first renal K channel identified and cloned in the kidney over two decades ago. Since then, several additional members, including classical and ATP-regulated K family classes, have been identified to be expressed in the kidney and to contribute to renal ion transport. Although the ATP-regulated K channel class remains the most well known due to severe pathological phenotypes associated with their mutations, progress is being made in defining the properties, localization, and physiological functions of other renal K channels, including those localized to the basolateral epithelium. This review is primarily focused on the current knowledge of the expression and localization of renal K channels but will also briefly describe their proposed functions in the kidney.
Topics: Animals; Gene Expression Regulation; Homeostasis; Humans; Kidney; Kidney Diseases; Membrane Potentials; Potassium; Potassium Channels, Inwardly Rectifying
PubMed: 31841387
DOI: 10.1152/ajprenal.00523.2019 -
IScience Jan 2023SLC17A9 is a vesicular ATP transport protein that plays an important role in determining cell functions and the onset and progression of different diseases. In this...
SLC17A9 is a vesicular ATP transport protein that plays an important role in determining cell functions and the onset and progression of different diseases. In this study, SLC17A9 was initially identified as a potential diagnostic and prognostic risk biomarker for clear cell renal cell carcinoma (ccRCC). Then, the aberrant expression levels of SLC17A9 were confirmed in both the cell lines and clinical tissues. Mechanistically, SLC17A9 could upregulate the expression of PTHLH, thus promoting epithelial-mesenchymal transition (EMT) in ccRCC. Functionally, SLC17A9 knockdown inhibited the proliferation, migration, and invasion activity of renal cancer cells, whereas its overexpression led to stronger cell viability and more malignant phenotype . The overexpression of SLC17A9 could significantly contribute to the growth of tumors. Finally, we found that SLC17A9 might be related to the drug resistance of vorinostat. Cumulatively, this study demonstrated that the SLC17A9-PTHLH-EMT axis could promote the progression of ccRCC.
PubMed: 36590170
DOI: 10.1016/j.isci.2022.105764