Purpose Thiazide use to prevent recurrent calcium nephrolithiasis is supported by randomized, controlled trials. Concerns regarding adverse metabolic effects of thiazides, which are also used to ...treat hypertension, have reemerged with analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. The risks posed by thiazide induced hyperglycemia, hyperuricemia, hypokalemia and dyslipidemia may decrease the expected cardiovascular benefit of lowering blood pressure in hypertensive patients. Whether these side effects occur and are clinically significant in nonhypertensive patients with kidney stones treated with thiazides is unclear. Materials and Methods A review of the literature was performed for randomized, controlled trials with thiazides for calcium nephrolithiasis. We sought data regarding metabolic effects in this population, including hyperglycemia, hyperuricemia, hypokalemia and dyslipidemia. Results Nine randomized, controlled trials of thiazide treatment for kidney stones were included. Mean patient age was 42 years and followup was 2.6 years. Only 2 of the 9 studies measured glucose and lipid levels, which did not significantly change with treatment. Three studies measured serum potassium and 2 showed a significant decrease. Three of the 9 studies measured serum uric acid levels, which increased in all 3. None of the trials studied the development of diabetes mellitus or cardiovascular disease. Conclusions There is a lack of data on the metabolic effects of thiazides used to prevent recurrent calcium nephrolithiasis. It remains unclear if metabolic effects occur and increase the risk of cardiovascular disease in otherwise healthy patients with recurrent nephrolithiasis on thiazide prophylaxis. Further research is needed to elucidate other alternatives for the treatment of recurrent nephrolithiasis.
Kidney HMGCS2 Protects Against Ischemic Kidney Injury Venable, Andrea H.; Lee, Lauren Elizabeth; Feola, Kyle C. ...
Journal of the American Society of Nephrology,
11/2022, Letnik:
33, Številka:
11S
Journal Article
Background: Sepsis is an exaggerated host response to infection that is associated with multiorgan failure and death. Although severe obesity is associated with increased sepsis mortality, the ...underlying ophysiology unclear. Alpha-melanocyte stimulating hormone (a-MSH), a cleavage product of pro-opiomelanocortin (POMC), regulates food intake and energy expenditure in the hypothalamus where it has been intensely studied. However, a-MSH is also produced in the pituitary gland and has anti-inflammatory properties. We recently developed a novel mouse model to delete a-MSH (aMSHKO mice) without affecting corticotropin function. We postulated that a-MSH has a critical function in counteracting excessive inflammation, which may have implications in sepsis. Methods: We challenged 10-14-week-old male aMSHKO and WT littermates with single i.p. injections of either saline or low-dose lipopolysaccharide (LPS, 100 p.g/kg) and monitored immune and metabolic responses. We used telemetry to measure core body temperature and activity, ELISA to measure circulating cytokines, corticosteroid and a-MSH, and metabolic chambers to measure food intake and respiration. We also developed a mass spectrometry method to measure three forms of a-MSH produced in mouse hypothalamus and pituitary gland for the first time. Gene expression analysis by qPCR was performed on hypothalamus, pituitary, lung, liver, spleen, and adipose tissue. Results: LPS induced an exaggerated immune response characterized by hypoactivity, hypothermia, reduced oxygen consumption, and increased cytokine expression in aMSHKO mice compared to WT controls. LPS induced a-MSH expression in the pituitary gland and circulation, but not in the hypothalamus, in WT and C57BL/6J mice. Conclusions: Our data indicate endogenous a-MSH opposes inflammatory immune responses triggered by low-dose LPS administration and suggests that modulation of the melanocortin system may be an effective target for sepsis therapy.
The Role of p204 in Kidney Injury Marlier, Arnaud; Huen, Sarah; Lengyel, Peter ...
The FASEB journal,
04/2015, Letnik:
29, Številka:
S1
Journal Article
Acute ischemic kidney injury is a common complication in hospitalized patients. Currently no treatment is available for augmenting kidney repair or preventing progressive kidney fibrosis. Activation ...of the innate immune system plays a major role in the systemic response to renal ischemia/reperfusion injury. Macrophages are key participants in the innate immune response. Macrophage depletion studies suggest that macrophages mediate the initial injury after reperfusion, promote tubular repair, and contribute to long-term kidney fibrosis after ischemic injury. The distinct functional outcomes as a result of macrophage depletion at different time points after ischemia/reperfusion injury suggest heterogeneity in macrophage activation states. To investigate the possible role of macrophage heterogeneity in the process of transitioning from the early stages of tubular injury to the later stages of proliferation and repair, macrophage marker analysis was combined with functional studies in a mouse model of kidney ischemia/reperfusion. Consistent with the findings of macrophage depletion studies, macrophages expressed pro-inflammatory markers during the initial period of reperfusion injury, whereas macrophages resembling the alternatively activated or trophic phenotype predominated during the recovery and repair phase. IFNγ-stimulated, pro-inflammatory bone marrow derived macrophages injected into a mouse 3 days after renal ischemia/reperfusion injury switch towards an alternative activation phenotype within the kidney. The phenotypic switching of macrophage activation that reflects a functional change from initial tubular cell injury to eventual repair can be mediated in response to signals from the microenvironment of the injured kidney. In vitro co-culture studies demonstrated that renal epithelial cells themselves can promote alternative activation in IFNγ-primed macrophages. In order to determine the mechanisms by which renal tubular cells can mediate macrophage alternative activation, in vitro studies utilizing renal tubule cell conditioned media were performed to identify signaling pathways activated in primary bone marrow derived macrophages. These studies revealed that secreted renal tubular factors can induce both pro-inflammatory and anti-inflammatory macrophage activation in a sequential fashion that mimics the phenotypic switch seen in vivo after ischemic renal injury. Bone marrow derived macrophages from knockout mice and the use of pharmacologic inhibitors led to the discovery that tubular mediated macrophage alternative activation is regulated by TLR/MyD88/NF-κB and STAT5 activation, while independent of the canonical STAT6 and STAT3 pathways. Macrophages also participate in late fibrotic responses. The fibrogenic role of macrophage-derived TGF-β1 in ischemic kidney injury was studied using the LysM-Cre;Tgfb1f/n mouse model. Homozygous deletion of Tgfb1 in myeloid lineage cells in mice heterozygous for Tgfb1 significantly reduces kidney Tgfb1 mRNA expression and Smad activation at late time points after renal ischemia/reperfusion injury. However, this reduction in kidney Tgfb1 expression and signaling results in only a modest reduction of isolated fibrosis markers and does not lead to decreased interstitial fibrosis in either ischemic or obstructive injury models. Thus, targeting macrophage-derived TGF-β1 does not appear to be an effective therapy for attenuating progressive renal fibrosis after kidney injury. Macrophage activation in response to ischemic kidney injury is complex and multifaceted. Identifying the pathways that regulate the transitions of macrophage activation is thus critical in understanding the mechanisms that govern macrophage mediated repair and fibrosis after kidney injury.
Background
Pressure ulcers (PU) are a common yet debilitating injury within the spinal cord injury (SCI) population. This retrospective data analysis is intended to identify the contributing factors, ...review the current management protocol, and risk of recurrence of PU in SCI patients at Victoria's state referral centre for traumatic spinal cord injuries.
Methods
A retrospective audit of the medical records of SCI patients with pressure ulcers was conducted for the period of January 2016 to August 2021. Patients aged 18 years and older who presented for surgical management of their PU were included in the study.
Results
Among the 93 patients who met the inclusion criteria, there were a total of 195 surgeries for 129 PU. Ninety‐seven percent were classified as grade of 3 or 4 and 53% had osteomyelitis on presentation. 58% were either current smokers or ex‐smokers, and 19% were diabetic. Debridement alone was the most common type of surgical management (58%), followed by flap reconstruction (25%). Those who underwent flap reconstruction were admitted for 71 days longer, on average. 41% of the surgeries were associated with a post‐operative complication, with the most prominent being an infection at 26%. Of the 129 PU, 11% recurred at least 4 months post initial presentation.
Conclusion
There are a multitude of a factors that impact prevalence, surgical complications, and recurrence of PU. This study provides insight into these factors to review our current practices and optimize surgical outcomes in the management of PU in the SCI population.
A retrospective audit of the medical records of spinal cord injury (SCI) patients with pressure ulcers (PU) was conducted at Victoria's state referral centre for traumatic spinal cord injuries. There are a multitude of a factors that impact prevalence, surgical complications, and recurrence of PU in these patients. This study provides insight into these factors to review our current practices and optimise surgical outcomes in this population.
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