ABSTRACT
When sodium-glucose cotransporter-2 (SGLT2) inhibitors were first introduced a decade ago, no one expected them to have substantial effects beyond their known glucose-lowering effects, until the emergence of evidence of their robust renal and cardiovascular benefits showing that they could attenuate progression of kidney disease, irrespective of diabetes, as well as prevent the development of acute kidney injury. Still, the precise and elaborate mechanisms underlying the major organ protection of SGLT2 inhibitors remain unclear. SGLT2 inhibitors inhibit the reabsorption of sodium and glucose in the proximal tubule of the kidney and then recovers tubuloglomerular feedback, whereby SGLT2 inhibitors reduce glomerular hyperfiltration. This simple demonstration of their beneficial effects has perplexed experts in seeking more plausible and as yet undisclosed explanations for the whole effects of SGLT2 inhibitors, including metabolism reprogramming and the modulation of hypoxia, inflammation, and oxidative stress. Given that the renal benefits of SGLT2 inhibitors in patients with kidney disease but without diabetes were comparable to those seen in patients with diabetes, it may be reasonable to keep the emphasis on their hemodynamic actions. In this context, the aim of the present review is to provide a comprehensive overview of renal hemodynamics in individuals with diabetes who are treated with SGLT2 inhibitors, with a focus on natriuresis associated with the regulation of tubuloglomerular feedback and potential aquaresis. Throughout the discussion of alterations in renal sodium and water transports, particular attention will be given to the potential enhancement of adenosine and its receptors following SGLT2 inhibition.
ABSTRACT
Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. Methods: A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. Results: Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. Conclusion: Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.
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Background/Aims@#Because weight control is important in treatment of type 2 diabetes, it is essential to understand the associations between weight change and the risk of microvascular complications among patients with type 2 diabetes. We examined whether weight changes early after new-onset diabetes have an impact on the clinical outcomes of diabetic nephropathy and retinopathy. @*Methods@#Using the Korean National Health Insurance Service-National Health Screening Cohort database, 181,872 patients newly diagnosed with type 2 diabetes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007 to 2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes diagnosis to 2 years later. @*Results@#We identified 180 cases of ESRD and 780 cases of PDR followed up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with 5% to 10% weight gain showed a significantly higher hazard ratio (HR) for ESRD, compared with those with ≤ 5% weight change after adjusting for several confounding factors, including the baseline estimated glomerular filtration rate (HR, 1.75; 95% confidence interval [CI], 1.14 to 2.70). Those with ≥ 10% weight loss showed the lowest HR for PDR (HR, 0.52; 95% CI, 0.33 to 0.83), whereas those with ≥ 10% weight gain showed the highest HR for PDR (HR, 3.20; 95% CI, 2.51 to 4.08). @*Conclusions@#Weight gain after new-onset diabetes was associated with increased risk of ESRD and PDR whereas weight loss with decreased risk of PDR, but not ESRD.
ABSTRACT
Background@#Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. @*Methods@#Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys. @*Results@#Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice. @*Conclusion@#These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.
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Background/Aims@#Because weight control is important in treatment of type 2 diabetes, it is essential to understand the associations between weight change and the risk of microvascular complications among patients with type 2 diabetes. We examined whether weight changes early after new-onset diabetes have an impact on the clinical outcomes of diabetic nephropathy and retinopathy. @*Methods@#Using the Korean National Health Insurance Service-National Health Screening Cohort database, 181,872 patients newly diagnosed with type 2 diabetes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007 to 2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes diagnosis to 2 years later. @*Results@#We identified 180 cases of ESRD and 780 cases of PDR followed up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with 5% to 10% weight gain showed a significantly higher hazard ratio (HR) for ESRD, compared with those with ≤ 5% weight change after adjusting for several confounding factors, including the baseline estimated glomerular filtration rate (HR, 1.75; 95% confidence interval [CI], 1.14 to 2.70). Those with ≥ 10% weight loss showed the lowest HR for PDR (HR, 0.52; 95% CI, 0.33 to 0.83), whereas those with ≥ 10% weight gain showed the highest HR for PDR (HR, 3.20; 95% CI, 2.51 to 4.08). @*Conclusions@#Weight gain after new-onset diabetes was associated with increased risk of ESRD and PDR whereas weight loss with decreased risk of PDR, but not ESRD.
ABSTRACT
Background@#Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. @*Methods@#Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys. @*Results@#Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice. @*Conclusion@#These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.
ABSTRACT
A novel robotic mirror therapy system was recently developed to provide proprioceptive stimulus to the hemiplegic arm during a mirror therapy. Validation of the robotic mirror therapy system was performed to confirm its synchronicity prior to the clinical study. The mean error angle range between the intact arm and the robot was 1.97 to 4.59 degrees. A 56-year-old male who had right middle cerebral artery infarction 11 months ago received the robotic mirror therapy for ten 30-minute sessions during 2 weeks. Clinical evaluation and functional magnetic resonance imaging (fMRI) studies were performed before and after the intervention. At the follow-up evaluation, the thumb finding test score improved from 2 to 1 for eye level and from 3 to 1 for overhead level. The Albert's test score on the left side improved from 6 to 11. Improvements were sustained at 2-month follow-up. The fMRI during the passive motion revealed a considerable increase in brain activity at the lower part of the right superior parietal lobule, suggesting the possibility of proprioception enhancement. The robotic mirror therapy system may serve as a useful treatment method for patients with supratentorial stroke to facilitate recovery of proprioceptive deficit and hemineglect.
Subject(s)
Humans , Male , Middle Aged , Arm , Brain , Clinical Study , Exoskeleton Device , Follow-Up Studies , Hemiplegia , Infarction, Middle Cerebral Artery , Magnetic Resonance Imaging , Methods , Neurological Rehabilitation , Parietal Lobe , Pilot Projects , Proprioception , Stroke , Thumb , Upper ExtremityABSTRACT
BACKGROUND: The aim of this study was to investigate the changes of body composition and muscle strength of North Korean refugees (NKRs) according to their duration of stay in South Korea. METHODS: NKRs who volunteered and were living in South Korea, aged 20 to 75 years were recruited. Body compositions were analyzed by bioelectrical impedance analysis. Muscle strength was measured with the hand grip test. Demographic and migration information was obtained with a questionnaire. RESULTS: A total of 158 volunteers were recruited at a mean age of 48.3+/-11.4 years. The mean time from when they escaped from North Korea and arrived in South Korea was 5.8+/-4.3 years. Height, weight, and body surface area were significantly smaller in all NKRs compared to South Korean controls, except for women aged over 50 years. In females of younger ages (<50 years), NKRs with more than a 4-year stay in South Korea had a higher weight and fat mass than that of those who had a shorter stay (less than 4 years) in South Korea. All NKRs had a weaker grip strength than that of the age-matched controls from South Korea. CONCLUSION: The NKRs showed relatively smaller physiques and weaker muscle strength than that of the South Korean controls. In younger female NKRs, shorter South Korean stay group showed small body weight and fat mass than that of longer South Korean stay group. Specific health support programs might be needed.
Subject(s)
Female , Humans , Body Composition , Body Surface Area , Body Weight , Democratic People's Republic of Korea , Electric Impedance , Hand , Hand Strength , Korea , Muscle Strength , Refugees , United Nations , VolunteersABSTRACT
BACKGROUND/AIMS: Multiple myeloma (MM) is frequently accompanied by renal insufficiency, which has been regarded as a poor prognostic factor for MM. It is known that the incidence and characteristics of MM in Asia differ from those in Western countries. The aim of this study was to evaluate risk factors for renal impairment and to investigate reversible factors for renal failure in patients with MM. METHODS: Patients newly diagnosed with MM from 2005 to 2008 were included. We investigated factors associated with renal insufficiency and those related to recovery from renal dysfunction after 12 weeks of treatment of MM. RESULTS: Renal failure was recognized in 86 (39%) of 221 patients at diagnosis. In the binary logistic regression analysis, low hemoglobin (odds ratio [OR], 0.813; p = 0.02), high beta2microglobulin (OR, 1.006; p < 0.01), and use of angiotensin-converting enzyme inhibitors (ACEi) (OR, 2.783; p < 0.04) at initial presentation were independent risk factors for renal failure in patients with multiple myeloma. After 12 weeks of treatment, 25 of 86 (29%) patients with renal failure had recovered renal function. Good response to chemotherapy (OR, 6.044; p < 0.01) and higher eGFR (OR, 1.084; p < 0.01) were associated with renal function recovery. CONCLUSIONS: Levels of hemoglobin and beta2microglobulin, and use of ACEi were independent risk factors for the development of renal failure in MM patients. The response to chemotherapy and eGFR at diagnosis significantly influenced recovery of renal function.
Subject(s)
Humans , Angiotensin-Converting Enzyme Inhibitors , Asia , Diagnosis , Drug Therapy , Incidence , Logistic Models , Multiple Myeloma , Recovery of Function , Renal Insufficiency , Risk FactorsABSTRACT
BACKGROUND/AIMS: Multiple myeloma (MM) is frequently accompanied by renal insufficiency, which has been regarded as a poor prognostic factor for MM. It is known that the incidence and characteristics of MM in Asia differ from those in Western countries. The aim of this study was to evaluate risk factors for renal impairment and to investigate reversible factors for renal failure in patients with MM. METHODS: Patients newly diagnosed with MM from 2005 to 2008 were included. We investigated factors associated with renal insufficiency and those related to recovery from renal dysfunction after 12 weeks of treatment of MM. RESULTS: Renal failure was recognized in 86 (39%) of 221 patients at diagnosis. In the binary logistic regression analysis, low hemoglobin (odds ratio [OR], 0.813; p = 0.02), high beta2microglobulin (OR, 1.006; p < 0.01), and use of angiotensin-converting enzyme inhibitors (ACEi) (OR, 2.783; p < 0.04) at initial presentation were independent risk factors for renal failure in patients with multiple myeloma. After 12 weeks of treatment, 25 of 86 (29%) patients with renal failure had recovered renal function. Good response to chemotherapy (OR, 6.044; p < 0.01) and higher eGFR (OR, 1.084; p < 0.01) were associated with renal function recovery. CONCLUSIONS: Levels of hemoglobin and beta2microglobulin, and use of ACEi were independent risk factors for the development of renal failure in MM patients. The response to chemotherapy and eGFR at diagnosis significantly influenced recovery of renal function.
Subject(s)
Humans , Angiotensin-Converting Enzyme Inhibitors , Asia , Diagnosis , Drug Therapy , Incidence , Logistic Models , Multiple Myeloma , Recovery of Function , Renal Insufficiency , Risk FactorsABSTRACT
Tubulointerstitial nephritis is one of the common manifestations of immunoglobulin G (IgG)4-related disease; however, among all cases of tubulointerstitial nephritis undergoing renal biopsies, IgG4-related tubulointerstitial nephritis seems to be relatively rare because of its trivial urinary findings. A previously healthy 54-year-old man was referred to our clinic with a 4-week history of lower leg purpura and renal dysfunction. A kidney biopsy was planned because of bilateral renomegaly, by imaging studies, and elevated serum creatinine levels. Pathological findings in the kidney showed prominent infiltration of IgG4-postive plasma cells in the tubulointerstitium, but not the glumeruli. A skin biopsy revealed leukocytoclastic vasculitis, accompanied by deposition of IgA and C3 in the vascular wall, indicating Henoch-Schonlein purpura (HSP). Although cases of combined IgG4-related disease and microvasculitis, including HSP, are extremely rare, the possibility of an association between two diseases deserves attention.
Subject(s)
Humans , Middle Aged , Biopsy , Creatinine , Immunoglobulin A , Immunoglobulin G , Kidney , Leg , Nephritis, Interstitial , Plasma Cells , Purpura , IgA Vasculitis , Skin , VasculitisABSTRACT
Shoulder pain is a common problem in the elderly, which can frequently lead to disabilities. Adhesive capsulitis, rotator cuff disease, and osteoarthritis are main causes of shoulder pain in the elderly. Because the use of the upper extremity is especially pertinent to maintain independence in the elderly, proper management of shoulder pain is crucial to preserve or restore functional independence by reducing the degree of pain as much as possible. Successful treatment of shoulder pain in the elderly depends on not only an accurate diagnosis of etiologies and appropriate treatments according to clinical characteristics, but also understanding that the mechanisms of developing those diseases were closely related to the degenerative changes with age.
Subject(s)
Aged , Humans , Bursitis , Geriatrics , Osteoarthritis , Rotator Cuff , Shoulder , Shoulder Pain , Upper ExtremityABSTRACT
A 35-year-old man with known coccidioidal meningitis developed a severe headache and vomiting during routine treatment. Hydrocephalus was visible on brain imaging, and CSF study revealed pleocytosis, lowering of glucose, and increased intracranial pressure. Dexamethasone and mannitol was used for intracranial pressure control. Intrathecal amphotericin B administration and switching to itraconazole resulted in gradual improvement of symptoms. After 4 months of discontinuing amphotericin B intrathecal administration, the patient developed severe headaches with vomiting, diplopia and tandem gait. Coccidioidal meningitis aggravation was suspected based on brain MRI and CSF studies. Ventriculo-peritoneal shunt insertion was performed for intracranial pressure control and the combined therapy of intrathecal amphotericin B administration and fluconazole was maintained. This combined regimen kept the meningitis stable for 1 month.
Subject(s)
Adult , Humans , Amphotericin B , Brain , Coccidioidomycosis , Dexamethasone , Diplopia , Fluconazole , Gait , Glucose , Headache , Hydrocephalus , Intracranial Pressure , Itraconazole , Leukocytosis , Mannitol , Meningitis , Neuroimaging , Ventriculoperitoneal Shunt , VomitingABSTRACT
OBJECTIVE: To investigate if adding fiberoptic endoscopic evaluation of swallowing (FEES) to the videofluoroscopic swallowing study (VFSS) will improve the detection of abnormalities related to swallowing and pharyngolaryngeal structures. METHOD: Sixty-nine subjects (47 men, aged 64.8+/-12.0 years) with dysphagia were evaluated using VFSS and FEES simultaneously. VFSS and FEES were independently interpreted by two different examiners, who were blinded to the results of the other study. The foods that were examined were a 5-ml semi-blended diet (SBD), plain yogurt, boiled rice (NRD), and 2-ml (small fluid, SF) and 5-ml (large fluid, LF) diluted liquid barium. The detection rates of penetration or aspiration and of the pharyngeal residues in VFSS and FEES were compared. RESULTS: Combining FEES with VFSS raised the detection rates of penetration (p=0.008 for SF and LF; p<0.001 for SBD, yogurt, and NRD) and of the pharyngeal residues (p<0.001 for SF, SBD, yogurt, and NRD; p=0.001 and 0.002 for LF in the vallecula and pyriform sinus, respectively) in all the food types. Adding FEES also improved the detection of fluid aspiration (p=0.03 and 0.02 for SF and LF, respectively). Oral and pharyngeal lesions such as candidiasis, and other mucosal abnormalities, were also detected by FEES. CONCLUSION: Combining FEES with VFSS raised the diagnostic sensitivities of penetration, aspiration, and pharyngeal residues compared to the evaluation using VFSS alone. It also enabled the visualization of the abnormal structural changes in the pharyngolarynx. FEES can be performed safely by physiatrists.
Subject(s)
Aged , Humans , Male , Barium , Candidiasis , Deglutition , Deglutition Disorders , Diet , Fees and Charges , Pyriform Sinus , YogurtABSTRACT
Pure epidural cavernous hemangiomas of the spinal canal are extremely rare. We describe a case of lumbar epidural hemangioma suspected as a lumbar radiculopathy in a 78-year-old man who presented with a 1-month history of the low back pain and right lower extremity pain. An electrodiagnostic study demonstrated right L4 radiculopathy. Noncontrast magnetic resonance image (MRI) showed a nodular lesion suggestive of a sequestered disc with compression of right L4 root, most likely. Contrast MRI revealed an oval enhancing nodular lesion, 1.4x0.5 cm in size, indicative of a hemangioma in right anterior epidural space at L4 level. He underwent an excisional biopsy. The pathological diagnosis was cavernous hemangioma. His symptoms resolved after the operation. Spinal epidural cavernous hemangioma should be considered as a cause of a lumbar radiculopathy.
Subject(s)
Aged , Humans , Biopsy , Caves , Epidural Space , Hemangioma , Hemangioma, Cavernous , Low Back Pain , Lower Extremity , Magnetic Resonance Spectroscopy , Radiculopathy , Spinal CanalABSTRACT
OBJECTIVE: To find out the actual state of smoking, which is one of major risk factors of cardiovascular diseases after spinal cord injury (SCI), of community-dwelling persons with SCI, and the differences of smoking behaviors from general populations. METHOD: The persons with SCI living in community drew up a self-report paper-based questionnaires which were made up based on The third Korea National Health and Nutrition Examination Survey questionnaires for data comparisons. Demographic data, smoking duration, amount, cessation attempt and plan were asked. RESULTS: Questionnaires were sent to 459 persons with SCI and 332 persons from twenties to sixties were finally analysed. In men, the lifetime smoking rates of SCI subjects in their forties and fifties were lower and the current smoking rate of tetraplegic subjects in their forties and fifties were lower than those of general population. But the amount of smoking and attempt to stop smoking were of no differences. In women, there were no significant differences in all parameters. CONCLUSION: There were no significant differences in smoking rates and amounts between SCI patients and general populations, but smokers with SCI showed weak intention to cease smoking.
Subject(s)
Female , Humans , Male , Cardiovascular Diseases , Intention , Korea , Nutrition Surveys , Surveys and Questionnaires , Risk Factors , Smoke , Smoking , Spinal Cord , Spinal Cord Injuries , Tobacco ProductsABSTRACT
Strongyloides stercoralis is a nematode that may involve any segment of the Gl tract or virtually every human organ because of its autoinfection cycle and hyperinfection. It may occur in either immunocompetent or immunocompromised individuals. A 72-year-old woman who had no notable medical history presented with chronic diarrhea and generalized edema and she revealed protein losing eneteropathy. She was diagnosed with Strongyloidiasis infection through EGD and a colonoscopic biopsy specimen at a time when there were rhabditiform larvae present. The patient was treated with albendazole 400 mg/day for three days. At the follow-up three months later, the endoscopic biopsy specimens revealed no evidence of Strongyloidiasis infection and her clinical symptoms had progressively improved. The present case represents a rare report of Strongyloidiasis in a immunocompetent patient diagnosed through EGD and the colonoscopic biopsy specimen concurrently. So, we report on this case along with a review of the relevant literature.
Subject(s)
Aged , Female , Humans , Albendazole , Biopsy , Colon , Diarrhea , Edema , Follow-Up Studies , Hypoalbuminemia , Larva , Stomach , Strongyloides , Strongyloides stercoralis , StrongyloidiasisABSTRACT
No abstract available.
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OBJECTIVE: To describe the frequency and reasons for rehospitalization in patients with spinal cord injury (SCI) living in the community. METHOD: A total 388 patients with SCI living in community participated in the nationwide questionnaire-based study. A self-administered questionnaire was used. RESULTS: Of the 459 patients originally enrolled, 388 completed questionnaires, yielding response rate of 84.5%. The reasons for rehospitalization were SCI related complications (71.7%), periodic health evaluation (44.7%), and other causes (28.3%). The most frequent SCI related complications for rehospitalization were urinary tract infections (45.2%), pressure sores (39.7%), fever (18.3%), pain (18.3%), and autonomic dysreflexia (7.6%). The number of rehospitalized cases due to SCI related complication including urinary tract infection was significantly higher in complete SCI. Rehospitalization due to pressures sore was more frequent in people with paraplegia, male and complete injuries. CONCLUSION: In our study, 71.7% of patients with SCI experienced rehospitalization for SCI related complication after initial hospitalization. Urinary tract infection and pressure sores were the most common SCI related complications for rehospitalization.