Chronic kidney disease (CKD) is a global health problem. CKD patients are at high risk of developing cardiovascular disease (CVD), including coronary artery disease, heart failure and stroke. Several ...factors invoke a vicious cycle of CKD and CVD, which is referred as to “cardiorenal syndrome”. Among these factors, the compounds retained through loss of renal excretion play a pathological role in causing atherosclerosis and CVD. These compounds have been broadly classified as uremic toxins because of their accumulation with declining renal function and cytotoxicity. The major uremic toxins contributing to CVD are asymmetric dimethylarginine (ADMA), advanced glycation endproducts (AGE), and trimethyl amine N-oxide (TMAO). ADMA is linked to CVD through regulation of nitric oxide, reactive oxygen species, and renal anemia. AGE not only directly accumulates in the heart and kidney, but interacts with the receptor for AGE (RAGE), leading to cell damage in CVD. TMAO correlates with a high prevalence of CVD and promotes organ fibrosis by itself. The levels of these and other uremic toxins rise with worsening CKD, inducing multiplicative damage in the heart and kidney. Therefore, a better understanding of uremic toxins has great clinical importance for preventing cardiorenal syndrome. This review highlights the molecular mechanism by which these uremic toxins are implicated in CVD and suggests the possible mutual relationship between them.
STUDY DESIGN.A retrospective single-center study.
OBJECTIVE.The aim of this study was to evaluate the compensatory mechanism of cervical lordosis (CL), the changes in cervical sagittal alignment, and ...range of motion (ROM) after muscle-preserving selective laminectomy (SL).
SUMMARY OF BACKGROUND DATA.CL increases as a compensatory mechanism for the adjustment of cervical sagittal balance or horizontal gaze. However, laminoplasty invades this mechanism and causes kyphosis in higher T1 (C7) slope patients.
METHODS.SL is a posterior surgery selecting the decompression laminae without disturbing the extensor musculature and facet joints. The clinical features and radiological findings of 125 cervical compressive myelopathy patients who underwent C6 single-level SL, C5-C6 two consecutive levels SL, C4-C6 three consecutive levels SL, and C3-C6 four consecutive levels SL were enrolled. Cervical spine lateral radiography was performed before surgery and at the final follow-up. The patients were divided into two groups according to the preoperative C7 slope. Postoperative cervical alignment change was compared between the higher and lower C7 slope groups. Subsequently, pre- and postoperative cervical alignment and cervical ROM were analyzed according to the number of consecutive laminae surgically treated.
RESULTS.Patients with higher C7 slope had greater lordotic cervical alignment and larger C2-C7 sagittal vertical axis (SVA) pre- and postoperatively. No kyphotic alignment change was observed, even in the higher C7 slope group. C6 SL and C5-C6 SL did not affect C2-C7 angle, and did not increase C2-C7 SVA after surgery. Although C4-C6 SL and C3-C6 SL demonstrated postoperative slight increase in C2-C7 SVA, C2-C7 angle never decreased after surgery. Cervical ROM slightly reduced in the C4-C6 SL and C3-C6 SL groups; however, no reduction of ROM was observed in the C6 SL and C5-C6 SL groups.
CONCLUSION.SL preserved the inherent compensatory CL that had been observed preoperatively and maintained cervical sagittal balance after surgery.Level of Evidence4
A non-enzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules, whose process has been known to progress at an ...accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs).
In this paper, we review the role of AGE–oxidative stress axis and its therapeutic interventions in vascular complications in diabetes.
AGEs elicit oxidative stress generation and subsequently cause inflammatory and thrombogenic reactions in various types of cells via interaction with a receptor for AGEs (RAGE), thereby being involved in vascular complications in diabetes. In addition, mitochondrial superoxide generation has been shown to play an important role in the formation and accumulation of AGEs under diabetic conditions. Further, we have recently found that a pathophysiological crosstalk between AGE–RAGE axis and renin–angiotensin system (RAS) could contribute to the progression of vascular damage in diabetes.
These observations suggest that inhibition of AGE–RAGE–oxidative stress axis or blockade of its interaction with RAS is a novel therapeutic strategy for preventing vascular complications in diabetes.
► AGEs elicit oxidative stress generation and subsequently cause inflammatory and thrombogenic reactions via interaction with a receptor for AGEs (RAGE). ► Mitochondrial superoxide generation plays an important role in the formation and accumulation of AGEs under diabetic conditions. ► A pathophysiological crosstalk between AGE–RAGE axis and renin–angiotensin system could contribute to vascular complications in diabetes. ► Inhibition of AGEs–RAGE–oxidative stress system is a therapeutic target for preventing vascular complications in diabetes.
Purpose
Between 2006 and 2010, we performed wide laminectomy (wide LAM) alone, with decompression performed between the bilateral medial margin of the zygapophyseal joints, or double-door ...laminoplasty (DL) combined with wide LAM for cervical compressive myelopathy (CCM). From 2010, instead of wide LAM and DL, we began to perform narrow LAM, where the laminectomy width was no more than 2–3 mm wider than the spinal cord width (SW). This study aimed to elucidate the risk factors for C5 palsy by reviewing surgical outcomes.
Methods
The clinical features and radiological findings of 263 CCM patients with or without C5 palsy were compared. Risk factors for C5 palsy were assessed using logistic regression analysis. The decompression width (DW) was defined as the laminectomy width or the width between the bilateral medial margins of the bony gutters in DL.
Results
Narrow LAM reduced the incidence of C5 palsy from 9.2 to 1.2%. DL was performed more frequently in the C5 palsy group. The difference between the DW and the SW (DW − SW) was significantly greater in the C5 palsy group. Posterior spinal cord shift, aging, and the number of consecutive laminae surgically treated were significantly higher in the C5 palsy group. The diameter of the foramen (DF) at C4/5 was significantly smaller in the C5 palsy patients. The logistic regression analysis revealed that DL, DW − SW, DF, and aging were risk factors for C5 palsy.
Conclusions
Cervical laminectomy of limited width prevented postoperative C5 palsy without compromising the functional recovery.
Background
Severe acute respiratory syndrome Coronavirus 2 has rapidly spread worldwide, with acute kidney injury (AKI) as one of the manifestations with unknown causal mechanisms. We aimed to ...investigate tubular injury by assessing tubular markers and their association with the severity of Coronavirus disease 2019 (COVID-19).
Methods
We examined the associations between laboratory markers and urinary levels of N-acetyl-β-
d
-glucosaminidase (uNAG), β2-microglobulin (u β2MG), α1-microglobulin (u α1MG), and liver-type fatty acid binding protein (L-FABP). We studied 18 COVID-19 patients without previous chronic kidney disease and analyzed the relationship between the urinary biomarkers and inflammatory markers in patients with severe (
n
= 7) or non-severe (
n
= 11) COVID-19, defined by requirements of supplemental oxygen.
Results
Fourteen patients (78%) showed abnormal urinalysis findings and two (11%) developed AKI. Patients with severe COVID-19 had significantly higher levels of proteinuria, uNAG, uβ2MG, uα 1MG, and L-FABP than those with non-severe disease. Serum levels of interleukin-6 (IL-6) were significantly higher on admission in all severe COVID-19 cases and correlated with the levels of L-FABP, uβ2MG, uα1MG, uNAG, and proteinuria. Moreover, the changes in serum IL-6 (ΔIL-6) levels from baseline to 7 days after admission significantly correlated with ΔL-FABP and Δuβ2MG.
Conclusions
Levels of tubular injury markers, especially L-FABP and uβ2MG, were significantly associated with IL-6 levels even in patients with no evident AKI. This suggests that L-FABP and uβ2MG could be useful as early detective biomarkers for COVID-19 associated renal injury.
Aims/Introduction
Urinary kidney injury molecule‐1 (KIM‐1) has been associated with proximal tubular damage in human and animal studies. Although it has been recognized as a biomarker of acute kidney ...injury and chronic kidney disease, its significance in the serum remains unclear. Therefore, we examined the relationship of serum and urinary KIM‐1 levels with renal parameters in patients with type 2 diabetes.
Materials and Methods
Serum and urinary KIM‐1 levels, together with urinary liver‐type fatty acid‐binding protein, were measured in 602 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. These were then compared with the urinary albumin‐to‐creatinine ratio and eGFR.
Results
The serum and urinary KIM‐1 levels were significantly different among the three (eGFR ≥60, 45–59, <45 mL/min/1.73 m2) groups. These levels were positively associated with the albumin‐to‐creatinine ratio and negatively associated with eGFR. In a multivariate logistic model, both serum and urinary KIM‐1 were associated with an increased albumin‐to‐creatinine ratio (>30 mg/g Cr), but only the serum KIM‐1 was associated with a lower eGFR (<60 mL/min/1.73 m2), after adjustment for covariates.
Conclusions
Renal parameters appear to be strongly associated with serum KIM‐1, and not urinary KIM‐1, in patients with type 2 diabetes and an eGFR ≥30 mL/min/1.73 m2.
Both serum and urinary kidney injury molecule‐1 were associated with an increased albumin‐to‐creatinine ratio, but only serum kidney injury molecule‐1 was associated with a lower estimated glomerular filtration rate after adjustment for covariates in patients with type 2 diabetes and an estimated glomerular filtration rate ≥30 mL/min/1.73 m2.
A 37-year-old woman with chronic kidney disease stage (CKD) G4 with membranoproliferative glomerulonephritis was hospitalized for nephrotic syndrome and hypertension due to superimposed preeclampsia ...at 27 weeks into her third pregnancy. Proteinuria did not worsen significantly after pulse steroid therapy. Delivery was induced at 30 weeks' gestation due to the maternal renal function and fetal growth. No obvious fetal complications other than preterm delivery were observed. In this case, we successfully managed a high-risk patient with membranoproliferative glomerulonephritis complicated by advanced CKD, nephrotic syndrome, and hypertension, which are independent risk factors for pregnancy complications.
Hypertension and constipation are major hemodialysis complications. Salt restriction is one of the most important nonpharmacological interventions in managing hypertension. In patients undergoing ...hemodialysis, nonpharmacological strategies to manage constipation are extremely difficult to develop owing to the presence of excess dietary potassium and fluids. Frugra®, which is a cereal food that has a low salt content of 0.5 g per serving, may help reduce salt intake. Additionally, Frugra is rich in dietary fiber, thereby beneficial for such patients. In this study, we evaluated the safety and efficacy of Frugra in patients undergoing hemodialysis, focusing mainly on blood pressure and bowel health by changing the usual breakfast meal to Frugra for 8 weeks. We enrolled 11 patients undergoing hemodialysis. Despite the absence of changes in the patients’ dry weight levels, their systolic blood pressure levels decreased from 155.5 ± 20.9 mmHg to 137.9 ± 10.3 mmHg after 2 months (P < 0.05). All participants reported improvements in bowel movement, and the levels of indoxyl sulfate, a representative gut-derived uremic toxin, were decreased from 49.3 μg/ml to 33.4 μg/ml. Furthermore, adverse events including electrolyte abnormalities were not observed. Therefore, Frugra may be useful to manage the health of patients undergoing hemodialysis.
Purpose
A high C7 slope induces C2–C7 lordosis to compensate for cervical sagittal balance adjustments. A muscle-preserving selective laminectomy (SL) can maintain this compensation postoperatively. ...This study evaluated the effect of an extremely high C7 slope on C2–C7 lordotic compensation following SL.
Methods
This study enrolled 151 cervical compressive myelopathy patients who underwent SL. Lateral cervical spine radiographs were taken before surgery and during final follow-up. Patients were divided into extremely high C7 slope (≥ 30°) (EH) and non-high C7 slope (< 30°) (NH) groups and the influence of a high C7 slope on radiological and surgical outcomes was examined.
Results
Mean age was higher in group EH (
p
< 0.001). Preoperatively, patients in group EH had a larger C2–C7 sagittal vertical axis (SVA) (
p
= 0.001) and greater cervical lordosis (
p
< 0.001). Although C2–C7 SVA increased after surgery, mean C2–C7 angle of group EH decreased. Mismatches between C7 slope and C2–C7 angle increased for group EH postoperatively (
p
= 0.015). Postoperative Japanese Orthopedic Association (JOA) score and recovery rate (RR) were slightly lower in group EH (
p
= 0.001 and
p
= 0.006, respectively). Multiple linear regression analyses revealed that extremely high C7 slope, not age, affected the RR of JOA score (
p
= 0.006).
Conclusions
Patients in group EH were older and had highly compensated cervical sagittal alignment preoperatively. They demonstrated postoperative cervical sagittal balance mismatch increases and slightly worse functional recovery. An extremely high C7 slope limited compensatory cervical lordosis following SL.
Graphical abstract
These slides can be retrieved under Electronic Supplementary Material.
In sleep apnea syndrome (SAS), chronic intermittent hypoxia (CIH) is believed to activate the sympathetic nerve system, and is thus involved in cardiovascular diseases (CVD). However, since patients ...with SAS are often already obese, and have diabetes and/or hypertension (HT), the effects of CIH alone on sympathetic nerve activation and its impacts on CVD are largely unknown. We, therefore, examined the effects of CIH on sympathetic nerve activation in non-obese mice to determine whether renal sympathetic nerve denervation (RD) could ameliorate CIH-mediated cardiovascular effects. Male C57BL/6 (WT) mice were exposed to normal (FiO
21%) or CIH (10% O
, 12 times/h, 8 h/day) conditions for 4 weeks with or without RD treatment. Increased urinary norepinephrine (NE), 8-OHdG, and angiotensinogen levels and elevated serum asymmetric dimethyl arginine levels were observed in the CIH model. Concomitant with these changes, blood pressure levels were significantly elevated by CIH treatment. However, these deleterious effects by CIH were completely blocked by RD treatment. The present study demonstrated that CIH-mediated renal sympathetic nerve activation is involved in increased systemic oxidative stress, endothelial dysfunction, and renin-angiotensin system activation, thereby contributing to the development of HT and CVD, thus could be an important therapeutic target in patients with SAS.
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