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1.
Intern Med ; 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37981309

ABSTRACT

A 65-year-old woman with a history of peritoneal dialysis undergoing hemodialysis at our hospital presented with a fever after experiencing gastroenteritis symptoms. She had an implanted peritoneal dialysis catheter for draining chylous ascites. After commencing empirical treatment with meropenem, peritoneal effluent samples revealed an increased white blood cell count, and peritonitis was diagnosed. Enterococcus gallinarum was detected in blood and effluent cultures. Meropenem was changed to vancomycin based on susceptibility testing but subsequently restarted and thereafter changed to ampicillin following exacerbation of peritonitis. Finally, catheter removal led to complete recovery. E. gallinarum is vancomycin-resistant and a rare cause of peritonitis.

2.
Clin Exp Nephrol ; 21(1): 55-62, 2017 Feb.
Article in English | MEDLINE | ID: mdl-26920126

ABSTRACT

BACKGROUND: The relationship between protein-energy wasting and chronic kidney disease (CKD) progression is unknown. In the present prospective cohort study, we evaluated the hypothesis that a combination of low body mass index (BMI) and serum albumin level is associated with rapid CKD progression. METHODS: The study cohort comprised 728 predialysis Japanese patients with CKD (stages 2-5) enrolled from 2010 to 2011. Patients were categorized into four groups according to their serum albumin levels and BMI: group 1, low serum albumin level (<4 g/dL) and low BMI (<23.5 kg/m2); group 2, high serum albumin level (≥4 g/dL) and low BMI; group 3, low serum albumin level and high BMI (≥23.5 kg/m2); and group 4, high serum albumin level and high BMI. The primary outcome was a 30 % decline in estimated glomerular filtration rate (eGFR) or start of dialysis within 2 years. The secondary outcome was an annual GFR decline (mL/min/1.73 m2/year). RESULTS: Logistic regression analysis adjusted for baseline characteristics (reference, group 4) showed that only group 1 was associated with a significant risk of CKD progression, with adjusted odds ratio of 3.51 [95 % confidence interval (CI) (1.63, 7.56)]. A multivariate linear regression analysis adjusted for baseline characteristics showed a significant difference in annual eGFR decline between groups 1 and 4 [coefficients ß (standard error) -2.62 (0.75), p = 0.001]. CONCLUSION: This study suggests that combined effects of low BMI (<23.5 kg/m2) and serum albumin level (<4 g/dL) are associated with CKD progression.


Subject(s)
Body Mass Index , Hypoalbuminemia/complications , Protein-Energy Malnutrition/complications , Renal Insufficiency, Chronic/complications , Serum Albumin/analysis , Thinness/complications , Aged , Aged, 80 and over , Biomarkers/blood , Chi-Square Distribution , Disease Progression , Down-Regulation , Female , Glomerular Filtration Rate , Humans , Hypoalbuminemia/blood , Hypoalbuminemia/diagnosis , Kidney/physiopathology , Linear Models , Logistic Models , Male , Middle Aged , Multivariate Analysis , Nutritional Status , Odds Ratio , Prospective Studies , Protein-Energy Malnutrition/blood , Protein-Energy Malnutrition/diagnosis , Protein-Energy Malnutrition/physiopathology , Renal Dialysis , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Risk Factors , Serum Albumin, Human , Thinness/diagnosis , Thinness/physiopathology , Time Factors , Tokyo
3.
Clin Exp Nephrol ; 21(1): 104-111, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27039905

ABSTRACT

BACKGROUND: Electrolyte abnormalities, particularly dysnatremia, are independent predictors of adverse outcome in individuals with and without renal failure. However, the association of serum chloride level (Cl-) with mortality or risk of cardiovascular (CV) events in chronic kidney disease (CKD) remains unclear. METHODS: This prospective cohort study included 923 pre-dialysis CKD G2-G5 patients among the participants of the CKD Research of Outcomes in Treatment and Epidemiology (CKD-ROUTE) study, who newly visited 16 nephrology centers. The primary outcome was a composite of overall death and CV events, and the secondary outcome was overall death. Data were analyzed using the Cox hazards model with adjustment for potential confounders. RESULTS: Median Cl- was 106.0 mEq/L at enrollment [quartile (Q) 1: ≤103.9, n =  207; Q2: 104.0-105.9, n =  207; Q3: 106.0-108.0, n =  289; Q4: ≥108.1, n = 220]. During a median follow-up of 33 months, there were 98 CV events, 66 deaths, and 154 composite outcomes. The hazard ratio (HR) for the composite outcome was higher for Q1 than Q3 [HR 1.72; 95 % confidence interval (CI) 1.08-2.72; P =  0.022]. As a continuous variable in a subset of patients whose Cl- was ≤106.0 mEq/L, higher Cl- was associated with lower risk of the composite outcome (HR 0.93; 95 % CI 0.87-0.99; P = 0.023). HR for all-cause mortality was also higher for Q1 than Q3 (HR 2.48; 95 % CI 1.22-5.03; P =  0.012). CONCLUSION: Low Cl- was associated with increased mortality and risk of CV events in pre-dialysis CKD patients. Cl- may be an additional prognostic indicator in CKD.


Subject(s)
Cardiovascular Diseases/blood , Cardiovascular Diseases/mortality , Chlorides/blood , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/mortality , Aged , Aged, 80 and over , Biomarkers/blood , Cardiovascular Diseases/diagnosis , Cause of Death , Chi-Square Distribution , Down-Regulation , Female , Humans , Japan/epidemiology , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , Prospective Studies , Renal Insufficiency, Chronic/diagnosis , Risk Factors , Time Factors
4.
Intern Med ; 54(11): 1375-80, 2015.
Article in English | MEDLINE | ID: mdl-26027990

ABSTRACT

The onset of hyperammonemia due to the flow of ammonia-rich portal vein blood through a portal-systemic shunt causes a type of encephalopathy known as chronic portal-systemic shunt encephalopathy (CPSE). We herein report two cases of CPSE that presented with opposite changes in the blood ammonia concentrations during hemodialysis. It is curious that the encephalopathy was ameliorated by hemodialysis in case 1, but not case 2. Therefore, it is necessary to recognize CPSE and assess the blood ammonia concentrations in dialysis patients who develop a disturbance of consciousness, even if the serum transaminase level is normal.


Subject(s)
Ammonia/blood , Brain Damage, Chronic/blood , Brain Damage, Chronic/etiology , Renal Dialysis/adverse effects , Aged , Brain Damage, Chronic/surgery , Female , Humans , Male , Middle Aged , Portal Vein , Treatment Outcome
5.
J Am Soc Nephrol ; 26(9): 2129-38, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25556166

ABSTRACT

Recently, the kelch-like protein 3 (KLHL3)-Cullin3 complex was identified as an E3 ubiquitin ligase for with no lysine (WNK) kinases, and the impaired ubiquitination of WNK4 causes pseudohypoaldosteronism type II (PHAII), a hereditary hypertensive disease. However, the involvement of WNK kinase regulation by ubiquitination in situations other than PHAII has not been identified. Previously, we identified the WNK3-STE20/SPS1-related proline/alanine-rich kinase-Na/K/Cl cotransporter isoform 1 phosphorylation cascade in vascular smooth muscle cells and found that it constitutes an important mechanism of vascular constriction by angiotensin II (AngII). In this study, we investigated the involvement of KLHL proteins in AngII-induced WNK3 activation of vascular smooth muscle cells. In the mouse aorta and mouse vascular smooth muscle (MOVAS) cells, KLHL3 was not expressed, but KLHL2, the closest homolog of KLHL3, was expressed. Salt depletion and acute infusion of AngII decreased KLHL2 and increased WNK3 levels in the mouse aorta. Notably, the AngII-induced changes in KLHL2 and WNK3 expression occurred within minutes in MOVAS cells. Results of KLHL2 overexpression and knockdown experiments in MOVAS cells confirmed that KLHL2 is the major regulator of WNK3 protein abundance. The AngII-induced decrease in KLHL2 was not caused by decreased transcription but increased autophagy-mediated degradation. Furthermore, knockdown of sequestosome 1/p62 prevented the decrease in KLHL2, suggesting that the mechanism of KLHL2 autophagy could be selective autophagy mediated by sequestosome 1/p62. Thus, we identified a novel component of signal transduction in AngII-induced vascular contraction that could be a promising drug target.


Subject(s)
Angiotensin II/pharmacokinetics , Microfilament Proteins/metabolism , Muscle Tonus/physiology , Nerve Tissue Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction/drug effects , Adaptor Proteins, Signal Transducing/genetics , Angiotensin II/pharmacology , Animals , Aorta , Autophagy/drug effects , Cells, Cultured , Gene Knockdown Techniques , Heat-Shock Proteins/genetics , Mice , Microfilament Proteins/drug effects , Microfilament Proteins/genetics , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Nerve Tissue Proteins/drug effects , Nerve Tissue Proteins/genetics , Protein Serine-Threonine Kinases/drug effects , Sequestosome-1 Protein , Sodium, Dietary/pharmacology , Solute Carrier Family 12, Member 2/metabolism , Vasoconstriction
6.
Hypertension ; 62(5): 872-8, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24019400

ABSTRACT

Na-K-Cl cotransporter isoform 1 (NKCC1) is involved in the regulation of vascular smooth muscle cell contraction. Recently, the with-no-lysine kinase (WNK)-STE20/SPS1-related proline/alanine-rich kinase (SPAK)-NKCC1 phosphorylation cascade in vascular smooth muscle cells was found to be important in the regulation of vascular tone. In this study, we investigated whether the WNK-SPAK-NKCC1 cascade in mouse aortic tissue is regulated by dietary salt intake and the mechanisms responsible. Phosphorylation of SPAK and NKCC1 was significantly reduced in the aorta in high-salt-fed mice and was increased in the aorta in low-salt-fed mice, indicating that the WNK-SPAK-NKCC1 phosphorylation cascade in the aorta was indeed regulated by dietary salt intake. Acute and chronic angiotensin II infusion increased phosphorylation of SPAK and NKCC1 in the mouse aorta. In addition, valsartan, an antagonist of angiotensin II type 1 receptor, inhibited low-salt diet-induced phosphorylation of SPAK and NKCC1, demonstrating that angiotensin II activates the WNK-SPAK-NKCC1 phosphorylation cascade through the angiotensin II type 1 receptor. However, a low-salt diet and angiotensin II together did not increase phosphorylation of SPAK and NKCC1 in the aorta in WNK3 knockout mice, indicating that activation of the WNK-SPAK-NKCC1 phosphorylation cascade induced by a low-salt diet and angiotensin II is dependent on WNK3. Indeed, angiotensin II-induced increases in blood pressure were diminished in WNK3 knockout mice. In addition, decreased response to angiotensin II in the mesenteric arteries was observed in WNK3 knockout mice. Our data also clarified a novel mechanism for regulation of vascular tonus by angiotensin II. Inhibition of this cascade could, therefore, be a novel therapeutic target in hypertension.


Subject(s)
Angiotensin II/pharmacology , Aorta/metabolism , Protein Serine-Threonine Kinases/metabolism , Solute Carrier Family 12, Member 2/metabolism , Angiotensin II Type 1 Receptor Blockers/pharmacology , Animals , Aorta/drug effects , Blood Pressure/drug effects , Blood Pressure/physiology , Mesenteric Arteries/drug effects , Mesenteric Arteries/metabolism , Mice , Mice, Knockout , Phosphorylation/drug effects , Protein Serine-Threonine Kinases/genetics , Sodium, Dietary , Tetrazoles/pharmacology , Valine/analogs & derivatives , Valine/pharmacology , Valsartan
7.
Biol Open ; 1(2): 120-7, 2012 Feb 15.
Article in English | MEDLINE | ID: mdl-23213404

ABSTRACT

Mutations in WNK1 and WNK4 kinase genes have been shown to cause a human hereditary hypertensive disease, pseudohypoaldosteronism type II (PHAII). We previously discovered that WNK kinases phosphorylate and activate OSR1/SPAK kinases that regulate renal SLC12A family transporters such as NKCC2 and NCC, and clarified that the constitutive activation of this cascade causes PHAII. WNK3, another member of the WNK kinase family, was reported to be a strong activator of NCC/NKCC2 when assayed in Xenopus oocytes, suggesting that WNK3 also plays a major role in regulating blood pressure and sodium reabsorption in the kidney. However, it remains to be determined whether WNK3 is in fact involved in the regulation of these transporters in vivo. To clarify this issue, we generated and analyzed WNK3 knockout mice. Surprisingly, phosphorylation and expression of OSR1, SPAK, NKCC2 and NCC did not decrease in knockout mouse kidney under normal and low-salt diets. Similarly, expression of epithelial Na channel and Na/H exchanger 3 were not affected in knockout mice. Na(+) and K(+) excretion in urine in WNK3 knockout mice was not affected under different salt diets. Blood pressure in WNK3 knockout mice was not lower under normal diet. However, lower blood pressure was observed in WNK3 knockout mice fed low-salt diet. WNK4 and WNK1 expression was slightly elevated in the knockout mice under low-salt diet, suggesting compensation for WNK3 knockout by these WNKs. Thus, WNK3 may have some role in the WNK-OSR1/SPAK-NCC/NKCC2 signal cascade in the kidney, but its contribution to total WNK kinase activity may be minimal.

8.
Biochem Biophys Res Commun ; 425(2): 456-61, 2012 Aug 24.
Article in English | MEDLINE | ID: mdl-22846565

ABSTRACT

Na-Cl cotransporter (NCC) is phosphorylated in its amino terminus based on salt intake under the regulation of the WNK-OSR1/SPAK kinase cascade. We have observed that total protein abundance of NCC and its apical membrane expression varies in the kidney based on the phosphorylation status. To clarify the mechanism, we examined NCC ubiquitination status in mice fed low, normal and high salt diets, as well as in a model mouse of pseudohypoaldosteronism type II (PHAII) where NCC phosphorylation is constitutively elevated. Low-salt diet decreased NCC ubiquitination, while high-salt diet increased NCC ubiquitination in the kidney, and this was inversely correlated with total and phosphorylated NCC abundance. In the PHAII model, the ubiquitination of NCC in kidney was also lower when compared to that in wild-type littermates. To evaluate the relationship between phosphorylation and ubiquitination of NCC, we expressed wild-type, phospho-deficient and -mimicking NCC in COS7 cells, and the ubiquitination of immunoprecipitated total and biotinylated surface NCC was evaluated. NCC ubiquitination was increased in the phospho-deficient NCC and decreased in phospho-mimicking NCC in both total and surface NCC. Thus, we demonstrated that NCC phosphorylation decreased NCC ubiquitination, which may contribute to the increase of NCC abundance mostly on plasma membranes.


Subject(s)
Diet, Sodium-Restricted , Protein Serine-Threonine Kinases/metabolism , Pseudohypoaldosteronism/metabolism , Receptors, Drug/metabolism , Symporters/metabolism , Ubiquitination , Animals , COS Cells , Chlorocebus aethiops , Disease Models, Animal , Mice , Mice, Inbred C57BL , Phosphorylation , Solute Carrier Family 12, Member 3
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