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1.
Nutrients ; 13(6)2021 May 31.
Article in English | MEDLINE | ID: mdl-34073024

ABSTRACT

L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months. Carnitine fractions were assessed by enzyme cycling methods. Plasma and red blood cell (RBC) acylcarnitines were profiled using tandem mass spectrometry. Cardiac function was evaluated using echocardiography and plasma B-type natriuretic peptide (BNP) levels. Reducing LC administration to once weekly significantly decreased plasma carnitine fractions and RBC-free carnitine levels during the study period, which were further decreased in the placebo group (p < 0.001). Plasma BNP levels were significantly elevated in the placebo group (p = 0.03). Furthermore, changes in RBC (C16 + C18:1)/C2 acylcarnitine ratio were positively correlated with changes in plasma BNP levels (ß = 0.389, p = 0.005). Reducing LC administration for six months significantly decreased both plasma and RBC carnitine levels, while the full termination of LC increased plasma BNP levels; however, it did not influence cardiac function in HD patients.


Subject(s)
Carnitine/blood , Carnitine/pharmacokinetics , Dietary Supplements , Heart Failure/prevention & control , Heart/drug effects , Kidney Failure, Chronic/therapy , Renal Dialysis/methods , Aged , Carnitine/administration & dosage , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Heart/physiopathology , Heart Failure/complications , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Male , Middle Aged , Prospective Studies , Single-Blind Method
2.
Kurume Med J ; 66(3): 153-160, 2021 Oct 06.
Article in English | MEDLINE | ID: mdl-32848104

ABSTRACT

BACKGROUND: Carnitine plays a pivotal role in energy synthesis through ß-oxidation in mitochondria. Serum and tissue levels of free carnitine are significantly decreased in dialysis patients, whereas acylcarnitine levels are increased. However, the precise kinetics and fate of carnitine fractions in chronic kidney disease (CKD) patients who are not on dialysis have not been clarified. This study aims to determine the kinetics of serum carnitine fractions in patients who were not on dialysis. METHODS: Seventy-five CKD patients not on dialysis were recruited in this study. Serum and urinary carnitine fraction levels were measured to evaluate the kinetics and regulation of serum carnitine fractions. Carnitine fractions were measured by the enzymatic cycling method. RESULTS: Total and free serum carnitine levels did not change with progression of CKD, whereas acylcarnitine levels and the acyl/free carnitine ratio significantly increased. Serum acylcarnitine levels were inversely associated with estimated glomerular filtration rate (r2 = 0.239, p < 0.001), but free carnitine levels were not. Serum free carnitine levels were positively associated with urinary free carnitine excretion (r2 = 0.214, p < 0.001), but serum acylcarnitine levels were not. Multiple stepwise regression analysis revealed that urinary free carnitine excretion and blood urea nitrogen were independent determinants of serum free carnitine and acylcarnitine levels, respectively. CONCLUSIONS: The present study demonstrated that serum acylcarnitine levels increased with renal dysfunction independent of urinary excretion levels. Serum free carnitine was not affected by renal function in CKD patients who were not on dialysis.


Subject(s)
Carnitine/blood , Kidney Failure, Chronic/physiopathology , Kidney/metabolism , Renal Insufficiency, Chronic/blood , Adult , Aged , Amino Acids , Carnitine/analogs & derivatives , Female , Glomerular Filtration Rate , Humans , Kinetics , Male , Middle Aged , Renal Insufficiency, Chronic/physiopathology , Urea/blood , Uric Acid/blood
3.
Clin Exp Nephrol ; 25(3): 251-260, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33141305

ABSTRACT

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder caused by mutations in the polycystic kidney disease (PKD) gene. Although tolvaptan has benefits for renal involvement, the different effects depending on the gene mutation type are unknown. Thus, we explore the different effects of tolvaptan on the annual changes in total kidney volume (%TKV) and estimated glomerular filtration rate (eGFR) according to the gene mutation type in ADPKD patients. METHODS: In total, 135 ADPKD patients were screened, and 22 patients taking tolvaptan for at least a year were retrospectively studied at the Kurume University Hospital. We examined the decline in renal function and %TKV by computed tomography and analyzed the gene mutation. Patients were classified into the following four groups according to gene mutation type: PKD1-truncated, PKD1-non-truncated, PKD2, and mutation not found. Patients were treated with tolvaptan, and the effects of tolvaptan were analyzed according to the gene mutation type. RESULTS: Patients (age: 52.3 ± 11.2 years) were administered tolvaptan at a dose of 45 or 60 mg. No variation was observed in the annual changes in eGFR (%eGFR) (before: - 10.5% ± 13.9%, after: - 14.4% ± 8.1%, P = 0.139), whereas %TKV was significantly improved after the tolvaptan treatment (before: 14.9% ± 8.0%, after: - 5.4% ± 7.6%, P < 0.001). Unlike %eGFR, tolvaptan treatment significantly improved %TKV, regardless of the type of gene mutation. CONCLUSIONS: A year treatment with tolvaptan significantly improved %TKV in patients with ADPKD, regardless of the gene mutation type.


Subject(s)
Antidiuretic Hormone Receptor Antagonists/therapeutic use , Kidney/drug effects , Mutation , Polycystic Kidney, Autosomal Dominant/drug therapy , TRPP Cation Channels/genetics , Tolvaptan/therapeutic use , Adult , Aged , Female , Genetic Predisposition to Disease , Glomerular Filtration Rate/drug effects , Humans , Kidney/diagnostic imaging , Kidney/physiopathology , Male , Middle Aged , Polycystic Kidney, Autosomal Dominant/diagnosis , Polycystic Kidney, Autosomal Dominant/genetics , Polycystic Kidney, Autosomal Dominant/physiopathology , Recovery of Function , Retrospective Studies , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
4.
Sci Rep ; 8(1): 2686, 2018 02 08.
Article in English | MEDLINE | ID: mdl-29422652

ABSTRACT

The mineralocorticoid receptor (MR) and its downstream signaling play an important role in hypertensive renal injury. The interaction of advanced glycation end products (AGE) with their receptor (RAGE) is involved in the progression of renal disease. However, the pathological crosstalk between AGE-RAGE axis and MR system in kidney derangement remains unclear. We screened DNA-aptamer directed against RAGE (RAGE-apt) in vitro and examined its effects on renal injury in uninephrectomized deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mice. RAGE, GTP-bound Rac-1 (Rac1), and MR were co-localized in the podocytes of DOCA mice. The deletion of RAGE gene significantly inhibited mesangial matrix expansion and tubulointerstitial fibrosis in DOCA mice, which was associated with the reduction of glomerular oxidative stress, MR, Rac1, and urinary albumin excretion (UAE) levels. RAGE-apt attenuated the increase in carboxymethyllysine (CML), RAGE, nitrotyrosine, Rac1, and MR levels in the kidneys and reduced UAE in DOCA mice. Aldosterone (Aldo) increased nitrotyrosine, CML, and RAGE gene expression in murine podocytes, whereas CML stimulated MR and Rac1 levels, which were blocked by RAGE-apt. The present study indicates the crosstalk between the AGE-RAGE axis and Aldo-MR system, suggesting that RAGE-apt may be a novel therapeutic tool for the treatment of MR-associated renal diseases.


Subject(s)
Acute Kidney Injury/drug therapy , Aptamers, Peptide/pharmacology , Receptor for Advanced Glycation End Products/genetics , Acetates/metabolism , Acute Kidney Injury/chemically induced , Acute Kidney Injury/metabolism , Aldosterone/metabolism , Animals , Blood Pressure/drug effects , Desoxycorticosterone Acetate/adverse effects , Desoxycorticosterone Acetate/pharmacology , Glycation End Products, Advanced/metabolism , Hypertension/etiology , Hypertension/metabolism , Hypertension/pathology , Kidney Diseases/pathology , Kidney Glomerulus/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptor for Advanced Glycation End Products/metabolism , Receptors, Mineralocorticoid/metabolism , Sodium Chloride, Dietary/adverse effects
5.
Clin Exp Nephrol ; 22(1): 35-44, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28421299

ABSTRACT

BACKGROUND: Hyperkalemia is prevalent in end-stage renal disease patients, being involved in life-threatening arrhythmias. Although polystyrene sulfonate (PS) is commonly used for the treatment of hyperkalemia, direct comparison of effects between calcium and sodium PS (CPS and SPS) on mineral and bone metabolism has not yet been studied. METHODS: In a randomized and crossover design, 20 pre-dialysis patients with hyperkalemia (>5 mmol/l) received either oral CPS or SPS therapy for 4 weeks. RESULTS: After 4-week treatments, there was no significant difference of changes in serum potassium (K) from the baseline (ΔK) between the two groups. However, SPS significantly decreased serum calcium (Ca) and magnesium (Mg) and increased intact parathyroid hormone (iPTH) values, whereas CPS reduced iPTH. ΔiPTH was inversely correlated with ΔCa and ΔMg (r = -0.53 and r = -0.50, respectively). Furthermore, sodium (Na) and atrial natriuretic peptide (ANP) levels were significantly elevated in patients with SPS, but not with CPS, whereas ΔNa and ΔANP were significantly correlated with each other in all the patients. We also found that ΔNa and Δ(Na to chloride ratio) were positively correlated with ΔHCO3-. In artificial colon fluid, CPS increased Ca and decreased Na. Furthermore, SPS greatly reduced K, Mg, and NH3. CONCLUSION: Compared with SPS, CPS may be safer for the treatment of hyperkalemia in pre-dialysis patients, because it did not induce hyperparathyroidism or volume overload.


Subject(s)
Bone and Bones/metabolism , Calcium/therapeutic use , Hyperkalemia/drug therapy , Minerals/metabolism , Polystyrenes/therapeutic use , Aged , Aged, 80 and over , Bone and Bones/drug effects , Calcium/blood , Cross-Over Studies , Female , Humans , Hyperkalemia/blood , Hyperkalemia/metabolism , Magnesium/blood , Male , Middle Aged , Parathyroid Hormone/blood , Prospective Studies , Renal Dialysis , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/metabolism , Sodium/blood
6.
Intern Med ; 56(7): 841-846, 2017.
Article in English | MEDLINE | ID: mdl-28381753

ABSTRACT

Fabry disease (FD) is an inherited lysosomal disorder caused by an X-linked α-galactosidase A deficiency. We report the case of a 50-year-old male FD patient on hemodialysis who presented with macroglossia-related speaking difficulty and gastrointestinal symptoms. An endoscopic analysis revealed multiple gastric ulcers, and a histological examination led to a diagnosis of amyloid light-chain amyloidosis. Serum free light-chain and bone marrow analyses detected multiple myeloma (MM). Treatment with bortezomib and dexamethasone significantly improved the patient's symptoms. This is the first case to demonstrate a potential pathogenic relationship between FD and MM. The similar gastrointestinal manifestations might have contributed to the diagnostic difficulty.


Subject(s)
Amyloidosis/complications , Fabry Disease/complications , Gastrointestinal Diseases/complications , Multiple Myeloma/complications , Renal Dialysis , Bortezomib/therapeutic use , Dexamethasone/therapeutic use , Humans , Immunoglobulin Light Chains , Male , Middle Aged , Multiple Myeloma/drug therapy
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