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1.
Intern Med ; 62(21): 3203-3207, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37438140

ABSTRACT

Encapsulating peritoneal sclerosis (EPS) is a fatal complication of peritoneal dialysis. A 68-year-old man undergoing peritoneal dialysis for 10 years started receiving daily 50 mg of glucocorticoids for idiopathic pulmonary sclerosis. At the transition to hemodialysis, a peritoneal biopsy was performed, which demonstrated mild histological changes, including no fibrin formation and mild T lymphocyte infiltration at the time of 6.5 mg glucocorticoids. However, five months later, he developed EPS when receiving 2.5 mg glucocorticoids. Afterward, over 5 mg daily glucocorticoids were required to avoid the recurrence of EPS. These findings suggest that glucocorticoids may conceal peritoneal inflammation, a main contributor to EPS.


Subject(s)
Peritoneal Dialysis , Peritoneal Fibrosis , Male , Humans , Aged , Peritoneal Fibrosis/etiology , Peritoneal Fibrosis/pathology , Glucocorticoids/adverse effects , Sclerosis , Peritoneal Dialysis/adverse effects , Peritoneum
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.
Ther Apher Dial ; 25(3): 304-313, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32777142

ABSTRACT

Serum carnitine is decreased in hemodialysis patients, which induces muscle atrophy. Thus, we examined the different effects of l-carnitine and exercise on exercise activity and muscle status in hemodialysis patients. Twenty patients were divided into l-carnitine and cycle ergometer groups and were followed for 3 months. Muscle and fat mass, physical activities, and muscle status were evaluated by an impedance, physical function test, and magnetic resonance imaging, respectively. The l-carnitine significantly increased muscle mass (P = .023) and thigh circumference (P = .027), decreased fat mass (P = .007), and shortened chair stand-up time (P = .002) and 10-m walk test (P = .037). The fat fraction was improved by the l-carnitine (P = .047). Compared with the exercise group, l-carnitine improved the changes in 10-m walk test (P = .026), chair stand-up time (P = .014), and thigh circumference (P = .022). Baseline fibroblast growth factor-21 and myostatin levels predicted the l-carnitine-associated changes in exercise activities. l-carnitine, rather than exercise, improved physical activity and muscle status in hemodialysis patients.


Subject(s)
Carnitine/administration & dosage , Dietary Supplements , Exercise Test/methods , Exercise/physiology , Muscles/drug effects , Renal Dialysis , Carnitine/blood , Exercise Test/statistics & numerical data , Female , Humans , Japan , Magnetic Resonance Imaging/methods , Male , Middle Aged , Muscles/diagnostic imaging , Muscles/physiology , Prospective Studies
5.
CEN Case Rep ; 8(3): 205-211, 2019 08.
Article in English | MEDLINE | ID: mdl-30927247

ABSTRACT

A 65-year-old male patient with nephrotic syndrome was admitted to our hospital due to worsening systemic edema and purpura on the limbs. He had an impaired renal function, low serum complement level, and elevated rheumatoid factor level. He was positive for cryoglobulin (monoclonal IgM-κ and polyclonal mixed-type IgG), and the results of his kidney biopsy showed a tissue profile of membranoproliferative glomerulonephritis (MPGN). Due to the fact that the secondary cause was unclear, he was diagnosed with MPGN due to essential mixed cryoglobulinemia. On hospital day 20, he was initiated on 50 mg/day prednisolone (PSL). On hospital day 43, oral mizoribine (MZR) at a dose of 150 mg/day was prescribed. On hospital day 49, cryofiltration was performed because the disease was steroid resistant. The treatment promptly decreased urine protein levels. Serum albumin and serum complement levels increased, and complete remission was achieved approximately three months after the initiation of treatment. The PSL and MZR doses were gradually reduced to 2 mg/day and 100 mg/day, respectively, without any reemergence of the symptoms of cryoglobulinemia or relapse of the nephrotic syndrome for three years. Here, we report this case with essential mixed cryoglobulinemia in whom we could achieve complete remission of the disease by adding cryofiltration to the oral corticosteroid and immunosuppressant therapy with mizoribine and could maintain for a long time.


Subject(s)
Blood Component Removal , Cryoglobulinemia/complications , Glomerulonephritis, Membranoproliferative/therapy , Immunosuppressive Agents/therapeutic use , Ribonucleosides/therapeutic use , Aged , Glomerulonephritis, Membranoproliferative/etiology , Glomerulonephritis, Membranoproliferative/pathology , Glucocorticoids/therapeutic use , Humans , Kidney/pathology , Male , Prednisolone/therapeutic use
6.
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
7.
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
8.
J Am Soc Nephrol ; 28(9): 2670-2680, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28600471

ABSTRACT

Erythropoietin-resistant anemia is associated with adverse cardiovascular events in patients with ESRD, but the underlying mechanism remains unclear. Here, we evaluated the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). In 54 patients with advanced CKD, erythrocyte but not plasma ADMA levels independently associated with low hemoglobin values, although levels of both types of ADMA were elevated compared with those in healthy volunteers. Furthermore, erythrocyte ADMA level associated with the erythropoietin resistance index in patients receiving a weekly injected dose of erythropoiesis-stimulating agents standardized for hemoglobin levels and body weight, whereas it correlated with the erythropoietin demand index (plasma erythropoietin units divided by the hemoglobin value) in patients not receiving erythropoiesis-stimulating agents. Compared with sham-operated controls, wild-type mice with 5/6 subtotal nephrectomy (Nx), a remnant kidney model with advanced CKD, had decreased hemoglobin, hematocrit, and mean corpuscular volume values but increased erythrocyte and plasma ADMA and plasma erythropoietin levels. In comparison, dimethylarginine dimethlaminohydrolase-1 transgenic (DDAH-1 Tg) mice, which efficiently metabolized ADMA, had significant improvements in all of the values except those for erythropoietin after 5/6 Nx. Additionally, wild-type Nx mice, but not DDAH-1 Tg Nx mice, had reduced splenic gene expression of erythropoietin receptor and erythroferrone, which regulates iron metabolism in response to erythropoietin. This study suggests that erythrocyte ADMA accumulation contributes to impaired response to erythropoietin in predialysis patients and advanced CKD mice via suppression of erythropoietin receptor expression.


Subject(s)
Anemia/drug therapy , Arginine/analogs & derivatives , Erythrocytes/metabolism , Erythropoietin/therapeutic use , Hematinics/therapeutic use , Plasma/metabolism , Renal Insufficiency, Chronic/blood , Aged , Amidohydrolases/genetics , Anemia/blood , Anemia/etiology , Animals , Arginine/blood , Cytokines/genetics , Drug Resistance , Erythrocyte Indices , Female , Gene Expression , Hematocrit , Hemoglobins/metabolism , Humans , Male , Mice , Middle Aged , Muscle Proteins/genetics , Nephrectomy , Receptors, Erythropoietin/genetics , Renal Insufficiency, Chronic/complications
9.
Nihon Jinzo Gakkai Shi ; 56(5): 606-11, 2014.
Article in Japanese | MEDLINE | ID: mdl-25130033

ABSTRACT

The patient was a 48-year-old man hospitalized for jaundice and anemia after a 6-day history of diarrhea. Examination demonstrated hemolytic anemia, renal dysfunction, and thrombocytopenia. Typical hemolytic uremic syndrome (HUS) was suspected based on the preceding colitis; however, plasma exchange (PE) was performed because the possibility of atypical HUS (aHUS) could not be ignored, given that the patient was an adult male. After 4 days of PE, his laboratory results improved. Stool culture on admission yielded negative results for Escherichia coli serotype O157 and ADAMTS13 activity. Antinuclear antibodies were normal, and no other drugs or infections indicating HUS were detected. Four months after onset, he suffered recurrence of aHUS after colitis. As a result, aHUS was suspected and therefore, PE was performed on the day of hospitalization. We diagnosed aHUS due to a result indicating complement dysregulation on hemolytic assay testing, which detected a complement factor H abnormality. After undergoing PE and maintaining a stable condition, the interval between PEs was extended; however, on day 17 after the last PE, he suffered a recurrent aHUS attack again. He could not be weaned from PE and started showing an allergic reaction to PE treatment, thereby leading to a switch from PE to eculizumab. Since switching to eculizumab treatment, the patient has not experienced another aHUS attack and his condition remains stable.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Hemolytic-Uremic Syndrome/drug therapy , Plasma Exchange , Atypical Hemolytic Uremic Syndrome , Complement Factor H/urine , Hemolytic-Uremic Syndrome/complications , Humans , Male , Middle Aged , Secondary Prevention , Treatment Outcome
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