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2.
PLoS One ; 16(5): e0251294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34043669

RESUMO

BACKGROUND: There are few studies describing the clinical course and spontaneous remission of IgA nephropathy (IgAN) in adult patients receiving conservative treatment. METHOD: Data from 62 adult patients with biopsy-diagnosed IgAN, who received conservative treatment at least 5 years prior, were retrospectively investigated. No patients received corticosteroids, other immunosuppressants, or tonsillectomy. Remission of proteinuria and hematuria were defined as proteinuria <0.3 g/gCr and urine red blood cells (RBC) <5 / high power field (HPF) on three consecutive urinalyses obtained during an observation period of ≥6 months. RESULT: Thirty-eight (61.3%) patients had remission of hematuria, 24 (38.7%) had remission of proteinuria, and 19 (30.6%) had remission of both. Remission rates increased in patients with proteinuria <0.5 g/g Cr at diagnosis. The median time to remission of hematuria was 2.8 years and that of proteinuria was 2.6 years. Patients who showed renal function decline (defined as 30% decline of estimated glomerular filtration rate [eGFR] from baseline) were older, had significantly lower eGFR, and higher proteinuria at diagnosis. Two patients with preserved renal function and normal proteinuria at diagnosis experienced renal function decline. Renal function did not decline within 3 years of diagnosis in patients with proteinuria <1 g/gCr at diagnosis. CONCLUSIONS: Relatively high rates of spontaneous remission were observed. Remission of both hematuria and proteinuria were frequent within 3 years after diagnosis, and renal function was well preserved during this period. These data indicate that it is rational to use conservative treatment for 3 years after the diagnosis instead of aggressive treatments.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34028524

RESUMO

BACKGROUND: Prognosticating disease progression in patients with diabetic kidney disease (DKD) is challenging, especially in the early stages of kidney disease. Anemia can occur in the early stages of kidney disease in diabetes. We therefore postulated that serum hemoglobin concentration, as a reflection of incipient renal tubulointerstitial impairment, can be used as a marker to predict DKD progression. METHODS: Drawing on nationally representative data of patients with biopsy-proven DKD, 246 patients who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at renal biopsy were identified: aged 56 (45, 63); 62.6% men; Hb 13.3 (12.0, 14.5) g/dL; eGFR 76.2 (66.6, 88.6) mL/min/1.73 m2; urine albumin-to-creatinine ratio [UACR] 534 (100, 1480) mg/g Crea. Serum hemoglobin concentration were divided into quartiles: ≤12, 12.1-13.3, 13.4-14.5, and ≥14.6 g/dL. The association between serum hemoglobin concentration and the severity of renal pathological lesions was explored. A multivariable Cox regression model was used to estimate the risk of DKD progression (new onset of end-stage kidney disease, 50% reduction of eGFR, or doubling of serum creatinine). The incremental prognostic value of DKD progression by adding serum hemoglobin concentration to the known risk factors of DKD was assessed. RESULTS: Serum hemoglobin levels negatively correlated with all renal pathological features, especially with the severity of interstitial fibrosis (ρ =-0.52; P < 0.001). During a median follow-up of 4.1 years, 95 developed DKD progression. Adjusting for known risk factors of DKD progression, the hazard ratio in the first, second, and third quartile (the fourth quartile as a reference) were 2.74 (95% CI 1.26-5.97), 2.33 (95% CI 1.07-5.75), and 1.46 (95% CI 0.71-3.64), respectively. Addition of the serum hemoglobin concentration to the known risk factors of DKD progression improved the prognostic value of DKD progression (the global chi-statistics increased from 55.1 to 60.8; P < 0.001). CONCLUSIONS: Serum hemoglobin concentration, which reflects incipient renal fibrosis, can be useful for predicting DKD progression in the early stages of kidney disease.

5.
Sci Rep ; 11(1): 8999, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33903733

RESUMO

Hyperuricaemia is a risk for premature death. This study evaluated the burden of hyperuricaemia (serum urate > 7 mg/dL) for all-cause and cardiovascular mortality in 515,979 health checkup participants using an index of population attributable fraction (PAF). Prevalence of hyperuricaemia at baseline was 10.8% in total subjects (21.8% for men and 2.5% for women). During 9-year follow-up, 5952 deaths were noted, including 1164 cardiovascular deaths. In the Cox proportional hazard analysis adjusted for confounding factors, hyperuricaemia was independently associated with all-cause and cardiovascular mortality (adjusted hazard ratios [95% confidence interval]; 1.36 [1.25-1.49] and 1.69 [1.41-2.01], respectively). Adjusted PAFs of hyperuricaemia for all-cause and cardiovascular deaths were 2.9% and 4.4% (approximately 1 in 34 all-cause deaths and 1 in 23 cardiovascular deaths), respectively. In the subgroup analysis, the association between hyperuricaemia and death was stronger in men, smokers, and subjects with renal insufficiency. Adjusted PAFs for all-cause and cardiovascular deaths were 5.3% and 8.1% in men; 5.8% and 7.5% in smokers; and 5.5% and 7.3% in subjects with renal insufficiency. These results disclosed that a substantial number of all-cause and cardiovascular deaths were statistically relevant to hyperuricaemia in the community-based population, especially men, smokers, and subjects with renal insufficiency.

6.
J Nephrol ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33929690

RESUMO

BACKGROUND: Association between physical activity and decline in renal function among the general population is not fully understood. METHODS: This is a longitudinal study on subjects who participated in the Japanese nationwide Specific Health Checkup program between 2008 and 2014. The exposure of interest was baseline self-reported walking habit. The outcomes were annual change and incidence of 30% decline in estimated glomerular filtration rate (eGFR). Changes in eGFR were compared using a linear mixed-effects model. Cox proportional hazard models were used to examine the association between self-reported walking habit and 30% decline in eGFR. RESULTS: Among 332,166 subjects, 168,574 reported walking habit at baseline. The annual changes in eGFR [95% confidence interval (CI)] among subjects with and without baseline self-reported walking habit were - 0.17 (- 0.19 to - 0.16) and - 0.26 (- 0.27 to - 0.24) mL/min/1.73 m2/year, respectively (P for interaction between time and baseline self-reported walking habit, < 0.001). During a median follow-up of 3.3 years, 9166 of 314,489 subjects exhibited 30% decline in eGFR. The incidence of 30% decline in eGFR was significantly lower among subjects with self-reported walking habit after adjustment for potential confounders including time-varying blood pressure, body mass index, lipid profile, and hemoglobin A1c, with hazard ratio (95% CI) of 0.93 (0.89-0.97). Sensitivity analysis restricted to subjects with unchanged self-reported walking habit from baseline or analysis with time-varying self-reported walking habit yielded similar results. CONCLUSIONS: Self-reported walking habit was associated with significantly slower decline in eGFR. This association appeared to be independent of its effects on metabolic improvement.

7.
Intern Med ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33840692

RESUMO

Membranous nephropathy often achieves spontaneous remission. However, there are scarce reports of spontaneous remission of thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy. A 64-year-old female presented with nephrotic syndrome and edema of the lower extremities. We diagnosed membranous nephropathy by kidney biopsy and confirmed positive THSD7A on immunofluorescence using frozen sections; serum THSD7A antibodies were also detected. Thirty-four months after the initial diagnosis, she achieved a spontaneous complete remission without immunosuppressive therapy. With the complete remission, no serum THSD7A levels were detected. In this study, we describe serial examinations of kidney biopsies and serum THSD7A antibodies.

8.
J Clin Hypertens (Greenwich) ; 23(5): 999-1007, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33645883

RESUMO

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are prescribed as conservative or adjunctive therapies for adult idiopathic nephrotic syndrome. However, studies on real-world practice patterns are scarce. This study aimed to examine the prevalence and incidence of ACEI/ARB prescription and their associated factors. This nationwide cohort study included adult Japanese patients with idiopathic nephrotic syndrome including minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and others. The outcomes were the prevalence of ACEI/ARB prescription at baseline (date of renal biopsy or date of immunosuppressant initiation) and at 2 months after baseline. Of the 326 eligible patients, 122 (37.4%) had already been prescribed ACEIs/ARBs. Of the remaining 204 patients, 67 (32.7%) were newly prescribed within the 2-month period. MN/FSGS (vs. MCD, adjusted odds ratio [AOR]: 4.96 [95% confidence interval {CI} 2.53-9.72] and 3.95 [95% CI 1.61-9.66], respectively), higher age (per 1-yr increase, AOR: 1.02 [95% CI 1.00-1.04]), other hypertensive agents (AOR: 2.18 [95% CI 1.21-3.92]), antidiabetic drug (AOR: 6.57 [95% CI 1.77-24.4]) were associated with a higher prevalence of ACEI/ARB prescription. MN (vs. MCD, AOR: 6.00 [95% CI 2.57-14.0]) and higher baseline systolic blood pressure (SBP) (per 10-mmHg increase, AOR: 1.36 [95% CI 1.09-1.70]) were associated with a higher incidence of ACEI/ARB prescription. On average, incidence of ACEI/ARB prescription increased from 19.2% to 40.8% as baseline SBP increased from 100 to 140 mmHg. Thus, Japanese nephrologists are likely to prescribe ACEIs/ARBs for nephrotic patients with MN or high baseline SBP, even below the hypertensive range.

10.
Intern Med ; 60(5): 689-697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642559

RESUMO

Objective Despite advances in medicine, aortic diseases (ADs), such as aneurysm rupture and aortic dissection, remain fatal and carry extremely high mortality rates. Due to its low frequency, the risk of developing AD has not yet been fully elucidated. Chronic kidney disease (CKD) is an established risk factor for cardiovascular disease and mortality. The aim of the present study was to examine whether or not CKD is a risk for AD-related mortality in the general population. Methods We used a nationwide database of 554,442 subjects (40-75 years old) who participated in the annual "Specific Health Check and Guidance in Japan" checkup between 2008 and 2013. Results There were 131 aortic aneurysm and dissection deaths during the follow-up period of 2,123,512 person-years. A Kaplan-Meier analysis revealed that subjects with CKD had a higher rate of AD-related deaths than those without it. A multivariate Cox proportional hazard regression analysis demonstrated that CKD was an independent risk factor for AD-related death in the general population after adjusting for cardiovascular risk factors. The addition of CKD to cardiovascular risk factors significantly improved the C, net reclassification, and integrated discrimination indexes. Conclusion CKD is an additional risk for AD-related death, suggesting that CKD may be a target for the prevention and early identification of subjects at high risk for AD-related death in the general population.


Assuntos
Aneurisma Aórtico , Doenças da Aorta , Doenças Cardiovasculares , Insuficiência Renal Crônica , Adulto , Idoso , Aneurisma Aórtico/epidemiologia , Estudos de Coortes , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco
11.
Nutrients ; 13(2)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671239

RESUMO

Whether dietary salt intake affects chronic kidney disease (CKD) progression remains unclear. We conducted a retrospective cohort study to analyze the effects of both daily salt intake (DSI) and volume status on renal outcomes in 197 CKD patients. DSI was estimated by 24-h urinary sodium excretion and volume status was assessed by the ratio of extracellular water (ECW) to total body water (TBW) measured by bioelectrical impedance analysis (BIA). We divided patients into two groups according to DSI (6 g/day) or median ECW/TBW (0.475) and compared renal outcomes of each group. Furthermore, we classified and analyzed four groups according to both DSI and ECW/TBW. The higher DSI group showed a 1.69-fold (95% confidence interval (CI) 1.12-2.57, p = 0.01) excess risk of outcome occurrence compared to the lower group. Among the four groups, compared with Group 1 (low DSI and low ECW/TBW), Group 3 (high DSI and low ECW/TBW) showed a 1.84-fold (95% CI 1.03-3.30, p = 0.04) excess risk of outcome occurrence; however, Group 2 (low DSI and high ECW/TBW) showed no significant difference. High salt intake appears to be associated with poor renal outcome independent of blood pressure (BP), proteinuria, and volume status.


Assuntos
Rim/patologia , Sódio/urina , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica , Estudos Retrospectivos , Cloreto de Sódio na Dieta/administração & dosagem , Equilíbrio Hidroeletrolítico
12.
Intern Med ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33583896

RESUMO

Objective Results from previous studies on the dose-dependent effect of adhering to multiple lifestyle factors on all-cause mortality in patients with chronic kidney disease (CKD) are inconsistent, despite the reported dose-dependent effect in the general population. This study aimed to examine whether CKD modifies the dose-dependent effect of adhering to multiple lifestyle factors on mortality. Methods This population-based prospective cohort study targeted 262,011 men and women aged 40-74 years at baseline. Of these, 18.5% had CKD, which was defined as GFR <60 ml/min/1.73 m2, ≥1+ proteinuria on urinalysis, or both. The following lifestyle behaviors were considered healthy: no smoking, body mass index <25 kg/m2, moderate or lower alcohol consumption, regular exercise, and healthy eating habits. Healthy lifestyle scores were calculated by adding the total number of lifestyle factors for which each participant was at low risk. Cox proportional hazards models were used to examine associations between healthy lifestyle scores and all-cause, cancer, and cardiovascular mortality, and whether CKD modified these associations. Results During a median follow-up of 4.7 years, 3,471 participants died. The risks of all-cause and cancer mortality decreased as the number of five healthy lifestyle factors that were adhered to increased, irrespective of the CKD status. The risk of cardiovascular mortality, however, was modified by CKD (interaction p=0.07), and an unhealthy lifestyle and CKD synergistically increased cardiovascular mortality. Conclusion A healthy lifestyle can reduce the risk of all-cause and cancer death in patients with or without CKD, while the prevention of CKD is essential for reducing the risk of cardiovascular death.

13.
Medicine (Baltimore) ; 100(5): e24460, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592898

RESUMO

RATIONAL: Immunoglobulin A (IgA) nephropathy is a common heterogeneous kidney disease. One of the causes of secondary immunoglobulin A nephropathy is infection-related glomerulonephritis (IRGN), however, its accurate diagnosis is difficult. PATIENT CONCERNS: We report a rare case of an 82-year-old male presenting rapidly progressive glomerulonephritis. Assessment of a kidney biopsy by light microscopy revealed endocapillary glomerulonephritis with subendothelial deposits, such as wire loop lesions and cellular crescents. Immunofluorescence demonstrated strong staining for IgA and C3 along the glomerular capillary. Additional tests included positive staining for nephritis-associated plasmin receptor and positive plasmin activity in the glomeruli. Moreover, IgA and galactose-deficient IgA1 (Gd-IgA1) staining merged using immunofluorescence, followed by confirmation of high serum levels of Gd-IgA1 (9.3 µg/mL) by ELISA was observed. DIAGNOSIS: The diagnosis of IgA-dominant IRGN was made. INTERVENTIONS AND OUTCOMES: We have initiated treatment with intravenous methylprednisolone 500 mg/day for 3 days, followed by oral prednisolone 25 mg/d as rapidly progressive glomerulonephritis. However immunosuppressive therapy was halted because of a poor response, and hemodialysis was initiated. LESSONS: This is a case of IgA-dominant IRGN patient exhibiting positive glomerular staining for nephritis-associated plasmin receptor accompanied with high titers of serum Gd-IgA1. Our observations suggest that serum and kidney tissue of Gd-IgA1 may be useful for the diagnosis of IgA-dominant IRGN.


Assuntos
Galactose/deficiência , Glomerulonefrite por IGA/patologia , Idoso de 80 Anos ou mais , Biomarcadores , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/diagnóstico , Humanos , Imunoglobulina A/sangue , Masculino , Receptores de Peptídeos/biossíntese
15.
Clin Exp Nephrol ; 25(4): 365-375, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33409761

RESUMO

BACKGROUND: The aim of this study is to investigate the renoprotective effect of the GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease (DKD) using an animal model of type 2 diabetes with several metabolic disorders. METHODS: Male 8-week-old spontaneously diabetic Torii (SDT) fatty rats (n = 19) were randomly assigned to three groups. The liraglutide group (n = 6) was injected subcutaneously with liraglutide. Another treatment group (n = 6) received subcutaneous insulin against hyperglycemia and hydralazine against hypertension for matching blood glucose levels and blood pressure with the liraglutide group. The control groups of SDT fatty (n = 7) and non-diabetic Sprague-Dawley rats (n = 7) were injected only with a vehicle. RESULTS: The control group of SDT fatty rats exhibited hyperglycemia, obesity, hypertension, hyperlipidemia, glomerular sclerosis, and tubulointerstitial injury with high urinary albumin and L-FABP levels. Liraglutide treatment reduced body weight, food intake, blood glucose and blood pressure levels, as well as ameliorated renal pathologic findings with lower urinary albumin and L-FABP levels. Liraglutide increased expressions of phosphorylated (p)-eNOS and p-AMPK in glomeruli, downregulated renal expression of p-mTOR, and increased renal expressions of LC3B-II, suggesting activation of autophagy. However, these effects were not caused by the treatments with insulin and hydralazine, despite comparable levels of hyperglycemia and hypertension to those achieved with liraglutide treatment. CONCLUSIONS: Liraglutide may exert a renoprotective effect via prevention of glomerular endothelial abnormality and preservation of autophagy in early-phase DKD, independent of blood glucose, and blood pressure levels.

16.
Sci Rep ; 11(1): 716, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436978

RESUMO

Based on questionnaires from 197,825 non-diabetic participants in a large Japanese cohort, we determined impact of (1) habit of exercise, (2) habit of active physical activity (PA) and (3) walking pace on new-onset of type 2 diabetes mellitus. Unadjusted and multivariable-adjusted logistic regression models were used to determine the odds ratio of new-onset diabetes mellitus incidence in a 3-year follow-up. There were two major findings. First, habits of exercise and active PA were positively associated with incidence of diabetes mellitus. Second, fast walking, even after adjusting for multiple covariates, was associated with low incidence of diabetes mellitus. In the subgroup analysis, the association was also observed in participants aged ≥ 65 years, in men, and in those with a body mass index ≥ 25. Results suggest that fast walking is a simple and independent preventive factor for new-onset of diabetes mellitus in the health check-up and guidance system in Japan. Future studies may be warranted to verify whether interventions involving walking pace can reduce the onset of diabetes in a nation-wide scale.

17.
Sci Rep ; 11(1): 982, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441837

RESUMO

We investigate whether suppressing the activation of the angiotensin II type 1a receptor (AT1a) can ameliorate severe chronic tubulointerstitial damage (TID) after renal ischemia reperfusion (IR) using AT1a knockout homozygous (AT1a-/-) male mice. To induce severe chronic TID after renal IR, unilateral renal ischemia was performed via clamping of the right renal pedicle in both AT1a-/- and wild-type (AT1a+/+) mice for 45 min. While marked renal atrophy and severe TID at 70 days postischemia was induced in the AT1a+/+ mice, such a development was not provoked in the AT1a-/- mice. Although the AT1a+/+ mice were administered hydralazine to maintain the same systolic blood pressure (SBP) levels as the AT1a-/- mice with lower SBP levels, hydralazine did not reproduce the renoprotective effects observed in the AT1a-/- mice. Acute tubular injury at 3 days postischemia was similar between the AT1a-/- mice and the AT1a+/+ mice. From our investigations using IR kidneys at 3, 14, and 28 days postischemia, the multiple molecular mechanisms may be related to prevention of severe chronic TID postischemia in the AT1a-/- mice. In conclusion, inactivation of the AT1 receptor may be useful in preventing the transition of acute kidney injury to chronic kidney disease.

19.
BMC Nephrol ; 21(1): 453, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129292

RESUMO

BACKGROUND: In chronic kidney disease (CKD), patients' adherence to prescriptions for diet and for medications might depend on the degree to which they have hope that they will enjoy life, and that hope could vary with the stage of CKD. The aims of this study were to quantify both the association of CKD stage with health-related hope (HR-Hope), and the association of that hope with psychological and physiological manifestations of adherence. METHODS: This was a cross-sectional study involving 461 adult CKD patients, some of whom were receiving dialysis. The main exposure was HR-Hope, measured using a recently-developed 18-item scale. The outcomes were perceived burden of fluid restriction and of diet restriction, measured using the KDQOL, and physiological manifestations of adherence (systolic and diastolic blood pressure [BP], and serum phosphorus and potassium levels). General linear models and generalized ordered logit models were fit. RESULTS: Participants at non-dialysis stage 4 and those at stage 5 had lower HR-Hope scores than did those at stage 2 or 3 (combined). Those at non-dialysis stage 5 had the lowest scores. HR-Hope scores of participants at stage 5D were similar to those of participants at stage 4, but they were lower than the scores of participants at stage 2 or 3 (combined). Higher HR-Hope scores were associated with lower perceived burdens of fluid restriction and of diet restriction (adjusted ORs per ten-point difference were 0.82 and 0.84, respectively). Higher HR-Hope scores were associated with lower systolic BP (adjusted mean difference in systolic BP per ten-point difference in HR-Hope scores was - 1.87 mmHg). In contrast, HR-Hope scores were not associated with diastolic BP, serum phosphorus levels, or serum potassium levels. CONCLUSIONS: Among CKD patients, HR-Hope is associated with disease stage, with psychological burden, and with some physiological manifestations of adherence.

20.
Clin Exp Nephrol ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33098526

RESUMO

BACKGROUND: Hyperkalemia is associated with many chronic diseases and renin-angiotensin-aldosterone system inhibitor therapy. Sodium zirconium cyclosilicate (SZC), an oral, highly selective cation-exchanger, is approved for the treatment of hyperkalemia. METHODS: This phase 3, multicenter, open-label, single-arm, flexible-dose study assessed the safety and efficacy of SZC in Japanese patients with hyperkalemia during a correction phase of up to 3 days and long-term (1 year) maintenance phase (NCT03172702). RESULTS: Overall, 150 patients received treatment during both study phases; the study population was generally representative of hyperkalemic Japanese patients in clinical practice. Most patients (78.7%) had three doses of SZC during the correction phase. All but one patient received SZC for ≤ 48 h before transitioning to the maintenance phase. In the maintenance phase, mean (standard deviation; SD) exposure to the study drug was 319.4 (98.1) days and mean (SD) dose was 7.38 (2.85) g/day. Adverse events (AEs) were reported in 131 patients (87.3%); most were mild. The most common treatment-related AEs as evaluated by investigators were constipation (6.7%), peripheral edema (4.0%), and hypertension (2.7%). In the correction phase, 78.7% of patients were normokalemic at 24 h and 98.7% within 48 h; ≥ 65.5% maintained normokalemia throughout the maintenance phase. CONCLUSION: After a year of exposure, SZC treatment was well tolerated by Japanese patients and potassium levels were well controlled.

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