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Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, frailty has no cure. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing dialysis prescription, and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.
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Fragilidade , Qualidade de Vida , Diálise Renal , Humanos , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/fisiopatologia , Diálise Renal/efeitos adversos , Idoso , Idoso Fragilizado , Polimedicação , Avaliação Geriátrica , Fatores de Risco , Falência Renal Crônica/terapia , Falência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/complicaçõesRESUMO
BACKGROUND: Diabetic kidney diseases (DKD) is a the most common cause of end-stage kidney disease (ESKD) around the world. Previous studies suggest that urinary podocyte stress biomarker, e.g. podocin:nephrin mRNA ratio, is a surrogate marker of podocyte injury in non-diabetic kidney diseases. METHOD: We studied 118 patients with biopsy-proved DKD and 13 non-diabetic controls. Their urinary mRNA levels of nephrin, podocin, and aquaporin-2 (AQP2) were quantified. Renal events, defined as death, dialysis, or 40% reduction in glomerular filtration rate, were determined at 12 months. RESULTS: Urinary podocin:nephrin mRNA ratio of DKD was significantly higher than the control group (p = 0.0019), while urinary nephrin:AQP2 or podocin:AQP2 ratios were not different between groups. In DKD, urinary podocin:nephrin mRNA ratio correlated with the severity of tubulointerstitial fibrosis (r = 0.254, p = 0.006). and was associated with the renal event-free survival in 12 months (unadjusted hazard ratio [HR], 1.523; 95% confidence interval [CI] 1.157-2.006; p = 0.003). After adjusting for clinical and pathological factors, urinary podocin:nephrin mRNA ratio have a trend to predict renal event-free survival (adjusted HR, 1.327; 95%CI 0.980-1.797; p = 0.067), but the result did not reach statistical significance. CONCLUSION: Urinary podocin:nephrin mRNA ratio has a marginal prognostic value in biopsy-proven DKD. Further validation is required for DKD patients without kidney biopsy.
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Diabetes Mellitus , Nefropatias Diabéticas , Podócitos , Humanos , Nefropatias Diabéticas/diagnóstico , Prognóstico , Aquaporina 2/genética , Diálise Renal , RNA MensageiroRESUMO
Anemia typically develops early in the course of diabetic kidney disease (DKD). There are data to show that dipeptidyl-peptidase-4 (DPP-4) inhibitors affect hematopoietic growth factor activity and hemoglobin level. We retrospectively reviewed 443 DKD patients who were started on DDP-4 inhibitor therapy in 2019. Their hemoglobin level at baseline (6-12 months before treatment), pretreatment (0-6 months before treatment), and post-treatment periods (within 6 months after DPP-4 inhibitor), concomitant estimated glomerular filtration rate (eGFR), HbA1c, peripheral blood white cell and platelet counts were reviewed. The severity of kidney failure was classified according to the Kidney Disease: Improving Global Outcomes stages. The hemoglobin level had a small but significant decline from 11.98 ± 2.07 to 11.87 ± 2.12 g/dL from pretreatment to post-treatment period (paired Student t test, P < .0001). From the pre- to post-treatment period, the decline of hemoglobin level was 0.10 ± 0.89 g/dL, which was significantly less than that from baseline to pretreatment period (0.24 ± 0.90 g/dL, P = .0008). The change in hemoglobin level had a positive correlation with the change in HbA1c level (R = 0.218, P < .0001), but did not correlate with the type of DPP-4 inhibitor or pretreatment eGFR. There was no significant change in peripheral blood white cell or platelet count during the same period. DPP-4 inhibitor ameliorates hemoglobin decline in DKD. The effect of DPP-4 inhibitor on hemoglobin is statistically significant but clinically modest, and did not correlate with the concomitant change in kidney function.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Inibidores da Dipeptidil Peptidase IV , Humanos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Dipeptidil Peptidase 4 , HipoglicemiantesRESUMO
BACKGROUND: Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis. METHOD: We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions. RESULTS: The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = -0.423, p = 0.018) and ANRIL levels (r = -0.483, p = 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = -0.383, p = 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis (p = 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = -0.321, p = 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy (p = 0.003) and minimal change nephropathy (p = 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706, p = 0.01). CONCLUSIONS: We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis.
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Glomerulonefrite Membranosa , Nefrite Lúpica , RNA Longo não Codificante , Humanos , Nefrite Lúpica/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Rim/metabolismo , Glomerulonefrite Membranosa/patologia , Biomarcadores/metabolismoRESUMO
BACKGROUND: Renal glycogen synthase kinase-3 beta (GSK3ß) overactivity has been associated with a diverse range of kidney diseases. GSK3ß activity in urinary exfoliated cells was reported to predict the progression of diabetic kidney disease (DKD). We compared the prognostic value of urinary and intrarenal GSK3ß levels in DKD and nondiabetic chronic kidney disease (CKD). METHODS: We recruited 118 consecutive biopsy-proved DKD patients and 115 nondiabetic CKD patients. Their urinary and intrarenal GSK3ß levels were measured. They were then followed for dialysis-free survival and rate of renal function decline. RESULTS: DKD group had higher intrarenal and urinary GSK3ß levels than nondiabetic CKD (p < 0.0001 for both), but their urinary GSK3ß mRNA levels were similar. Urinary p-GSK3ß level is statistically significantly correlated with the baseline estimated glomerular filtration rate (eGFR), but urinary GSK3ß level by ELISA, its mRNA level, the p-GSK3ß level, or the p-GSK3ß/GSK3ß ratio had no association with dialysis-free survival or the slope of eGFR decline. In contrast, the intrarenal pY216-GSK3ß/total GSK3ß ratio significantly correlated with the slope of eGFR decline (r = -0.335, p = 0.006) and remained an independent predictor after adjusting for other clinical factors. CONCLUSION: Intrarenal and urinary GSK3ß levels were increased in DKD. The intrarenal pY216-GSK3ß/total GSK3ß ratio was associated with the rate of progression of DKD. The pathophysiological roles of GSK3ß in kidney diseases deserve further studies.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Taxa de Filtração Glomerular/fisiologia , Glicogênio Sintase Quinase 3 beta , Diálise Renal , Insuficiência Renal Crônica/complicações , RNA MensageiroRESUMO
Rationale & Objective: Diabetic kidney diseases (DKDs) are the most common cause of dialysis-dependent kidney disease around the world. Previous studies have suggested that urinary level of podocyte-associated molecules may predict the prognosis of DKD. Study Design: Observational cohort. Setting & Participants: 118 consecutive patients with biopsy-proven DKD; 13 nondiabetic patients with hypertensive nephrosclerosis as controls. Predictors: Urinary podocalyxin and podocin levels were obtained by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) and the corresponding intrarenal levels by western blotting. Outcomes: Dialysis-free survival; kidney event-free survival; rate of kidney function decline in 12 months. Analytical Approach: Correlation and time to event analysis. Results: Urinary podocalyxin level was closely correlated with its messenger RNA (mRNA) level (r = 0.562, P < 0.001), but this did not predict the progression of DKD. Intrarenal podocalyxin level had only modest correlation with its urinary mRNA and ELISA levels, was an independent predictor of dialysis-free survival (adjusted HR, 1.85; 95% CI, 1.21-2.82; P = 0.005), and showed an insignificant trend of predicting kidney event-free survival (adjusted HR, 1.36; 95% CI, 0.94-1.95; P = 0.10). Urinary podocin level by ELISA had a modest correlation with the rate of kidney function decline (r = 0.238, P = 0.01) but did not predict dialysis-free survival. Limitations: Small sample size; lack of serial measurement. Conclusions: Intrarenal podocalyxin level, but not its urinary level, was an independent predictor of dialysis-free survival, whereas urinary podocin level by ELISA correlated with the rate of kidney function decline. Although intrarenal podocalyxin level has prognostic value, it may not be suitable for routine clinical use.
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BACKGROUND: There were limited data on the efficacy and safety profile on use of sodium-glucose co-transporter 2 receptor (SGLT2) inhibitors in diabetic patients with advanced chronic kidney disease (CKD). We aimed to evaluate the efficacy, in terms of improvement in glycemic profile, kidney function, prevention of adverse kidney and cardiovascular events, and the safety profile of SGLT2 inhibitors in a group of diabetic patients at CKD stage 3B-5 from a real-world population-based cohort. METHODS: We performed a retrospective observational cohort study of type 2 diabetic patients at CKD stage 3B-5 who received SGLT2 inhibitors as compared to control from 1 January 2015 through 31 December 2021. Propensity score assignment by logistic regression and matching with control by the nearest score at 1:3 ratio was done. All patients were followed for 1 year. Outcomes were kidney-related adverse events and major adverse cardiovascular events (MACE), change in estimated glomerular filtration rate (eGFR), glycemic control, and side effects profiling. RESULTS: We analyzed 1,450 SGLT2 inhibitor users. They had significantly lower rates of kidney-related adverse events (7.7 % versus 24.1 %, p < 0.001) and MACE (9.6 % versus 15.1 %, p < 0.001) as compared to control group. Their eGFR also significantly improved (0.4 ± 9.3 versus -5.5 ± 10.6 ml/min/1.73 m2, p < 0.001). These patients also had a greater reduction in HbA1c (-0.40 ± 1.13 versus -0.04 ± 1.47 %, p < 0.001), and insulin requirement (-8.8 ± 35.2 versus 4.1 ± 19.4 units/day, p < 0.001). After adjusting for confounders, SGLT2 inhibitors protected against kidney-related adverse events (odds ratio [OR] 0.48, 95 % confidence interval [CI] 0.33 - 0.71, p < 0.001) and MACE (OR 0.47, 95 % CI 0.37 - 0.60, p < 0.001). Apart from a marginally higher rate of fungal urinary tract infection (0.08 ± 0.66 versus 0.03 ± 0.23 episodes per year, p < 0.001), SGLT2 inhibitor use was not associated with other side effects. CONCLUSIONS: SGLT2 inhibitor improved kidney function, glycemic profile, and reduced adverse kidney-related and cardiovascular events in diabetic patients with advanced CKD.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Nefropatias Diabéticas/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos de Coortes , Estudos Retrospectivos , Pontuação de Propensão , Rim , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológicoRESUMO
There were limited data on adipose and serum zinc alpha-2-glycoprotein (ZAG) expression and its association with body composition in patients with advanced chronic kidney disease (CKD). This study aimed to quantify adipose and serum ZAG expression and evaluate their association with body composition and its longitudinal change, together with mortality in incident dialysis patients. We performed a single-center prospective cohort study. Patients who were planned for peritoneal dialysis were recruited. ZAG levels were measured from serum sample, subcutaneous and pre-peritoneal fat tissue obtained during peritoneal dialysis catheter insertion. Body composition and functional state were evaluated by bioimpedance spectroscopy and Clinical Frailty Scale respectively at baseline and were repeated 1 year later. Primary outcome was 2-year survival. Secondary outcomes were longitudinal changes of body composition. At baseline, the average adipose and serum ZAG expression was 13.4 ± 130.0-fold and 74.7 ± 20.9 µg/ml respectively. Both adipose and serum ZAG expressions independently predicted adipose tissue mass (ATM) (p = 0.001, p = 0.008, respectively). At 1 year, ATM increased by 3.3 ± 7.4 kg (p < 0.001) while lean tissue mass (LTM) remained similar (p = 0.5). Adipose but not serum ZAG level predicted change in ATM (p = 0.007) and LTM (p = 0.01). Serum ZAG level predicted overall survival (p = 0.005) and risk of infection-related death (p = 0.045) after adjusting for confounders. In conclusion, adipose and serum ZAG levels negatively correlated with adiposity and predicted its longitudinal change of fat and lean tissue mass, whilst serum ZAG predicted survival independent of body mass in advanced CKD patient.
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Adiposidade , Caquexia , Diálise Renal , Insuficiência Renal Crônica , Glicoproteína Zn-alfa-2 , Adipocinas , Tecido Adiposo/metabolismo , Caquexia/metabolismo , Humanos , Obesidade/metabolismo , Estudos Prospectivos , Proteínas de Plasma Seminal/metabolismo , Taxa de Sobrevida , Glicoproteína Zn-alfa-2/metabolismoRESUMO
BACKGROUND: Urinary micro-RNA (miRNA) level may serve as non-invasive disease markers for immunoglobulin A nephropathy (IgAN), but urinary miRNA targets identified in previous studies may represent kidney scarring rather than being specific for IgAN. We aim to identify urinary miRNA targets for the diagnosis of IgAN by including hypertensive nephrosclerosis (HTN) as a control group. Methods In the development cohort, we performed complete miRNA profiling of urinary sediment in 33 patients with IgAN, 9 with HTN, and 9 healthy controls (CTL). Potential miRNA targets were quantified by a separate validation cohort of 72 IgAN, 34 HTN, and 20 healthy controls. Results In the development cohort, we identified 6 miRNA targets with urinary levels significantly increased in IgAN as compared to both HTN and CTL. In the validation study, all 6 miRNA targets remained increased than the other groups, although the result of miR-345 did not reach statistical significance. The area-under-curve of the receiver operating characteristic (ROC) curve for urinary mi-106a level for the diagnosis of IgAN was 0.742 (p < 0.0001), and the diagnostic performance was not further improved by having additional miRNA targets. At the cut-off ≥ 800 copy per 1000 copies of housekeeping gene, urinary miR-106a has 100% sensitivity and 14.8% specificity in detecting IgA nephropathy. Conclusions We identified 6 miRNA targets whose urinary levels are significantly elevated in IgAN, and urinary miR-106a level has an excellent sensitivity for the identification of IgAN. Further validation studies are needed to confirm its role in disease screening.
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Glomerulonefrite por IGA , MicroRNAs , Biomarcadores/urina , Feminino , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/patologia , Humanos , Rim , Biópsia Líquida , Masculino , MicroRNAs/genética , Curva ROCRESUMO
BACKGROUND AND AIM: Gut dysbiosis is associated with immune dysfunction and severity of COVID-19. Whether targeting dysbiosis will improve outcomes of COVID-19 is unknown. This study aimed to assess the effects of a novel gut microbiota-derived synbiotic formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID-19 patients. METHODS: This was an open-label, proof-of-concept study. Consecutive COVID-19 patients admitted to an infectious disease referral center in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID-19 patients and healthy population. COVID-19 patients who were admitted under another independent infectious disease team during the same period without receiving SIM01 acted as controls. All patients received standard treatments for COVID-19 according to the hospital protocol. We assessed antibody response, plasma proinflammatory markers, nasopharyngeal SARS-CoV-2 viral load, and fecal microbiota profile from admission up to week 5. RESULTS: Twenty-five consecutive COVID-19 patients received SIM01 for 28 days; 30 patients who did not receive the formula acted as controls. Significantly more patients receiving SIM01 than controls developed SARS-CoV-2 IgG antibody (88% vs 63.3%; P = 0.037) by Day 16. One (4%) and 8 patients (26.7%) in the SIM01 and control group, respectively, failed to develop positive IgG antibody upon discharge. At week 5, plasma levels of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor (TNF-α), and IL-1RA reduced significantly in the SIM01 but not in the control group. There was a significant negative correlation of nasopharyngeal SARS-CoV-2 viral load and SIM01 intervention. Metagenomic analysis showed that bacterial species in SIM01 formula were found in greater abundance leading to enrichment of commensal bacteria and suppression of opportunistic pathogens in COVID-19 patients by week 4 and week 5. CONCLUSIONS: This proof-of-concept study suggested that the use of a novel gut microbiota-derived synbiotic formula, SIM01, hastened antibody formation against SARS-CoV-2, reduced nasopharyngeal viral load, reduced pro-inflammatory immune markers, and restored gut dysbiosis in hospitalised COVID-19 patients.
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COVID-19 , Microbioma Gastrointestinal , Simbióticos , Bactérias , COVID-19/terapia , Disbiose , Humanos , Imunoglobulina G , Projetos Piloto , SARS-CoV-2RESUMO
Background: Hyponatremia is common in COVID-19, but its epidemiology and impact on clinical outcomes in relation to different variants, especially the Omicron variant, requires further clarification. Methods: This was a territory-wide retrospective study to investigate the epidemiology and outcomes of COVID-19 patients with hyponatremia from January 1, 2020 to March 31, 2022 in Hong Kong. The primary outcome was 30-day mortality of patients with COVID-19 and hyponatremia at presentation. Secondary outcomes included rate of hospitalization, intensive care unit (ICU) hospitalization, overall duration of hospitalization, and duration of ICU hospitalization. Results: A total of 53,415 COVID-19 patients were included for analysis, of which 14,545 (27.2%) had hyponatremia at presentation. 9813 (67.5%), 2821 (19.4%), and 1911 (13.1%) had mild (130 to <135 mmol/L), moderate (125 to <130 mmol/L), and severe hyponatremia (<125 mmol/L) at presentation respectively. Age, male sex, diabetes, active malignancy, white cell count, serum creatinine, hypoalbuminemia, C-reactive protein, and viral loads were independent predictors for hyponatremia in COVID-19 patients (P < 0.001, for all). Hyponatremic patients had increased 30-day mortality (9.7 vs. 5.7%, P < 0.001), prolonged hospitalization (11.9 ± 15.1 days vs. 11.5 ± 12.1 days, P < 0.001), and more ICU admissions (7.0% vs. 3.3%, P < 0.001). Patients diagnosed during the "fifth wave" Omicron BA.2 outbreak had 2.29-fold risk (95% CI 2.02-2.59, P < 0.001) of presenting with hyponatremia compared to other waves. Conclusion: Hyponatremia is common among COVID-19 patients, and may serve as a prognostic indicator for unfavorable outcomes and increased healthcare utilization in the evolving COVID-19 outbreak.
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BACKGROUND: Peritonitis is a common and serious complication of peritoneal dialysis (PD). Translocation of gut bacteria to peritoneum is an important mechanism, which may be enhanced by gastrointestinal endoscopy. METHODS: In this retrospective observational cohort study, we identified 450 gastroscopies performed in PD patients within a single centre between 2014 and 2019. Gastroscopy-related peritonitis was defined by peritonitis within 1 week after endoscopy. RESULTS: A total of 408 endoscopic episodes in 216 patients were analysed after excluding 42 cases with either pre-existing peritonitis before endoscopy, or concomitant biliary, small bowel or large bowel endoscopy. There were 16 episodes of peritonitis within 1 week of endoscopy (3.9%). One-quarter of cases were polymicrobial (four episodes, 25.0%). Logistic regression model showed that patient's age, number of endoscopic biopsies, and histamine-2 receptor blocker use were independently associated with peritonitis, while prior antibiotics exposure was associated with lower risk of peritonitis, odds ratio 0.23 (95% confidence interval 0.06-0.95; p = 0.04). CONCLUSION: Peritonitis can complicate gastroscopy in PD patients and occurs more often in elderly or after repeated biopsy procedures.
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Diálise Peritoneal , Peritonite , Idoso , Antibacterianos/uso terapêutico , Gastroscopia/efeitos adversos , Humanos , Diálise Peritoneal/efeitos adversos , Peritonite/diagnóstico , Peritonite/epidemiologia , Peritonite/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
RATIONALE & OBJECTIVE: Previous studies have suggested that microRNA-21 (miR-21) plays an important role in kidney fibrosis. We examined the relationship between intrarenal miR-21 level and rate of kidney function loss in immunoglobulin A nephropathy (IgAN). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 40 patients with IgAN and 10 with hypertensive nephrosclerosis as controls. PREDICTORS: miR-21 levels in kidney biopsy specimen and urinary sediment, quantified as ratio to the housekeeping gene. OUTCOMES: Kidney event-free survival and rate of kidney function decline. ANALYTIC APPROACH: Time-to-event and correlation analysis. RESULTS: The IgAN group had significantly higher intrarenal miR-21 expression compared with the hypertensive nephrosclerosis group (1.71 [IQR, 0.99-2.77] vs 0.31 [IQR, 0.25-1.32]; P < 0.0001), but urinary miR-21 levels were similar. Intrarenal miR-21 expression had significant but modest correlation with severity of glomerulosclerosis (r = 0.293; P = 0.05) and tubulointerstitial fibrosis (r = 0.341; P = 0.03). Patients with high intrarenal miR-21 expression had significantly higher risk for developing kidney end points compared with those with low expression (log-rank test, P = 0.017). Univariate Cox analysis showed that intrarenal miR-21 expression significantly predicted the development of kidney end points (unadjusted HR, 1.586; 95% CI, 1.179-2.134; P = 0.002). However, the result was just short of statistical significance after adjusting for the severity of histologic damage (P = 0.06). There was also a significant correlation between intrarenal miR-21 expression and the slope of kidney function decline by univariate analysis (r = -0.399; P = 0.02). LIMITATIONS: Small sample size; uncertain cellular origin of miR-21. CONCLUSIONS: We found that intrarenal miR-21 expression is increased in patients with IgAN, modestly correlated with the severity of histologic damage, and predictive of subsequent kidney function loss.
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We report a patient with chronic diabetes and was referred for recent onset proteinuria. Light microscopy of the renal biopsy specimen showed mildly expanded mesangium with mesangial hypercellularity and segmental sclerosis, features compatible with diabetic glomerulosclerosis. However, crystalglobulin-induced nephropathy with crystal deposit was identified on electron microscopy. Renal biopsy is often performed for diabetic patients who present with proteinuria and light microscopy often shows features of diabetic glomerulosclerosis. Additional information may occasionally be revealed on electron microscopy, altering the subsequent plan of management.
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Nefropatias Diabéticas , Mesângio Glomerular , Biópsia , Mesângio Glomerular/patologia , Humanos , Proteinúria/etiologia , Proteinúria/patologia , EscleroseRESUMO
Hyperglycemia causes mitochondrial damage renal tubular cells, which contribute to the progression of diabetic kidney disease. However, the metabolic aberration of renal tubular cells in an hyperglycemic milieu has not been fully elucidated. In this study, human proximal renal tubular cell line (HK-2 cell) are incubated in glucose and mannitol at 5 mM or 25 mM. Cellular metabolome was determined by capillary electrophoresis time of flight mass spectrometer (CE-TOF/MS) and capillary electrophoresis-triple quadrupole mass spectrometry (CE-QqQMS). A total of 116 metabolites were quantified. Principal component analysis (PCA) revealed excellent clustering of metabolomic changes for different treatment conditions, and exposure to glucose at 5 and 25 mM lead to distinct metabolomic profiles as compared to samples treated with serum-free medium or mannitol as osmotic control. Hierarchical clustering analysis showed a number of characteristic changes in metabolic profile following exposure to 5 mM or 25 mM glucose. Notably, lactate-to-pyruvate ratio was significantly increased, while cellular levels of citric acid, α-ketoglutaric acid (i.e. 2-oxoglutaric acid), and fumaric acid were significantly reduced after exposure to glucose at 25 mM but not 5 mM. Moreover, cellular levels of reduced glutathione and total glutathione were significantly decreased, and S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratio was significantly increased after exposure to glucose 25 mM but not 5 mM. We conclude that in response to high glucose, HK-2 cells characteristic metabolomic changes, including increase in lactate-to-pyruvate ratio, reduction in Krebs cycle metabolites, reduction in glutathione antioxidant activity, and increase in cellular methylation potential. Our results may shed light on the pathogenesis of diabetic kidney disease, but the expression of glucose metabolism-related protein and enzyme activity in HK-2 cells after hyperglycemia condition need to be confirmed by further studies.
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Glucose/farmacologia , Túbulos Renais Proximais/metabolismo , Linhagem Celular , Relação Dose-Resposta a Droga , Eletroforese Capilar , Glutationa/metabolismo , Humanos , Hiperglicemia/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Manitol/farmacologia , Espectrometria de Massas , Metabolômica , Análise de Componente PrincipalRESUMO
BACKGROUND: Endocan is associated with endothelial dysfunction. In peritoneal dialysis (PD) patients, cardiovascular disease is a common cause of mortality. We examined the relationship between serum endocan level and clinical outcome of PD patients. METHODS: We recruited 193 new PD patients (118 males, mean age 58.8 ± 11.6 years). Serum endocan levels were determined and stratified into tertile 1 (lowest) to 3 (highest). Nutritional status, arterial pulse wave velocity (PWV) and serum C-reactive protein (CRP) levels were measured. The patients were followed for at least 4 years for clinical outcomes. RESULTS: For the whole cohort, patients with higher serum endocan levels had lower serum albumin and subjective global assessment score, higher carotid-femoral PWV, and higher serum CRP. For patients with suboptimal blood pressure (BP) control, cardiovascular event-free survival was 95.0, 95.5, and 78.5% for tertiles 1, 2, and 3 at 60 months respectively (p = 0.019). Multivariate Cox regression analysis showed that serum endocan level was an independent predictor of cardiovascular event-free survival. No association with cardiovascular event-free survival was found for patients with adequate BP control (95.0, 92.3, and 100% for tertile 1, 2, and 3 at 60 months, respectively, p = 0.6). CONCLUSIONS: Higher serum endocan level is associated with unfavourable nutritional, arterial and inflammatory conditions in PD patients. In patients with suboptimal BP control, higher serum endocan is also associated with worse cardiovascular outcome.
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Proteínas de Neoplasias/sangue , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Proteoglicanas/sangue , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Despite the increasing use of erythropoiesis-stimulating agent (ESA) in patients receiving dialysis, few studies have examined the benefits of ESA for patients with chronic kidney disease receiving palliative care. OBJECTIVE: We designed a retrospective observational study to evaluate the effect of ESA in treating anemia of renal disease among adult patients receiving palliative care instead of dialysis. The primary objective was to assess whether ESA can reduce the transfusion burden and hospitalization. RESULTS: Thirty-nine patients receiving ESA were matched with a control group of 39 patients without ESA. Their mean age and glomerular filtration rates were 76.7 (10.2) years and 11.6 (5.7) mL/min/1.73 m2, respectively. Baseline hemoglobin levels were comparable in the ESA and control groups; their corresponding values were 10.2 (1.5) and 10.1 (1.4) g/dL. During 1-year observation period, 34 units of red cell transfusion occurred in patients receiving ESA, whereas 128 units of red cell were transfused to patients in control group. Patients in the control group had higher transfusion rate (incidence rate ratio [IRR]: 3.63; 95% confidence interval [CI]: 2.49-5.31; P < .00001) and higher admission rates (IRR: 2.34; 95% CI: 1.80-3.03; P < .000001) than the ESA group even after adjustment for comorbidities. CONCLUSIONS: High disease burden of palliative care among patients with stage 4 to 5 chronic kidney disease was reflected by transfusion requirement and hospitalization rates, both of which were shown to be significantly ameliorated by ESA treatment.
Assuntos
Transfusão de Eritrócitos/estatística & dados numéricos , Hematínicos/uso terapêutico , Cuidados Paliativos/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Diálise Renal/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/terapia , Masculino , Diálise Renal/métodos , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Peritoneal protein clearance has been suggested to be a marker of peritoneal inflammation and systemic endothelial dysfunction. METHODS: We enrolled 711 consecutive incident PD patients. Baseline peritoneal protein clearance and other clinical information were reviewed. All patients were followed for at least 1 year for all-cause and cardiovascular mortality. RESULTS: The average PD effluent protein loss was 6.41 ± 2.16 g/day; peritoneal protein clearance was 97.15 ± 41.55 mL/day. The average duration of follow-up was 50.8 ± 36.2 months. Multivariate linear regression analysis showed that serum albumin, C-reactive protein, and mass transfer area coefficients of creatinine were independently associated with peritoneal protein clearance. By multivariate Cox regression analysis, age, Charlson comorbidity score, volume of overhydration and peritoneal protein clearance were independent predictors of all-cause mortality. Every 10 mL/day increase in peritoneal protein clearance confers 10.4% increase in risk of all-cause mortality (95% confidence interval 2.6-18.7%, p = 0.008). Peritoneal protein clearance was also associated with cardiovascular mortality by univariate analysis, but the association became insignificant after adjusting for confounding factors Cox regression analysis. CONCLUSIONS: Baseline peritoneal protein clearance is an independent predictor of all-cause mortality in incident PD patients. Routine measurement of peritoneal protein clearance may facilitate patient risk stratification.
Assuntos
Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Peritônio/metabolismo , Proteínas/metabolismo , Idoso , Proteína C-Reativa/metabolismo , Causas de Morte , Creatinina/sangue , Soluções para Diálise/química , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal , Modelos de Riscos Proporcionais , Proteínas/análise , Albumina Sérica/metabolismoRESUMO
BACKGROUND: Urinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). In this study, we determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD. METHODS: We recruited 102 non-diabetic CKD patients (43 with kidney biopsy that showed non-specific nephrosclerosis). Urinary mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 48.3 ± 31.8 months for renal events (need of dialysis or over 30% reduction in estimated glomerular filtration rate [eGFR]). RESULTS: The median urinary mtDNA level was 1519.42 (inter-quartile range 511.81-3073.03) million copy/mmol creatinine. There were significant correlations between urinary mtDNA level and baseline eGFR (r = 0.429, p < 0.001), proteinuria (r = 0.368, p < 0.001), severity of glomerulosclerosis (r = - 0.537, p < 0.001), and tubulointerstitial fibrosis (r = - 0.374, p = 0.014). The overall rate of eGFR decline was - 2.18 ± 5.94 ml/min/1.73m2 per year. There was no significant correlation between the rate of eGFR decline and urinary mtDNA level. By univariate analysis, urinary mtDNA level predicts dialysis-free survival, but the result became insignificant after adjusting for clinical and histological confounding factors. CONCLUSION: Urinary mtDNA levels have no significant association with the rate of renal function decline in non-diabetic CKD, although the levels correlate with baseline renal function, proteinuria, and the severity of histological damage. Urinary mtDNA level may be a surrogate marker of permanent renal damage in non-diabetic CKD.
Assuntos
DNA Mitocondrial/urina , Taxa de Filtração Glomerular , Nefroesclerose/patologia , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/urina , Adulto , Idoso , Biomarcadores/urina , Feminino , Fibrose , Humanos , Glomérulos Renais/patologia , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Proteinúria/urina , Insuficiência Renal Crônica/fisiopatologiaRESUMO
Background: Mitochondrial dysfunction plays an important role in the pathogenesis and progression of diabetic nephropathy (DN). We study the relation between urinary and intra-renal mitochondrial deoxyribonucleic acid (mtDNA) levels and renal dysfunction in DN. Methods: We recruited 92 patients with biopsy-proven DN. Urinary sediment, urinary supernatant and intra-renal mtDNA levels were measured and compared with baseline renal biopsy, kidney scarring and renal function decline in the subsequent 24 months. Results: mtDNA could be detected in all urine supernatant, urine sediment and renal biopsy specimens. There was a modest but statistically significant inverse correlation between urinary supernatant and intra-renal mtDNA levels (r = -0.453, P = 0.012). Urinary supernatant mtDNA level had modest but statistically significant correlations, inversely with estimated glomerular filtration rate (r = -0.214, P = 0.04), and positively with interstitial fibrosis (r = 0.300, P = 0.005). Intra-renal mtDNA had significant inverse correlation with interstitial fibrosis (r = -0.537, P = 0.003). However, there was no significant relation between renal function decline and urinary supernatant, urinary sediment or intra-renal mtDNA levels. Conclusions: mtDNA is readily detectable in urinary supernatant and kidney tissue, and their levels correlate with renal function and scarring in DN. Further studies are needed to determine the accuracy of urinary supernatant mtDNA level as a prognostic indicator of DN, as well as its role in other kidney diseases.