ResearchPad - creatinine https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Dialysis timing may be deferred toward very late initiation: An observational study]]> https://www.researchpad.co/article/elastic_article_14499 The optimal timing to initiate dialysis among patients with an estimated glomerular filtration rate (eGFR) of <5 mL/min/1.73 m2 is unknown. We hypothesized that dialysis initiation time can be deferred in this population even with high uremic burden. A case-crossover study with case (0–30 days before dialysis initiation [DI]) and control (90–120 days before DI) periods was conducted in 1,079 hemodialysis patients aged 18–90 years at China Medical University Hospital between 2006 and 2015. The uremic burden was quantified based on 7 uremic indicators that reached the predefined threshold in case period, namely hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate. Dialysis timing was classified as standard (met 0–2 uremic indicators), late (3–5 indicators), and very late (6–7 indicators). Median eGFR-DI of the 1,079 patients was 3.4 mL/min/1.73 m2 and was 2.7 mL/min/1.73 m2 in patients with very late initiation. The median follow-up duration was 2.42 years. Antibiotics, diuretics, antihypertensive medications, and non-steroidal anti-inflammatory drugs (NSAIDs) were more prevalently used during the case period. The fully adjusted hazards ratios of all-cause mortality for the late and very late groups were 0.97 (95% confidence interval 0.76–1.24) and 0.83 (0.61–1.15) compared with the standard group. It is safe to defer dialysis initiation among patients with chronic kidney disease (CKD) having an eGFR of <5 mL/min/1.73 m2 even when patients having multiple biochemical uremic burdens. Coordinated efforts in acute infection prevention, optimal fluid management, and prevention of accidental exposure to NSAIDs are crucial to prolong the dialysis-free survival.

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<![CDATA[Renal injury after uninephrectomy in male and female intrauterine growth-restricted aged rats]]> https://www.researchpad.co/article/5c8acce7d5eed0c48499029e

Epidemiological studies report an inverse association between birth weight and risk for kidney disease that may differ between males and females, but studies investigating this association are limited. This study tested the hypothesis that male intrauterine growth-restricted offspring in a model of low birth weight induced by placental insufficiency in the rat exhibit enhanced renal injury in response to a persistent secondary renal insult while female growth-restricted offspring are protected. For this study, control offspring from sham-operated dams and growth-restricted offspring from reduced uterine perfusion dams underwent uninephrectomy or a sham procedure at 18 months of age. One month later, urinary markers of renal injury, renal function, and histological damage were measured. Results were analyzed using 2-way ANOVA. Male and female offspring were assessed separately. Proteinuria and urinary neutrophil gelatinase-associated lipocalin were significantly elevated in male growth-restricted offspring exposed to uninephrectomy when compared to male uninephrectomized control. Urinary kidney injury marker-1 was elevated in male uninephrectomized growth-restricted offspring relative to male sham growth-restricted but not to male uninephrectomized controls. Likewise, urinary neutrophil gelatinase-associated lipocalin was elevated in female uninephrectomized growth-restricted offspring but only when compared to female sham growth-restricted offspring. Markers of renal function including glomerular filtration rate and serum creatinine were impaired after uninephrectomy in female offspring regardless of birth weight. Histological parameters did not differ between control and growth-restricted offspring. Collectively, these studies suggest that both male and female growth-restricted offspring demonstrate susceptibility to renal injury following uninephrectomy; however, only male growth-restricted offspring exhibited an increase in renal markers of injury in response to uninephrectomy relative to same-sex control counterparts. These findings further suggest that urinary excretion of protein, kidney injury marker-1, and neutrophil gelatinase-associated lipocalin may be early markers of kidney injury in growth-restricted offspring exposed to a secondary renal insult such as reduction in renal mass.

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<![CDATA[Leisure-time physical activity and DNA damage among Japanese workers]]> https://www.researchpad.co/article/5c706785d5eed0c4847c717f

Background

It remains unclear whether daily physical activity is associated with DNA damage. This cross-sectional study examined the association between leisure-time physical activity and urinary 8-hydroxydeoxyguanosine (8-OH-dG), a biomarker of oxidative DNA damage, or urinary 7-methylguanine (m7Gua), a biomarker of methylating DNA damage.

Methods

Participants included 501 workers (294 men and 207 women), aged 20–65 years, from municipal offices in Japan. Urinary 8-OH-dG and m7Gua were measured using column-switching HPLC. Physical activity was evaluated using a self-reported questionnaire. The associations between leisure-time physical activity and urinary DNA damage markers were assessed by multiple linear regression analysis, with stratification by occupational physical activity.

Results

After adjusting for covariates, leisure-time physical activity showed a suggestive inverse correlation with urinary 8-OH-dG levels (P for trend = 0.06), and a significant inverse association with urinary m7Gua levels (P for trend = 0.03). In analysis stratified by occupation, inverse correlations were observed in sedentary workers (walking < 30 min/day at work: P for trend = 0.06 and = 0.03 for urinary 8-OH-dG and m7Gua, respectively), but not in physically active workers (walking ≥ 30 min/day at work). In analysis for each intensity of leisure-time physical activity, light-intensity exercise was associated with lower levels of urinary 8-OH-dG (P for trend = 0.03), whereas moderate-to-high-intensity exercise was associated with lower levels of urinary m7Gua (P for trend = 0.02).

Conclusions

Our results suggest that high levels of leisure-time physical activity are associated with decreased levels of DNA damage in individuals with low physical activity at work.

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<![CDATA[Association between physical activity and change in renal function in patients after acute myocardial infarction]]> https://www.researchpad.co/article/5c75abf7d5eed0c484d07f41

Background

Combined renal dysfunction worsens the subsequent prognosis in patients after acute myocardial infarction (AMI). Therefore, establishing a therapeutic modality to maintain or improve renal function in AMI patients is necessary. This study aimed to elucidate the association between physical activity level and change in renal function in such patients.

Design

Prospective and observational study.

Methods

We enrolled 41 patients (35 men; average age, 67.5 ± 12.6 years) after AMI onset. Blood biochemistry, urinalysis, and physical function tests were conducted at discharge and 3 months after discharge. Renal function was evaluated based on cystatin C based-estimated glomerular filtration rate (eGFRcys). The number of steps was recorded for 3 months post-discharge. Generalized estimating equations (GEE) was used to test the association between physical activity level and within-patient changes in eGFRcys.

Results

Patients were stratified into low (n = 21; number of steps, 2335 ± 1219 steps/day) and high groups (n = 20; number of steps, 7102 ± 2365 steps/day). eGFRcys significantly increased from baseline to after 3 months in the high group (76.5 ± 13.8 to 83.2 ± 16.0 mL/min/1.73 m2, q = 0.004), whereas no significant change was observed in the low group (65.1 ± 15.9 to 62.2 ± 20.2 mL/min/1.73 m2, q = 0.125). Result of GEE adjusted for potential confounding variables showed a significant positive association between physical activity level and within-patient changes in eGFRcys (p = 0.003). Changes in eGFRcys was -2.9 mL/min/1.73 m2 among low group versus +6.7 mL/min/1.73 m2 among high group.

Conclusions

Physical activity level was positively associated with changes in renal function, demonstrating that high physical activity may suppress renal function decline in patients after AMI.

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<![CDATA[Serum creatinine and estimated glomerular filtration rates in HIV positive and negative adults in Ethiopia]]> https://www.researchpad.co/article/5c6c75bfd5eed0c4843d00e4

Background

Glomerular filtration rate estimating equations using serum creatinine are not validated in most African settings. We compared serum creatinine and estimated glomerular filtration rate (eGFR) in HIV positive and negative adults and assessed the performance of eGFR equations ((Cockcroft and Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) compared to 24-hour creatinine clearance in HIV positive adults.

Methods

Data were collected on demographic, anthropometric, body composition, clinical parameters and serum creatinine in HIV positive and negative adults. 24-hour urine was collected from some of the HIV positive adults who volunteered. Bias was calculated as mean difference between 24-hr creatinine clearance and eGFR (eGFR– 24 hour creatinine clearance) and the accuracy of each eGFR equation was calculated as the percentage of estimates within 30% of creatinine clearance.

Results

A total of 340 HIV positive and 100 HIV negative adults were included in this study. Creatinine clearance was determined for 46 of HIV positive adults. Serum creatinine increased with increasing age, weight, height, body surface area, fat free mass and grip strength in both HIV positive and negative adults (P<0.05). No difference was observed in eGFR between HIV positive and HIV negative adults. For all eGFR equations, the correlation between eGFR and 24-hr creatinine clearance was 0.45–0.53 and the accuracy within 30% of 24-hr creatinine clearance was 24–46%. Removing ethnic coefficient reduced the bias and improved accuracy of the CKD-EPI and the MDRD estimates.

Conclusion

Ethiopian HIV positive adults in the present study had good kidney function at the initiation of antiretroviral treatment. However, all eGFR equations overestimated 24-hr creatinine clearance in the study population. Creatinine based eGFR equations that accounts for low muscle mass and body surface area are needed.

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<![CDATA[Natural evolution of ductus arteriosus with noninterventional conservative management in extremely preterm infants born at 23-28 weeks of gestation]]> https://www.researchpad.co/article/5c6dc9e3d5eed0c48452a424

This study aimed to determine the natural course of patent ductus arteriosus (PDA) with noninterventional conservative management and whether the presence and/or prolonged duration of hemodynamically significant (HS) PDA increased the risk of mortality and morbidities in extremely preterm (EPT) infants. We retrospectively reviewed the medical records of EPT infants born at 23–28 weeks of gestation (n = 195) from January 2011 to June 2014, when PDA was managed with noninterventional conservative treatment. We stratified infants into three subgroups of 23–24, 25–26, and 27–28 weeks and analyzed the prevalence and natural evolution of HS PDA, defined as ventilator dependency and PDA size ≥2 mm. Multivariate regression analyses determined if the presence and/or prolonged duration of HS PDA increased the risk for mortality and/or morbidities. The overall incidence of HS PDA was 57% (111/195) at the end of the first postnatal week. In subgroup analyses, infants with 23–24 weeks of gestation had the highest incidence (93%, 50/54), with 64% (47/74) for 25–26 weeks and 21% (14/67) for 27–28 weeks. Six (5%) of 111 infants with HS PDA were discharged without ductus closure, 4 had spontaneous PDA closure on follow up, and device closure was performed for 2 infants. In the multivariate analyses, the presence or prolonged duration (per week) of HS PDA was not associated with the risk of mortality and/or morbidities. Spontaneous closure of HS PDA was mostly achieved, even in EPT infants, with a noninterventional conservative approach. In conclusion, our data showed the incidence and natural course of HS PDA in EPT infants and suggested that the presence or prolonged duration of HS PDA might not increase the rate of mortality or morbidities.

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<![CDATA[Biochemical metabolic levels and vitamin D receptor FokⅠ gene polymorphisms in Uyghur children with urolithiasis]]> https://www.researchpad.co/article/5c6b2681d5eed0c484289bc2

Because of lacking studies of urolithiasis in children, we detected the biochemical metabolic levels and FokⅠ polymorphisms in the vitamin D receptor (VDR) in Uyghur children with urolithiasis, and evaluated the associations of biochemical metabolic levels with FokⅠ genotypes. We included 142 Uyghur children (108 males) under age 14 years with a diagnosis of urolithiasis and 238 Uyghur children (154 males) under age 14 years without a history of urolithiasis as controls. Baseline information and data for serum and urine parameters were obtained from medical records. PCR-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the VDR FokⅠ polymorphisms. In univariate analyses adjusting for age and sex, carbon dioxide combining power (CO2CP) (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.07–1.19), serum magnesium (Mg) (OR = 1.27, 95% CI: 1.03–1.56) and serum chlorine (Cl) (OR = 0.93, 95% CI: 0.88–0.97) were related to Uyghur children urolithiasis risk. A multiple logistic regression model showed CO2CP (OR = 1.17, 95% CI: 1.09–1.26), levels of uric acid (OR = 1.01, 95% CI: 1.00–1.01) and serum sodium (Na) (OR = 0.90, 95% CI: 0.82–0.99) were associated with pediatric urolithiasis. The risk of urolithiasis was increased with the F versus f allele overall (OR = 1.42; 95% CI: 1.01–2.00) and for males (OR = 1.52, 95% CI: 1.02–2.27). However, metabolic levels did not differ by FokⅠ genotypes. In our population, CO2CP and levels of uric acid and serum Na as well as polymorphism of the F allele of the VDR FokⅠ may provide important clues to evaluate the risk of urolithiasis in Uyghur children.

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<![CDATA[Serum Axl predicts histology-based response to induction therapy and long-term renal outcome in lupus nephritis]]> https://www.researchpad.co/article/5c6b261bd5eed0c484289315

Axl is a receptor tyrosine kinase with important functions in immune regulation. We investigated serum levels of soluble (s)Axl in lupus nephritis (LN) in association with renal disease activity, tissue damage and treatment response. We surveyed 52 patients with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III/IV LN and 20 healthy controls. Renal biopsies were performed at the time of active LN and post-treatment. Patients were classified as clinical responders (CRs) or clinical non-responders based on the American College of Rheumatology (ACR) criteria. Improvement by ≥50% in renal activity index scores defined histological responders (HRs). sAxl levels were elevated in patients compared to controls (median: 18.9 ng/mL), both at baseline (median: 45.7; P<0.001) and post-treatment (median: 41.2 ng/mL; P<0.001). Baseline sAxl levels were higher in patients with class IV (median: 47.7 ng/mL) versus class III (median: 37.5 ng/mL) nephritis (P = 0.008), and showed moderate correlations with albuminuria (r = 0.30, P = 0.030) and creatinine (r = 0.35, P = 0.010). Baseline sAxl levels decreased in CRs (P = 0.002) and HRs (P<0.001), but not in non-responders; levels ≥36.6 ng/mL yielded a >5 times higher probability of histology-based response (odds ratio, OR: 5.5; 95% confidence interval, CI: 1.2–25.1). High post-treatment sAxl levels were associated with worsening in chronicity index scores (P = 0.025); low levels predicted favourable renal outcome (creatinine ≤88.4 μmol/L) 10 years after the baseline renal biopsy (area under the curve: 0.71; 95% CI: 0.54–0.89). In conclusion, sAxl may prove useful as a marker of renal activity, histological response to immunosuppression, and renal damage progression in LN. Persistently high sAxl levels after completion of treatment may be indicative of a need for treatment intensification.

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<![CDATA[The association between urinary genistein levels and mortality among adults in the United States]]> https://www.researchpad.co/article/5c79b007d5eed0c4841e3c82

Background

Current research on the relationship between phytoestrogens and mortality has been inconclusive. We explored the relationship between genistein, a phytoestrogen, and mortality in a large cohort representative of the United States population.

Methods

Data were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999–2010. Normalized urinary genistein (nUG) was analyzed as a log-transformed continuous variable and in quartiles. Mortality data were obtained from the National Death Index and matched to the NHANES participants. Survival analyses were conducted using the Kaplan-Meier analysis. Cox proportional hazard models were constructed for all-cause and cause-specific mortality without and with adjustment for potential confounding variables.

Results

Of 11,497 participants, 944 died during the 64,443 person-years follow-up. The all-cause mortality rate was significantly lower in the lowest quartile compared to the highest quartile (incidence rate ratio = 2.14, 95%CI = 1.76 to 2.60). Compared to the lowest quartile, the highest quartile had significantly higher adjusted all-cause (HR = 1.57, 95%CI = 1.23 to 2.00), cardiovascular (HR = 1.67, 95%CI = 1.04 to 2.68), and other-cause (HR = 1.85, 95%CI = 1.33 to 2.57) mortality.

Conclusion

We found that high urinary genistein levels were associated with increased risk of all-cause, cardiovascular, and other-cause mortality. This is contrary to popular opinion on the health benefits of genistein and needs further research.

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<![CDATA[Prediction of all-cause mortality after liver transplantation using left ventricular systolic and diastolic function assessment]]> https://www.researchpad.co/article/5c79afc8d5eed0c4841e3741

Although pretransplant cardiac dysfunction is considered a major predictor of poor outcomes after liver transplantation (LT), the ability of left ventricular (LV) systolic/diastolic function (LVSF/LVDF), together or individually, to predict mortality after LT is poorly characterized. We retrospectively evaluated pretransplant clinical and Doppler echocardiographic data of 839 consecutive LT recipients from 2009 to 2012 aged 18–60 years. The primary endpoint was all-cause mortality at 4 years. The overall survival rate was 91.2%. In multivariate Cox analysis, reduced LV ejection fraction (LVEF, P = 0.014) and decreased transmitral E/A ratio(P = 0.022) remained significant prognosticators. In LVSF analysis, patients with LVEF≤60% (quartile [Q]1) had higher mortality than those with LVEF>60% (hazard ratio = 1.90, 95% confidence interval = 1.15–3.15, P = 0.012). In LVDF analysis, patients with an E/A ratio<0.9(Q1) had a 2.19-fold higher risk of death (95% confidence interval = 1.11–4.32, P = 0.024) than those with an E/A ratio>1.4(Q4). In combined LVDF and LVSF analysis, patients with an E/A ratio<0.9 and LVEF≤60% had poorer survival outcomes than patients with an E/A ratio≥0.9 and LVEF>60% (79.5% versus 93.3%, P = 0.001). Patients with an early mitral inflow velocity/annular velocity (E/e’ ratio)>11.5(Q4) and LV stroke volume index (LVSVI)<33mL/m2(Q1) showed worse survival than those with an E/e’ ratio≤11.5 and LVSVI ≥33mL/m2(78.4% versus 92.2%, P = 0.003). A combination of LVSF and LVDF is a better predictor of survival than LVSF or LVDF alone.

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<![CDATA[Trauma induced acute kidney injury]]> https://www.researchpad.co/article/5c57e693d5eed0c484ef37fb

Background

Injured patients are at risk of developing acute kidney injury (AKI), which is associated with increased morbidity and mortality. The aim of this study is to describe the incidence, timing, and severity of AKI in a large trauma population, identify risk factors for AKI, and report mortality outcomes.

Methods

A prospective observational study of injured adults, who met local criteria for trauma team activation, and were admitted to a UK Major Trauma Centre. AKI was defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariable logistic regression and Cox proportional hazard modelling was used to analyse parameters associated with AKI and mortality.

Results

Of the 1410 patients enrolled in the study, 178 (12.6%) developed AKI. Age; injury severity score (ISS); admission systolic blood pressure, lactate and serum creatinine; units of Packed Red Blood Cells transfused in first 24 hours and administration of nephrotoxic therapy were identified as independent risk factors for the development of AKI. Patients that developed AKI had significantly higher mortality than those with normal renal function (47/178 [26.4%] versus 128/1232 [10.4%]; OR 3.09 [2.12 to 4.53]; p<0.0001). After adjusting for other clinical prognostic factors, AKI was an independent risk factor for mortality.

Conclusions

AKI is a frequent complication following trauma and is associated with prolonged hospital length of stay and increased mortality. Future research is needed to improve our ability to rapidly identify those at risk of AKI, and develop resuscitation strategies that preserve renal function in trauma patients.

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<![CDATA[Epidermal growth factor and its influencing variables in healthy children and adults]]> https://www.researchpad.co/article/5c5369cbd5eed0c484a46735

Background & objective

Epidermal growth factor (EGF) stimulates cell proliferation and differentiation after binding to its receptor. Next to its role in magnesium homeostasis, EGF disturbances have been described in oncology, diabetes and autism spectrum disorders. The aim of this study was to determine EGF serum and urine values for both healthy children and adults. Next, we investigated the relation between several variables and urinary and serum EGF concentrations.

Methods

Both healthy adults (n = 50) and children (n = 78) were included. Serum and urinary EGF concentrations were measured with ELISA technology.

Results

Serum EGF was inversely correlated with age (r = —0.873; p<0.001) and positively correlated with serum magnesium (r = 0.597; p<0.001). The urinary EGF was also inversely correlated with age (r = -0.855; p<0.001). In adults and children older than 13 years of age, the urinary EGF significantly differed between sexes (p = 0.001). Urinary EGF was positively correlated with serum magnesium (r = 0.583; p<0.001) and creatinine clearance (r = 0.524; p<0.001) and negatively correlated with the fractional excretion of magnesium (r = 0.248; p = 0.014). In a multivariate model, age and serum magnesium remained independently related to serum EGF while age, serum EGF and serum magnesium remained independently related to urinary EGF.

Conclusions

This study provides valuable insights in urinary and serum EGF patterns in healthy subjects. By systematically correcting EGF for body surface, significant correlations with age, gender and magnesium were observed.

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<![CDATA[Improving peak concentrations of a single dose regime of gentamicin in patients with sepsis in the emergency department]]> https://www.researchpad.co/article/5c50c447d5eed0c4845e8434

Objective

To achieve an optimal effect in patients with sepsis at the emergency department (ED), the gentamicin peak-concentration should be sufficiently high (i.e. peak-concentration/MIC ≥8–10). ICU patients with sepsis often need higher gentamicin doses to achieve sufficiently high peak-concentrations. The aim of this study is to investigate which dose is needed to reach adequate peak-concentrations in patients presenting with sepsis at the ED.

Methods

Patients with sepsis at the ED were included from August 2015 until February 2017. Peak-concentrations were measured in blood 30 minutes after the first gentamicin dose. The study consisted of three phases. In the first phase, peak-concentrations were measured after a standard dose of 5mg/kg. In the second phase, a simulation ((peak-concentration/actual dose) × simulated dose) was performed to determine which dose was needed to reach adequate gentamicin peak-concentrations of ≥16mg/L. In the third phase, peak-concentrations were measured for the best simulated dose.

Results

In phase one, of 86 patients who received a dose of 5mg/kg, 34 (39.5%) patients did not reach the target peak-concentration of ≥16mg/L, and 73 (84.9%) did not reach ≥20mg/L. In phase two, the simulation showed that with a dose of 7mg/kg 83 (96.5%) patients would reach peak-concentrations ≥16mg/L, and 67 (77.9%) of ≥20mg/L. In phase three, 53 patients received a dose of 7mg/kg, of whom 45 (84.9%) reached peak-concentrations of ≥16mg/L, and 31 (58.5%) of ≥20mg/L.

Conclusion

Patients with sepsis at the ED need higher doses of gentamicin. A dose of 7mg/kg is needed to achieve adequate peak-concentrations in the majority of patients.

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<![CDATA[Polyomavirus BK, BKV microRNA, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis]]> https://www.researchpad.co/article/5c466538d5eed0c484518127

Objective

Lupus nephritis (LN) frequently progresses to end-stage renal disease. Finding a biomarker for LN and a predictor for the development of chronic kidney disease (CKD) is important for patients with systemic lupus erythematosus (SLE).

Methods

Ninety patients with SLE were divided into biopsy-proven LN (n = 54) and no kidney involvement (non-LN) (n = 36) groups and followed up for 54 months.

Results

Of 36 patients with LN, 3 (5.6%) had class II disease, 3 (5.6%) had class III, 35 (64.8%) had class IV, 10 (18.5%) had class V, and 3 (5.6%) had class VI (advanced sclerosis). Compared to the non-LN group, patients in the LN group had higher autoimmunity evidenced by a higher proportion of low C3 and C4 levels, positive anti-double-stranded DNA antibody levels, and lower estimated glomerular filtration rates (eGFR). Urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels were significantly higher in the LN group (LN vs non-LN, 670 vs 33 ng/mL, respectively). The patients with LN had a higher urinary polyomavirus BK (BKV) load (3.6 vs 3.0 log copies/mL) and a lower urinary BKV miRNA (miR-B1) 5p level (0.29 vs 0.55 log copies/mL, p = 0.025), while there was no significant difference in the level of miR-B1-3p. Urinary miR-B1-5p level but not urinary BKV load was negatively correlated with uNGAL level (r = -0.22, p = 0.004). At the cutoff value of 80 ng/mL, the receiver operating characteristic curve analysis showed that uNGAL level as a predictor of the presence of LN had a high sensitivity (98%) and specificity (100%) (area under the curve [AUC], 0.997; p < 0.001). During the 54-month follow-up period, 14 (7%) patients with LN and none of the non-LN patients developed CKD. Multivariate Cox regression analysis revealed that baseline uNGAL level was the only predictive factor for CKD development, while baseline serum creatinine level and eGFR were not.

Conclusion

An elevated urinary BKV viral load with a decreased level of miR-B1 implies the presence of LN. In addition, an increased uNGAL level is a good biomarker not only in predicting the presence of LN but also for prediction of CKD development in patients with SLE.

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<![CDATA[The association of the difference in hemoglobin levels before and after hemodialysis with the risk of 1-year mortality in patients undergoing hemodialysis. Results from a nationwide cohort study of the Japanese Renal Data Registry]]> https://www.researchpad.co/article/5c40f767d5eed0c4843860a0

Background

Few clinical studies have directly examined the associations of hemoglobin (Hb) levels after hemodialysis (HD) and of the difference in Hb levels before and after HD (ΔHb) with patient outcomes. The present study aimed to determine ΔHb and post-HD Hb levels with nationwide data and to examine their associations with all-cause mortality in patients undergoing HD.

Methods

This study is based on data from 2008 and 2009 recorded in the Japanese Renal Data Registry. Study endpoints were all-cause mortality within 1-year. The ΔHb and post-HD Hb level as categorical variables using Cox regression for 1-year mortality, adjusting for potential confounders.

Results

The median ΔHb was 1.0 g/dl, and the post-HD Hb level was 11.3 g/d. The median pre-HD Hb level was 10.4 g/dl. The risk of mortality was lower with a ΔHb of 0 to 1.0 g/dl (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.70–1.01) or > 1.0 g/dl (aHR, 0.73; 95% CI, 0.64–0.84) than with a ΔHb < 0 g/dl. The risk for mortality was also lower with a post-HD Hb of 10 to 11 g/dl (aHR, 0.82; 95% CI, 0.73–0.92), 11 to 12 g/dl (aHR, 0.77; 95% CI, 0.68–0.87), or > 12 g/dl (aHR, 0.77; 95% CI, 0.68–0.87) than with a post-HD Hb < 10 g/dl.

Conclusions

Both a low ΔHb and a low post-HD Hb level were associated with a higher risk of 1-year mortality.

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<![CDATA[Alemtuzumab induction combined with reduced maintenance immunosuppression is associated with improved outcomes after lung transplantation: A single centre experience]]> https://www.researchpad.co/article/5c478c9dd5eed0c484bd36c6

Question addressed by the study

The value of induction therapy in lung transplantation is controversial. According to the ISHLT, only about 50% of patients transplanted within the last 10 years received induction therapy. We reviewed our institutional experience to investigate the impact of induction therapy on short- and long-term outcomes.

Materials/Patients and methods

Between 2007 and 2015, 446 patients with a complete follow-up were included in this retrospective analysis. Analysis comprised long-term kidney function, infectious complications, incidence of rejection and overall survival.

Results

A total of 231 patients received alemtuzumab, 50 patients antithymocyte globulin (ATG) and 165 patients did not receive induction therapy (NI). The alemtuzumab group revealed the lowest rate of chronic kidney insufficiency (NI: 52.2%; ATG: 60%; alemtuzumab: 36.6%; p = 0.001). Both, the NI group (p<0.001) and the ATG group (p = 0.010) showed a significant increase of serum creatinine during follow-up compared to alemtuzumab patients. Furthermore, alemtuzumab group experienced the lowest rate of infection in the first year after transplantation. Finally, improved survival, low rates of acute cellular rejection (ACR), lymphocytic bronchiolitis (LB) and chronic lung allograft dysfunction (CLAD) were found in patients treated either with alemtuzumab or ATG.

Conclusion

Alemtuzumab induction therapy followed by reduced maintenance immunosuppression is associated with a better kidney function compared to no induction and ATG. Survival rate as well as freedom from ACR and CLAD were comparable between alemtuzumab and ATG.

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<![CDATA[Longitudinal stability in cigarette smokers of urinary biomarkers of exposure to the toxicants acrylonitrile and acrolein]]> https://www.researchpad.co/article/5c390bd9d5eed0c48491ea77

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

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<![CDATA[Increased water intake reduces long-term renal and cardiovascular disease progression in experimental polycystic kidney disease]]> https://www.researchpad.co/article/5c3667b9d5eed0c4841a61de

Polycystic kidney disease (PKD) is the most common inherited cause of kidney failure and currently has limited treatment options. Increasing water intake reduces renal cyst growth in the pck rat (a genetic ortholog of autosomal recessive PKD) but it is not clear if this beneficial effect is present in other models of PKD. In this study, we tested the hypothesis that high water intake (HWI) reduces the progression of cystic renal disease in Lewis polycystic kidney (LPK) rats (a genetic ortholog of human nephronophthisis-9). Groups of female and male LPK (n = 8–10 per group) and Lewis (n = 4 per group) rats received water ad libitum supplemented with or without 5% glucose [to simulate HWI or normal water intake (NWI) respectively] from postnatal weeks 3 to 16. Water intake increased ~1.3-fold in the LPK+HWI group compared to LPK+NWI rats between weeks 3 to 10 but the differences were not significant at later timepoints. In LPK rats, HWI reduced the increases in the kidney to body weight ratio by 54% at week 10 and by 42% at week 16 compared to NWI (both p<0.01). The reduction in kidney enlargement was accompanied by decreases in the percentage renal cyst area, percentage renal interstitial collagen and proteinuria (all p<0.05). At week 16, HWI reduced systolic blood pressure and the heart to body to weight ratio by 16% and 21% respectively in males LPK rats (both p<0.01). In conclusion, a modest increase in water intake during the early phase of disease was sufficient to attenuate renal cystic disease in LPK rats, with secondary benefits on hypertension and cardiovascular disease. These data provide further preclinical evidence that increased water intake is a potential intervention in cystic renal diseases.

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<![CDATA[Alteration of urinary neutrophil gelatinase–associated lipocalin as a predictor of tacrolimus-induced chronic renal allograft fibrosis in tacrolimus dose adjustments following kidney transplantation]]> https://www.researchpad.co/article/5c269729d5eed0c48470ecbb

Despite tacrolimus (TAC) drug-level monitoring, TAC-induced chronic renal allograft fibrosis remains an important problem. This study investigated the potential of urinary neutrophil gelatinase–associated lipocalin (uNGAL) as a chronic renal allograft fibrosis biomarker in a two-phase study (proof of concept and cohort). In the proof of concept stage of the study, increased TAC-doses at 3 days after dose adjustment compared with the baseline were associated with elevated uNGAL (+ΔuNGAL) and urinary interleukin 18 (IL-18), but normal serum creatinine (SCr), despite the therapeutic trough levels of TAC. In the cohort study, the patients with elevated uNGAL post-recruitment in comparison with the baseline (+ΔuNGAL) was associated with the more severe renal allograft fibrosis from renal pathology of the protocol biopsy at 12 months post kidney transplantation (post-KT). A cut-off value of uNGAL ≥ 125.2 ng/mL during a 3, 6, 9 and 12 months post-KT was associated with a higher fibrosis score, with an area under the receiver operating characteristics curve of 0.80 (95% confidence interval [CI] 0.72 to 0.88, p < 0.0001) and a hazard ratio (HR) of 2.54 (95% CI 1.45 to 9.33; p < 0.001). We conclude that uNGAL is a sensitive biomarker of TAC induced subtle renal injury and TAC-induced chronic renal allograft fibrosis. We propose that uNGAL measurements, in addition to trough levels of TAC, should be used to predict TAC-induced chronic renal allograft fibrosis in the recipients of KT.

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<![CDATA[Evaluation of renal oxygen saturation using photoacoustic imaging for the early prediction of chronic renal function in a model of ischemia-induced acute kidney injury]]> https://www.researchpad.co/article/5c215158d5eed0c4843f9cb9

Purpose

To evaluate the utility of photoacoustic imaging in measuring changes in renal oxygen saturation after ischemia-induced acute kidney injury, and to compare these measurements with histological findings and serum levels of kidney function.

Material and Methods

Acute kidney injury was induced by clamping the left renal pedicle in C57Bl/6 mice, with a 35-min ischemic period used to induce mild renal injury (14 mice) and a 50-min period for severe injury (13 mice). The oxygen saturation was measured before induction, and at 5 time-points over the first 48 h after induction, starting at 4 h after induction. Oxygen saturation, histological score, kidney volume, and the 24 h creatinine clearance rate and serum blood urea nitrogen were also measured on day 28. Between-group differences were evaluated using a Mann-Whitney U-test and Dunn’s multiple comparisons. The association between oxygen saturation and measured variables was evaluated using Spearman’s correlation. A receiver operator characteristic curve was constructed from oxygen saturation values at 24 h after heminephrectomy to predict chronic renal function.

Results

The oxygen saturation was higher in the mild than severe renal injury group at 24 h after induction (73.7% and 66.9%, respectively, P<0.05). Between-group comparison on day 28 revealed a higher kidney volume (P = 0.007), lower tubular injury (P<0.001), lower serum level of blood urea nitrogen level (P = 0.016), and lower 24 h creatinine clearance rate (P = 0.042) in the mild compared with the severe injury group. The oxygen saturation at 24 h correlated with the 24 h creatinine clearance rate (P = 0.036) and serum blood urea nitrogen (P<0.001) on day 28, with an area under the receiver operating curve of 0.825.

Conclusion

Oxygen saturation, measured by photoacoustic imaging at 24 h after acute kidney injury can predict the extent of subsequent histological alterations in the kidney early after injury.

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