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Nephron Extra
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This is an Open Access Journal

Open Access journal
ISSN (Online) 1664-5529
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Dietary Oxidative Balance Scores and Biomarkers of Inflammation among
Individuals with and without Chronic Kidney Disease
- Abstract: Background: Oxidative stress and inflammation are proposed mechanisms of nonspecific kidney injury and progressive kidney failure. Higher dietary oxidative balance scores (OBS) are associated with lower prevalence of chronic kidney disease (CKD). Methods: We investigated the association between OBS and biomarkers of inflammation using data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Nutrient estimates from the Block Food Frequency Questionnaires were used to define tertiles of 11 pro- and antioxidant factors. Points for each OBS component were summed, with a higher score indicating predominance of antioxidant exposures. Multivariable linear regression models were used to estimate the association between OBS and biomarkers of inflammation (interleukin-6 [IL-6], interleukin-8 [IL-8], interleukin-10 [IL-10], fibrinogen, C-reactive protein [CRP], white blood cell count, and cystatin C). An interaction term was included to determine if associations between OBS and inflammatory markers differed between individuals with and without CKD. Results: Of 682 participants, 22.4% had CKD. In adjusted models, OBS was associated with CRP and IL-6. For every 5-unit increase in OBS, the CRP concentration was –15.3% lower (95% CI: –25.6, –3.6). The association of OBS with IL-6 differed by CKD status; for every 5-unit increase in OBS, IL-6 was –10.7% lower (95% CI: –16.3, –4.7) among those without CKD, but there was no association among those with CKD (p = 0.03). Conclusion: This study suggests that a higher OBS is associated with more favorable levels of IL-6 and CRP, and that the association of OBS and IL-6 may be modified by CKD status.
  Nephron Extra 2018;8:11–23
  PubDate: Tue, 21 Aug 2018 16:17:47 +020
Proteinuria and the Clinical Course of Dobrava-Belgrade Hantavirus
Infection
- Abstract: Purpose: Human infection with Dobrava-Belgrade virus (DOBV) in Northern Germany causes a mild form of hantavirus disease predominantly characterized by acute kidney injury due to interstitial nephritis. We evaluated the largest number of DOBV-infected patients so far regarding clinical course, proteinuria, and prognostic markers. Patients and Methods: Patients with DOBV-associated hantavirus disease admitted to the Renal Division of the University of Lübeck (Germany) between 1997 and 2012 were included in this study. Symptoms, clinical course, laboratory parameters, and urinary protein analysis were investigated at admission (baseline, t0), 3–5 days (t3–5), 10–17 days (t10–17), and after 1 year of follow-up (t365). Results: Of the 34 patients (male/female ratio: 23/11; age: 41 ± 14 years) included in the study, 4 underwent hemodialysis (HD). Glomerular filtration rate was 17 ± 14 mL/min at t0 and increased to 27 ± 26 mL/min (t3–5), 57 ± 20 mL/min (t10–17), and 84 ± 16 mL/min (t365). Albuminuria and tubular proteinuria (α1- and β2-microglobulin) decreased during follow-up; the urinary α1-microglobulin concentration in patients who required HD was significantly higher than that in patients not requiring HD (t0: 186 ± 51 vs. 45 ± 26 mg/g creatinine; t3–5: 87 ± 14 vs. 32 ± 16 mg/g creatinine; t10–17: 63 ± 18 vs. 28 ± 12 mg/g creatinine; p #x3c; 0.001). Conclusions: DOBV infection of inpatients in Northern Germany is associated with severe kidney injury that recovers within a few weeks and normalizes within 1 year. Tubular proteinuria is associated with the severity of kidney injury and the necessity of renal replacement therapy in these DOBV-infected patients.
  Nephron Extra 2018;8:1–10
  PubDate: Fri, 09 Feb 2018 10:03:36 +010
Evaluation of the Relationship between the Serum Alkaline Phosphatase
Level at Dialysis Initiation and All-Cause Mortality: A Multicenter,
Prospective Study
- Abstract: Background/Aim: High serum alkaline phosphatase (ALP) levels predict mortality independent of bone metabolism parameters and liver function test results in patients on hemodialysis. The relationship between serum ALP at dialysis initiation and mortality during maintenance dialysis is unknown; therefore, we aimed to identify an association. Methods: This multicenter, prospective cohort study analyzed 1,213 patients registered in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis from October 2011 to September 2013. Patients were divided into 2 groups based on serum ALP levels. All-cause mortality and incidences of cardiovascular events after dialysis initiation were compared using the log-rank test and multivariate Cox proportional hazard regression analysis. We performed stratified analysis based on parathyroid hormone (PTH) levels. Results: During the follow-up, 109 (18.0%) and 86 (14.1%) patients died in the high ALP group (232 ≥IU/L; High ALP group) and low ALP group (232 #x3c;IU/L; Low ALP group), respectively. All-cause mortality was significantly higher in the High ALP group than in the Low ALP group (p = 0.014). The serum ALP level was significantly correlated with the all-cause mortality rate (hazard ratio = 1.17 per 100 IU/L increase of ALP, 95% confidence interval: 1.11–1.24, p #x3c; 0.001). The all-cause mortality rate was significantly higher in the High ALP group among patients with low (#x3c;150 pg/mL) or normal (150–300 pg/mL) PTH levels (p = 0.012 and p = 0.005, respectively) than in the Low ALP group; there was no significant difference among patients with a high (≥300 pg/mL) PTH level (p = 1.000). Conclusion: The serum ALP level at dialysis initiation is associated with all-cause mortality during maintenance dialysis.
  Nephron Extra 2017;7:78–88
  PubDate: Tue, 28 Nov 2017 10:26:54 +010
Urinary Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Acute
Kidney Injury, Severe Kidney Injury, and the Need for Renal Replacement
Therapy in the Intensive Care Unit
- Abstract: Background: Recent attempts were made to identify early indicators of acute kidney injury (AKI) in order to accelerate treatment and hopefully improve outcomes. This study aims to assess the value of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a predictor of AKI, severe AKI, and the need for renal replacement therapy (RRT). Methods: We conducted a prospective study and included adults admitted to our intensive care unit (ICU) at King Abdulaziz University Hospital (KAUH), between May 2012 and June 2013, who had at least 1 major risk factor for AKI. They were followed up throughout their hospital stay to identify which potential characteristics predicted any of the above 3 outcomes. We collected information on patients’ age and gender, the Acute Physiology And Chronic Health Evaluation, version II (APACHE II) score, the Sepsis-Related Organ Failure Assessment (SOFA) score, serum creatinine and cystatin C levels, and uNGAL. We compared ICU patients who presented with any of the 3 outcomes with others who did not. Results: We included 75 patients, and among those 21 developed AKI, 18 severe AKI, and 17 required RRT. Bivariate analysis revealed intergroup differences for almost all clinical variables (e.g., patients with AKI vs. patients without AKI); while multivariate analysis identified mean arterial pressure as the only predictor for AKI (p #x3c; 0.001) and the SOFA score (p = 0.04) as the only predictor for severe AKI. For RRT, day 1 maximum uNGAL was the stronger predictor (p #x3c; 0.001) when compared to admission diagnosis (p = 0.014). Day 1 and day 2 maximum uNGAL levels were good and excellent predictors for future RRT, but only fair to good predictors for AKI and severe AKI. Conclusions: Maximum urine levels of uNGAL measured over the first and second 24 h of an ICU admission were highly accurate predictors of the future need for RRT, however less accurate at detecting early and severe AKI.
  Nephron Extra 2017;7:62–77
  PubDate: Wed, 12 Jul 2017 09:38:44 +020
In IgA Nephropathy, Glomerulosclerosis Is Associated with Increased
Urinary CD80 Excretion and Urokinase-Type Plasminogen Activator
Receptor-Positive Podocyturia
- Abstract: Background: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN), the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR) participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80) in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis. Methods: The groups were as follows: controls (G1), n = 20 and IgAN group (G2), n = 39, subdivided into M1E0S0T0 (G2A), n = 21 and M1E0S1T0 (G2B), n = 18. Among the included variables, we determined uPAR-positive podocytes/gram of urinary creatinine (gUrCr) and uCD80 ng/gUrCr. Biopsies with interstitial fibrosis and tubular atrophy #x3c;10% were included. Results: Groups were not different in age and gender; urinary protein-creatinine (uP/C) ratio, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, uPAR-positive podocytes/gUrCr, and uCD80 were significantly increased in G2 versus G1. G2A and G2B were not different in age, gender, hypertension, and follow-up. G2B displayed significantly higher uP/C, uPAR-positive podocytes, uCD80, and lower CKD-EPI versus G2A. Strong significant correlations were encountered between uCD80 and podocyturia in G2A and G2B. However, when G1 was compared to G2A and G2B separately, the differences with respect to uP/C, uPAR-positive podocytes, and podocyturia were significantly stronger versus G2B than versus G2A. Conclusions: IgAN presents elevated uCD80 excretion and uPAR-positive podocyturia, while CD80 correlates with podocyturia. Glomerulosclerosis (S1) at the time of biopsy is associated with higher uP/C, lower renal function, increased uPAR-positive podocyturia, and CD80 excretion, and is independent of M1. In IgAN, uPAR may participate in podocyte detachment.
  Nephron Extra 2017;7:52–61
  PubDate: Tue, 16 May 2017 10:34:09 +020
Changes in Cerebral Oxygenation Associated with Intradialytic Blood
Transfusion in Patients with Severe Anemia Undergoing Hemodialysis
- Abstract: Background: Hemodialysis (HD) patients frequently suffer from severe anemia caused by various hemorrhagic disorders in addition to renal anemia. Intradialytic blood transfusion is sometimes performed; however, the cerebral oxygenation changes associated with this procedure remain unclear. Methods: Sixteen HD patients with severe anemia who required intradialytic blood transfusion were included (12 men and 4 women; mean age, 64.8 ± 9.8 years). Cerebral regional oxygen saturation (rSO2) was monitored using near-infrared spectroscopy, and cerebral fractional oxygen extraction (FOE) was calculated before and after HD. Twenty-five HD patients with well-maintained hemoglobin (Hb) levels were included as a control group. Results: Cerebral rSO2 values were significantly lower in HD patients with severe anemia than in the control group (42.4 ± 9.9 vs. 52.5 ± 8.5%, p = 0.001). Following intradialytic blood transfusion (385 ± 140 mL of concentrated red blood cells), Hb levels significantly increased (from 7.2 ± 0.9 to 9.1 ± 1.1 g/dL, p #x3c; 0.001), and cerebral rSO2 values significantly improved after HD (from 42.4 ± 9.9 to 46.3 ± 9.0%, p #x3c; 0.001). Cerebral FOE values before HD in patients with severe anemia were significantly higher than those in the control group (severe anemia, 0.56 ± 0.10; controls, 0.45 ± 0.08; p #x3c; 0.001). After HD with intradialytic blood transfusion, these values significantly decreased (0.52 ± 0.09 after HD versus 0.56 ± 0.10 before HD, p = 0.002). Conclusion: HD patients with severe anemia represented cerebral oxygen metabolism deterioration, which could be significantly improved by intradialytic blood transfusion.
  Nephron Extra 2017;7:42–51
  PubDate: Fri, 28 Apr 2017 12:20:54 +020
MicroRNA-155 and Anti-Müllerian Hormone: New Potential Markers of
Subfertility in Men with Chronic Kidney Disease
- Abstract: Background/Aims: Men with terminal renal failure are often infertile. Anti-müllerian hormone (AMH), a marker of Sertoli cell function, is decreased among men with chronic kidney disease (CKD). Recently, a microRNA, miR-155, has been shown to be a potential marker for subfertility. We studied miR-155 and semen parameters in patients with CKD who were not yet on dialysis. We also aimed to study possible associations between AMH, miR-155, and semen parameters to evaluate them as markers of fertility. Methods: Thirty male patients with CKD 1–4 as well as 18 healthy controls were enrolled. Results: Serum levels of miR-155 were significantly higher among men with CKD stages 1–2 (4.51 ± 3.81 [p = 0.01]) and stages 3–4 (2.75 ± 1.77 [p = 0.006]) than in controls (1.09 ± 0.44). Sperm concentration was significantly lower among men with CKD 3–4 (42 ± 29) ×106/mL compared to controls (88 ± 42) ×106/mL (p = 0.011). High levels of miR-155 were associated with a relatively low sperm concentration (p = 0.02) and with a low total sperm number (p = 0.005). Low AMH levels were associated with a decreased percentage of motile sperm cells (p = 0.02). Conclusions: We conclude that men with stage 3–4 CKD had lower sperm concentrations than healthy fertile men and that increased serum miR-155 in men with stage 1–4 CKD was associated with semen parameters that indicate subfertility. Low AMH levels were associated with a low percentage of the total number of motile sperm cells. miR-155 and AMH may be potential markers of subfertility in men with CKD.
  Nephron Extra 2017;7:33–41
  PubDate: Fri, 07 Apr 2017 08:31:14 +020
Improving CKD Diagnosis and Blood Pressure Control in Primary Care: A
Tailored Multifaceted Quality Improvement Programme
- Abstract: Background: Chronic kidney disease (CKD) is a worldwide public health issue. From 2009 to 2014, the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care Greater Manchester (NIHR CLAHRC GM) in England ran 4 phased, 12-month quality improvement (QI) projects with 49 primary care practices in GM. Two measureable aims were set – halve undiagnosed CKD in participating practices using modelled estimates of prevalence; and optimise blood pressure (BP) control (#x3c;140/90 mm Hg in CKD patients without proteinuria; #x3c;130/80 mm Hg in CKD patients with proteinuria) for 75% of recorded cases of CKD. The 4 projects ran as follows: P1 = Project 1 with 19 practices (September 2009 to September 2010), P2 = Project 2 with 11 practices (March 2011 to March 2012), P3 = Project 3 with 12 practices (September 2012 to October 2013), and P4 = Project 4 with 7 practices (April 2013 to March 2014). Methods: Multifaceted intervention approaches were tailored based on a contextual analysis of practice support needs. Data were collected from practices by facilitators at baseline and again at project close, with self-reported data regularly requested from practices throughout the projects. Results: Halving undiagnosed CKD as per aim was exceeded in 3 of the 4 projects. The optimising BP aim was met in 2 projects. Total CKD cases after the programme increased by 2,347 (27%) from baseline to 10,968 in a total adult population (aged ≥18 years) of 231,568. The percentage of patients who managed to appropriate BP targets increased from 34 to 74% (P1), from 60 to 83% (P2), from 68 to 71% (P3), and from 63 to 76% (P4). In nonproteinuric CKD patients, 88, 90, 89, and 91%, respectively, achieved a target BP of #x3c;140/90 mm Hg. In proteinuric CKD patients, 69, 46, 48, and 45%, respectively, achieved a tighter target of #x3c;130/80 mm Hg. Analysis of national data over similar timeframes indicated that practices participating in the programme achieved higher CKD detection rates. Conclusions: Participating practices identified large numbers of “missing” CKD patients with comparator data showing they outperformed non-QI practices locally and nationally over similar timeframes. Improved BP control also occurred through this intervention, but overall achievement of the tighter BP target in proteinuric patients was notably less.
  Nephron Extra 2017;7:18–32
  PubDate: Fri, 07 Apr 2017 08:26:29 +020
The Dialysis Sodium Gradient: A Modifiable Risk Factor for Fluid Overload
- Abstract: Background: Fluid overload in patients on conventional hemodialysis is a frequent complication, associated with increased cardiovascular morbidity and mortality. The dialysate sodium prescription is a potential modifiable risk factor. Our primary objective was to describe associations between dialysate-to-serum sodium gradient and parameters of fluid status. A secondary objective was to evaluate the 6-month risk of hospitalization and mortality in relation to sodium gradient. Methods: We performed a cross-sectional study of 110 prevalent conventional hemodialysis patients at a single center. The associations of sodium gradient with interdialytic weight gain index (IDWG%), ultrafiltration (UF) rate, and blood pressure (BP) were analyzed. Results: The mean serum sodium gradient was 4.6 ± 3.6 mEq/L. There was a direct correlation between sodium gradient and IDWG% (r = 0.48, p #x3c; 0.01) as well as UF rate (r = 0.44, p #x3c; 0.01). In a logistic regression model, a 1 mEq/L higher sodium gradient was associated with increased risk of IDWG% #x3e;3% (OR 1.33, p #x3c; 0.01) and increased risk of UF rate #x3e;10 mL/kg/h (OR 1.16, p = 0.03), but there were no associations with intradialytic hypotension, intradialytic hypertension or BP. No significant differences were found with 6-month hospitalization or mortality risk in relation to sodium gradient. Conclusion: A higher sodium gradient was associated with significant increases in IDWG and UF rates, known to be associated with poor outcomes, but was not associated with intradialytic hypotension. Individualizing the dialysate sodium prescription to minimize sodium gap may lead to less fluid overload in conventional hemodialysis patients.
  Nephron Extra 2017;7:10–17
  PubDate: Thu, 09 Feb 2017 12:49:49 +010
Immunohistochemical Glomerular Expression of Phospholipase A2 Receptor in
Primary and Secondary Membranous Nephropathy: A Retrospective Study in an
Indian Cohort with Clinicopathological Correlations
- Abstract: Background: Limited published literature exists on the utility and standardization of anti-phospholipase A2 receptor (anti-PLA2R) immunohistochemistry (IHC) for the diagnosis of primary membranous nephropathy (MN). The study aimed to validate anti-PLA2R IHC for the diagnosis of primary MN and clinicopathological correlations in an Indian cohort. Methods: Subjects included patients with primary and secondary MN diagnosed between January 2012 and August 2014 with an adequate renal biopsy and at least 1 year of clinical follow-up. Anti-PLA2R IHC was performed in all cases with miscellaneous renal lesions as controls. Electron microscopy was performed in selected cases. Sensitivity and specificity of anti-PLA2R IHC to identify primary MN was evaluated. Histopathological analyses of primary and secondary MN were done with clinicopathological correlations including serum creatinine, eGFR, chronic kidney disease stage, 24-h urine protein, serum cholesterol, serum albumin, and hypertension at presentation and follow-up, using the Kruskal-Wallis test and Spearman rank correlation. A p value of ≤0.05 was considered statistically significant. Results: In 153 MN patients (99 primary, 54 secondary) and 37 miscellaneous controls, anti-PLA2R IHC differentiated primary from secondary MN with a sensitivity of 70.2% and a specificity of 96.6%. Secondary MN had increased mesangial matrix expansion compared to primary MN (p = 0.001). Severe nephrotic syndrome, impaired renal function, and hypertension were all more common in primary than in secondary MN. Conclusion: Anti-PLA2R IHC is a specific marker to distinguish primary MN from secondary MN.
  Nephron Extra 2017;7:1–9
  PubDate: Thu, 09 Feb 2017 12:49:04 +010

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