Early response to erythropoiesis-stimulating agents in non-dialysis chronic kidney disease patients

Background

Renal anemia complicated with chronic kidney disease is usually treated with erythropoiesis-stimulating agents (ESAs). However, few studies have compared the early response of hemoglobin (Hb) to different kinds of ESAs.

Methods

The effects of three types of ESAs—epoetin alfa or beta (EPO), darbepoetin alfa (DPO), and epoetin beta pegol (EPObp)—on renal anemia were followed in 416 pre-dialysis chronic kidney disease (CKD) patients. After the initial 12-week administration of ESAs, ΔHb/ESA dose/kg was calculated as an index of efficacy of each ESA. Furthermore, independent variables associated with ΔHb/ESA dose/kg (dependent variable) were determined using multiple linear regression analysis. The ten independent variables selected for analysis were: presence of diabetic nephropathy, estimated glomerular filtration rate (eGFR), Hb, albumin, iron (Fe), transferrin saturation (TSAT), ferritin, phosphate (P), intact parathyroid hormone (iPTH), and C-reactive protein.

Results

The efficacy of DPO and EPObp were similar and higher than EPO. TSAT was most strongly correlated with ΔHb/EPO dose/kg in all three types of ESAs. Other significant independent factors were Hb, albumin, P, iPTH, and diabetic nephropathy in the EPO group, eGFR in the DPO group, and Fe in the EPObp group. The adjusted coefficient of determination (R ²) ranged from 0.415 to 0.520 in the three ESA groups.

Conclusions

The study results suggest that TSAT is the best predictor of the initial 12-week responsiveness to ESA, irrespective of the type. Variables not investigated in this study also affect responsiveness to ESA in Japanese pre-dialysis CKD patients.

     

Quality of life in children with chronic kidney disease

Background

Progressive chronic kidney disease (CKD), irrespective of the underlying etiology, affects the quality of life (QoL) of children due to the need for regular follow-up visits, a strict medication program and diet intake.

Methods

The Greek version of the KIDSCREEN-52 multidimensional questionnaire was used in children with CKD, renal transplantation (RT) and in a control group (CG) of healthy children.

Results

Fifty-five patients between 8 and 18 years, with CKD (n?=?25), RT (n?=?16) and with end-stage renal disease (ESRD) on peritoneal dialysis (PD) (n?=?14) were included. Each group of studied children was compared with the CG (n?=?55), the validation sample (VS) (n?=?1200) and the parent proxy scores. Physical well-being of all studied children was significantly lower compared to CG (p?=?0.004). In contrast, all studied children between 8 and 11 years showed better social acceptance compared to VS (p?=?0.0001). When QoL of children with CKD was compared with parent proxy QoL, conflicting opinions were observed in several dimensions, such as self-perception (p?=?0.023), autonomy (p?=?0.012), school environment (p?=?0.012) and financial resources (p?=?0.03).

Conclusions

QoL and mainly the dimension of physical well-being, may be affected dramatically in children with CKD unrelated to disease stage. In early school years children with CKD seem to feel higher social acceptance than the healthy controls, exhibiting better score in this dimension. Optimal care requires attention not only to medical management, but also to an assessment of QoL factors, that may help promote pediatric patient’s health.

     

Prevalence and correlates of 25-hydroxyvitamin D deficiency in the Chronic Kidney Disease in Children (CKiD) cohort

Background

Vitamin D plays an important role in the mineral and bone disorder seen in chronic kidney disease (CKD). Deficiency of 25-hydroxyvitamin D (25OHD) is highly prevalent in the adult CKD population.

Methods

The prevalence and determinants of 25OHD deficiency (defined as a level <20 ng/ml) were examined longitudinally in 506 children in the CKiD cohort. Predictors of secondary hyperparathyroidism and the determinants of 1,25-dihydroxyvitamin D (1,25(OH)₂D) levels were also evaluated.

Results

Deficiency of 25OHD was observed in 28 % of the cohort at enrollment. Significant predictors of 25OHD deficiency were older age, non-white race, higher body mass index, assessment during winter, less often than daily milk intake, non-use of nutritional vitamin D supplement and proteinuria. Lower values of glomerular filtration rate (GFR), serum 25OHD, calcium and higher levels of FGF23 were significant determinants of secondary hyperparathyroidism. Lower GFR, low serum 25OHD, nephrotic-range proteinuria, and high FGF23 levels were significant determinants of serum 1,25(OH)₂ D levels.

Conclusions

Deficiency of 25OHD is prevalent in children with CKD and is associated with potentially modifiable risk factors such as milk intake, nutritional vitamin D supplement use, and proteinuria. 25OHD deficiency is a risk factor for secondary hyperparathyroidism and decreased serum 1,25(OH)₂D in children with CKD.

     

Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays

Summary

A comparison of the association of different forms of 25-hydroxyvitamin D [25(OH)D] with parathyroid hormone (PTH) and with areal and volumetric bone mineral density (BMD) demonstrated that bioavailable and free 25(OH)D do not provide a better index of vitamin D status in terms of bone health compared to total 25(OH)D.

Introduction

This study aims to compare measures of vitamin D-binding protein (DBP) using a monoclonal versus polyclonal ELISA and assess correlations of total versus estimated free and bioavailable 25(OH)D with BMD and PTH concentrations.

Methods

DXA and peripheral quantitative CT (pQCT) scans were obtained in 304 adults (158 black, 146 white), ages 21–80 years. Free and bioavailable 25(OH)D were calculated from total 25(OH)D, DBP, and albumin concentrations. Multivariable linear regression with standardized beta coefficients was used to evaluate associations of bone measures and PTH with total, free, and bioavailable 25(OH)D.

Results

Measures of DBP obtained using a monoclonal versus polyclonal ELISA were not correlated (r _s?=?0.02, p?=?0.76). Free and bioavailable 25(OH)D based on the polyclonal assay were lower in black versus white participants (p?<?0.0001); this race difference was not evident using the monoclonal assay. Adjusted for age, sex, calcium intake, and race, all forms of 25(OH)D were negatively associated with PTH, but the absolute coefficient was greatest for total 25(OH)D (?0.34, p?<?0.001) versus free/bioavailable 25(OH)D (?0.18/?0.24 depending on DBP assay, p?≤?0.003). In analyses stratified on race, none of the measures of 25(OH)D were associated with BMD across DXA and pQCT sites.

Conclusions

The monoclonal versus polyclonal ELISA yielded highly discrepant measures of DBP, particularly among black individuals, likely related to established race differences in DBP polymorphisms. Contrary to prior studies, our findings indicate that using DBP to estimate bioavailable and free 25(OH)D does not provide a better index of vitamin D status in terms of bone health.

     

Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease

Purpose

Hypovitaminosis D is common in chronic kidney disease (CKD) and is associated with endothelial dysfunction and cardiovascular events. This study aimed to investigate the effects of vitamin D supplementation on endothelial dysfunction in non-dialysis CKD patients.

Materials and methods

Seventy-one non-dialysis CKD patients with low vitamin D (serum 25(OH)D < 30 ng/mL) were recruited. Patients received oral cholecalciferol 50,000 units once a week for 12 weeks. Changes in endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were studied.

Results

There was a significant increase in serum levels of 25(OH)D after cholecalciferol supplementation (33.7 ± 12.1 vs. 13.2 ± 5.4 ng/mL, P < 0.001). Multivariable regression analysis showed that higher proteinuria (β = ? 0.548, P < 0.001) and lower levels of 25(OH)D (β = 0.360, P < 0.001) at baseline were related to lower 25(OH)D level after supplementation. FMD increased significantly from 4.4 ± 1.3 to 5.1 ± 1.5% (P < 0.001), and soluble endothelial biomarkers decreased: sVCAM-1 from 926.9 ± 158.0 to 867.0 ± 129.0 ng/mL (P < 0.001), and sE-selectin 69.7 ± 15.8 to 63.3 ± 14.7 ng/mL (P < 0.001).

Conclusions

Vitamin D supplementation can improve endothelial dysfunction in pre-dialysis CKD patients.

     

Serum vitamin D level may be a novel potential risk factor for premature ejaculation: a comparative study

Purpose

To compare serum level of vitamin D [25(OH)D] in patients with life-long premature ejaculation (LPE) versus healthy controls.

Methods

Healthy married potent males were recruited from February 2017 to January 2018. Group A included 40 patients suffering from LPE who were compared versus 40 healthy controls (Group B). Participants suffering from hormonal disorders, obesity, neurological, psychological, or chronic diseases or taking medications that may affect ejaculatory function, serum level of vitamin D, or the accuracy of intra-vaginal ejaculation latency time (IELT) were excluded. LPE was self-reported by the patients with subsequent feelings of frustration and measured by premature ejaculation diagnostic tool (PEDT) and IELT using stopwatch handled by their partners. 25(OH)D was measured by obtaining 2 ml of venous blood. Statistical analysis was performed using Student t, Mann–Whitney, Chi square tests, logistic regression analysis, and Spearman correlation.

Results

Sixteen (20%) participants had vitamin D insufficiency/deficiency. All of them were in PE group. 25(OH)D correlated significantly with IELT (r²?=?0.349; p?<?0.001) and PEDT (r²?=?0.425; p?<?0.001). There was no statistically significant difference in age (p?=?0.341), BMI (p?=?1) or IIEF-5 (p?=?0.408) in both groups. 25(OH)D was significantly lower in patients than controls (35.75 vs. 58.92 ng/ml, p?<?0.001). ROC analysis revealed that the best cut-off value of 25(OH)D to detect patients suffering from LPE was 50.65 ng/ml with a sensitivity and specificity of 85% for both. 25(OH)D remained a significant risk factor for LPE in the logistic regression analysis (p?<?0.001).

Conclusions

The current study showed that vitamin D has significant association with LPE and correlates significantly with IELT and PEDT.

     

Effect of essential amino acid кetoanalogues and protein restriction diet on morphogenetic proteins (FGF-23 and Кlotho) in 3b–4 stages chronic кidney disease patients: a randomized pilot study

Background

A low protein diet (LPD) with essential amino acid ketoanalogue supplementation (KA) may contribute in improving of chronic kidney disease (CKD), while the exact mechanisms of KA’s effect are not established yet. We have conducted a prospective, randomized, controlled comparative study of LPD?+?KA and LPD alone in relation to serum Klotho, FGF-23 levels in CKD patients.

Methods

79 non-diabetic CKD 3b–4 stage patients, compliant with LPD diet (0.6 g/kg of body weight/day), had been selected. The patients were randomized into two groups. The first group (42 patients) received LPD + КA. The second group (37 patients) continued the LРD alone. In addition to routine tests, serum Klotho, FGF-23 levels, as well as bioimpedance analysis, sphygmography (stiffness (augmentation) indices (AI), central (aortal) blood pressure) with a «SphygmaCor» device; echocardiography (valvular calcification score (VCS) and LVMMI), were performed.

Results

There were body mass indices’ decrease (p?=?0.046), including muscle body mass in men (p?=?0.027) and woman (p?=?0.044) in the LPD group to the end of study (14th month). In addition, lower FGF-23 (p?=?0.029), and higher sKlotho (p?=?0.037) were detected in the LPD?+?KA group compared to the LPD one. The increase in AI (p?=?0.034), VCS (p?=?0.048), and LVMMI (p?=?0.023) was detected more often in the LPD group at the end of study.

Conclusion

LPD?+?KA provides support for nutrition status and contributes to more efficient correction of FGF-23 and Klotho abnormalities that may result in cardiovascular calcification and cardiac remodeling decreasing in CKD. At the same time, a prolonged LPD alone may lead to malnutrition.

     

Are radiographic indices reliable indicators for quantitative bone mineral density and vitamin D status after femoral neck fractures? A retrospective study in 112 elderly patients

Background

Radiographic parameters and indices obtained from hip x-rays are a potential tool to promptly estimate bone quality in elderly hip fracture patients. Preoperative decision in whether to use cemented or cement augmented implants might be supported by this information and thus improve patient safety. Subsequently, this study was conducted to evaluate radiographic parameters as a prescreening tool for bone quality.

Methods

A retrospective analysis of 112 elderly patients with a femoral neck fracture after low-energy trauma was performed (81 % female, 19 % male). Three radiological indices were calculated on hip x-rays: cortical index antero-posterior CTI (ap), cortical index lateral CTI (lat) and canal to calcar ratio CCR. These indices were analyzed for correlations with DXA T-Scores and serum 25-hydroxyvitamin D (25(OH)D) using the Spearman test.

Results

Median age of patients was 80 (IQR 72–86) years. A linear correlation was found for CTI (lat) and T-Score at the total hip (p?<?0.001, r?=?0.589), femoral neck (p?=?0.005, r?=?0.405) and the lumbar spine (p?=?0.002, r?=?0.299). A significant correlation was also indicated between CTI (lat) and 25(OH)D (p?=?0.002, r?=?0.293). CTI (lat) at a cut-off level of 0.4 showed a sensitivity of 79 % and a specificity of 56 % in predicting a T-score?≤??2.5 at the total hip. Gender specific analysis revealed a higher sensitivity (100 %) and specificity (73 %) of CTI (lat) at a cut-off level of 0.4 for men. For severe vitamin D deficiency (<10 ng/ml) sensitivity and specificity were 75 % and 65 %.

Conclusion

Radiographic indices as the CTI (lat) exhibit a direct correlation to BMD and serum 25OH vitamin D levels. A CTI (lat) cut-off level of 0.4 is recommended for identifying patients at risk of osteoporosis expressed by T-Scores?≤??2.5 and severe vitamin D deficiency.

     

Adiponectin is related to markers of endothelial dysfunction and neoangiogenesis in diabetic patients

Purpose

Adiponectin an adipokine, produced by mature adipocyte, has an important effect on several aspects of endothelial function, including leukocyte adhesion (mediated by adhesion molecules like intercellular adhesion molecule 1 (ICAM1) endothelial cell selective adhesion molecule ESAM). Recently, it has been linked to vascular endothelial growth factor (VEGF)-modulated angiogenesis. ESAM might also be involved in modulating VEGF-dependent actions. We studied relationship of adiponectin to ESAM, ICAM1, and VEGF in type 2 diabetic patients (T2DP) with or without microvascular complications.

Methods

Incident T2DP referred for nephrologic evaluation were included (patients with no nephropathy or stage 1–4 nephropathy). T2DP with stage 5 chronic kidney disease (CKD) were selected from a dialysis center. Clinical, standard laboratory assessment and adiponectin, ESAM, ICAM1, and VEGF (ELISA) were recorded.

Results

Eighty-seven patients were included, 15 had no CKD, 30 with stage 1 or 2 CKD, 20 with stage 3 or 4 CKD and 22 patients on dialysis. ESAM was higher in patients with CKD than in those without CKD (p?=?0.02), adiponectin, ICAM1, and VEGF were similar. Adiponectin correlated in univariate analysis to ESAM (r?=?0.32, p?=?0.002), ICAM1 (r?=?0.23, p?=?0.038), and CRP (r?=?0.31, p?=?0.012), and inversely to serum albumin (r?=???0.57, <?0.0001). In predialysis patients, adiponectin also correlated to albuminuria (r?=?0.54, p?<?0.0001) and glomerular filtration rate (r?=???0.46, p?=?0.0001). In multivariate regression ESAM (p?=?0.04), VEGF (p?=?0.03), and albumin (p?<?0.0001) are significant predictors of adiponectin. None of these cytokines were different when comparing patients with and without retinopathy.

Conclusion

Adiponectin is directly linked to adhesion molecules and VEGF in T2DP.

     

Ghrelin and acyl ghrelin levels are associated with inflammatory and nutritional markers and with cardiac and vascular dysfunction parameters in hemodialysis patients

Purpose

Exogenous ghrelin is associated with cardiovascular protection in experimental and human studies. Nevertheless ESRD patients have increased ghrelin levels and severe cardiovascular comorbidities. This study aims to elucidate the metabolic factors influencing endogenous ghrelin/acyl ghrelin levels and to analyze the relation between endogenous ghrelin/acyl ghrelin levels and cardiac and vascular function markers in hemodialysis patients.

Methods

The cross-sectional study was conducted in hemodialysis patients (n?=?88); 50 of them were men, mean age 61.1?±?13.5 years, 17% had diabetes. We assessed nutritional and inflammatory status and analyzed the determinants of ghrelin/acyl ghrelin and their relation with cardiac and vascular function.

Results

Ghrelin is correlated with IL-1β (r?=?0.88, p?<?0.0001), triglycerides, total cholesterol (TC), and Kt/V. IL-1β is the strongest predictor of ghrelin levels (p?<?0.0001). Acyl ghrelin is correlated with TC (r?=?0.36, p?=?0.001), LDL-cholesterol, serum bicarbonate, body mass index. TC is the strongest predictor for acyl ghrelin levels (p?=?0.038). Patients with high ghrelin levels had significantly decreased nitroglycerin-mediated dilation (p?=?0.05) and higher IL-1β levels (p?<?0.001); increased NT-proBNP is associated with lower levels of acyl ghrelin (r?=???0.33, p?=?0.02) in male patients.

Conclusion

The inflammatory marker IL-1β is in our study the strongest predictor of ghrelin levels while the nutritional marker-total cholesterol is the strongest predictor for acyl ghrelin levels in HD patients. High endogenous ghrelin level is associated with high IL-1β and with vascular smooth muscle cell dysfunction. Low acyl ghrelin level is associated with high NT-proBNP (a cardiac dysfunction marker) in male HD patients. There is a direct correlation between endogenous ghrelin level and inflammatory markers, which is not related with cardiovascular protection.

     

Low serum 25-hydroxyvitamin D is associated with increased risk of stress fracture during Royal Marine recruit training

Summary

The aim of this study was to investigate vitamin D status and stress fracture risk during Royal Marine military training. Poor vitamin D status was associated with an increased risk of stress fracture. Vitamin D supplementation may help to reduce stress fracture risk in male military recruits with low vitamin D status.

Introduction

Stress fracture is a common overuse injury in military recruits, including Royal Marine (RM) training in the UK. RM training is recognised as one of the most arduous basic training programmes in the world. Associations have been reported between serum 25-hydroxyvitamin D (25(OH)D) and risk of stress fracture, but the threshold of 25(OH)D for this effect remains unclear. We aimed to determine if serum 25(OH)D concentrations were associated with stress fracture risk during RM training.

Methods

We prospectively followed 1082 RM recruits (males aged 16–32 years) through the 32-week RM training programme. Troops started training between September and July. Height, body weight and aerobic fitness were assessed at week 1. Venous blood samples were drawn at weeks 1, 15 and 32. Serum samples were analysed for 25(OH)D and parathyroid hormone (PTH).

Results

Seventy-eight recruits (7.2 %) suffered a total of 92 stress fractures. Recruits with a baseline serum 25(OH)D concentration below 50 nmol L^?1 had a higher incidence of stress fracture than recruits with 25(OH)D concentration above this threshold (χ² ₍₁₎?=?3.564, p?=?0.042; odds ratio 1.6 (95 % confidence interval (CI) 1.0–2.6)). Baseline serum 25(OH)D varied from 47.0?±?23.7 nmol L^?1 in February, to 97.3?±?24.6 nmol L^?1 in July (overall mean 69.2?±?29.2 nmol L^?1, n?=?1016). There were weak inverse correlations between serum 25(OH)D and PTH concentrations at week 15 (r?=??0.209, p?<?0.001) and week 32 (r?=??0.214, p?<?0.001), but not at baseline.

Conclusion

Baseline serum 25(OH)D concentration below 50 nmol L^?1 was associated with an increased risk of stress fracture. Further studies into the effects of vitamin D supplementation on stress fracture risk are certainly warranted.

     

Associations of total and free 25OHD and 1,25(OH)<Subscript>2</Subscript>D with serum markers of inflammation in older men

Summary

Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors.

Introduction

Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D.

Methods

We tested serum total 25OHD, total 1,25(OH)₂D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)₂D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study.

Results

IL-6 was lower in men with higher 25OHD (?0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) ?0.07 to ?0.38 μg/mL) and with higher 1,25(OH)₂D (?0.20 μg/mL, 95 % CI ?0.0004 to ?0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)₂D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)₂D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)₂D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)₂D).

Conclusions

Associations of 1,25(OH)₂D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)₂D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.

     

Chronic kidney disease predicts a lower probability of improvement in patient-reported experience measures among patients with fractures: a prospective multicenter cohort study

Summary

Patient-reported experience measures (PREMs) are integral component of care for fracture patients. Using a multicenter cohort, we showed that the presence of chronic kidney disease (CKD) attenuated the probability of PREM improvement in fracture patients.

Introduction

Assessing PREM can assist physicians in improving patients’ experiences. Patients with CKD are at an increased risk of exhibiting poor PREM and developing fractures. We aimed to assess whether CKD influences the probability of PREM improvement during follow-up among patients with fractures.

Methods

We prospectively enrolled patients with hip or vertebral fractures from different institutes into a fracture liaison service program. After registering clinical histories, they received a baseline PREM assessment based on EuroQol group–5 dimension content, including self-care, daily activity, and pain severity using a 5-point Likert scale. A follow-up PREM assessment was arranged 4 months later, and we evaluated whether baseline CKD was predictive of PREM improvement.

Results

Among 593 fracture patients (18% with CKD), 37.3% and 62.7% presented with hip and vertebral fractures, respectively. Self-care, daily activity, and pain severity improved after follow-up in 32%, 27%, and 43% participants; those with CKD exhibited worse self-care ability and daily activity than those without. Multivariate logistic regression analyses showed that baseline CKD was significantly associated with lower possibility of improvement in daily activity (odds ratio [OR] 0.58, p?=?0.049) and pain severity (OR 0.52, p?=?0.01), and an insignificant change in the possibility of improvement in self-care ability (OR 0.61, p?=?0.09).

Conclusions

The presence of CKD predicts a significantly lower probability of PREM improvement among fracture patients. An early emphasis on renal function during fracture care should be considered.

     

Comparison of reticulocyte hemoglobin equivalent with traditional markers of iron and erythropoiesis in pediatric dialysis

Background

Anemia is a major complication for patients on chronic dialysis. Erythropoietin is effective if iron is available, however unnecessary iron supplementation results in iron overload. Reticulocyte hemoglobin equivalent (Ret-He) may be useful for assessing iron status.

Methods

A national retrospective cohort study including all children on chronic dialysis in New Zealand between 2007 and 2013, pairing Ret-He with demographic information, anemia indices, and markers of iron status.

Results

In 606 observations, we found a modest relationship between Ret-He and transferrin saturation (TSAT) (r?=?0.34, p?<?0.001) and a poor correlation between Ret-He and ferritin (r?=?0.09, p?=?0.04). There was a negative correlation between ferritin and hemoglobin (r?=??0.14, p?=?0.002), a weak positive correlation between TSAT and hemoglobin (r?=?0.12, p?=?0.007), and a modest positive correlation between Ret-He and hemoglobin (r?=?0.22, p?<?0.001). The diagnostic performance of Ret-He to detect absolute iron deficiency (cut-off value 28.9 pg, sensitivity 90 %, specificity 75 %, AUC 0.87) was good.

Conclusions

Ret-He is a more relevant marker of iron status than ferritin and TSAT. This supports prospectively testing Ret-He to distinguish between iron deficiency and suboptimal erythropoietin dosing as competing causes for anemia. Ferritin is an unhelpful biomarker of iron deficiency in this setting.

     

Diversity of the midstream urine microbiome in adults with chronic kidney disease

Purpose

To examine the characteristics of the midstream urine microbiome in adults with stage 3–5 non-dialysis-dependent chronic kidney disease (CKD).

Methods

Patients with non-dialysis-dependent CKD (estimated glomerular filtration rate [eGFR]?<?60 ml/min/1.73 m²) and diuretic use were recruited from outpatient nephrology clinics. Midstream voided urine specimens were collected using the clean-catch method. The bacterial composition was determined by sequencing the hypervariable (V4) region of the bacterial 16S ribosomal RNA gene. Extraction negative controls (no urine) were included to assess the contribution of extraneous DNA from possible sources of contamination. Midstream urine microbiome diversity was assessed with the inverse Simpson, Chao and Shannon indices. The diversity measures were further examined by demographic characteristics and by comorbidities.

Results

The cohort of 41 women and 36 men with detectable bacterial DNA in their urine samples had a mean age of 71.5 years (standard deviation [SD] 7.9) years (range 60–91 years). The majority were white (68.0%) and a substantial minority were African-American (29.3%) The mean eGFR was 27.2 (SD 13.6) ml/min/1.73 m². Most men (72.2%) were circumcised and 16.6% reported a remote history of prostate cancer. Many midstream voided urine specimens were dominated (>?50% reads) by the genera Corynebacterium (n?=?11), Staphylococcus (n?=?9), Streptococcus (n?=?7), Lactobacillus (n?=?7), Gardnerella (n?=?7), Prevotella (n?=?4), Escherichia_Shigella (n?=?3), and Enterobacteriaceae (n?=?2); the rest lacked a dominant genus. The samples had high levels of diversity, as measured by the inverse Simpson [7.24 (95% CI 6.76, 7.81)], Chao [558.24 (95% CI 381.70, 879.35)], and Shannon indices [2.60 (95% CI 2.51, 2.69)]. Diversity measures were generally higher in participants with urgency urinary incontinence and higher estimated glomerular filtration rate (eGFR). After controlling for demographics and diabetes status, microbiome diversity was significantly associated with estimated eGFR (P?<?0.05).

Conclusions

The midstream voided urine microbiome of older adults with stage 3–5 non-dialysis-dependent CKD is diverse. Greater microbiome diversity is associated with higher eGFR.

     

Dyslipidemia,carotid intima-media thickness and endothelial dysfunction in children with chronic kidney disease

Background

Chronic kidney disease (CKD) predisposes to accelerated atherosclerosis that is measured by carotid artery intima-media thickness (cIMT) and brachial artery flow-mediated dilation (FMD). Information on the association of these parameters with dyslipidemia in pre-dialysis pediatric CKD is limited.

Methods

Eighty patients aged 9.9?±?3.2 years, with estimated glomerular filtration rate of 38.8?±?10.8 ml/1.73 m²/min, and 42 pediatric controls underwent cross-sectional analysis of lipid profile, cIMT, and brachial artery FMD. Significant differences in these parameters between patients and controls were analyzed using Student’s t test. Predictors of cIMT and dyslipidemia were assessed using linear and logistic regression respectively.

Results

Patients had elevated blood levels of triglyceride and of total and LDL cholesterol than controls (P?≤?0.001); 73.8 % were dyslipidemic. Mean cIMT was higher (0.421?±?0.054 mm vs 0.388?±?0.036 mm, P?=?0.001) and brachial artery FMD was reduced (10.6?±?4.9 % vs 18.9?±?4.1 %, P?<?0.0001) in patients compared with controls. On multivariate analysis, hypertension (OR 3.68, P?=?0.044) and male gender (OR 10.21, P?=?0.004) were associated with dyslipidemia; cIMT was significantly associated with LDL cholesterol (β?=?28.36, P?=?0.033).

Conclusion

Dyslipidemia was prevalent and cIMT significantly elevated in pre-dialysis pediatric CKD, indicating increased cardiovascular risk. Elevated LDL cholesterol predicted increased cIMT, strengthening the association between dyslipidemia and atherosclerosis in early CKD.

     

Comparison of functional outcomes of robotic and open partial nephrectomy in patients with pre-existing chronic kidney disease: a multicenter study

Background

We compared renal functional outcomes of robotic (RPN) and open partial nephrectomy (OPN) in patients with chronic kidney disease (CKD), a definite indication for nephron-sparing surgery.

Methods

A multicenter retrospective analysis of OPN and RPN in patients with baseline ≥?CKD Stage III [estimated glomerular filtration rate (eGFR) <?60 mL/min/1.73 m²] was performed. Primary outcome was change in eGFR (ΔeGFR, mL/min/1.73 m²) between preoperative and last follow-up with respect to RENAL nephrometry score group [simple (4–6), intermediate (7–9), complex (10–12)]. Secondary outcomes included eGFR decline >?50%.

Results

728 patients (426 OPN, 302 RPN, mean follow-up 33.3 months) were analyzed. Similar RENAL score distribution (p?=?0.148) was noted between groups. RPN had lower median estimated blood loss (p?<?0.001), and hospital stay (3 vs. 5 days, p?<?0.001). Median ischemia time (OPN 23.7 vs. RPN 21.5 min, p?=?0.089), positive margin (p?=?0.256), transfusion (p?=?0.166), and 30-day complications (p?=?0.208) were similar. For OPN vs. RPN, mean ΔeGFR demonstrated no significant difference for simple (0.5 vs. 0.3, p?=?0.328), intermediate (2.1 vs. 2.1, p?=?0.384), and complex (4.9 vs. 6.1, p?=?0.108). Cox regression analysis demonstrated that decreasing preoperative eGFR (OR 1.10, p?=?0.001) and complex RENAL score (OR 5.61, p?=?0.03) were independent predictors for eGFR decline >?50%. Kaplan–Meier analysis demonstrated 5-year freedom from eGFR decline >?50% of 88.6% for OPN and 88.3% for RPN (p?=?0.724).

Conclusions

RPN and OPN demonstrated similar renal functional outcomes when stratified by tumor complexity group. Increasing tumor age and tumor complexity were primary drivers associated with functional decline. RPN provides similar renal functional outcomes to OPN in appropriately selected patients.

     

Prognostic implications of preoperative chronic kidney disease and anemia in patients undergoing coronary artery bypass graft surgery

Purpose

Chronic kidney disease (CKD) and anemia are independent preoperative risk factors for coronary artery bypass graft (CABG) surgery. We evaluated the implications of the coexistence of these two factors and their associated prognosis for CABG surgery.

Methods

We analyzed, retrospectively, consecutive patients who underwent elective CABG surgery between 2004 and 2014. The patients were classified into four groups depending on the presence or absence of preoperative CKD and anemia. We assessed the major adverse cardiac and cerebrovascular event (MACCE), defined as composite outcomes of cardio- and cerebrovascular death, revascularization through surgery or percutaneous intervention, hospitalization for congestive heart failure, and cerebral infarction.

Results

The study population consisted of 510 patients (73 % male; median age 71 years old), followed up for a median period of 2.8 years. Multivariate analysis indicated that neither the CKD/no-anemia group [hazard ratio (HR) 0.98, 95 % confidence interval (CI) 0.39–2.51, P = 0.973] nor the no-CKD/anemia group (HR 1.20, 95 % CI 0.69–2.09, P = 0.512) had significantly poorer prognoses than the no-CKD/no-anemia group. However, the CKD/anemia group had a significantly higher risk of a MACCE (HR 2.01, 95 % CI 1.01–3.98, P = 0.046).

Conclusion

The presence of both CKD and anemia in patients undergoing CABG for coronary artery disease is synergistically associated with a worse outcome.

     

Clinical and ultrasonographic evaluation of the pelvic floor in primiparous women: a cross-sectional study

Introduction and hypothesis

We used clinical examination and transperineal 3D/4D ultrasound (US) to evaluate pelvic floor muscles (PFM) after different delivery modes.

Methods

Women were surveyed using validated questionnaires. PFM were evaluated and classified according to the Modified Oxford Scale following 3D/4D transperineal US. For statistical analysis, Kruskal–Wallis, Mann–Whitney, chi-square, and Fisher exact tests were used.

Results

Fifty-three women were evaluated: 32 with previous vaginal delivery (VD) and 21 with cesarean section (CS) (8 nonelective and 13 elective). No significant difference among groups was observed regarding urinary incontinence (UI) after delivery (p?=?0.39), loss of muscle strength referred by the patient (p?=?0.48), or evaluated through digital examination (p?=?0.87). No patient with elective CS had avulsion, with difference between VD and elective CS (p?=?0.008). US evaluation identified no differences in bladder-neck elevation (p?=?0.69) or descent (p?=?0.65) , and no difference in genital hiatus size (p?=?0.35), levator ani thickness (p?=?0.35 –0.44), or presence of major or minor levator ani avulsion (p?=?0.10).

Conclusions

We evaluated primiparous women within 12 to 24 months of delivery and found that VD was associated with PFM avulsion. There was no difference among VD and nonelective or elective CS in symptomatology or other anatomic alterations evaluated through 3D/4D transperineal US.