Effects of a Renal Rehabilitation Exercise Program in Patients with CKD: A Randomized,Controlled Trial

Background and objectives

Patients with CKD have a high prevalence of cardiovascular disease associated with or exacerbated by inactivity. This randomized, controlled study investigated whether a renal rehabilitation exercise program for patients with stages 3 or 4 CKD would improve their physical function and quality of life.

Design, setting, participants, & measurements

In total, 119 adults with CKD stages 3 and 4 were randomized, and 107 of these patients proceeded to usual care or the renal rehabilitation exercise intervention consisting of usual care plus guided exercise two times per week for 12 weeks (24 sessions). Physical function was determined by three well established performance-based tests: 6-minute walk test, sit-to-stand test, and gait-speed test. Health-related quality of life was assessed by the RAND 36-Item Short Form Health Survey.

Results

At baseline, no differences in self-reported level of activity, 6-minute walk test, and sit-to-stand test scores were observed between the usual care (n=48) and renal rehabilitation exercise (n=59) groups, although baseline gait-speed test score was higher in the renal rehabilitation exercise group (P<0.001). At follow-up, the renal rehabilitation exercise group but not the usual care group showed significant improvements in the 6-minute walk test (+210.4±266.0 ft [19% improvement] versus −10±219.9 ft; P<0.001), the sit-to-stand test (+26.9±27% of age prediction [29% improvement] versus +0.7±12.1% of age prediction; P<0.001), and the RAND-36 physical measures of role functioning (P<0.01), physical functioning (P<0.01), energy/fatigue levels (P=0.01), and general health (P=0.03) and mental measure of pain scale (P=0.04). The renal rehabilitation exercise regimen was generally well tolerated.

Conclusions

A 12-week/24-session renal rehabilitation exercise program improved physical capacity and quality of life in patients with CKD stages 3 and 4. Longer follow-up is needed to determine if these findings will translate into decreased mortality rates.     

Folic Acid Therapy and Cardiovascular Disease in ESRD or Advanced Chronic Kidney Disease: A Meta-Analysis

Summary

Background and objectives

The efficacy of folic acid therapy to lower homocysteine (Hcy) levels in an effort to reduce cardiovascular disease (CVD) risk in patients with ESRD or advanced chronic kidney disease (ACKD; creatinine clearance, <30 ml/min) remains inconclusive. We conducted a meta-analysis of relevant randomized trials to further examine this issue.

Design, setting, participants, & measurements

This meta-analysis included 3886 patients with ESRD/ACKD from seven qualified randomized trials using folic acid therapy and with CVD reported as one of the end points.

Results

When pooling the seven trials, folic acid therapy reduced the risk of CVD by 15% (RR, 0.85; 95% CI, 0.76 to 0.96; P = 0.009). A greater beneficial effect was observed among those trials with a treatment duration >24 months (RR, 0.84; 95% CI, 0.72 to 0.98; P = 0.02), a decrease in Hcy level >20% (RR, 0.83; 95% CI, 0.73 to 0.95; P = 0.007), and no or partial folic acid fortification (RR, 0.80; 95% CI, 0.65 to 0.99; P = 0.04). The beneficial effect also was seen when Hcy levels decreased >20%, even in the presence of folic acid fortification (RR, 0.85; 95% CI, 0.73 to 0.99; P = 0.04). In the corresponding comparison groups, the estimated RRs were attenuated and insignificant.

Conclusions

Folic acid therapy can reduce CVD risk in patients with ESRD/ACKD by 15%. A greater beneficial effect was observed among those trials with no or partial folic acid fortification or a decrease in Hcy level >20% regardless of folic acid fortification.     

Differences in GFR and Tissue Oxygenation,and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease

Background and objectives

Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization.

Design, setting, participants, & measurements

Nonrandomized inpatient studies were performed in patients with unilateral ARAS (>60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R²* as a measure of deoxyhemoglobin) was determined by blood oxygen level–dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase–associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured.

Results

Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (+2.2[−1.8 to 10.5] versus −5.3[−7.3 to −0.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6±19.7 to 36.6±19.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R²* >30/s: 22.1%±20% versus 14.9%±18.3%; P<0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=−0.65; P<0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P<0.001), and MCP-1 (r=0.96; P<0.001).

Conclusions

These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines.     

Flow-Mediated Vasodilation in End-Stage Renal Disease

Summary

Background and objectives

An intact endothelium is essential for adaptations between arterial vasomotor tone and shear stress (SS), i.e., flow-mediated vasodilation (FMD). Endothelial dysfunction occurs in hypertension, cardiac insufficiency, diabetes, atherosclerosis, and in end-stage renal disease (ESRD) patients, whose renal failure is associated with many of those cardiovascular diseases (CVD).

Design, setting, participants, & measurements

Using a progressive hand-warming protocol and repeated measures ANOVA, we analyzed SS-mediated increase of brachial artery diameter (ΔBA) in 22 healthy controls, 18 CVD-negative ESRD patients (ESRD-CVD⁻), and 17 CVD-positive ESRD patients (ESRD-CVD⁺) to analyze the role of uremia versus CVD on FMD.

Results

Hand-warming increased SS (P < 0.001) and ΔBA (P < 0.001). Negative interactions were observed between ΔBA and ESRD (P < 0.001), and between ΔBA and CVD⁺ (P < 0.02), but there was no interaction between ESRD and CVD⁺ (P = 0.69). For low and mild SS increases, ESRD-CVD⁻ patients were characterized by similar ΔBA as controls, but it was lower than controls at higher SS (P < 0.01). In ESRD-CVD⁺ patients, brachial artery diameter did not respond to mild and moderate SS increases, and showed “paradoxical” vasoconstriction at higher SS (P < 0.05). In ESRD, a positive and independent interaction was observed between ΔBA and 25(OH) vitamin D₃ insufficiency (≤15 μg/L; P < 0.02).

Conclusions

These observations indicate that, independently of each other, ESRD and CVD⁺ history are associated with endothelial dysfunction. They also suggest the importance of considering the relationships between SS and endothelial function in different clinical conditions.     

CKD and Acute and Long-Term Outcome of Patients with Peripheral Artery Disease and Critical Limb Ischemia

Background and objectives

Despite the many studies showing an association between CKD and a high risk of ischemic events and mortality, the association of CKD with peripheral arterial disease (PAD) still has not been well described.

Design, setting, participants, & measurements

This large cohort study assessed the association of CKD, even in the earlier stages, with morbidity, short- and long-term outcome, and costs among patients with PAD.

Results

We identified 41,882 patients with PAD who had an index hospitalization between January 1, 2009, and December 31, 2011. Of these, 8470 (20.2%) also had CKD (CKD stage 2: n=2158 [26%]; stage 3: n=3941 [47%]; stage 4: n=935 [11%]; stage 5: n=1436 [17%]). The ratio of women to men was 1:1.2. Compared with patients without known CKD, those with CKD had higher frequencies of coronary artery disease (1.8-fold higher; P<0.001), chronic heart failure (3.3-fold higher; P<0.001), and Rutherford PAD categories 5 and 6 (1.8-fold higher; P<0.001); underwent significantly fewer revascularizations (0.9-fold fewer; P<0.001); had a nearly two-fold higher amputation rate (P<0.001); had higher frequencies of in-hospital infections (2.1-fold higher; P<0.001), acute renal failure (2.8-fold higher; P<0.001), and sepsis (1.9-fold higher; P<0.001); had a 2.5-fold higher frequency of myocardial infarction (P<0.001); and had a nearly three-fold higher in-hospital mortality rate (P<0.001). In an adjusted multivariable Cox regression model, CKD remained a significant predictor of long-term outcome of patients with PAD during follow-up for up to 4 years (until December 31, 2012; median, 775 days; 25th–75th percentiles, 469–1120 days); the hazard ratio was 2.59 (95% confidence interval, 2.21 to 2.78; P<0.001). The projected mortality rates after 4 years were 27% in patients without known CKD and 46%, 52%, 72%, and 78% in those with CKD stages 2, 3, 4, and 5, respectively. Lengths of hospital stay and reimbursement costs were on average nearly 1.4-fold higher (P<0.001) in patients who also had CKD.

Conclusions

This analysis illustrates the significant and important association of CKD with in-hospital and long-term mortality, morbidity, amputation rates, duration and costs of hospitalization, in-hospital treatment, and complications in patients with PAD.     

The family partners for health study: a cluster randomized controlled trial for child and parent weight management

Objective:

The purpose of this study was to test a two-phased nutrition and exercise education, coping skills training, and exercise intervention program for overweight or obese low-income ethnic minority 2nd to 4th grade children and their parents in rural North Carolina, USA.

Methods:

A cluster randomized controlled trial was carried out with 358 children (7–10 years) and a parent for each child (n=358). General linear mixed models were used to determine the effects of the intervention on weight, adiposity, health behaviors, and eating and exercise self-efficacy by examining changes in children and parents from baseline to completion of the study (18 months).

Results:

At 18 months, children in the experimental group did not have a significantly decreased body mass index (BMI) percentile (P=0.470); however, they showed a reduction in the growth rate of their triceps (P=0.001) and subscapular skinfolds (P<0.001) and an improvement in dietary knowledge (P=0.018) and drank less than one glass of soda per day (P=0.052) compared with the control group. Parents in the experimental group had decreased BMI (P=0.001), triceps (P<0.001) and subscapular skinfolds (P<0.001) and increased nutrition (P=0.003) and exercise (P<0.001) knowledge and more often drank water or unsweetened drinks (P=0.029). At 18 months, children in the experimental group did not show significant improvement in eating (P=0.956) or exercise self-efficacy (P=0.976). Experimental parents demonstrated improved socially acceptable eating self-efficacy (P=0.013); however, they did not show significant improvement in self-efficacy pertaining to emotional eating (P=0.155) and exercise (P=0.680).

Conclusion:

The results suggest that inclusion of children and parents in the same intervention program is an effective way to decrease adiposity and improve nutrition behaviors in both children and parents and improve weight and eating self-efficacy in parents.     

The Relationship between Epicardial Adipose Tissue and Malnutrition,Inflammation, Atherosclerosis/Calcification Syndrome in ESRD Patients

Summary

Background and objectives

Malnutrition, inflammation, atherosclerosis/calcification (MIAC) and endothelial dysfunction are the most commonly encountered risk factors in the pathogenesis of cardiovascular disease in ESRD patients. Epicardial adipose tissue (EAT) is the true visceral fat depot of the heart. The relationship between CAD and EAT was shown in patients with high risk of coronary artery disease. In this study, we aimed to investigate the relationship between EAT and MIAC syndrome in ESRD patients.

Design, setting, participants, & measurements

Eighty ESRD patients and 27 healthy subjects enrolled in this cross-sectional study. EAT and coronary artery calcification score were measured by a multidetector computed tomography (MDCT) scanner. Patients with serum albumin <3.5 mg/dl were defined as patients with malnutrition; those with serum C-reactive protein level >10 ng/dl (normal range, 0–5 ng/dl) had inflammation; and those with CACS >10 had atheroscleosis/calcification.

Results

Total CACS and EAT measurements were significantly higher in ESRD patients when compared with healthy subjects. There was a statistically significant relationship between EAT and CACS in ESRD patients (r = 0.48). EAT measurements were higher in PD patients than HD patients. Twenty-four of the patients had no component, 31 had one component, 17 had two components, and nine had all of the MIAC components. EAT was found to be significantly increased when the presence of MIAC components increased. EAT was positively correlated with age, body mass index, and presence of MIAC. These parameters were also found as independent predictors of increased EAT.

Conclusions

We found a relationship between EAT and components of MIAC syndrome in ESRD patients.     

Extra virgin olive oil use is associated with improved post-prandial blood glucose and LDL cholesterol in healthy subjects

Objectives:

Extra virgin olive oil (EVOO) is a key component of the Mediterranean diet and seems to account for the protective effect against cardiovascular disease. However, the underlying mechanism is still elusive.

Design:

We tested the effect of EVOO, added to Mediterranean-type meal, on post-prandial glycemic and lipid profile.

Subjects:

Post-prandial glycemic and lipid profile were investigated in 25 healthy subjects who were randomly allocated in a cross-over design to a Mediterranean-type meal added with or without 10 g EVOO (first study), or Mediterranean-type meal with EVOO (10 g) or corn oil (10 g; second study). Glycemic profile, which included glucose, insulin, dipeptidyl-peptidase-4 (DPP-4) protein and activity, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and lipid profile, which included, low-density lipoprotein (LDL) cholesterol (LDL-C), oxidized LDL (ox-LDL), triglycerides and high-density lipoprotein (HDL) cholesterol (HDL-C), were analyzed before and 2 h after the meal.

Results:

In the first study, 2 h after meal, subjects who assumed a meal with EVOO had significantly lower blood glucose (P<0.001), DPP-4 protein (P<0.001) and activity (P<0.001), LDL-C (P<0.001) and ox-LDL (P<0.001) and higher insulin (P<0.05), GLP-1 (P<0.001) and GIP (P<0.05) compared with those without EVOO. The second study showed that compared with corn oil, EVOO improved both glycemic and lipid profile. Thus, a significantly smaller increase of glucose (P<0.05), DPP4 protein (P<0.001) and activity (P<0.05) and higher increase of insulin (P<0.001) and GLP-1 (P<0.001) were observed. Furthermore, compared with corn oil, EVOO showed a significantly less increase of LDL-C (P<0.05) and ox-LDL (P<0.001).

Conclusions:

We report for the first time that EVOO improves post-prandial glucose and LDL-C, an effect that may account for the antiatherosclerotic effect of the Mediterranean diet.     

Total pancreatectomy: a national study

Background:

Total pancreatectomy (TP) is performed for various indications. Historically, morbidity and mortality have been high. Recent series reporting improved peri-operative mortality have renewed interest in TP. We performed a national review of TP including indication, patient/hospital characteristics, complications and peri-operative mortality.

Methods:

The Nationwide Inpatient Sample (NIS) was queried to identify TPs performed during 1998 to 2006. Univariate analyses were used to compare patient/hospital characteristics. Multivariable logistic regression was performed to identify predictors of in-hospital mortality. Post-operative complications/disposition were assessed.

Results:

From 1998 to 2006, 4013 weighted patient-discharges occurred for TP. Fifty-three per cent were male; mean age 58 years. Indication: neoplastic disease 67.8%. Post-operative complications occurred in 28%. Univariate analyses: TPs increased significantly (1998, n= 384 vs. 2006 n= 494, P < 0.01). 77.1% of TPs occurred in teaching hospitals (P < 0.0001), 86.4% in hospitals performing <five pancreatectomies/year (P < 0.0001). In-patient mortality was 8.5% with a significant decrease (12.4% 1998–2000 vs. 5.9% 2002–2006, P < 0.01). Multivariable analyses: advanced age [referent ≤50 years; ≥70 Adjusted odds ratio (AOR) 3.4, 95% confidence interval (CI) 1.33–8.67], select patient comorbidities and year (referent = 2004–2006; 1998–2000 AOR 2.70; 95% CI 1.41–5.14) independently predicted in-patient mortality whereas hospital surgical volume did not.

Discussion:

TP is increasingly performed nationwide with a concomitant decrease in peri-operative mortality. Patient characteristics, rather than hospital volume, predicted increased mortality.     

Acylation stimulating protein reduction precedes insulin sensitization after BPD-DS bariatric surgery in severely obese women

Objective:

The mechanisms involved in early resolution of insulin resistance and type 2 diabetes mellitus after biliopancreatic diversion with duodenal switch (BPD-DS) surgery are still unknown. We evaluated early effects of BPD-DS on plasma acylation stimulating protein (ASP), an adipokine involved in lipid and glucose metabolism.

Subjects:

32 non-diabetic and 22 diabetic severely obese women (BMI⩾40 kg m⁻²) were evaluated for body composition and plasma parameters before, 24 h, 5 days, 6 and 12 months after surgery.

Results:

Within the early postoperative period (24 h), ASP decreased 25 and 30% in non-diabetic and diabetic women, respectively (P<0.001). Twenty-four hours after surgery, triglyceride, cholesterol, HDL-Chol, LDL-Chol and C3 also decreased, while glucose, insulin and high-sensitivity C-reactive protein (hsCRP) increased (all P<0.001). By 5 days, without significant weight loss, the decreases in ASP, cholesterol, HDL-Chol and LDL-Chol levels were all maintained. At this time, glucose, insulin and HOMA-IR also decreased 11 to 52% (all P<0.001). At 6 and 12 months, with pronounced weight loss and decreased per cent fat mass, there were further decreases in ASP (maximal −56% non-diabetic, −61% diabetic, P<0.001), as well as in glucose, insulin, HOMA-IR, triglyceride, cholesterol, LDL-Chol, HDL-Chol and hsCRP levels. Improved insulin resistance/diabetes at 5 days was predicted by 24 h changes as follows: per cent change ASP, HDL-Chol, hsCRP and total cholesterol predicted HOMA-IR (5 days) (r²=0.454, P<0.001), and per cent change ASP, HDL-Chol and hsCRP predicted change (5 days vs baseline) in HOMA-IR (r²=0.351, P<0.001).

Conclusion:

Acute postoperative decreases in ASP are associated with early improvement of insulin resistance/diabetes after BPD-DS surgery.     

Renal Outcomes in Critically Ill Patients Receiving Propofol or Midazolam

Background and objectives

Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is limited to patients undergoing cardiac surgery. There are no data about its association with oliguria and AKI in critically ill patients.

Design, setting, participants, & measurements

We obtained data from the Multiparameter Intelligent Monitoring in Intensive Care II database (2001–2008). Patient selection criteria included adult patients in their first intensive care unit (ICU) admission, need for mechanical ventilation, and treatment with propofol or midazolam. Propensity score analysis (1:1) was used and renal-related outcomes (AKI, oliguria, cumulative fluid balance, and need for RRT) were evaluated during the first 7 days of ICU stay.

Results

There were 1396 propofol/midazolam-matched patients. AKI in the first 7-day ICU time period was statistically lower in propofol-treated patients compared with midazolam-treated patients (55.0% versus 67.3%, P<0.001). Propofol was associated with lower AKI incidence using both urine output (45.0% versus 55.7%, P<0.001) and serum creatinine criteria (28.8% versus 37.2%, P=0.001). Patients receiving propofol had oliguria (<400 ml/d) less frequently (12.4% versus 19.6%, P=0.001) and had diuretics prescribed less often (8.5% versus 14.3%, P=0.001). In addition, during the first 7 days of ICU stay, patients receiving propofol less frequently achieved cumulative fluid balance >5% of body weight (50.1% versus 58.3%, P=0.01). The need for RRT in the first 7 days of ICU stay was also less frequent in propofol-treated patients (3.4% versus 5.9%, P=0.03). ICU mortality was lower in propofol-treated patients (14.6% versus 29.7%, P<0.001).

Conclusions

In this large, propensity-matched ICU population, patients treated with propofol had a lower risk of AKI, fluid-related complications, and need for RRT.     

CKD and Its Risk Factors among Patients with Cystinuria

Background and objectives

Cystinuria is an autosomal recessive disorder affecting renal cystine reabsorption; it causes 1% and 8% of stones in adults and children, respectively. This study aimed to determine epidemiologic and clinical characteristics as well as comorbidities among cystinuric patients, focusing on CKD and high BP.

Design, setting, participants, & measurements

This retrospective study was conducted in France, and involved 47 adult and pediatric nephrology and urology centers from April 2010 to January 2012. Data were collected from 442 cystinuric patients.

Results

Median age at onset of symptoms was 16.7 (minimum to maximum, 0.3–72.1) years and median diagnosis delay was 1.3 (0–45.7) years. Urinary alkalinization and cystine-binding thiol were prescribed for 88.8% and 52.2% of patients, respectively, and 81.8% had at least one urological procedure. Five patients (1.1%, n=4 men) had to be treated by dialysis at a median age of 35.0 years (11.8–70.7). Among the 314 patients aged ≥16 years, using the last available plasma creatinine, 22.5% had an eGFR≥90 ml/min per 1.73 m² (calculated by the Modification of Diet in Renal Disease equation), whereas 50.6%, 15.6%, 7.6%, 2.9%, and 0.6% had an eGFR of 60–89, 45–59, 30–44, 15–29, and <15, respectively. Among these 314 patients, 28.6% had high BP. In multivariate analysis, CKD was associated with age (odds ratio, 1.05 [95% confidence interval, 1.03 to 1.07]; P<0.001), hypertension (3.30 [1.54 to 7.10]; P=0.002), and severe damage of renal parenchyma defined as a past history of partial or total nephrectomy, a solitary congenital kidney, or at least one kidney with a size <10 cm in patients aged ≥16 years (4.39 [2.00 to 9.62]; P<0.001), whereas hypertension was associated with age (1.06 [1.04 to 1.08]; P<0.001), male sex (2.3 [1.3 to 4.1]; P=0.003), and an eGFR<60 ml/min per 1.73 m² (2.7 [1.5 to 5.1]; P=0.001).

Conclusions

CKD and high BP occur frequently in patients with cystinuria and should be routinely screened.     

A Randomized Trial of Cinacalcet versus Vitamin D Analogs as Monotherapy in Secondary Hyperparathyroidism (PARADIGM)

Background and objectives

Direct comparison of cinacalcet and vitamin D analogs as monotherapies to lower parathyroid hormone (PTH) levels has not been undertaken.

Design, setting, participants, & measurements

This was a prospective, multicenter, phase 4, randomized, open-label study that enrolled participants from 2010 to 2012. Adult participants (n=312) on hemodialysis with PTH >450 pg/ml were randomized 1:1 to 12 months of treatment with either cinacalcet (n=155) or vitamin D analogs (n=157) to evaluate the mean percentage change in plasma PTH level (primary end point) and the proportion of participants achieving plasma PTH <300 pg/ml or a ≥30% decrease in PTH (secondary end points). A preplanned analysis to determine whether there were important region-by-treatment interactions was also undertaken.

Results

Baseline mean PTH was 846 pg/ml (n=155) for cinacalcet and 816 pg/ml (n=157) for vitamin D analog therapy. The mean (95% confidence interval) percentage change from baseline in PTH was −12.1% (−20.0% to −4.1%) in the cinacalcet arm and −7.0% (−14.9% to 0.8%) in the vitamin D analog arm, a difference of −5.0% (−15.4% to 5.4%) (P=0.35). Similarly, there was no difference in achievement of secondary efficacy end points between arms (19.4% and 15.3% of participants with PTH≤300 pg/ml and 42.6% and 33.8% of participants had a PTH reduction >30% in the cinacalcet and vitamin D analog arms, respectively). A prespecified analysis revealed a large treatment-by-region interaction, with nominally greater response to cinacalcet compared with vitamin D analogs in non–United States participants (US versus non-US participants, P<0.001). Hypocalcemia was more common in the cinacalcet arm, whereas hypercalcemia and hyperphosphatemia occurred more often in the vitamin D analog arm.

Conclusions

Participants had similar modest reductions in PTH with either cinacalcet or vitamin D analog monotherapy over 52 weeks of treatment, but effects varied by region. Treatments differed with regard to effect on calcium and phosphorus levels.     

Patient selection and the volume effect in pancreatic surgery: unequal benefits?

Background

The volume effect in pancreatic surgery is well established. Regionalization to high-volume centres has been proposed. The effect of this proposal on practice patterns is unknown.

Methods

Retrospective review of pancreatectomy patients in the Nationwide Inpatient Sample 2004–2011. Inpatient mortality and complication rates were calculated. Patients were stratified by annual centre pancreatic resection volume (low <5, medium 5–18, high >18). Multivariable regression model evaluated predictors of resection at a high-volume centre.

Results

In total, 129 609 patients underwent a pancreatectomy. The crude inpatient mortality rate was 4.3%. 36.0% experienced complications. 66.5% underwent a resection at high-volume centres. In 2004, low-, medium- and high-volume centres resected 16.3%, 24.5% and 59.2% of patients, compared with 7.6%, 19.3% and 73.1% in 2011. High-volume centres had lower mortality (P < 0.001), fewer complications (P < 0.001) and a shorter median length of stay (P < 0.001). Patients at non-high-volume centres had more comorbidities (P = 0.001), lower rates of private insurance (P < 0.001) and more non-elective admissions (P < 0.001).

Discussion

In spite of a shift to high-volume hospitals, a substantial cohort still receives a resection outside of these centres. Patients receiving non-high-volume care demonstrate less favourable comorbidities, insurance and urgency of operation. The implications are twofold: already disadvantaged patients may not benefit from the high-volume effect; and patients predisposed to do well may contribute to observed superior outcomes at high-volume centres.     

A comparison of effects of lard and hydrogenated vegetable shortening on the development of high-fat diet-induced obesity in rats

Background:

Obesity is associated with increased consumption and preference for dietary fat. Experimental models of fat-induced obesity use either lard or vegetable shortening. Yet, there are no direct comparisons of these commonly used fat sources, or the influence of their fatty acid composition, on the development of diet-induced obesity.

Objective:

To compare the effects of lard and hydrogenated vegetable-shortening diets, which differ in their fatty acid composition, on weight gain and the development of obesity and insulin resistance in rats.

Methods and design:

Male Wistar rats were fed ad libitum for 14 weeks high-fat diets containing either (1) high vegetable fat (HVF, 60 kcal% from vegetable shortening) or (2) high lard fat (HLF, 60 kcal% from lard). Rats fed normal-fat (NF, 16 kcal% from vegetable shortening) diet served as control. Body weight, food intake, adipose tissue mass, serum 25[OH]D₃, glucose, insulin and fatty acid composition of diets were measured.

Results:

Rats fed either of the two high-fat diets had higher energy intake, weight gain and fat accretion than rats fed normal-fat diet. However, rats fed the HLF diet consumed more calories and gained more weight and body fat with greater increases of 32% in total (158.5±8.2 vs 120.2±6.6 g, P<0.05), 30% in visceral (104.4±5.2 vs 80.3±4.2 g, P<0.05) and 36% in subcutaneous fat mass (54.1±3.6 vs 39.9±3.1 g, P<0.05), compared with rats fed the HVF diet. Higher visceral adiposity was positively correlated with serum insulin (r=0.376, P<0.05) and homeostatic model assessment insulin resistance (r=0.391, P<0.05).

Conclusion:

We conclude that lard-based high-fat diets accentuate the increase in weight gain and the development of obesity and insulin resistance more than hydrogenated vegetable-shortening diets. These results further point to the importance of standardizing fatty acid composition and type of fat used in determining outcomes of consuming high-fat diets.     

Predicting patient survival after pancreaticoduodenectomy for malignancy: histopathological criteria based on perineural infiltration and lymphovascular invasion

Background:

Accurate and simple prognostic criteria based on histopathology following pancreaticoduodenectomy would be helpful in assessing prognosis and considering and evaluating adjuvant therapy. This study analysed the histological parameters influencing outcome following pancreaticoduodenectomy for periampullary malignancy.

Methods:

A total of 110 pancreaticoduodenectomies were performed from 1998 to 2008. The median age of patients was 69 years (range 20–89 years). The median follow-up was 4.9 years. Of the procedures, 87% (96) were performed for malignancies and the remainder (n= 14) for benign aetiologies. Of the 96 malignancies, 60 were pancreatic adenocarcinoma and the rest were ampullary (14), cholangio (9), duodenal (9) carcinomas and others. Statistical analysis was performed using log-rank and Cox regression multivariate analyses.

Results:

Patients who underwent resection had 1-, 3- and 5-year survival rates of 70%, 46% and 41%, respectively. The 1-, 3- and 5-year survival rates for periampullary cancers other than pancreatic adenocarcinoma were 83%, 69% and 61%, respectively; those for pancreatic adenocarcinoma were 62%, 31% and 27%, respectively (P < 0.003). Poor tumour differentiation (P < 0.02), tumour size >3 cm (P < 0.04), margin ≤2 mm (P < 0.02), nodal involvement (P < 0.003), perineural infiltration (P < 0.0001) and lymphovascular invasion (P < 0.002) were associated with poorer prognosis. In a multivariate analysis, histologically identified perineural infiltration (P < 0.03) and lymphovascular invasion (P= 0.05) were significant factors influencing outcome. Five-year survival was 77% in patients negative for both factors and 15% in patients positive for both (P < 0.0001). In the pancreatic adenocarcinoma subgroup, patients who were negative for both factors had a 5-year survival of 71%, whereas those who were positive for both had a 5-year survival of 16% (P < 0.02).

Conclusions:

The presence of perineural infiltration and lymphovascular invasion on histopathology is highly significant in predicting 5-year outcomes after pancreaticoduodenectomy for periampullary and pancreatic malignancies.     

Association of Indoxyl Sulfate with Heart Failure among Patients on Hemodialysis

Background and objectives

Indoxyl sulfate, a protein-bound uremic toxin, may be associated with cardiovascular events and mortality in patients with CKD. This study aimed to investigate the relationship between indoxyl sulfate and heart failure in patients on hemodialysis.

Design, setting, participants, & measurements

Patients on hemodialysis for >6 months were enrolled within 6 months. Patients with congestive heart failure, angina pectoris, acute myocardial infarction, cerebral infarction, or cerebral hemorrhage within 3 months before the study or those <18 years old were excluded. The primary end point was first heart failure event during follow-up.

Results

In total, 258 patients (145 men) with a mean age of 57.0±14.6 years old were enrolled. Median plasma indoxyl sulfate level was used to categorize patients into two groups: the low-indoxyl sulfate group (indoxyl sulfate ≤32.35 μg/ml) and the high-indoxyl sulfate group (indoxyl sulfate >32.35 μg/ml). Then, patients were prospectively followed up for a median of 48.0 (interquartile range: 33.5–48.0) months. During follow-up, 68 patients experienced episodes of first heart failure. Kaplan–Meier analysis revealed the incidence of first heart failure event in the high–indoxyl sulfate group was significantly higher than in the low-indoxyl sulfate group (log rank P<0.001). Cox regression analysis showed indoxyl sulfate was significantly associated with first heart failure event (indoxyl sulfate as the continuous variable: hazard ratio, 1.02; 95% confidence interval [95% CI], 1.01 to 1.03; P=0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 3.49; 95% CI, 1.97 to 6.20; P<0.001). After adjustment for other confounding factors, the results remained significant (indoxyl sulfate as the continuous variable: hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P<0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 5.31; 95% CI, 2.43 to 11.58; P<0.001).

Conclusions

Plasma indoxyl sulfate was associated with first heart failure event in patients on hemodialysis. Whether indoxyl sulfate is only a biomarker or involved in the pathogenesis of heart failure in hemodialysis warrants additional study.     

Relationship between Serum Soluble Urokinase Plasminogen Activator Receptor Level and Steroid Responsiveness in FSGS

Background and objectives

Soluble urokinase plasminogen activator receptor (suPAR) was initially proposed as a pathogenic and predictive biomarker of primary FSGS, but the findings were controversial. This study aimed to clarify the clinical implications of suPAR.

Design, setting, participants, & measurements

The study enrolled 109 patients with biopsy-proven primary FSGS who were administered prednisone between January 2011 and May 2013 and followed up for 6–24 months (median duration of follow-up, 12 months). Ninety-six healthy volunteers, 20 patients with minimal-change disease (MCD), and 22 patients with membranous nephropathy (MN) served as controls. Serum suPAR levels were measured using ELISA.

Results

suPAR levels in patients with FSGS (median, 3512 [interquartile range (IQR), 2232–4231] pg/ml) were significantly higher than in healthy controls (median, 1823 [IQR, 1563–2212] pg/ml; P<0.001), patients with MCD (median, 1678 [IQR, 1476–2182] pg/ml; P<0.001), and patients with MN (median, 1668 [IQR, 1327–2127] pg/ml; P<0.001). With 3000 pg/ml used as a threshold, suPAR levels were elevated in 48.6% of patients with FSGS, in contrast to 5% of patients with MCD and 4.5% of those with MN. suPAR levels were independently associated with steroid response in patients with FSGS (odds ratio, 85.02; P=0.001). Patients who were sensitive to steroids had significantly higher suPAR levels than nonsensitive patients (median, 3426 [IQR, 2670–5655] pg/ml versus 2523 [IQR, 1977–3460] pg/ml; P=0.001). A suPAR level of 3400 pg/ml was chosen as the optimal cutoff value for steroid response. At the 6-month follow-up in 84 patients with FSGS, suPAR levels were significantly decreased in those with suPAR level ≥3400 pg/ml (median, 4553 [IQR, 3771–6120] pg/ml versus 3149 [IQR, 2278–3953]; P=0.002) but were unchanged in patients with suPAR level <3400 pg/ml (median, 2359 [IQR, 2023–2842] pg/ml versus 2490 [IQR, 1916–3623] pg/ml; P=0.09).

Conclusions

suPAR is specifically elevated in some patients with FSGS, which differs from the finding in patients with MCD and MN. A suPAR assay may help predict steroid response in patients with primary FSGS.     

Predictors of survival and incidence of hepatoblastoma in the paediatric population

Objectives

This study evaluates current trends in incidence, clinical outcomes and factors predictive of survival in children with hepatoblastoma (HB).

Methods

The Surveillance, Epidemiology and End Results (SEER) database was queried for the period 1973–2009 for all patients aged <20 years with HB.

Results

A total of 606 patients were identified. The age-adjusted incidence was 0.13 patients per 100 000 in 2009. An annual percentage change of 2.18% (95% confidence interval (CI) 1.10–3.27; P < 0.05) was seen over the study period. Overall survival rates at 5, 10 and 20 years were 63%, 61% and 59%, respectively. Ten-year survival rates significantly improved in patients with resectable disease who underwent operative treatment in comparison with those with non-resectable HB (86% versus 39%; P < 0.0001). Multivariate analysis showed surgical treatment (hazard ratio (HR) = 0.23, 95% CI 0.17–0.31; P < 0.0001), Hispanic ethnicity (HR = 0.61, 95% CI 0.43–0.89; P = 0.01), local disease at presentation (HR = 0.43, 95% CI 0.29–0.63; P < 0.0001) and age < 5 years (HR = 0.63, 95% CI 0.41–0.95; P < 0.03) to be independent prognostic factors of survival.

Conclusions

The incidence of paediatric HB has increased over time. Hepatoblastoma is almost exclusively seen in children aged < 5 years. When HB presents after the age of 5 years, the prognosis is most unfavourable. Tumour extirpation markedly improves survival in paediatric patients with local disease.