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1.  A personalized follow-up of kidney transplant recipients using video conferencing based on a 1-year scoring system predictive of long term graft failure (TELEGRAFT study): protocol for a randomized controlled trial 
BMC Nephrology  2015;16:6.
Background
Numerous well-established clinical parameters are taken into consideration for the follow-up adaptation of kidney transplant recipients, but there are important disparities between countries, centres and clinicians. Therefore, novel scoring systems have been developed, for instance the Kidney Transplant Failure Score (KTFS) which aims to stratify patients according to their risk of return to dialysis. We hypothesize that the efficiency of the follow-up after one year post-transplantation can be improved by adapting it to the risk of graft failure defined by the KTFS estimation.
Methods/design
We propose a phase IV, open label, randomized, multicentric and prospective study. The study is registered with the Clinical Trials Registry NCT01615900. 250 patients will be allocated to one of two arms: the eHealth program versus the standard of care at hospital. In the standard group, patients classified at low-risk (KTFS ≤ 4.17) will be scheduled 4 visits at hospital per year, whilst high-risk patients will visit hospital 6 times. In the eHealth group, patients classified at low-risk will be interviewed 3 times by video conferencing and once at hospital, whilst 6 visits at hospital and 6 video conferencing will be scheduled for high-risk patients.
Discussion
The current study allows to scientifically evaluate the etiologic impact of a novel eHealth program. This is important to clarify the possible contribution of telemedicine in the improvement of medical follow-up. The proposed design based on 4 different sub-groups can be interesting to evaluate other personalized medicine programs.
doi:10.1186/1471-2369-16-6
PMCID: PMC4417310  PMID: 25631635
Kidney transplantation; Personalized follow-up; Video conferencing; Randomized clinical trial
2.  Urinary albumin excretion in healthy adults: a cross sectional study of 24-hour versus timed overnight samples and impact of GFR and other personal characteristics 
BMC Nephrology  2015;16:8.
Background
Urinary albumin can be measured in 24 h or spot samples. The 24 h urinary albumin excretion rate is considered the gold standard, but is cumbersome to collect. Instead, often an overnight sample is collected, and adjusted for dilution. Proxies for 24 h excretion rate have been studied in diabetics, but seldom in healthy individuals. Our aims were to compare 24 h and overnight albumin excretion, to assess the impact of personal characteristics, and to examine correlations between the 24 h excretion rate and proxies such as the albumin to creatinine ratio (ACR).
Methods
Separate 24 h and overnight urine samples were collected from 152 healthy kidney donors. Urinary creatinine, specific gravity, collection time, and sample volume determined. Differences between 24 h and overnight samples were examined, and the effects of age, sex, smoking, body mass, glomerular filtration rate, and urinary flow rate were assessed.
Results
The 24 h albumin excretion rate and ACR were both significantly higher than their overnight counterparts. Unadjusted albumin was unsurprisingly higher in the more concentrated overnight samples, while concentrations adjusted for specific gravity were similar. In multivariate analysis, the 24 h excretion rate and proxies were positively associated with glomerular filtration rate, as was ACR in overnight samples. There were positive associations between urinary albumin and body mass.
Conclusions
Proxies for the 24 h albumin excretion rate showed relatively high correlations with this gold standard, but differences due to sampling period, adjustment method, and personal characteristics were large enough to be worth considering in studies of albumin excretion in healthy individuals.
doi:10.1186/1471-2369-16-8
PMCID: PMC4417247  PMID: 25616740
Glomerular filtration rate; Urinary albumin; Timed urine samples; 24-hour samples; Overnight samples
3.  Primary myelofibrosis associated glomerulopathy: significant improvement after therapy with ruxolitinib 
BMC Nephrology  2015;16:121.
Background
Primary myelofibrosis (PMF) is a type of myeloproliferative neoplasm (MPN) characterized by the predominant proliferation of megakaryocytes and granulocytes in the bone marrow, leading to the deposition of fibrous tissue, and by a propensity toward extramedullary hematopoiesis. Renal involvement in PMF is rare, but kidney tissue samples from these patients reveal MPN-related glomerulopathy, a recently discovered condition, in the late stages of the disease.
Case presentation
We present the first case described in the medical literature of a patient with early renal glomerular involvement in PMF/MPN. A 60-year-old man with stage 4 chronic kidney disease and a recent diagnosis of PMF (within 4 weeks of presentation at our renal division) presented with generalized body swelling, acute kidney injury, and massive nephrotic-range proteinuria. Kidney biopsy was performed to determine the etiology of the patient’s renal dysfunction and revealed early renal glomerular involvement that was histologically characteristic of MPN-related glomerulopathy. Early diagnosis and prompt medical management returned the patient’s kidney functionality to the levels seen on initial presentation at our hospital.
Conclusion
Large studies with long follow-up durations are necessary to identify and categorize the risk factors for the development of MPN-related glomerulopathy, to standardize therapeutic regimens, and to determine whether aggressive management of the myelofibrosis slows the progression of kidney disease.
doi:10.1186/s12882-015-0121-6
PMCID: PMC4521341  PMID: 26232031
Myelofibrosis; Glomerulopathy; Proteinuria; Acute kidney injury
4.  Prevalence and determinants of chronic kidney disease in rural and urban Cameroonians: a cross-sectional study 
BMC Nephrology  2015;16:117.
Background
Chronic kidney disease (CKD) is a global public health problem that disproportionally affects people of African ethnicity. We assessed the prevalence and determinants of CKD and albuminuria in urban and rural adults Cameroonians.
Methods
This was a cross-sectional study of 6-month duration (February to July 2014), conducted in the health district of Dschang (Western Region of Cameroon), using a multistage cluster sampling. All adults diagnosed with albuminuria (≥30 mg/g) and/or decreased estimated glomerular filtration rate (eGFR) (<60 ml/min/1.73 m2) were re-examined three months later. Logistic regression models were used to relate baseline characteristics with prevalent CKD.
Results
We included 439 participants with a mean age of 47 ± 16.1 years; with 185 (42.1 %) being men and 119 (27.1 %) being urban dwellers. There was a high prevalence of hypertension (25.5 %), diabetes (9.8 %), smoking (9.3 %), alcohol consumption (59.7 %), longstanding use of herbal medicine (90.9 %) and street medications (87.5 %), and overweight/obesity (53.3 %) which were predominant in rural area. The prevalence of CKD was 13.2 % overall, 14.1 % in rural and 10.9 % in urban participants. Equivalents figures for CKD stages G3-G4 and albuminuria were 2.5 %, 1.6 % and 5.0 %; and 12.1 %, 14.1 % and 6.7 % respectively. Existing hypertension and diabetes were associated with all outcomes. Elevated systolic blood pressure and the presence of hypertension and diabetes were the predictors of albuminuria and CKD while urban residence was associated with CKD stages G3-G4.
Conclusion
The prevalence of CKD and albuminuria was high in this population, predominantly in rural area, and driven mostly by the commonest risk factors.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0111-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0111-8
PMCID: PMC4518633  PMID: 26220538
5.  Rhabdomyolysis-induced acute kidney injury in a cancer patient exposed to denosumab and abiraterone: a case report 
BMC Nephrology  2015;16:118.
Background
Denosumab and abiraterone were approved by the United States Food and Drug Administration in 2011 for the treatment of metastatic castration-resistant prostate cancer. Neither denosumab nor abiraterone is known to cause rhabdomyolysis.
Case presentation
A 76-year-old Caucasian man with metastatic prostate cancer presented with non-oliguric severe acute kidney injury (AKI) 3 weeks after receiving simultaneous therapy with denosumab and abiraterone. The patient had been on statin therapy for more than 1 year with no recent dose adjustments. His physical exam was unremarkable. Blood work on admission revealed hyperkalemia, mild metabolic acidosis, hypocalcemia, and elevated creatine kinase (CK) at 44,476 IU/L. Kidney biopsy confirmed the diagnosis of rhabdomyolysis-induced AKI. The patient responded well to intravenous isotonic fluids and discontinuation of denosumab, abiraterone, and rosuvastatin, with normalization of CK and recovery of kidney function.
Conclusion
We report the first case of biopsy-proven rhabdomyolysis-induced AKI in a cancer patient acutely exposed to denosumab and abiraterone. Whether one of these drugs individually, or the combination, was the bona fide culprit of muscle breakdown is unknown. Nonetheless, our report is hypothesis-generating for further investigations on the effect of these drugs on muscle cells.
doi:10.1186/s12882-015-0113-6
PMCID: PMC4519001  PMID: 26220655
Denosumab; Abiraterone; Acute kidney injury; Rhabdomyolysis
6.  Association between acetylsalicylic acid and the risk of dialysis-related infections or septicemia among incident hemodialysis patients: a nested case–control study 
BMC Nephrology  2015;16:115.
Background
Vascular access-related infections and septicemia are the main causes of infections among hemodialysis patients, the majority of them caused by Staphylococcus species. Acetylsalicylic acid (ASA) has recently been reported with a probable antistaphylococcal activity. This study aimed to evaluate the effect of ASA on the risk of dialysis-related infection and septicemia among incident chronic hemodialysis patients.
Methods
In a nested case–control study, we identified 449 cases of vascular access-related infections and septicemia, and 4156 controls between 2001 and 2007 from our incident chronic hemodialysis patients’ cohort. Cases were defined as patients hospitalized with a main diagnosis of vascular access-related infection or septicemia on the discharge sheet (ICD-9 codes). Up to ten controls per case were selected by incidence density sampling and matched to cases on age, sex and follow-up time. ASA exposure was measured at the admission and categorized as: no use, low dose (80–324 mg/d), high dose (≥325 mg/d). Odds ratios (OR) for infections were estimated using multivariable conditional logistic regression analysis, adjusting for potential confounders.
Results
Compared to no use, neither dose of ASA was associated with a decreased risk of infection: low dose (OR 1.03, 95 % CI 0.82-1.28) and high dose (OR 1.30, 95 % CI 0.96-1.75). However, diabetes (OR = 1.32, 95 % CI = 1.07–1.62) and anticoagulant use (OR = 1.62, 95 % CI = 1.30–2.02) were associated with a higher risk.
Conclusion
Among hemodialysis patients, ASA use was not associated with a reduced risk of hospitalizations for dialysis-related infections or septicemia. However, ASA may remain beneficial for its cardiovascular indications.
doi:10.1186/s12882-015-0112-7
PMCID: PMC4517421  PMID: 26215587
Epidemiology; Infections; Kidney failure; Chronic; Registries; Renal dialysis
7.  Urinary phosphorus excretion per creatinine clearance as a prognostic marker for progression of chronic kidney disease: a retrospective cohort study 
BMC Nephrology  2015;16:116.
Background
Whether phosphate itself has nephrotoxicity in patients with chronic kidney disease (CKD) is controversial, although phosphate excretion into urine may cause tubular damage in rat models. To evaluate actual phosphate load on each nephron, we examined the association between 24-h urinary phosphorus excretion per creatinine clearance (24-h U-P/CCr), a newly proposed index that is a surrogate for nephron load, and CKD progression in patients with CKD.
Methods
We conducted a single-center, retrospective cohort study. To avoid potential confounders for protein intake, only patients on our educational program for CKD with a fixed diet regimen and aged 20 years or older were included. The observation period was 3 years. Primary outcomes were CKD progression defined as a composite of end-stage kidney disease (ESKD) or 50 % reduction of estimated glomerular filtration rate. Patients were stratified by quartiles of 24-h U-P/CCr levels as Quartiles 1–4. The association was examined in three models: unadjusted (Model 1), adjusted for risk factors for CKD progression (Model 2), and factors that affect renal phosphate handling (Model 3).
Results
A total of 191 patients met the eligibility criteria. Patients with higher 24-h U-P/CCr showed a higher risk for the composite outcomes. The hazard ratios [95 % confidence interval] for 24-h U-P/CCr levels in Quartile 2, 3, and 4, respectively, versus Quartile 1 were 2.56 (1.15–6.24), 7.53 (3.63–17.62), and 12.17 (5.82–28.64) in Model 1; 1.66 (0.63–4.97), 3.57 (1.25–11.71), and 5.34 (1.41–22.32) in Model 2; and 3.07 (0.97–11.85), 7.52 (2.13–32.69), and 7.89 (1.74–44.33) in Model 3.
Conclusions
Our study showed that higher phosphorus excretion per creatinine clearance was associated with CKD progression.
doi:10.1186/s12882-015-0118-1
PMCID: PMC4517498  PMID: 26215643
Collected urine; Chronic kidney diseases; End-stage kidney disease; Bone diseases; Metabolic; Protein intake
8.  Burden of chronic kidney disease in resource-limited settings from Peru: a population-based study 
BMC Nephrology  2015;16:114.
Background
The silent progression of chronic kidney diseases (CKD) and its association with other chronic diseases, and high treatment costs make it a great public health concern worldwide. The population burden of CKD in Peru has yet to be fully described.
Methods
We completed a cross sectional study of CKD prevalence among 404 participants (total study population median age 54.8 years, 50.2 % male) from two sites, highly-urbanized Lima and less urbanized Tumbes, who were enrolled in the population-based CRONICAS Cohort Study of cardiopulmonary health in Peru. Factors potentially associated with the presence of CKD were explored using Poisson regression, a statistical methodology used to determine prevalence ratios.
Results
In total, 68 participants (16.8 %, 95 % CI 13.5–20.9 %) met criteria for CKD: 60 (14.9%) with proteinuria, four (1%) with eGFR <60mL/min/1.73m2 , and four (1%) with both. CKD prevalence was higher in Lima (20.7 %, 95 % CI 15.8–27.1) than Tumbes (12.9 %, 95 % CI 9.0–18.5). Among participants with CKD, the prevalence of diabetes and hypertension was 19.1 % and 42.7 %, respectively. After multivariable adjustment, CKD was associated with older age, female sex, greater wealth tertile (although all wealth strata were below the poverty line), residence in Lima, and presence of diabetes and hypertension.
Conclusions
The high prevalence rates of CKD identified in Lima and Tumbes are similar to estimates from high-income settings. These findings highlight the need to identify occult CKD and implement strategies to prevent disease progression and secondary morbidity.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0104-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0104-7
PMCID: PMC4512019  PMID: 26205002
Chronic kidney disease; Prevalence; Chronic diseases
9.  13-year nationwide cohort study of chronic kidney disease risk among treatment-naïve patients with chronic hepatitis B in Taiwan 
BMC Nephrology  2015;16:110.
Background
Chronic hepatitis B virus (HBV) infection and chronic kidney disease (CKD) have high prevalences in Taiwan and worldwide. However, the association of untreated chronic hepatitis B virus (HBV) infection with chronic kidney disease (CKD) remains unclear.
Methods
This cohort study used claims data in the Taiwan National Health Insurance Research Database in 1996–2010, in which all diseases were classified by ICD-9-CM codes. We identified 17796 adults who had chronic HBV infection and did not take nucleos(t)ide analogues from 1998 to 2010 and also randomly selected 71184 matched controls without HBV in the same dataset. Cumulative incidences and adjusted hazard ratio (aHR) of incident CKD were evaluated through the end of 2010 after adjusting for competing mortality.
Results
The risk of CKD was significantly higher in the HBV cohort (13-year cumulative incidence, 6.2 %; 95 % confidence interval [CI], 5.4–7.1 %) than in the non-HBV cohort (2.7 %; 95 % CI, 2.5–3.0 %) (p < 0.001), and the aHR was 2.58 (95 % CI, 1.95-3.42; p < 0.001). Multivariable stratified analysis further verified significant associations of CKD with HBV in men of any age (aHR, 2.98; 95 % CI, 2.32–3.83, p < 0.001 for men aged <50 years; aHR, 1.58; 95 % CI, 1.31–1.91, p < 0.001 for men aged ≧50 years) and women under the age of 50 (aHR, 2.99; 95 % CI, 2.04–4.42, p < 0.001), but no significant association in women aged 50 or over.
Conclusion
Untreated chronic HBV infection is associated with increased risk of CKD. Hence, high-risk HBV-infected subjects should have targeted monitoring for the development of CKD.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0106-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0106-5
PMCID: PMC4508999  PMID: 26199000
HBV infection; Chronic kidney disease; Cohort study; Taiwan National Health Insurance Research Database; Competing mortality
10.  A retrospective, longitudinal study estimating the association between interdialytic weight gain and cardiovascular events and death in hemodialysis patients 
BMC Nephrology  2015;16:113.
Background
Greater interdialytic weight gain (IDWG) is associated with risk of all-cause mortality and hospitalization. Dialysis patients are also at greater risk of cardiovascular (CV) events than patients without kidney disease. This retrospective study examined the potential association between IDWG and specific types of CV events.
Methods
Data were obtained from United States Renal Data System claims and the electronic health records of Medicare patients who initiated hemodialysis between 01 January 2007 and 31 December 2008 at a large dialysis organization. Absolute IDWG was defined as predialysis weight minus postdialysis weight from the prior treatment, and relative IDWG was calculated as percentage of postdialysis weight with mean values for each, calculated over dialysis days 91 to 180. Patient outcomes were considered beginning on day 181, continuing until death, discontinuation of care, censoring, or study end (31 December 2009). Outcomes included all-cause mortality, CV mortality, hospitalization for nonfatal heart failure/volume overload, hospitalization for nonfatal myocardial infarction, MACE (a composite measure of nonfatal myocardial infarction, nonfatal ischemic stroke, or CV death), and MACE+ (events comprising MACE as well as arrhythmia, nonfatal hemorrhagic stroke, or hospitalization for heart failure). Associations between IDWG and outcomes over the exposure period were estimated using proportional hazards regression and adjusted for baseline characteristics.
Results
39,256 patients qualified for analysis. In general, associations of relative IDWG with outcomes were more potent, consistent, and monotonic than those for absolute IDWG. Relative IDWG > 3.5 % body weight was independently associated with all outcomes studied: point estimates ranged from 1.18 (myocardial infarction) to 1.26 (CV mortality) and were consistent among patients with and without diabetes, and with and without baseline heart failure. Absolute IDWG > 3 kg was associated with outcomes other than myocardial infarction: point estimates ranged from 1.11 (MACE) to 1.20 (heart failure).
Conclusions
Greater IDWG is associated with an increased risk of CV morbid events. Strategies that mitigate IDWG may improve CV health and survival among hemodialysis patients.
doi:10.1186/s12882-015-0110-9
PMCID: PMC4510887  PMID: 26197758
Blood pressure; Cardiovascular death; Chronic kidney disease; Fluid accumulation; Heart failure; Volume overload; Heart disease; Hemodialysis
11.  Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis: report of the font clinical trial group 
BMC Nephrology  2015;16:111.
Background
Patients with resistant focal segmental glomerulosclerosis (FSGS) who are unresponsive to corticosteroids and other immunosuppressive agents are at very high risk of progression to end stage kidney disease. In the absence of curative treatment, current therapy centers on renoprotective interventions that reduce proteinuria and fibrosis. The FONT (Novel Therapies for Resistant FSGS) Phase II clinical trial (NCT00814255, Registration date December 22, 2008) was designed to assess the efficacy of adalimumab and galactose compared to standard medical therapy which was comprised of lisinopril, losartan, and atorvastatin.
Methods
Key eligibility criteria were biopsy confirmed primary FSGS or documentation of a causative genetic mutation, urine protein:creatinine ratio >1.0 g/g, and estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m2. The experimental treatments – adalimumab, galactose, standard medical therapy-- were administered for 26 weeks. The primary endpoint was a 50 % reduction in proteinuria with stable eGFR.
Results
Thirty-two subjects were screened and 21 were assigned to one of the three study arms. While none of the adalimumab-treated subjects achieved the primary outcome, 2 subjects in the galactose and 2 in the standard medical therapy arm had a 50 % reduction in proteinuria without a decline in eGFR. The proteinuria response did not correlate with serial changes in the serum glomerular permeability activity measured by the Palb assay or soluble urokinase plasminogen activator receptor (suPAR). There were no serious adverse effects related to treatments in the study.
Conclusions
Recruitment into this trial that addressed patients with resistant FSGS fell short of the enrollment goal. Our findings suggest that future studies of novel therapies for rare glomerular diseases such as FSGS may benefit from enrollment of patients earlier in the course of their disease. In addition, better identification of patients who are likely to respond to a new treatment based on biomarkers suggesting involvement of the disease pathway targeted by the experimental agent may reduce the required sample size and increase the likelihood of a favorable outcome.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0094-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0094-5
PMCID: PMC4511259  PMID: 26198842
FSGS; Galactose; Adalimumab; Renoprotective; Antifibrotic; Permeability factors
12.  Prognostic robustness of serum creatinine based AKI definitions in patients with sepsis: a prospective cohort study 
BMC Nephrology  2015;16:112.
Background
It is unclear how modifications in the way to calculate serum creatinine (sCr) increase and in the cut-off value applied, influences the prognostic value of Acute Kidney Injury (AKI). We wanted to evaluate whether these modifications alter the prognostic value of AKI for prediction of mortality at 3 months, 1 and 2 years.
Methods
We prospectively included 195 septic patients and evaluated the prognostic value of AKI by using three different algorithms to calculate sCr increase: either as the difference between the highest value in the first 24 h after ICU admission and a pre-admission historical (ΔHIS) or an estimated (ΔEST) baseline value, or by subtracting the ICU admission value from the sCr value 24 h after ICU admission (ΔADM). Different cut-off levels of sCr increase (0.1, 0.2, 0.3, 0.4 and 0.5 mg/dl) were evaluated.
Results
Mortality at 3 months, 1 and 2 years in AKI defined as ΔADM > 0.3 mg/dl was 48.1 %, 63.0 % and 63.0 % vs 27.7 %, 39.8 % and 47.6 % in no AKI respectively (OR(95%CI): 2.42(1.06-5.54), 2.58(1.11-5.97) and 1.87(0.81-4.33); 0.3 mg/dl was the lowest cut-off value that was discriminatory. When AKI was defined as ΔHIS > 0.3 mg/dl or ΔEST > 0.3 mg/dl, there was no significant difference in mortality between AKI and no AKI.
Conclusions
The prognostic value of a 0.3 mg/dl increase in sCr, on mortality in sepsis, depends on how this sCr increase is calculated. Only if the evolution of serum creatinine over the first 24 h after ICU admission is taken into account, an association with mortality is found.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0107-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0107-4
PMCID: PMC4511260  PMID: 26199072
AKI; Sepsis; Critical illness; Prognosis; Diagnosis; Mortality
13.  Pretransplant malnutrition, inflammation, and atherosclerosis affect cardiovascular outcomes after kidney transplantation 
BMC Nephrology  2015;16:109.
Background
Malnutrition, inflammation, and atherosclerosis (MIA) syndrome is associated with a high mortality rate in patients with end-stage renal disease. However, the clinical relevance of MIA syndrome in kidney transplantation (KT) recipients remains unknown.
Methods
We enrolled 1348 adult KT recipients. Recipients were assessed based on serum albumin, cholesterol, or body mass index for the malnutrition factor and C-reactive protein level for the inflammation factor. Any history of cardiovascular (CV), cerebrovascular, or peripheral vascular disease satisfied the atherosclerosis factor. Each MIA factors were assessed by univariate analysis and we calculated an overall risk score by summing up scores for each independent variable. The enrolled patients were divided into 4 groups depending on the MIA score (0, 2–4, 6, 8–10).
Results
The patients with higher MIA score showed worse outcome of fatal/non-fatal acute coronary syndrome (ACS) (p < 0.001) and composite outcomes of ACS and all-cause mortality (p < 0.001) than with the lower MIA score. In multivariate analysis, ACS showed significantly higher incidence in the MIA score 8-10 group than in the MIA score 0 group (Hazard ratio 6.12 95 % Confidence interval 1.84–20.32 p = 0.003).
Conclusions
The presence of MIA factors before KT is an independent predictor of post-transplant CV outcomes.
doi:10.1186/s12882-015-0108-3
PMCID: PMC4508766  PMID: 26194096
Acute Coronary Syndrome; Atherosclerosis; Cardiovascular Outcome; Inflammation; Kidney Transplantation; Malnutrition
14.  Left ventricular global longitudinal strain is associated with cardiovascular risk factors and arterial stiffness in chronic kidney disease 
BMC Nephrology  2015;16:106.
Background
Global longitudinal strain (GLS) has emerged as a superior method for detecting left ventricular (LV) systolic dysfunction compared to ejection fraction (EF) on the basis that it is less operator dependent and more reproducible. The 2-dimensional strain (2DS) method is easily measured and integrated into a standard echocardiogram. This study aimed to determine the relationship between GLS and traditional and chronic kidney disease (CKD)-related risk factors of cardiovascular disease (CVD) in patients with CKD.
Methods
A cross sectional study of patients with moderate CKD stages 3 and 4 (n = 136). Clinical characteristics, anthropometric, biochemical data including markers of inflammation [C-reactive protein (CRP)], uremic toxins [indoxyl sulphate (IS), p-cresyl sulphate (PCS)], and arterial stiffness [pulse wave velocity (PWV)] were measured. Inducible ischemia was detected using exercise stress echocardiogram. GLS was determined from 3 standard apical views using 2-dimensional speckle tracking and EF was measured using Simpson’s rule. Associations between GLS and traditional and CKD-related risk factors were explored using multivariate models.
Results
The study population parameters included: age 59.4 ± 9.8 years, 58 % male, estimated glomerular filtration rate (eGFR) 44.4 ± 10.1 ml/min/1.73 m2, GLS −18.3 ± 3.6 % and EF 65.8 % ± 7.8 %. This study demonstrated that GLS correlated with diabetes (r = 0.21, p = 0.01), history of heart failure (r = 0.20, p = 0.01), free IS (r = 0.24, p = 0.005) free PCS (r = 0.23, p = 0.007), body mass index (BMI) (r = 0.28, p < 0.001), and PWV (r = 0.24, p = 0.009). Following adjustment for demographic, baseline co-morbidities and laboratory parameters,GLS was independently associated with free IS, BMI and arterial stiffness (R2 for model = 0.30, p < 0.0001).
Conclusions
In the CKD cohort, LV systolic function assessed using GLS was associated with uremic toxins, obesity and arterial stiffness.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0098-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0098-1
PMCID: PMC4506621  PMID: 26187506
Left ventricular function; Global longitudinal strain; Arterial stiffness; Obesity; Uremic toxins
15.  Hyperphosphatemia as an independent risk factor for coronary artery calcification progression in peritoneal dialysis patients 
BMC Nephrology  2015;16:107.
Background
Coronary artery calcification (CAC) is associated with cardiovascular mortality in end-stage renal disease (ESRD) patients. The present study aimed to identify modifiable risk factors for CAC progression in peritoneal dialysis (PD) patients.
Methods
Adult patients who received regular PD for more than 6 months and underwent a series of coronary artery calcification score (CaCS) measurements by multislice spiral computed tomography (MSCT) with an interval of ≥ 6 months were included in this observational cohort study. The demographic characteristics and clinical data, including laboratory data and adequacy of PD, were collected. Curve estimation was used to fit the straight line and obtain the slope. Binary logistic regression was performed to identify the independent risk factors for CAC progression in the PD patients, and multivariate linear regression was conducted to identify factors associated with hyperphosphatemia.
Results
A total of 207 adult patients on PD (116 men, 56.0 %) with a mean age of 59.8 ± 15.9 years were recruited to this study, and 157 of them (75.8 %) received three or more CaCS assessments. The patients were divided into a slow group (n = 137) and a rapid group (n = 70) according to the linear regression slope or the average speed of development. The follow-up time was 33.0 ± 18.8 months. Multivariate logistic regression revealed that age and serum phosphate level were independent risk factors for CAC progression after adjustments. Multivariate linear regression revealed that hyperphosphatemia was associated with elevations in the transferrin and serum albumin levels and normalized protein catabolic rate (nPCR) and reductions in the hemoglobin level, residual Ccr, and PD Ccr.
Conclusions
Hyperphosphatemia is an independent risk factor for CAC progression, and the serum phosphate level may be associated with protein intake and PD adequacy. These results provide important information for the clinical management of ESRD patients.
doi:10.1186/s12882-015-0103-8
PMCID: PMC4506628  PMID: 26187601
Coronary artery calcification; Peritoneal dialysis; Hyperphosphatemia; ESRD
16.  Autoimmune haemolytic anaemia associated with epstein barr virus infection as a severe late complication after kidney transplantation and successful treatment with rituximab: case report 
BMC Nephrology  2015;16:108.
Background
Autoimmune haemolytic anaemia (AIHA) is a rare complication following kidney transplantation and usually occurs early in its course. It is characterised by autoantibodies or alloantibodies directed against red blood cells (RBCs).
Case presentation
We describe a 44 year old woman who presented 5 years after kidney transplantation with profound transfusion dependent warm AIHA. Investigations confirmed an IgG autoantibody against RBCs and high titre Epstein-Barr virus (EBV) viraemia. The patient was at higher risk for EBV disease being seronegative at the time of transplantation but had detectable EBV capsid IgG antibody at the time of presentation. The haemolysis was refractory to high dose steroid and intravenous immunoglobulin. There was a rapid and complete resolution of both the anaemia and the viraemia following rituximab therapy, with no adverse events. Twenty-six units of blood were required during the course of treatment.
Conclusions
To our knowledge this is the first reported case of EBV associated AIHA in a renal transplant recipient. It highlights a rare pathology associated with post-transplant EBV infection, of broad interest to transplant physicians, haematologists, and microbiologists, and the effective novel use of monoclonal anti-CD20 therapy.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0096-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0096-3
PMCID: PMC4506635  PMID: 26187383
EBV; Kidney transplantation; AIHA; Rituximab
17.  Perspectives of continuous renal replacement therapy in the intensive care unit: a paired survey study of patient, physician, and nurse views 
BMC Nephrology  2015;16:105.
Background
Recent studies suggest discrepancies between patients and providers around perceptions of hemodialysis prognosis. Such data are lacking for continuous renal replacement therapy (CRRT). We aim to assess patient and provider understanding of outcomes around CRRT.
Methods
From February 1 to August 31, 2013, a triad of (1) a patient on CRRT (or health care proxy [HCP]), (2) physician and (3) primary nurse from the intensive care unit (ICU) team were surveyed. Univariate chi-square and qualitative analysis techniques were used.
Results
Ninety-six total participants (32 survey triads) were completed. Ninety one percent of patients/HCPs correctly identified that CRRT replaced the function of the kidneys. Six percent of patients/HCPs, 44 % of physicians, and 44 % of nurses identified rates of survival to hospital discharge that were consistent with published literature. Both physicians and nurses were more likely than patients/HCPs to assess survival consistently with published data (p = 0.001). Patients/HCPs were more likely to overestimate survival rates than physicians and nurses (p < 0.001). Thirty eight percent of patients/HCPs, 38 % of physicians, and 28 % of nurses identified rates of lifelong dialysis-dependence among surviving patients that were consistent with published literature.
Conclusions
There is mismatch between patients, HCPs, and providers around prognosis of CRRT. Patients/HCPs are more likely to overestimate chances of survival than physicians or nurses. Further intervention is needed to improve this knowledge gap.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0086-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0086-5
PMCID: PMC4501124  PMID: 26169052
Continuous renal replacement therapy; Intensive care unit; Kidney injury; Mismatch; Patient and provider perspectives; Survey
18.  Simultaneous exposure to multiple heavy metals and glyphosate may contribute to Sri Lankan agricultural nephropathy 
BMC Nephrology  2015;16:103.
Background
Sri Lankan Agricultural Nephropathy (SAN), a new form of chronic kidney disease among paddy farmers was first reported in 1994. It has now become the most debilitating public health issue in the dry zone of Sri Lanka. Previous studies showed SAN is a tubulo-interstitial type nephropathy and exposure to arsenic and cadmium may play a role in pathogenesis of the disease.
Methods
Urine samples of patients with SAN (N = 10) from Padavi-Sripura, a disease endemic area, and from two sets of controls, one from healthy participants (N = 10) from the same endemic area and the other from a non-endemic area (N = 10; Colombo district) were analyzed for 19 heavy metals and for the presence of the pesticide- glyphosate.
Results
In both cases and the controls who live in the endemic region, median concentrations of urinary Sb, As, Cd, Co, Pb, Mn, Ni, Ti and V exceed the reference range. With the exception of Mo in patients and Al, Cu, Mo, Se, Ti and Zn in endemic controls, creatinine adjusted values of urinary heavy metals and glyphosate were significantly higher when compared to non-endemic controls. Creatinine unadjusted values were significant higher for 14 of the 20 chemicals studied in endemic controls and 7 in patients, compared to non-endemic controls. The highest urinary glyphosate concentration was recorded in SAN patients (range 61.0-195.1 μg/g creatinine).
Conclusions
People in disease endemic area exposed to multiple heavy metals and glyphosate. Results are supportive of toxicological origin of SAN that is confined to specific geographical areas. Although we could not localize a single nephrotoxin as the culprit for SAN, multiple heavy metals and glyphosates may play a role in the pathogenesis. Heavy metals excessively present in the urine samples of patients with SAN are capable of causing damage to kidneys. Synergistic effects of multiple heavy metals and agrochemicals may be nephrotoxic.
doi:10.1186/s12882-015-0109-2
PMCID: PMC4499177  PMID: 26162605
Chronic kidney disease; Heavy metals; Pesticides; Sri Lanka; Synergistic effect
19.  PAlliative Care in chronic Kidney diSease: the PACKS study—quality of life, decision making, costs and impact on carers in people managed without dialysis 
BMC Nephrology  2015;16:104.
Background
The number of patients with advanced chronic kidney disease opting for conservative management rather than dialysis is unknown but likely to be growing as increasingly frail patients with advanced renal disease present to renal services. Conservative kidney management includes ongoing medical input and support from a multidisciplinary team. There is limited evidence concerning patient and carer experience of this choice. This study will explore quality of life, symptoms, cognition, frailty, performance decision making, costs and impact on carers in people with advanced chronic kidney disease managed without dialysis and is funded by the National Institute of Health Research in the UK.
Methods
In this prospective, multicentre, longitudinal study, patients will be recruited in the UK, by renal research nurses, once they have made the decision not to embark on dialysis. Carers will be asked to ‘opt-in’ with consent from patients. The approach includes longitudinal quantitative surveys of quality of life, symptoms, decision making and costs for patients and quality of life and costs for carers, with questionnaires administered quarterly over 12 months. Additionally, the decision making process will be explored via qualitative interviews with renal physicians/clinical nurse specialists.
Discussion
The study is designed to capture patient and carer profiles when conservative kidney management is implemented, and understand trajectories of care-receiving and care-giving with the aim of optimising palliative care for this population. It will explore the interactions that lead to clinical care decisions and the impact of these decisions on informal carers with the intention of improving clinical outcomes for patients and the experiences of care givers.
doi:10.1186/s12882-015-0084-7
PMCID: PMC4499188  PMID: 26163382
Carers; Conservative kidney management; End-of-life; Mixed methods research; Palliative care; Quality of life renal
20.  Understanding barriers to optimal medication management for those requiring long-term dialysis: rationale and design for an observational study, and a quantitative description of study variables and data 
BMC Nephrology  2015;16:102.
Background
Rates of medication non-adherence in dialysis patients are high, and improving adherence is likely to improve outcomes. Few data are available regarding factors associated with medication adherence in dialysis patients, and these data are needed to inform effective intervention strategies.
Methods/design
This is an observational cross-sectional study of a multi-ethnic dialysis cohort from New Zealand, with the main data collection tool being an interviewer-assisted survey. A total of 100 participants were randomly sampled from a single centre, with selection stratified by ethnicity and dialysis modality (facility versus home). The main outcome measure is self-reported medication adherence using the Morisky 8-Item Medication Adherence Scale (MMAS-8). Study data include demographic, clinical, social and psychometric characteristics, the latter being constructs of health literacy, medication knowledge, beliefs about medications, and illness perceptions. Psychometric constructs were assessed through the following survey instruments; health literacy screening questions, the Medication Knowledge Evaluation Tool (Okuyan et al.), the Beliefs about Medication Questionnaire (Horne et al.), the Brief Illness Perception Questionnaire (Broadbent et al.). Using the study data, reliability analysis for internal consistency is satisfactory for the scales evaluating health literacy, medication knowledge, and beliefs about medications, with Chronbach’s α > 0.7 for all. Reliability analysis indicated poor internal consistency for scales relating to illness perceptions. MMAS-8 and all psychometric scores are normally distributed in the study data.
Discussion
This study will provide important information on the factors involved in medication non-adherence in New Zealand dialysis patients. The resulting knowledge will inform long-term initiatives to reduce medication non-adherence in dialysis patients, and help ensure that they are addressing appropriate and evidence based targets for intervention.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0097-2) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0097-2
PMCID: PMC4499205  PMID: 26162369
Medication adherence; Dialysis; Health literacy; Medication knowledge; Beliefs about medications; Illness perception
21.  Focal segmental glomerulosclerosis: molecular genetics and targeted therapies 
BMC Nephrology  2015;16:101.
Recent advances show that human focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy caused by podocyte-specific gene mutations including NPHS1, NPHS2, WT-1, LAMB2, CD2AP, TRPC6, ACTN4 and INF2. This review focuses on genes discovered in the investigation of complex FSGS pathomechanisms that may have implications for the current FSGS classification scheme. It also recounts recent recommendations for clinical management of FSGS based on translational studies and clinical trials. The advent of next-generation sequencing promises to provide nephrologists with rapid and novel approaches for the diagnosis and treatment of FSGS. A stratified and targeted approach based on the underlying molecular defects is evolving.
doi:10.1186/s12882-015-0090-9
PMCID: PMC4496884  PMID: 26156092
Focal segmental glomerulosclerosis; Podocyte gene mutation; Proteinuria; Next-generation sequencing
22.  Cross-sectional examination of metabolites and metabolic phenotypes in uremia 
BMC Nephrology  2015;16:98.
Background
Although metabolomic approaches have begun to document numerous changes that arise in end stage renal disease (ESRD), how these alterations relate to established metabolic phenotypes in uremia is unknown.
Methods
In 200 incident hemodialysis patients we used partial least squares discriminant analysis to identify which among 166 metabolites could best discriminate individuals with or without diabetes, and across tertiles of body mass index, serum albumin, total cholesterol, and systolic blood pressure.
Results
Our data do not recapitulate metabolomic signatures of diabetes and obesity identified among individuals with normal renal function (e.g. elevations in branched chain and aromatic amino acids) and highlight several potential markers of diabetes status specific to ESRD, including xanthosine-5-phosphate and vanillylmandelic acid. Further, our data identify significant associations between elevated tryptophan and long-chain acylcarnitine levels and both decreased total cholesterol and systolic blood pressure in ESRD. Higher tryptophan levels were also associated with higher serum albumin levels, but this may reflect tryptophan’s significant albumin binding. Finally, an examination of the uremic retention solutes captured by our platform in relation to 24 clinical phenotypes provides a framework for investigating mechanisms of uremic toxicity.
Conclusions
In sum, these studies leveraging metabolomic and metabolic phenotype data acquired in a well-characterized ESRD cohort demonstrate striking differences from metabolomics studies in the general population, and may provide clues to novel functional pathways in the ESRD population.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0100-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0100-y
PMCID: PMC4491861  PMID: 26149577
Dialysis; Metabolism; Metabolomics; Uremic toxins
23.  Assessing protein energy wasting in a Malaysian haemodialysis population using self-reported appetite rating: a cross-sectional study 
BMC Nephrology  2015;16:99.
Background
Poor appetite could be indicative of protein energy wasting (PEW) and experts recommend assessing appetite in dialysis patients. Our study aims to determine the relationship between PEW and appetite in haemodialysis (HD) patients.
Methods
HD patients (n=205) self-rated their appetite on a scale of 1 to 5 as very good (1), good (2), fair (3), poor (4) or very poor (5). Nutritional markers were compared against appetite ratings. Using logistic regression analysis associations between dichotomized appetite with PEW diagnosis were determined as per the International Society of Renal Nutrition and Metabolism (ISRNM) criteria and alternate objective measures. Data was adjusted for socioeconomic and demographic characteristics.
Results
Poorer appetite ratings were significantly associated with lower income (P = 0.021), lower measurements (P < 0.05) for mid-arm muscle circumference, mid-arm muscle area and lean tissue mass (LTM), serum urea (P = 0.007) and creatinine (P = 0.005). The highest hsCRP (P = 0.016) levels occurred in patients reporting the poorest appetite. Serum albumin did not differ significantly across appetite ratings. Poor oral intake represented by underreporting (EI/BMR < 1.2) was evident for all appetite ratings. PEW was prevalent irrespective of appetite ratings (very good: 17.6 %, good: 40.2 %, fair: 42.3 % and poor: 83.3 %). After dichotomizing appetite ratings into normal and diminished categories, there was a marginal positive association between diminished appetite and overall PEW diagnosis (ORadj: 1.71; 95 % CI: 0.94–3.10, P = 0.079). Amongst individual ISRNM criteria, only BMI <23 kg/m2 was positively associated with diminished appetite (ORadj: 2.17; 95 % CI: 1.18–3.99). However, patients reporting diminished appetite were more likely to have lower LTM (ORadj: 2.86; 95 % CI: 1.31–6.24) and fat mass (ORadj: 1.91; 95 % CI: 1.03–3.53), lower levels of serum urea (ORadj: 2.74; 95 % CI: 1.49–5.06) and creatinine (ORadj: 1.99; 95 % CI: 1.01–3.92), higher Dialysis Malnutrition Score (ORadj: 2.75; 95 % CI: 1.50–5.03), Malnutrition Inflammation Score (ORadj: 2.15; 95 % CI: 1.17–3.94), and poorer physical (ORadj: 3.49; 95 % CI: 1.89–6.47) and mental (ORadj: 5.75; 95 % CI: 3.02–10.95) scores.
Conclusions
A graded but non-significant increase in the proportion of PEW patients occurred as appetite became poorer. However, after dichotomization, a positive but marginally significant association was observed between diminished appetite and PEW diagnosis.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0073-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0073-x
PMCID: PMC4492004  PMID: 26149396
Appetite; Haemodialysis; Protein energy wasting; Nutritional status; Anorexia
24.  Mortality and complications after hip fracture among elderly patients undergoing hemodialysis 
BMC Nephrology  2015;16:100.
Background
Osteoporotic hip fractures cause high mortality and morbidity in elderly adults. Compared to the general population, subjects with end-stage renal disease and hemodialysis often develop mineral bone disorders and have a higher risk for hip fractures.
Methods
We conducted a matched cohort study design and used competing risk analysis to estimate the cumulative incidence of the complication rate. Subjects aged greater than 60 years with hip fracture were selected from Taiwan’s National Health Insurance Research Database covering a period from 1997 to 2007, and these subjects were followed up until 2009. We used the Kaplan–Meier method to estimate the overall survival and used the log-rank test and multiple Cox proportional hazards model to explore the risk factors for survival. The cumulative incidence of the first complication was estimated using competing risk analysis.
Results
Among hemodialysis subjects, the three-month, one-year, two-year and five-year mortality rates were 17.3 %, 37.2 %, 51.5 %, and 80.5 %, respectively; the one-year and five-year cumulative incidences of the first surgical complication were 14.2 % and 20.6 %, respectively; and the three-month cumulative incidence of the first medical complication was 24.1 %. Hemodialysis subjects presented a 2.32 times (95 % CI: 2.16–2.49) higher hazard ratio of overall death, 1.15 times (95 % CI: 1.01–1.30) higher sub-hazard ratio (sub-HR) of surgical complications, and 1.35 times (95 % CI: 1.21–1.52) higher sub-HR of the first medical complication than non-hemodialysis controls.
Conclusions
The overall mortality and complication rates of hemodialysis subjects after surgery for hip fracture were significantly higher than those of non-hemodialysis subjects. Further prospective studies which include important risk factors are necessary to more precisely quantify the adjusted effect of hemodialysis.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0099-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12882-015-0099-0
PMCID: PMC4492013  PMID: 26149489
End-stage renal disease; Hemodialysis; Osteoporotic hip fracture; Mortality; Surgical complication; Medical complication; Elderly patient
25.  Fluctuation of the renal function after discharge from hospital and its effects on drug dosing in elderly patients – study protocol 
BMC Nephrology  2015;16:95.
Background
Chronic kidney disease (CKD) is associated with an increased mortality rate, risk of cardiovascular events and morbidity. Impaired renal function is common in elderly patients, and their glomerular filtration rate (GFR) should be taken into account when prescribing renally excreted drugs. In a hospital care setting the GFR may fluctuate substantially, so that the renal function group and therefore the recommended dose, can change within a few days. The magnitude and prevalence of the fluctuation of renal function in daily clinical practice and its potential effects on appropriateness of drug prescriptions after discharge from the hospital is unknown.
Methods/design
This is a prospective observational study. Patients ≥ 70 years with renal impairment (eGFR <60 ml/min/1.73 m2) admitted to a geriatric ward are eligible to participate. Participants undergo blood sample collection to measure serum creatinine level at three time points: at discharge from hospital, 14 days, and 2 months after discharge. At these time points the actual medication of the participants is assessed and the number of incorrect prescriptions according to the Dutch guidelines in relation to their estimated renal function is measured. In addition, for a hypothetical selection of drugs, the need for drug dose adaptation in relation to renal function is measured. The outcome of interest is the percentage of patients that changes from renal function group after discharge from hospital compared to the renal function at discharge. In addition, the percentages of patients whose actual medications are incorrectly prescribed and for the hypothetical selection of drugs that would have required dose adaptation will be determined at discharge, 14 days and 2 months after discharge. For each outcome, risk factors which may lead to increased risk for fluctuation of renal function and/or incorrect drug prescribing will also be identified and analysed.
Discussion
This study will provide data on changes in renal function in elderly patients after discharge from the hospital with a focus on the medications used. The benefits for healthcare professionals comprise of the creation, adjustment or confirmation of recommendations for the monitoring of the renal function after discharge from hospital of elderly patients.
doi:10.1186/s12882-015-0095-4
PMCID: PMC4492070  PMID: 26149449
Renal function; Elderly; Drug therapy management; Fluctuation; Study protocol

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