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1.  CD4+ lymphocyte adenosine triphosphate - a new marker in sepsis with acute kidney injury? 
BMC Nephrology  2014;15(1):203.
Background
AKI frequently develops in sepsis patients, significantly decreasing the overall prognosis. There are currently no diagnostic markers available which reliably predict the prognosis of sepsis-associated AKI. Recently, ATP content of CD4+ T cells (ATP_CD4) has been shown to correlate with survival in sepsis. The aim of the study was to determine ATP_CD4 in sepsis-associated AKI.
Methods
Thirty-three patients with sepsis were prospectively analyzed for ATP_CD4 at three different time points. Results were related to survival, renal recovery, and further clinical/laboratory findings.
Results
ATP_CD4 tended to lower in concentration at 48 h after onset of sepsis in those patients with complete renal recovery. There were no differences between patients with no AKI and those with AKI of different severity (AKIN 1-3). Urinary NGAL did not correlate with renal prognosis.
Conclusion
ATP_CD4 may serve as risk predictor in sepsis-associated AKI. Lower concentrations may indicate a higher chance of complete renal recovery in sepsis.
doi:10.1186/1471-2369-15-203
PMCID: PMC4320623  PMID: 25522739
ATP_CD4; Sepsis; AKI; Mortality; Kidney regeneration
2.  Hepatocyte growth factor signalizes peritoneal membrane failure in peritoneal dialysis 
BMC Nephrology  2014;15(1):201.
Background
Hepatocyte growth factor (HGF) counteracts peritoneal fibrosis in animal models and in-vitro studies, but no study explored effluent HGF in peritoneal dialysis (PD) patients with ultrafiltration failure (UFF). Our aim was to assess the relationship between effluent HGF with UF profile, free water transport (FWT) and small-solute transport.
Methods
We performed 4-hour, 3.86% PET with additional UF measurement at 60 minutes in 68 PD patients. MTACcreatinine, FWT, small-pore ultrafiltration, and effluent HGF were quantified.
Results
Effluent HGF negatively correlated with UF (r = −0.80, p = 0.009) and FWT (r = −0.69, p = 0.04). Patients with UFF had higher dialysate HGF (103 pg/mL vs 77 pg/mL, p = 0.018) and, although not statistically significant, those with FWT compromise had also higher dialysate HGF compared with subgroup of UFF without FWT compromise (104 pg/mL vs 88 pg/mL, p = 0.08). FWT ≤ 45% without clinical UFF was documented in some patients who also had increased effluent HGF.
Conclusions
Dialysate HGF concentration is significantly higher among patients with UFF, specially, if FWT is impaired, being a sign of peritoneal membrane deterioration.
doi:10.1186/1471-2369-15-201
PMCID: PMC4277824  PMID: 25519900
Hepatocyte growth factor; Peritoneal membrane; Ultrafiltration failure; Water transport
3.  Is the kidney disease quality of life-36 (KDQOL-36) a valid instrument for Chinese dialysis patients? 
BMC Nephrology  2014;15(1):199.
Background
The aim of this study is to determine the validity and reliability of the Cantonese Chinese version of the Kidney Disease Quality of Life-36 (KDQOL-36™) questionnaire. The scale has been translated into Cantonese Chinese, but has not been tested among the Cantonese-speaking populations.
Methods
A total of 110 dialysis patients and 122 renal transplant patients were recruited. The data for the KDQOL-36™ were extracted from the KDQOL-Short Form. The criterion validity and scale equivalence were examined using the KDQOL-Short Form scores as the gold standard. The Hospital Anxiety and Depression scale was used to identify the correlations between depression, anxiety, and quality of life to establish the convergent validity. Discriminant validity was examined using the transplant patients to compare the quality of life of dialysis patients. The Cronbach’s alpha coefficient and test-retest were used for estimating reliability.
Results
There were very strong positive correlations for the physical and mental component summary between the KDQOL-36™ and KDQOL-Short Form. Despite the strong correlations, the effect size was 0.6 and 0.13 for the physical composite summary and mental composite summary score, respectively. Most of the subscales demonstrated significant moderate correlations with the Hospital Anxiety and Depression Scale, from -0.265 to -0.516. The discriminant validity was confirmed with a significant difference between the dialysis and transplant group patients. A high intraclass correlation of >0.98 was demonstrated in the test-retest.
Conclusion
The Cantonese Chinese KDQOL-36™ was reliable. Further testing will be required to determine its validity for the physical health summary scale.
doi:10.1186/1471-2369-15-199
PMCID: PMC4274701  PMID: 25511462
Chinese; Dialysis patients; Kidney disease quality of life; Reliability; Validity
4.  Chronic kidney disease and underdiagnosis of renal insufficiency among diabetic patients attending a hospital in Southern Ethiopia 
BMC Nephrology  2014;15(1):198.
Background
Diabetic patients with chronic kidney disease (CKD), as defined by a reduced glomerular filtration rate (GFR), are at greater risk for cardiovascular and renal events and mortality. The aim of this study was to determine the prevalence of CKD among diabetic patients attending a hospital in southern Ethiopia, and to assess underdiagnosis of renal insufficiency among those with normal serum creatinine.
Methods
A total of 214 randomly selected diabetics attending the follow-up clinic at Butajira hospital of southern Ethiopia participated in this study during the period from September 1 to October 31, 2013. All patients completed an interviewer-administered questionnaire and underwent clinical assessment. The simplified Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault (C-G) equations were used to estimate GFR (eGFR) from serum creatinine.
Results
CKD, defined as eGFR < 60 ml/min/1.73 m2, was present in 18.2% and 23.8% of the study participants according to the MDRD and Cockcroft-Gault (C-G) equations, respectively. Only 9.8% of the total participants, and 48.7% (for the MDRD) and 37.3% (for C-G) of those with eGFR <60 ml/min/1.73 m2 had abnormal serum creatinine values, i.e. > 1.5 mg/dl. Normal serum creatinine was observed in 90.2% of participants attending the hospital. A large proportion of participants ranging from 38.9-56.5% have shown to have mild to moderate renal insufficiency (stage 2–3 CKD) despite normal creatinine levels. CKD, eGFR < 60 ml/min/1.73 m2, was found in 10.4 and 16.9% of participants with normal serum creatinine using the MDRD and C-G equations, respectively.
Conclusion
CKD is present in no less than 18% of diabetics attending the hospital, but it is usually undiagnosed. A significant number of diabetics have renal insufficiency corresponding to stages 2–3 CKD despite normal creatinine levels. Therefore, GFR should be considered as an estimate of renal insufficiency, regardless of serum creatinine levels being in normal range.
doi:10.1186/1471-2369-15-198
PMCID: PMC4277829  PMID: 25511372
Chronic kidney disease; Diabetes; Estimated glomerular filtration rate; Serum creatinine; Renal insufficiency
5.  Understanding physicians’ behavior toward alerts about nephrotoxic medications in outpatients: a cross-sectional analysis 
BMC Nephrology  2014;15(1):200.
Background
Although most outpatients are relatively healthy, many have chronic renal insufficiency, and high override rates for suggestions on renal dosing have been observed. To better understand the override of renal dosing alerts in an outpatient setting, we conducted a study to evaluate which patients were more frequently prescribed contraindicated medications, to assess providers’ responses to suggestions, and to examine the drugs involved and the reasons for overrides.
Methods
We obtained data on renal alert overrides and the coded reasons for overrides cited by providers at the time of prescription from outpatient clinics and ambulatory hospital-based practices at a large academic health care center over a period of 3 years, from January 2009 to December 2011. For detailed chart review, a group of 6 trained clinicians developed the appropriateness criteria with excellent inter-rater reliability (κ = 0.93). We stratified providers by override frequency and then drew samples from the high- and low-frequency groups. We measured the rate of total overrides, rate of appropriate overrides, medications overridden, and the reason(s) for override.
Results
A total of 4120 renal alerts were triggered by 584 prescribers in the study period, among which 78.2% (3,221) were overridden. Almost half of the alerts were triggered by 40 providers and one-third was triggered by high-frequency overriders. The appropriateness rates were fairly similar, at 28.4% and 31.6% for high- and low-frequency overriders, respectively. Metformin, glyburide, hydrochlorothiazide, and nitrofurantoin were the most common drugs overridden. Physicians’ appropriateness rates were higher than the rates for nurse practitioners (32.9% vs. 22.1%). Physicians with low frequency override rates had higher levels of appropriateness for metformin than the high frequency overriders (P = 0.005).
Conclusion
A small number of providers accounted for a large fraction of overrides, as was the case with a small number of drugs. These data suggest that a focused intervention targeting primarily these providers and medications has the potential to improve medication safety.
doi:10.1186/1471-2369-15-200
PMCID: PMC4279964  PMID: 25511564
Medication safety; Clinical decision support system; Renal insufficiency; Drug prescribing; Chronic kidney disease
6.  Patients’ and carers’ experiences of interacting with home haemodialysis technology: implications for quality and safety 
BMC Nephrology  2014;15(1):195.
Background
Little is known about patients’ and carers’ experiences of interacting with home haemodialysis (HHD) technology, in terms of user experience, how the design of the technology supports safety and fits with home use, and how the broader context of service provision impacts on patients’ use of the technology.
Methods
Data were gathered through ethnographic observations and interviews with 19 patients and their carers associated with four different hospitals in the UK, using five different HHD machines. All patients were managing their condition successfully on HHD. Data were analysed qualitatively, focusing on themes of how individuals used the machines and how they managed their own safety.
Results
Findings are organised by three themes: learning to use the technology, usability of the technology, and managing safety during dialysis. Home patients want to live their lives fully, and value the freedom and autonomy that HHD gives them; they adapt use of the technology to their lives and their home context. They also consider the machines to be safe; nevertheless, most participants reported feeling scared and having to learn through mistakes in the early months of dialysing at home. Home care nurses and technicians provide invaluable support. Although participants reported on strategies for anticipating problems and keeping safe, perceived limitations of the technology and of the broader system of care led some to trade off safety against immediate quality of life.
Conclusions
Enhancing the quality and safety of the patient experience in HHD involves designing technology and the broader system of care to take account of how individuals manage their dialysis in the home. Possible design improvements to enhance the quality and safety of the patient experience include features to help patients manage their dialysis (e.g. providing timely reminders of next steps) and features to support communication between families and professionals (e.g. through remote monitoring).
doi:10.1186/1471-2369-15-195
PMCID: PMC4268796  PMID: 25495826
Home haemodialysis; Human factors; Medical device design; Patient safety; Patient satisfaction; User-computer interface
7.  Perceived barriers and facilitators of using dietary modification for CKD prevention among African Americans of low socioeconomic status: a qualitative study 
BMC Nephrology  2014;15(1):194.
Background
Factors influencing the use of dietary interventions for modification of CKD risk among African Americans have not been well-explored. We assessed perceived barriers and facilitators of CKD prevention through dietary modifications among African Americans with low socioeconomic status (SES) and at high risk for CKD.
Methods
We conducted a qualitative study involving three 90 minute focus groups of low SES (limited education, unemployed, uninsured, or income < $25,000/year) African American residents of Baltimore, Maryland (N = 17), who were aged 18-60 years, with no known history of CKD and (1) a family history of end stage renal disease and (2) self-reported diabetes, hypertension, cardiovascular disease, HIV or obesity. A trained moderator asked a series of 21 closed and open-ended questions. Group sessions were recorded, transcribed, and two independent investigators reviewed transcripts to identify common themes.
Results
Participants’ mean (SD) age was 39.8 (12.4) years. Most (59%) were female and earned < $5,000/year (71%). One quarter (24%) had self-reported diabetes and over half had hypertension (53%). Few (12%) perceived their CKD risk as high. Perceived barriers to CKD prevention through dietary change included the expense and unavailability of healthy foods, family member preferences, convenience of unhealthy foods, and inability to break lifelong habits. They identified vouchers for healthy foods, family-based interventions, nutritional counseling and group gatherings for persons interested in making dietary changes as acceptable facilitators of dietary CKD prevention efforts.
Conclusions
Low SES African Americans at high risk for CKD had limited perception of their risk but they identified multiple barriers and potential facilitators of CKD prevention via dietary modifications which can inform future studies and public health interventions.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-194) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-194
PMCID: PMC4268853  PMID: 25481019
Renal; Diet; Disparities; Race; Chronic kidney disease
8.  Efficacy and safety of mycophenolate mofetil treatment in IgA nephropathy: a systematic review 
BMC Nephrology  2014;15(1):193.
Background
IgA nephropathy is the most common primary glomerular disease worldwide and also the most frequent cause of kidney failure. Mycophenolate mofetil (MMF) is a selective immunosuppressant widely used in many autoimmune diseases. However, the benefits and risks of MMF for the treatment of IgA nephropathy remain uncertain.
Methods
A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to assess the efficacy and safety of MMF in IgA nephropathy patients, using the statistical software Review Manager 5.1.
Results
Eight RCTs involving 357 patients were identified and included in this review. Overall, no statistical difference was found in the therapeutic effect of MMF treatment compared with other therapies. MMF had no significant effects on reducing proteinuria or protecting renal function. However, subgroup analysis indicated that relatively short-term therapy (<18 months) might be beneficial in IgA nephropathy patients while longer term MMF use conferred no advantage. There was also no statistical difference between MMF and control groups in the incidence of side effects. When compared with other immunosuppressants, MMF was considered superior to cyclophosphamide in terms of better therapeutic effects and fewer adverse reactions, but no difference was found between MMF and leflunomide.
Conclusions
Our current evidence indicates that a relatively short course of MMF may be beneficial in treating IgA nephropathy. However, high-quality RCTs with large sample size as well as a well-designed study to evaluate the long-term effects of MMF are needed to further evaluate the efficacy and safety of MMF in this disease.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-193) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-193
PMCID: PMC4267433  PMID: 25475967
IgA nephropathy; Mycophenolate mofetil; Immunosuppressant; Systematic review
9.  Low income, community poverty and risk of end stage renal disease 
BMC Nephrology  2014;15(1):192.
Background
The risk of end stage renal disease (ESRD) is increased among individuals with low income and in low income communities. However, few studies have examined the relation of both individual and community socioeconomic status (SES) with incident ESRD.
Methods
Among 23,314 U.S. adults in the population-based Reasons for Geographic and Racial Differences in Stroke study, we assessed participant differences across geospatially-linked categories of county poverty [outlier poverty, extremely high poverty, very high poverty, high poverty, neither (reference), high affluence and outlier affluence]. Multivariable Cox proportional hazards models were used to examine associations of annual household income and geospatially-linked county poverty measures with incident ESRD, while accounting for death as a competing event using the Fine and Gray method.
Results
There were 158 ESRD cases during follow-up. Incident ESRD rates were 178.8 per 100,000 person-years (105 py) in high poverty outlier counties and were 76.3 /105 py in affluent outlier counties, p trend = 0.06. In unadjusted competing risk models, persons residing in high poverty outlier counties had higher incidence of ESRD (which was not statistically significant) when compared to those persons residing in counties with neither high poverty nor affluence [hazard ratio (HR) 1.54, 95% Confidence Interval (CI) 0.75-3.20]. This association was markedly attenuated following adjustment for socio-demographic factors (age, sex, race, education, and income); HR 0.96, 95% CI 0.46-2.00. However, in the same adjusted model, income was independently associated with risk of ESRD [HR 3.75, 95% CI 1.62-8.64, comparing the < $20,000 income group to the > $75,000 group]. There were no statistically significant associations of county measures of poverty with incident ESRD, and no evidence of effect modification.
Conclusions
In contrast to annual family income, geospatially-linked measures of county poverty have little relation with risk of ESRD. Efforts to mitigate socioeconomic disparities in kidney disease may be best appropriated at the individual level.
doi:10.1186/1471-2369-15-192
PMCID: PMC4269852  PMID: 25471628
ESRD; Chronic kidney disease; Socioeconomic status; Disparity; Geospatial
10.  From dialysis to transplantation: a 5-year longitudinal study on self-reported quality of life 
BMC Nephrology  2014;15(1):191.
Background
Little is known how health related quality of life (HRQOL) change in the transition from dialysis to renal transplantation (RTX). Longitudinal data addressing the patient-related outcomes are scarce, and particularly data regarding kidney-specific HRQOL are lacking. Thus, the aim of the current study was to assess HRQOL in patients followed from dialysis to RTX. Furthermore, to compare HRQOL in RTX patients and the general population.
Methods
In a prospective study, HRQOL was measured in a cohort of 110 patients (median age 53.5 (IQR 39–62) years, GFR 54 (45–72) ml/min/1.73 m2) in dialysis and after RTX using the self-administered Kidney Disease and Quality of Life Short Form version 1.3 (KDQOL-SF). Generic HRQOL in the RTX patients was compared to that of the general population (n = 5903) using the SF-36. Clinical important change after RTX was defined as difference in HRQOL of SD/2.
Results
Follow-up time was 55 (IQR 50–59) months, and time after RTX was 41 (34–51) months. Four of nine domains in kidney-specific HRQOL improved after RTX, i.e. burden of kidney disease, effect of kidney disease, symptoms and work status. In SF-36, general health, vitality, social function and role physical improved after RTX, but none of the domains improved sufficiently to be regarded as clinically relevant change. There were highly significant differences in HRQOL between RTX patients and the general population after adjustment for age and gender for all items of SF-36 except for bodily pain and mental health.
Conclusions
HRQOL improved in the transition from dialysis to transplantation, but clinical relevant change was only obtained in the kidney specific domains. HRQOL was perceived considerably poorer in RTX patients than in the general population. Our observations point to the need of improving HRQOL even after RTX, and should encourage further longitudinal research and clinical attention during treatment shift.
doi:10.1186/1471-2369-15-191
PMCID: PMC4258806  PMID: 25465066
Dialysis; Kidney transplantation; HRQOL; KDQOL-SF; Longitudinal; Clinical relevant change
11.  Serum sclerostin is an independent predictor of mortality in hemodialysis patients 
BMC Nephrology  2014;15(1):190.
Background
Sclerostin (Scl) has recently emerged as a novel marker of bone remodeling and vascular calcification. However, whether high circulating Scl is also a risk factor for death is not well established. The purpose of this study was to test whether serum Scl would be associated with mortality.
Methods
we measured serum Scl in a hemodialysis patients’ cohort, which was followed during a ten-year period. Competing risk regression models were applied, as during the follow-up, patients were exposed to both events kidney transplant and death.
Results
Ninety-one patients aged 42.3 ± 18.8 years (55% of male gender, 15% of diabetes) were included. During the follow-up, 32 patients underwent kidney transplant and 26 patients died. Non-survivals presented higher FGF23, higher Scl and lower creatinine. There was an association between all-cause mortality and higher Scl (HR = 2.2), higher age (HR = 1.04) and presence of diabetes (HR = 2.27), by competing risk analyses. Even including potential markers of mortality, as creatinine, FGF 23, and gender, Scl, age and diabetes remained significantly related to higher mortality.
Conclusion
Serum Scl is an independent predictor of mortality in dialysis patients. However, whether clinical interventions to modulate Scl would be able to improve these patients survival needs to be determined.
doi:10.1186/1471-2369-15-190
PMCID: PMC4265422  PMID: 25465028
Sclerostin; Chronic renal failure; CKD-MBD; Hemodialysis; Mortality risk
12.  Association between ratio of measured extracellular volume to expected body fluid volume and renal outcomes in patients with chronic kidney disease: a retrospective single-center cohort study 
BMC Nephrology  2014;15(1):189.
Background
Excess extracellular volume is a major clinical problem in patients with chronic kidney disease (CKD). However, whether the extracellular volume status is associated with disease progression is unclear. We investigated the association between the extracellular volume status and renal outcomes.
Methods
We performed a retrospective cohort study of 149 patients with CKD who underwent bioelectrical impedance analysis (BIA) from 2005 to 2009. Patients were categorized according to tertiles of extracellular volume status. The extracellular volume status was assessed by examining the ratio of extracellular water measured by BIA (ECWBIA) to the total body water calculated using the Watson formula (TBWWatson). The main outcomes were adverse renal outcomes as defined by a decline of ≥50% from the baseline glomerular filtration rate or initiation of renal replacement therapy.
Results
A higher %ECWBIA/TBWWatson ratio tended to be associated with older age, male sex, diabetes mellitus, resistant hypertension, lower renal function, lower serum albumin levels, higher proteinuria levels, and a higher frequency of furosemide use. In the multivariate analysis, proteinuria remained independently associated with the %ECWBIA/TBWWatson ratio. Both the intracellular and extracellular water volumes decreased with age (correlation between ICW and age, r = -0.30, P < 0.001; correlation between ECW and age, r = -0.17, P = 0.03). Consequently, the %ECWBIA in the body fluid composition increased with age. During a median follow-up of 4.9 years, patients in the highest tertile of the %ECWBIA/TBWWatson ratio were at greater risk of adverse renal outcomes (16.6 per 100.0 patient years) than were those in the lowest tertile (8.1 per 100.0 patient years) or second tertile (5.6 per 100.0 patient years) (log-rank P = 0.005). After adjustment for covariates, the %ECWBIA/TBWWatson ratio was significantly associated with adverse renal outcomes (hazard ratio, 1.21; 95 % confidence interval, 1.10–1.34; P < 0.001).
Conclusions
The ECWBIA/TBWWatson ratio was independently associated with adverse renal outcomes. Proteinuria was independently associated with the extracellular volume status. The balance between ICW and ECW changes with age in that the percentage of ECW content in the body fluid composition increases. Elderly patients with CKD may thus be susceptible to volume overload.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-189) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-189
PMCID: PMC4268815  PMID: 25435421
Chronic kidney disease; Extracellular volume excess; Kidney disease progression
13.  Kidney function as an underestimated factor for reduced health related quality of life in patients with Fabry disease 
BMC Nephrology  2014;15(1):188.
Background
Impairments of health related quality of life (HRQoL) are frequently observed in Fabry disease (FD) and are known to be related to neuropathic pain and cardiovascular events. This study aimed to explore the role of chronic kidney disease (CKD) in a large cohort of patients with FD.
Methods
In 96 patients (53% female; age 40 ± 12 yrs) with genetically proven FD, HRQoL was assessed by the Medical Outcomes Study (SF-36) questionnaire. All patients were naïve to enzyme replacement therapy. Three categories for kidney dysfunction were chosen, eGFR ≥/<60 ml/min/1.73 m2 or need of renal replacement therapy (RRT). Minor (e.g. arrhythmia, angina pectoris, etc.) and major (e.g. myocardial infarction, coronary artery bypass, stroke or implantable cardioverter-defibrillator) vascular events as well as pain and pain therapy were considered in linear regression analyses with the dimensions of HRQoL.
Results
Ten patients (10%) had impaired kidney function and a further nine were on RRT (9.4%). Kidney function and pain emerged as the main factors associated with lower scores on the SF 36, in particular on physical components (PCS beta-coefficients for CKD −6.2, for RRT −11.8, for pain −9.1, p < 0.05, respectively), while controlling for gender, vascular event and pain-therapy. Relationships were found for mental aspects of HRQoL. Age and history of vascular events were not related to HRQoL.
Conclusion
Cardiovascular events and pain are important factors related to HRQoL, social functioning and depression. Our study highlights impaired chronic kidney disease, in particular after initiation of RRT, as a strong determinant of reduced HRQoL in FD.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-188) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-188
PMCID: PMC4280765  PMID: 25432518
Quality of life; SF-36; Chronic kidney disease; Fabry disease
14.  The impact of comorbidity on survival after hemorrhagic stroke among dialysis patients: a nationwide population-based study 
BMC Nephrology  2014;15(1):186.
Background
This study was aimed at determining the outcome and examining the association between comorbidities and mortality after intracerebral hemorrhage in chronic dialysis patients.
Methods
We used the Taiwan National Health Insurance Research Database and enrolled patients who underwent maintenance dialysis between 2000 and 2007. Annual incidence of intracerebral hemorrhage in patients receiving dialysis from 2000 to 2007 was determined. To identify predictors of hemorrhagic stroke, we used logistic regression model to estimate the relative ratio of factors for intracerebral hemorrhage in the most recent cohort (2007). The cumulative survival rate and comorbid conditions associated with mortality after intracerebral hemorrhage among all dialysis patients between 2000 and 2007 was calculated using the Kaplan-Meier method and Cox regression analysis.
Results
We identified 57,261 patients on maintenance dialysis in the cohort of 2007, and 340 patients had history of intracerebral hemorrhage among them. Hypertension was the most common comorbidity of dialysis patients. The incidence rate of intracerebral hemorrhage among dialysis patients was about 0.6%. Adjusted logistic regression model showed that male gender, middle age (45–64 years), hypertension, and previous history of stroke were the independent predictors for the occurrence of intracerebral hemorrhage among chronic dialysis patients. 1,939 dialysis patients with development of intracerebral hemorrhage in the analysis period from 2000 to 2007 were identified. In-hospital mortality was high (36.15%) following intracerebral hemorrhage. They were followed up after intracerebral hemorrhage for a mean time of 41.56 months. Adjusted Cox regression analyses demonstrated that the factors independently associated with mortality after intracerebral hemorrhage among dialysis patients included diabetes mellitus, malignancy and a history of prior stroke.
Conclusions
Dialysis patients who have history of prior stroke, diabetes and malignancy have worse survival than patients without these comorbidities. Attention must focus on providing optimal medical care after hemorrhagic stroke for these target groups to reduce mortality.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-186) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-186
PMCID: PMC4256891  PMID: 25427630
Intracerebral hemorrhage; Dialysis; Comorbidity; Mortality
15.  Presence of early CKD-related metabolic complications predict progression of stage 3 CKD: a case-controlled study 
BMC Nephrology  2014;15(1):187.
Background
Only a subset of patients who enter stage 3 chronic kidney disease (CKD) progress to stage 4. Identifying which patients entering stage 3 are most likely to progress could improve outcomes, by allowing more appropriate referrals for specialist care, and spare those unlikely to progress the adverse effects and costliness of an unnecessarily aggressive approach. We hypothesized that compared to non-progressors, patients who enter stage 3 CKD and ultimately progress have experienced greater loss of renal function, manifested by impairment of metabolic function (anemia, worsening acidosis and mineral abnormalities), than is reflected in the eGFR at entry to stage 3. The purpose of this case-controlled study was to design a prediction model for CKD progression using laboratory values reflecting metabolic status.
Methods
Using data extracted from the electronic health record (EHR), two cohorts of patients in stage 3 were identified: progressors (eGFR declined >3 ml/min/1.73m2/year; n = 117) and non-progressors (eGFR declined <1 ml/min/1.73m2; n = 364). Initial laboratory values recorded a year before to a year after the time of entry to stage 3, reflecting metabolic complications (hemoglobin, bicarbonate, calcium, phosphorous, and albumin) were obtained. Average values in progressors and non-progressors were compared. Classification algorithms (Naïve Bayes and Logistic Regression) were used to develop prediction models of progression based on the initial lab data.
Results
At the entry to stage 3 CKD, hemoglobin, bicarbonate, calcium, and albumin values were significantly lower and phosphate values significantly higher in progressors compared to non-progressors even though initial eGFR values were similar. The differences were sufficiently large that a prediction model of progression could be developed based on these values. Post-test probability of progression in patients classified as progressors or non-progressors were 81% (73% − 86%) and 17% (13% − 23%), respectively.
Conclusions
Our studies demonstrate that patients who enter stage 3 and ultimately progress to stage 4 manifest a greater degree of metabolic complications than those who remain stable at the onset of stage 3 when eGFR values are equivalent. Lab values (hemoglobin, bicarbonate, phosphorous, calcium and albumin) are sufficiently different between the two cohorts that a reasonably accurate predictive model can be developed.
doi:10.1186/1471-2369-15-187
PMCID: PMC4258953  PMID: 25431293
16.  Prevalence and variation of Chronic Kidney Disease in the Irish health system: initial findings from the National Kidney Disease Surveillance Programme 
BMC Nephrology  2014;15(1):185.
Background
Chronic Kidney Disease (CKD) is a major non-communicable chronic disease that is associated with adverse clinical and economic outcomes. Passive surveillance systems are likely to improve efforts for prevention of chronic kidney disease (CKD) and inform national service planning. This study was conducted to determine the overall prevalence of CKD in the Irish health system, assess period trends and explore patterns of variation as part of a novel surveillance initiative.
Methods
We identified 207, 336 adult patients, age 18 and over, with serum creatinine measurements recorded from a provincial database between 2005-2011 in the Northwest of Ireland. Estimated glomerular filtration rates (eGFR) were determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation from standardized creatinine measurements and the presence of CKD was defined as eGFR <60 ml/min per 1.73 m2. Age and sex-specific prevalence estimates were determined for each group while generalized estimating equations (GEE) and multivariable logistic regression were used to explore associations using adjusted odds ratios (AOR) and 95% confidence intervals (95% CI).
Results
The prevalence of CKD in the health system was 11.8% (95% CI 11.8-12.1); 10.9% in men (10.7-11.1) and 12.6% in women (12.4-12.8). This corresponded to a detection rate of 4.5% (5.1% in women and 3.9% in men). The prevalence of CKD was significantly higher in women than in men (12.6% versus 10.9%, P < 0.001), older age groups, and among patients with a history of Acute Kidney Injury (AKI) than without (45.2% versus 10.7%, P < 0.0001). Multivariable analysis identified advancing age, female gender, location of medical supervision, county of residence, and AKI as significant determinants of prevalence.
Conclusion
The prevalence of CKD in the Irish health system is 11.8% corresponding to a detection rate of 4.5% in the general population. Demographic, geographic factors and acute kidney injury episodes are important determinants of disease burden. Passive surveillance of CKD is both feasible and desirable within the Irish health system, and offers huge opportunities for targeted prevention programmes and improved clinical outcomes.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-185) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-185
PMCID: PMC4258258  PMID: 25425510
CKD surveillance; Health system; Epidemiology; Risk factors
17.  Long-term risk of chronic kidney disease and mortality in children after acute kidney injury: a systematic review 
BMC Nephrology  2014;15(1):184.
Background
Acute kidney injury (AKI) is associated with significant short-term morbidity and mortality in children. However, the risk for long-term outcomes after AKI is largely unknown.
Methods
We performed a systematic review and meta-analysis to determine the cumulative incidence rate of proteinuria, hypertension, decline in glomerular filtration rate (GFR), and mortality after an episode of AKI. After screening 1934 published articles from 1985–2013, we included 10 cohort studies that reported long-term outcomes after AKI in children.
Results
A total of 346 patients were included in these studies with a mean follow-up of 6.5 years (range 2–16) after AKI. The studies were of variable quality and had differing definitions of AKI with five studies only including patients who required dialysis during an AKI episode. There was a substantial discrepancy in the outcomes across these studies, most likely due to study size, disparate outcome definitions, and methodological differences. In addition, there was no non-AKI comparator group in any of the published studies. The cumulative incidence rates for proteinuria, hypertension, abnormal GFR (<90 ml/min/1.73 m2), GFR < 60 ml/min/1.73 m2, end stage renal disease, and mortality per 100 patient-years were 3.1 (95% CI 2.1-4.1), 1.4 (0.9-2.1), 6.3 (5.1-7.5), 0.8 (0.4 -1.4), 0.9 (0.6-1.4), and 3.7 (2.8-4.5) respectively.
Conclusions
AKI appears to be associated with a high risk of long-term renal outcomes in children. These findings may have implications for care after an episode of AKI in children. Future prospective studies with appropriate non-AKI comparator groups will be required to confirm these results.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-184) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-184
PMCID: PMC4251927  PMID: 25416588
Pediatrics; Acute kidney injury; Progression; Proteinuria; Hypertension; Chronic kidney disease; Long-term survival
18.  Low serum calcium is associated with poor renal outcomes in chronic kidney disease stages 3–4 patients 
BMC Nephrology  2014;15(1):183.
Background
Mineral disorders are associated with adverse renal outcomes in chronic kidney disease (CKD) patients. Previous studies have associated hypercalcemia and hypocalcemia with mortality; however, the association between serum calcium and renal outcome is not well-described. Whether adding calcium besides phosphorus or in the form of calcium-phosphorus (Ca × P) product into the model of survival analysis could improve the prediction of renal outcomes is not known.
Methods
A prospective cohort of 2144 outpatients with CKD stages 3–4 was evaluated. Cox proportional hazard analysis was performed according to calcium quartiles.
Results
The mean calcium level was 9.2 ± 0.7 mg/dL. Low serum calcium (<9.0 mg/dL) was associated with increased risk of requiring renal replacement therapy (RRT) (hazards ratio [HR]:2.12 (95% CI: 1.49–3.02, P <0.05) and rapid renal function progression (odds ratio [OR]: 1.65 (95% CI: 1.19–2.27, P <0.05) compared with high serum calcium (>9.8 mg/dL). Adding calcium into the survival model increased the integrated discrimination improvement by 0.80% (0.12% – 1.91%) while calcium-phosphorus product did not improve risk prediction.
The combination of high serum phosphorus (>4.2 mg/dL) and low serum calcium (<9.1 mg/dL) was associated with the highest risk of RRT (HR:2.31 (95% CI: 1.45–3.67, P < 0.05).
Conclusion
Low serum calcium is associated with increased risk of RRT and rapid renal function progression in CKD stage 3–4 patients. The integration of serum calcium and phosphorus, but not calcium-phosphorus product should be considered in a predictive model of renal outcome.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-183) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-183
PMCID: PMC4255427  PMID: 25412875
Calcium; Chronic kidney disease; Renal replacement therapy
19.  Identification of people with autosomal dominant polycystic kidney disease using routine data: a cross sectional study 
BMC Nephrology  2014;15(1):182.
Background
Autosomal dominant polycystic kidney disease (ADPKD) causes progressive renal damage and is a leading cause of end-stage renal failure. With emerging therapies it is important to devise a method for early detection. We aimed to identify factors from routine clinical data which can be used to distinguish people with a high likelihood of having ADPKD in a primary health care setting.
Method
A cross-sectional study was undertaken using data from the Quality Intervention in Chronic Kidney Disease trial extracted from 127 primary care practices in England. The health records of 255 people with ADPKD were compared to the general population. Logistic regression was used to identify clinical features which distinguish ADPKD. These clinical features were used to stratify individual risk using a risk score tool.
Results
Renal impairment, proteinuria, haematuria, a diastolic blood pressure over 90 mmHg and multiple antihypertensive medications were more common in ADPKD than the general population and were used to build a regression model (area under the receiver operating characteristic curve; 0.79). Age, gender, haemoglobin and urinary tract infections were not associated with ADPKD. A risk score (range −3 to +10) of ≥0 gave a sensitivity of 70.2% and specificity 74.9% of for detection.
Conclusions
Stratification of ADPKD likelihood from routine data may be possible. This approach could be a valuable component of future screening programs although further longitudinal analyses are needed.
doi:10.1186/1471-2369-15-182
PMCID: PMC4258046  PMID: 25412767
Autosomal dominant polycystic kidney disease; Screening; Early detection; Primary care records
20.  Impact of partial nephrectomy on kidney function in patients with renal cell carcinoma 
BMC Nephrology  2014;15(1):181.
Background
This study aimed to compare the changes in kidney function and the association of tumor size and renal outcomes between patients with renal cell carcinoma (RCC) who underwent radical nephrectomy (RN) and those who underwent partial nephrectomy (PN).
Methods
A retrospective cohort study was conducted for 557 patients with an RCC of ≤7 cm in diameter and normal contralateral kidney function who underwent PN or RN. PN was performed for 218 (39%) patients. Renal outcomes included the incidence of acute kidney injury (AKI), new-onset chronic kidney disease (CKD), and a ≥25% decline in eGFR 1 year after surgery.
Results
Serial changes in eGFR were compared during the 3 years of follow-up. Postoperative eGFR was significantly lower in patients undergoing RN than in those undergoing PN. The incidence of AKI and new-onset CKD was significantly higher in patients after RN (70.1% vs. 24.3%, respectively; P <0.001) than after PN (55.7% vs. 6.2%, respectively; P <0.001). According to the multivariable logistic regression analysis, RN was an independent risk factor for a ≥25% decline in kidney function after 1 year regardless of the tumor size, even after adjusting for various covariates.
Conclusions
Compared to PN, RN for even a moderate sized RCC leads to an increased incidence of AKI and new-onset CKD, and is a significant risk factor for kidney function decline. Therefore, PN should be considered as the choice of surgical treatment for RCCs that are ≤7 cm in diameter in order to preserve renal function postoperatively.
doi:10.1186/1471-2369-15-181
PMCID: PMC4246517  PMID: 25410757
Kidney function; Nephrectomy; Renal cell carcinoma
21.  Renal function, uraemia and early arteriovenous fistula failure 
BMC Nephrology  2014;15(1):179.
Background
Guidance varies regarding the optimal timing of arteriovenous fistula (AVF) creation. The aim of this study was to evaluate the association between uraemia, haemodialysis and early AVF failure.
Methods
Immunoblotting and cell proliferation assays were performed on vascular smooth muscle cells (VSM) cells isolated from long saphenous vein samples to evaluate the cells’ ability to proliferate when stimulated with uraemic (post-dialysis) and hyperuraemic (pre-dialysis) serum. Clinical data was collected prospectively for 569 consecutive radiocephalic (RCF) and brachiocephalic (BCF) fistulae. The primary outcome was AVF failure at 6 weeks. Dialysis status (haemodialysis (HD); pre-dialysis (Pre-D)), eGFR and serum urea were evaluated to determine if they affected early AVF failure.
Results
Human VSM cells demonstrated increased capacity to proliferate when stimulated with hyperuraemic serum. There was no significant difference in early failure rate of either RCF or BCF depending on dialysis status (pre-D RCF 31.4% (n = 188); pre-D BCF 22.4% (n = 165); HD RCF 29.3% (n = 99); HD BCF 25.9% (n = 116); p = 0.34). There was no difference in mean eGFR between those patients with early AVF failure and those without (11.2+/-0.2 ml/min/1.73 m2 vs. 11.6+/-0.4 ml/min/1.73 m2; p = 0.47). Uraemia was associated with early AVF failure (serum urea: 35.0+/-0.7 mg/dl vs. 26.6+/-0.3 mg/dl (p < 0.001)).
Conclusions
We present the first in vivo evidence of an association between adverse early AVF outcomes and uraemia. This is supported mechanistically by in vitro work demonstrating a pro-mitogenic effect of hyperuraemic serum. We hypothesise that uraemia-driven upregulation of VSM cell proliferation at the site of surgical insult in contributes to higher early AVF failure rates.
doi:10.1186/1471-2369-15-179
PMCID: PMC4239391  PMID: 25403339
Arteriovenous fistula; Uraemia; Renal function; Maturation; Vascular smooth muscle cells
22.  TL1-A can engage death receptor-3 and activate NF-kappa B in endothelial cells 
BMC Nephrology  2014;15(1):178.
Background
Death receptors (DRs) play an important role in renal pathology. We have shown that DR3 is inducibly expressed on renal tubular epithelial cells in the setting of inflammatory injuries. In this study we investigate the expression of DR3 in renal endothelial cells and their response to TL1A, the only known ligand of DR3.
Methods
We did RT-PCR, flow cytometry and subcellular immunoblotting to examine the expression and function of DR3 in cells in vitro. We did organ culture of human and mouse tissue to examine expression and signal of DR3 in vivo.
Results
DR3 is expressed in some interstitial vascular endothelial cells (EC) in human kidney in situ; these EC also respond to its ligand TL1A by activating NF-κB. Very low levels of DR3 can be detected on the cell surface of cultured human umbilical vein (HUV) EC, which do not respond to TL1A. HUVEC transfected to overexpress DR3 become responsive to TL1A, assessed by IκBα degradation and E-selectin induction, indicating that the signaling components needed for DR3 responsiveness are expressed. TL1A induces NF-κB activation in EC in renal and cardiac tissue from wild type but not DR3 knock-out mice.
Conclusion
TL1A and DR3 activate NF-κB in vascular endothelial cells, and can be an important regulator of renal interstitial vascular injury.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-178) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-178
PMCID: PMC4239315  PMID: 25399326
Kidney; Endothelial cells; Death receptor; Inflammation
23.  Actual versus ideal body weight for acute kidney injury diagnosis and classification in critically Ill patients 
BMC Nephrology  2014;15(1):176.
Background
In the current acute kidney injury (AKI) definition, the urine output (UO) criterion does not specify which body weights (BW), i.e. actual (ABW) versus ideal (IBW), should be used to diagnose and stage AKI, leading to heterogeneity across research studies.
Methods
This is a single center, retrospective, observational study conducted at a tertiary referral hospital. All adult patients who were admitted to intensive care units (ICUs) at our institution for a minimum of 6 continuous hours between January and March 2010 and had a urinary catheter for hourly urine output monitoring were eligible for this study. Patients’ AKI stages, based on UO criterion, were assessed by calculating each milliliter of urine per kilogram per hour, using ABW versus IBW.
Results
A total of 493 ICU patients were included in the analysis. The median ABW and IBW were 82 (IQR 68-96) and 70 (IQR 60-77) kg, respectively. Using the IBW criterion, 154 patients (31.2%) were diagnosed with AKI, while 204 (41.4%) were diagnosed using the ABW measurement (P-value < .01). Patients who had AKI regardless of BW type had an adjusted odds ratio of 1.76 (95% CI 1.05-2.95) for 90-day mortality, whereas patients who had AKI according to ABW but not IBW had no significant increase in the risk of 90-day mortality, adjusted OR 0.76; (95% CI 0.25-1.91), compared to patients who had no AKI.
Conclusions
Using ABW to diagnose and stage AKI by UO criterion is more sensitive and less specific than IBW. Based on the application of the definition, different BW types could be utilized.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-176) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-176
PMCID: PMC4236495  PMID: 25398596
Acute kidney injury; Actual body weight; Ideal body weight; Urine output
24.  Association of physical function with predialysis blood pressure in patients on hemodialysis 
BMC Nephrology  2014;15(1):177.
Background
New information from various clinical settings suggests that tight blood pressure control may not reduce mortality and may be associated with more side effects.
Methods
We performed cross-sectional multivariable ordered logistic regression to examine the association between predialysis blood pressure and the short physical performance battery (SPPB) in a cohort of 749 prevalent hemodialysis patients in the San Francisco and Atlanta areas recruited from July 2009 to August 2011 to study the relationship between systolic blood pressure and objective measures of physical function. Mean blood pressure for three hemodialysis sessions was analyzed in the following categories: <110 mmHg, 110-129 mmHg (reference), 130-159 mmHg, and ≥160 mmHg. SPPB includes three components: timed repeated chair stands, timed 15-ft walk, and balance tests. SPPB was categorized into ordinal groups (≤6, 7-9, 10-12) based on prior literature.
Results
Patients with blood pressure 130-159 mmHg had lower odds (OR 0.57, 95% CI 0.35-0.93) of scoring in a lower SPPB category than those whose blood pressure was between 110 and 129 mmHg, while those with blood pressure ≥160 mmHg had 0.56 times odds (95% CI 0.33-0.94) of scoring in a lower category when compared with blood pressure 110-129 mmHg. When individual components were examined, blood pressure was significantly associated with chair stand (130-159 mmHg: OR 0.59, 95% CI 0.38-0.92) and gait speed (≥160 mmHg: OR 0.59, 95% CI 0.35-0.98). Blood pressure ≥160 mmHg was not associated with substantially higher SPPB score compared with 130-159 mmHg.
Conclusions
Patients with systolic blood pressure at or above 130 mmHg had better physical performance than patients with lower blood pressure in the normotensive range. The risk-benefit tradeoff of aggressive blood pressure control, particularly in low-functioning patients, should be reexamined.
doi:10.1186/1471-2369-15-177
PMCID: PMC4247716  PMID: 25399253
Blood pressure; End-stage renal disease; Physical function
25.  Whole exome sequencing reveals novel COL4A3 and COL4A4 mutations and resolves diagnosis in Chinese families with kidney disease 
BMC Nephrology  2014;15(1):175.
Background
Collagen IV-related nephropathies, including thin basement membrane nephropathy and Alport Syndrome (AS), are caused by defects in the genes COL4A3, COL4A4 and COL4A5. Diagnosis of these conditions can be hindered by variable penetrance and the presence of non-specific clinical or pathological features.
Methods
Three families with unexplained inherited kidney disease were recruited from Shanghai, China. Whole exome sequencing (WES) was performed in the index case from each family and co-segregation of candidate pathogenic mutations was tested by Sanger sequencing.
Results
We identified COL4A4 missense variants [c.G2636A (p.Gly879Glu) and c.C4715T (p.Pro1572Leu)] in the 21-year-old male proband from family 1, who had been diagnosed with mesangial proliferative nephropathy at age 14. COL4A4 c.G2636A, a novel variant, co-segregated with renal disease among maternal relatives. COL4A4 c.C4715T has previously been associated with autosomal recessive AS and was inherited from his clinically unaffected father. In family 2, a novel COL4A3 missense mutation c.G2290A (p.Gly997Glu) was identified in a 45-year-old male diagnosed with focal segmental glomerulosclerosis and was present in all his affected family members, who exhibited disease ranging from isolated microscopic hematuria to end stage renal disease (ESRD). In family 3, ESRD occurred in both male and females who were found to harbor a known AS-causing COL4A5 donor splice site mutation (c.687 + 1G > A). None of these variants were detected among 100 healthy Chinese individuals.
Conclusion
WES identified 2 novel and 2 known pathogenic COL4A3/COL4A4/COL4A5 mutations in 3 families with previously unexplained inherited kidney disease. These findings highlight the clinical range of collagen IV-related nephropathies and resolved diagnostic confusion arising from atypical or incomplete clinical/histological findings, allowing appropriate counselling and treatment advice to be given.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-175) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2369-15-175
PMCID: PMC4233041  PMID: 25381091
Collagen IV-related nephropathies; Whole exome sequencing; Novel mutation; Misdiagnosis

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