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1.  Effects of thyroid hormone analogue and a leukotrienes pathway-blocker on renal ischemia/reperfusion injury in mice 
BMC Nephrology  2011;12:70.
Background
Acute renal failure (ARF) is an important clinical problem with a high mortality and morbidity. One of the primary causes of ARF is ischemia/reperfusion (I/R). Inflammatory process and oxidative stress are thought to be the major mechanisms causing I/R. MK-886 is a potent inhibitor of leukotrienes biosynthesis which may have anti-inflammatory and antioxidant effects through inhibition of polymorphonuclear leukocytes (PMNs) infiltration into renal tissues. 3, 5-diiodothyropropionic acid (DITPA) have evidences of improving effects on I/R in heart through modulation of cellular signaling in response to ischemic stress. The objective of present study was to assess the effects of MK-886 and DITPA on renal I/R injury.
Methods
A total of 24 Adult males of Swiss albino mice were randomized to four groups: I/R group (n = 6), mice underwent 30 minute bilateral renal ischemia and 48 hr reperfusion. Sham group (n = 6), mice underwent same anesthetic and surgical procedures except for ischemia induction. MK-886-treated group: (n = 6), I/R + MK-886 (6 mg/kg) by intraperitoneal injection. DITPA-treated group: (n = 6), I/R + DITPA (3.75 mg/kg) by intraperitoneal injection.
After the end of reperfusion phase mice were sacrificed, blood samples were collected directly from the heart for determination of serum TNF-a, IL-6, urea and Creatinine. Both kidney were excised, the right one homogenized for oxidative stress parameters (MDA and GSH) measurements and the left kidney fixed in formalin for histological examination.
Results
Serum TNF-α, IL-6, urea and Creatinine, kidney MDA levels and scores of histopathological changes were significantly (P < 0.05) elevated in I/R group as compared with that of sham group. Kidney GSH level was significantly (P < 0.05) decreased in I/R group as compared with that of sham group. MK-886 treated group has significantly (P < 0.05) lowered levels of all study parameters except for GSH level which was significantly (P < 0.05) higher as compared with that of I/R group. DITPA caused non-significant (P > 0.05) changes in levels of all study parameters as compared with that of I/R group.
Conclusion
The results of the present study show that MK-886 significantly ameliorated kidney damage that resulted from I/R. For DITPA, as its administration might not be successful, administration using a different protocol may give different effects on I/R.
doi:10.1186/1471-2369-12-70
PMCID: PMC3259032  PMID: 22196041
2.  Survival in dialysis patients is not different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition 
BMC Nephrology  2011;12:69.
Background
On dialysis, survival among patients with diabetes mellitus is inferior to survival of non-diabetic patients. We hypothesized that patients with diabetes as primary renal disease have worse survival compared to patients with diabetes as a co-morbid condition and aimed to compare all-cause mortality between these patient groups.
Methods
Data were collected from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a multicenter, prospective cohort study in which new patients with end stage renal disease (ESRD) were monitored until transplantation or death. Patients with diabetes as primary cause of ESRD were compared with patients with diabetes as co-morbid condition and both of these patient groups were compared to patients without diabetes. Analysis was performed using Kaplan-Meier and Cox regression.
Results
Fifteen % of the patients had diabetic nephropathy as primary renal disease (N = 281); 6% had diabetes as co-morbid condition (N = 107) and 79% had no diabetes (N = 1465). During follow-up 42% of patients (N = 787) died. Compared to non-diabetic patients, mortality risk was increased for both patients with diabetes as primary renal disease HR: 1.9 (95% CI 1.6, 2.3) and for patients with diabetes as co-morbid condition HR: 1.7 (95% CI 1.3, 2.2). Mortality was not significantly higher in patients with diabetes as primary renal disease compared to patients with diabetes as co-morbid condition (HR 1.06; 95% CI 0.79, 1.43).
Conclusions
This study in patients with ESRD showed no survival difference between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition. Both conditions were associated with increased mortality risk compared to non-diabetic patients.
doi:10.1186/1471-2369-12-69
PMCID: PMC3259092  PMID: 22182634
3.  The clinical and imaging presentation of acute "non complicated" pyelonephritis: A new profile for an ancient disease 
BMC Nephrology  2011;12:68.
Background
Acute pyelonephritis (APN) is differently defined according to imaging or clinical criteria. In adults information on the relationship between imaging and clinical data is lacking.
Our study was aimed at analysing the relationship between the clinical and imaging presentation of APN, defined according to imaging criteria (parenchymal involvement at MR or CT scan).
Methods
All consecutive patients hospitalized for "non-complicated" APN were considered (June 2005-December 2009). Clinical, biochemical and imaging data at hospitalization were analyzed by univariate and logistic regression analysis.
Results
There were 119 patients, all females, median age 32 years (15-72). At hospitalization, inflammatory markers were elevated (CRP median: 12.1 mg/dL, normal < 0.8). Incomplete presentations were frequent: fever was absent in 6.7%, pain in 17.8%, lower urinary tract symptoms in 52.9%. At CT or MR scan the lesions were bilateral in 12.6%, multiple in 79.8%; abscesses were present in 39.5%. Renal scars were found in 15.1%. Positive cultures were correlated with multiple foci (multivariate OR 4.2; CI 1.139-15.515). No other sign/symptom discriminated between small lesions, abscesses or multifocal involvement.
Conclusions
APN is a protean disease. In the absence of strict correlation with clinical or biochemical markers, imaging studies are required to assess the severity of kidney involvement.
doi:10.1186/1471-2369-12-68
PMCID: PMC3268718  PMID: 22171968
Acute pyelonephritis; upper urinary tract infections; computed tomography; nuclear magnetic resonance; kidney scars; epidemiology
4.  Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors 
BMC Nephrology  2011;12:67.
Background
High-dose erythropoiesis-stimulating agents (ESA) for anemia of chronic kidney disease (CKD) have been associated with adverse clinical outcomes and do not always improve erythropoiesis. We hypothesized that high-dose ESA requirement would be associated with elevated inflammatory biomarkers, decreased adipokines, and increased circulating, endogenous soluble erythropoietin receptors (sEpoR).
Methods
A cross-sectional cohort of anemic 32 CKD participants receiving ESA were enrolled at a single center and cytokine profiles, adipokines, and sEpoR were compared between participants stratified by ESA dose requirement (usual-dose darbepoetin-α (< 1 μg/kg/week) and high-dose (≥1 μg/kg/week)).
Results
Baseline characteristics were similar between groups; however, hemoglobin was lower among participants on high-dose (1.4 μg/kg/week) vs usual-dose (0.5 μg/kg/week) ESA.
In adjusted analyses, high-dose ESA was associated with an increased odds for elevations in c-reactive protein and interleukin-6 (p < 0.05 for both). There was no correlation between high-dose ESA and adipokines. Higher ESA dose correlated with higher levels of sEpoR (rs = 0.39, p = 0.03). In adjusted analyses, higher ESA dose (per μcg/kg/week) was associated with a 53% greater odds of sEpoR being above the median (p < 0.05).
Conclusion
High-dose ESA requirement among anemic CKD participants was associated with elevated inflammatory biomarkers and higher levels of circulating sEpoR, an inhibitor of erythropoiesis. Further research confirming these findings is warranted.
Trial registration
Clinicaltrials.gov NCT00526747
doi:10.1186/1471-2369-12-67
PMCID: PMC3254065  PMID: 22152013
5.  International practice patterns and factors associated with non-conventional hemodialysis utilization 
BMC Nephrology  2011;12:66.
Background
The purpose of our study was to determine characteristics that influence the utilization of non-conventional hemodialysis (NCHD) therapies and its subtypes (nocturnal (NHD), short daily (SDHD), long conventional (LCHD) and conventional hemodialysis (CHD) as well as provider attitudes regarding the evidence for NCHD use.
Methods
An international cohort of subscribers of a nephrology education website http://www.nephrologynow.com was invited to participate in an online survey. Non-conventional hemodialysis was defined as any forms of hemodialysis delivered > 3 treatments per week and/or > 4 hours per session. NHD and SDHD included both home and in-centre. Respondents were categorized as CHD if their centre only offered conventional thrice weekly hemodialysis. Variables associated with NCHD and its subtypes were determined using multivariate logistic regression analysis. The survey assessed multiple domains regarding NCHD including reasons for initiating and discontinuing, for not offering and attitudes regarding evidence.
Results
544 surveys were completed leading to a 15.6% response rate. The final cohort was limited to 311 physicians. Dialysis modalities utilized among the respondents were as follows: NCHD194 (62.4%), NHD 83 (26.7%), SDHD 107 (34.4%), LCHD 81 (26%) and CHD 117 (37.6%). The geographic regions of participants were as follows: 11.9% Canada, 26.7% USA, 21.5% Europe, 6.1% Australia/New Zealand, 10% Africa/Middle East, 10.9% Asia and 12.9% South America. Variables associated with NCHD utilization included NCHD training (OR 2.47 CI 1.25-4.16), government physician reimbursement (OR 2.66, CI 1.11-6.40), practicing at an academic centre (OR 2.28 CI 1.25-4.16), higher national health care expenditure and number of ESRD patients per centre. Hemodialysis providers with patients on NCHD were significantly more likely to agree with the statements that NCHD improves quality of life, improves nutritional status, reduces EPO requirements and is cost effective. The most common reasons to initiate NCHD were driven by patient preference and the desire to improve volume control and global health outcomes.
Conclusion
Physician attitudes toward the evidence for NCHD differ significantly between NCHD providers and conventional HD providers. Interventions and health policy targeting these areas along with increased physician education and training in NCHD modalities may be effective in increasing its utilization.
doi:10.1186/1471-2369-12-66
PMCID: PMC3241205  PMID: 22142369
6.  Predicting hospital cost in CKD patients through blood chemistry values 
BMC Nephrology  2011;12:65.
Background
Controversy exists in predicting costly hospitalization in patients with chronic kidney disease and co-morbid conditions. We therefore tested associations between serum chemistry values and the occurrence of in-patient hospital costs over a thirteen month study period. Secondarily, we derived a linear combination of variables to estimate probability of such occurrences in any patient.
Method
We calculated parsimonious values for select variables associated with in-patient hospitalization and compared sensitivity and specificity of these models to ordinal staging of renal disease.
Data from 1104 de-identified patients which included 18 blood chemistry observations along with complete claims data for all medical expenses.
We employed multivariable logistic regression for serum chemistry values significantly associated with in-patient hospital costs exceeding $3,000 in any single month and contrasted those results to other models by ROC area curves.
Results
The linear combination of weighted Z scores for parathyroid hormone, phosphorus, and albumin correlated with in-patient hospital care at p < 0.005. ROC curves derived from weighted variables of age, eGFR, hemoglobin, albumin, creatinine, and alanine aminotransferase demonstrated significance over models based on non-weighted Z scores for those same variables or CKD stage alone. In contrast, the linear combination of weighted PTH, PO4 and albumin demonstrated better prediction, but not significance over non-weighted Z scores for PTH alone.
Conclusion
Further study is justified to explore indices that predict costly hospitalization. Such metrics could assist Accountable Care Organizations in evaluating risk adjusted compensation for providers.
doi:10.1186/1471-2369-12-65
PMCID: PMC3377913  PMID: 22133421
7.  Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function 
BMC Nephrology  2011;12:64.
Background
Glomerular damage in IgA nephropathy (IgAN) is mediated by complement activation via the alternative and lectin pathways. Therefore, we focused on molecules stabilizing and regulating the alternative pathway C3 convertase in urine which might be associated with IgAN pathogenesis.
Methods
Membrane attack complex (MAC), properdin (P), factor H (fH) and Complement receptor type 1 (CR1) were quantified in urine samples from 71 patients with IgAN and 72 healthy controls. Glomerular deposition of C5, fH and P was assessed using an immunofluorescence technique and correlated with histological severity of IgAN and clinical parameters. Fibrotic changes and glomerular sclerosis were evaluated in renal biopsy specimens.
Results
Immunofluorescence studies revealed glomerular depositions of C5, fH and P in patients with IgAN. Urinary MAC, fH and P levels in IgAN patients were significantly higher than those in healthy controls (p < 0.001), but CR1 was significantly lower than that in healthy controls (p < 0.001). Urinary MAC and fH levels were positively correlated with serum creatinine (sCr), urinary N-acetyl-β-D-glucosaminidase (u-NAG), urinary β2 microglobulin (u-Bm), urinary protein (p < 0.001), interstitial fibrosis (MAC: p < 0.01, fH: p < 0.05) and the percentage of global glomerular sclerosis (p < 0.01). Urinary P was positively correlated with u-NAG, u-Bm, and urinary protein (p < 0.01).
Conclusions
Complement activation occurs in the urinary space in IgAN and the measurement of levels of MAC and fH in the urine could be a useful indicator of renal injury in patients with IgAN.
doi:10.1186/1471-2369-12-64
PMCID: PMC3283454  PMID: 22111871
8.  Duration of temporary catheter use for hemodialysis: an observational, prospective evaluation of renal units in Brazil 
BMC Nephrology  2011;12:63.
Background
For chronic hemodialysis, the ideal permanent vascular access is the arteriovenous fistula (AVF). Temporary catheters should be reserved for acute dialysis needs. The AVF is associated with lower infection rates, better clinical results, and a higher quality of life and survival when compared to temporary catheters. In Brazil, the proportion of patients with temporary catheters for more than 3 months from the beginning of therapy is used as an evaluation of the quality of renal units. The aim of this study is to evaluate factors associated with the time between the beginning of hemodialysis with temporary catheters and the placement of the first arteriovenous fistula in Brazil.
Methods
This is an observational, prospective non-concurrent study using national administrative registries of all patients financed by the public health system who began renal replacement therapy (RRT) between 2000 and 2004 in Brazil. Incident patients were eligible who had hemodialysis for the first time. Patients were excluded who: had hemodialysis reportedly started after the date of death (inconsistent database); were younger than 18 years old; had HIV; had no record of the first dialysis unit; and were dialyzed in units with less than twenty patients. To evaluate individual and renal unit factors associated with the event of interest, the frailty model was used (N = 55,589).
Results
Among the 23,824 patients (42.9%) who underwent fistula placement in the period of the study, 18.2% maintained the temporary catheter for more than three months until the fistula creation. The analysis identified five statistically significant factors associated with longer time until first fistula: higher age (Hazard-risk - HR 0.99, 95% CI 0.99-1.00); having hypertension and cardiovascular diseases (HR 0.94, 95% CI 0.9-0.98) as the cause of chronic renal disease; residing in capitals cities (HR 0.92, 95% CI 0.9-0.95) and certain regions in Brazil - South (HR 0.83, 95% CI 0.8-0.87), Midwest (HR 0.88, 95% CI 0.83-0.94), Northeast (HR 0.91, 95% CI 0.88-0.94), or North (HR 0.88, 95% CI 0.83-0.94) and the type of renal unit (public or private).
Conclusion
Monitoring the provision of arteriovenous fistulas in renal units could improve the care given to patients with end stage renal disease.
doi:10.1186/1471-2369-12-63
PMCID: PMC3227575  PMID: 22093280
9.  Ocular fundus pathology and chronic kidney disease in a Chinese population 
BMC Nephrology  2011;12:62.
Background
Previous study indicated a high prevalence of ocular fundus pathology among patients with chronic kidney disease (CKD), while the relationship between them has never been explored in a Chinese Population.
Methods
This cross-sectional study included 9 670 participants enrolled in a medical screening program. Ocular fundus examination was performed by ophthalmologists using ophthalmoscopes. The presence of eGFR less than 60 mL/min/1.73 m2 and/or proteinuria was defined as CKD.
Results
Compared to participants without CKD, participants with CKD had higher prevalence of retinopathy (28.5% vs. 16.3%, P < 0.001), glaucoma suspect (3.1% vs. 1.8%, P = 0.004), age-related macular degeneration (1.7% vs. 0.9%, P = 0.01) and overall eye pathology (32.0% vs. 19.4%, P < 0.001). After adjusting for potential confounders, the odds ratio of proteinuria for overall eye pathology and retinopathy was 1.29 (95% confidence interval [CI] 1.07-1.55) and 1.37 (95% CI 1.12-1.67), respectively. The results were robust after excluding participants with hypertension or with diabetes.
Conclusions
Ocular fundus pathology is common among Chinese patients with CKD. Regular eye exam among persons with proteinuria is warranted.
doi:10.1186/1471-2369-12-62
PMCID: PMC3240828  PMID: 22093232
10.  Ozonated autohemotherapy: protection of kidneys from ischemia in rats subjected to unilateral nephrectomy 
BMC Nephrology  2011;12:61.
Background
Ozonated autohemotherapy (OA) has been previously successfully used in the treatment of patients affected by peripheral occlusive arterial disease. OA consists of an intrafemoral reinfusion of autologous blood previously exposed to a mixture of oxygen/ozone (O2/O3). This study analyzes the effects of OA in protecting rat kidney from ischemia and ischemia/reperfusion damage.
Methods
We performed OA 30 min before the induction of 60 min renal ischemia or at the induction of 60 min postischemic reperfusion in rats subjected to unilateral nephrectomy. In addition, to evidence the possible protection induced by O2/O3 on endothelial functions, the present study analyzes the in vitro effects of O2/O3 on oxygen consumption by human umbilical vein endothelial cells (HUVEC).
Results
1) OA preserves rat kidney functions and architecture, as demonstrated by the improved levels of serum creatinine and blood urea nitrogen and by histology; 2) such protection does not correlate with the increase of plasmatic nitric oxide, but is compatible with a focal renal increase of renal βNADPH-diaphorase; 3) treatment of HUVEC with O2/O3 significantly increases both the rate of oxygen consumption and the mitochondrial activity assessed by confocal microscopy.
Conclusion
The preservation of the mitochondrial activity of endothelium could in vivo limit the endothelial dysfunction provoked by the Isc or Isc/R processes.
doi:10.1186/1471-2369-12-61
PMCID: PMC3261102  PMID: 22081953
11.  Evaluation of High Resolution Melting analysis as an alternate tool to screen for risk alleles associated with small kidneys in Indian newborns 
BMC Nephrology  2011;12:60.
Background
Single nucleotide polymorphisms (SNPs) are the most common forms of sequence variations in the human genome. They contribute to the human phenotypic spectrum and are associated with variations in response to pathogens, drugs and vaccines. Recently, SNPs in three human genes involved in kidney development (RET, PAX2 and ALDH1A2) have been reported to be associated with variation in renal size and function. These known SNPs could potentially be used in the clinic as markers for identifying babies who may have smaller kidneys and permit close follow up for early detection of hypertension and acquired renal dysfunction. The aim of this study was to evaluate the use of High Resolution Melting technique (HRM) as a tool for detecting the known SNPs in these three genes in comparison to sequencing which is the gold standard.
Methods
High resolution melting analysis was performed on 75 DNA samples that were previously sequenced for the known polymorphisms in RET (rs1800860), PAX2 (rs11190688) and ALDH1A2 (rs7169289) genes. The SNPs were G > A transitions in RET and PAX2 and A > G in ALDH1A2 gene. A blinded assessment was performed on these samples for evaluation of the HRM technique as compared to sequencing.
Results
Each variant had a unique melt curve profile that was reproducible. The shift in melting temperature (Tm) allowed visual discrimination between the homozygous alleles (major and minor) in all three genes. The shape of the melting curve as compared to the major allele homozygous curve allowed the identification of the heterozygotes in each of the three SNPs. For validation, HRM was performed on 25 samples for each of the three SNPs. The results were compared with the sequencing results and 100% correct identification of the samples was obtained for RET, PAX2, and ALDA1H2 gene.
Conclusion
High Resolution Melting analysis is a simple, rapid and cost effective technique that could be used in a large population to identify babies with the risk alleles. These high risk children could be followed up for early detection of hypertension and acquired renal dysfunction.
doi:10.1186/1471-2369-12-60
PMCID: PMC3219565  PMID: 22035350
12.  The relationships between exogenous and endogenous antioxidants with the lipid profile and oxidative damage in hemodialysis patients 
BMC Nephrology  2011;12:59.
Background
We sought to investigate the relationships among the plasma levels of carotenoids, tocopherols, endogenous antioxidants, oxidative damage and lipid profiles and their possible effects on the cardiovascular risk associated with hemodialysis (HD) patients.
Methods
The study groups were divided into HD and healthy subjects. Plasma carotenoid, tocopherol and malondialdehyde (MDA) levels, as well as erythrocyte reduced glutathione (GSH), were measured by HPLC. Blood antioxidant enzymes, kidney function biomarkers and the lipid profiles were analyzed by spectrophotometric methods.
Results
Plasma lycopene levels and blood glutathione peroxidase (GPx) activity were significantly decreased in HD patients compared with healthy subjects. Total cholesterol, low-density lipoprotein cholesterol (LDL-c), creatinine, urea, MDA, GSH, superoxide dismutase (SOD) and catalase (CAT) were significantly increased in HD (p < 0.05). Lycopene levels were correlated with MDA (r = -0.50; p < 0.01), LDL-c (r = -0.38; p = 0.01) levels, the LDL-c/HDL-c index (r = -0.33; p = 0.03) and GPx activity (r = 0.30; p = 0.03). Regression models showed that lycopene levels were correlated with LDL-c (β estimated = -31.59; p = 0.04), while gender was correlated with the TC/HDL-c index and triglycerides. Age did not present a correlation with the parameters evaluated. GPx activity was negatively correlated with MDA levels and with the LDL-c/HDL-c and CT/HDL-c indexes.
Conclusions
Lycopene may represent an additional factor that contributes to reduced lipid peroxidation and atherogenesis in hemodialysis patients.
doi:10.1186/1471-2369-12-59
PMCID: PMC3213013  PMID: 22029620
13.  Modulation of oxidative stress and microinflammatory status by colloids in refractory dialytic hypotension 
BMC Nephrology  2011;12:58.
Background
Intradialytic hypotension may adversely affect the outcome of chronic hemodialysis. Therapeutic albumin has powerful anti-oxidant and anti-inflammatory properties. We have recently shown that systematic colloid infusion during hemodialysis sessions improves hemodynamic parameters in most dialysis hypotension-prone patients unresponsive to usual of preventive measures.
We postulated that frequent hypotensive episodes may lead to a noxious inflammatory response mediated by oxidative stress induced by ischemia-reperfusion. The aim of this study was therefore to analyze the effect of 20% albumin and 4% gelatin infusions on oxidative stress and microinflammatory status in hypotension-prone patients unresponsive to usual preventive measures.
Methods
Prospective cross-over study (lasting 20 weeks) of routine infusion of 200 ml of 20% albumin versus 200 ml of 4% gelatin in 10 patients with refractory intradialytic hypotension. We analyzed the effect of 20% albumin and 4% gelatin on microinflammatory status, oxidative stress, serum nitrite and nitrate levels by analysis of variance.
Results
A significant decrease in serum ceruloplasmin and serum C3 was observed during the albumin period (p < 0.05, repeated measure ANOVA). A significant decrease in serum hydrogen peroxide was seen during albumin and gelatin administration (p < 0.01, repeated measure ANOVA) and a very large decrease in serum lipid peroxides was observed during the albumin period only (p < 0.01, Friedman test). Serum lactoferrin, serum proinflammatory cytokines and serum nitrite and nitrate levels remained stable during the different periods of this pilot trial.
Conclusions
We conclude that the improvement in microinflammatory status observed during colloid infusion in hypotension-prone dialysis patients may be related to a decrease in ischemia-reperfusion of noble organs, together with a specific reduction in oxidative stress by albumin.
Trial registration
ISRCTN 20957055
doi:10.1186/1471-2369-12-58
PMCID: PMC3231981  PMID: 22013952
dialytic hypotension; 4% gelatin; 20% hyperoncotic albumin; microinflammatory status; oxidative stress
14.  High Resolution Melt analysis for mutation screening in PKD1 and PKD2  
BMC Nephrology  2011;12:57.
Background
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder. It is characterized by focal development and progressive enlargement of renal cysts leading to end-stage renal disease. PKD1 and PKD2 have been implicated in ADPKD pathogenesis but genetic features and the size of PKD1 make genetic diagnosis tedious.
Methods
We aim to prove that high resolution melt analysis (HRM), a recent technique in molecular biology, can facilitate molecular diagnosis of ADPKD. We screened for mutations in PKD1 and PKD2 with HRM in 37 unrelated patients with ADPKD.
Results
We identified 440 sequence variants in the 37 patients. One hundred and thirty eight were different. We found 28 pathogenic mutations (25 in PKD1 and 3 in PKD2 ) within 28 different patients, which is a diagnosis rate of 75% consistent with literature mean direct sequencing diagnosis rate. We describe 52 new sequence variants in PKD1 and two in PKD2.
Conclusion
HRM analysis is a sensitive and specific method for molecular diagnosis of ADPKD. HRM analysis is also costless and time sparing. Thus, this method is efficient and might be used for mutation pre-screening in ADPKD genes.
doi:10.1186/1471-2369-12-57
PMCID: PMC3206831  PMID: 22008521
15.  Carotid artery calcification at the initiation of hemodialysis is a risk factor for cardiovascular events in patients with end-stage renal disease: a cohort study 
BMC Nephrology  2011;12:56.
Background
Vascular calcification has been recognized as a risk factor for cardiovascular (CV) events in patients with end-stage renal disease (ESRD). However, the association of carotid artery calcification (CAAC) with CV events remains unknown. The aim of this study was to elucidate whether CAAC is associated with composite CV events in ESRD patients.
Methods
One-hundred thirty-three patients who had been started on hemodialysis between 2004 and 2008 were included in this retrospective cohort study. These patients received multi-detector computed tomography to assess CAAC at the initiation of hemodialysis. Composite CV events, including ischemic heart disease, heart failure, cerebrovascular diseases, and CV deaths after the initiation of hemodialysis, were examined in each patient.
Results
CAAC was found in 94 patients (71%). At the end of follow-up, composite CV events were seen in 47 patients: ischemic heart disease in 20, heart failure in 8, cerebrovascular disease in 12, and CV deaths in 7. The incidence of CAAC was 87% in patients with CV events, which was significantly higher than the rate (62%) in those without. Kaplan-Meier analysis showed a significant increase in composite CV events in patients with CAAC compared with those without CAAC (p = 0.001, log-rank test). Univariate analysis using a Cox hazards model showed that age, smoking, common carotid artery intima-media thickness and CAAC were risk factors for composite CV events. In multivariate analysis, only CAAC was a significant risk factor for composite CV events (hazard ratio, 2.85; 95% confidence interval, 1.18-8.00; p = 0.02).
Conclusions
CAAC is an independent risk factor for CV events in ESRD patients. The assessment of CAAC at the initiation of hemodialysis is useful for predicting the prognosis.
doi:10.1186/1471-2369-12-56
PMCID: PMC3206830  PMID: 21999942
16.  Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels? 
BMC Nephrology  2011;12:55.
Background
Aluminium (Al) toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps) whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water.
Methods
HD patients only treated with Reverse Osmosis(RO) treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies.
Results
39 patients (34 anuric) were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration) and the total amount of Al ingested.
No patients had unexplained EPO resistance or biochemical evidence of adynamic bone.
Conclusions
Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R2 = 0.07) and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric.
doi:10.1186/1471-2369-12-55
PMCID: PMC3206420  PMID: 21992770
17.  Kidney transplant survival in pediatric and young adults 
BMC Nephrology  2011;12:54.
Background
There is a perception that kidney transplant recipients transferred from pediatric centers to adult care have an increased risk of graft loss. It is not clear whether young adults transplanted in adult centers also suffer from high graft loss rates.
Methods
We examined death censored graft survival in 3 cohorts of young patients transplanted at a single center. Pediatric (PED) patients transplanted at the pediatric center were compared to a cohort of young adults (YAD; age 18- < 25) and a cohort of adults (ADL; age 25-35).
Results
In a multivariate Cox model for death-censored graft survival, PED survival was statistically similar to the YAD (HR 0.86, 95% CI 0.44, 1.7, p = 0.66), however the ADL cohort (HR 0.45, 95% CI 0.25, 0.82, p = 0.009) demonstrated better survival. Admitted non-adherence rates were not different among cohorts. Patients were transferred within a narrow age window (18.6 ± 1.0 age in years) but at a wide range of times from the date of transplantation (5.1 ± 3.5 years) and with a wide range of graft function (serum creatinine 182 ± 81 μmol/L).
Conclusions
The perception that pediatric transfers do poorly reflects advanced graft dysfunction in some at the time of transfer. The evidence also suggests that it is not the transfer of care that is the critical issue but rather recipients, somewhere between the ages of 11-14 and 25, are a unique and vulnerable cohort. Effective strategies to improve outcomes across this age group need to be identified and applied consistently.
doi:10.1186/1471-2369-12-54
PMCID: PMC3198885  PMID: 21982270
18.  Baseline characteristics of patients with chronic kidney disease stage 3 and stage 4 in spain: the MERENA observational cohort study 
BMC Nephrology  2011;12:53.
Background
To obtain information on cardiovascular morbidity, hypertension control, anemia and mineral metabolism based on the analysis of the baseline characteristics of a large cohort of Spanish patients enrolled in an ongoing prospective, observational, multicenter study of patients with stages 3 and 4 chronic kidney diseases (CKD).
Methods
Multicenter study from Spanish government hospital-based Nephrology outpatient clinics involving 1129 patients with CKD stages 3 (n = 434) and 4 (n = 695) defined by GFR calculated by the MDRD formula. Additional analysis was performed with GFR calculated using the CKD-EPI and Cockcroft-Gault formula.
Results
In the cohort as a whole, median age 70.9 years, morbidity from all cardiovascular disease (CVD) was very high (39.1%). In CKD stage 4, CVD prevalence was higher than in stage 3 (42.2 vs 35.6% p < 0.024). Subdividing stage 3 in 3a and 3b and after adjusting for age, CVD increased with declining GFR with the hierarchy (stage 3a < stage 3b < stage 4) when calculated by CKD-EPI (31.8, 35.4, 42.1%, p 0.039) and Cockcroft-Gault formula (30.9, 35.6, 43.4%, p 0.010) and MDRD formula (32.5, 36.2, 42.2%,) but with the latter, it did not reach statistical significance (p 0.882). Hypertension was almost universal among those with stages 3 and 4 CKD (91.2% and 94.1%, respectively) despite the use of more than 3 anti-hypertensive agents including widespread use of RAS blockers. Proteinuria (> 300 mg/day) was present in more than 60% of patients and there was no significant differences between stages 3 and 4 CKD (1.2 ± 1.8 and 1.3 ± 1.8 g/day, respectively). A majority of the patients had hemoglobin levels greater than 11 g/dL (91.1 and 85.5% in stages 3 and 4 CKD respectively p < 0.001) while the use of erythropoiesis-stimulating agents (ESA) was limited to 16 and 34.1% in stages 3 and 4 CKD respectively. Intact parathyroid hormone (i-PTH) was elevated in stage 3 and stage 4 CKD patients (121 ± 99 and 166 ± 125 pg/mL p 0.001) despite good control of calcium-phosphorus levels.
Conclusion
This study provides an overview of key clinical parameters in patients with CKD Stages 3 and 4 where delivery or care was largely by nephrologists working in a network of hospital-based clinics of the Spanish National Healthcare System.
doi:10.1186/1471-2369-12-53
PMCID: PMC3203029  PMID: 21970625
19.  Development and reproducibility of a computed tomography-based measurement of renal sinus fat 
BMC Nephrology  2011;12:52.
Background
Renal sinus fat may mediate obesity-related vascular disease, although this fat depot has not been assessed in a community-based sample. We sought to develop a protocol to quantify renal sinus fat accumulation using multi-detector computed tomography (MDCT).
Methods
Protocol development was performed in participants in the Framingham Offspring cohort who underwent MDCT. Volumetric renal sinus fat was measured separately within the right and left kidneys, and renal sinus fat area within a single MDCT scan slice was measured in the right kidney. Due to the high correlation of volumetric and single-slice renal sinus fat in the right kidney (Pearson correlation [r] = 0.85, p < 0.0001), we optimized a single-slice protocol to capture renal sinus fat in the right kidney alone. Pearson correlation coefficients were used to compare to assess the correlation of volumetric and single-slice renal sinus fat in the right kidney with other measures of adiposity. Inter- and intra-reader reproducibility was assessed using intra-class correlation coefficients.
Results
Single-slice measurements were obtained in 92 participants (mean age 60 years, 49% women, median renal sinus fat 0.43 cm2). Intra- and inter-reader intra-class correlation coefficients were 0.93 and 0.86, respectively. Single-slice renal sinus fat was correlated with body mass index (r = 0.35, p = 0.0006), waist circumference (r = 0.31, p = 0.003), and abdominal visceral fat (r = 0.48, p < 0.0001). Similar correlations were observed for volumetric renal sinus fat in the right kidney.
Conclusions
Measuring renal sinus fat is feasible and reproducible using MDCT scans in a community-based sample.
doi:10.1186/1471-2369-12-52
PMCID: PMC3198884  PMID: 21970591
20.  Cardiac and vascular structure and function parameters do not improve with alternate nightly home hemodialysis: An interventional cohort study 
BMC Nephrology  2011;12:51.
Background
Nightly extended hours hemodialysis may improve left ventricular hypertrophy and function and endothelial function but presents problems of sustainability and increased cost. The effect of alternate nightly home hemodialysis (NHD) on cardiovascular structure and function is not known.
Methods
Sixty-three patients on standard hemodialysis (SHD: 3.5-6 hours/session, 3-5 sessions weekly) converted to NHD (6-10 hours/session overnight for 3-5 sessions weekly). 2Dimensional transthoracic echocardiography and ultrasound measures of brachial artery reactivity (BAR), carotid intima-media thickness (CIMT), total arterial compliance (TAC) and augmentation index (AIX) were performed post dialysis at baseline and 18-24 months following conversion to NHD. In 37 patients, indices of oxidative stress: plasma malonyldialdehyde (MDA) and anti-oxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured at baseline, 3 and 6 months.
Results
Left ventricular mass index (LVMI) remained stable. Despite significant derangement at baseline, there were no changes in diastolic function measures, CIMT, BAR and TAC. AIX increased. Conversion to NHD improved bone mineral metabolism parameters and blood pressure control. Interdialytic weight gains increased. No definite improvements in measures of oxidative stress were demonstrated.
Conclusions
Despite improvement in uremic toxin levels and some cardiovascular risk factors, conversion to an alternate nightly NHD regimen did not improve cardiovascular structure and function. Continuing suboptimal control of uremic toxins and interdialytic weight gains may be a possible explanation. This study adds to the increasing uncertainty about the nature of improvement in cardiovascular parameters with conversion to intensive hemodialysis regimens. Future randomized controlled trials will be important to determine whether increases in dialysis session duration, frequency or both are most beneficial for improving cardiovascular disease whilst minimizing costs and the impact of dialysis on quality of life.
doi:10.1186/1471-2369-12-51
PMCID: PMC3202231  PMID: 21962236
Diastolic Function; Ejection Fraction; Left Ventricular Mass Index; Left Ventricular Hypertrophy; Nocturnal Hemodialysis; Carotid Intima-Media Thickness; Oxidative Stress; Arterial Compliance
21.  Haemodialysis in an emerging centre in a developing country: a two year review and predictors of mortality 
BMC Nephrology  2011;12:50.
Background
Haemodialysis is the most common form of renal replacement therapy in Nigeria. The high cost of haemodialysis has made optimal therapy of end-stage renal disease difficult in Nigeria. This paper is a review of data collected over two years of provision of dialysis services in a new tertiary hospital in Southern Nigeria.
Methods
This retrospective analysis is done on data obtained from the patient case files and dialysis records in the first two years of provision of dialysis services in our centre. A gender comparison of the patients' baseline sociodemographic, clinical and biochemical was performed and a logistic regression model used to assess the predictors of mortality.
Results
A total of 98 patients had 471 sessions in the two years under review. Males and females had similar characteristics at baseline except for a higher median serum urea in the males. The commonest causes of end-stage renal disease were chronic glomerulonephritis (34.5%), hypertension (32.1%) and diabetes mellitus (17.9%). The main predictor of mortality was under treatment with haemodialysis due to inability to pay for more than a few dialysis sessions.
Conclusions
This study has highlighted the unchanging demographics of our advanced kidney failure patients. Efforts should be aimed at subsidizing the cost of dialysis for our teeming population of dialysis dependent chronic kidney disease patients.
doi:10.1186/1471-2369-12-50
PMCID: PMC3198883  PMID: 21962220
22.  Conversion to lanthanum carbonate monotherapy effectively controls serum phosphorus with a reduced tablet burden: a multicenter open-label study 
BMC Nephrology  2011;12:49.
Abstract
Background
Lanthanum carbonate (FOSRENOL®) is an effective, well-tolerated phosphate binder. The ability of lanthanum to reduce serum phosphorus levels to ≤5.5 mg/dL in patients with end-stage renal disease (ESRD) was assessed in a clinical practice setting.
Methods
A 16-week, phase IV study enrolled 2763 patients at 223 US sites to evaluate the efficacy of lanthanum carbonate in controlling serum phosphorus in patients with ESRD, and patient and physician satisfaction with, and preference for, lanthanum carbonate after conversion from other phosphate-binder medications. Patients received lanthanum carbonate prescriptions from physicians. These prescriptions were filled at local pharmacies rather than obtaining medication at the clinical trial site. Changes from serum phosphorus baseline values were analyzed using paired t tests. Patient and physician preferences for lanthanum carbonate versus previous medications were assessed using binomial proportion tests. Satisfaction was analyzed using the McNemar test. Daily dose, tablet burden, and laboratory values including albumin-adjusted serum calcium, calcium × phosphorus product, and parathyroid hormone levels were secondary endpoints.
Results
Serum phosphorus control (≤5.5 mg/dL) was effectively maintained in patients converting to lanthanum carbonate monotherapy; 41.6% of patients had controlled serum phosphate levels at 16 weeks. Patients and physicians expressed markedly higher satisfaction with lanthanum carbonate, and preferred lanthanum carbonate over previous medication. There were significant reductions in daily dose and daily tablet burden after conversion to lanthanum carbonate.
Conclusions
Serum phosphorus levels were effectively maintained in patients converted from other phosphate-binder medications to lanthanum carbonate, with increased satisfaction and reduced tablet burden.
Trial Registration
ClinicalTrials.gov: NCT0016012
doi:10.1186/1471-2369-12-49
PMCID: PMC3197476  PMID: 21962172
23.  Positron emission tomography in the diagnostic pathway for intracystic infection in adpkd and "cystic" kidneys. a case series 
BMC Nephrology  2011;12:48.
Background
Intracystic infection, in Autosomal Dominant Polycystic Kidney Disease (ADPKD) and in kidneys with multiple cysts, is a diagnostic and therapeutic challenge, as conventional imaging techniques may not discriminate among "complicated" cysts (infection, bleeding, neoplasia), and as the clinical picture may be attenuated, in particular in early phases. Positron Emission Tomography with fluorodeoxyglucose (FDG-PET) was recently suggested as a tool to detect infection in ADPKD, in single cases and small series.
The aim of the study was to report on the role of FDG-PET in the work-up of 10 cases of suspected cystic infections, affected by ADPKD or with multiple kidney cysts.
Methods
Observational study. Review of clinical charts and of the imaging data since the use of FDG-PET for detecting cystic infections (2008-2010).
Results
In 2008-2010, 6 patients with ADPKD and 4 with multiple kidney cysts were referred for suspected intracystic infections (3 males, 7 females, aged 55-83 years, in all CKD stages); in one case the imaging was done in the work-up of a complicated "uremic" cyst. The clinical picture, the usual inflammatory markers and/or the conventional imaging techniques did not allow conclusive diagnosis at referral or during follow-up (ultrasounds in all, CT in 8/10). Nine patients displayed inflammatory signs (increase in C-reactive protein and other biochemical markers) and constitutional symptoms (fever in 9/10).
FDG-PET was positive in 6 cases (5 kidney and 1 liver cyst), was repeated during follow-up in 4 patients and was negative in 4 cases. In the positive cases, FDG-PET guided the therapeutic choices; in particular, the duration of therapy was supported by imaging data in the 4 cases with multiple scans. No relapse was recorded after discontinuation of antibiotic therapy in the treated patients. The negative cases did not develop clinical signs of cystic infection over follow-up.
Conclusion
In this case series, the largest prospective one so far published and the only one including different types of renal cysts, FDG-PET is confirmed as a promising diagnostic tool for detecting intracystic infection in ADPKD and in multiple kidney cysts, and a potential guide for tailoring therapy. Further larger and multicenter studies are needed to evaluate the cost-benefit ratio and the limits of this imaging technique in the clinical setting.
doi:10.1186/1471-2369-12-48
PMCID: PMC3197475  PMID: 21957932
Positron emission tomography; polycystic kidney disease; infection; kidney cysts; long-term antibiotic therapy
24.  Evaluation of an electronic warfarin nomogram for anticoagulation of hemodialysis patients 
BMC Nephrology  2011;12:46.
Background
Warfarin nomograms to guide dosing have been shown to improve control of the international normalized ratio (INR) in the general outpatient setting. However, the effectiveness of these nomograms in hemodialysis patients is unknown. We evaluated the effectiveness of anticoagulation using an electronic warfarin nomogram administered by nurses in outpatient hemodialysis patients, compared to physician directed therapy.
Methods
Hemodialysis patients at any of the six outpatient clinics in Calgary, Alberta, treated with warfarin anticoagulation were included. Two five-month time periods were compared: prior to and post implementation of the nomogram. The primary endpoint was adequacy of anticoagulation (proportion of INR measurements within range ± 0.5 units).
Results
Overall, 67 patients were included in the pre- and 55 in the post-period (with 40 patients in both periods). Using generalized linear mixed models, the adequacy of INR control was similar in both periods for all range INR levels: in detail, range INR 1.5 to 2.5 (pre 93.6% (95% CI: 88.6% - 96.5%); post 95.6% (95% CI: 89.4% - 98.3%); p = 0.95); INR 2.0 to 3.0 (pre 82.2% (95% CI: 77.9% - 85.8%); post 77.4% (95% CI: 72.0% - 82.0%); p = 0.20); and, INR 2.5 to 3.5 (pre 84.3% (95% CI: 59.4% - 95.1%); post 66.8% (95% CI: 39.9% - 86.0%); p = 0.29). The mean number of INR measurements per patient decreased significantly between the pre- (30.5, 95% CI: 27.0 - 34.0) and post- (22.3, 95% CI: 18.4 - 26.1) (p = 0.003) period. There were 3 bleeding events in each of the periods.
Conclusions
An electronic warfarin anticoagulation nomogram administered by nurses achieved INR control similar to that of physician directed therapy among hemodialysis patients in an outpatient setting, with a significant reduction in frequency of testing. Future controlled trials are required to confirm the efficacy of this nomogram.
doi:10.1186/1471-2369-12-46
PMCID: PMC3189863  PMID: 21943221
Anticoagulation; Hemodialysis; Warfarin nomogram
25.  Patient and provider determinants of nephrology referral in older adults with severe chronic kidney disease: a survey of provider decision making 
BMC Nephrology  2011;12:47.
Background
Although chronic kidney disease (CKD) disproportionately affects older adults, they are less likely to be referred to a nephrologist. Factors that influence the referral decisions of primary care providers (PCPs) specifically for older CKD patients have been incompletely described. Patient factors such as dementia, functional disability, and co-morbidity may complicate the decision to refer an older adult. This study evaluated the role of patient and PCP factors in the referral decisions for older adults with stage 4 CKD.
Methods
We administered a two-part survey to study the decisions of practicing PCPs. First, using a blocked factorial design, vignettes systematically varied 6 patient characteristics: age, race, gender, co-morbidity, functional status, and cognitive status. CKD severity, patient preferences, and degree of anemia were held constant. Second, covariates from a standard questionnaire included PCP estimates of life expectancy, demographics, reaction to clinical uncertainty, and risk aversion. The main outcome was the decision to refer to the nephrologist. Random effects logistic regression models tested independent associations of predictor variables with the referral decision.
Results
More than half (62.5%) of all PCP decisions (n = 680) were to refer to a nephrologist. Vignette-based factors that independently decreased referral included older patient age (OR = 0.27; 95% CI, 0.15 to 0.48) and having moderate dementia (OR = 0.14; 95%CI, 0.07 to 0.25). There were no associations between co-morbidity or impaired functional activity with the referral decision. Survey-based PCP factors that significantly increased the referral likelihood include female gender (OR = 7.75; 95%CI, 2.07 to 28.93), non-white race (OR = 30.29; 95%CI, 1.30 to 703.73), those who expect nephrologists to discuss goals of care (OR = 53.13; 95%CI, 2.42 to 1168.00), those with higher levels of anxiety about uncertainty (OR = 1.28; 95%CI, 1.04 to 1.57), and those with greater risk aversion (OR = 3.39; 95%CI, 1.02 to 11.24).
Conclusions
In this decision making study using hypothetical clinical vignettes, we found that the PCP decision to refer older patients with severe CKD to a nephrologist reflects a complex interplay between patient and provider factors. Age, dementia, and several provider characteristics weighed more heavily than co-morbidity and functional status in PCP referral decisions. These results suggest that practice guidelines should develop a more nuanced approach to the referral of older adults with CKD.
doi:10.1186/1471-2369-12-47
PMCID: PMC3192737  PMID: 21943241

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