BMC Nephrology - Latest Articles

Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study

Hyo Jin Kim — 2013-05-25T00:00:00Z

Background: Elevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients.Objectives: The CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23.DesignMulticenter, open-labeled, randomized controlled studySetting: Seven university-affiliated hospitals in KoreaParticipants: Overall, 66 peritoneal dialysis patients were enrolledIntervention: Sixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome.Main outcome measures: Achievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary). Results: 72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 +/- 18.0 mg/day of cinacalcet and 0.13 +/- 0.32 mug/d oral vitamin D (P < 0.001 vs. control with 0.27 +/- 0.18 mug/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (- 42.54% vs. 15.83%, P = 0.008). After adjustment, cinacalcet treatment was independently associated with the serum FGF23 reduction. Conclusion: Cinacalcet treatment was independently associated with the reduction of FGF23 in our PD patients.Trial registration: Controlled trials NCT01101113 (http://www.clinicaltrials.gov)

Peritoneal dialysis peritonitis by anaerobic pathogens: a retrospective case series

Chia-Ter Chao — 2013-05-24T00:00:00Z

Background: Bacterial infections account for most peritoneal dialysis (PD)-associated peritonitis episodes. However, anaerobic PD peritonitis is extremely rare and intuitively associated with intra-abdominal lesions. In this study, we examined the clinical characteristics of PD patients who developed anaerobic peritonitis. Methods: We retrospectively identified all anaerobic PD peritonitis episodes from a prospectively collected PD registry at a single center between 1990 and 2010. Only patients receiving more than 3 months of PD were enrolled. We analyzed clinical features as well as outcomes of anaerobic PD peritonitis patients. Results: Among 6 patients, 10 episodes of PD-associated peritonitis were caused by anaerobic pathogens (1.59% of all peritonitis episodes during study the period), in which the cultures from 5 episodes had mixed growth. Bacteroides fragilis was the most common species identified (4 isolates). Only 3 episodes were associated with gastrointestinal lesions, and 4 episodes were related to a break in sterility during exchange procedures. All anaerobic pathogens were susceptible to clindamycin and metronidazole, but penicillin resistance was noted in 4 isolates. Ampicillin/sulbactam resistance was found in 2 isolates. In 5 episodes, a primary response was achieved using the first-generation cephalosporin and ceftazidime or aminoglycoside. In 3 episodes, the first-generation cephalosporin was replaced with aminoglycosides. Tenckhoff catheter removal was necessary in 2 episodes. Only one episode ended with mortality (due to a perforated bowel). Conclusion: Anaerobic PD-associated peritonitis might be predominantly caused by contamination, rather than intra-abdominal events. Half of anaerobic PD-associated peritonitis episodes had polymicrobial growth. The overall outcome of anaerobic peritonitis is fair, with a high catheter survival rate.

Modelling competing risks in nephrology research: an example in peritoneal dialysis

Laetitia Teixeira — 2013-05-24T00:00:00Z

Background: Modelling competing risks is an essential issue in Nephrology Research. In peritoneal dialysis studies, sometimes inappropriate methods (i.e. Kaplan-Meier method) have been used to estimate probabilities for an event of interest in the presence of competing risks. In this situation a competing risk analysis should be preferable. The objectives of this study are to describe the bias resulting from the application of standard survival analysis to estimate peritonitis-free patient survival and to provide alternative statistical approaches taking competing risks into account. Methods: The sample comprises patients included in a university hospital peritoneal dialysis program between October 1985 and June 2011 (n = 449). Cumulative incidence function and competing risk regression models based on cause-specific and subdistribution hazards were discussed. Results: The probability of occurrence of the first peritonitis is wrongly overestimated using Kaplan-Meier method. The cause-specific hazard model showed that factors associated with shorter time to first peritonitis were age (>=55 years) and previous treatment (haemodialysis). Taking competing risks into account in the subdistribution hazard model, age remained significant while gender (female) but not previous treatment was identified as a factor associated with a higher probability of first peritonitis event. Conclusions: In the presence of competing risks outcomes, Kaplan-Meier estimates are biased as they overestimated the probability of the occurrence of an event of interest. Methods which take competing risks into account provide unbiased estimates of cumulative incidence for each specific outcome experienced by patients. Multivariable regression models such as those based on cause-specific hazard and on subdistribution hazard should be used in this competing risk setting.

Monitoring of hemodialysis quality-of-care indicators: why is it important?

Steven Grangé — 2013-05-24T00:00:00Z

Background: Meeting specific guideline targets is associated with improved survival rates and reduced hospitalizations in the dialysis population. This prospective work evaluated the adequacy of hemodialysis quality indicators in an in-center hemodialysis population with severe comorbidities, and assessed whether clinical practice could impact intermediate outcomes. Methods: All the chronic hemodialysis patients treated in Rouen University Hospital hemodialysis Unit between January 2009 and April 2010 were included in this observational study. Every quarter, mean levels and prevalence of conformity were collected for the following indicators: anemia, dialysis dose, serum calcium and phosphorus, PTH, 25OH-vitamin D, albumin, serum bicarbonate, LDL-cholesterol, serum beta2-microglobulin, systolic and diastolic blood pressure, intradialytic hypotension and vascular access. Conformity of quality-of-care indicators was determined according to targets defined by international guidelines, whenever available. Results: Altogether, 124 patients were included in the study. Thirty-three patients were evaluated during the entire follow-up period. An improvement in the percentage of conformity was observed for hemoglobin, dialysis dose, phosphates, PTH, serum bicarbonate and beta2-microglobulin in the global population. Failure to improve conformity rates for several indicators, including serum albumin, was found, possibly depending on patients' comorbidities rather than on quality of care. Conclusion: Overall, this study shows that following quality-of-care indicators can improve clinical practice by identifying center-specific weaknesses, prompting the establishment of corrective measures. Finally, we suggest that the definition and targets of some indicators, especially hypertension and LDL-cholesterol, be reviewed, since evidence of their association with mortality is not demonstrated.

Transcultural adaptation and initial validation of Brazilian-Portuguese version of the Basel assessment of adherence to immunosuppressive medications scale (BAASIS) in kidney transplants

Elisa Marsicano — 2013-05-21T00:00:00Z

Background: Transplant recipients are expected to adhere to a lifelong immunosuppressant therapeutic regimen. However, nonadherence to treatment is an underestimated problem for which no properly validated measurement tool is available for Portuguese-speaking patients. We aimed to initially validate the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS(R)) to accurately estimate immunosuppressant nonadherence in Brazilian transplant patients. Methods: The BAASIS(R) (English version) was transculturally adapted and its psychometric properties were assessed. The transcultural adaptation was performed using the Guillemin protocol. Psychometric testing included reliability (intraobserver and interobserver reproducibility, agreement, Kappa coefficient, and the Cronbach's alpha) and validity (content, criterion, and construct validities). Results: The final version of the transculturally adapted BAASIS(R) was pretested, and no difficulties in understanding its content were found. The intraobserver and interobserver reproducibility variances (0.007 and 0.003, respectively), the Cronbach's alpha (0.7), Kappa coefficient (0.88) and the agreement (95.2%) suggest accuracy, preciseness and reliability. For construct validity, exploratory factorial analysis demonstrated unidimensionality of the first three questions (r = 0.76, r = 0.80, and r = 0.68). For criterion validity, the adapted BAASIS(R) was correlated with another self-report instrument, the Measure of Adherence to Treatment, and showed good congruence (r = 0.65). Conclusions: The BAASIS(R) has adequate psychometric properties and may be employed in advance to measure adherence to posttransplant immunosuppressant treatments. This instrument will be the first one validated to use in this specific transplant population and in the Portuguese language.

Chronic kidney disease is associated with adverse outcomes among elderly patients taking clopidogrel after hospitalization for acute coronary syndrome

Michael Fischer — 2013-05-20T00:00:00Z

Background: Chronic kidney disease (CKD) is associated with worse outcomes among patients with acute coronary syndrome (ACS). Less is known about the impact of CKD on longitudinal outcomes among clopidogrel treated patients following ACS. Methods: Using a retrospective cohort design, we identified patients hospitalized with ACS between 10/1/2005 and 1/10/10 at Department of Veterans Affairs (VA) facilities and who were discharged on clopidogrel. Using outpatient serum creatinine values, estimated glomerular filtration rate [eGFR (1.73 ml/min/m2)] was calculated using the CKD-EPI equation. The association between eGFR and mortality, hospitalization for acute myocardial infarction (AMI), and major bleeding were examined using Cox proportional hazards models. Results: Among 7413 patients hospitalized with ACS and discharged taking clopidogrel, 34.5% had eGFR 30--60 and 11.6% had eGFR < 30. During 1-year follow-up after hospital discharge, 10% of the cohort died, 18% were hospitalized for AMI, and 4% had a major bleeding event. Compared to those with eGFR > =60, individuals with eGFR 30--60 (HR 1.45; 95% CI: 1.18-1.76) and < 30 (HR 2.48; 95% CI: 1.97-3.13) had a significantly higher risk of death. A progressive increased risk of AMI hospitalization was associated with declining eGFR: HR 1.20; 95% CI: 1.04-1.37 for eGFR 30--60 and HR 1.47; 95% CI: 1.22-1.78 for eGFR < 30. eGFR < 30 was independently associated with over a 2-fold increased risk in major bleeding (HR 2.09; 95% CI: 1.40-3.12) compared with eGFR > = 60. Conclusion: Lower levels of kidney function were associated with higher rates of death, AMI hospitalization, and major bleeding among patients taking clopidogrel after hospitalization for ACS.

Reflex anuria following acute cardiac event

Vijayabala Jeevagan — 2013-05-20T00:00:00Z

Background: Reflex anuria is an uncommon cause for acute renal failure, which occurs almost always after manipulation or irritation to kidneys, ureter, bladder or other pelvic organs.Case presentationHere we describe a case of acute renal failure due to reflex anuria following acute cardiac event. This patient had background history of urolithiasis. In the absence of other pre renal, renal or post- renal causes for acute kidney injury, we believe reflex anuria is the causative entity for acute renal failure in our patient. Conclusion: Acute renal failure due to reflex anuria is related to a reflex mechanism involving arteriolar vasoconstriction and urethral spasm. Patients with reflex anuria can be successfully managed with medical or surgical interventions. Our case suggests that reflex anuria should be considered as one of the differential diagnosis of acute renal failure following acute cardiac event, especially in patients with background urological problem.

Bilirubin attenuates the renal tubular injury by inhibition of oxidative stress and apoptosis

Se Won Oh — 2013-05-17T00:00:00Z

Background: Bilirubin (BIL) has been recognized as an endogenous antioxidant that shows a protective effect for cardiorenal diseases. We investigated whether administration of BIL had a protective effect on cyclosporine (CsA)-induced nephropathy (CIN), and examined the effects of BIL on the oxidative stress and apoptosis. Methods: BIL was pretreated intraperitoneally three times for a week (60mg/kg), and CsA was injected for 4 weeks (15mg/kg/day, subcutaneous). Proximal tubular epithelial (HK2) cells were pretreated with 0.1mg/ml of BIL for 24 hours, and then treated with 20 muM of CsA for another 24 hours. Results: CsA induced marked increases in urine kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) concentrations (P < 0.05). BIL reduced urine Kim-1 in CIN (P < 0.05), while urine NGAL exhibited a decreasing tendency. In CsA-treated rat kidneys, the protein expression of NOX4 and p22phox was reduced by BIL (P < 0.05). BIL ameliorated CsA-induced arteriolopathy, tubulointerstitial fibrosis, tubular injury, and the apoptosis examined by TUNEL assay (P < 0.01). In HK2 cells, BIL reduced intracellular reactive oxygen species in CsA-treated cells. CsA increased the protein expression of bax, cleaved caspase-9, caspase-3 and the activity of caspase-3; however, the anti-apoptotic bcl-2 protein was reduced. These changes were recovered by BIL (P < 0.05). Conclusions: The direct administration of BIL protected against CsA-induced tubular injury via inhibition of oxidative stress and apoptosis.

A novel TRPC6 mutation in a family with podocytopathy and clinical variability

Amy Mottl — 2013-05-10T00:00:00Z

Background: Mutation in several podocyte-specific genes have been noted to result in phenotypic heterogeneity. Herein, we report a novel, autosomal dominant TRPC6 mutation in a family with disease ranging from asymptomatic minimal change disease to end-stage kidney disease.Case presentationA 35 year old woman developed asymptomatic, nephrotic range proteinuria during pregnancy that did not resolve after delivery. Her mother had end-stage kidney disease of unknown etiology and her brother had asymptomatic proteinuria. Kidney biopsy revealed minimal change disease in both the proband and her brother. Genetic testing was performed in the proband and mother, revealing a novel frameshift mutation in TRPC6, D873fsX878. The proband continues to have subnephrotic range proteinuria and normal creatinine but her brother has since developed progressive chronic kidney disease. Conclusions: The current case report underscores the heterogeneity of disease in podocytopathies and related genes. Genetic testing of podocyte genes is useful in order to understand the pathophysiologic processes underlying these overlapping diseases.

Competing-risk analysis of death and dialysis initiation among elderly (¿80 years) newly referred to nephrologists: a French prospective study

Bernadette Faller — 2013-05-07T00:00:00Z

Background: Reasons underlying dialysis decision-making in Octogenarians and Nonagenarians have not been further explored in prospective studies. Methods: This regional, multicentre, non-interventional and prospective study was aimed to describe characteristics and quality of life (QoL) of elderly (≥80 years of age) with advanced chronic kidney disease (stage 3b-5 CKD) newly referred to nephrologists. Predictive factors of death and dialysis initiation were also assessed using competing-risk analyses. Results: All 155 included patients had an estimated glomerular filtration rate (eGFR) below 45 ml/min/1.73 m2. Most patients had a non anaemic haemoglobin level (Hb) with no iron deficiency, and normal calcium and phosphate levels. They were well-fed and had a normal cognitive function and a good QoL. The 3-year probabilities of death and dialysis initiation reached 27% and 11%, respectively. The leading causes of death were cardiovascular (32%), cachexia (18%), cancer (9%), infection (3%), trauma (3%), dementia (3%), and unknown (32%). The reasons for dialysis initiation were based on uncontrolled biological abnormalities, such as hyperkalemia or acidosis (71%), uncontrolled digestive disorders (35%), uncontrolled pulmonary or peripheral oedema (29%), and uncontrolled malnutrition (12%). No patients with acute congestive heart failure or cancer initiated dialysis. Predictors of death found in both multivariate regression models (Cox and Fine & Gray) included acute congestive heart failure, age, any walking impairment and Hb <10 g/dL. Regarding dialysis initiation, eGFR <23 mL/min/1.73 m2 was the only predictor found in the Cox multivariate regression model whereas eGFR <23 mL/min/1.73 m2 and diastolic blood pressure were both independently associated with dialysis initiation in the Fine & Gray analysis. Such findings suggested that death and dialysis were independent events. Conclusions: Octogenarians and Nonagenarians newly referred to nephrologists by general practitioners were highly selected patients, without any symptoms of the common geriatric syndrome. In this population, nephrologists’ dialysis decision was based exclusively on uremic criteria.