Kidney Function

Analytical and Biological Variation in Measures of Anemia and Iron Status in Patients Treated With Maintenance Hemodialysis – Corrected Proof

David B. Van Wyck, Harry Alcorn, Resmi Gupta — Tue, 20 Jul 2010 02:00:00 +0000

Background: To make informed decisions in dosing erythropoiesis-stimulating agents and intravenous iron therapy, clinicians must determine whether differences between current and previous test results for anemia and iron status markers reflect expected variation, a significant change, or an actual trend.Study Design: Prospective observational cohort study.Setting & Participants: 30 patients undergoing thrice-weekly in-center hemodialysis.Predictor: Within-patient biological variations in hemoglobin (Hb) level, hematocrit (Hct), reticulocyte Hb content, transferrin saturation (TSAT), and ferritin level were determined over 12 consecutive treatment days.Outcomes & Measurements: We separately measured same-sample analytical variation and within-patient biological variation (coefficient of variation), then calculated the number of sampling days needed to determine the true or homeostatic value for each analyte with 95% probability. We also evaluated whether results differed among the first, second, and third dialysis days of the week.Results: Biological variation differed by analyte. Hb level (4.0%), Hct (4.0%), and reticulocyte Hb content (4.8%) showed much lower variation than TSAT (38.2%) or ferritin level (15.1%). Analytical variation ranged from 2.0%-6.9% for all analytes. We found that one sample day would be sufficient to establish the true mean Hb level or Hct within a level of closeness ±20% and 95% probability. For the same levels of closeness and probability, one sample day would be needed for reticulocyte Hb content, 15 for TSAT, and 3 for ferritin level. No pairwise comparison for any of the 5 analytes yielded a significant difference between results obtained on the first, second, or third dialysis day of the week.Limitations: These findings may not apply to other patient populations.Conclusions: Low biological variation renders Hb level, Hct, and reticulocyte Hb content, but not TSAT and ferritin level, suitable for trend analysis using results from 2 successive samples. TSAT and ferritin test results, unlike reticulocyte Hb content, have limited value in evaluating changes in iron status within individual hemodialysis patients.

Prognostic Value of Plasma Myeloperoxidase in ESRD Patients – Corrected Proof

Tue, 20 Jul 2010 02:00:00 +0000

Background: Myeloperoxidase (MPO) has been suggested to have a role in atherosclerosis through its strong oxidative capacity. We hypothesized that MPO level may predict clinical outcomes in patients with end-stage renal disease receiving long-term peritoneal dialysis (PD) therapy.Study Design: Prospective cohort study.Setting & Participants: 236 long-term PD patients were recruited from a single regional dialysis unit in Hong Kong between April 1999 and February 2001.Predictor: Level of plasma MPO, analyzed using a sandwich enzyme-linked immunosorbent assay.Outcome & Measurement: Mortality and fatal or nonfatal cardiovascular events at 3 years.Results: The distribution of MPO levels was skewed with a median of 31.8 μg/L (25th-75th percentiles, 24.4-42.7). There were 69 deaths and 81 cardiovascular events. Adjusting for traditional and nontraditional risk factors and C-reactive protein, cardiac troponin T, and N-terminal pro-brain natriuretic peptide levels, a doubling in plasma MPO level was associated independently with a 46% (95% CI, 1.02-2.08; P = 0.04) and 60% (95% CI, 1.17-2.18; P = 0.003) increase in risks of mortality and cardiovascular events, respectively. Log2MPO showed significant additional predictive value for mortality (P = 0.04) and cardiovascular events (P = 0.005) when included in Cox regression models consisting of clinical, demographic, dialysis, echocardiographic, and biochemical parameters, as well as C-reactive protein, cardiac troponin T, and N-terminal pro-brain natriuretic peptide levels.Limitations: MPO was measured at a single time and did not reflect changes over time.Conclusions: These data suggest that plasma MPO level has significant independent and additional prognostic value beyond the standard clinical, biochemical, and echocardiographic parameters and is useful for outcome stratification in long-term PD patients. MPO may be an important mediator of increased cardiovascular risk in patients with end-stage renal disease and warrants further investigation.

Reasons to Avoid or Stop Dialysis

admin — Wed, 14 Jul 2010 18:56:11 +0000

Specific reasons some people may elect not to start dialysis treatment (as they approach end stage renal failure) or choose to stop dialysis (even if they have done well on it in the past) are as follows:

The presence of development of unrelated disease that causes unrelenting pain and suffering (such as widespread cancer), extreme physical disability (such as severe stroke or multiple amputations), or will cause a difficult death in a very short period of time.
Such severe dementia that they are unable to relate to others or to understand their own illness and the necessary dialysis treatment (e.g., dementia from Alzheimer’s disease or as a result of multiple strokes)
The occurrence of such severe brain injury that they are permanently unconscious (e.g., from an automobile accident or from a cardiac or pulmonary arrest).

Fortunately, these various conditions, with rare exception (such as a stroke in a dialysis patient with uncontrolled hypertension or blindness and amputations in a severe diabetic), are no more common in patients with end-stage renal disease. They do occur, however, just as they do in other people or in otherwise healthy individuals, and one should prepare for unexpected as well as for foreseeable problems.

Validation of Clinical Scores Predicting Severe Acute Kidney Injury After Cardiac Surgery – Corrected Proof

Wed, 14 Jul 2010 02:00:00 +0000

Background: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) in patients undergoing cardiac surgery is associated strongly with adverse patient outcomes. Recently, 3 predictive risk models for RRT have been developed. The aims of our study are to validate the predictive scoring models for patients requiring postoperative RRT and test applicability to the broader spectrum of patients with postoperative severe AKI.Study Design: Diagnostic test study.Setting & Participants: 12,096 patients undergoing cardiac surgery with cardiopulmonary bypass at Mayo Clinic, Rochester, MN, from 2000 through 2007.Index Test: Cleveland Clinic score, Mehta score, and Simplified Renal Index (SRI) score.Reference Test or Outcome: Incidence of postoperative RRT or composite outcome of severe AKI, defined as serum creatinine level >2.0 mg/dL, and a 2-fold increase compared with the preoperative baseline creatinine level or RRT.Results: RRT was used in 254 (2.1%) patients, whereas severe AKI was present in 467 (3.9%). Discrimination for the prediction of RRT and severe AKI was good for all scoring models measured using areas under the receiver operating characteristic curve (AUROCs): 0.86 (95% CI, 0.84-0.88) for RRT and 0.81 (95% CI, 0.79-0.83) for severe AKI using the Cleveland score, 0.81 (95% CI, 0.78-0.86) and 0.76 (95% CI, 0.73-0.80) using the Mehta score, and 0.79 (95% CI, 0.77-0.82) and 0.75 (95% CI, 0.72-0.77) using the SRI score. The Cleveland score and Mehta score consistently showed significantly better discrimination compared with the SRI score (P < 0.001). Despite lower AUROCs for the prediction of severe AKI, the Cleveland score AUROC was still >0.80. The Mehta score is applicable in only a subgroup of patients.Limitations: Single-center retrospective cohort study.Conclusions: The Cleveland scoring system offers the best discriminative value to predict postoperative RRT and covers most patients undergoing cardiac surgery. It also can be used for prediction of the composite end point of severe AKI, which enables broader application to patients at risk of postoperative kidney dysfunction.

A Randomized Clinical Trial of Immunization With Combined Hepatitis A and B Versus Hepatitis B Alone for Hepatitis B Seroprotection in Hemodialysis Patients – Corrected Proof

Jennifer Tung, Euan Carlisle, Marek Smieja, Peter T. Kim, Christine H. Lee — Wed, 14 Jul 2010 02:00:00 +0000

Background: The Centers for Disease Control and Prevention recommend immunizing susceptible high-risk groups, such as hemodialysis patients, against hepatitis B virus. However, hemodialysis patients may not develop seroprotective antibodies despite receiving high doses of the vaccine. Recent reports indicate that combined vaccination against hepatitis B and hepatitis A viruses may improve the immunogenicity of hepatitis B vaccine in healthy individuals, but the effectiveness of this strategy in hemodialysis patients is unknown.Study Design: Prospective randomized controlled trial.Setting & Participants: Hepatitis B virus–seronegative hemodialysis patients with undetectable antibody levels at baseline.Intervention: Intramuscular administration of Twinrix (inactivated hepatitis A virus [720 ELISA units] and purified hepatitis B virus surface antigen [20 μg]; GlaxoSmithKline) and Engerix-B (purified hepatitis B virus surface antigen [20 μg]) at 0, 1, and 6 months plus Engerix-B, 40 μg, at month 2 (intervention arm) or Engerix-B, 40 μg, at 0, 1, 2, and 6 months (control arm). Both groups received a total dose of 160 μg of hepatitis B antigen.Outcomes: The primary outcome was the difference in seroprotection rates at 7 months, defined by antibody titers >10 mIU/mL. The secondary outcome was frequency of adverse events.Measurements: Antibody response at months 3 and 7.Results: 96 patients were enrolled, and 73 completed the investigation. At 3 months, there was no difference in the groups' seroprotection rates (25% vs 27%; P = 0.4). At the completion of the vaccination series, using per-protocol analysis, 27 of 40 (68%) and 16 of 33 (49%) had antibody titers >10 mIU/mL in the treatment and control groups, respectively (P = 0.05; RR, 1.4; absolute abatement, 19%). Intention-to-treat analysis showed 58% and 38% seroprotection rates in the treatment and control groups, respectively (P = 0.02; RR, 1.5; absolute abatement, 20%). There was no difference in adverse events.Limitations: Lack of evidence of long-term protection.Conclusion: Vaccination of hemodialysis patients with a combined hepatitis A and hepatitis B regimen resulted in a statistically significant and clinically important improvement in seroprotection against hepatitis B virus compared with hepatitis B monovalent vaccine.

Peritoneal Dialysis Outflow Failure From Omental Wrapping Diagnosed by Catheterography – Corrected Proof

Jing-Yuan Xie, Hong Ren, Krzysztof Kiryluk, Nan Chen — Wed, 14 Jul 2010 02:00:00 +0000

Peritoneal dialysis outflow failure caused by omental wrapping is a serious complication that is difficult to diagnose noninvasively. We report a case of outflow failure in which catheterography showed several characteristics of omental wrapping: “pseudocele” formation, delayed catheter emptying, and uneven distribution of contrast in the abdominal cavity. A laparoscopic procedure was performed with identification of peritoneal adhesion and greater omental wrapping. The catheter was stripped from the omentum and repositioned in the Douglas peritoneal sac. Catheterography is a reliable, safe, noninvasive, and inexpensive alternative procedure to diagnose outflow failure caused by omental wrapping.

Infection-Related Hospitalizations in Older Patients With ESRD – Corrected Proof

Fri, 09 Jul 2010 02:00:00 +0000

Background: Infection is an important cause of hospitalization and death in patients receiving dialysis. Few studies have examined the full range of infections experienced by dialysis patients. The purpose of this study is to examine types, rates, and risk factors for infection in older persons starting dialysis therapy.Study Design: Retrospective observational cohort study.Setting & Participants: The cohort was assembled from the US Renal Data System and included patients aged 65-100 years who initiated dialysis therapy between January 1, 2000, and December 31, 2002. Exclusions included prior kidney transplant, unknown dialysis modality, or death, loss to follow-up, or transplant during the first 90 days of dialysis therapy. Patients were followed up until death, transplant, or study end on December 31, 2004.Predictors: Baseline demographics, comorbid conditions, and serum albumin and hemoglobin levels.Outcomes & Measurements: Infection-related hospitalizations were ascertained using discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Hospitalization rates were calculated for each type of infection. The Wei-Lin-Weissfeld model was used to examine risk factors for up to 4 infection-related events.Results: 119,858 patients were included, 7,401 of whom were on peritoneal dialysis therapy. During a median follow-up of 1.9 years, infection-related diagnoses were observed in approximately 35% of all hospitalizations. Approximately 50% of patients had at least 1 infection-related hospitalization. Rates (per 100 person-years) of pulmonary, soft-tissue, and genitourinary infections ranged from 8.3-10.3 in patients on peritoneal dialysis therapy and 10.2-15.3 in patients on hemodialysis therapy. Risk factors for infection included older age, female sex, diabetes, heart failure, pulmonary disease, and low serum albumin level.Limitations: Use of ICD-9-CM codes, reliance on Medicare claims to capture hospitalizations, use of the Medical Evidence Form to ascertain comorbid conditions, and absence of data for dialysis access.Conclusion: Infection-related hospitalization is frequent in older patients on dialysis therapy. A broad range of infections, many unrelated to dialysis access, result in hospitalization in this population.

Proteomic Identification of Early Biomarkers of Acute Kidney Injury After Cardiac Surgery in Children – Corrected Proof

Mon, 05 Jul 2010 02:00:00 +0000

Background: Serum creatinine is a delayed marker of acute kidney injury (AKI). Our purpose is to discover and validate novel early urinary biomarkers of AKI after cardiac surgery.Study Design: Diagnostic test study.Setting & Participants: Children undergoing cardiopulmonary bypass surgery. The test set included 15 participants with AKI and 15 matched controls (median age, 1.5 year) of 45 participants without AKI. The validation set included 365 children (median age, 1.9 year).Index Tests: Biomarkers identified using proteomic profiling: α1-microglobulin, α1-acid glycoprotein, and albumin.Reference Test: AKI, defined as ≥50% increase in serum creatinine level from baseline within 3 days of surgery.Results: Proteomic profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) showed 3 protein peaks that appeared consistently within 2 hours in children who developed AKI after cardiopulmonary bypass surgery. The proteins were identified as α1-microglobulin, α1-acid glycoprotein, and albumin. Using clinical assays, results were confirmed in a test set and validated in an independent prospective cohort. In the validation set, 135 (37%) developed AKI, in whom there was a progressive increase in urinary biomarker concentrations with severity of AKI. Areas under the curve for urinary α1-microglobulin, α1-acid glycoprotein, and albumin at 6 hours after cardiac surgery were 0.84 (95% CI, 0.79-0.89), 0.87 (95% CI, 0.83-0.91), and 0.76 (95% CI, 0.71-0.81), respectively. Participants with increasing quartiles of biomarkers showed increasing lengths of hospital stays and durations of AKI (P < 0.001).Limitations: Single-center study of children with normal kidney function at recruitment. The SELDI-TOF MS technique has limited sensitivity for the detection of proteins greater than the 20-kDa range.Conclusions: Urinary α1-microglobulin, α1-acid glycoprotein, and albumin represent early, accurate, inexpensive, and widely available biomarkers of AKI after cardiac surgery. They also offer prognostic information about the duration of AKI and length of hospitalization after cardiac surgery.

Predictors of Incident Albuminuria in the Framingham Offspring Cohort – Corrected Proof

Mon, 05 Jul 2010 02:00:00 +0000

Background: Predictors for incident albuminuria are not well known in population-based cohorts. The purpose of this study is to identify predictors of incident albuminuria in an unselected middle-aged population.Study Design: Observational cohort study.Setting & Participants: Framingham Offspring Study participants who attended both the sixth (baseline; 1995-1998) and eighth (2005-2008) examination cycles.Predictors: Standard clinical predictors were used. Predictors of incident albuminuria were identified using stepwise logistic regression analysis with age and sex forced into the model.Outcomes & Measurements: Albuminuria was defined as urine albumin-creatinine ratio (UACR) ≥17 mg/g (men) or ≥25 mg/g (women). Individuals with albuminuria at baseline were excluded.Results: 1,916 participants were available for analysis (mean age, 56 years; 54% women). Albuminuria developed in 10.0% of participants (n = 192) during 9.5 years. Age (OR, 2.09; P < 0.001), baseline diabetes (OR, 1.93; P = 0.01), smoking (OR, 2.09; P < 0.001), and baseline log UACR (OR per 1-SD increase in log UACR, 1.56; P < 0.001) were associated with incident albuminuria in a stepwise model. An inverse relationship with female sex (OR, 0.53; P < 0.001) and high-density lipoprotein (HDL) cholesterol level (OR, 0.80; P = 0.007) also was observed. Results were similar when participants with baseline chronic kidney disease (n = 102), defined as estimated glomerular filtration rate <60 mL/min/1.73 m2, were excluded from the model. Age, male sex, low HDL cholesterol level, smoking, and log UACR continued to be associated with incident albuminuria when baseline diabetes (n = 107) was excluded. Age, male sex, and log UACR correlated with incident albuminuria after participants with baseline hypertension were excluded (n = 651).Limitations: Causality may not be inferred because of the observational nature of the study. One-third of participants did not return for follow-up, potentially attenuating the observed risks of albuminuria.Conclusions: The known cardiovascular risk factors of increasing age, male sex, diabetes, smoking, low HDL cholesterol level, and albuminuria within the reference range are correlates of incident albuminuria in the general population.

Pregnancy and Progression of IgA Nephropathy: Results of an Italian Multicenter Study – Corrected Proof

Mon, 05 Jul 2010 02:00:00 +0000

Background: Whether pregnancy impacts on the long-term outcome of immunoglobulin A (IgA) nephropathy is unknown. This study aims to compare the long-term outcome of kidney disease in women with IgA nephropathy and preserved kidney function who did and did not become pregnant.Study Design: Multicenter longitudinal cohort study.Setting & Participants: Women of childbearing age with biopsy-proven IgA nephropathy, serum creatinine level ≤1.2 mg/dL at diagnosis, and minimum follow-up of 5 years after biopsy recruited from 35 nephrology centers participating in a national collaborative study group of pregnancy and kidney disease sponsored by the Italian Society of Nephrology.Predictors: Pregnancy, treated as a time-dependent variable; baseline proteinuria; hypertension; and kidney biopsy histologic characteristics.Outcome & Measures: Rate of change in estimated creatinine clearance, change in proteinuria, and new-onset hypertension.Results: 245 patients were enrolled. Of these, 223 women (136 and 87 in the pregnancy and nonpregnancy groups, respectively) had serum creatinine levels ≤1.2 mg/dL at diagnosis. Baseline data (including age, estimated creatinine clearance, prevalence of hypertension, and histologic grade of kidney damage) were similar between groups with the exception of proteinuria (protein excretion, 1.33 vs 0.95 g/d in the pregnancy vs nonpregnancy groups, respectively; P = 0.03). Kidney function decreased 1.31 mL/min/y (95% CI, 0.99-1.63) during a median follow-up of 10 years (range, 5-31 years) and did not differ between groups. Baseline proteinuria predicted a faster decrease, but did not modify the effect of pregnancy. Pregnancy did not affect changes in proteinuria over time or risk of new-onset hypertension.Limitations: Unrecognized or unmeasured factors associated with the decision of becoming pregnant might have influenced results.Conclusions: Pregnancy does not seem to affect the long-term outcome of kidney disease in women with IgA nephropathy and preserved kidney function.