American Journal of Kidney Diseases

World Kidney Day 2010: Diabetic Kidney Disease—Act Now or Pay Later

Robert C. Atkins, Paul Zimmet — 2010-02-01

In 2003, the International Society of Nephrology (ISN) and the International Diabetes Federation (IDF) launched a booklet called “Diabetes and Kidney Disease: Time to Act” to highlight the global pandemic of type 2 diabetes and diabetic kidney disease. It aimed to alert governments, health organizations, providers, doctors, and patients to the increasing health and socioeconomic problems due to diabetic kidney disease and its sequelae, end-stage kidney disease requiring dialysis and cardiovascular death. Seven years later, the same message has become even more urgent. World Kidney Day 2010, under the auspices of the ISN and the International Federation of Kidney Foundations (IFKF), together with the IDF, provides yet another chance to underline the importance of diabetic kidney disease, stress the lack of awareness of this disease at both public and government levels, and emphasize that its management involves prevention, recognition, and treatment of its complications. Primary prevention of type 2 diabetes will require massive lifestyle changes in the developing and developed worlds, supported by strong governmental commitment to promote lifestyle and societal change.

Doc, Don't Procrastinate…Rehabilitate, Palliate, and Advocate

S. Vanita Jassal, Diane Watson — 2010-02-01

Why Do Patients Develop Proteinuria With Sirolimus? Do We Have the Answer?

Jeremy R. Chapman, Gopala K. Rangan — 2010-02-01

The 2009 Proposed Rule for Prospective ESRD Payment: Historical Perspectives and Public Policies—Bundle Up!

Daniel E. Weiner, Suzanne G. Watnick — 2010-02-01

The costs of health care in the United States account for 16% of gross domestic product and are rising at 6.7% per year, exceeding the rate of rise in wages or inflation. In parallel, the costs associated with end-stage renal disease (ESRD) care rose by 6% in 2007 to $24 billion (). This expenditure constitutes 5.8% of the overall Medicare budget, including Part D, but accounts for less than 1% of Medicare beneficiaries. Facing an increasing prevalence of ESRD in the United States and therefore increased costs, even in the setting of relatively stable per patient costs, the Medicare ESRD program is now the target of legislative efforts to curb expenditures while maintaining quality and availability. This editorial will outline economic aspects of dialysis care in the United States, including an overview of the history and structure of the current reimbursement system, a review of the Medicare Improvements for Patients and Providers Act of 2008 (MIPPA) with a focus on the subsequent expanded bundle system proposed by the Centers for Medicare & Medicaid Services (CMS), and a brief summary of potential advantages and disadvantages associated with the expanded bundle.

The 2009 Proposed Rule for Prospective ESRD Payment: Perspectives From a Large Dialysis Organization

Allen R. Nissenson, Tracy J. Mayne, Mahesh Krishnan — 2010-02-01

On September 15, 2009, the Centers for Medicare & Medicaid Services (CMS) released the proposed rules of coverage for the new prospective payment system governing reimbursement for end-stage renal disease. There are numerous implications for the forthcoming changes in coverage; some are common to the entire kidney community while some are unique to specific segments. We discuss here the implications of the changes for patients and dialysis facilities.

The 2009 Proposed Rule for Prospective ESRD Payment: Perspectives From a Medium-Sized Dialysis Organization

John Moran — 2010-02-01

The variation in observed costs not predicted by the case-mix model is substantial. To the extent that some facilities cannot respond appropriately to the incentives in the bundled system to reduce costs without compromising patient outcomes, these facilities may face material financial risk.University of Michigan Kidney Epidemiology and Cost Center (KECC) Report, September 2009

The 2009 Proposed Rule for Prospective ESRD Payment: Perspectives From a Not-for-Profit Small Dialysis Organization

John H. Sadler — 2010-02-01

Conceptually, combining routine components of repetitive therapy into a single payment is rational. However, it can work only if the elements included and payments for them are reasonable. Sadly, as seen in the end-stage renal disease (ESRD) prospective payment system proposed by the Centers for Medicare & Medicaid Services (CMS), some parts of the new proposed rule are not reasonable, and critically, are not based on complete or accurate evidence. Some of the assumptions used to create the expanded bundle are not realistic, and too many adjustments may only serve to create expense and confusion rather than fairness. Under these proposed regulations, most small dialysis organizations are no longer viable.

The 2009 Proposed Rule for Prospective ESRD Payment: Perspectives From a For-Profit Small Dialysis Organization

J. Ganesh Bhat, Premila Bhat — 2010-02-01

According to the 2009 US Renal Data System Annual Data Report, large dialysis organizations (LDOs), specifically Fresenius Medical Care North America, DaVita Inc, and Dialysis Clinic Inc, provide dialysis services for approximately 65% of dialysis patients in the United States. The remaining 35% of patients, approximately 135,000 individuals in all, receive dialysis at small regional chain operations, independent facilities, or hospital-based dialysis centers. Nearly 2,000 in number, these small dialysis organizations (SDOs) constitute a diverse group, which includes for-profit regional chains; independently owned and operated facilities, frequently with physician investment; not-for-profit entities; and a variety of hospital-operated centers. While these groups have diverse characteristics, they share common concerns regarding the imminent conversion to a “bundled” prospective payment system (PPS) proposed by the Centers for Medicare & Medicaid Services (CMS). Fundamental to these concerns is an imbalance between SDOs and LDOs with regard to the ability to spread risk over larger pools of patients, economies of scale, and legal obstacles barring organizational efficiencies such as establishment of pharmacies and laboratories.

The 2009 Proposed Rule for Prospective ESRD Payment: Perspectives From the Forum of ESRD Networks

Cynthia Kristensen, Jay Wish — 2010-02-01

The Forum of ESRD Networks welcomes the opportunity to comment on the proposed rule for the end-stage renal disease (ESRD) prospective payment system (PPS). The Forum is a not-for-profit organization that advocates on behalf of the 18 regional ESRD Networks, coordinates projects and activities of mutual interest to the Networks, and facilitates the flow of information to and between the Networks. This editorial reflects the consensus of Forum leadership, including Network Executive Directors and nephrologists from all 18 Networks. The Networks and Forum are not involved with reimbursement policy except as it affects quality of care.

AURORA: Is There a Role for Statin Therapy in Dialysis Patients?

Sabin Shurraw, Marcello Tonelli — 2009-11-18

Commentary on Fellstrom BC, Jardine AG, Schmieder RE, et al; AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360(14):1395-1407.

Nephrologists' Perspectives on the Effect of Guidelines on Clinical Practice: A Semistructured Interview Study

2010-01-04

Background: A consistent gap exists between evidence-based guideline recommendations and clinical practice across all medical disciplines, including nephrology. This study aims to explore nephrologists' perspectives on guidelines and elicit their perspectives on the effects of guidelines on clinical decisions.Methods: Semistructured face-to-face interviews were undertaken with 19 nephrologists from a variety of clinical settings across Australia. Participants were asked about their views of clinical practice guidelines in nephrology, both local (Caring for Australasians With Renal Impairment [CARI]) and international, and their opinions of other factors that shape their decision making. Interviews were recorded, transcribed, and analyzed qualitatively.Results: 4 major themes were identified. First, overall, the nephrologists interviewed trusted the CARI guideline process and output. Second, guidelines served a variety of purposes, providing a good summary of evidence, a foundation for practice, an educational resource, and justification for funding requests to policy makers, as well as promoting patient adherence to treatment. Third, guidelines were only one input into decision making. Other inputs included individual patient quality of life and circumstances, opinion leaders, peers, nephrologists' own experiences, the regulation and subsidy framework for drugs and devices, policies and work practices of the local unit, and other sources of evidence. Fourth, guideline uptake varied. Factors that favored the use of guidelines included having a strong evidence base, being current, including specific targets and an explicit treatment algorithm, being sent frequent reminders, and having local peer support for implementation and the necessary personnel and other resources for effective implementation.Conclusions: Evidence-based guidelines appear to impact strongly on clinical decision making of Australian nephrologists, but are only one input. Improvements in the evidence that underpins guidelines and improvements in the content and formatting of guidelines are likely to make them more influential on decision making. Trust in the guideline groups' processes is a prerequisite for implementation.

Prediction of ESRD in Pauci-immune Necrotizing Glomerulonephritis: Quantitative Histomorphometric Assessment and Serum Creatinine

2010-01-04

Background: Clinical and pathologic features that predict outcome have important potential application in patients with pauci-immune necrotizing glomerulonephritis (usually antineutrophil cytoplasmic antibody–associated vasculitis). This study examines the predictive value of simple quantitative renal histologic measurements in a large cohort with extended follow-up.Study Design: Cohort study.Setting & Participants: 390 consecutive patients with pauci-immune necrotizing glomerulonephritis at a single hospital (1983-2002); 90 patients underwent repeated kidney biopsy during follow-up.Predictors: Age and serum creatinine concentration at biopsy, antineutrophil cytoplasmic antibody specificity, percentage of normal glomeruli, percentage of glomeruli with active lesions, and index of chronic damage (quantitative measurement of established cortical damage) in the initial kidney biopsy for all patients. The same factors were assessed in both biopsy specimens for patients undergoing an additional biopsy.Outcomes & Measurements: End-stage renal disease and patient survival.Results: Mortality at 1 and 5 years was 23% and 40%, respectively: standardized mortality ratio, 4.74 (95% CI, 3.62-6.32). End-stage renal disease was reached by 14% and 18% at 1 and 5 years, respectively. In multivariable analysis, serum creatinine level at biopsy and percentage of normal glomeruli in the initial biopsy specimen were the best predictors of kidney survival. C Statistics were 0.80 for creatinine level alone and 0.83 for creatinine level with normal glomeruli. In patients undergoing an additional biopsy, rapid progression in the index of chronic damage and serum creatinine level at the second biopsy were associated with kidney survival in multivariable analysis.Limitations: Retrospective analysis. External validity of the index of chronic damage requires further assessment. Selection bias may influence repeated biopsy analyses.Conclusions: Serum creatinine level at biopsy best predicts kidney survival in patients with pauci-immune necrotizing glomerulonephritis overall.

Is Presence of ANCA in Crescentic IgA Nephropathy a Coincidence or Novel Clinical Entity? A Case Series

2009-12-31

Background: There are few anecdotal reports of circulating antineutrophil cytoplasmic autoantibodies (ANCAs) in patients with immunoglobulin A (IgA) nephropathy.Study Design: Retrospective case series.Setting & Participants: We studied 8 patients with crescentic IgA nephropathy associated with ANCAs against myeloperoxidase (n = 5) and proteinase 3 (n = 3) followed up for 2.4 ± 1.7 years. They were compared with 26 patients with IgA nephropathy with > 10% crescentic glomeruli, but negative for ANCAs.Outcomes: We analyzed clinical and histologic features of patients and their response to treatment.Measurements: Screening for ANCAs was performed using indirect immunofluorescence, and positive results were verified using enzyme-linked immunosorbent assay.Results: All patients with crescentic IgA nephropathy and positive for ANCAs, compared with only one-third of ANCA-negative patients, presented with the clinical syndrome of rapid progressive glomerulonephritis. ANCA-positive patients reached a higher peak serum creatinine level within the first 3 months (4.2 ± 2.2 vs 2.5 ± 1.9 mg/dL; estimated glomerular filtration rate, 19.3 ± 10.2 vs 45.9 ± 30.1 mL/min/1.73 m2). ANCA-positive patients with IgA nephropathy had a higher percentage of crescentic glomeruli (54.3% ± 18%) compared with ANCA-negative patients with crescentic IgA nephropathy (34.5% ± 26%). ANCA-positive patients were treated using cyclophosphamide and corticosteroids. Kidney function improved in all these patients: serum creatinine level decreased from the peak of 4.2 ± 2.2 to 1.7 ± 0.7 mg/dL at the end of follow up (estimated glomerular filtration rate, 19.3 ± 10.2 to 44.6 ± 11.1 mL/min/1.73 m2). In contrast, no significant improvement was achieved in ANCA-negative patients.Conclusion: Patients with IgA nephropathy, crescents, and positive for ANCAs represent a clinical entity with a diverse more exaggerated clinical and histologic picture. However, disease in these patients responded well to aggressive immunosuppressive therapy.

Sleep and Fatigue Symptoms in Children and Adolescents With CKD: A Cross-sectional Analysis From the Chronic Kidney Disease in Children (CKiD) Study

2009-12-25

Background: Although symptoms of sleepiness and fatigue are common in adults with chronic kidney disease (CKD), little is known about the prevalence of these symptoms in children with CKD.Study Design: Cross-sectional analysis within a cohort study.Setting & Participants: We describe the frequency and severity of sleep problems and fatigue and assess the extent of their association with measured glomerular filtration rate (mGFR) and health-related quality of life (HRQOL) in 301 participants of the Chronic Kidney Disease in Children cohort.Outcomes & Measurements: Sleep and fatigue-related items from the Pediatric Quality of Life Inventory 4.0 Generic Scales and the CKD-related Symptoms List were used.Results: Median mGFR was 42.0 mL/min/1.73 m2 (25th-75th percentiles, 31.2-53.2), and median age was 13.9 years (25th-75th percentiles, 10.8-16.2). Children with mGFR of 40-<50, 30-<40, or <30 mL/min/1.73 m2 had 2.07 (95% CI, 1.05-4.09), 2.35 (95% CI, 1.17-4.72), and 2.59 (95% CI, 1.15-5.85) higher odds of having more severe parent reports of low energy than children with mGFR ≥ 50 mL/min/1.73 m2. Compared with participants with mGFR ≥ 50 mL/min/1.73 m2, those with mGFR < 30 mL/min/1.73 m2 had 3.92 (95% CI, 1.37-11.17) higher odds of reporting more severe weakness, and those with mGFR of 40-<50 mL/min/1.73 m2 had 2.95 (95% CI, 1.26-6.88) higher odds of falling asleep during the day. Low energy, trouble sleeping, and weakness were associated with lower HRQOL scores.Limitations: Symptoms of sleep and fatigue represent the child's or parent's perception of symptom severity, whereas individual items can lead to imprecise measurements of sleep and fatigue.Conclusions: Lower mGFR was associated with increased weakness, low energy, and daytime sleepiness. Furthermore, a strong association between trouble sleeping, low energy, and weakness with decreases in overall HRQOL was observed. Detection and treatment of poor sleep and fatigue may improve the development and HRQOL of children and adolescents with CKD.

Associations Between Renal Duplex Parameters and Adverse Cardiovascular Events in the Elderly: A Prospective Cohort Study

2010-02-01

Background: Atherosclerotic renovascular disease is associated with an increased risk of cardiovascular disease (CVD) events. This study examines associations between Doppler-derived parameters from the renal artery and renal parenchyma and all-cause mortality and fatal and nonfatal CVD events in a cohort of elderly Americans.Study Design: Cohort study.Setting: A subset of participants from the Cardiovascular Health Study (CHS). Through an ancillary study, 870 (70% recruitment) Forsyth County, NC, CHS participants consented to undergo renal duplex sonography to define the prevalence of renovascular disease in the elderly, resulting in 726 (36% men; mean age, 77 years) technically adequate complete studies included in this investigation.Predictor: Renal duplex sonography–derived Doppler signals from the main renal arteries and renal parenchyma. Spectral analysis from Doppler-shifted frequencies and angle of insonation were used to estimate renal artery peak systolic and end diastolic velocity (both in meters per second). Color Doppler was used to identify the corticomedullary junction. Using a 3-mm Doppler sample, the parenchymal peak systolic and end diastolic frequency shift (both in kilohertz) were obtained. Resistive index was calculated as (1 − [end diastolic frequency shift/peak systolic frequency shift]) using Doppler samples from the hilar arteries of the left or right kidney with the higher main renal artery peak systolic velocity.Outcomes & Measurements: Proportional hazard regression analysis was used to determine associations between renal duplex sonography–derived Doppler signals and CVD events and all-cause mortality adjusted for accepted cardiovascular risk factors. Index CVD outcomes were defined as coronary events (angina, myocardial infarction, and coronary artery bypass grafting/percutaneous coronary intervention), cerebrovascular events (stroke or transient ischemic attack), and any CVD event (angina, congestive heart failure, myocardial infarction, stroke, transient ischemic attack, and coronary artery bypass grafting [CABG]/percutaneous transluminal coronary intervention [PTCI]).Results: During follow-up, 221 deaths (31%), 229 CVD events (32%), 122 coronary events (17%), and 92 cerebrovascular events (13%) were observed. Renal duplex sonography–derived Doppler signals from the renal parenchyma were associated independently with all-cause mortality and CVD outcomes. In particular, increased parenchymal end diastolic frequency shift was associated significantly with any CVD event (HR, 0.73; 95% CI, 0.62-0.87; P < 0.001). Marginally significant associations were observed between increases in parenchymal end diastolic frequency shift and decreased risk of death (HR, 0.86; 95% CI, 0.73-1.00; P = 0.06) and decreased risk of cerebrovascular events (HR, 0.78; 95% CI, 0.61-1.01; P = 0.06). Parenchymal end diastolic frequency shift was not significantly predictive of coronary events (HR, 0.84; 95% CI, 0.67-1.06; P = 0.1).Limitations: CHS participants showed a “healthy cohort” effect that may underestimate the rate of CVD events in the general population.Conclusion: Renal duplex sonographic Doppler signals from the renal parenchyma showed significant associations with subsequent CVD events after controlling for other significant risk factors. In particular, a standard deviation increase in parenchymal end diastolic frequency shift was associated with 27% risk reduction in any CVD event.

Kidney Function and Rate of Bone Loss at the Hip and Spine: The Canadian Multicentre Osteoporosis Study

2009-12-31

Background: The relationship between kidney function and bone loss is unclear.Study Design: A prospective observational study.Setting & Participants: 191 men and 444 women aged ≥ 50 years participating in a population-based observational study designed to determine risk factors for bone loss and fractures.Predictors: The primary predictor of change in bone mineral density (BMD) was estimated creatinine clearance (using the Cockcroft-Gault formula) measured at baseline and stratified by quartiles. Our secondary predictor was estimated glomerular filtration rate using the Modification of Diet in Renal Disease Study equation, also stratified by quartiles.Outcomes & Measurements: Changes in BMD at the lumbar spine, total hip, and femoral neck during 5 years.Results: Compared with participants in the first quartile of estimated creatinine clearance (>101.2 mL/min), those in remaining quartiles were older (quartile 1, 50.0 years; quartile 2 [101.2-83.4 mL/min], 54.7 years; quartile 3 [83.4-68.3 mL/min], 60.5 years; and quartile 4 [<68.3 mL/min], 68.3 years); weighed less; reported more sedentary hours; were less likely to report excellent, very good, or good self-reported health; consumed less caffeine; and had lower serum calcium and phosphate and higher serum parathyroid hormone levels. After adjusting for age, weight, sex, baseline BMD, and these differences, compared with those in the first quartile, those in the fourth quartile had decreases in BMD of 0.08 g/cm2 (95% CI, 0.04-0.1) at the lumbar spine, 0.08 g/cm2 (95% CI, 0.06-0.1) at the femoral neck, and 0.09 g/cm2 (95% CI, 0.07-0.1) at the total hip. Bone loss did not increase with worsening kidney function (P for trend > 0.05). Results were not substantially different using estimated glomerular filtration rate.Limitations: Observational study design and indirect measures of kidney function.Conclusions: Men and women with impaired kidney function are at increased risk of bone loss, even with minimal reduction in kidney function.

Outcomes of Hemodialysis Patients in a Long-term Care Hospital Setting: A Single-Center Study

Charuhas V. Thakar, Margaret Quate-Operacz, Anthony C. Leonard, Mark H. Eckman — 2009-12-14

Background: Long-term care hospitals (LTCHs) provide intermediary care after an acute-care hospitalization and usually furnish care to patients with complex medical problems. Outcomes of hemodialysis patients admitted to LTCHs, which includes patients with either end-stage renal disease (ESRD) or acute kidney injury (AKI) requiring dialysis therapy, are not known.Study Design: Observational study.Setting & Participants: All consecutive hemodialysis patients admitted to an LTCH.Predictors: Demographic characteristics, comorbid and laboratory variables, ESRD, and AKI status during LTCH stay.Outcomes: Disposition from LTCHs was classified as discharge to home, nursing home, death in LTCH or hospice care, and re-admission to the hospital. In patients with AKI, renal recovery was defined as discontinuation of dialysis therapy before meeting disposition outcomes.Results: 96 of 206 (46.6%) patients had ESRD, whereas 110 of 206 (53.3%) developed AKI requiring dialysis therapy during the acute-care hospitalization. 63 of 206 (31%) were discharged to home, 11 of 206 (5.4%) died or transferred to hospice, 81 of 206 (40%) went to a nursing home, and 49 of 206 (24%) were re-admitted to a hospital; mortality after re-admission was 32%. Older age (OR, 0.96; 95% CI, 0.93-0.98), diabetes mellitus (OR, 0.45; 95% CI, 0.23-0.94), number of re-admissions to the hospital (OR, 0.38; 95% CI, 0.18-0.78), aminoglycoside use (OR, 0.16; 95% CI, 0.04-0.64), and duration of hospitalization before LTCH admission (OR, 0.96; 95% CI, 0.94-0.99) were associated with lower odds of discharge to home. Of 110 patients with AKI requiring dialysis therapy, 30% (33 patients) discontinued dialysis therapy, whereas 70% were deemed to have ESRD on discharge.Limitations: Retrospective observational study.Conclusions: Most dialysis patients at LTCHs are either re-admitted to acute-care hospitals or require nursing home placement. Only 30% of patients with AKI recover sufficiently to discontinue dialysis therapy, whereas 70% are deemed to have ESRD.

A Randomized, Parallel, Open-Label Study to Compare Once-Daily Sevelamer Carbonate Powder Dosing With Thrice-Daily Sevelamer Hydrochloride Tablet Dosing in CKD Patients on Hemodialysis

2009-12-31

Background: Sevelamer carbonate powder for oral suspension is a new dosage form of sevelamer, which may be suited to once-daily dosing.Study Design: Randomized parallel open-label study.Setting & Participants: Hemodialysis patients.Intervention: After a 2-week phosphate-binder washout, patients were randomly assigned to once-daily sevelamer carbonate powder or thrice-daily sevelamer hydrochloride tablets.Outcomes: Assessment of noninferiority with respect to change from baseline in serum phosphorus levels.Measurements: Serum phosphorus to 24 weeks.Results: After washout, mean serum phosphorus level decreased 2.0 ± 1.8 mg/dL (from 7.3 ± 1.3 mg/dL) for sevelamer carbonate and 2.9 ± 1.3 mg/dL (from 7.6 ± 1.3 mg/dL) for sevelamer hydrochloride (both P < 0.001). The upper CI bound was 1.50 mg/dL; therefore, noninferiority was not shown. 54% of sevelamer carbonate powder–treated patients and 64% of sevelamer hydrochloride tablet–treated patients had serum phosphorus levels within the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) target (≥3.5 and ≤5.5 mg/dL). Overall, the percentage of patients with treatment-emergent adverse events was similar between groups. However, a greater percentage of treatment-related upper gastrointestinal events, including nausea (10% vs 3%) and vomiting (6% vs 1%), were noted with sevelamer carbonate powder once daily. In addition, 4 (3%) sevelamer carbonate–treated patients experienced stimulation of the gag reflex and 2 (1%) experienced dislike of the taste with sevelamer carbonate powder. A greater percentage of sevelamer carbonate powder–treated patients discontinued treatment because of these treatment-related events or consent withdrawal.Limitations: Study was not blinded. Once-daily dose may not have been with the highest phosphate content meal; further exploration of alternative dosing schemes is warranted.Conclusions: Once-daily administration of sevelamer carbonate powder was not as effective in decreasing serum phosphorus levels as thrice-daily administration of sevelamer hydrochloride tablets. Nevertheless, once-daily sevelamer carbonate powder decreased serum phosphorus levels significantly, reaching the KDOQI phosphorus target in most patients. Therefore, once-daily dosing of sevelamer carbonate may be a reasonable alternative.

Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy: The Prospective Pediatric Continuous Renal Replacement Therapy Registry

2009-12-31

Background: Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT.Study Design: Prospective observational study.Setting & Participants: 297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry.Predictor: Fluid overload from intensive care unit (ICU) admission to CRRT initiation, defined as a percentage equal to (fluid in [L] − fluid out [L])/(ICU admit weight [kg]) × 100%.Outcome & Measurements: The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness.Results: 153 patients (51.5%) developed < 10% fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93 patients (31.3%) developed ≥ 20% fluid overload. Patients who developed ≥ 20% fluid overload at CRRT initiation had significantly higher mortality (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those with < 10% fluid overload (45/153; 29.4%). The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized to ≥ 20% and < 20%, patients with ≥ 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8-25.7).Limitations: This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality.Conclusions: Critically ill children who develop greater fluid overload before initiation of CRRT experience higher mortality than those with less fluid overload. Further goal-directed research is required to accurately define optimal fluid overload thresholds for initiation of CRRT.

Secondary Hyperparathyroidism and Anemia in Children Treated by Hemodialysis

2010-02-01

Background: Many patients treated using hemodialysis remain anemic despite exogenous erythropoietin therapy, suggesting that the anemia experienced by these patients is multifactorial in cause. Iron deficiency, infection, inflammation, and malnutrition have been implicated in this process. Additionally, secondary hyperparathyroidism has been associated with anemia in adults, but few data exist about this topic in children.Study Design: Cross-sectional retrospective.Setting & Participants: Children treated in hemodialysis centers (N = 588) within the Centers for Medicare & Medicaid Services' 2002 Clinical Performance Measures Project.Predictor: Intact parathyroid hormone (iPTH) levels assessed in October, November, and December 2001 and categorized as quintiles.Outcomes & Measurements: Achievement of serum hemoglobin level ≥ 11 g/dL was assessed using Poisson regression adjusting for sex, age, race, dialysis vintage, vascular access type, single-pool Kt/V, serum albumin level, normalized protein catabolic rate, calcium-phosphorus product, and erythropoietin alfa dose.Results: Using the second quintile (iPTH, 103-224 pg/mL) as the reference quintile, there was no association between iPTH quintile and achievement of the hemoglobin goal: quintile 1 prevalence ratio, 1.0 (95% CI, 0.9-1.2); quintile 3, 0.95 (95% CI, 0.8-1.1); quintile 4, 0.99 (95% CI, 0.8-1.2); and quintile 5, 0.97 (95% CI, 0.8-1.1). Only serum albumin level ≥ 3.5 g/dL (bromocresol green assay method) or ≥ 3.2 g/dL (bromocresol purple assay method) was significantly associated with meeting the hemoglobin goal: 1.4 (95% CI, 1.2-1.6).Limitations: The simultaneous collection of iPTH and hemoglobin limits causal inference. Iron stores and iron therapy are potential confounders not accounted for in this study.Conclusions: In the largest study of this topic in children, no association was found between iPTH level and achievement of a hemoglobin level ≥ 11 g/dL. Serum albumin level was associated strongly with achievement of the hemoglobin goal.

Tubular Toxicity in Sirolimus- and Cyclosporine-Based Transplant Immunosuppression Strategies: An Ancillary Study From a Randomized Controlled Trial

2009-11-18

Background: Sirolimus has been promoted as an agent to provide immunosuppression for kidney transplant recipients that, in contrast to calcineurin inhibitors, would not be nephrotoxic. However, several reports have observed proteinuria in patients treated with sirolimus, ranging from low grade to nephrotic range. Accordingly, we compared markers of tubular and glomerular damage in an ancillary study of a randomized trial comparing sirolimus and cyclosporine.Study Design: Single-center, open-label, randomized, prospective trial.Setting & Participants: Patients undergoing cadaveric or living donor kidney transplant at the University Hospital in Basel, Switzerland, between January 2001 and July 2004.Intervention: Immunosuppression regimen consisting of cyclosporine, mycophenolate mofetil, and prednisone versus sirolimus, mycophenolate mofetil, and prednisone.Outcomes: The primary outcome was kidney function, assessed using serum creatinine level. Secondary outcomes included patient and graft survival, number of rejections, and evidence of kidney damage, assessed using glomerular and tubular urine biomarker levels.Measurements: Urine and serum were collected at 0, 7, 30, and 90 days. Kidney function was estimated using serum creatinine level. Urinary markers included α1-microglobulin and retinol-binding protein (tubular), transferrin and albumin (glomerular), and semiquantitative assessment of glucosuria. Protocol kidney biopsies were performed at days 90 and 180.Results: There were 63 patients randomly assigned to cyclosporine-based regimens, and 64, to sirolimus-based regimens. Kidney function was similar in both groups, whereas levels of markers associated with glomerular damage (albumin, 19.5 vs 8.96 mg/mmol creatinine; P < 0.001; transferrin, 13.1 vs 5.7 mg/mmol creatinine; P < 0.001) and those associated with tubular damage (α1-microglobulin, 11 vs 7.6 mg/mmol creatinine; P = 0.004; retinol-binding protein, 19.6 vs 9.6 mg/mmol creatinine; P = 0.002) were higher beginning at day 7 in patients randomly assigned to sirolimus therapy, with similar findings through day 90. Glucosuria incidence was higher in patients randomly assigned to sirolimus therapy beginning by day 30 (65% vs 30% on day 30; P = 0.002; 51% vs 22% on day 90; P < 0.001). On histologic examination, the overall severity of tubular lesions was significantly higher in patients randomly assigned to sirolimus therapy.Limitations: Small sample size, short-term follow-up likely insufficient to appreciate calcineurin-associated nephropathy.Conclusion: Compared with a cyclosporine-based immunosuppression regimen, a sirolimus-based regimen is associated with de novo low-grade glomerular proteinuria, increased excretion of markers associated with tubular damage, and evidence of tubular damage on kidney biopsy.

Successful Treatment With Retinoids in Patients With Lupus Nephritis

2009-07-24

Lupus nephritis is a major manifestation of systemic lupus erythematosus. Treatment with such immunosuppressive agents as corticosteroids or cyclophosphamide can decrease the progression of lupus nephritis; however, these agents have potentially severe adverse reactions. Therefore, the development of new drugs with fewer side effects is needed. Here, we report 2 patients with lupus that were treated successfully with retinoids. Initially, both patients were treated with 60 mg/d of prednisolone. However, nephrotic syndrome was not improved. Subsequently, treatment with 10 mg/d of all-trans-retinoic acid was started orally and elicited a good response, showing a decrease in proteinuria. Although additional controlled clinical studies are needed to confirm these findings, we suggest that therapy using retinoids may represent a novel approach to the treatment of patients with lupus nephritis.

Embolic Complications From Central Venous Hemodialysis Catheters Used With Hypertonic Citrate Locking Solution

Michelle Kay Willicombe, Katherine Vernon, Andrew Davenport — 2009-10-05

Many hemodialysis patients continue to dialyze using central venous access catheters in clinical practice. Catheters are associated with a number of recognized complications, including infection, catheter-associated fibrin sheath and thrombus leading to malfunction, central venous stenosis, and right atrial thrombus. However, symptomatic catheter embolus rarely is reported. We report our experience of catheter-associated emboli in patients dialyzing with a twin catheter designed with multiple small side holes in combination with a hypertonic citrate locking solution. 8 patients developed symptomatic emboli from catheter-associated thrombus, typically resulting in sudden hypotension and chest pain shortly after starting hemodialysis, with documented pulmonary and cerebral emboli in 3 cases. Catheters with multiple side holes are susceptible to seepage of the catheter locking solution through the side holes and therefore may be at greater risk of catheter thrombus formation. This may be exacerbated by the use of a hypertonic citrate lock given to just fill the internal catheter lumen because hyperosmolar locks are more likely to leave the catheter tip, resulting in increased risk of catheter associated thrombus.

Is There a Role for Intradialytic Parenteral Nutrition? A Review of the Evidence

Ramanath Dukkipati, Kamyar Kalantar-Zadeh, Joel D. Kopple — 2009-10-26

Protein-energy wasting (PEW) is highly prevalent in people with stages 4 and 5 chronic kidney disease, particularly in maintenance dialysis patients, and many indicators of PEW correlate strongly with mortality. Consequently, the causes, prevention, and treatment of PEW are active areas of investigation. A major cause of PEW is insufficient intake of nutrients, especially protein and energy (calories). Standard methods for increasing nutritional intake in patients with chronic kidney disease with PEW include dietary counseling and use of food supplements. If nutrient intake does not increase sufficiently, tube feeding and total parenteral nutrition may be considered. For maintenance hemodialysis patients, intradialytic parenteral nutrition (IDPN), an intravenous infusion of essential nutrients during hemodialysis treatments, may be used. Many studies have evaluated the effectiveness and safety of IDPN and show that IDPN has a good safety profile and also may improve protein-energy status. However, most studies have limitations in experimental design, such as small numbers of patients, lack of adequate controls, inclusion of patients without PEW, uncontrolled or unmonitored oral intake, nonrandomized design, or short duration. Additionally, most studies used nutritional or inflammatory indicators, rather than the more important outcomes of morbidity, mortality, or quality of life. Thus, although IDPN may partially satisfy the nutritional needs of maintenance hemodialysis patients who have or are at risk of PEW and who have substantial, but not adequate, protein and/or energy intake, longer term randomized prospective clinical trials with appropriate control groups are necessary to more definitively evaluate the clinical effectiveness and indications for IDPN.

The Management of Diabetic Neuropathy in CKD

2009-12-31

A 64-year-old man with a 15-year history of poorly controlled type 2 diabetes and a 10-year history of hypertension and hyperlipidemia had developed multiple diabetes-related complications within the last 5 years. He first developed albuminuria 5 years ago, and during the next several years, he experienced a fairly rapid decrease in kidney function, with an estimated glomerular filtration rate of 55 mL/min/1.73 m2 noted 2 years ago. Proliferative retinopathy was diagnosed 5 years ago, and he underwent laser photocoagulation. Four years ago, he noted symptoms of peripheral neuropathy manifested as shooting pain and numbness with loss of light touch, thermal, and vibratory sensation in a stocking distribution. Last year, he developed a nonhealing ulcer on the plantar aspect of his left foot that was complicated by gangrene and resulted in a below-the-knee amputation of the left leg 1 year ago. He now reports new onset of weakness, lightheadedness, and dizziness on standing that affects his daily activities. He reports lancinating pain in his right lower extremity, worse in the evening. Medications include neutral protamine Hagedorn insulin twice daily and regular insulin on a sliding scale; metoprolol, 50 mg/d; lisinopril, 40 mg/d; atorvastatin, 80 mg/d; furosemide, 40 mg/d; and aspirin, 81 mg/d. Blood pressure is 127/69 mm Hg with a pulse rate of 96 beats/min while supine and 94/50 mm Hg with a pulse rate of 102 beats/min while standing. Strength is normal, but with complete loss of all sensory modalities to the knee in his remaining limb and up to the wrists in both upper extremities, and he is areflexic. Today's laboratory evaluations show a serum creatinine level of 2.8 mg/dL, estimated glomerular filtration rate of 24 mL/min/1.73 m2, hemoglobin A1c level of 7.9%, and urine protein excretion of 2.1 g/1 g of creatinine. What would be the most appropriate management for this patient?

An Uncommon Cause of Membranous Glomerulonephritis

Anjali A. Satoskar, Paul Kovach, Kevin O'Reilly, Tibor Nadasdy — 2009-07-31

Membranous glomerulonephritis (MGN) is one of the most common causes of nephrotic syndrome in the adult population, characterized by the formation of subepithelial immune complexes in the glomerular capillary wall and associated with heavy proteinuria. MGN is not a single disease entity, but a pattern of injury in the kidney with diverse causes. MGN can be primary/idiopathic (cause unknown) or secondary. Known causes of secondary MGN are described under 4 broad categories: (1) drugs/medications, (2) infections, (3) autoimmune disorders, and (4) malignancy.

Membranoproliferative Glomerulonephritis, Chronic Lymphocytic Leukemia, and Cryoglobulinemia

2009-08-07

The coexistence of chronic lymphocytic leukemia (CLL) and nephrotic syndrome was described first by Scott in 1957. The incidence of nephrotic syndrome in patients with CLL is approximately 1% to 2%. Although membranous glomerulonephritis, minimal change, crescentic glomerulonephritis, light-chain deposition disease, amyloidosis, and focal segmental glomerulosclerosis may account for nephrotic syndrome in some instances, the most common lesion is membranoproliferative glomerulonephritis (MPGN). MPGN in the setting of CLL may be caused by cryoglobulinemia, predominantly type II, or be associated with organized immunotactoid deposits made of a monoclonal immunoglobulin G (IgG), classically without cryoglobulinemia and complement activation. The link between CLL and glomerular disease is the monoclonal immunoglobulin produced by the B-cell clone. Furthermore, similar organized deposits with microtubule formation may be found in leukemic lymphocytes and glomeruli of patients with immunotactoid glomerulopathy. The causal relationship between CLL and the glomerulopathy is supported further by parallel improvement of the 2 diseases with chemotherapy.

Radiographic Features of Malpositioning of a Hemodialysis Catheter in the Azygos Vein

Uei Pua — 2009-09-27

Percutaneous image-guided insertion of a tunneled hemodialysis catheter is a common procedure practiced by interventional nephrologists and radiologists. Among the myriads of reasons for catheter dysfunction presenting as poor flow during dialysis, inadvertent placement of the catheter into the azygos vein is a known, but rare, cause. This malpositioning can be difficult to detect during catheter insertion, as well as on chest radiography, given the subtle clinical and imaging findings. Familiarity with the radiographic features, therefore, is crucial for detection. We hereby illustrate the radiographic features of this malposition.

Toxic Nephropathies: Core Curriculum 2010

Mark A. Perazella — 2009-12-31

Toxic nephropathies are an important and relatively common category of kidney damage. Although they generally are reversible when detected early, they may be permanent, leading to chronic kidney disease (CKD). Toxic nephropathies are defined primarily as kidney injury caused by any number of medications, diagnostic agents, alternative products, herbal adulterants, or other toxin exposures, which includes environmental agents and chemicals. Because the kidney performs a number of essential bodily functions, including clearance of endogenous waste products, control of volume status, maintenance of electrolyte and acid-base balance, and modulation of endocrine activity, loss of kidney function leads to a number of clinical problems. Furthermore, metabolism and excretion of exogenously administered medications and environmental exposures is a critically important function. In its role as the primary eliminator of exogenous drugs and toxins, the kidney is vulnerable to develop various forms of injury.

Masthead

2010-02-01

The American Journal of Kidney Diseases (ISSN 0272-6386) is published monthly by Elsevier Inc., 360 Park Avenue South, New York, NY 10010-1710. Periodicals postage paid at New York, NY and additional mailing offices.

Editorial Board

2010-02-01

Feature Editors & Advisory Boards

2010-02-01

Scott J. Gilbert, MD Boston, MA

2010-02-01

March Highlights

2010-02-01

Pruritus in Advanced CKD Min-Yu Chang, Hsi-Hao Wang, Yi-Jer Lee, and Shih-Yuan Hung

Abbreviated Information for Authors

2010-02-01

The American Journal of Kidney Diseases (AJKD) serves clinicians and scientists who treat and investigate kidney disease and associated conditions. AJKD is dedicated to providing high-quality, clinically relevant information in the form of original investigations, case reports, narrative reviews, editorials, and features.

Announcement

2010-02-01

The National Kidney Foundation 2010 Spring Clinical Meetings (SCM10) presents a unique opportunity for front line kidney health care providers to learn new developments related to the care of patients covering the entire spectrum of kidney disease. The meeting is specially designed for nephrologists in the private sector and academia as well as fellows and residents with a special interest in kidney disease, general internists, pharmacists, and advanced practitioners.

This Month in AJKD

2010-02-01

See Thakar et al, pages 300-306; and Jassal and Watson, pages 209-212. Outcomes of hemodialysis patients admitted to long-term care hospitals (LTCHs) are not known. In this issue, Thakar et al perform a retrospective observational study of dialysis-dependent patients with either ESRD or acute kidney injury admitted to a single LTCH and followed them through until their discharge. They found that only 31% of patients were able to return home from LTCH, and patients were more likely to be discharged to a nursing home (40%) or to be transferred back into an acute care hospital (24%) than to return home. In an accompanying editorial, Drs Jassal and Watson praise the work by Thakar et al to shift the emphasis to consider outcomes in addition to survival. They stress that future studies should continue to address quality of life, functionality, rehabilitation, and considering whether patients die “good deaths” or “bad deaths.”

Shared Journeys

Joseph Duffy, Kenar D. Jhaveri — 2010-02-01

I was a second-year fellow when Mr Duffy came to the hospital in 2008 with acute kidney injury. Kidney biopsy showed rapidly progressive glomerulonephritis from antineutrophil cytoplasmic antibody (ANCA) vasculitis. He was treated with immune-modulatory agents, including plasmapheresis, and eventually discharged to see me as an outpatient for his ongoing care.

Quiz Page February 2010: A Hemodialysis Patient With Muscle Cramps and Malaise After Virtual Colonoscopy

2010-02-01

A 58-year-old woman with end-stage renal disease caused by AA amyloidosis on hemodialysis therapy for the past 7 years presents with severe malaise, nausea, vomiting, and diffuse muscle cramps. Symptoms began the previous evening after the patient underwent a virtual colonoscopy required for her maintenance on the kidney transplant waiting list. The procedure had been uneventful.

American Journal of Kidney Diseases

World Kidney Day 2010: Diabetic Kidney Disease—Act Now or Pay Later

Doc, Don't Procrastinate…Rehabilitate, Palliate, and Advocate

Why Do Patients Develop Proteinuria With Sirolimus? Do We Have the Answer?

The 2009 Proposed Rule for Prospective ESRD Payment: Historical Perspectives and Public Policies—Bundle Up!

The 2009 Proposed Rule for Prospective ESRD Payment: Perspectives From a Large Dialysis Organization

The 2009 Proposed Rule for Prospective ESRD Payment: Perspectives From a Medium-Sized Dialysis Organization

The 2009 Proposed Rule for Prospective ESRD Payment: Perspectives From a Not-for-Profit Small Dialysis Organization

The 2009 Proposed Rule for Prospective ESRD Payment: Perspectives From a For-Profit Small Dialysis Organization

The 2009 Proposed Rule for Prospective ESRD Payment: Perspectives From the Forum of ESRD Networks

AURORA: Is There a Role for Statin Therapy in Dialysis Patients?

Nephrologists' Perspectives on the Effect of Guidelines on Clinical Practice: A Semistructured Interview Study

Prediction of ESRD in Pauci-immune Necrotizing Glomerulonephritis: Quantitative Histomorphometric Assessment and Serum Creatinine

Is Presence of ANCA in Crescentic IgA Nephropathy a Coincidence or Novel Clinical Entity? A Case Series

Sleep and Fatigue Symptoms in Children and Adolescents With CKD: A Cross-sectional Analysis From the Chronic Kidney Disease in Children (CKiD) Study

Associations Between Renal Duplex Parameters and Adverse Cardiovascular Events in the Elderly: A Prospective Cohort Study

Kidney Function and Rate of Bone Loss at the Hip and Spine: The Canadian Multicentre Osteoporosis Study

Outcomes of Hemodialysis Patients in a Long-term Care Hospital Setting: A Single-Center Study

A Randomized, Parallel, Open-Label Study to Compare Once-Daily Sevelamer Carbonate Powder Dosing With Thrice-Daily Sevelamer Hydrochloride Tablet Dosing in CKD Patients on Hemodialysis

Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy: The Prospective Pediatric Continuous Renal Replacement Therapy Registry

Secondary Hyperparathyroidism and Anemia in Children Treated by Hemodialysis

Tubular Toxicity in Sirolimus- and Cyclosporine-Based Transplant Immunosuppression Strategies: An Ancillary Study From a Randomized Controlled Trial

Successful Treatment With Retinoids in Patients With Lupus Nephritis

Embolic Complications From Central Venous Hemodialysis Catheters Used With Hypertonic Citrate Locking Solution

Is There a Role for Intradialytic Parenteral Nutrition? A Review of the Evidence

The Management of Diabetic Neuropathy in CKD

An Uncommon Cause of Membranous Glomerulonephritis

Membranoproliferative Glomerulonephritis, Chronic Lymphocytic Leukemia, and Cryoglobulinemia

Radiographic Features of Malpositioning of a Hemodialysis Catheter in the Azygos Vein

Toxic Nephropathies: Core Curriculum 2010

Masthead

Editorial Board

Feature Editors & Advisory Boards

Contents

March Highlights

Abbreviated Information for Authors

Announcement

This Month in AJKD

Shared Journeys

Quiz Page February 2010: A Hemodialysis Patient With Muscle Cramps and Malaise After Virtual Colonoscopy