Kidney Function » Uncategorized

Prediction of ESRD and Death Among People With CKD: The Chronic Renal Impairment in Birmingham (CRIB) Prospective Cohort Study – Corrected Proof

Mon, 01 Nov 2010 16:00:00 +0000

Background:: Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD).Study Design:: Prospective cohort study with validation in a separate cohort.Setting & Participants:: Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort).Factors:: 44 baseline characteristics (including 30 blood and urine assays).Outcomes:: ESRD and all-cause mortality.Results:: In the CRIB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CI, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death.Limitations:: Other important factors may have been missed because of limited study power.Conclusions:: Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results.

Use of Kidney Function End Points in Kidney Transplant Trials: A Systematic Review – Corrected Proof

Christine A. White, Deborah Siegal, Ayub Akbari, Greg A. Knoll — Mon, 01 Nov 2010 16:00:00 +0000

Background:: Clinical trials in kidney transplantation are beginning to include markers of kidney function as end points now that traditional outcomes, such as acute rejection, become increasingly rare events. The frequency and type of kidney function end points used are unknown.Study Design:: Systematic review.Setting & Population:: Randomized controlled trials in adult kidney transplant recipients reported in 5 major general medical journals and 5 major subspecialty journals in nephrology and transplantation between January 2003 and November 2008.Selection Criteria:: Inclusion of at least one kidney function end point at least 1 month posttransplant.Results:: 133 (79%) of 169 randomized trials identified used a kidney function end point. Of these, 37 (28%) used one or more measures of kidney function as the primary end point, and 81 (61%), as a secondary end point. For the primary end point, 21 (57%) trials used a creatinine-based estimated glomerular filtration rate (eGFR), 18 (49%) used serum creatinine level, and 7 (19%) used measured GFR. Overall, eGFR was an end point in 81 (61%) trials, and measured GFR, in 12 (9%) trials.Limitations:: This review is limited by the poor quality of the included trials, with many not defining either primary or secondary end points.Conclusions:: Measures of kidney function are used commonly as surrogate end points in kidney transplant trials, with eGFR becoming more frequently used over time. Further data are needed to properly validate these surrogate end points and fully understand their limitations when designing and interpreting randomized trials.

Association of CKD With Disability in the United States – Corrected Proof

Mon, 01 Nov 2010 16:00:00 +0000

Background:: Little is known about disability in early-stage chronic kidney disease (CKD).Study Design:: Cross-sectional national survey (National Health and Nutrition Examination Survey 1999-2006).Setting & Participants:: Community-based survey of 16,011 noninstitutionalized US civilian adults (aged ≥20 years).Predictor:: CKD, categorized as no CKD, stages 1 and 2 (albuminuria and estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2), and stages 3 and 4 (eGFR, 15-59 mL/min/1.73 m2).Outcome:: Self-reported disability, defined by limitations in working, walking, and cognition and difficulties in activities of daily living (ADL), instrumental ADL, leisure and social activities, lower-extremity mobility, and general physical activity.Measurements:: Albuminuria and eGFR assessed from urine and blood samples; disability, demographics, access to care, and comorbid conditions assessed using a standardized questionnaire.Results:: Age-adjusted prevalence of reported limitations generally was significantly greater with CKD: for example, difficulty with ADL was reported by 17.6%, 24.7%, and 23.9% of older (≥65 years) and 6.8%, 11.9%, and 11.0% of younger (20-64 years) adults with no CKD, stages 1 and 2, and stages 3 and 4, respectively. CKD also was associated with greater reported limitations and difficulty in other activities after age adjustment, including instrumental ADL, leisure and social activities, lower-extremity mobility, and general physical activity. Other demographics, socioeconomic status, and access to care generally only slightly attenuated the observed associations, particularly in older individuals; adjustment for cardiovascular disease, arthritis, and cancer attenuated most associations such that statistical significance no longer was achieved.Limitations:: Inability to establish causality and possible unmeasured confounding.Conclusion:: CKD is associated with a higher prevalence of disability in the United States. Age and other comorbid conditions account for most, but not all, of this association.

Tubular Transport: Core Curriculum 2010 – Corrected Proof

Marta Christov, Seth L. Alper — Mon, 01 Nov 2010 16:00:00 +0000

The renal tubular epithelial cells that line the multiple distinct nephron segments stretching beyond the glomerulus confront the extraordinary daily task of converting 180 L of glomerular filtrate into 1-2 L of urine. Beyond simple reabsorption of solutes and water, nephron epithelial cells respond to and control the overall organismal balance of acid, solutes, fluid, hormones, vitamins, and xenobiotics. Transport functions of these epithelial cells are accomplished by solute-specific transporters and channels that, aided by specific accessory proteins, provide translocation pathways across the permeability barriers posed by the phospholipid bilayer of the plasma membrane. Transepithelial transport depends on the establishment and maintenance of epithelial cell polarity. Insults to epithelial cell polarity, such as ischemic kidney injury, can lead to loss of transport function. Normal nephron function also requires the collective and consecutive efforts of axially heterogeneous nephron segments of differing water permeabilities and energy requirements, expressing distinct profiles of transporters, channels, and other determinants of epithelial permeability. Thus, the effectiveness of diuretics is determined not only by inhibition of specific transporters, but also by the consequences of increased solute delivery to downstream nephron segments.

Effect of Remote Ischemic Preconditioning on Acute Kidney Injury in Nondiabetic Patients Undergoing Coronary Artery Bypass Graft Surgery: A Secondary Analysis of 2 Small Randomized Trials – Corrected Proof

Vinod Venugopal, Chris M. Laing, Andrew Ludman, Derek M. Yellon, Derek Hausenloy — Mon, 25 Oct 2010 16:00:00 +0000

Background:: Novel treatment strategies are required to reduce the development of acute kidney injury (AKI) in patients undergoing cardiac surgery. In this respect, remote ischemic preconditioning (RIPC), a phenomenon in which transient nonlethal ischemia applied to an organ or tissue protects another organ or tissue from subsequent lethal ischemic injury, is a potential renoprotective strategy.Study Design:: Secondary analysis of 2 randomized trials.Setting & Participants:: 78 consenting selected nondiabetic patients in a university teaching hospital undergoing elective coronary artery bypass graft (CABG) surgery recruited to 2 previously reported randomized studies.Intervention:: RIPC consisted of three 5-minute cycles of right forearm ischemia, induced by inflating a blood pressure cuff on the upper arm to 200 mm Hg, with an intervening 5 minutes of reperfusion, during which time the cuff was deflated. The control consisted of placing an uninflated cuff on the arm for 30 minutes.Outcomes:: AKI measured using Acute Kidney Injury Network (AKIN) criteria, duration of hospital stay, in-hospital and 30-day mortality.Results:: Numbers of participants with AKI stages 1, 2, and 3 were 1 (3%), 3 (8%), and 0 in the intervention group compared with 10 (25%), 0, and 0 in the control group, respectively (P = 0.005). The decrease in AKI was independent of the effect of concomitant aortic valve replacement and cross-clamp times, which were distributed unevenly between the 2 groups.Limitations:: Retrospective analysis of data. More patients in the RIPC group underwent concomitant aortic valve replacement with CABG; although we have corrected statistically for this imbalance, it remains an important confounding variable.Conclusions:: RIPC induced using transient forearm ischemia decreased the incidence of AKI in nondiabetic patients undergoing elective CABG surgery in this retrospective analysis. A large prospective clinical trial is required to study this effect and clinical outcomes in patients undergoing cardiac surgery.

Rare Association of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, ANCAs, and Pauci-immune Crescentic Glomerulonephritis – Corrected Proof

Kammi J. Henriksen, Richard B. Hong, Maria I. Sobrero, Anthony Chang — Mon, 25 Oct 2010 16:00:00 +0000

We report a 69-year-old African American woman with hemoptysis and hematuria caused by a focally crescentic pauci-immune glomerular injury associated with the presence of antineutrophil cytoplasmic antibodies (ANCAs). An incidental diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma also was established based on the kidney biopsy. Given that a subset of patients with CLL can develop autoantibodies to red blood cells, platelets, or, rarely, neutrophils, the simultaneous presence of CLL, ANCA, and a pauci-immune crescentic glomerulonephritis may not be a coincidence. Recent advances in the pathogenic role of ANCAs in pauci-immune crescentic glomerulonephritis may link the underlying CLL to this patient’s glomerular injury. Awareness of this possible association may be important for clinicians who manage patients with CLL, as well as for renal pathologists who diagnose pauci-immune crescentic glomerulonephritis.

Association of Carotid Intima-Media Thickness With Progression of Urine Albumin-Creatinine Ratios in the Multi-Ethnic Study of Atherosclerosis (MESA) – Corrected Proof

Mon, 25 Oct 2010 16:00:00 +0000

Background:: The association between measures of subclinical cardiovascular disease and progression of urine albumin-creatinine ratios (UACRs) over time is uncertain.Study Design:: Prospective cohort study.Setting & Participants:: The Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of adults aged 45-84 years without baseline clinical cardiovascular disease. Examinations were completed approximately every 1.5 years, and UACR was measured during the first 3 examinations. Analysis was limited to 4,878 participants without baseline micro- or macroalbuminuria.Predictor:: 1–standard deviation (SD) unit difference in baseline maximum common and internal carotid intima-media thickness (CIMT) measured using ultrasonography.Outcomes & Measurements:: Baseline UACR was categorized as normal or high-normal. UACR progression was categorized as no progression (consistent UACR category across all 3 examinations or regression to a lower category) and definite progression (higher UACR category at examination 2 compared with baseline, then stabilizing or progressing at examination 3). UACR changes not consistent with definite or no UACR progression were classified as intermediate UACR progression. Change in log UACR also was examined.Results:: In the 4,878 participants, median baseline UACR was 4.6 mg/g (range, 0.4-24.6 mg/g). Definite and intermediate UACR progression was noted in 279 and 807, respectively. Every 1-SD unit difference in common CIMT was associated with a 22% increased adjusted odds of definite compared with no UACR progression (95% CI, 1.07-1.41). No significant association was noted between 1-SD unit difference in maximum internal CIMT and definite UACR progression after adjusting for covariates (OR, 1.08; 95% CI, 0.96-1.21). In the mixed-effects model, changes in log UACR were 0.029 (95% CI, 0.012-0.046) and 0.019 mg/g (95% CI, 0.001-0.037) per 1-SD difference in maximum common and internal CIMT after adjustment for covariates, respectively.Limitations:: UACR was measured in a single spot urine specimen at each exam.Conclusion:: Higher common CIMT is associated with UACR progression.

Signs and Symptoms Associated With Earlier Dialysis Initiation in Nursing Home Residents – Corrected Proof

Manjula Kurella Tamura, Ann M. O'Hare, Charles E. McCulloch, Kirsten L. Johansen — Mon, 25 Oct 2010 16:00:00 +0000

Background:: Factors driving the trend of earlier dialysis initiation for persons with end-stage renal disease are unknown. We wanted to determine the association of the number and type of signs and symptoms with timing of initiation of dialysis in US nursing home residents.Study Design:: Observational study.Setting & Participants:: We used data from the US Renal Data System linked with the Minimum Data Set, a national registry of nursing home residents. The cohort consisted of 2,402 nursing home residents who initiated dialysis between 1998 and 2000 and had at least 2 recorded clinical assessments in the year before dialysis initiation.Predictors:: We evaluated 7 clinical signs and symptoms: dependence in activities of daily living, cognitive function, edema, dyspnea, nutritional problems, vomiting, and body size.Outcomes:: Earlier dialysis initiation was defined as estimated glomerular filtration rate ≥15 mL/min/1.73 m2 at the start of dialysis.Results:: Median estimated glomerular filtration rate at the start of dialysis was 9.8 (25th-75th percentile, 7.4-13.4) mL/min/1.73 m2. After adjustment for age, sex, race, and comorbid conditions, each additional sign or symptom was associated with a higher odds for earlier dialysis initiation (OR, 1.16 per symptom; 95% CI, 1.06-1.28), as was each adversely changing sign or symptom (OR, 1.26 per symptom; 95% CI, 1.16-1.38). The population-attributable risk for earlier dialysis initiation associated with having one or more signs and symptoms of volume overload, cognitive decline, increasing activities of daily living dependence, and weight loss was 31%; volume overload had the largest aggregate population-attributable risk.Limitations:: We lacked information about metabolic indications for dialysis initiation.Conclusions:: Volume overload, cognitive decline, increasing activities of daily living dependence, and weight loss were associated with earlier dialysis initiation; however, these factors explained less than one-third of cases of earlier dialysis initiation in nursing home residents.

Drug-Induced Granulomatous Interstitial Nephritis in a Patient With Ankylosing Spondylitis During Therapy With Adalimumab – Corrected Proof

Mon, 25 Oct 2010 16:00:00 +0000

Tumor necrosis factor α (TNF-α) inhibitors are used in the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn disease, ankylosing spondylitis, and juvenile idiopathic arthritis. Use of TNF inhibitors is associated with the induction of autoimmunity (systemic lupus erythematosus, vasculitis, psoriasis, and sarcoidosis/sarcoid-like granulomas). We report a case of interstitial granulomatous nephritis in a patient with ankylosing spondylitis after 18 months of treatment with adalimumab. Previously reported cases of sarcoid-like reactions secondary to the use of TNF-α inhibitors involved the liver, lung, lymph nodes, central nervous system, and skin. Granulomatous nephritis after adalimumab treatment has not been described. Close observation of patients undergoing treatment with TNF inhibitors for evolving signs and symptoms of autoimmunity is required. Organ involvement is unpredictable, which makes correct diagnosis and management extremely challenging.

Systolic Blood Pressure and Mortality Among Older Community-Dwelling Adults With CKD – Corrected Proof

Thu, 21 Oct 2010 16:00:00 +0000

Background:: Chronic kidney disease (CKD) is an increasingly common condition, especially in older adults. CKD manifests differently in older versus younger patients, with a risk of death that far outweighs the risk of CKD progressing to the point that dialysis is required. Current CKD guidelines recommend a blood pressure target <130/80 mm Hg for all patients with CKD; however, it is unknown how lower versus higher baseline blood pressures may affect older adults with CKD.Study Design:: Retrospective cohort study.Setting & Participants:: Older patients (aged ≥75 years) with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) in a community-based health maintenance organization.Predictor:: Baseline systolic blood pressure (SBP) <130, 130-160 (reference group), and >160 mm Hg.Outcomes:: Participants were followed up for 5 years to examine rates of mortality (primary outcome) and cardiovascular disease hospitalizations (secondary outcome).Results:: At baseline, 3,099 participants (38.5%) had SBP <130 mm Hg, 3,772 (46.9%) had SBP of 131-160 mm Hg, and 1,171 (14.6%) had SBP >160 mm Hg. A total of 3,734 (46.4%) died and 2,881 (35.8%) were hospitalized. Adjusted HRs for mortality in the groups with SBP <130 and >160 mm Hg were 1.22 (95% CI, 1.11-1.34) and 1.06 (95% CI, 0.93-1.22), respectively. Adjusted HRs for cardiovascular hospitalization in these groups were 1.10 (95% CI, 0.99-1.23) and 1.26 (95% CI, 1.09-1.45), respectively.Limitations:: Although causality should not be inferred from this retrospective analysis, results from this study can generate hypotheses for future randomized controlled trials to investigate the relationship between blood pressure and outcomes in older patients with CKD.Conclusions:: Our study suggests that lower baseline SBP (≤130 mm Hg) may predict poorer outcomes in terms of both mortality and cardiovascular hospitalizations in older adults with CKD. Conversely, higher baseline SBP (>160 mm Hg) may predict increased risk of cardiovascular hospitalizations, but does not predict mortality. Clinical trials are required to test this hypothesis.