American Journal of Kidney Diseases - Articles in Press

Donor Pretreatment With Dopamine and Graft Function Following Kidney Transplant: A Strategy to Improve Transplant Outcomes? - Corrected Proof

John S. Gill, William Gourlay, Jagbir Gill — 2010-03-18

Commentary on Schnuelle P, Gottmann U, Hoeger S, et al. Effects of donor pretreatment with dopamine on graft function after kidney transplantation: a randomized controlled trial. JAMA. 2009;302(10):1067-1075.

Renal Research in 19th Century Germany - Corrected Proof

Eberhard Ritz, Nadezda Koleganova, August Heidland — 2010-03-15

In the 19th century, clinical nephrology had not been established as a specific discipline of internal medicine, but major contributions to the understanding of renal physiology and kidney disease had been made by a number of authors from the German-speaking world. This essay describes the introduction of the concept of glomerular filtration by Carl Ludwig, the brilliant analysis of renal histology by Jacob Henle, the histologic description and insight into the evolution of chronic kidney disease by Friedrich Theodor von Frerichs, and the recognition of albuminuria in patients without primary kidney disease by Hermann Senator.

Optimal Search Filters for Renal Information in EMBASE - Corrected Proof

2010-03-15

Background: EMBASE is a popular database used to retrieve biomedical information. Our objective was to develop and test search filters to help clinicians and researchers efficiently retrieve articles with renal information in EMBASE.Study Design: We used a diagnostic test assessment framework because filters operate similarly to screening tests.Settings & Participants: We divided a sample of 5,302 articles from 39 journals into development and validation sets of articles.Index Test: Information retrieval properties were assessed by treating each search filter as a “diagnostic test” or screening procedure for the detection of relevant articles. We tested the performance of 1,936,799 search filters made of unique renal terms and their combinations.Reference Standard & Outcome: The reference standard was manual review of each article. We calculated the sensitivity and specificity of each filter to identify articles with renal information.Results: The best renal filters consisted of multiple search terms, such as “renal replacement therapy,” “renal,” “kidney disease,” and “proteinuria,” and the truncated terms “kidney,” “dialy,” “neph,” “glomerul,” and “hemodial.” These filters achieved peak sensitivities of 98.7% (95% CI, 97.9-99.6) and specificities of 98.5% (95% CI, 98.0-99.0). The retrieval performance of these filters remained excellent in the validation set of independent articles.Limitations: The retrieval performance of any search will vary depending on the quality of all search concepts used, not just renal terms.Conclusions: We empirically developed and validated high-performance renal search filters for EMBASE. These filters can be programmed into the search engine or used on their own to improve the efficiency of searching.

Pathogenesis of Hypertension: Interactions Among Sodium, Potassium, and Aldosterone - Corrected Proof

2010-03-11

Arterial hypertension is a major cause of disease-related morbidity and mortality worldwide. It is nearly absent in populations that consume natural foods low in sodium. However, in industrial countries, where the individual intake of sodium is at least 10 times higher, the prevalence of hypertension is ∼40%. Major population-based studies link a high-sodium and low-potassium diet to an increase in blood pressure. A hallmark of arterial hypertension is endothelial dysfunction characterized by decreased synthesis of nitric oxide (NO). Plasma sodium and potassium are major determinants for the mechanical stiffness of endothelial cells. High plasma sodium levels stiffen endothelial cells and block NO synthesis. Aldosterone is a prerequisite for this action. However, high plasma potassium levels soften endothelial cells and activate NO release. There is increasing evidence that sodium can be stored transiently in considerable amounts and osmotically inactive in the interstitium. Taken together, it is recommended to maintain plasma sodium levels in the low physiologic range and potassium levels in the high physiologic range while suppressing plasma aldosterone as much as possible. A restriction in sodium intake that is accompanied by increased intake of potassium can profoundly improve the prevalence of hypertension and cardiovascular disease.

Hemolysis in a Patient With Alkaptonuria and Chronic Kidney Failure - Corrected Proof

2010-03-08

In alkaptonuria, the absence of homogentisic acid oxidase results in the accumulation of homogentisic acid (HGA) in the body. Fatal disease cases are infrequent, and death often results from kidney or cardiac complications. We report a 24-year-old alkaptonuric man with severe decreased kidney function who developed fatal metabolic acidosis and intravascular hemolysis. Hemolysis may have been caused by rapid and extensive accumulation of HGA and subsequent accumulation of plasma soluble melanins. Toxic effects of plasma soluble melanins, their intermediates, and reactive oxygen side products are increased when antioxidant mechanisms are overwhelmed. A decrease in serum antioxidative activity has been reported in patients with chronic decreased kidney function. However, despite administration of large doses of an antioxidant agent and ascorbic acid and intensive kidney support, hemolysis and acidosis could not be brought under control and hemolysis led to the death of the patient.

A Randomized Double-Blind Controlled Trial of Taurolidine-Citrate Catheter Locks for the Prevention of Bacteremia in Patients Treated With Hemodialysis - Corrected Proof

2010-03-08

Background: Bacteremia is a major cause of morbidity in patients using intravascular catheters. Interdialytic locking with antibiotics decreases the incidence of bacteremia, but risks antibiotic resistance. Taurolidine is a nontoxic broad-spectrum antimicrobial agent that has not been associated with resistance. Preliminary evidence suggests that taurolidine-citrate locks decrease bacteremia, but cause flow problems in established catheters.Study Design: Double-blind randomized controlled trial.Intervention: Interdialytic locking with taurolidine and citrate (1.35% taurolidine and 4% citrate) compared with heparin (5,000 U/mL) started at catheter insertion.Setting & Participants: 110 adult hemodialysis patients with tunneled cuffed intravascular catheters inserted at 3 centers in Northwest England.Outcomes & Measurements: Primary end points were time to first bacteremia episode from any cause and time to first use of thrombolytic therapy.Results: There were 11 bacteremic episodes in the taurolidine-citrate group and 23 in the heparin group (1.4 and 2.4 episodes/1,000 patient-days, respectively; P = 0.1). There was no significant benefit of taurolidine-citrate versus heparin for time to first bacteremia (hazard ratio, 0.66; 95% CI, 0.2-1.6: P = 0.4). Taurolidine-citrate was associated with fewer infections caused by Gram-negative organisms than heparin (0.2 vs 1.1 infections/1,000 patient-days; P = 0.02); however, there was no difference for Gram-positive organisms (1.1 vs 1.2 infections/1,000 patient-days; P = 0.8). There was a greater need for thrombolytic therapy in the taurolidine-citrate versus heparin group (hazard ratio, 2.5; 95% CI, 1.3-5.2; P = 0.008).Limitations: Small sample size. The study included bacteremia from all causes and was not specific for catheter-related bacteremia.Conclusions: Taurolidine-citrate use did not decrease all-cause bacteremia and was associated with a greater need for thrombolytic treatment. There was a decrease in infections caused by Gram-negative organisms and a trend to a lower frequency of bacteremia, which warrants further study.

Poverty, Race, and CKD in a Racially and Socioeconomically Diverse Urban Population - Corrected Proof

2010-03-08

Background: Low socioeconomic status (SES) and African American race are both independently associated with end-stage renal disease and progressive chronic kidney disease (CKD). However, despite their frequent co-occurrence, the effect of low SES independent of race has not been well studied in CKD.Study Design: Cross-sectional study.Setting & Participants: 2,375 community-dwelling adults aged 30-64 years residing within 12 neighborhoods selected for both socioeconomic and racial diversity in Baltimore City, MD.Predictors: Low SES (self-reported household income <125% of 2004 Department of Health and Human Services guideline), higher SES (≥125% of guideline); white and African American race.Outcomes & Measurements: CKD defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. Logistic regression used to calculate ORs for relationship between poverty and CKD, stratified by race.Results: Of 2,375 participants, 955 were white (347 low SES and 608 higher SES) and 1,420 were African American (713 low SES and 707 higher SES). 146 (6.2%) participants had CKD. Overall, race was not associated with CKD (OR, 1.05; 95% CI, 0.57-1.96); however, African Americans had a much greater odds of advanced CKD (estimated glomerular filtration rate <30 mL/min/1.73 m2). Low SES was independently associated with 59% greater odds of CKD after adjustment for demographics, insurance status, and comorbid disease (OR, 1.59; 95% CI, 1.27-1.99). However, stratified by race, low SES was associated with CKD in African Americans (OR, 1.91; 95% CI, 1.54-2.38), but not whites (OR, 0.95; 95% CI, 0.58-1.55; P for interaction = 0.003).Limitations: Cross-sectional design; findings may not be generalizable to non-urban populations.Conclusions: Low SES has a profound relationship with CKD in African Americans, but not whites, in an urban population of adults, and its role in the racial disparities seen in CKD is worthy of further investigation.

Pulse Cyclophosphamide Therapy and Clinical Remission in Atypical Hemolytic Uremic Syndrome With Anti–Complement Factor H Autoantibodies - Corrected Proof

2010-03-04

We report 3 children with atypical hemolytic uremic syndrome associated with anti–complement factor H (CFH) autoantibodies who presented with sustained remission with low antibody titers and normal kidney function after plasma exchanges (PEs) and cyclophosphamide pulses. The 3 children initially presented with acute vomiting, fatigue, gross hematuria, hypertension, hemolytic anemia, thrombocytopenia, nephrotic syndrome, and acute kidney injury. C3 levels were normal in patients 1 and 3 and low in patient 2 (0.376 mg/mL [0.376 g/L]). CFH antibody titers were increased (15,000 to > 32,000 arbitrary units [AU]). Patient 1, an 11-year-old boy, was treated with 12 PEs, leading to a decrease in CFH antibody titer (to 800 AU). A first relapse 1 month later was treated with 6 PEs and 4 rituximab infusions. A second relapse 3 months later required 5 PEs, and the patient received oral steroids (0.5 mg/d/kg body weight) and 5 cyclophosphamide pulses (1 g/1.73 m2), leading to sustained remission with normal kidney function (estimated glomerular filtration rate [eGFR], 120 mL/min/1.73 m2 [2.0 mL/s/1.73 m2]) and a stable decrease in CFH antibody titer (to 2,000 AU) 3 years later. Patient 2, a 5-year-old boy, required dialysis therapy for 2 weeks. He received 3 plasma infusions without remission. Six PEs associated with 2 cyclophosphamide pulses (0.5 g/1.73 m2) and steroids (1 mg/d/kg body weight) led to rapid remission, with eGFR of 107 mL/min/1.73 m2 [1.78 mL/s/1.73 m2] and a prolonged decrease in CFH antibody titer after 15 months (1,300 AU). Patient 3, a 16-month-old boy, was treated with oral steroids (1 mg/d/kg body weight), 2 PEs, and 2 cyclophosphamide pulses (0.5 g/1.73 m2), resulting in a stable decrease in CFH antibody titer to 276 AU. Kidney function quickly normalized (eGFR, 110 mL/min/1.73 m2 [1.83 mL/s/1.73 m2]) and has remained normal after 14 months. All 3 patients show a homozygous deletion mutation of the CFHR1 and CFHR3 genes. Cyclophosphamide pulses with PE may lead to a prolonged decrease in CFH antibody titers and a favorable outcome of atypical hemolytic uremic syndrome and kidney function.

Hemoglobin A1c and Fructosamine for Assessing Glycemic Control in Diabetic Patients With CKD Stages 3 and 4 - Corrected Proof

2010-03-04

Background: Hemoglobin A1c (HbA1c) and fructosamine can be used to monitor glycemic control in diabetic patients with normal kidney function, but their validity in patients with chronic kidney disease (CKD) has not been evaluated. In this study, we evaluated the correlation and accuracy of these 2 measures of glycemic control in type 2 diabetic patients with CKD stages 3-4.Study Design: Diagnostic test study.Setting & Participants: Type 2 diabetic patients with normal (n = 30) and abnormal kidney function (n = 30) were recruited in Taipei Veterans General Hospital, Taiwan.Index Tests: HbA1c and fructosamine.Reference Test: Self-monitoring of blood glucose levels.Measurements: Blood glucose measurements consisted of 6 preprandial, 6 postprandial, and 2 bedtime assessments in a week with a cycle of 4-week intervals for 12 weeks.Results: Correlation coefficients between HbA1c level or fructosamine-albumin ratio and mean blood glucose levels were 0.836 and 0.645 in participants with normal kidney function and 0.813 and 0.649 in participants with CKD stages 3-4, respectively. In patients with CKD stages 3-4, mean blood glucose levels in weeks 1-12 were 21.9 mg/dL (95% CI, 11.6-32.5) higher than estimated average glucose (eAG) levels calculated from HbA1c levels in participants with normal kidney function. In patients with CKD stages 3-4, mean blood glucose levels in weeks 10-12 were 15.5 mg/dL (95% CI, 5.2-30.5) higher than eAG levels calculated from fructosamine levels in participants with normal kidney function, but without statistical significance when eAG calculated from fructosamine level was corrected for serum albumin level (difference of 5.6 mg/dL; 95% CI, −8.6 to 19.8).Limitations: Relatively small number of participants with limited amount of blood glucose measurement data.Conclusion: Our data show that eAG calculated from HbA1c and fructosamine levels might underestimate mean blood glucose levels in patients with CKD stages 3-4. References ranges may need to be modified when interpreting results of measurements of glycemic control in type 2 diabetic patients with CKD.

Risk Implications of the New CKD Epidemiology Collaboration (CKD-EPI) Equation Compared With the MDRD Study Equation for Estimated GFR: The Atherosclerosis Risk in Communities (ARIC) Study - Corrected Proof

Kunihiro Matsushita, Elizabeth Selvin, Lori D. Bash, Brad C. Astor, Josef Coresh — 2010-03-02

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently published an equation for estimated glomerular filtration rate (eGFR) using the same variables (serum creatinine level, age, sex, and race) as the Modification of Diet in Renal Disease (MDRD) Study equation. Although the CKD-EPI equation estimates GFR more precisely compared with the MDRD Study equation, whether this equation improves risk prediction is unknown.Study Design: Prospective cohort study, the Atherosclerosis Risk in Communities (ARIC) Study.Setting & Participants: 13,905 middle-aged participants without a history of cardiovascular disease with median follow-up of 16.9 years.Predictor: eGFR.Outcomes & Measurements: We compared the association of eGFR in categories (≥120, 90-119, 60-89, 30-59, and <30 mL/min/1.73 m2) using the CKD-EPI and MDRD Study equations with risk of incident end-stage renal disease, all-cause mortality, coronary heart disease, and stroke.Results: The median value for eGFRCKD-EPI was higher than that for eGFRMDRD (97.6 vs 88.8 mL/min/1.73 m2; P < 0.001). The CKD-EPI equation reclassified 44.9% (n = 3,079) and 43.5% (n = 151) of participants with eGFRMDRD of 60-89 and 30-59 mL/min/1.73 m2, respectively, upward to a higher eGFR category, but reclassified no one with eGFRMDRD of 90-119 or <30 mL/min/1.73 m2, decreasing the prevalence of CKD stages 3-5 from 2.7% to 1.6%. Participants with eGFRMDRD of 30-59 mL/min/1.73 m2 who were reclassified upward had lower risk compared with those who were not reclassified (end-stage renal disease incidence rate ratio, 0.10 [95% CI, 0.03-0.33]; all-cause mortality, 0.30 [95% CI, 0.19-0.48]; coronary heart disease, 0.36 [95% CI, 0.21-0.61]; and stroke, 0.50 [95% CI, 0.24-1.02]). Similar results were observed for participants with eGFRMDRD of 60-89 mL/min/1.73 m2. More frequent reclassification of younger, female, and white participants explained some of these trends. Net reclassification improvement in participants with eGFR < 120 mL/min/1.73 m2 was positive for all outcomes (P < 0.001).Limitations: Limited number of cases with eGFR < 60 mL/min/1.73 m2 and no measurement of albuminuria.Conclusions: The CKD-EPI equation more appropriately categorized individuals with respect to long-term clinical risk compared with the MDRD Study equation, suggesting improved clinical usefulness in this middle-aged population.

A Case Series of Proton Pump Inhibitor–Induced Hypomagnesemia - Corrected Proof

2010-03-02

Proton pump inhibitor (PPI)-induced hypomagnesemia has been recognized since 2006. Our aim was to further characterize the clinical consequences and possible mechanisms of this electrolyte disorder using 4 cases. Two men (aged 63 and 81 years) and 2 women (aged 73 and 62 years) had been using a PPI (esomeprazole, pantoprazole, omeprazole, and rabeprazole, 20-40 mg) for 1-13 years. They developed severe hypomagnesemia (magnesium, 0.30 ± 0.28 mEq/L; reference, 1.40-2.10 mEq/L) with hypocalcemia (calcium, 6.4 ± 1.8 mg/dL), relative hypoparathyroidism (parathyroid hormone, 43 ± 6 pg/mL), and extremely low urinary calcium and magnesium excretion. One patient was admitted with postanoxic encephalopathy after a collapse likely caused by arrhythmia. The others had electrocardiogram abnormalities (prolonged QT interval, ST depression, and U waves). Concomitant hypokalemia (potassium, 2.8 ± 0.1 mEq/L) was considered the trigger for these arrhythmias. Hypomagnesemia-induced kaliuresis (potassium excretion, 65 ± 24 mEq/L) was identified as the cause of hypokalemia. This series of PPI-induced hypomagnesemia shows that this is a generic effect. It also indicates that hypomagnesemia may occur within 1 year of PPI therapy initiation and can have serious clinical consequences, likely triggered by the associated hypokalemia. A high index of suspicion is required in PPI users for unexplained hypomagnesemia, hypocalcemia, hypokalemia, or associated symptoms.

Multiple Listing in Kidney Transplantation - Corrected Proof

Mohammad Sanaei Ardekani, Janis M. Orlowski — 2010-03-02

The increasing number of patients with end-stage renal disease and the expanding waiting lists for various solid-organ transplants, particularly kidney transplants, has compelled prospective transplant recipients and their care teams to explore novel ways to accelerate this process, initiating the practice of multiple listing. Multiple listing is defined as being listed for an organ transplant at more than 1 transplant center. Current policy allows patients to be listed at more than 1 transplant center in 1 or more organ procurement organization. Multiple listing can be beneficial for different groups of transplant candidates. Current data support a beneficial effect for the patient on multiple waiting lists, most notably portending a survival advantage for transplant recipients. The kidney transplant list has the most patients who are multiply listed (4.7%), followed by the liver transplant list at 3.8%. The main potential downside of multiple listing is its effect on patients not on multiple lists, as well as the cost accrued to achieve multiple listings. With the newly clarified policy of the United Network for Organ Sharing, a pivotal role for nephrologists in educating patients about the option of multiple listing becomes more apparent. In this article, current practices and policies regarding multiple listing are reviewed and opinions and ethics relating to the practice are discussed.

Carbohydrate Antigen 19-9 as a Diagnostic Marker for Hepatic Cyst Infection in Autosomal Dominant Polycystic Kidney Disease - Corrected Proof

Nada Kanaan, Eric Goffin, Yves Pirson, Olivier Devuyst, Ziad Hassoun — 2010-03-02

The diagnosis of hepatic cyst infection is difficult in patients with autosomal dominant polycystic kidney disease (ADPKD). We hypothesized that carbohydrate antigen 19-9 (CA 19-9), secreted by the biliary epithelium lining the cysts, is overproduced in the case of cyst infection. In this report, we describe 3 patients with ADPKD with hepatic cyst infection, all with functioning kidney transplants, who had markedly increased serum CA 19-9 levels. Furthermore, CA 19-9 level was extremely increased in cystic fluid obtained in 2 of these individuals. Corresponding with clinical improvement, there was a marked decrease in serum CA 19-9 level in all 3 patients. To assess the potential applicability of these findings, serum CA 19-9 was measured in asymptomatic patients with ADPKD with known liver cysts and in controls without ADPKD. Although serum CA 19-9 levels were significantly higher in asymptomatic patients with ADPKD than in controls, they were markedly increased in patients with cyst infection compared with either asymptomatic ADPKD patients or controls. Immunostaining for CA 19-9 showed strong positivity in biliary tree epithelia and cysts of polycystic livers from patients with ADPKD that appeared more intense than in normal livers. Although further study is necessary, these data suggest that serum CA 19-9 level is markedly increased during liver cyst infection in kidney transplant recipients with ADPKD and has potential utility as a diagnostic marker.

ADMA, C-Reactive Protein, and Albuminuria in Untreated Essential Hypertension: A Cross-sectional Study - Corrected Proof

2010-03-02

Background: Asymmetric dimethylarginine (ADMA) and subclinical inflammation are associated with atherosclerosis progression, whereas microalbuminuria is an established index of hypertensive organ damage.Study Design: Cross-sectional.Setting & Participants: In an outpatient hypertensive unit, 296 nondiabetic and untreated participants with hypertension were studied. Participants with atherosclerotic cardiovascular disease, severe valvulopathy, congestive heart failure, presence of neoplastic or other concurrent systemic disease, atrial fibrillation, serum creatinine level > 1.5 mg/dL in men and > 1.4 mg/dL in women, and urinary albumin excretion > 300 mg/24 h were excluded.Predictors: ADMA and high-sensitivity C-reactive protein (hs-CRP) levels.Outcome Variable: : Albuminuria assessed using albumin-creatinine ratio (ACR).Measurements: Participants underwent ambulatory blood pressure monitoring, echocardiography, routine assessment of metabolic profile, ADMA, and hs-CRP, whereas ACR was determined as the mean of 3 values in nonconsecutive morning spot urine samples.Results: 64 participants had an ACR of 30-300 mg/g. Stratification based on ADMA level showed that participants with hypertension in quartile [Q] 4 compared with those in Q3, Q2, and Q1 showed the highest ACRs (53.2 vs 31.2 vs 30.4 vs 16.7 mg/g; P < 0.008 for all). Moreover, stratification based on hs-CRP level showed that participants with hypertension in Q4 (69.8% had microalbuminuria) showed the highest ACRs (72.2 vs 25.6, 16.2, and 19.2 mg/g for Q3, Q2, and Q1, respectively; P < 0.008 for all). Stepwise regression analysis showed that age, 24-hour systolic blood pressure, hs-CRP level, ADMA level, and the interaction of hs-CRP with ADMA were independent predictors of ACR (R2 = 0.674; P < 0.001).Limitations: Cross-sectional study.Conclusions: In patients with untreated essential hypertension, increased hs-CRP and ADMA levels are associated with microalbuminuria, suggesting the involvement of inflammation and endothelial dysfunction in vascular and kidney damage.

Molecular Mechanisms of Hepcidin Regulation: Implications for the Anemia of CKD - Corrected Proof

Jodie L. Babitt, Herbert Y. Lin — 2010-03-02

Anemia is prevalent in patients with chronic kidney disease (CKD) and is associated with lower quality of life and higher risk of adverse outcomes, including cardiovascular disease and death. Anemia management in patients with CKD currently revolves around the use of erythropoiesis-stimulating agents and supplemental iron. However, many patients do not respond adequately and/or require high doses of these medications. Furthermore, recent clinical trials have shown that targeting higher hemoglobin levels with conventional therapies leads to increased cardiovascular morbidity and mortality, particularly when higher doses of erythropoiesis-stimulating agents are used and in patients who are poorly responsive to therapy. One explanation for the poor response to conventional therapies in some patients is that these treatments do not fully address the underlying cause of the anemia. In many patients with CKD, as with patients with other chronic inflammatory diseases, poor absorption of dietary iron and the inability to use the body's iron stores contribute to the anemia. Recent research suggests that these abnormalities in iron balance may be caused by increased levels of the key iron regulatory hormone hepcidin. This article reviews the pathogenesis of anemia in CKD, the role and regulation of hepcidin in systemic iron homeostasis and the anemia of CKD, and the potential diagnostic and therapeutic implications of these findings.

Cigarette Smoking, Kidney Function, and Mortality After Live Donor Kidney Transplant - Corrected Proof

2010-02-22

Background: The role of smoking as a risk factor for adverse renal outcomes after kidney transplant has not been well studied. We therefore undertook this investigation to assess the association of smoking with transplant outcomes.Study Design: Retrospective cohort study.Setting & Participants: 997 consecutive laparoscopic live donor kidney transplant recipients at a tertiary-care transplant center.Predictor: Smoking at the time of the transplant evaluation.Outcomes & Measurements: Primary outcome is transplant survival.Results: At the time of pretransplant evaluation, 329 participants had ever smoked and 668 participants had never smoked. Transplant survival was worse in ever smokers compared with never smokers (adjusted HR, 1.47; 95% CI, 1.08-1.99; P = 0.01), as was patient survival (adjusted HR, 1.60; 95% CI, 1.06-2.41; P = 0.02). First-year rejection-free survival was substantially worse (adjusted HR, 1.46; 95% CI, 1.05-2.03; P = 0.03) and risk of rejection on or before posttransplant day 10 was much higher (adjusted HR, 1.8; 95% CI, 1.10-2.94; P = 0.02) in ever smokers compared with never smokers. Glomerular filtration rate (estimated using the Modification of Diet in Renal Disease Study equation) at 1 year posttransplant was lower and poor early transplant function was more common in ever smokers on univariate, but not multivariate, analysis.Limitations: Lack of quantitation of smoking exposure and uncertainty about whether patients were still smoking at the time of transplant.Conclusions: Our results suggest that any history of smoking before transplant is associated with impaired transplant and patient survival and increases the risk of early rejection after live donor kidney transplant. Further study is needed to determine whether smoking may impart immunomodulatory and perhaps nephrotoxic effects.

Recurrence of Amyloidosis in a Kidney Transplant - Corrected Proof

Sanjeev Sethi, Fernando C. Fervenza, Dylan Miller, Suzanne Norby, Nelson Leung — 2010-02-22

There are many causes of late kidney transplant dysfunction. Common causes include chronic transplant injury resulting from rejection and nonimmunologic causes, such as hypertension, calcineurin-inhibitor nephrotoxicity, urinary obstruction, viral or bacterial infections, and, less commonly, recurrent disease. We present an interesting case in which the cause of late transplant dysfunction was identified on a transplant biopsy.

Lack of Toxic Effects of Methanol in a Patient With HIV - Corrected Proof

2010-02-22

Ingestion of a very large amount of methanol usually causes serious toxicity. Methanol is metabolized by alcohol dehydrogenase in the liver to formaldehyde and then quickly transformed by aldehyde dehydrogenase to formic acid. Although methanol is directly responsible for the initial signs and symptoms of inebriation, formaldehyde and formate are responsible for the characteristic blindness and metabolic acidosis with a high plasma anion gap. Lactic acid accumulation also can occur through inhibition of mitochondrial cytochrome oxidase by formate.

Prospective Quality-of-Life Monitoring of Simultaneous Pancreas and Kidney Transplant Recipients Using the 36-Item Short Form Health Survey - Corrected Proof

Graeme C. Smith, Thomas Trauer, Peter G. Kerr, Steven J. Chadban — 2010-02-22

Background: Few risk factors for quality-of-life outcomes of simultaneous pancreas and kidney transplant recipients are known because of a paucity of data from prospective studies.Study Design: Pretransplant assessment and prospective 3-year follow-up.Setting & Participants: Consecutive potential recipients at a university teaching hospital assessed by Liaison Psychiatry.Predictors: Demographic data; pretransplant Transplant Evaluation Rating Scale scores; current, past 12 months, and prior lifetime psychiatric disorder.Outcomes & Measurements: 36-Item Short Form Health Survey (SF-36) scores.Results: 37 simultaneous pancreas and kidney transplant recipients were assessed pretransplant and at 4 months posttransplant. Posttransplant at 1 year, 29 (81% of survivors); at 2 years, 26 (79% of survivors and those reaching 2 years); and at 3 years, 22 (92% of survivors and those reaching 3 years) patients were assessed. SF-36 Mental Component Summary (MCS) scores (mean pretransplant, 46.8 ± 8.2 [SD]; 4 months, 51.7 ± 8.5; 1 year, 50.1 ± 9.7; 2 years, 51.8 ± 8.9; and 3 years, 50.8 ± 13.8) and Physical Component Summary (PCS) scores (pretransplant, 40.6 ± 10.6; 4 months, 43.6 ± 12.0; 1 year, 45.6 ± 11.3; 2 years, 48.1 ± 10.2; and 3 years, 46.8 ± 9.1) showed sustained improvement posttransplant. MCS scores became similar to population norms. Functionally significant decreases in MCS and PCS scores were seen in 4%-21% and 8%-30% at times posttransplant. Male sex predicted higher scores at 4 months for the MCS (P = 0.003; regression coefficient, −8.28 [95% CI, −13.6 to −2.9]; effect size, 0.22) and PCS (P = 0.05; regression coefficient, −6.91 [95% CI, −13.9 to 0.9]; effect size, 0.08). Current psychiatric disorder at pretransplant evaluation predicted higher PCS scores at 4 months (P = 0.002; regression coefficient, −15.42 [95% CI, −24.6 to −6.2]; effect size, 0.22) and 1 year (P = 0.002; regression coefficient, −17.3 [95% CI, −27.9 to −6.7]; effect size, 0.29). Psychiatric disorder before the 12 months before the pretransplant evaluation predicted lower PCS scores at 4 months posttransplant (P < 0.001; regression coefficient, 14.98 [95% CI, 7.1-22.8]; effect size, 0.29).Limitations: Cohort size.Conclusions: Although half experienced sustained quality-of-life improvement, up to one-third experienced a decrease. Past psychiatric disorder is a risk factor. Patients should be educated and monitored appropriately.

CKD in a Patient With Pancreatic Carcinoma - Corrected Proof

2010-02-16

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. The incidence of pancreatic cancer increased between the 1930s and 1970s, but has been relatively stable since that time. The lifetime risk of pancreatic carcinoma being diagnosed in the United States is 1.27%. With the use of adjuvant chemo- and radiotherapy, the survival rate for patients with pancreatic cancer has increased significantly. This is resulting in a new set of complications associated with either the disease or various treatment modalities. We report a case of a 54-year-old white woman with a history of metastatic pancreatic carcinoma who presented with chronic kidney disease 7 years after her primary carcinoma was diagnosed.

Prevalence and Risk Factors for CKD in Spouses and Relatives of Hemodialysis Patients - Corrected Proof

2010-02-16

Background: A higher prevalence of chronic kidney disease (CKD) has been found in genetic relatives of patients with end-stage renal disease. However, the risk of CKD in nongenetic spouses of patients with end-stage renal disease is still unknown.Study Design: Cross-sectional study.Setting & Participants: 196 first- and second-degree relatives and 95 spouses of 178 hemodialysis (HD) patients were enrolled. Two sex- and age-stratified matched counterpart controls were randomly selected from the population of a community screening program for CKD.Predictors: Relatives or spouses of HD patients and kidney disease risk factors.Outcomes: Prevalence of CKD (albuminuria or low estimated glomerular filtration rate).Measurement: Albuminuria (urine albumin-creatinine ratio ≥ 30 mg/g), low estimated glomerular filtration rate (<60 mL/min/1.73 m2), and kidney disease risk factors of age, hypertension, diabetes mellitus, metabolic syndrome, and lifestyle.Results: A significantly higher prevalence of CKD was found in relatives (15.8% vs 7.5%; P = 0.01) and spouses (41.1% vs 15.8%; P < 0.001) of HD patients compared with their counterpart controls. Multiple logistic regression analysis showed that age (OR, 1.05) and hypertension (OR, 3.13) were significant independent risk factors for CKD in relatives of HD patients, whereas diabetes mellitus (OR, 3.51) was a significant risk factor for CKD in spouses of HD patients. For all pooled participants, being relatives (OR, 2.55) or spouses (OR, 2.80) of HD patients, age (OR, 1.06), female sex (OR, 1.81), diabetes mellitus (OR, 3.95), hypertension (OR, 1.85), and hyperuricemia (OR, 2.06) were independent significant risk factors for CKD.Limitations: Cross-sectional research design, single laboratory measurement, and limited numbers of participants.Conclusions: A comprehensive screening program for CKD is equally important in both relatives and spouses of HD patients, especially for participants with the renal risk factors of older age, hypertension, and diabetes mellitus. Spousal concordance of CKD suggests that the shared environmental factors and health behaviors might have important roles in the development of CKD.

Early Urinary Markers of Diabetic Kidney Disease: A Nested Case-Control Study From the Diabetes Control and Complications Trial (DCCT) - Corrected Proof

Elizabeth F.O. Kern, Penny Erhard, Wanjie Sun, Saul Genuth, Miriam F. Weiss — 2010-02-08

Background: Urinary markers were tested as predictors of macroalbuminuria or microalbuminuria in patients with type 1 diabetes.Study Design: Nested case-control of participants in the Diabetes Control and Complications Trial (DCCT).Setting & Participants: 87 cases of microalbuminuria were matched to 174 controls in a 1:2 ratio, while 4 cases were matched to 4 controls in a 1:1 ratio, resulting in 91 cases and 178 controls for microalbuminuria. 55 cases of macroalbuminuria were matched to 110 controls in a 1:2 ratio. Controls were free of micro-/macroalbuminuria when their matching case first developed micro-/macroalbuminuria.Predictors: Urinary N-acetyl-β-d-glucosaminidase (NAG), pentosidine, advanced glycation end product (AGE) fluorescence, and albumin excretion rate (AER).Outcomes: Incident microalbuminuria (2 consecutive annual AERs > 40 but ≤ 300 mg/d) or macroalbuminuria (AER > 300 mg/d).Measurements: Stored urine samples from DCCT entry and 1-9 years later when macro- or microalbuminuria occurred were measured for the lysosomal enzyme NAG and the AGE pentosidine and AGE fluorescence. AER and adjustor variables were obtained from the DCCT.Results: Submicroalbuminuric AER levels at baseline independently predicted microalbuminuria (adjusted OR, 1.83; P < 0.001) and macroalbuminuria (adjusted OR, 1.82; P < 0.001). Baseline NAG excretion independently predicted macroalbuminuria (adjusted OR, 2.26; P < 0.001) and microalbuminuria (adjusted OR, 1.86; P < 0.001). Baseline pentosidine excretion predicted macroalbuminuria (adjusted OR, 6.89; P = 0.002). Baseline AGE fluorescence predicted microalbuminuria (adjusted OR, 1.68; P = 0.02). However, adjusted for NAG excretion, pentosidine excretion and AGE fluorescence lost the predictive association with macroalbuminuria and microalbuminuria, respectively.Limitations: Use of angiotensin-converting enzyme inhibitors was not directly ascertained, although their use was proscribed during the DCCT.Conclusions: Early in type 1 diabetes, repeated measurements of AER and urinary NAG excretion may identify individuals susceptible to future diabetic nephropathy. Combining the 2 markers may yield a better predictive model than either one alone. Renal tubule stress may be more severe, reflecting abnormal renal tubule processing of AGE-modified proteins, in individuals susceptible to diabetic nephropathy.

Dialysis Research and N-of-1 Trials: Made for Each Other? - Corrected Proof

Deborah R. Zucker, Aneet Deo, Christopher H. Schmid — 2010-02-08

The American Journal of Kidney Diseases Acid-Base and Electrolyte Teaching Case from Saito et al, which appeared in a recent issue of the journal, presents a teaching opportunity about research designs and in particular the use of single-subject (N-of-1 or N=1) trials. Saito et al observed instability in a patient with congenital methylmalonic acidemia during hemodialysis (HD) using an acetate-containing dialysate. Based on biochemistry, they assumed that this response likely was caused by the acetate. They tested an acetate-free citrate HD dialysate in the same patient and did not find this response. Their study looked to more rigorously compare the effectiveness of these 2 buffers and also to verify the connection between the observed adverse reactions (hypotension) and the acetate-based dialysate in this individual.

Comparison of the Prevalence and Mortality Risk of CKD in Australia Using the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study GFR Estimating Equations: The AusDiab (Australian Diabetes, Obesity and Lifestyle) Study - Corrected Proof

Sarah L. White, Kevan R. Polkinghorne, Robert C. Atkins, Steven J. Chadban — 2010-02-08

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is more accurate than the Modification of Diet in Renal Disease (MDRD) Study equation. We applied both equations in a cohort representative of the Australian adult population.Study Design: Population-based cohort study.Setting & Participants: 11,247 randomly selected noninstitutionalized Australians aged ≥ 25 years who attended a physical examination during the baseline AusDiab (Australian Diabetes, Obesity and Lifestyle) Study survey.Predictors & Outcomes: Glomerular filtration rate (GFR) was estimated using the MDRD Study and CKD-EPI equations. Kidney damage was defined as urine albumin-creatinine ratio ≥ 2.5 mg/mmol in men and ≥ 3.5 mg/mmol in women or urine protein-creatinine ratio ≥ 0.20 mg/mg. Chronic kidney disease (CKD) was defined as estimated GFR (eGFR) ≥ 60 mL/min/1.73 m2 or kidney damage. Participants were classified into 3 mutually exclusive subgroups: CKD according to both equations; CKD according to the MDRD Study equation, but no CKD according to the CKD-EPI equation; and no CKD according to both equations. All-cause mortality was examined in subgroups with and without CKD.Measurements: Serum creatinine and urinary albumin, protein, and creatinine measured on a random spot morning urine sample.Results: 266 participants identified as having CKD according to the MDRD Study equation were reclassified to no CKD according to the CKD-EPI equation (estimated prevalence, 1.9%; 95% CI, 1.4-2.6). All had an eGFR ≥ 45 mL/min/1.73 m2 using the MDRD Study equation. Reclassified individuals were predominantly women with a favorable cardiovascular risk profile. The proportion of reclassified individuals with a Framingham-predicted 10-year cardiovascular risk ≥ 30% was 7.2% compared with 7.9% of the group with no CKD according to both equations and 45.3% of individuals retained in stage 3a using both equations. There was no evidence of increased all-cause mortality in the reclassified group (age- and sex-adjusted hazard ratio vs no CKD, 1.01; 95% CI, 0.62-1.97). Using the MDRD Study equation, the prevalence of CKD in the Australian population aged ≥ 25 years was 13.4% (95% CI, 11.1-16.1). Using the CKD-EPI equation, the prevalence was 11.5% (95% CI, 9.42-14.1).Limitations: Single measurements of serum creatinine and urinary markers.Conclusions: The lower estimated prevalence of CKD using the CKD-EPI equation is caused by reclassification of low-risk individuals. Am J Kidney Dis 00:00-00

Light Microscopic Features of Membranous Nephropathy With Unusual Changes of the Podocytes and Glomerular Basement Membrane in a Patient With Sudden Onset of Nephrotic Syndrome - Corrected Proof

Yoshikuni Nagayama, Hiroyuki Morita, Eri Kawashima, Ashio Yoshimura — 2010-02-08

Membranous nephropathy (MN) is a pathologic entity characterized by a spectrum of changes in the glomerular basement membrane (GBM). Diagnostic features include subepithelial immune deposits and thickening of the GBM. In 1968, Ehrenreich and Churg proposed a morphologic classification of MN using electron microscopic findings. This classification was based on immune deposits in the GBM, GBM reaction to the deposits, and resolution of glomerular injury with resorption of the deposits. However, some biopsy specimens with features of MN also show spherical microparticles and podocyte microvillous entrapment in thickened GBM on electron microscopy. The presence of such features has been the source of considerable confusion. In this report, we describe an adult patient with the membranous pattern of injury using light microscopy and atypical electron microscopy findings. It is likely that this represents a distinct pathologic entity unrelated to classic membranous nephropathy.

Reappraisal of the Impact of Race on Survival in Patients on Dialysis - Corrected Proof

Vardaman M. Buckalew, Barry I. Freedman — 2010-02-08

Racial differences in the cause, natural history, and effects of chronic kidney disease have long been the subject of investigation. Dialysis-dependent kidney failure occurs nearly 4 times more often in African Americans than European Americans. Despite this observation, studies repeatedly show that African Americans have a significant survival advantage after initiating dialysis therapy. Although this phenomenon has been attributed to environmental and socioeconomic factors, recent studies show that inherited factors strongly influence racial differences in the development of diverse kidney diseases and may affect the risk of nephropathy-associated cardiovascular disease. We review relevant studies and propose the hypothesis that inherited factors leading to organ-limited kidney diseases and a lower burden of systemic atherosclerosis contribute in part to the improved survival rates in African American patients on dialysis therapy.

Potential New Therapeutic Agents for Diabetic Kidney Disease - Corrected Proof

Faruk Turgut, Warren Kline Bolton — 2010-02-08

Diabetic nephropathy is the leading cause of end-stage renal disease, and both the incidence and prevalence of diabetic nephropathy continue to increase. Currently, various treatment regimens and combinations of therapies provide only partial renoprotection. It is obvious that new approaches are desperately needed to retard the progression of diabetic nephropathy. Recently, a number of new agents have been described that have the potential to delay the progression of diabetic kidney disease and minimize the growing burden of end-stage renal disease. These include inhibitors and breakers of advanced glycation end products, receptor antagonists for advanced glycation end products, protein kinase C inhibitors, NADPH (reduced nicotinamide adenine dinucleotide phosphate) oxidase inhibitors, glycosaminoglycans, endothelin receptor antagonists, antifibrotic agents, and growth factor inhibitors. This review addresses these promising new therapeutic agents for delaying the progression of diabetic kidney disease.

Effect of Thiazolidinediones on Albuminuria and Proteinuria in Diabetes: A Meta-analysis - Corrected Proof

2010-01-29

Background: Because of the major clinical and economic burden of diabetic nephropathy, new therapeutic tools to delay its progression are needed. Recent studies suggest that thiazolidinediones have renal benefits. We aimed to evaluate the effect of thiazolidinediones on urinary albumin and protein excretion in patients with diabetes mellitus.Study Design: Systematic review and meta-analysis by searching MEDLINE/PubMed, EMBASE, and Cochrane CENTRAL databases (1991 to September 2009).Setting & Population: Patients with diabetes mellitus.Selection Criteria for Studies: Randomized controlled trials.Intervention: Thiazolidinediones (rosiglitazone and pioglitazone) compared with placebo or other antidiabetic agents.Outcomes: Weighted (WMDs) and standardized mean differences (SMDs) for changes in urine albumin or protein excretion between the thiazolidinedione and control groups.Results: Of 171 originally identified articles, 15 studies (5 with rosiglitazone and 10 with pioglitazone) involving 2,860 patients were included in the analysis. In participants with baseline normo- or microalbuminuria, the WMD of proportional changes between the thiazolidinedione and control groups in urinary albumin excretion measured using time-specified collections was −64.8% (95% CI, −75.6 to −53.9) and the WMD of changes in albumin-creatinine ratio was −24.8% (95% CI, −39.6 to −10.0). Overall, in participants with normo- and microalbuminuria, thiazolidinedione treatment was associated with a significant decrease in urinary albumin excretion (SMD, −0.6 units of standard deviation [SD]; 95% CI, −0.8 to −0.4). Similarly, thiazolidinediones were associated with a significant decrease in urinary protein excretion in patients with proteinuria (SMD, −1.1 units of SD; 95% CI, −1.8 to −0.4).Limitations: Significant heterogeneity across included studies in several subgroup analyses; patient-level data not available.Conclusions: Treatment with thiazolidinediones significantly decreases urinary albumin and protein excretion in patients with diabetes. This finding calls for clinical trials with hard renal outcomes to elucidate the potential benefits of thiazolidinediones on diabetic nephropathy.

Culture-Negative Peritonitis in Peritoneal Dialysis Patients in Australia: Predictors, Treatment, and Outcomes in 435 Cases - Corrected Proof

2010-01-29

Background: Reports of culture-negative peritoneal dialysis (PD)-associated peritonitis have been sparse, conflicting, and limited to small single-center studies. The aim of this investigation is to examine the frequency, predictors, treatment, and outcomes of culture-negative PD-associated peritonitis.Study Design: Observational cohort study using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data.Setting & Participants: All Australian PD patients between October 1, 2003, and December 31, 2006.Predictors: Demographic, clinical, and facility variables.Outcomes & Measurements: Culture-negative PD-associated peritonitis occurrence, relapse, hospitalization, catheter removal, hemodialysis transfer, and death.Results: Of 4,675 patients who received PD in Australia during the study period, 435 episodes of culture-negative peritonitis occurred in 361 individuals. Culture-negative peritonitis was not associated with demographic or clinical variables. A history of previous antibiotic treatment for peritonitis was more common with culture-negative than culture-positive peritonitis (42% vs 35%; P = 0.01). Compared with culture-positive peritonitis, culture-negative peritonitis was significantly more likely to be cured using antibiotics alone (77% vs 66%; P < 0.001) and less likely to be complicated by hospitalization (60% vs 71%; P < 0.001), catheter removal (12% vs 23%; P < 0.001), permanent hemodialysis therapy transfer (10% vs 19%; P < 0.001), or death (1% vs 2.5%; P = 0.04). Relapse rates were similar between the 2 groups. Patients with relapsed culture-negative peritonitis were more likely to have their catheters removed (29% vs 10% [P < 0.001]; OR, 3.83; 95% CI, 2.00-7.32). Administration of vancomycin or cephalosporin in the initial empiric antibiotic regimen and the timing of catheter removal were not significantly associated with clinical outcomes.Limitations: Limited covariate adjustment. Residual confounding and coding bias could not be excluded.Conclusions: Culture-negative peritonitis is a common complication with a relatively benign outcome. A history of previous antibiotic treatment is a significant risk factor for this condition.

Thrombocytopenia Associated With Use of a Biocompatible Hemodialysis Membrane: A Case Report - Corrected Proof

James B. Post — 2010-01-29

Biocompatibility of a dialyzer membrane has been defined largely by the degree to which it activates complement. Modifications of the cellulose membrane and the development of synthetic membranes have minimized the activation of complement and its associated complications. However, less is known about the blood–dialyzer membrane interactions that may occur in membranes made of the same synthetic polymer. A patient is described who developed dialysis-associated thrombocytopenia using a Fresenius Medical Care Optiflux polysulfone membrane (F-160) that significantly improved when switched to the polysulfone Asahi REXEED 25S membrane (AR-25S). A comparison of postdialysis d-dimer level suggests that the F-160 membrane activated the coagulation pathway to a greater extent than the AR-25S. Subtle differences between the internal surfaces of the membranes that are manufacturer specific may be responsible for exposing this patient's unique predisposition to thrombosis and thrombocytopenia. Despite the advances in membrane biocompatibility, differences may exist among membranes made of the same synthetic polymer.

Is Collapsing C1q Nephropathy Another MYH9-Associated Kidney Disease? A Case Report - Corrected Proof

2010-01-29

C1q nephropathy is a rare kidney disease that can present with nephrotic syndrome and typically has the histologic phenotype of either minimal change disease or focal segmental glomerulosclerosis (FSGS). Disagreement exists about whether it is a distinct immune complex–mediated glomerulopathy or it resides in the spectrum of FSGS-minimal change disease. Two African American patients with C1q nephropathy histologically presenting as the collapsing variant of FSGS (collapsing C1q nephropathy) and rapid loss of kidney function were genotyped for polymorphisms in the non–muscle myosin heavy chain 9 gene (MYH9). Both cases were homozygous for the MYH9 E1 risk haplotype, the variant strongly associated with idiopathic FSGS, collapsing FSGS in human immunodeficiency virus–associated nephropathy, and focal global glomerulosclerosis (historically attributed to hypertensive nephrosclerosis). Collapsing C1q nephropathy with rapid progression to end-stage renal disease appears to reside in the MYH9-associated disease spectrum.

Intensive Versus Conventional Therapy to Slow the Progression of Idiopathic Glomerular Diseases - Corrected Proof

Stefano Bianchi, Roberto Bigazzi, Vito M. Campese — 2010-01-25

Background: Chronic kidney disease (CKD) caused by idiopathic glomerular diseases usually is progressive. Inhibition of the renin-angiotensin system (RAS) retards, but does not abrogate, CKD progression. Statins and spironolactone may decrease the rate of CKD progression independently or in addition to RAS inhibition.Study Design: Randomized open-label study.Setting & Participants: We recruited 128 patients (82 men and 46 women) with a clinical diagnosis of idiopathic chronic glomerulonephritis and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 (range, 36-102 mL/min/1.73 m2), and urine protein-creatinine ratio ranging from 1.1-5.2 g/g.Intervention: Intensive therapy (a combination of RAS inhibitors [angiotensin-converting enzyme [ACE] inhibitors plus angiotensin receptor blockers [ARBs] plus a high-dose statin and spironolactone) versus conventional therapy (a regimen based on ACE inhibitors with a low-dose statin).Outcomes: Changes in eGFR, proteinuria, and adverse events after 3 years of therapy.Results: With intensive therapy, urine protein-creatinine ratio decreased from 2.65 (range, 1.1-5.2) to 0.45 (0.14-1.51) g/g (P < 0.001) and eGFR did not significantly change over time (64.6 ± 2.1 vs 62.9 ± 2.9 mL/min/1.73 m2). With conventional therapy, urine protein-creatinine ratio decreased from 2.60 (range, 1.32-5.4) to 1.23 (0.36-3.42) g/g (P < 0.001) and eGFR decreased from 62.5 ± 1.7 to 55.8 ± 1.9 mL/min/1.73 m2 (P < 0.001). Comparison of the decreases in proteinuria and GFR between intensive versus conventional therapy was significantly different starting in the 1st and 12th months, respectively. Systolic blood pressure was lower with intensive than conventional therapy (113.5 ± 1.4 vs 122.7 ± 1.2 mm Hg; P < 0.01). We found an inverse relationship between percentage of decrease in proteinuria and change in eGFR (P < 0.001). Patients on intensive therapy were more likely to develop adverse events, such as hyperkalemia (9 vs 3 patients in the conventional therapy group) and discontinue therapy (15 vs 8 patients in the conventional therapy group).Limitations: Open-label design.Conclusions: A more intensive therapy that includes a combination of ACE inhibitors and ARBs plus high-dose statins and spironolactone may retard CKD progression more effectively than conventional therapy based on ACE inhibitors plus low-dose statin, but may lead to more adverse effects and discontinuation of therapy.

Incidence and Outcomes of Contrast-Induced Nephropathy After Computed Tomography in Patients With CKD: A Quality Improvement Report - Corrected Proof

2010-01-25

Background: Although there has been considerable investigation of the general characteristics of contrast-induced nephropathy (CIN), it has not been studied adequately in a computed tomography (CT) population. We assessed the incidence and outcomes of CIN after contrast-enhanced CT in patients with chronic kidney disease pretreated with saline and N-acetylcysteine (NAC).Design: Quality improvement report.Setting & Participants: 520 patients registered in a CIN prevention program.Quality Improvement Plan: We initiated the CIN prevention program in January 2007. In this program, patients with chronic kidney disease undergoing contrast-enhanced CT in an outpatient setting were automatically referred to nephrologists, and patients received saline and NAC before and after CT. The development of CIN was assessed 48-96 hours after CT.Outcomes: Incidence of CIN and time to renal replacement therapy.Measurements: Baseline serum creatinine, hemoglobin, and serum albumin levels; type and volume of contrast agents; and post-CT serum creatinine level.Results: Overall, CIN occurred in 13 (2.5%) patients. Incidences of CIN were 0.0%, 2.9%, and 12.1% in patients with an estimated glomerular filtration rate of 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. The risk of CIN was increased in patients with severely decreased kidney function and diabetes. The development of CIN consequently increased the risk of renal replacement therapy (P < 0.001 by log-rank), and the risk was significantly accentuated in patients with estimated glomerular filtration rate <30 mL/min/1.73 m2.Limitations: A single-center study and comparison with previous studies.Conclusions: The incidence of CIN was relatively low in patients treated with saline and NAC. The development of CIN predisposed to poor kidney survival in the long term.

Long-term Effects of Arteriovenous Fistula Closure on Echocardiographic Functional and Structural Findings in Hemodialysis Patients: A Prospective Study - Corrected Proof

2010-01-20

Background: The arteriovenous fistula (AVF) provides an effective vascular access for hemodialysis; however, the associated hemodynamic effects may alter cardiac structure and function. The objective of this study is to evaluate the effect of AVF closure on functional and structural echocardiographic findings.Study Design: Prospective observational study.Setting & Participants: In a single center between 2003 and 2006, we enrolled 25 consecutive hemodialysis patients with AVF malfunction who underwent AVF closure and conversion to a tunneled central venous catheter because of exhaustion of alternative vascular sites and 36 matched controls with a well-functioning AVF.Predictor: AVF closure.Outcomes & Measurements: Outcomes were changes in findings on echocardiograms obtained before and 6 months after AVF closure for patients in the AVF-closure group and at baseline and 6 months later for controls. Echocardiographic measurements included left ventricular (LV) internal diastolic diameter, interventricular septum thickness, diastolic posterior wall thickness, LV mass (LVM), LVM index (LVMi), and LV ejection fraction (LVEF). Dialysis modality and scheme were unchanged.Results: In the AVF-closure group, LVM decreased from 225 ± 55 to 206 ± 51 g (P < 0.001) and LVMi decreased from 135 ± 40 to 123 ± 35 g/m2 (P < 0.001). LV internal diastolic diameter, interventricular septum thickness, and diastolic posterior wall thickness decreased significantly, whereas LVEF increased from 56% ± 7% to 59% ± 6% (P < 0.001). No significant changes were observed in controls. In patients with AVF closure, LV morphologic characteristics showed a decrease in both eccentric and concentric hypertrophy in favor of normalization or a pattern of concentric remodeling. No significant changes were observed in controls.Limitations: Use of matched rather than randomized controls.Conclusions: Closure of an AVF determines a significant decrease in LV internal diastolic diameter, interventricular septum thickness, and diastolic posterior wall thickness. This is associated with significant improvement in LVEF, a significant decrease in LVM and LVMi, and a more favorable shift of cardiac geometry toward normality.

Bone Marrow Iron, Iron Indices, and the Response to Intravenous Iron in Patients With Non–Dialysis-Dependent CKD - Corrected Proof

2010-01-18

Background: Information about iron stores and their relationship with transferrin saturation (TSAT), serum ferritin, and the erythropoietic response to iron therapy is scarce in anemic non–dialysis-dependent patients with chronic kidney disease (CKD). We examined the diagnostic utility of peripheral-iron indices and the erythropoietic response to intravenous iron as indices of iron store depletion using bone marrow iron as a reference test in anemic non–dialysis-dependent patients with CKD.Study Design: Diagnostic test study.Setting & Participants: 100 anemic (hemoglobin <11 g/dL) patients with CKD stages 3-5, not receiving epoetin and iron.Index Tests: TSAT index and serum ferritin level at baseline and increase in hemoglobin level 1 month after 200 mg of iron sucrose daily for 5 days.Reference Test: Bone marrow iron (assessed using aspiration and Perls' stain), depleted versus replete, at baseline.Measurements: Area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of peripheral-iron indices and erythropoietic response to describe bone marrow iron stores.Results: Bone marrow iron stores were depleted in 48% of patients at baseline. In iron-depleted versus -replete subjects, mean hemoglobin level, median TSAT index, median serum ferritin level, and hemoglobin level increase after iron sucrose administration were 8.74 ± 1.1 (SD) versus 9.22 ± 0.9 g/dL (P = 0.02), 19% (interquartile range [IQR], 15%) versus 28% (IQR, 12%; P < 0.001), 100 (IQR, 131) versus 220 ng/mL (IQR, 213; P < 0.001), and 1.2 ± 0.4 versus 0.8 ± 0.3 g/dL (P < 0.001), respectively. TSAT, ferritin level, and increase in hemoglobin level AUROCs were similar: 0.75 (95% CI, 0.66-0.85), 0.76 (95% CI, 0.66-0.85), and 0.74 (95% CI, 0.65-0.84), respectively.Limitations: Bone marrow iron as the index of iron stores.Conclusions: Half the anemic patients with CKD stages 3-5 had depleted iron stores. Peripheral-iron indices and erythropoietic response had equivalent, but limited, utility in identifying depletion of bone marrow iron stores. Use of these indices to indicate depletion of iron stores should be reconsidered.

Binder Blinders—Niacin of Omission? - Corrected Proof

Andrew G. Bostom — 2010-01-18

It is common knowledge to every schoolboy and even every Bachelor of Arts,That all sin is divided into two parts.One kind of sin is called a sin of commission, and that is very important,And it is what you are doing when you are doing something you ortant,And the other kind of sin is just the opposite and is called a sin of omissionand is equally bad in the eyes of all right-thinking people, fromBilly Sunday to Buddha,And it consists of not having done something you shuddha….From Ogden Nash, “Portrait of the Artist as Prematurely Old Man”

Subcapsular Fluid Collection: An Unusual Manifestation of Nephrotic Syndrome - Corrected Proof

Nisar A. Wani, Farooq Mir, Tariq Gojwari, Umar A. Qureshi, Rayees Ahmad — 2010-01-11

Nephrotic syndrome is characterized by heavy proteinuria (protein excretion >3.5 g/24 h in adults or 40 mg/m2/h in children), hypoalbuminemia (albumin <2.5 g/dL), edema, and hyperlipidemia. Edema results from fluid accumulation in the subcutaneous tissue. Fluid also commonly accumulates in the peritoneal and pleural cavities. Rarely, fluid may accumulate in the subcapsular space around the kidneys. Such subcapsular fluid accumulation has been reported as a complication of nephrotic syndrome or in association with severe pulmonary hypertension. We describe a patient with nephrotic syndrome who presented with hypertension and pain in the left lumbar region. Ultrasonography and magnetic resonance imaging (MRI) showed a massive subcapsular collection around the left kidney. The patient was treated successfully with ultrasonography-guided drainage of the collection and medical treatment. The kidney biopsy specimen showed changes of focal segmental glomerulosclerosis.

Nutcracker Syndrome and Radiographic Evaluation of Loin Pain and Hematuria - Corrected Proof

Amir Bhanji, Paul Malcolm, Mahzuz Karim — 2009-12-21

Loin pain and hematuria are common symptoms, presenting in patients of all ages. There are various underlying pathologic causes, including renal or ureteric calculi or tumors, intrinsic kidney disease (including glomerulonephritis), and loin pain hematuria syndrome. Since some of these causes are potentially serious and may be treatable if identified early, it is important to establish a diagnosis. Patients therefore often undergo multiple investigations and procedures. However, in some cases, no cause is identified unless rarer pathologic states are considered. We describe a patient with loin pain and hematuria who proved to be a diagnostic dilemma for several years before the diagnosis of nutcracker syndrome was established.

Extensive Infiltrating Renal Cell Carcinoma With Minimal Distortion of the Renal Anatomy Mimicking Benign Renal Vein Thrombosis - Corrected Proof

2009-12-07

Malignancies of the kidney can present with an infiltrative appearance and may include lymphoma; metastatic disease; epithelial tumors, such as invasive transitional cell carcinoma; medullary carcinoma; renal sarcoma; and occasionally, aggressive renal cell carcinoma (RCC). Although an infiltrative appearance is not common for RCC, it can occur in up to 6% of cases. These tumors do not present as discrete expansile masses, but instead show an infiltrative pattern of growth preserving the overall size and contour of the kidney. The normal internal architecture of the kidney is replaced and obliterated by tumor. This infiltrative appearance can even mimic benign infectious and inflammatory processes, such as bacterial and xanthogranulomatous pyelonephritis or benign renal vein thrombosis.

First Identification of an Antigen in Autoimmune Idiopathic Membranous Nephropathy: Toward Targeted Therapy? - Corrected Proof

Pierre Ronco, Hanna Debiec — 2009-11-18

Commentary on Beck LH Jr, Bonegio RG, Lambeau G, et al. M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009;361(1):11-21.

Incidental Discovery of a Renal Cell Carcinoma on Native Kidney Biopsy - Corrected Proof

C. John Sperati, Nada Alachkar, Ronald Rodriguez, Mark Haas, Michael J. Choi — 2009-11-02

Although definitive management of kidney cysts and tumors typically is performed by urologists, the initial diagnosis and longitudinal follow-up often are the responsibility of nephrologists. As such, understanding the natural history and spectrum of disease associated with kidney cysts is important to practicing nephrologists. We present the case of an incidentally detected renal cell carcinoma (RCC) on a biopsy of a native kidney and discuss therapeutic considerations in the management of cystic kidney lesions.

Maintenance of Kidney Function Following Treatment With Eculizumab and Discontinuation of Plasma Exchange After a Third Kidney Transplant for Atypical Hemolytic Uremic Syndrome Associated With a CFH Mutation - Corrected Proof

2009-10-26

Kidney transplant in patients with atypical hemolytic uremic syndrome (aHUS) is associated with a poor outcome because of recurrent disease, especially in patients known to have a factor H mutation. Long-term prophylactic plasma exchange and combined liver-kidney transplant have prevented graft loss caused by recurrence. However, the mortality associated with liver transplant is not negligible, and prophylactic plasma exchange requires permanent vascular access and regular hospitalization and exposes the patient to potential allergic reactions to plasma. Eculizumab is a high-affinity humanized monoclonal antibody that binds to C5 and thus prevents generation of C5a and the membrane attack complex. We report the case of a 17-year-old girl with aHUS associated with a mutation in the gene for complement factor H (CFH; c.3572C>T, Ser1191Leu) who was highly dependent on plasma exchange. Because of severe allergic reactions to plasma after the third renal graft, eculizumab was introduced in place of plasma exchange without problems. This and other reports suggest that the promise of complement inhibitors in the management of aHUS is going to be fulfilled.

Plasma Cell Dyscrasia Causing Light Chain Tubulopathy Without Fanconi Syndrome - Corrected Proof

Matthew R. Elliott, Cherise Cortese, Alvaro Moreno-Aspitia, Jamie P. Dwyer — 2009-10-22

Light chain tubulopathy is a rare complication associated with plasma cell dyscrasias. There are no more than 80 cases reported in the English literature; the defining series was 17 patients described by Maldonado et al in 1975. That original work showed in patients with acquired Fanconi syndrome an association with monoclonal immunoglobulin light chain proteinuria, slow progression of the plasma cell dyscrasia, and crystal formation in proximal tubule cells. Since that time, a variety of clinical and pathologic findings have been reported with respect to light chain tubulopathy. Messiaen et al reported a series of 11 cases, 3 of which had no crystal formation, 2 had only partial Fanconi syndrome, and the degree of plasma cell dyscrasia ranged from monoclonal gammopathy of undetermined significance (MGUS) to full-blown multiple myeloma. The timing of kidney manifestations in relation to the diagnosis of plasma cell dyscrasia also varies. Most reports show that the investigation of proteinuria, kidney failure, Fanconi syndrome, or osteomalacia leads to the discovery of plasma cell dyscrasia; however, there are instances in which light chain tubulopathy proceeded the diagnosis of plasma cell dyscrasia. Additionally, light chain tubulopathy rarely occurs without Fanconi syndrome, as was described recently in 1 case report. We report a case of light chain tubulopathy without Fanconi syndrome found to have significant crystalline inclusions in tubular epithelial cells and podocytes discovered many years after the diagnosis of MGUS.

Permanent Hearing Loss With Iopamidol Following Aortic Angiography in a Hemodialysis Patient: A Case Report and Review of the Literature - Corrected Proof

Mohammed R. Karim, Leah Balsam, Sofia Rubinstein — 2009-10-22

Nonionic low-osmolar contrast agents are considered safe for intravenous or intra-arterial administration and are used widely in the general population, as well as in patients on hemodialysis therapy. There are data limited to case reports for contrast-induced hearing loss; however, the ototoxicity induced by contrast agents in patients with chronic kidney disease has never been described. We report a case of permanent sensorineural deafness after abdominal aortic angiography with iopamidol in a woman with end-stage renal disease on hemodialysis therapy and review the literature relating to contrast use with the development of hearing impairment.

New-Onset Proteinuria With Massive Amorphous Glomerular Deposits - Corrected Proof

Dylan V. Miller, Ahmet Dogan, Sanjeev Sethi — 2009-07-21

We present 2 patients with long-standing mild hypertension who presented with new-onset proteinuria and decreased kidney function. We describe interesting and unusual kidney biopsy findings in these 2 patients.