James A. Tumlin

Incidence of Contrast-Induced Nephropathy after Contrast-Enhanced Computed Tomography in the Outpatient Setting

BACKGROUND AND OBJECTIVESnNo prospective study has reported the incidence of contrast-induced nephropathy (CIN) or the associated morbidity and mortality after contrast-enhanced computed tomography (CECT) in the outpatient setting.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnWe enrolled and followed a prospective, consecutive cohort (June 2007 through January 2009) of patients who received intravenous contrast for CECT in the emergency department of a large, academic, tertiary care center. Outcomes measured were as follows (1) CIN: An increase in serum creatinine > or =0.5 mg/dl or > or =25% 2 to 7 d after contrast administration; (2) severe renal failure: An increase in serum creatinine to > or =3.0 mg/dl or the need for dialysis at 45 d; and (3) renal failure as a contributing cause of death (consensus of three independent physicians) at 45 d.nnnRESULTSnThe incidence of CIN was 11% (70 of 633) among the 633 patients enrolled. Fifteen (2%) patients died within 45 d, including six deaths after study-defined CIN. Seven (1%) patients developed severe renal failure, six of whom had study-defined CIN. Of the six patients with CIN and severe renal failure, four died, and adjudicators determined that renal failure significantly contributed to all four deaths. Thus, CIN was associated with an increased risk for severe renal failure and death from renal failure.nnnCONCLUSIONSnCIN occurs in >10% of patients who undergo CECT in the outpatient setting and is associated with a significant risk for severe renal failure and death.

Risk factors for acute renal failure: inherent and modifiable risks

Purpose of reviewOur purpose is to discuss established risk factors in the development of acute renal failure and briefly overview clinical markers and preventive measures. Recent findingsFindings from the literature support the role of older age, diabetes, underlying renal insufficiency, and heart failure as predisposing factors for acute renal failure. Diabetics with baseline renal insufficiency represent the highest risk subgroup. An association between sepsis, hypovolemia, and acute renal failure is clear. Liver failure, rhabdomyolysis, and open-heart surgery (especially valve replacement) are clinical conditions potentially leading to acute renal failure. Increasing evidence shows that intraabdominal hypertension may contribute to the development of acute renal failure. Radiocontrast and antimicrobial agents are the most common causes of nephrotoxic acute renal failure. In terms of prevention, avoiding nephrotoxins when possible is certainly desirable; fluid therapy is an effective prevention measure in certain clinical circumstances. Supporting cardiac output, mean arterial pressure, and renal perfusion pressure are indicated to reduce the risk for acute renal failure. Nonionic, isoosmolar intravenous contrast should be used in high-risk patients. Although urine output and serum creatinine lack sensitivity and specificity in acute renal failure, they remain the most used parameters in clinical practice. SummaryThere are identified risk factors of acute renal failure. Because acute renal failure is associated with a worsening outcome, particularly if occurring in critical illness and if severe enough to require renal replacement therapy, preventive measures should be part of appropriate management.

A Longitudinal Study of Uremic Pruritus in Hemodialysis Patients

BACKGROUND AND OBJECTIVESnAlthough uremic pruritus (UP) is a highly prevalent complication of chronic kidney disease, it remains poorly characterized. There have been no longitudinal studies of natural history, and no health-related quality of life (HR-QOL) instruments have been developed for UP. The objectives of this study were to describe the natural history of UP, to compare rating scales of itching intensity, and to assess usefulness and validity of HR-QOL instruments for UP.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnThe intensity, severity, and effects of pathologic itching on HR-QOL were assessed prospectively in 103 patients with UP on chronic hemodialysis. Outcome measures were obtained at scheduled intervals over 3.5 months.nnnRESULTSnItching daily or nearly daily was reported by 84% of patients and had been ongoing for >1 year in 59%. In 83%, pruritus involved large, nondermatomal areas with striking bilateral symmetry. Two thirds of the patients were using medications such as antihistamines, steroids, and various emollients without satisfactory relief of itching. Statistically significant associations were found among itching intensity, severity, and HR-QOL measures in domains such as mood, social relations, and sleep. Among patients with moderate-to-severe UP, changes in itching intensity of 20% or greater were associated with significant reductions in HR-QOL measures.nnnCONCLUSIONSnThis first longitudinal study of UP describes key features of UP and its effect on HR-QOL. The assessment instruments we have developed are easily used, are responsive to changes in UP intensity, and should facilitate clinical evaluation and research to meet the needs of afflicted patients.

Prospective Study of the Incidence of Contrast-induced Nephropathy Among Patients Evaluated for Pulmonary Embolism by Contrast-enhanced Computed Tomography

OBJECTIVESnContrast-enhanced computed tomography (CECT) of the pulmonary arteries (CTPA) has become the mainstay to evaluate patients with suspected pulmonary embolism (PE) and is one of the most common CECT imaging studies performed in the emergency department (ED). While contrast-induced nephropathy (CIN) is a known complication, this risk is not well defined in the ED or other ambulatory setting. The aim of this study was to define the risk of CIN following CTPA.nnnMETHODSnThe authors enrolled and followed a prospective, consecutive cohort (June 2007 through January 2009) of patients who received intravenous (IV) contrast for CTPA in the ED of a large, academic tertiary care center. Study outcomes included 1) CIN defined as an increase in serum creatinine (sCr) of ≥ 0.5 mg/dL or ≥ 25%, 2 to 7 days following contrast administration; and 2) severe renal failure defined as an increase in sCr to ≥ 3.0 mg/dL or the need for dialysis within 45 days and/or renal failure as a contributing cause of death at 45 days, determined by the consensus of three independent physicians.nnnRESULTSnA total of 174 patients underwent CTPA, which demonstrated acute PE in 12 (7%, 95% confidence interval [CI]u2003= 3% to 12%). Twenty-five patients developed CIN (14%, 95% CI = 10% to 20%) including one with acute PE. The development of CIN after CTPA significantly increased the risk of the composite outcome of severe renal failure or death from renal failure within 45 days (relative risk = 36, 95% CI = 3 to 384). No severe adverse outcomes were directly attributable to complications of venous thromboembolism (VTE) or its treatment.nnnCONCLUSIONSnu2002 In this population, CIN was at least as common as the diagnosis of PE after CTPA; the development of CIN was associated with an increased risk of severe renal failure and death within the subsequent 45 days. Clinicians should consider the risk of CIN associated with CTPA and discuss this risk with patients.

Pathophysiology of the cardiorenal syndromes: executive summary from the eleventh consensus conference of the Acute Dialysis Quality Initiative (ADQI).

Cardiorenal syndromes (CRS) have been recently classified into five distinct entities, each with different major pathophysiologic mechanisms. CRS type 1 most commonly occurs in the setting of acutely decompensated heart failure where approximately 25% of patients develop a rise in serum creatinine and a reduction of urine output after the first several doses of intravenous diuretics. Altered cardiac and renal hemodynamics are believed to be the most important determinants of CRS type 1. CRS type 2 is the hastened progression of chronic kidney disease (CKD) in the setting of chronic heart failure. Accelerated renal cell apoptosis and replacement fibrosis is considered to be the dominant mechanism. CRS type 3 is acutely decompensated heart failure after acute kidney injury from inflammatory, toxic, or ischemic insults. This syndrome is precipitated by salt and water overload, acute uremic myocyte dysfunction, and neurohormonal dysregulation. CRS type 4 is manifested by the acceleration of the progression of chronic heart failure in the setting of CKD. Cardiac myocyte dysfunction and fibrosis, so-called CKD cardiomyopathy, is believed to be the predominant pathophysiologic mechanism. Type 5 CRS is simultaneous acute cardiac and renal injury in the setting of an overwhelming systemic insult such as sepsis. In this scenario, the predominant pathophysiological disturbance is microcirculatory dysfunction as a result of acutely abnormal immune cell signaling, catecholamine cellular toxicity, and enzymatic activation which result in simultaneous organ injury often extending beyond both the heart and the kidneys. This paper will summarize these and other key findings from an international consensus conference on the spectrum of pathophysiologic mechanisms at work in the CRS.

Evaluation of 32 urine biomarkers to predict the progression of acute kidney injury after cardiac surgery

Biomarkers for acute kidney injury (AKI) have been used to predict the progression of AKI but a systematic comparison of the prognostic ability of each biomarkers alone or in combination has not been performed. In order to assess this, we measured the concentration of 32 candidate biomarkers in the urine of 95 patients with AKIN stage 1 after cardiac surgery. Urine markers were divided into eight groups based on the putative pathophysiologic mechanism they reflect. We then compared the ability of the markers alone or in combination to predict the primary outcome of worsening AKI or death (23 patients) and the secondary outcome of AKIN stage 3 or death (13 patients). IL-18 was the best predictor of both outcomes (AUC of 0.74 and 0.89). L-FABP (AUC of 0.67 and 0.85), NGAL (AUC of 0.72 and 0.83) and KIM-1 (AUC of 0.73 and 0.81) were also good predictors. Correlation between most of the markers was generally related to their predictive ability but KIM-1 had a relatively weak correlation with other markers. The combination of IL-18 and KIM-1 had a very good predictive value with an AUC of 0.93 to predict AKIN 3 or death. Thus, combination of IL-18 and KIM-1 would result in improved identification of high risk patients for enrollment in clinical trials.

Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel

Purpose: A synthetic adrenocorticotropin (ACTH) analog has shown efficacy in Europe as primary and secondary therapy for nephrotic syndrome, but there is no published experience using the natural, highly purified ACTH gel formulation, available in the United States, for nephrotic syndrome. We therefore investigated the use of ACTH gel for nephrotic syndrome in the United States. Patients and methods: Twenty-one patients with nephrotic syndrome treated with ACTH gel outside of research settings in the United States, with initiation of therapy by December 31, 2009, allowing a minimum 6 months follow-up. We defined complete remission as stable renal function with proteinuria falling to <500 mg/day, and partial remission as stable renal function with >50% reduction in proteinuria from 500 to 3500 mg/day. Results: Twenty-one patients with nephrotic syndrome were treated: 11 with idiopathic membranous nephropathy (iMN), 4 with membranoproliferative glomerulonephritis (MPGN), 1 with focal segmental glomerulosclerosis (FSGS), 1 with minimal change disease (MCD), 1 with immunoglobulin A (IgA) nephropathy, 1 with class V systemic lupus erythematosus (SLE) glomerulonephritis, 1 with monoclonal diffuse proliferative glomerulonephritis, and 1 with unbiopsied nephrotic syndrome. ACTH was used as primary therapy for 3 patients; the remaining patients had previously failed a mean 2.3 immunosuppressive regimens. Eleven patients achieved a complete or partial remission, with 4 (19%) in complete remission. Of the 11 patients who achieved remission, 9 had iMN, 1 had FSGS, and 1 had IgA nephropathy. Of the 11 patients with iMN, 3 (27%) achieved complete remission and 6 (55%) achieved partial remission despite having previously failed a mean 2.4 therapies. Five patients reported steroid-like adverse effects, but there were no severe infections. The limitations were retrospective data analysis with short-term follow-up. Conclusion: ACTH gel may be a viable treatment option for resistant nephrotic syndrome due to membranous nephropathy. Short-term data suggest that remission rates may approach 80%.

Cardiorenal syndrome type 4: insights on clinical presentation and pathophysiology from the eleventh consensus conference of the Acute Dialysis Quality Initiative (ADQI).

In developed countries, the continuing rise in the prevalence of hypertension, hyperlipidemia and diabetes has contributed to an overall increase in the incidence of both cardiovascular disease (CVD) and chronic kidney disease (CKD). The observation that even modest reductions in renal function correlate with increased CVD morbidity and mortality has led to the recognition that CKD is an independent risk factor for CVD. Conversely, there is a growing recognition that many pathologic conditions that contribute to CVD, including coronary artery disease, left ventricular hypertrophy and diastolic dysfunction, can accelerate the decline in renal function. In addition, physiologic mechanisms designed to compensate for reduced glomerular filtration rate including activation of the renin-angiotensin-aldosterone axis, the release of fibroblastic growth factor 23 and other mechanisms for calcium-phosphate homeostasis as well as and the pathophysiologic effects of uremic toxins can also directly contribute to CVD. The end result of the interaction between changes in pressure and volume overload and the physiologic compensation for the loss of function in both the heart and the kidney leads to accelerated decline in both organ systems. This complex physiologic and pathophysiologic interplay between the cardiovascular and renal systems is collectively referred to as the cardiorenal syndrome. The discussion which follows is aimed at outlining the pathophysiologic mechanisms linking advanced CKD (4 and 5) to the development of cardiac abnormalities which occur with unique frequency and severity in patients with severe impairment of renal function.

The Effect of the Selective Cytopheretic Device on Acute Kidney Injury Outcomes in the Intensive Care Unit: A Multicenter Pilot Study

Acute kidney injury (AKI) is characterized by deterioration in kidney function resulting in multisystem abnormalities. Much of the morbidity and mortality associated with AKI result from a systemic inflammatory response syndrome (SIRS). This study described herein is a prospective, single‐arm, multicenter US study designed to evaluate the safety and efficacy of the Selective Cytopheretic Device (SCD) treatment on AKI requiring continuous renal replacement therapy (CRRT) in the ICU. The study enrolled 35 subjects. The mean age was 56.3u2003±u200315. With regard to race, 71.4% of the subjects were Caucasian, 22.9% were Black, and 5.7% were Hispanic. Average SOFA score was 11.3u2003±u20033.6. Death from any cause at Day 60 was 31.4%. Renal recovery, defined as dialysis independence, was observed in all of the surviving subjects at Day 60. The results of this pilot study indicate the potential for a substantial improvement in patient outcomes over standard of care therapy, which is associated with a greater than 50% 60‐day mortality in the literature. The SCD warrants further study in scientifically sound, pivotal trial to demonstrate reasonable assurance of safety and effectiveness.

A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction

IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m2, to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.