Paul J. Scheel

Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease

Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis. Recent findings suggest that ECD is a clonal disorder, marked by recurrent BRAFV600E mutations in >50% of patients, in which chronic uncontrolled inflammation is an important mediator of disease pathogenesis. Although ∼500 to 550 cases have been described in the literature to date, increased physician awareness has driven a dramatic increase in ECD diagnoses over the last decade. ECD frequently involves multiple organ systems and has historically lacked effective therapies. Given the protean clinical manifestations and the lack of a consensus-derived approach for the management of ECD, we provide here the first multidisciplinary consensus guidelines for the clinical management of ECD. These recommendations were outlined at the First International Medical Symposium for ECD, comprised of a comprehensive group of international academicians with expertise in the pathophysiology and therapy of ECD. Detailed recommendations on the initial clinical, laboratory, and radiographic assessment of ECD patients are presented in addition to treatment recommendations based on critical appraisal of the literature and clinical experience. These formalized consensus descriptions will hopefully facilitate ongoing and future research efforts in this disorder.

Percutaneous Translumbar Inferior Vena Cava Cannulation for Hemodialysis

The purpose of this study was to evaluate the percutaneous translumbar approach for long-term hemodialysis catheter access. Seventeen double-lumen hemodialysis catheters were placed percutaneously from the right flank to the inferior vena cava in 12 patients. Catheter placement was successful in all patients. Adequate flow rates were obtained. Seven episodes of thrombosis-related access failure occurred (0.33 episodes/100 days at risk). Two catheters were removed and five catheters were managed with urokinase infusion. Six episodes of infection occurred (0.28 episodes/100 days at risk). Four required catheter removal. Two catheters were removed after defects developed in the catheter. Five catheters were removed electively because catheter hemodialysis was discontinued. Four catheters remained in place. Cumulative patency was 52% at 6 months and 17% at 12 months. Translumbar inferior vena cava hemodialysis catheters represent a valuable alternative in cases in which traditional catheter sites have failed.

Acute renal failure associated with immunoglobulin therapy

Four cases of acute renal failure induced by intravenous immunoglobulin are presented, and the literature on the subject is reviewed. The clinical course varies from asymptomatic serum creatinine elevation to anuric renal failure occurring within days of the institution of therapy, followed by the rapid recovery of renal function after termination of therapy. The renal histology demonstrates severe tubular vacuolization with cellular swelling and preservation of the brush border. Glomerular endothelial, mesangial, and epithelial cells also may demonstrate swelling and vacuolization. There is no evidence for inflammatory or immune complex-mediated etiologies. The immunoglobulins or carbohydrate additives in the preparations appear to have a unique and reversible effect on the glomerular and tubular cell function.

Observations on a Cohort of HIV-Infected Patients Undergoing Native Renal Biopsy

Aims: This study aims to explore the spectrum of renal disease in HIV-infected patients, identify clinical predictors of HIV-associated nephropathy (HIVAN), and investigate the performance of renal biopsy in HIV-infected patients. Method: Of 263 HIV-infected patients with renal disease evaluated between 1995 and 2004, 152 had a renal biopsy, while 111 had not. A group comparison was performed. Results: The leading biopsy diagnoses were HIVAN (35%), noncollapsing focal segmental glomerulosclerosis (22%), and acute interstitial nephritis (7.9%), amongst over a dozen others. There was a trend of decreasing yearly incidence of HIVAN diagnoses, paralleling the use of antiretroviral therapy. By multivariate logistic regression, CD4 counts >200 cells/mm3 and higher estimated glomerular filtration rate were strong negative predictors of HIVAN. HIVAN patients were more likely to require dialysis (p < 0.0001) and had worse overall survival (p = 0.02). Younger age and lower estimated glomerular filtration rate were significant predictors of renal biopsy in multivariate regression analysis. More biopsied patients progressed to dialysis (51 vs. 25%, p = 0.001) and death (15 vs. 5.4%, p = 0.001), despite more frequent corticosteroid treatment (29 vs. 3.6%, p = 0.001). Conclusion: These findings may reflect more severe acute and/or chronic disease at the time of biopsy and suggests that earlier renal biopsy may be warranted in HIV-infected patients, especially in light of the changing spectrum of renal disease in this group.

Uremic lung: new insights into a forgotten condition

The high mortality rate of acute kidney injury (AKI) despite advances in dialysis led to a renewed appreciation of the impact of AKI on distant organ dysfunction. Mechanistic studies demonstrated that AKI induces increased lung vascular permeability, soluble and cellular inflammation, and dysregulated salt and water channels. AKI also affects the brain, heart, liver, bone marrow, and gastrointestinal tract. Klein et al. now demonstrate that interleukin-6 is a direct mediator of AKI-induced lung changes.

Combined Prednisone and Mycophenolate Mofetil Treatment for Retroperitoneal Fibrosis: A Case Series

BACKGROUND Small case series suggest that a combination of mycophenolate mofetil and prednisone may be an effective treatment for patients with retroperitoneal fibrosis. OBJECTIVE To describe the outcomes of adults with retroperitoneal fibrosis who received a combination of prednisone and mycophenolate mofetil. DESIGN Prospective case series of patients followed between 1 April 2005 and 1 July 2009. SETTING Single tertiary care facility. PATIENTS 28 patients with retroperitoneal fibrosis. INTERVENTION Prednisone, 40 mg/d, tapered over 6 months, and mycophenolate mofetil, 1000 mg twice daily, for a mean of 24.3 months. MEASUREMENTS Clinical course, laboratory assessment, and measurement of periaortic mass. Mean follow-up was 1012 days, and no patients were lost to follow-up. RESULTS Systemic symptoms resolved in all patients; 89% had a 25% or greater reduction in periaortic mass. Elevated erythrocyte sedimentation rate and serum creatinine level and decreased hemoglobin level normalized in all patients. Disease recurred in 2 of 28 patients. LIMITATION This was a small case series. CONCLUSION Combined prednisone and mycophenolate mofetil therapy is a potentially effective treatment for retroperitoneal fibrosis that warrants evaluation in randomized trials. PRIMARY FUNDING SOURCE None.

HIV Type 1 RNA Level as a Clinical Indicator of Renal Pathology in HIV-Infected Patients

To determine the value of human immunodeficiency virus type 1 (HIV-1) RNA level in distinguishing HIV-associated nephropathy from non-HIV-associated nephropathy renal pathological conditions, we retrospectively compared renal histopathological findings for 86 HIV-infected patients according to HIV-1 RNA levels. We found that HIV-associated nephropathy was unlikely among patients with HIV-1 RNA levels <400 copies/mL. Hypertensive vascular disease surpassed HIV-associated nephropathy as the most common renal pathological finding among the entire cohort. HIV-1 RNA level did not correlate with renal survival.

Screening for Dialysis Access Graft Malfunction: Comparison of Physical Examination with US

PURPOSE To test the reliability and performance of two physical diagnosis algorithms for use in physical examination of vascular access grafts. MATERIALS AND METHODS Grafts were assessed in 39 patients by means of physical examination performed by four observers. Grafts were characterized as having a thrill, pulse, or indeterminate examination at three locations (arterial, midpoint, venous). Findings with this algorithm were compared with those from ultrasound (US) with volume flow measurements. RESULTS Patients with a thrill at all three locations of the graft all had volume flows greater than 450 mL/min (negative predictive value = 100%). Of patients with a pulse at any of three locations, only 28% (positive predictive value) had a volume flow of 450 mL/min or less. CONCLUSION Physical examination is a good screening test for ruling out the low flows associated with impending access graft failure, thereby eliminating the need for routine US for many patients.

Clinicopathologic correlates of prednisone treatment of human immunodeficiency virus-associated nephropathy

A 43-year-old man with rapidly evolving renal failure from biopsy-proven human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) and superimposed thrombotic microangiopathic changes was treated with prednisone. His serum creatinine decreased from 7.5 to 3.9 mg/dL, and the 24-hour protein excretion decreased from 15.7 to 6.1 g over 6 to 8 weeks. As the prednisone was tapered, however, the creatinine began to increase, and a repeat biopsy was done to assist with therapeutic decisions. The major differences from the pretreatment biopsy were marked reductions in interstitial lymphocytes and macrophages and absence of thrombotic microangiopathic lesions. This is the first report comparing pretreatment and posttreatment renal biopsy specimens and the findings provide some insight into the means by which prednisone exerts its beneficial clinical effects acutely on this disease.

Guide Wire Directed Manipulation of Malfunctioning Peritoneal Dialysis Catheters: A Critical Analysis

PURPOSE To evaluate patency rates after guide wire directed manipulation of malfunctioning continuous ambulatory peritoneal dialysis (CAPD) catheters. MATERIALS AND METHODS During a 58-month period, 23 patients underwent 34 outpatient guide wire directed manipulations of their CAPD catheter to improve function (n = 30) or reduce pain and improve function (n = 4) during dialysis. Catheter patency rates were subsequently determined by review of departmental, hospital, and dialysis center charts; procedural reports; and patient telephone interviews. RESULTS Among 12 patients who underwent a single guide wire directed manipulation, long-term (> 30 days) catheter patency was achieved in seven (58%). With use of the Kaplan-Meier survival method, the 3-, 6-, and 12-month probability of patency after a single guide wire manipulation was 0.61, 0.54, and 0.11, respectively. The mean duration of patency achieved in this group was 131 days (range, 2-421 days). In those patients (n = 8) who underwent multiple catheter manipulations (n = 19), 11 (58%) procedures resulted in long-term patency, with each patient (100%) achieving at least one such period. The Kaplan-Meier survival method determined the probability of patency in this group at 3, 6, and 12 months to be 0.75, 0.69, and 0.54, respectively. The mean secondary catheter patency was 235 days (range, 2-646 days). Overall, 75% of patients followed up achieved at least one period of long-term catheter patency during the time of this study. One (3%) episode of postprocedure peritonitis occurred. CONCLUSION Guide wire directed CAPD catheter manipulation is a relatively simple outpatient procedure that restores long-term catheter function for most patients with minimal risk for a major complication. Patients with nonfunctioning CAPD catheters who do not have peritonitis or sepsis will most likely benefit from at least one attempt at radiologic manipulation of their catheter.