LECT-2 amyloidosis: what do we know?

Amyloidosis is a rare group of diseases characterized by abnormal folding of proteins and extracellular deposition of insoluble fibrils. It can be localized to one organ system or can have systemic involvement. The kidney is the most common organ to be involved in systemic amyloidosis often leading to renal failure and the nephrotic syndrome. The two most common types of renal amyloidosis are immunoglobulin light chain-derived amyloidosis (AL) and reactive amyloidosis (AA). A novel form of amyloidosis (ALECT2) derived from leukocyte chemotactic factor 2 (LECT-2) and primarily involving the kidneys was first described by Benson et al in 2008. The liver was subsequently identified as the second most common organ involved in ALECT2 amyloidosis. LECT-2 is a unique protein that can form amyloid deposits even in its unmutated form. Patients with ALECT2 present with minimal proteinuria in contrast to other forms of amyloidosis especially AL and AA. They may present with slightly elevated serum creatinine. Nephrotic syndrome and hematuria are rare. ALECT2 can be found in association with other types of amyloidosis as well as malignancies or autoimmune diseases. ALECT2 may be confused with amyloidosis associated with light and heavy chain monoclonal gammopathy if the immunofluorescence is positive with anti-light chain and anti-AA sera. The other organs involved are the duodenum, adrenal gland, spleen, prostate, gall bladder, pancreas, small bowel, parathyroid gland, heart, and pulmonary alveolar septa, but consistently uninvolved organs included brain and fibroadipose tissue. A renal biopsy along with characteristic features found on immunohistochemistry and mass spectrometry is diagnostic of ALECT2. ALECT2 should be suspected when all markers for AL and AA are negative. Proper diagnosis of ALECT2 can determine need for supportive care versus more aggressive interventions.

Acute Interstitial Nephritis: A Rare and Unusual Side Effect of Omalizumab.

Acute interstitial nephritis (AIN) is a relatively common cause of acute kidney injury with etiologies that include drug therapy, infections, and systemic diseases. Of these etiologies, drug therapy accounts for ~70% of AIN cases. Although any drug can cause AIN, there are no reported cases of AIN caused by omalizumab, a humanized monoclonal antibody that binds to and inhibits circulating immunoglobulin E. In this article, we share the first reported case of AIN following administration of omalizumab for the treatment of moderate to severe persistent asthma.

A Rare Case of Spontaneous Bilateral Subcapsular Renal Hematoma.

Spontaneous bilateral renal subcapsular hematoma is a rare condition. On literature review, only 2 case reports have elucidated possible etiologies for such a presentation; however, no definite conclusions have been made. We present a rare case of a 52-year-old female with diabetes mellitus type 2, chronic kidney disease stage 4, hypertension, hyperlipidemia, prior traumatic brain injury via motor vehicle accident, who presented to our hospital with diabetic ketoacidosis and clinical signs of pyelonephritis; subsequently, imaging demonstrated spontaneous bilateral renal subcapsular hematoma. Risk factors for the rare presentation in this patient included pyelonephritis, history of bilateral ureteral stent placement, and a remote history of a mild unilateral renal laceration secondary to a motor vehicle accident. Typically, patients with this condition achieve spontaneous resolution with conservative management. Our patient initially presented with diabetic ketoacidosis and pyelonephritis but gradually developed retroperitoneal bleeding and hemorrhagic shock. Our patient's critical condition required close monitoring in an intensive care unit and a more invasive approach including unilateral left renal artery embolization followed by a unilateral left nephrectomy. The patient ultimately recovered and continued to be followed outpatient without any serious long-term complications.

Inflammasome-regulated cytokines are critical mediators of acute lung injury.

RATIONALE: Despite advances in clinical management, there are currently no reliable diagnostic and therapeutic targets for acute respiratory distress syndrome (ARDS). The inflammasome/caspase-1 pathway regulates the maturation and secretion of proinflammatory cytokines (e.g., IL-18). IL-18 is associated with injury in animal models of systemic inflammation. OBJECTIVES: We sought to determine the contribution of the inflammasome pathway in experimental acute lung injury and human ARDS. METHODS: We performed comprehensive gene expression profiling on peripheral blood from patients with critical illness. Gene expression changes were assessed using real-time polymerase chain reaction, and IL-18 levels were measured in the plasma of the critically ill patients. Wild-type mice or mice genetically deficient in IL-18 or caspase-1 were mechanically ventilated using moderate tidal volume (12 ml/kg). Lung injury parameters were assessed in lung tissue, serum, and bronchoalveolar lavage fluid. MEASUREMENTS AND MAIN RESULTS: In mice, mechanical ventilation enhanced IL-18 levels in the lung, serum, and bronchoalveolar lavage fluid. IL-18-neutralizing antibody treatment, or genetic deletion of IL-18 or caspase-1, reduced lung injury in response to mechanical ventilation. In human patients with ARDS, inflammasome-related mRNA transcripts (CASP1, IL1B, and IL18) were increased in peripheral blood. In samples from four clinical centers, IL-18 was elevated in the plasma of patients with ARDS (sepsis or trauma-induced ARDS) and served as a novel biomarker of intensive care unit morbidity and mortality. CONCLUSIONS: The inflammasome pathway and its downstream cytokines play critical roles in ARDS development.

Elevation of blood urea nitrogen is predictive of long-term mortality in critically ill patients independent of "normal" creatinine.

OBJECTIVE: We hypothesized that elevated blood urea nitrogen can be associated with all-cause mortality independent of creatinine in a heterogeneous critically ill population. DESIGN: Multicenter observational study of patients treated in medical and surgical intensive care units. SETTING: Twenty intensive care units in two teaching hospitals in Boston, MA. PATIENTS: A total of 26,288 patients, age ≥ 18 yrs, hospitalized between 1997 and 2007 with creatinine of 0.80-1.30 mg/dL. INTERVENTIONS: None. MEASUREMENTS: Blood urea nitrogen at intensive care unit admission was categorized as 10-20, 20-40, and >40 mg/dL. Logistic regression examined death at days 30, 90, and 365 after intensive care unit admission as well as in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. MAIN RESULTS: Blood urea nitrogen at intensive care unit admission was predictive for short- and long-term mortality independent of creatinine. Thirty days following intensive care unit admission, patients with blood urea nitrogen of >40 mg/dL had an odds ratio for mortality of 5.12 (95% confidence interval, 4.30-6.09; p < .0001) relative to patients with blood urea nitrogen of 10-20 mg/dL. Blood urea nitrogen remained a significant predictor of mortality at 30 days after intensive care unit admission following multivariable adjustment for confounders; patients with blood urea nitrogen of >40 mg/dL had an odds ratio for mortality of 2.78 (95% confidence interval, 2.27-3.39; p < .0001) relative to patients with blood urea nitrogen of 10-20 mg/dL. Thirty days following intensive care unit admission, patients with blood urea nitrogen of 20-40 mg/dL had an odds ratio of 2.15 (95% confidence interval, 1.98-2.33; <.0001) and a multivariable odds ratio of 1.53 (95% confidence interval, 1.40-1.68; p < .0001) relative to patients with blood urea nitrogen of 10-20 mg/dL. Results were similar at 90 and 365 days following intensive care unit admission as well as for in-hospital mortality. A subanalysis of patients with blood cultures (n = 7,482) demonstrated that blood urea nitrogen at intensive care unit admission was associated with the risk of blood culture positivity. CONCLUSION: Among critically ill patients with creatinine of 0.8-1.3 mg/dL, an elevated blood urea nitrogen was associated with increased mortality, independent of serum creatinine.