Pathogenesis of cerebral edema in patients with acute renal and liver failure and the role of the nephrologist in the management.

PURPOSE OF REVIEW: Acute liver failure (ALF) is a severe and complex illness and one of the most daunting conditions managed in the ICU. Because the renal care is intertwined with multiple disciplines, the aim of this review is to examine the multifactorial pathogenesis of cerebral edema in ALF, covering basic established facts as well as recent advances in our understanding of this condition. RECENT FINDINGS: Acetaminophen remains the most common cause of ALF in the United States and many European countries. The incidence of cerebral edema continues to decline owing to earlier detection and improved management. The pathogenesis of cerebral edema has shifted from a unifactorial hypothesis involving the failed liver to a multifactorial cause. Recent evidence focuses on the role of liver-induced systemic inflammation and its implication in increasing the permeability of the blood-brain barrier. The role of brain aquaporin-4 in mediating water entry into the brain is further clarified. Controversial data regarding the effect of acute kidney injury on the brain emerged. Hyponatremia has been shown to worsen the outcome in acute-on-chronic liver failure patients thus validating findings in animal models. New evidence shed the light on the changes in serum osmolality and potential tissue hypoxia during continuous renal replacement therapy and points to the risks associated with such therapy. SUMMARY: ALF is a severe systemic illness that is potentially reversible. Understanding the interaction between the multiple failed organs will help the nephrologist provide well tolerated and efficient care.

Review of Extracorporeal Membrane Oxygenation and Dialysis-Based Liver Support Devices for the Use of Nephrologists.

Acute kidney injury in the intensive care unit (ICU) is a manifestation of an underlying severe illness that commonly involves other organ systems. Pulmonary, cardiac, and hepatic failures are the most prevalent. This article provides a simplified review of the technical aspects of extracorporeal cardiopulmonary and liver support devices used in the adult ICU patient, as well as a summary of the most relevant and up-to-date clinical evidence that supports their use.

Nonresolving pneumonia.

A 58-year-old man admitted for evaluation of weight loss and dry cough. Initially, he was diagnosed with community-acquired pneumonia. Despite receiving antibiotics, his clinical status deteriorated and was intubated. Fiber optic bronchoscopy revealed a significant amount of mucopurulent secretions. Bronchoalveolar lavage showed marked amount of sulfur granules identified on stain. Microbiology culture was compatible with Actinomyces israelii. Pulmonary actinomycosis is a rare but important and challenging diagnosis to make. It presents with wide spectrum of clinical and radiologic characteristics. Failure to recognize the disease early may result in drastic complications.

Cisplatin-induced renal salt wasting syndrome.

Cisplatin was the first platinum compound to be introduced as a chemotherapeutic agent with antineoplastic activity against a wide variety of solid tumors. Renal impairment with a decline in glomerular filtration has been the classical nephrotoxicity of cisplatin. Renal salt wasting syndrome is yet another, though it is not common. Previous studies were identified by searching the Pubmed database using the following keywords: cisplatin, cisplatin nephrotoxicity, renal salt wasting, and salt loosing nephropathy. Renal salt wasting syndrome has been described in 17 case reports since 1984. It is a rare side effect of cisplatin that manifests with polyuria, hypovolemia, and hyponatremia, and, because of similarities in clinical settings and laboratory values, it is frequently misdiagnosed as a syndrome of inappropriate antidiuretic hormone. Other causes of polyuria and hyponatremia should be excluded. Treatment aims at restoring the lost water and salt. Substituting cisplatin with carboplatin depends on individual clinical settings. Prognosis is excellent, as recovery was the rule in all the reported cases.

Contrast-induced nephropathy: current practices among cardiologists.

OBJECTIVE: Contrast-induced nephropathy (CIN) is a serious complication of diagnostic and therapeutic coronary angiography. There are an increasing number of guidelines in the literature to help lessen this complication. Practice patterns in the cardiology community remain relatively unknown. This survey is an effort to better understand such practices. METHODS: Questions were written based on the American College of Cardiology (ACC), the American Heart Association (AHA), and the Society of Cardiovascular Angiography and Intervention (SCAI) guidelines to identify cardiologist background and experience. The survey was emailed to 5000 randomly chosen cardiologists in December 2009. RESULTS: A total of 291 responses were received. Among these, 97% reported checking renal function in all patients prior to angiography, 45% checked both estimated glomerular filtration rate (eGFR) and serum creatinine (SCr), 31% checked SCr alone, 19% checked eGFR alone, and 2% checked albumin-to-creatinine (A-C) ratio. Among responding cardiologists, 70% considered eGFR level less than 60 mL/min/1.73 m(2) a high risk for CIN whereas 25% considered a level less than 30 mL/min/1.73 m(2) a high risk. Thirty percent used only isosmolar media in high-risk patients, 33% used only low osmolar media, and 37% used either one. CONCLUSIONS: There is significant diversity in the measures taken by cardiologists to prevent CIN. More studies and clearer guidelines are needed to unify the practices.

Amino acids in the rat intestinal lumen regulate their own absorption from a distant intestinal site.

Intestinal nutrient transport is altered in response to changes in dietary conditions and luminal substrate level. It is not clear, however, whether an amino acid in the intestinal lumen can acutely affect its own absorption from a distant site. Our aim is to study the effect of an amino acid present in rat small intestinal segment on its own absorption from a proximal or distal site and elucidate the underlying mechanisms. The effect of instillation of alanine (Ala) in either jejunum or ileum on its own absorption at ileal or jejunal level was examined in vivo. The modulation of this intestinal regulatory loop by the following interventions was studied: tetrodotoxin (TTX) added to Ala, subdiaphragmatic vagotomy, chemical ablation of capsaicin-sensitive primary afferent (CSPA) fibers, and IV administration of calcitonin gene-related peptide (CGRP) antagonist. In addition, the kinetics of jejunal Ala absorption and the importance of Na+-dependent transport were studied in vitro after instilling Ala in the ileum. Basal jejunal Ala absorption [0.198 +/- 0.018 micromol x cm(-1) x 20 min(-1) (means +/- SD)] was significantly decreased with the instillation of 20 mM Ala in the ileum or in an adjacent distal jejunal segment (0.12 +/- 0.015; P < 0.0001 and 0.138 +/- 0.014; P < 0.002, respectively). Comparable inhibition was observed in the presence of proline in the ileum. Moreover, basal Ala absorption from the ileum (0.169 +/- 0.025) was significantly decreased by the presence of 20 mM Ala in the jejunum (0.103 +/- 0.027; P < 0.01). The inhibitory effect on jejunal Ala absorption was abolished by TTX, subdiaphragmatic vagotomy, neonatal capsaicin treatment, and CGRP antagonism. In vitro studies showed that Ala in the ileum affects Na+-mediated transport and increases K(m) without affecting Vmax. Intraluminal amino acids control their own absorption from a distant part of the intestine, by affecting the affinity of the Na+-mediated Ala transporter, through a neuronal mechanism that involves CSPA and CGRP.

Control of metabolic predisposition to cardiovascular complications of chronic kidney disease by effervescent calcium magnesium citrate: a feasibility study.

AIMS: Cardiovascular (CV) complications are common in chronic kidney disease (CKD). Numerous metabolic disturbances including hyperphosphatemia, high circulating calciprotein particles (CPP), hyperparathyroidism, metabolic acidosis, and magnesium deficiency are associated with, and likely pathogenic for CV complications in CKD. The goal of this feasibility study was to determine whether effervescent calcium magnesium citrate (EffCaMgCit) ameliorates the aforementioned pathogenic intermediates. METHODS: Nine patients with Stage 3 and nine patients with Stage 5D CKD underwent a randomized crossover study, where they took EffCaMgCit three times daily for 7 days in one phase, and a conventional phosphorus binder calcium acetate (CaAc) three times daily for 7 days in the other phase. Two-hour postprandial blood samples were obtained on the day before and on the 7th day of treatment. RESULTS: In Stage 5D CKD, EffCaMgCit significantly increased T50 (half time for conversion of primary to secondary CPP) from baseline by 63% (P = 0.013), coincident with statistically non-significant declines in serum phosphorus by 25% and in saturation of octacalcium phosphate by 35%; CaAc did not change T50. In Stage 3 CKD, neither EffCaMgCit nor CaAc altered T50. With EffCaMgCit, a significant increase in plasma citrate was accompanied by statistically non-significant increase in serum Mg and phosphate. CaAc was without effect in any of these parameters in Stage 3 CKD. In both Stages 3 and 5D, both drugs significantly reduced serum parathyroid hormone. Only EffCaMgCit significantly increased serum bicarbonate by 3 mM (P = 0.015) in Stage 5D. CONCLUSIONS: In Stage 5D, EffCaMgCit inhibited formation of CPP, suppressed PTH, and conferred magnesium and alkali loads. These effects were unique, since they were not observed with CaAc. In Stage 3 CKD, neither of the regimens have any effect. These metabolic changes suggest that EffCaMgCit might be useful in protecting against cardiovascular complications of CKD by ameliorating pathobiologic intermediates.

High sodium continuous veno-venous hemodialysis with regional citrate anticoagulation and online dialysate generation in patients with acute liver failure and cerebral edema.

INTRODUCTION: Acute liver failure is associated with a high mortality rate. Induction of plasma hypertonicity with mannitol or hypertonic saline remains the cornerstone in the management of resultant cerebral edema. Significant disadvantages of this approach include poor or unpredictable control of serum sodium concentration and volume expansion, among others. METHODS: We used high sodium continuous veno-venous hemodialysis with regional citrate anticoagulation and online dialysate generation to accurately control the serum sodium in eleven patients with acute liver failure, renal failure, and cerebral edema. We used a Fresenius 2008 K/K2 machine in hemodialysis mode to deliver a blood flow of 60 ml/minute and dialysate flow of 400 ml/minute. Our previously published protocol results in complete removal of infused citrate by the dialyzer. On-line clearance calculations were used to model the time required to reach the target serum sodium. FINDINGS: All patients achieved serum sodium within 2 mEq/L of target without fluctuations or rebound. Nine patients survived without requiring liver transplantation and two died despite reaching the prescribed serum sodium target. We did not encounter any citrate toxicity. DISCUSSION: We describe a novel approach for delivering continuous osmotherapy to patients with acute liver failure, renal failure, and cerebral edema. In comparison to standard therapy, the described modality enables precise titration of serum sodium without undesirable fluctuations in extracellular fluid volume. A particular advantage is zero delivery of citrate to this vulnerable group of patients with acute liver failure.

Interstitial Nephritis in a Patient with Inflammatory Bowel Disease.

Tubulointerstitial nephritis in patients with inflammatory bowel disease has been linked to the use of 5-ASA derivatives. Various aspects of this theory have been challenged with a potential role for the underlying autoimmune disorder. Steroids are the mainstay of treatment and mycophenolate mofetil might be an effective alternative. We report a patient who responded well to mycophenolate despite continuing mesalamine, the suspected offending agent.

Experimental colitis in rats induces de novo synthesis of cytokines at distant intestinal sites: role of capsaicin-sensitive primary afferent fibers.

Increased levels of pro- and anti-inflammatory cytokines were observed in various segments of histologically-intact small intestine in animal models of acute and chronic colitis. Whether these cytokines are produced locally or spread from the inflamed colon is not known. In addition, the role of gut innervation in this upregulation is not fully understood. To examine whether cytokines are produced de novo in the small intestine in two rat models of colitis; and to investigate the role of capsaicin-sensitive primary afferents in the synthesis of these inflammatory cytokines. Colitis was induced by rectal instillation of iodoacetamide (IA) or trinitrobenzene sulphonic acid (TNBS) in adult Sprague-Dawley rats. Using reverse transcriptase (RT) and real-time PCR, TNF-α, and IL-10 mRNA expression was measured in mucosal scrapings of the duodenum, jejunum, ileum and colon at different time intervals after induction of colitis. Capsaicin-sensitive primary afferents (CSPA) were ablated using subcutaneous injections of capsaicin at time 0, 8 and 32 h, and the experiment was repeated at specific time intervals to detect any effect on cytokines expression. TNF-α mRNA expression increased by 3-40 times in the different intestinal segments (p<0.05 to p<0.001), 48h after IA-induced colitis. CSPA ablation completely inhibited this upregulation in the small intestine, but not in the colon. Similar results were obtained in TNBS-induced colitis at 24 h. Intestinal IL-10 mRNA expression significantly decreased at 12 h and then increased by 6-43 times (p<0.05 to p<0.001) 48h after IA administration. This increase was abolished in rats subjected to CSPA ablation except in the colon, where IL-10 further increased by twice (p<0.05). In the TNBS group, there was 4-12- and 4-7-fold increases in small intestinal IL-10 mRNA expression at 1 and 21 days after colitis induction, respectively (both p<0.01). This increase was not observed in rats pretreated with capsaicin. Capsaicin-treated and untreated rats had comparable visual ulcer scores after colitis induction. Inflammatory cytokines are produced de novo in distant intestinal segments in colitis. CSPA fibers play a key role in the upregulation of this synthesis.

Mucormycosis in a renal transplant recipient: case report and comprehensive review of literature.

Mucormycosis is a rare but devastating infection. We present a case of fatal disseminated mucormycosis infection in a renal transplant patient. Uncontrolled diabetes mellitus and immunosuppression are the major predisposing factors to infection with Mucorales. Mucorales are angioinvasive and can infect any organ system. Lungs are the predominant site of infection in solid organ transplant recipients. Prompt diagnosis is challenging and influences outcome. Treatment involves a combination of surgical and medical therapies. Amphotericin B remains the cornerstone in the medical management of mucormycosis, although other agents have been used. Newer agents are promising.