Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy

Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, which provides cardiopulmonary and end-organ support in critically ill patients when other measures fail. These patients receive large amounts of fluid for volume resuscitation, blood products and caloric intake, which results in fluid overload and which in turn is associated with impairment of oxygen transport and increased incidence of multiple organ failure especially heart, lungs and brain. It is common to see a decrease in urine output during ECMO that may be associated with acute renal failure. The acute renal failure is a manifestation of multiple organ system failure due to acute decompensated heart failure, sepsis, hemolysis, use of vasopressors/inotropes, nephrotoxic medications, and activation of complement system during ECMO support. It is associated with poor prognosis and higher mortality in ECMO patients. Continuous renal replacement therapy (CRRT) in patients on ECMO provides an efficient and potentially beneficial method of fluid overload and acute kidney injury management. In addition, recent data suggest that the use of CRRT may remove inflammatory cytokine released as a result of circulation of blood across synthetic surfaces during ECMO. The two most common methods to provide CRRT are through the use of an inline hemofilter or through a traditional CRRT device connected to the extracorporeal circuit. The primary objective of this chapter is to discuss current state and role of renal replacement therapy in patients on ECMO and address the controversies and challenges about its application

Role of tolvaptan in the management of hyponatremia in patients with lung and other cancers: current data and future perspectives.

Hyponatremia is the most frequently observed electrolyte abnormality in clinical practice, and its frequency is almost double in hospitalized cancer patients. As a subset of cancer, hyponatremia is quite common in lung cancer patients, and it is often coupled with the diagnosis of syndrome of inappropriate antidiuretic hormone secretion. The presence of hyponatremia is consequential in that its presence adversely affects cancer patients' prognosis and outcomes. Limited data suggest that correcting hyponatremia in lung cancer patients can increase response to anticancer treatment, may help reduce length of hospital stay and cost, and reduce morbidity and mortality. The type of treatment for hyponatremia depends on several factors; the key factors are the duration and severity of neurological symptoms of hyponatremia and the status of extracellular volume. When hyponatremia is caused by syndrome of inappropriate antidiuretic hormone, hypertonic saline is indicated for acute symptomatic cases, whereas fluid restriction is recommended in chronic asymptomatic hyponatremia. The latter allows a slower rate of correction, thus avoiding the dreaded complication of osmotic demyelination syndrome. Fluid restriction is, however, insufficient or impractical, and often the use of pharmacological therapy such as antidiuretic hormone receptor antagonists becomes necessary. Availability of these antagonists as an effective treatment in the management of hyponatremia has been a major breakthrough, and furthermore, its clinical or investigational use in cancer-related hyponatremia may offer a potential opportunity to gain further insights into the prognostic impact of hyponatremia correction on cancer patients' outcomes. Tolvaptan is a prototype of ADH receptor antagonists that acts at renal tubular levels to increase free water excretion without inducing major systemic electrolyte abnormalities such as hypokalemia or alkalosis. The aim of this paper is to provide a brief review while focusing on cancer hyponatremia; (1) of the epidemiology of hyponatremia and its pathophysiology and diagnostic approaches and (2) of the pharmacokinetics of tolvaptan and its clinical efficacy, safety, and compliance

Leukocyte Cell-Derived Chemotaxin 2-Associated Renal Amyloidosis: A Case Report

Amyloidosis is a disorder characterized by the deposition of abnormal protein fibrils in tissues. Leukocyte cell-derived chemotaxin 2-associated amyloidosis is a recently recognized entity and is characterized by a distinctive clinicopathologic type of amyloid deposition manifested in adults by varying degrees of impaired kidney function and proteinuria. There are only a limited number of cases reported in the literature. We present a 64-year-old Hispanic female with a history of hypertension who was referred for chronic kidney disease management. The review of her laboratory tests revealed a serum creatinine of 1.5–1.8 mg/dL and microalbuminuria (in the presence of a bland urine sediment) in the past year. She denied any history of diabetes, rheumatologic disorders or exposure to intravenous contrast, nonsteroidal anti-inflammatory drugs, herbals, and heavy metals. Serological workup was negative. A renal biopsy showed diffuse infiltration of glomerulus with pale eosinophilic material strongly positive for Congo red stain and a similar eosinophilic material in the interstitium, muscular arteries, and arterioles. Electron microscopy showed marked infiltration of the mesangium, capillary loops, and interstitium with haphazardly arranged fibrillary deposits (9.8 nm thick). Liquid chromatography tandem mass spectrometry confirmed leukocyte cell-derived chemotaxin 2 (LECT2) amyloid deposition. LECT2 amyloidosis (ALECT2) should be suspected in renal biopsy specimens exhibiting extensive and strong mesangial as well as interstitial congophilia. Individuals with LECT2 renal amyloidosis have a varying prognosis. Therapeutic options include supportive measures and consideration of a kidney transplant for those with end-stage renal disease

Histoplasma Peritonitis: An Extremely Rare Complication of Peritoneal Dialysis

Bacterial peritonitis is a common complication of peritoneal dialysis, but fungal peritonitis is unusual and is mostly due to Candida species. Peritonitis due to Histoplasma capsulatum is rare and we report one such case. A 63-year-old female presented with progressively worsening abdominal pain, fever, and altered mental status. She had end-stage renal disease and had been on peritoneal dialysis for 4 years. She had abdominal tenderness without rebound or guarding. Laboratory studies and CT of abdomen were significant for leukocytosis and peritoneal membrane thickening, respectively. Peritoneal dialysis fluid study was consistent with peritonitis and culture of the fluid grew Histoplasma capsulatum. Treatment recommendations include removal of catheter and initiation of antifungal therapy. With the availability of newer antifungals, medical management without removal of PD catheter is possible, but at the same time if there is no response to treatment within a week, PD catheter should be removed promptly

Focal Segmental Glomerulosclerosis in Waldenström’s Macroglobulinemia

Renal involvement in Waldenström’s macroglobulinemia is a rare manifestation. Although most renal involvement is due to monoclonal immune deposits, pathology can also be unrelated to it. Here, we describe a 68-year-old female with a history of Waldenström’s macroglobulinemia who presented with generalized edema and nephrotic range proteinuria. A renal biopsy showed findings consistent with focal segmental glomerulosclerosis. Treatment with oral prednisone leads to the resolution of proteinuria. This case highlights the importance of identifying pathology that might not be directly related to monoclonal gammopathy, which could have implications on the management

Outcome of patients with infective endocarditis who were treated with extracorporeal membrane oxygenation and continuous renal replacement therapy

Infective endocarditis is a potentially life threatening condition. It is associated with high mortality and morbidity resulting mostly due to cardiorespiratory failure. Extracorporeal membrane oxygenation is a modality of treatment used to support hypoxic respiratory failure especially in patients who are already on mechanical ventilation. Continuous renal replacement therapy is added mainly for maintaining fluid and electrolyte balance. Here we report a case series of patients diagnosed with infective endocarditis who were treated with combined extracorporeal membrane oxygenation and continuous renal replacement therapy. Three patients in the age group 20-60 years were admitted with clinical features suggestive of infective endocarditis. During the course of hospital stay they developed cardiorespiratory failure requiring mechanical ventilation and extracorporeal membrane oxygenation support for refractory hypoxia. It was complicated by heart failure, renal failure and fluid overload which required initiation of continuous renal replacement therapy. All the three patients succumbed in spite of the aggressive treatment. In addition to the role played by each complication, delayed start of continuous renal replacement therapy might have also contributed to the high mortality. Early initiation of continuous renal replacement therapy for management of fluid overload needs to be considered in the management of these critically ill patients

Improvement in glomerular filtration rate may decrease mortality among type-2 diabetics with chronic kidney disease lacking proteinuria: A retrospective study

Twenty percent of patients with type-2 diabetes mellitus without albuminuria progress to chronic kidney disease (CKD). The various factors related to development of CKD, the natural course of renal dysfunction as well as mortality in this sub-group of diabetics has not been studied in detail. The medical records of 121 patients (all males) above the age of 40 years with type-2 diabetes mellitus and CKD, and without proteinuria, were reviewed in this retrospective study. The outcomes measured included: (a) all-cause mortality, (b) need for hemodialysis (HD), (c) appearance of proteinuria and (d) trend in kidney function. The all-cause mortality was 33%, with mean age at death being 75.9 years. Sixty-three percent of the patients had improvement in estimated glomerular filtration rate (eGFR) at the end of the follow-up period. The mortality was higher in patients with worsening eGFR compared with those with improvement in eGFR (61% vs 39%, P = 0.040). 5.8% of the patients ended up on HD and 16.51% developed proteinuria at the end of the follow-up period. Patients who developed proteinuria showed a higher tendency for progression of renal failure. Multivariate logistic regression for trend toward improving versus worsening of the eGFR revealed no statistically significant predictors. This observational study suggests that in type-2 diabetic patients with CKD, a substantial number of patients will have improvement in eGFR over time. Careful search for potential reversible causes of kidney damage could help in reducing mortality

Improvement in Gemcitabine-Induced Thrombotic Microangiopathy with Rituximab in a Patient with Ovarian Cancer: Mechanistic Considerations.

Gemcitabine is a potent and widely used anticancer drug. We report a case of gemcitabine-induced thrombotic microangiopathy (GCI-TMA), a known but not widely recognized complication of gemcitabine use, and our experience of treating GCI-TMA with rituximab. A 74-year-old woman was referred to our clinic for an evaluation of worsening renal function. She has recently been treated for ovarian cancer (diagnosed in 2011) with surgery (tumor debulking and bilateral salpingo-oophorectomy) along with cisplatin chemotherapy in 2012, followed by carboplatin/doxorubicin in 2013 and recent therapy for resistant disease with gemcitabine. Laboratory tests showed anemia, normal platelets and elevated lactate dehydrogenase. A peripheral smear revealed numerous schistocytes, and a kidney biopsy showed acute as well as chronic TMA. The patient continued on gemcitabine therapy, and treatment with plasma exchange was started. Since there was no response to treatment even after 5 sessions of plasma exchange, one dose of rituximab was given, which was associated with a drop in the creatinine level to 2 mg/dl. The pathogenesis of renal injury could be the effect of direct injury to the endothelium mediated by cytokines. Usual treatment includes withdrawing the drug and initiation of treatment with plasmapheresis with or without steroids. In cases resistant to plasmapheresis, treatment with rituximab can be tried. The mechanism of action of rituximab might be due to the reduced production of B-cell-dependent cytokines that drive endothelial dysfunction by depleting B cells. Patients receiving gemcitabine chemotherapy should be monitored for the development of TMA, and early treatment with plasma exchange along with rituximab might benefit these patients who already have a bad prognosis