Robert W. Schrier

Endotoxemic shock is associated with approximately 50% incidence of acute kidney injury (AKI) and 70% mortality. Experimental studies indicate that endotoxemia-related AKI is associated with both hemodynamic and proinflammatory perturbations. We hypothesize that combined administration of albumin with pentoxifylline may protect against the development of AKI during endotoxemic shock in mice by maintaining the integrity of arterial circulation and exerting anti-inflammatory properties. We tested this hypothesis using an endotoxemic shock model produced by administering a high dose of lipopolysaccharide (LPS) (15 mg/kg intraperitoneal). LPS-treated mice developed hypotension compared to control mice (mean arterial pressure [MAP] 65.6 +/- 2.2 vs. 85.7 +/- 0.8 mm Hg, p < 0.05). Normal saline did not attenuate LPS-related hypotension (62.7 +/- 2.2 vs. 65.6 +/- 2.2 mm Hg, NS). Pentoxifylline, a phosphodiesterase inhibitor, worsened the LPS-related hypotension (50.7 +/- 6.9 vs. 65.6 +/- 2.2 mm Hg, p = 0.15) in a non-significant manner. Albumin alone caused a significant increase in MAP (79.3 +/- 4.7 vs. 62.7 +/- 2.2 mm Hg, p = 0.02), but had a non-significant modest effect on glomerular filtration rate (GFR; 60.8 +/- 24.7 vs. 38.2 +/- 18.2 microl/min, NS) compared to normal saline. However, the combination of albumin and pentoxifylline profoundly protected GFR (148.6 +/- 28.7 microl/min, vs. 38.2 +/- 18.2 microl/min, p < 0.01) as compared to normal saline. The combined administration of albumin and pentoxifylline significantly attenuated the renal iNOS protein expression and increased cardiac output. In summary, neither normal saline nor albumin nor pentoxifylline alone protected against endotoxemic shock-related AKI. However, the combination of albumin and pentoxifylline was effective in preventing AKI during endotoxemic shock. Thus, in endotoxemic shock, a multifactorial approach involving hemodynamic and anti-inflammatory effect may be necessary to decrease AKI.

Renal failure, a challenging complication of cirrhosis, is one of the most important risk factors for liver transplantation. In recent years, substantial progress has been made toward understanding the pathogenesis and natural history of renal failure in cirrhosis. This review discusses recently identified information about renal failure in cirrhosis and clinical interventions that may assist in the prevention and management of this complication.

This Review describes the cardiovascular manifestations of autosomal-dominant polycystic kidney disease (ADPKD), including hypertension, left ventricular hypertrophy, aneurysms and cardiac valvular disorders. The authors focus particularly on hypertension, with a detailed discussion of the pathogenesis of this condition in ADPKD and a comprehensive review of the renal and cardiovascular effects of antihypertensive treatment in the ADPKD setting. Recommendations for the optimal cardiovascular management of ADPKD are provided. Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal-dominant polycystic kidney disease (ADPKD). Hypertension is a common early symptom of ADPKD, and occurs in approximately 60% of patients before renal function has become impaired. Hypertension is associated with an increased rate of progression to end-stage renal disease and is the most important potentially treatable variable in ADPKD. Left ventricular hypertrophy, which is a powerful, independent risk factor for cardiovascular morbidity and mortality, also occurs frequently in patients with ADPKD. Both hypertension and left ventricular hypertrophy have important roles in cardiovascular complications in these individuals. Moreover, biventricular diastolic dysfunction, endothelial dysfunction, increased carotid intima–media thickness, and impaired coronary flow velocity reserve are present even in young patients with ADPKD who have normal blood pressure and well-preserved renal function. These findings suggest that cardiovascular involvement starts very early in the course of ADPKD. Intracranial and extracranial aneurysms and cardiac valvular defects are other potential cardiovascular problems in patients with ADPKD. Early diagnosis and treatment of hypertension, with drugs that block the renin–angiotensin–aldosterone system, has the potential to decrease the cardiovascular complications and slow the progression of renal disease in ADPKD.

Purpose of review Hyponatremia is the most common electrolyte disorder present in hospitalized patients. Acute and severe hyponatremia can cause significant morbidity and mortality. The present review discusses the epidemiology, causes, and a practical approach to the diagnosis and management of acute and chronic hyponatremia, including the appropriate use of hypertonic saline and potential future use of the new V2 vasopressin receptor antagonists in critically ill patients. Recent findings The increasing knowledge of aquaporin water channels and the role of vasopressin in water homeostasis have enhanced our understanding of hyponatremic disorders. Increased vasopressin secretion due to nonosmotic stimuli leads to decreased electrolyte-free water excretion with resulting water retention and hyponatremia. Vasopressin receptor antagonists induce electrolyte-free water diuresis without natriuresis and kaliuresis. Phase three trials indicate that these agents predictably reduce urine osmolality, increase electrolyte-free water excretion, and raise serum sodium concentration. They are likely to become a mainstay of treatment of euvolemic and hypervolemic hyponatremia. Summary The correct diagnosis and management of hyponatremia is complex and requires a systematic approach. Vasopressin receptor antagonists are potential tools in the management of hyponatremia. Further studies are needed to determine their role in the treatment of acute, severe, life-threatening hyponatremia as well as chronic hyponatremia.

Excessive glucocorticoid hormone, as occurs with Cushing syndrome, is known to be associated with altered body water homeostasis, but the molecular mechanisms are unknown. In this study, rats treated with daily dexamethasone (Dex) for 14 d provided a model of Cushing syndrome. Compared with control rats, Dex-treated rats demonstrated increased mean arterial pressure, urine flow rate, and urinary excretion of both sodium and urea. Dex-treated rats had increased abundance of aquaporin 1 (AQP1), AQP3, and Na-K-2Cl co-transporter proteins and a marked reduction of the urea transporters UT-A1 and UT-A3. In response to an acute water load, Dex-treated rats increased water excretion more than control rats, but both groups exhibited similar AQP2 expression. In response to fluid deprivation, Dex-treated rats demonstrated an impaired urinary concentrating capacity: Urine flow rate was higher and urine osmolality was lower than control rats despite an increase in AQP1, AQP3, and Na-K-2Cl co-transporter expression. AQP2 expression was similar between the two groups, but UT-A1 and UT-A3 were decreased and urinary urea excretion was increased in Dex-treated rats. Because Dex-treated rats ingested less food and water compared with controls, paired food and water studies were performed; these substantiated the previous results. In summary, the alterations in body water observed with glucocorticoid excess may be a result, in part, of impaired urinary concentrating capacity; downregulation of UT-A1 and UT-A3 and increased urea excretion may contribute to this impairment.

In this article, the pathophysiology of left ventricular failure is reviewed. By contrast, the paucity of information about pulmonary arterial hypertension and right ventricular failure is acknowledged. The potential mechanisms whereby renal sodium and water retention in right ventricular failure secondary to pulmonary arterial hypertension can occur, despite normal left ventricular function, are discussed. With right ventricular failure as the primary cause of death in patients with pulmonary hypertension, more information about the mechanisms of renal sodium and water retention in these patients is direly needed. Specifically, studies to examine the activation of the neurohumoral axis at various stages of pulmonary arterial hypertension and right ventricular failure, including inhibition of mineralocorticoid and V2 vasopressin receptors, are indicated.