Elwaleed Elhassan

Hyponatremia: Diagnosis, complications, and management including V2 receptor antagonists

Purpose of reviewRecent studies have consistently demonstrated the common prevalence of hyponatremia in the hospital and intensive care settings, and how it correlates with untoward outcomes. This review discusses the classification, diagnosis, and pathophysiology of hyponatremia and how these agents may influence its management, and also examines the available treatment options and their weaknesses and strengths. Recent findingsThis review is timely and relevant, as mild degrees of serum sodium lowering may be associated with adverse neurologic and musculoskeletal effects. These findings have the potential to transform our approach to managing hyponatremia. A major advance in our ability to treat hyponatremia was the introduction and approval of aquaretics (vaptans). Emerging data on vaptans and their potential role to treat hyponatremia in the settings of the syndrome of inappropriate antidiuretic hormone secretion, congestive heart failure, and liver cirrhosis are presented. SummaryVaptans will likely play an important role in treating hyponatremia, given their clinical effectiveness and tolerability. Cost remains a hindrance for vaptans, and more studies are needed to further define their best utilization in hyponatremic patients.

Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease

Renal cysts, pain, and hematuria are common presentations of autosomal dominant polycystic kidney disease (ADPKD) in children. Renal function, however, is typically preserved in these patients despite increased renal volume. Since angiogenesis has been implicated in promotion of renal cyst growth in ADPKD, we measured the serum level of various angiogenic factors and early renal structural changes and cardiovascular parameters in 71 patients with ADPKD, with a mean age of 16 years. Renal structure and left ventricular mass index were measured by magnetic resonance imaging or by echocardiogram. Renal function was assessed by creatinine clearance and urinary protein excretion. Serum growth factor levels were measured by enzyme-linked immunosorbent assay. Because of skewed distributions, the various parameters are reported as log(10). Serum log(10) vascular endothelial growth factor was positively correlated with renal and cardiac structure, but negatively with creatinine clearance. Serum angiopoietin 1 levels significantly correlated with structural change in both the kidney and the heart and with urinary protein. Thus, the correlation between angiogenic growth factors with both renal and cardiac disease severity is compatible with a possible role for angiogenesis in the early progression of disease in ADPKD.

Prolonged Duration of Peritoneal Dialysis Catheter Embedment Does Not Lower the Catheter Success Rate

♦ Objective: Since 2000, we have used the Moncrief–Popovich technique as our standard method for peritoneal dialysis (PD) catheter insertion. The subcutaneous portion of the catheter is externalized immediately before initiation of PD. We undertook the present review to investigate whether duration of catheter embedment affects catheter or patient outcome. ♦ Methods: All catheters inserted beginning 1 January 2000 and externalized by 31 December 2008 were included. The primary outcome was catheter survival. Secondary outcomes were catheter patency (no fibrin plug or omental wrap) and complications within 90 days after externalization. A standard peritoneal equilibration test was used to classify peritoneal membrane transport status. Proportional hazards regression models were used to test whether duration of embedment affected catheter outcomes. The models treated embedment duration as both a continuous predictor and a categorical predictor categorized by tertile. ♦ Results: A total of 134 catheters were implanted and externalized. Twelve patients received 2 catheters each. To ensure statistical independence of the observations, 12 of the latter 24 catheters were excluded (1 chosen randomly from each patient), resulting in a useable sample size of 122 catheters. The total duration of observation was 2359 patient–months. The median duration of catheter embedment was 40.5 days (range: 2 – 788 days). After controlling for sex, race, age, and diabetes status, embedment duration did not have a significant effect on catheter survival as a continuous predictor or as a categorical predictor. Additionally, the 95% confidence interval for the 30-day effect of embedment duration ruled out a change of more than 20.6% in the hazard of catheter malfunction or infection. Of the studied catheters, 89.3% were patent and functioned properly immediately upon externalization. The remaining 13 catheters (10.7%) lacked patency on externalization because of fibrin plug or kinking (n = 10) or omental wrap (n = 3); however, 12 of the 13 non-patent catheters were corrected laparoscopically, and the patients resumed PD. Only 1 patient transferred to hemodialysis. Overall, 121 of 122 buried catheters (99.2%) were used for PD. Other complications within 90 days of catheter externalization included incision site and tunnel infection in 2 cases (1.6%), exit-site leak in 2 cases (1.6%), and coagulase-negative staphylococcal peritonitis in 1 case (0.8%). ♦ Conclusions: Duration of catheter embedment before externalization did not affect catheter survival and did not influence subsequent peritoneal membrane transport status. The overall effect of increasing embedment duration by 30 days is, at most, a 20.6% increase or decrease in the hazard of catheter failure, but the actual hazard may be much smaller or nonexistent. Larger studies are needed to further explore the ideal duration of embedment.

Role of Vasopressin and Vasopressin Receptor Antagonists in Type I Cardiorenal Syndrome

The pathogenesis of cardiac failure involves activation of the neurohumoral axis including stimulation of the sympathetic nervous system, the renin-angiotensin-aldosterone, and nonosmotic vasopressin systems. While these responses are critical in maintaining arterial pressure, they are associated with renal vasoconstriction, as well as sodium and water retention. In advanced circumstances, renal dysfunction and hyponatremia occur with cardiac failure. Even a modest rise in serum creatinine related to diminished renal function in heart failure patients is associated with increased risk for cardiovascular morbidity and mortality. Similarly, increased thirst and the nonosmotic stimulation of vasopressin in advanced cardiac failure leads to hyponatremia, which is also a major risk factor for mortality. Currently, V2 vasopressin receptor antagonists have been shown to correct hyponatremia in cardiac failure. One such agent, conivaptan, also is a V1 receptor antagonist which could theoretically benefit heart failure patients by decreasing cardiac afterload and remodeling. The effect of V2 receptor antagonists to correct hyponatremia in heart failure patients appears to be quite safe. However, to date no effect on mortality has been demonstrated.

The use of vasopressin receptor antagonists in hyponatremia.

Introduction: Considerable data have recently characterized hyponatremia as fairly common in the intensive care and general hospital settings. Moreover, mounting evidence suggests the association of mild degrees of hyponatremia with untoward neurocognitive and musculoskeletal outcomes. A key development in our ability to treat hyponatremia was the introduction and approval of aquaretics (vaptans). These vasopressin receptor antagonists work by increasing electrolyte-free water excretion and thus raising serum sodium concentration. Areas covered: This review presents a diagnostic approach for hyponatremia and discusses some therapeutic considerations. It displays new evidence linking mild chronic hyponatremia with unfavorable outcomes and examines the available treatment options and their limitations and strengths. New data on vaptans and their potential role to treat hyponatremia in different clinical settings are reviewed. Expert opinion: Vaptans are likely to play an important role in treating hyponatremia, given their clinical efficacy and tolerability. High cost remains an impediment for vaptans, and more studies are needed to further define their best use in hyponatremic patients.