Kurakazu Shimizu

Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myelocytic leukemia

A 31-year-old man diagnosed as having chronic myelocytic leukemia (CML) developed renal insufficiency with nephrotic-range proteinuria during alpha-interferon (IFN) therapy for CML. A renal biopsy specimen showed remarkable thrombotic microangiopathic lesions resembling those of hemolytic-uremic syndrome. The patient had papules on both lower legs, and a cutaneous biopsy showed similar microangiopathic lesions in dermal and subcutaneous vessels. Although discontinuation of IFN and initiation of prednisolone therapy resulted in resolution of proteinuria, renal insufficiency persisted. These findings suggest that long-term IFN therapy can induce late-onset thrombotic microangiopathy in systemic microvessels.

Effect of Hyperosmolality on Vasopressin Secretion in Intradialytic Hypotension: A Mechanistic Study

BACKGROUND Administration of a small volume of hypertonic solution has been used as an effective treatment for patients with intradialytic hypotension. Hypertonic solutions have been considered to act as plasma volume expanders. This clinical study examines whether arginine vasopressin (AVP) is involved in this mechanism of blood pressure control. STUDY DESIGN Nonrandomized trial. SETTING & PARTICIPANTS 42 patients on long-term hemodialysis therapy at a single hospital. INTERVENTION Effects of intravenous infusions of 20 mL of 10% saline, 20 mL of 50% glucose, 200 mL of 0.9% saline, or physiological doses of AVP were examined during intradialytic hypotension. OUTCOMES & MEASUREMENTS Changes in plasma AVP levels, osmolality, plasma volume, and blood pressure were analyzed. RESULTS Hypertonic saline infusion increased plasma osmolality (mean, 292.7 to 302.3 mOsm/kg H(2)O; P < 0.001), plasma AVP levels (3.9 to 7.8 pg/mL; P = 0.03), and mean arterial pressure (66.6 to 71.8 mm Hg; P = 0.01). The increase in plasma volume (2.3%; P = 0.03) was too small to increase blood pressure because of volume alone. Hypertonic glucose infusion yielded similar results. Isotonic saline infusion increased blood pressure with an abrupt increase in plasma volume (12.7%; P < 0.001). AVP infusion increased blood pressure and plasma AVP to levels similar to those induced by the hypertonic solutions. LIMITATIONS There are limitations in accurately measuring changes in plasma volume during hemodialysis. CONCLUSIONS Results strongly suggest that the osmotic stimulation of AVP secretion by hypertonic solutions has an important role in increasing blood pressure in patients with intradialytic hypotension. Manipulating plasma AVP appropriately may help correct and prevent intradialytic hypotension.

Vasopressin secretion by hypertonic saline infusion during hemodialysis: effect of cardiopulmonary recirculation

BACKGROUND Intradialytic hypotension is the most common and severe acute complication of hemodialysis therapy. In our previous study, infusion of 20 mL of 10% saline into the venous line of a dialyzer increased blood pressure during dialysis hypotension by stimulating arginine vasopressin (AVP) secretion, independent of its effect on plasma volume (PV). This study examines the mechanism by which a small amount of hypertonic solution stimulates AVP secretion. METHODS Hemodialysis patients were infused with 20 mL of 2.5 M saline (100 mOsm) over 5 (Protocol 1) or 2 min (Protocol 2) or with isotonic saline (Protocol 3) into the venous line. RESULTS Arterial plasma osmolality (Posm) increased by 28.1 and 16.0 (P < 0.0001), while peripheral venous Posm increased by only 8.6 and 8.9 mOsm/kg H(2)O (P < 0.001) in Protocols 2 and 1, respectively. Plasma AVP (P(AVP)) increased significantly by 18.6 and 5.6 pg/mL, PV by 7.2 and 5.5% and mean arterial pressure (MAP) by 15.0 and 7.2 mmHg in Protocols 2 and 1, respectively. Thus, there were large differences in Posm between arterial and peripheral venous blood; osmolar gap, P(AVP) and MAP increased in proportion to the infusion rate. Isotonic saline (30.8 mOsm) infusion increased PV by 8.7% and MAP by 7.2 mmHg. CONCLUSION Our results indicate that by a mechanism similar to cardiopulmonary recirculation, hypertonic saline infusion caused a striking increase in arterial Posm that enhanced AVP secretion and raised blood pressure. The effect of hypertonic saline on PV was less than one-third of isotonic saline under similar osmolar loads.

Solute-Free versus Electrolyte-Free Water Clearance in the Analysis of Osmoregulation

Background: Although attention has recently focused on electrolyte-free water clearance (E-C_H2O) as a replacement for solute-free water clearance (C_H2O), especially from the viewpoint of plasma sodium regulation, a thorough comparison of the two has yet to be conducted. Methods: C_H2O and E-C_H2O were systematically compared in normal subjects in different diuretic stages, including furosemide-induced solute diuresis, and in patients with renal disease. Results: The normal renal ability to conserve free water based on E-C_H2O was only 41% of that based on C_H2O. E-C_H2O remained positive until the urinary osmolality exceeded 500 mosm/kg H₂O, markedly different from the 300 mosm/kg H₂O for C_H2O. The difference between E-C_H2O and C_H2O could ultimately be attributed to urea osmolar clearance, i.e., urea excretion rate/plasma osmolality, which accounted for about 40% of the osmolar clearance. C_H2O underestimated the free water clearance by about 1 ml/min on average at all diuretic stages. Conclusions: E-C_H2O is a more correct parameter than C_H2O with regard to the regulation of both plasma sodium and plasma osmolality. However, there is the opinion that the concept of E-C_H2O is difficult to understand and that E-C_H2O is still not a generally accepted parameter. It is expected that the results of the present study will lead to more general acceptance.