Effect of estradiol on the expression of renal sodium transporters in rats.

BACKGROUND: Although estradiol has been thought to perform an important role in blood pressure regulation, the effects of estradiol on the expression of renal sodium transporters are not fully understood. METHODS: Female Sprague-Dawley rats were treated with 17ß-estradiol or vehicle for 10 days after ovariectomy, and after both ovariectomy and adrenalectomy to eliminate the effect of aldosterone. RESULTS: In the ovariectomized (OVX) rats, estradiol decreased the abundance of the Na-K-2Cl cotransporter (NKCC2) (31.5% of control (OVX), p < 0.01), Na-Cl cotransporter (NCC) proteins (40.5% of control (OVX), p < 0.01) and α- and γ-subunits of the epithelial sodium channel (ENaC) (44.7% and 11.0% of control (OVX), p < 0.01). Estradiol also reduced plasma aldosterone levels (OVX + 17ß-estradiol vs. OVX, 116.3 ± 44.4 vs. 184.2 ± 33.4 pmol/l, p < 0.05) and systolic blood pressure (OVX + 17ß-estradiol vs. OVX, 115 ± 4 vs. 132 ± 2 mmHg, p < 0.05). In rats having undergone adrenalectomy and ovariectomy, estradiol did not reduce systolic blood pressure, or the expression of sodium transporters. CONCLUSION: Estradiol decreased systolic blood pressure, plasma aldosterone levels, and the expression of renal sodium transporters. After aldosterone was eliminated, estradiol did not affect blood pressure or the expression of sodium transporters, which indicates that the effect of estradiol on the renal sodium transporters is at least partly influenced by aldosterone.

Effective removal of leptin via hemodiafiltration with on-line endogenous reinfusion therapy.

AIMS: Leptin is a middle-molecular weight uremic toxin. Hemodiafiltration with on-line endogenous reinfusion (HFR) is a novel dialytic method combining the processes of diffusion, convection and adsorption. We performed a prospective crossover study of patients with end-stage renal disease to investigate the effect of HFR therapy on the level of leptin as compared to conventional low flux hemodialysis (LHD). METHODS: Eleven stable hemodialysis patients were treated with LHD for 12 weeks and then treated with HFR (SG30 Plus; Sorin Group Italia S.r.1, Mirandola, Italy) for 12 weeks. RESULTS: After 12 weeks of HFR treatment, serum leptin levels significantly decreased (17.1 (2.66 - 39.5) at Week 12 vs. 12.3 (1.80 - 24.3) ng/ml at Week 24, p = 0.014). Although serum adiponectin levels also decreased (1.66 (1.44 - 1.86) at Week 12 vs. 1.12 (0.79 - 1.34) g/ml at Week 24, p = 0.001), the ratio of leptin to adiponectin did not increase after HFR treatment. Serum beta2-microglobulin (beta2M) levels significantly decreased (37.7 (29.8 - 42.6) at Week 12 vs. 28.3 (26.5 - 32.2) mg/dl at Week 24, p = 0.002). Dry weight, Kt/V(urea), normalized protein equivalent of nitrogen appearance, subjective global assessment, and serum albumin levels of the patients were not changed after HFR treatment. There was no difference in the serum levels of C-reactive protein or interleukin-6 between Week 12 and Week 24. CONCLUSIONS: The results of our study indicate that HFR may be a better therapy than LHD for removal of middle-molecular-weight uremic toxins such as leptin and b2M.

Transtubular potassium concentration gradient (TTKG) and urine ammonium in differential diagnosis of hypokalemia.

BACKGROUND: Hypokalemia is a common and sometimes serious clinical problem, whose etiological diagnosis can frequently be based on the patient's history and the clinical setting. Measurement of urinary indices such as excretory rate of K+, random urine K+ concentrations and blood acid-base parameters have been employed in the pathophysiological diagnosis, though with some pitfalls. METHODS: To investigate the diagnostic usefulness of the transtubular potassium concentration gradient (TTKG) and urine ammonium in the differentiation of hypokalemia, we measured serum K+ and osmolality, random urine electrolytes, osmolality and ammonium, the urinary [Na]/[K] ratio (U(Na)/K), plasma aldosterone and TTKG in 7 patients with diarrhea, 6 with vomiting, 7 with mineralocorticoid excess, 6 with diuretic usage, and compared them with those of 7 overnight fasted and acid-loaded healthy volunteers. RESULTS: The urine K+ concentrations did not reflect urinary loss of potassium according to the subjects' hydration status. U(Na)/k in the hypokalemic patients with mineralocorticoid excess (1.4 +/- 0.5) was lower than in normal subjects (2.3 +/- 0.4) (p<0.05). TTKG was higher in hypokalemic patients with mineralocorticoid excess (13.3 +/- 4.4) and diuretic usage (8.6 +/- 1.3) and lower in those with diarrhea (1.6 +/- 0.3) than in the normal controls (5.0 +/- 0.7) (p<0.5). TTKG in the patients with vomiting (3.5 +/- 0.6) was the same as in normal controls. TTKG was stronger correlated with the plasma aldosterone levels in the hypokalemic patients due to renal potassium loss. Urine ammonium concentrations of the acid-loaded normal subjects (73.3 +/- 5.0 mEq/L), patients with diarrhea (74.4 +/- 2.0 mEq/L) and patients with mineralocorticoid excess (68.7 +/- 6.9 mEq/L) were higher than in overnight-fasted normal subjects (31.3 +/- 4.9 mEq/L). CONCLUSION: TTKG and random urine ammonium were useful in the pathophysiological differential diagnosis of hypokalemia.

The clinical significances of simple renal cyst: Is it related to hypertension or renal dysfunction?

Simple renal cyst has controversy related to hypertension and renal dysfunction. We analyzed the impacts of cyst on hypertension and renal dysfunction, focusing on elimination of the confounding factors. We grouped 436 patients and 436 controls by characteristics of cyst and stratified with clinical parameters among 6603 patients who had routine health check-up in Seoul National University Bundang Hospital, Seongnam, Korea. The presence of cyst was related to hypertension but not to renal dysfunction. The number and the size of cyst were independent risk factors to the prevalence of hypertension. The presence of multiple renal cysts was related to hypertension in males, in persons over the age of 60 years, in persons with glomerular filtration rate (GFR) more than 60 ml/min/1.73 m2, or in persons without proteinuria. The effect of the large cyst and the peripheral cyst on the prevalence of hypertension was similar to that of the multiple cyst. The blood pressure of the multiple-cyst group, the large-cyst group, or the peripheral-cyst group was higher than that of the single-cyst group, the small-cyst group, or the perihilar-cyst group, respectively, regardless of antihypertensive medications. In conclusion, the presence of cysts or characteristics of cyst were not related to the decreased GFR. In conclusion, the presence of simple renal cyst was related to hypertension but not to renal dysfunction. The effect of simple cyst on hypertension was evident in males, aged persons, and persons without the evidence of renal disease. The number, size, and location were important characteristics of cyst related to hypertension.

Does albumin preinfusion potentiate diuretic action of furosemide in patients with nephrotic syndrome?

The aim of this cross-over study was to investigate whether albumin infusion before furosemide administration could potentiate the diuretic action of furosemide. Seven patients with nephrotic syndrome were given the following infusions in random order on two separate days: 1) a sham solution followed by 160 mg of furosemide, 2) 100 ml of 20% human albumin followed by 160 mg of furosemide. Urine and serum furosemide concentrations were measured by high-performance liquid chromatography. The increment of urine volume was greater in albumin preinfusion than in furosemide alone. However, the increments of sodium and chloride excretions between furosemide alone and albumin preinfusion were not different. No significant differences in the pharmacokinetic parameters between the two treatments were observed: area under the concentration-time curve (AUC: 12.7+/-2.2 vs 15.1+/-4.4 g/ml hr), total plasma clearance (253+/-41 vs 256+/-54 ml/min), volume of distribution (341+/-34 vs 494+/-153 ml/kg), elimination half life (4.0+/-1.1 vs 4.6+/-0.8 hr), and urine furosemide excretion of the administered amount (16.5+/-7.3 vs 7.5+/-1.6%). In conclusion, these data show that albumin preinfusion potentiated diuresis, but not natriuresis, of furosemide without any change in the pharmacokinetics of the agent in patients with nephrotic syndrome.