Urinary excretion of beta2-microglobulin as a prognostic marker in immunoglobulin A nephropathy

BACKGROUND/AIMS: beta2-microglobulin (beta2-MG) is freely filtered at the glomerulus and subsequently reabsorbed and catabolized by proximal renal tubular cells. Urinary beta2-MG is an early and sensitive biomarker of acute kidney injury; however, its utility as a biomarker of immunoglobulin A nephropathy (IgAN) is unclear. METHODS: We included urinary beta2-MG levels in the routine laboratory examination of all inpatients with biopsy-proven IgAN at our hospital from 2006 to 2010. We retrospectively analyzed the correlation between beta2-MG levels and clinical parameters as a prognostic biomarker of IgAN. RESULTS: A total of 51 patients (30 males, 21 females; mean age, 33.01 +/- 12.73 years) with IgAN were included in this study. Initial demographic, clinical, and laboratory data for all patients are listed. The mean initial estimated glomerular filtration rate and 24-hour urine protein levels were 94.69 +/- 34.78 mL/min/1.73 m2 and 1.28 +/- 1.75 g/day, respectively. The mean level of urinary beta2-MG was 1.92 +/- 7.38 microg/mg creatinine. There was a significant correlation between initial serum creatinine (iSCr), urine protein creatinine ratio (UPCR), and the level of beta2-MG (r = 0.744, r = 0.667, p < 0.01). There was also a significant correlation between renal function tests and the level of urinary beta2-MG (p < 0.01). Cox regression analysis showed that albumin, beta2-MG, iSCr, and UPCR were significant predictors of disease progression in IgAN. CONCLUSIONS: Urinary beta2-MG levels showed a significant correlation with renal function and proteinuria in IgAN. Thus, we propose that urinary beta2-MG may be an additional prognostic factor in patients with IgAN.

Severe Hyponatremia Associated with the Use of Angiotensin II Receptor Blocker/thiazide Combinations

There are several widely used combinations of angiotensin II receptor blocker (ARB)/thiazide. The complimentary mechanism of action for such anti-hypertensive therapies is that, while ARB inhibits the vasoconstricting and aldosterone-secreting effects of angiotensin II, hydrochlorothiazide affects the renal tubular mechanisms of electrolyte reabsorption and increases excretion of sodium and chloride in the distal tubule, consequently promoting water excretion. In addition, hypokalemia, which may be triggered by a hydrochlorothiazide-induced increase in urinary potassium loss, is resisted by the use of ARB. Hence, the ARB/thiazide combination is safe in terms of potassium imbalance. For these reasons, fixed-dose ARB/thiazide combination anti-hypertensive drugs have been widely used for the treatment of hypertension. However, there have not been many studies done regarding cases where patients under such regimens showed severe hyponatremia, even when the amount of thiazide included was low. Here we report two cases in which severe hyponatremia occurred following treatment with the ARB/thiazide combinations. Upon discontinuation of the regimen, both patients showed recovery from hyponatremia.

A Case of Severe Hypercalcemia after Treatment with Teriparatide for Osteoporosis

Recombinant human parathyroid hormone 1-34 (rHPTH; 1-34, teriparatide) increases bone mass and increases osteoporotic fracture by stimulating new bone formation. It was approved in the United States for treatment of osteoporosis in men and women, and its effectiveness and safety was proved. Mild hypercalcemia was observed, but persistent and severe hypercalcemia was not observed in the studies of teriparatide. In this case, severe hypercalcemia was developed from patient having gait disturbance who was treated with vitamin D, calcium and teripartide for two months to treat osteoporosis after subtrochanteric fracture. Hypercalcemia was resolved with discontinuation of teriparatide. Severe hypercalcemia is not a common complication of teriparatide and monitoring of serum calcium level is routinely not recommended. But it is necessary to pay close attention to patients who were treated with teriparatide, especially in immobilized patients.

A Case of Severe Hypercalcemia after Treatment with Teriparatide for Osteoporosis

Recombinant human parathyroid hormone 1-34 (rHPTH; 1-34, teriparatide) increases bone mass and increases osteoporotic fracture by stimulating new bone formation. It was approved in the United States for treatment of osteoporosis in men and women, and its effectiveness and safety was proved. Mild hypercalcemia was observed, but persistent and severe hypercalcemia was not observed in the studies of teriparatide. In this case, severe hypercalcemia was developed from patient having gait disturbance who was treated with vitamin D, calcium and teripartide for two months to treat osteoporosis after subtrochanteric fracture. Hypercalcemia was resolved with discontinuation of teriparatide. Severe hypercalcemia is not a common complication of teriparatide and monitoring of serum calcium level is routinely not recommended. But it is necessary to pay close attention to patients who were treated with teriparatide, especially in immobilized patients.

Etiology of Hypokalemic Paralysis in Korea: Data from a Single Center

Recognizing the underlying causes of hypokalemic paralysis seems to be essential for the appropriate management of affected patients and their prevention of recurrent attacks. There is, however, a paucity of documented reports on the etiology of hypokalemic paralysis in Korea. We retrospectively analyzed 34 patients with acute flaccid weakness due to hypokalaemia who were admitted during the 5-year study period in order to determine the spectrum of hypokalemic paralysis in Korea and to identify the differences in clinical parameters all across the causes of hypokalemic paralysis. We divided those 34 patients into 3 groups; the 1st group, idiopathic hypokalemic periodic paralysis (HPP), the 2nd, thyrotoxic periodic paralysis (TPP), and the 3rd group, secondary hypokalemic paralysis (HP) without TPP. Seven of the patients (20.6%) were diagnosed as idiopathic HPP considered the sporadic form, and 27 patients (79.4%) as secondary HP. Among the patients diagnosed as secondary HP, 16 patients (47.1%) had TPP. Patients of secondary hypokalemic paralysis without TPP required a longer recovery time compared with those who had either idiopathic HPP or TPP. This is due to the fact that patients of secondary HP had a significantly negative total body potassium balance, whereas idiopathic HPP and TPP were only associated with intracellular shift of potassium. Most of the TPP patients included in our study had overt thyrotoxicosis while 3 patients had subclinical thyrotoxicosis. This study shows that TPP is the most common cause of hypokalemic paralysis in Korea. And we suggest that doctors should consider the presence of TPP in patients of hypokalemic paralysis even if they clinically appear to be euthyroid state.

Evaluation of Mean Pulmonary Artery Pressure Following Experimental Pulmonary Embolism in Dogs

In various autopsy series, overdiagnosis as well as underdiagnosis of pulmonary embolism has been reported. During the past decade, mortality rate has not declined despite advances in diagnostic methods. To evaluate the hypothesis that changes of hemodynamic parameters responded by mean pulmonary arterial pressure differences are of paramount importance to guide prognosis, experimental model of anesthetized dogs was used. Six dogs were anesthetized with 15 milligrams per kilogram of pentobarbital sodium, given intravenously and paralyzed with 2 milligrams of pancuronium bromide. 0.3 to 0.8 gram per kilogram of autologous blood clot was infused into the right atrium through a left external jugular vein. The dogs after embolization were divided into group A(mean pulmonary arterial pressure 33mmHg) and group B(mean pulmonary arterial pressure 43 mmHg). Each group of three dogs was monitored for a total of 4.5 hours. A 7F Swan-Ganz catheter was positioned and used to measure with fluid-filled transducer pulmonary capillary wedge pressure, mean pulmonary arterial pressure and mean right atrial pressure. Cardiac ouput was measured in triplicate by thermodilution and divided by weight to obtain the cardiac index. Blood gases, pH and saturation of arterial blood were measured. White blood cell and platerlets were counted in arterial blood. The results are as follows : 1) Changes in mean arterial pressure showed no significant differences between group A and group B following embolization. 2) Changes in mean pulmonary arterial pressure showed significant differences between group A and group B(p<0.05). 3) Changes in cardiac index showed significant differences between group A and group B after 45 minutes following embolization(p<0.05). 4) Changes in total pulmonary resistance showed significant differences between group A and group B after 45 minutes following embolization(p<0.05). 5) PaO2 showed significant differences between group A and group B after one hour following embolization(p<0.05), but arterial pH showed no significant difference. 6) Changes in mean pulmonary capillary wedge pressure, mean right atrial pressure and heart rates showed no significant differences between group A and group B following embolization. In conclusion, changes in mean pulmonary arterial pressure, cardiac index, total pulmonary resistance and PaO2 showed significant differences between group A and group B following embolization.