Etiology and Clinical Outcomes of Renovascular Hypertension / 대한신장학회잡지

BACKGROUND: Renovascular hypertension has variable etiologic diseases and therapeutic outcomes. We performed a retrospective analysis of the causes and treatment results of renovascular hypertension to elucidate long-term prognosis with respect to blood pressure and renal function. METHODS: We reviewed patients who were admitted to Seoul National University Hospital for evaluation of renovascular hypertension in period from January, 1983 to December, 2002. Diagnosis of renovascular hypertension was made by combination of positive functional studies such as captopril renal scintigraphy and/or captopril test and angiographic demonstration of significant stenoses in one or both of renal arteries. Patients who were followed up for more than six months were included and classified according to the etiologic disease and treatment modalities. Responses of blood pressure and renal function in each patient were periodically evaluated. RESULTS: Of 74 patients included, 37 were male and 37 were female. The median age of the patients was 40. Atherosclerotic renal artery stenosis was the most common diagnosis (31, 41.9%), followed by Takayasu's arteritis (21, 28.4%) and fibromuscular dysplasia (14, 18.9%). Control of blood pressure and preservation of renal function were significant in medical, radiological, and surgical therapy group. There was no significant difference in response of blood pressure and renal function to treatment among treatment groups. Poor response of blood pressure and deterioration of renal function were observed more frequently in patients with atherosclerotic renal artery stenosis than in those with Takayasu's arteritis or fibromuscular dysplasia. CONCLUSION: Atherosclerosis was the most common etiologic diagnosis of renovascular hypertension. Medical treatment showed satisfactory treatment results as compared to radiologic and surgical revascularization. Patients with atherosclerotic renal artery stenosis showed poorer control of blood pressure and preservation of renal function.

The Changes of Aquaporin-2 Expression in Rats with Lithium Induced Nephrogenic Diabetes Insipidus after Hydrochlorothiazide Administration / 대한신장학회잡지

BACKGROUND: Thiazides have been used in nephrogenic diabetes insipidus (NDI) patients to decrease urine volume, but the mechanism of antidiuretic effect is not known yet. Recently, it has been demonstrated that abundance of aquaporin-2 (AQP2) was decreased in lithium induced NDI. We performed this study to investigate the effect of hydrochlorothiazide (HCTZ) in lithium induced NDI rats and the change of AQP2 expression. METHODS: NDI was induced in 7 male Spraque- Dawley rats by feeding lithium carbonate containing rat chow (40 mmol/kg) for 5 weeks. 4 rats were control group. HCTZ 3.75 mg/day (n=3 among lithium treated; Li+TZ) or vehicle (n=4 among lithium treated and control; Li and Control, respectively) was infused to the rats through osmotic minipump for the last 7 days. Urine volume and urine osmolality were measured. Kidneys were processed for immunohistochemistry and immunoblotting using antibody to AQP2. RESULTS: Li+TZ showed decreased urine volume (46+/-11 mL/day for Li+TZ vs. 127+/-1 mL/day for Li, p<0.05) and higher urine osmolality (557+/-139 mmol/kgH2O for Li+TZ vs. 207+/-9 mmol/kgH2O for Li, p<0.05) comparing to Li. In semi-quantitative immunoblotting using whole kidney homogenate, Li+TZ showed increase in AQP2 expression comparing to Li (39+/-2% for Li+TZ vs. 20+/-9% for Li, p<0.05, % of normal controls). In immunohistochemistry, AQP2 expression in cortex was markedly decreased after lithium treatment. But, AQP2 expression was slightly increased after HCTZ treatment. CONCLUSION: HCTZ treatment partially increased urine concentrating ability and AQP2 expression in rats with lithium induced NDI. We concluded that partial improvement in urine concentrating ability might be associated with upregulation of AQP2.

Diversity of initial manifestations in renal tubular acidosis / 대한내과학회지

BACKGROUND: Diagnosis of RTA (renal tubular acidosis) is not easy due to its nonspecific and various manifestations. To find out the clues to diagnosis, we investigated initial manifestations, laboratory features and clinical course of RTA patients. METHODS: Thirty-seven patients with RTA type I or II, whose follow-up period was over 6 months were included in the study. We reviewed their medical records retrospectively. RESULTS: Male to female ratio was 5:32 and the average age at the time of diagnosis was 38.7 (15~60). Twenty-five patients had RTA type I, nine had type II, and three had both. The average follow-up period was 6.4 years. Initial manifestations were asthenia (54%), nausea (46%), urinary stone (24%), paresthesia (24%), lower extremity weakness (22%), and paralysis (11%). Underlying diseases at the time of diagnosis include Sjogren's syndrome (14%), SLE (8%), drug-induced nephropathy (11%), diabetic nephropathy (5.4%), Sjogren's syndrome combined with SLE (2.7%), and medullary sponge kidney (2.7%). Laboratory tests revealed acidosis with hypokalemia (59%), acidosis without hypokalemia (14%), and hypokalemia without acidosis (24%). The level of total CO2 was 22 mmol/L or lower in 27 patients. The Na:Cl ratio on the average was 1:1.26 and for 33 patients below 1:1.35. Renal function deteriorated in 8 patients and 7 of them had underlying diseases. Urinary stone developed in 2 patients with RTA type I. CONCLUSION: When patients with nonspecific symptoms show decreased levels of serum total CO2, potassium, or Na:Cl ratio, RTA should always be considered.

Chronic Furosemide Administration Alters Abundance of Sodium Transporters in Rat Kidney / 대한신장학회잡지

BACKGROUND: Furosemide inhibit NaCl absorption in the thick ascending limb and produce an increase in distal delivery of Na+. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic furosemide infusion is associated with compensatory increases in the abundance of Na+ transporters in distal nephron. METHODS: Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day of furosemide(n=6) with simultaneous administration of 0.8% NaCl and 0.1% KCl in drinking water for 7 days. RESULTS: Compared with vehicle infused controls, urine volume and urine sodium amount were increased. However, there were no differences in body weight, serum aldosterone, and creatinine clearance. The abundance of Na+-K+-2Cl- cotransporter after furosemide infusion was increased in cortex (151+/-10 vs. 100+/-10%, p< 0.05) and outer medulla (122+/-5 vs. 100+/-3%, p< 0.01). In furosemide infusion group, the abundance of all three subunits of epithelial sodium channel (ENaC) was increased both in cortex (alpha: 187+/-25 vs. 100+/-17%, p< 0.05; beta: 155+/-8 vs. 100+/-15%, p< 0.05; gamma: 168+/-16 vs. 100+/-9%, p< 0.05) and outer medulla (alpha: 171+/-27 vs. 100+/-17%, p< 0.05; beta: 986+/-91 vs. 100+/-33%, p< 0.01; gamma: 242+/-24 vs. 100+/-22%, p< 0.01). Consistent with these results, ENaC beta-subuint immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with furosemide treatment. CONCLUSION: These increases in the abundance of ENaC protein may account for the generation of diuretic tolerance.