ABSTRACT
BACKGROUND: The angiotensin receptor blocker losartan inhibited urate transporter 1 (URAT1) according to in vitro experiments. However, it is still unknown whether the inhibitory effect of losartan on URAT1 contributes to its uricosuric action in humans. METHODS: Thirty-two patients with hypertension and nine patients with idiopathic renal hypouricemia (five with and four without hypertension) were enrolled for this study. Hypertensive patients were prescribed oral losartan (50 mg/day, n = 16) or candesartan (8 mg/day, n = 16). Before and after 1-month treatment, the serum concentration of urate (Sur) and creatinine (Scr), and the clearance value of urate (Cur) and creatinine (Ccr) were determined. Clearance studies using the URAT1 inhibitor benzbromarone (100 mg/day) or losartan (50 mg/day) loading test were also performed in these patients. RESULTS: Blood pressure (BP) significantly decreased in the patients treated with either losartan or candesartan. Losartan significantly reduced Sur, which was associated with a concomitant increase in the Cur/Ccr ratio, whereas candesartan did not alter these parameters. In hypertensive patients with loss-of-function mutation of URAT1, losartan did not alter either Sur or Cur/Ccr, nor did benzbromarone. The lack of effect of URAT1 inhibitors on renal excretion of urate was independent of the renal function of hypouricemic patients. On the other hand, both losartan and benzbromarone increased Cur/Ccr ratio in hypertensive patients harboring the wild URAT1 gene, regardless of the presence of hypouricemia. CONCLUSIONS: These findings suggested that losartan inhibited URAT1 and thereby it lowered Sur levels in hypertensive patients.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Hypertension/drug therapy , Hyperuricemia/metabolism , Losartan/therapeutic use , Organic Anion Transporters/antagonists & inhibitors , Organic Cation Transport Proteins/antagonists & inhibitors , Administration, Oral , Aged , Angiotensin II Type 1 Receptor Blockers/administration & dosage , Benzimidazoles/administration & dosage , Biphenyl Compounds , Blood Pressure/physiology , DNA/genetics , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Hypertension/metabolism , Hypertension/physiopathology , Hyperuricemia/etiology , Hyperuricemia/genetics , Losartan/administration & dosage , Male , Mutation , Organic Anion Transporters/genetics , Organic Anion Transporters/metabolism , Organic Cation Transport Proteins/genetics , Organic Cation Transport Proteins/metabolism , Polymerase Chain Reaction , Tetrazoles/administration & dosage , Treatment Outcome , Uric Acid/metabolismABSTRACT
Secondary amyloidosis is well recognized as a severe complication in the late stages of rheumatoid arthritis (RA). However, there have been few reported cases of secondary amyloidosis developing early during the course of RA. We here report the case of a 35-year-old woman, in whom RA who had been diagnosed 1 year before, with intractable watery diarrhea as a symptom of RA-induced secondary intestinal amyloidosis. Combination treatment with intravenous hyperalimentation, corticosteroids, and methotrexate (MTX) resulted in a dramatic improvement of her symptoms and objective findings of serological abnormalities. Subsequent administration of corticosteroids and MTX resulted in long-term survival without recurrence. This case indicates that we should be alert for the development of secondary amyloidosis, even in patients with a short history of RA, when the disease is active. Furthermore, combination therapy with intravenous hyperalimentation and strong immunosuppressive agents seems to be very efficacious in the treatment of RA-associated secondary intestinal amyloidosis.
Subject(s)
Amyloidosis/pathology , Arthritis, Rheumatoid/complications , Gastrointestinal Diseases/pathology , Acute Disease , Adrenal Cortex Hormones/metabolism , Adult , Amyloidosis/diagnosis , Congo Red/pharmacology , Female , Humans , Immunosuppressive Agents/pharmacology , Methotrexate/pharmacology , Recurrence , Time FactorsABSTRACT
Autonomic failure is rare in patients with Sjögren syndrome (SS). We report the case of a 46-year-old woman with severe autonomic cardiovascular failure, manifested by incapacitating postural hypotension, as the first symptom of primary SS. Treatment with glucocorticoid resulted in a dramatic improvement of her symptoms and objective findings of autonomic cardiovascular dysfunction. We suggest that SS should be considered in patients with idiopathic autonomic cardiovascular neuropathy, especially in those with idiopathic orthostatic hypotension. Furthermore, glucocorticoid therapy seems to be very efficacious in the treatment of SS-associated autonomic cardiovascular neuropathy.
