Nephrology

OBJECTIVE: To review rules and formulas for solving even the most complex acid-base problems. SOURCES OF INFORMATION: MEDLINE was searched from January 1966 to December 2003. The search was limited to English-language review articles involving human subjects. Nine relevant review papers were found and provide th background. As this information is well established and widely accepted, it is not judged for strength of evidence, a is standard practice. MAIN MESSAGE: An understanding of the body's responses to acidemia or alkalemia can be gained through a set of four rules and two formulas that can be used to interpret almost any acid-base problems...

BACKGROUND: The course of autosomal dominant polycystic kidney disease (ADPKD) is often associated with pain, hypertension, and kidney failure. Preclinical studies indicated that vasopressin V(2)-receptor antagonists inhibit cyst growth and slow the decline of kidney function. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio to receive tolvaptan, a V(2)-receptor antagonist, at the highest of three twice-daily dose regimens that the patient found tolerable, or placebo...

BACKGROUND: The TEMPO 3:4 Trial results suggested that tolvaptan had no effect compared with placebo on albuminuria in autosomal-dominant polycystic kidney disease (ADPKD) patients. However, the use of categorical 'albuminuria events' may have resulted in a loss of sensitivity to detect changes. The aim of this study is to investigate the effects of tolvaptan on albuminuria as a continuous variable. METHODS: Post hoc analysis of a 3-year prospective, blinded randomized controlled trial, including 1375 ADPKD patients...

Tolvaptan (Jinarc(®)) is a highly selective vasopressin V2 receptor antagonist indicated for use in patients with autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan is the first pharmaceutical agent to be approved in Europe for delaying the progression of ADPKD in adults with stage 1-3 chronic kidney disease at initiation of treatment. In the large phase III TEMPO 3:4 trial in adults with ADPKD, 3 years' treatment with oral tolvaptan significantly reduced growth in total kidney volume and slowed renal function decline relative to placebo...

OBJECTIVE: European guidelines do not recommend tolvaptan for treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH), principally owing to concerns about risk of overly rapid correction of hyponatraemia. This study evaluated the real-life effectiveness and safety of tolvaptan. DESIGN: Consecutive case series. PATIENTS: Inpatients treated with tolvaptan for SIADH in 2 UK hospitals over a 3-year period. MEASUREMENTS: The primary outcome measures were serum sodium (sNa) correction at 24 and 48 h after tolvaptan therapy...

INTRODUCTION: Subjects with autosomal dominant polycystic kidney disease (ADPKD) who were taking tolvaptan experienced aminotransferase elevations more frequently than those on placebo in the TEMPO 3:4 (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and its Outcomes) clinical trial. METHODS: An independent, blinded, expert Hepatic Adjudication Committee re-examined data from TEMPO 3:4 and its open-label extension TEMPO 4:4, as well as from long-term (>14 months) non-ADPKD tolvaptan trials, using the 5-point Drug-Induced Liver Injury Network classification...

Tolvaptan, a selective vasopressin V2 receptor antagonist, slows the increase in total kidney volume and the decline in kidney function in patients with the results of the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Outcome (TEMPO) 3:4 trial. However, it was unclear which dose of tolvaptan was optimal or whether tolvaptan was able to delay progression to end-stage renal disease (ESRD). Here we examined the relationship with aquaresis and the inhibitory effect on cyst development in short-term treatment and mortality as an index of ESRD in long-term treatment with tolvaptan using DBA/2FG-pcy mice, an animal model of nephronophthisis...

Tolvaptan, a vasopressin receptor 2 antagonist used to treat hyponatremia, has recently been reported to be associated with an increased risk of liver injury. In this study, we explored the underlying mechanisms of hepatotoxicity of tolvaptan using human HepG2 cells. Tolvaptan inhibited cell growth and caused cell death in a concentration- and time-dependent manner. Tolvaptan treatment led to delayed cell cycle progression, accompanied by decreased levels of several cyclins and cyclin-dependent kinases. Tolvaptan was found to cause DNA damage, as assessed by alkaline comet assays; this was confirmed by increased levels of 8-oxoguanine and phosphorylation of histone H2AX...

PURPOSE: This study aimed to investigate the pharmacokinetics, pharmacodynamics, efficacy and safety of tolvaptan, an orally effective vasopressin V2-receptor antagonist. METHODS: This was a multicenter, randomized, double-blind, parallel group study. Tolvaptan was administered at 7.5 or 15 mg, in combination with furosemide, for 7 days in Japanese heart failure (HF) patients with volume overload that had not resolved despite receiving furosemide. RESULTS: The blood concentration of tolvaptan was maintained at a higher concentration for a longer time in patients who received 15 mg/day when compared with patients who received 7...

BACKGROUND: Kidney pain is a common complication in patients with autosomal dominant polycystic kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on kidney pain in this patient group. Because pain is difficult to measure, the incidence of kidney pain leading to objective medical interventions was used in the present study to assess pain. STUDY DESIGN: Secondary analysis from a randomized controlled trial...

BACKGROUND: This trial assessed the effect of tolvaptan on cognition, gait, and postural stability in adult patients with mild to moderate asymptomatic hyponatremia. STUDY DESIGN: Phase 3b, multicenter, randomized, double-blind, placebo-controlled, parallel-group pilot study. SETTING & PARTICIPANTS: 57 men and women 50 years or older with chronic asymptomatic euvolemic or hypervolemic hyponatremia (serum sodium concentration >120-<135 mEq/L) at 16 sites...

The vasopressin-cAMP-osmolality axis is abnormal in autosomal dominant polycystic kidney disease (ADPKD). In the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 Trial, a 3-year randomized, placebo-controlled trial in adults, the vasopressin V2 receptor antagonist tolvaptan slowed ADPKD progression in patients with preserved GFR. Here, we investigated the determinants of baseline urine osmolality (Uosm) and its value as a severity marker of ADPKD, the factors influencing the response to tolvaptan, and whether change in Uosm associated with key trial end points...

Patients with chronic kidney disease (CKD), including those with end-stage renal disease, treated with dialysis, or renal transplant recipients have an increased risk for cardiovascular disease (CVD) morbidity and mortality. Dyslipidemia, often present in this patient population, is an important risk factor for CVD development. Specific quantitative and qualitative changes are seen at different stages of renal impairment and are associated with the degree of glomerular filtration rate declining. Patients with non-dialysis-dependent CKD have low high-density lipoproteins (HDL), normal or low total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol, increased triglycerides as well as increased apolipoprotein B (apoB), lipoprotein(a) (Lp (a)), intermediate- and very-low-density lipoprotein (IDL, VLDL; "remnant particles"), and small dense LDL particles...

Acid-base disturbances can result from kidney or nonkidney disorders. We present a case of high-volume ileostomy output causing large bicarbonate losses and resulting in a non-anion gap metabolic acidosis. Non-anion gap metabolic acidosis can present as a form of either acute or chronic metabolic acidosis. A complete clinical history and physical examination are critical initial steps to begin the evaluation process, followed by measuring serum electrolytes with a focus on potassium level, blood gas, urine pH, and either direct or indirect urine ammonium concentration...

In both atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) complement plays a primary role in disease pathogenesis. Herein we report the outcome of a 2015 Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference where key issues in the management of these 2 diseases were considered by a global panel of experts. Areas addressed included renal pathology, clinical phenotype and assessment, genetic drivers of disease, acquired drivers of disease, and treatment strategies. In order to help guide clinicians who are caring for such patients, recommendations for best treatment strategies were discussed at length, providing the evidence base underpinning current treatment options...

OBJECTIVES: We describe a 62-year-old woman with a 15-year history of a plasma cell dyscrasia (monoclonal IgGκ), manifested by type I cryoglobulinemia and dermal vasculitis. METHODS: In addition to the clinical examinations, light microscopy with immunohistochemistry, sequential multicolor immunohistochemistry, and electron microscopy were used to characterize the crystalline deposits. RESULTS: At initial presentation and for a later flare, she was treated with cyclophosphamide and prednisolone with good clinical response...

The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a significant reduction in major cardiovascular events and all-cause mortality with intensive blood pressure control in older individuals at high cardiovascular risk, including patients with chronic kidney disease and mild proteinuria. Nephrologists should consider the SPRINT results when determining the optimal blood pressure target for patients with chronic kidney disease.

BACKGROUND: Star fruit (Averrhoa carambola) is commonly consumed as a herbal remedy for various ailments in tropical countries. However, the dangers associated with consumption of star fruit are not commonly known. Although star fruit induced oxalate nephrotoxicity in those with existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. We report two unique clinical presentation patterns of star fruit nephrotoxicity following consumption of the fruit as a remedy for diabetes mellitus-the first, in a patient with normal renal function and the second case which we believe is the first reported case of chronic kidney disease (CKD) due to prolonged and excessive consumption of star fruits...

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