Medication adherence assessment: high accuracy of the new Ingestible Sensor System in kidney transplants.

BACKGROUND: This open-label single-arm exploratory study evaluated the accuracy of the Ingestible Sensor System (ISS), a novel technology for directly assessing the ingestion of oral medications and treatment adherence. METHODS: ISS consists of an ingestible event marker (IEM), a microsensor that becomes activated in gastric fluid, and an adhesive personal monitor (APM) that detects IEM activation. In this study, the IEM was combined to enteric-coated mycophenolate sodium (ECMPS). Twenty stable adult kidney transplants received IEM-ECMPS for a mean of 9.2 weeks totaling 1227 cumulative days. RESULTS: Eight patients prematurely discontinued treatment due to ECMPS gastrointestinal symptoms (n=2), skin intolerance to APM (n=2), and insufficient system usability (n=4). Rash or erythema due to APM was reported in 7 (37%) patients, all during the first month of use. No serious or severe adverse events and no rejection episode were reported. IEM detection accuracy was 100% over 34 directly observed ingestions; Taking Adherence was 99.4% over a total of 2824 prescribed IEM-ECMPS ingestions. ISS could detect accurately the ingestion of two IEM-ECMPS capsules taken at the same time (detection rate of 99.3%, n=2376). CONCLUSIONS: ISS is a promising new technology that provides highly reliable measurements of intake and timing of intake of drugs that are combined with the IEM.

Adult Refsum disease: a form of tapetoretinal dystrophy accessible to therapy.

Adult Refsum disease is characterized by an elevated plasma phytanic acid level and high concentrations of phytanic acid in a variety of tissues. Besides tapetoretinal degeneration, additional symptoms are anosmia, skeletal malformations, chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, ichthyosis, and cardiac abnormalities. A diet low in phytanic acid ameliorates polyneuropathy and ataxia and slows or even stops the other manifestations. In order to be able to apply dietary therapy, as many patients as possible (even better if all of them are) have to be identified at an early stage. The ophthalmologist plays a crucial role in achieving this goal because of the early manifestation of the tapetoretinal degeneration.

Avosentan for overt diabetic nephropathy.

In the short term, the endothelin antagonist avosentan reduces proteinuria, but whether this translates to protection from progressive loss of renal function is unknown. We examined the effects of avosentan on progression of overt diabetic nephropathy in a multicenter, multinational, double-blind, placebo-controlled trial. We randomly assigned 1392 participants with type 2 diabetes to oral avosentan (25 or 50 mg) or placebo in addition to continued angiotensin-converting enzyme inhibition and/or angiotensin receptor blockade. The composite primary outcome was the time to doubling of serum creatinine, ESRD, or death. Secondary outcomes included changes in albumin-to-creatinine ratio (ACR) and cardiovascular outcomes. We terminated the trial prematurely after a median follow-up of 4 months (maximum 16 months) because of an excess of cardiovascular events with avosentan. We did not detect a difference in the frequency of the primary outcome between groups. Avosentan significantly reduced ACR: In patients who were treated with avosentan 25 mg/d, 50 mg/d, and placebo, the median reduction in ACR was 44.3, 49.3, and 9.7%, respectively. Adverse events led to discontinuation of trial medication significantly more often for avosentan than for placebo (19.6 and 18.2 versus 11.5% for placebo), dominated by fluid overload and congestive heart failure; death occurred in 21 (4.6%; P = 0.225), 17 (3.6%; P = 0.194), and 12 (2.6%), respectively. In conclusion, avosentan reduces albuminuria when added to standard treatment in people with type 2 diabetes and overt nephropathy but induces significant fluid overload and congestive heart failure.

Avosentan reduces albumin excretion in diabetics with macroalbuminuria.

Despite the first-line use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), there is still a large need to improve the prevention and progression of diabetic nephropathy and its associated cardiovascular events. Endothelin antagonists have shown anti-inflammatory, antifibrotic, and antiproteinuric effects in experimental studies. This study was a randomized, placebo-controlled, double-blind, parallel-design, dosage-range study of the effect of the endothelin-A antagonist avosentan (SPP301) on urinary albumin excretion rate (UAER) in patients with diabetic nephropathy. We randomly assigned 286 patients with diabetic nephropathy, macroalbuminuria (UAER 0.2 to 5.6 mg/min), and BP <180/110 mmHg to 12 wk of avosentan (5, 10, 25, and 50 mg) or placebo, in addition to standard ACEI/ARB therapy. Relative to baseline, all avosentan dosages decreased mean relative UAER (-16.3 to -29.9%) compared with placebo (35.5%). Median relative UAER decreased with all avosentan dosages (-28.7 to -44.8%) compared with placebo (12.1%). Creatinine clearance and BP were unchanged at 12 wk. The main adverse events were peripheral edema (12%), mainly with high (>/=25 mg) dosages of avosentan; significant increases in liver enzymes did not occur. Twenty-one (7.3%) patients experienced adverse events that led to withdrawal from study medication. In summary, the endothelin-A antagonist avosentan given in addition to standard ACEI/ARB treatment decreases UAER in patients with diabetic nephropathy and macroalbuminuria.