Comparison of Bone and Renal Effects In HIV-infected Adults Switching to Abacavir or Tenofovir Based Therapy in a Randomized Trial

Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy.In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers were compared across study arms.Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (-1.8% and -2.5%) and week 48 (-2.1% and -2.1%), whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients.Switching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed.Clinicaltrials.gov NCT00647244

Association of kidney function with inflammatory and procoagulant markers in a diverse cohort: A cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Prior studies using creatinine-based estimated glomerular filtration rate (eGFR) have found limited associations between kidney function and markers of inflammation. Using eGFR and cystatin C, a novel marker of kidney function, the authors investigated the association of kidney function with multiple biomarkers in a diverse cohort. Methods: The Multi-Ethnic Study of Atherosclerosis consists of 6,814 participants of white, African-American, Hispanic, and Chinese descent, enrolled from 2000-2002 from six U.S. communities. Measurements at the enrollment visit included serum creatinine, cystatin C, and six inflammatory and procoagulant biomarkers. Creatinine-based eGFR was estimated using the fourvariable Modification of Diet in Renal Disease equation, and chronic kidney disease was defined by an eGFR less than 60 mL/min/1.73 m2. Results: Adjusted partial correlations between cystatin C and all biomarkers were statistically significant: C-reactive protein (r = 0.08), interleukin-6 (r = 0.16), tumor necrosis factor-a soluble receptor 1 (TNF-aR1; r = 0.75), intercellular adhesion molecule-1 (r = 0.21), fibrinogen (r = 0.14), and factor VIII (r = 0.11; two-sided p less than 0.01 for all). In participants without chronic kidney disease, higher creatinine-based eGFR was associated only with higher TNF-aR1 levels. Conclusion: In a cohort characterized by ethnic diversity, cystatin C was directly associated with multiple procoagulant and inflammatory markers. Creatinine-based eGFR had similar associations with these biomarkers among subjects with chronic kidney disease.This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI)

The Acute Porphyrias: a diagnostic and theraputic challenge in internal and emergency medicine

The porphyrias are a heterogeneous group ofmetabolic diseases resulting from a variable catalytic defectof one of the eight enzymes involved in the heme biosynthesispathway; they are mostly inherited diseases, but insome circumstances the metabolic disturbance may beacquired. The specific patterns of tissue overproduction (andhence accumulation and excretion) of toxic heme precursors,associated with each enzymatic deficiency, are responsiblefor the characteristic biochemical and clinical features ofeach of these diseases. Moreover, even in the presence of aspecific inherited enzymatic defect, many different environmentalfactors (such as drugs, calorie restriction, hormones,sunlight exposition, infections, etc.) often play a keyrole in triggering the clinical expression of the various formsof porphyrias. The porphyrias are often misdiagnosed diseases,due their multiform clinical manifestations, able tomimic many other more common diseases. For this reason,many different specialists, such as surgeons, psychiatrists,gastroenterologists, neurologists, emergency physicians anddermatologists may be variably involved in the diagnosticprocess, especially for the forms presenting with acute andlife-threatening clinical features. According to the clinicalfeatures, the porphyrias can be classified into neuropsychiatric(characterized by neurovisceral crises involving autonomicand central nervous system but also the liver and thekidney with possible consequences in terms of neurological,psychic, cardiac, respiratory, liver and kidney functions),dermatological (mostly presenting with cutaneous lesionsdue to photosensitivity), and mixed forms. From a strictlyclinical point of view, porphyrias presenting with neurovisceralattacks are also referred as acute porphyrias: they arethe object of the present review. An accurate diagnosis ofacute porphyria requires knowledge and the use of correctdiagnostic tools, and it is mandatory to provide a moreappropriate therapeutic approach and prevent the use ofpotentially unsafe drugs, able to severely precipitate thesediseases, especially in the presence of life-threateningsymptoms. To date, availability of a relatively stable haempreparation (haem arginate) has significantly improved thetreatment outcome of acute porphyric attacks, so theknowledge about the diagnosis and the management of thesediseases may be relevant for physicians working in internalmedicine, neurology and emergency units