Medium-grade proteinuria is a risk factor for incident markers of chronic kidney disease.

OBJECTIVE: Medium-grade proteinuria (100-500 mg/g creatinine) is common among people living with HIV/AIDS (PLWHA) but is often undetected or ignored. This prospective, observational cohort study examined medium-grade proteinuria as a risk factor for markers of chronic kidney disease (CKD). METHODS: Quantitative urine samples were collected from 241 PLWHA without known renal disease at baseline between January 2009 and February 2011 and at follow-up 240 weeks later. Multivariate analysis was performed to assess medium-grade proteinuria as a risk factor for incident markers of CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 , albuminuria, phosphaturia). RESULTS: Incident markers of CKD were identified in 33 patients (14%), of whom 24 (74%) had medium-grade proteinuria at baseline. Of these, 22 even had proteinuria of < 200 mg/g creatinine. Multivariate analysis showed an adjusted relative risk (aRR) of 2.4 for patients with baseline medium-grade proteinuria to develop signs of CKD. Age was identified as an additional independent predictor. By testing for interaction, tenofovir disoproxil fumarate (TDF)-independent proteinuria was strongly associated with incident CKD markers (aRR = 12.1). CONCLUSION: Medium-grade proteinuria of 100-500 mg/g creatinine is both frequent in PLWHA and a significant risk factor for developing markers of CKD, especially in the absence of TDF. Relevant risk seems to be associated with proteinuria levels as low as 100-200 mg/g creatinine. Current guidelines recommend specific action for proteinuria exceeding 135-200 mg/g but still will miss a relevant number of PLWHA potentially at risk for CKD. An even lower cut-off to trigger nephrological work-up and potentially renoprotective interventions appears to be indicated.

Medium-grade tubular proteinuria is common in HIV-positive patients and specifically associated with exposure to tenofovir disoproxil Fumarate.

OBJECTIVES: The aim of this cross-sectional study was to evaluate the prevalence and risk factors of medium-grade proteinuria (100-500 mg/g creatinine) among HIV-positive adults. METHODS: Spot urine samples of HIV-positive adults without known renal disease were analyzed quantitatively between January 2009 and February 2011. Demographic and medical data were collected. Multivariate regression models for different patterns of proteinuria were constructed. RESULTS: Among 411 patients, 18 (4.4 %) presented albuminuria >300 mg/g creatinine and/or proteinuria >500 mg/g creatinine and were excluded from further analyses. Among the study population of 393 patients, 181 (46.1 %) had no significant proteinuria or albuminuria (<100 and <30 mg/g creatinine, respectively), 60 (15.3 %) had moderate albuminuria, while 152 (38.7 %) had proteinuria without albuminuria, suggesting tubular proteinuria. Independent predictors for medium-grade tubular proteinuria in multivariate analysis were exposure to tenofovir (DF), a CD4 nadir <500/µl, older age, and anti-HCV-antibodies. There was no association with classic renal risk factors like diabetes mellitus and arterial hypertension, or with estimated glomerular filtration rate (eGFR). CONCLUSIONS: We detected significant proteinuria in 230 (56.0 %) of 411 HIV-positive patients. Among this group, 152 (66.1 %) had medium-grade proteinuria without albuminuria, which was significantly associated with exposure to tenofovir, older age, a lower CD4 nadir and Hepatitis C. Nephrologic or HIV treatment guidelines fail to detect most of these patients but rather identify patients with high cardiovascular risk. In the absence of an association with eGFR the role of medium-grade tubular proteinuria as a potential early marker of chronic kidney disease remains unclear. Prospective studies are needed.

Gustatory and olfactory function in patients with granulomatosis with polyangiitis (Wegener's).

OBJECTIVES: Recent findings suggest that autoimmune disorders predispose to a diminished capacity to taste and smell. This has been shown for patients with systemic lupus erythematosus as well as for patients with rheumatoid arthritis (RA). Granulomatosis with polyangiitis (GPA), with its particular manifestations in the upper respiratory tract, may therefore have an even higher impact on these senses. The aims of this study were to evaluate the gustatory and olfactory function in patients with GPA, to compare them to sex- and age-matched healthy controls, and to correlate these findings with their GPA disease severity. METHOD: Patients with established GPA were analysed by standardized assessments for gustatory and olfactory functions and examined for disease activity, stage of disease, and treatment. RESULTS: Forty-four GPA patients were tested for their chemosensory functions. Compared to age- and sex-matched healthy controls, GPA patients showed significantly decreased olfactory scores along with diminished scores for their gustatory functions. The diminished sense of smell in GPA patients correlated significantly with elevated C-reactive protein (CRP) values whereas the gustatory impairment correlated with the duration and extent of the disease. CONCLUSIONS: Our results indicate that olfactory and gustatory functions are significantly decreased in GPA. As the olfactory function of these patients was comparable to patients with RA, chemosensory impairment may not simply be a consequence of the involvement of the upper respiratory tract, but rather a common complication of systemic autoimmune diseases.

Endogenous endophthalmitis with azole-resistant Candida albicans--Case report and review of the literature.

Candida endophthalmitis accounts for the majority of fungal endophthalmitis. Despite its clinical relevance there are no controlled trials on different treatment regimens. We report a case of endogenous endophthalmitis caused by azole-resistant Candida albicans following abdominal surgery in an otherwise healthy woman, and review the literature concerning treatment recommendations. In consideration of the serious outcome with loss of sight in insufficiently treated endophthalmitis we like to increase awareness to this disease entity and the possibility of azole-resistance, even in treatment-naive patients.

Mild hyperhomocysteinemia: risk factor or just risk predictor for cardiovascular diseases?

Elevated plasma levels of homocysteine (hyperhomocysteinemia) are increasingly recognized as a potential risk for atherothrombotic vascular diseases by numerous epidemiological and clinical studies. There are increasing experimental data that indicate mechanisms by which homocysteine may alter the vasculature in a way that predisposes to atherosclerotic vascular disease. A key event in the vascular pathobiology of hyperhomocysteinemia seems to involve the induction of endothelial dysfunction due to a reduction of the endogenous antiatherothrombotic molecular nitric oxide. Elevated homocysteine levels can be efficiently and safely reduced in most of hyperhomocysteinemic patients by supplementation of folic acid and cobalamin. This reduction is associated with an improvement in endothelial function and other surrogate markers of atherothrombosis, like carotid plaque area and the rate of abnormal stress electrocardiograms. Whether or not this translates into clinical benefits, is still under investigation. The first clinical study on homocysteine-lowering vitamin supplementation in patients that had undergone coronary intervention showed a benefitial effect on the rate on restenosis and the need for revascularization which translated into a reduction of major coronary events. In contrast, in three larger scaled secondary intervention trials in patients with stable coronary disease or post non-disabling stroke, vitamin supplementation had no effect on future vascular events although baseline homocysteine levels were significantly associated with a worse prognosis. Until the results of more clinical trials are available, the clinical relevant question whether or not homocysteine is just a risk predictor or a modifiable risk factor can not definitely be answered.