Chronic renal failure among HIV-1-infected patients

BACKGROUND: The role of exposure to antiretrovirals in chronic renal failure (CRF) is not well understood. Glomerular filtration rates (GFR) are estimated using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations. METHODS: Baseline was arbitrarily defined as the first recorded GFR; patients with two consecutive GFR < or = 60 ml/min per 1.73 m(2) were defined as having CRF. Logistic regression was used to determine odds ratio (OR) of CRF at baseline. ART exposure (yes/no or cumulative exposure) prior to baseline was included in multivariate models (adjusted for region of Europe, age, prior AIDS, CD4 cell count nadir, viral load, hypertension and use of nephrotoxic anti-infective therapy). RESULTS: Using CG, the median GFR at baseline (n = 4474) was 94.4 (interquartile range, 80.5-109.3); 158 patients (3.5%) had CRF. Patients with CRF were older (median, 61.9 versus 43.1 years), had lower CD4 cell count nadirs (median, 80 versus 137 cells/microl), and were more likely to be diagnosed with AIDS (44.3 versus 30.4%), diabetes (16.5 versus 4.3%) or hypertension (53.8 versus 26.4%), all P < 0.001. In a multivariate model any use of indinavir [odds ratio (OR) 2.49; 95% confidence interval (CI), 1.62-3.83] or tenofovir (OR, 2.18; 95% CI, 1.25-3.81) was associated with increased odds of CRF, as was cumulative exposure to indinavir (OR, 1.15 per year of exposure; 95% CI, 1.06-1.25) or tenofovir (OR, 1.60; 95% CI, 1.20-2.15). Highly consistent results were seen using the MDRD formula. CONCLUSIONS: Among antiretrovirals, only exposure to indinavir or tenofovir was associated with increased odds of CRF. We used a confirmed low GFR to define CRF to increase the robustness of our analysis, although there are several potential biases associated with this cross-sectional analysis.     

非酒精性脂肪性肝病胰岛素抵抗程度与全血细胞计数的相关性

目的探讨伴或不伴2型糖尿病(T2DM)的非酒精性脂肪性肝病(NAFLD)胰岛素抵抗(IR)程度与全血细胞计数各参数的相关性。方法选取糖耐量正常并除外糖尿病史的单纯NAFLD患者102例,T2DM合并NAFLD患者104例,正常对照104例为研究对象,测定空腹血糖(FPG)、空腹胰岛素(FINS)和全血细胞计数,分析胰岛素抵抗指数(HOMA-IR)与全血细胞计数各参数的相关性。结果 T2DM合并NAFLD患者IR及全血细胞计数异常程度较单纯NAFLD患者更重;相关性研究表明男性HOMA-IR与WBC、NEU、LYM、RBC、HGB、HCT呈正相关,女性HOMA-IR与WBC、NEU、LYM、MID、RBC、HGB、HCT呈正相关。结论 NAFLD时白细胞参数和红细胞参数的变化与IR密切相关,T2DM的存在加重了IR对上述血细胞参数的影响。全血细胞计数可以作为反映NAFLD患者IR程度的一种简单实用的检验指标。     

The association between renal function and structural parameters: a pig study

Background

The study examines differences regarding quality of life (QoL), mental health and illness beliefs between in-centre haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD/PD) patients. Differences are examined between patients who recently commenced treatment compared to patients on long term treatment.

Methods

144 End-Stage Renal Disease (ESRD) patients were recruited from three treatment units, of which 135 provided full data on the variables studied. Patients consisted of: a) 77 in-centre haemodialysis (HD) and 58 continuous ambulatory peritoneal dialysis (CAPD/PD) patients, all currently being treated by dialysis for varied length of time. Patients were compared for differences after being grouped into those who recently commenced treatment (< 4 years) and those on long term treatment (> 4 years). Next, cases were selected as to form two equivalent groups of HD and CAPD/PD patients in terms of length of treatment and sociodemographic variables. The groups consisted of: a) 41 in-centre haemodialysis (HD) and b) 48 continuous ambulatory peritoneal dialysis (CAPD/PD) patients, fitting the selection criteria of recent commencement of treatment and similar sociodemographic characteristics. Patient-reported assessments included: WHOQOL-BREF, GHQ-28 and the MHLC, which is a health locus of control inventory.

Results

Differences in mean scores were mainly observed in the HD patients with > 4 years of treatment, providing lower mean scores in the QoL domains of physical health, social relationships and environment, as well as in overall mental health. Differences in CAPD/PD groups, between those in early and those in later years of treatment, were not found to be large and significant. Concerning the analysis on equivalent groups derived from selection of cases, HD patients indicated significantly lower mean scores in the QoL domain of environment and higher scores in the GHQ-28 subscales of anxiety/insomnia and severe depression, indicating more symptoms in these areas of mental health. With regards to illness beliefs, HD patients who recently commenced treatment provided higher mean scores in the dimension of internal health locus of control, while CAPD/PD patients on long term treatment indicated higher mean scores in the dimension of chance. Regarding differences in health beliefs between equivalent groups of HD and CAPD/PD patients, HD patients focused more on the dimension of internal health locus of control.

Conclusion

The results provide evidence that patients in HD treatment modality, particularly those with many years of treatment, were experiencing a more compromised QoL in comparison to CAPD/PD patients.     

Pneumocystis pneumonia in HIV-1-infected patients

Pneumocystis pneumonia (PCP) is an opportunistic disease that mainly affects patients with a deficiency of cell-mediated immunity, especially acquired immunodeficiency syndrome (AIDS). The incidence of PCP in these patients has declined substantially owing to the widespread use of antiretroviral therapy and PCP prophylaxis. However, PCP is still a major AIDS-related opportunistic infection, particularly in patients with advanced immunosuppression in whom human immunodeficiency virus type 1 (HIV-1) infection remains undiagnosed or untreated. The clinical manifestations, diagnosis, treatment, and prevention of PCP in patients with HIV-1 infection are addressed in this review.     

Renal dysfunction in HIV-1-infected patients

Improved therapy directed against opportunistic infection and HIV-1 itself has resulted in greatly enhanced patient survival in the past decade among patients infected with HIV-1. Since patients are living longer, HIV-1 infection is associated with a rising burden of kidney disease. Approximately 14% of black patients and 6% of white patients dying with HIV-1 infection in 1999 in the United States had renal disease. Overall, 10% of patients dying with HIV-1 infection had renal failure. The most common glomerular diseases are focal segmental glomerulosclerosis and immune complex glomerulonephritis. Appropriate therapy for focal segmental glomerulosclerosis includes effective antiretroviral therapy and angiotensin antagonist medication. Drug toxicity is also common, often manifesting as electrolyte abnormalities, acute renal failure, interstitial nephritis, or nephrolithiasis. In particular, indinavir is associated with crystalluria, nephrolithiasis, interstitial nephritis, and lower urinary tract inflammation. Appropriate screening for renal disease and appropriate intervention will likely reduce the morbidity and mortality associated with progressive renal disease.     

No association between GB virus C infection and disease progression in HIV-2-infected patients from the French ANRS HIV-2 cohort

Out of 183 HIV-2-infected patients tested in the ANRS CO8 HIV-2 cohort, 69 were exposed to GB virus C (GBV-C), yielding a prevalence of 38% (95% CI 30.7, 45.2). There was no significant difference between the CD4 cell count and HIV-2-RNA plasma viral load in patients exposed and not exposed to GBV-C. After adjusting for age and CD4 cell count, co-infection with GBV-C was not associated with clinical progression (hazard ratio 0.78; 95% CI 0.24-2.56, 16 clinical events).     

Imbalance in cytokine production by whole blood related to presence of cytopathogenic HIV-1 strains in HIV-1-infected patients

Summary The possible association between the emergence of cytopathogenic HIV-1 variants and disturbance of the cytokine production in the course of HIV-1 infection was studied in 18 infected patients. The cytopathogenicity of the isolates was studied in a microassay based on the use of HIV-1-infectible Hela-CD4 cells carrying the bacterial LacZ gene under the control of the HIV-LTR (P4 cells). In addition, the production of cytokines by heparinized whole blood (HWB) obtained the same day from HIV-1(+) patients was measured. TNF-α was determined in a one-step procedure combining HWB culture in the presence of LPS+PHA for 24 h and detection of cytokines in the same wells. In separate experiments HWB was cultured in the presence of LPS+PHA for 48 h, then the supernatants were collected and stored until assayed by ELISA for IFN-γ and IL-4. Higher TNF-α levels were found in activated HWB of patients with cytopathic strains (n=9) than in patients with non-cytopathic strains (n=9, p=0.02) as assed with P4 cells. A defective production of type 1 cytokine (IFN-γ) and no increased secretion of type 2 cytokines (IL-4) was observed in patients with cytopathic strains. IFN-γ/IL-4 ratios were significantly lower in patients with cytopathic strains (n=9) than in other patients (n=9, p=0.009). The results show that the disarray of cytokine production, as assessed with whole blood culture, is associated with the cytopathogenicity of HIV-1 isolates in HIV-1-infected individuals.     

Alternatives to HIV-1 RNA concentration and CD4 count to predict mortality in HIV-1-infected children in resource-poor settings

Cheaper, simpler alternatives to CD4 lymphocyte count and HIV-1 RNA detection for assessing the prognosis of HIV-1 infection are needed for resource-poor settings. However, little is known about the predictive value of alternative assays, in particular in children. We assessed the prognostic value of total lymphocyte count, immune complex-dissociated p24 antigen, white blood cell count, packed-cell volume (haematocrit), and serum albumin for mortality in 376 HIV-1-infected, mainly African-American or Hispanic children enrolled during March, 1988 to January, 1991. In a Cox proportional hazards model, including all assay-alternatives to CD4 and RNA, total lymphocyte count (p<0.0001) and serum albumin (p=0.0107) independently predicted mortality. Further assessment of these markers is warranted in resource-poor settings.     

Automated screening for myelodysplastic syndromes through analysis of complete blood count and cell population data parameters

The diagnosis of myelodysplastic syndromes (MDS) requires a high clinical index of suspicion to prompt bone marrow studies as well as subjective assessment of dysplastic morphology. We sought to determine if data collected by automated hematology analyzers during complete blood count (CBC) analysis might help to identify MDS in a routine clinical setting. We collected CBC parameters (including those for research use only and cell population data) and demographic information in a large (>5,000), unselected sequential cohort of outpatients. The cohort was divided into independent training and test groups to develop and validate a random forest classifier that identifies MDS. The classifier effectively identified MDS and had a receiver operating characteristic area under the curve (AUC) of 0.942. Platelet distribution width and the standard deviation of red blood cell distribution width were the most discriminating variables within the classifier. Additionally, a similar classifier was validated with an additional, independent set of >200 patients from a second institution with an AUC of 0.93. This retrospective study demonstrates the feasibility of identifying MDS in an unselected outpatient population using data routinely collected during CBC analysis with a classifier that has been validated using two independent data sets from different institutions. Am. J. Hematol. 89:369–374, 2014. © 2013 Wiley Periodicals, Inc.