αKlotho decreases after reduced weight-bearing from both spaceflight and hindlimb unloading.

Alpha(α)Klotho, a soluble transmembrane protein, facilitates calcium-phosphorus homeostasis through feedback between bone and kidney and is a potential systemic biomarker for bone-kidney health during spaceflight. We determined if: (1) plasma αKlotho was reduced after both spaceflight aboard the ISS and hindlimb unloading (HU); and (2) deficiency could be reversed with exercise. Both spaceflight and HU lowered circulating plasma αKlotho: plasma αKlotho recovered with exercise after HU.

Drug-Induced Hypertension.

Untoward side effects of pharmaceuticals can result in considerable morbidity and expense to the health care system. There is likely a sizable fraction of the hypertensive population with disease either induced or exacerbated by polypharmacy. The elevation of blood pressure in drug-induced hypertension occurs through a variety of mechanisms, most notably, sodium and fluid retention, activation of the renin-angiotensin-aldosterone system, alteration of vascular tone, or a combination of these pathways. Recognition of common medications causing drug-induced hypertension is important to effectively control blood pressure. The epidemiology, pathophysiology, and management of these agents are discussed.

Association of HIV Suppression With Kidney Disease Progression Among HIV-Positive African Americans With Biopsy-Proven Classic FSGS.

BACKGROUND: In the era of combined antiretroviral therapy, classic focal segmental glomerulosclerosis (FSGS) is the most common histopathological finding in African American HIV-positive patients with kidney disease. We sought to determine whether HIV suppression is associated with lower risk of progression to end-stage renal disease (ESRD) among HIV-positive African Americans with biopsy-confirmed classic FSGS. METHODS: HIV-positive African Americans who underwent kidney biopsies at a single tertiary hospital between January 1996 and June 2011 were confirmed as having classic FSGS by the presence of segmental glomerulosclerosis without features of HIV-associated nephropathy. Multivariable Cox proportional hazards models were used to examine the independent association of viral suppression (HIV-RNA < 400 copies per milliliter at biopsy) with time to progression to ESRD. RESULTS: Of the 55 HIV-positive African Americans with classic FSGS, 26 had suppressed viral loads at the time of biopsy. Compared to viremic patients, those who were virally suppressed had a significantly higher mean CD4 cell count (452 vs. 260 cell/mm, respectively; P = 0.02) and median estimated glomerular filtration rate (53.5 vs 35.5 mL/min/1.73 m, respectively; P = 0.002). Adjusting for sex and baseline CD4 cell count, estimated glomerular filtration rate, and proteinuria, those with HIV-RNA levels <400 copies per milliliter at baseline had a 75% lower risk of progressing to ESRD (hazard ratio = 0.25; 95% CI: 0.07 to 0.88) during a median follow-up time of 2.70 years (interquartile range: 0.80-5.15 years). CONCLUSIONS: HIV suppression is associated with significantly lower risk of progression to ESRD among HIV-infected African Americans with classic FSGS, supporting the potential role of combined antiretroviral therapy for this histopathology in addition to HIV-associated nephropathy among HIV-positive individuals.

Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney Biopsy.

BACKGROUND AND OBJECTIVES: Prior studies have shown that the APOL1 risk alleles are associated with a greater risk of HIV-associated nephropathy and FSGS among blacks who are HIV positive. We sought to determine whether the APOL1 high-risk genotype incrementally improved the prediction of these underlying lesions beyond conventional clinical factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cross-sectional study, we analyzed data from 203 blacks who are HIV positive, underwent kidney biopsies between 1996 and 2011, and were genotyped for the APOL1 G1 and G2 alleles. Predictive logistic regression models with conventional clinical factors were compared with those that also included APOL1 genotype using receiver-operating curves and bootstrapping analyses with crossvalidation. RESULTS: The addition of APOL1 genotype to HIV-related risk factors for kidney disease in a predictive model improved the prediction of non-HIV-associated nephropathy FSGS, specifically, increasing the c statistic from 0.65 to 0.74 (P=0.04). Although two risk alleles were significantly associated with higher odds of HIV-associated nephropathy, APOL1 genotype did not add incrementally to the prediction of this specific histopathology. CONCLUSIONS: APOL1 genotype may provide additional diagnostic information to traditional clinical variables in predicting underlying FSGS spectrum lesions in blacks who are HIV positive. In contrast, although APOL1 risk genotype predicts HIV-associated nephropathy, it lacked a high c statistic sufficient for discrimination to eliminate the role of kidney biopsy in the clinical care of blacks who are HIV positive with nephrotic proteinuria or unexplained kidney disease.

Plasmacytoma presenting as missing rib on chest film: a case report and review of the literature.

A 33-year-old man presented to the emergency department (ED) with chief complaint of chest pain, persisting for approximately one year. Chest X-ray revealed he was missing the right posterior fifth rib. Physical examination showed no surgical scars, and he reported no history of chest trauma. A CT of his chest demonstrated a mass involving the posterior aspect of the right fifth rib, and subsequent biopsy revealed plasma cells. Laboratory results indicated the tumor was a solitary plasmacytoma of the rib. He was referred to oncology and treated with radiation therapy. This case report illustrates an unusual presentation of a solitary plasmacytoma of the rib.

Drug interactions and antiretroviral drug monitoring.

Owing to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS-related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors, which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs that are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals.

Comparison of risk factors and outcomes in HIV immune complex kidney disease and HIV-associated nephropathy.

BACKGROUND AND OBJECTIVES: HIV-associated nephropathy (HIVAN) is well described, but the clinical features of a group of renal pathologies characterized by Ig or immune complex depositions referred to as HIV-associated immune complex kidney disease (HIVICK) have not been well established. The objective of this study is to assess risk factors for HIVICK compared with contemporaneous control participants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A nested case-control study of 751 HIV-infected patients followed from January 1996 to June 2010 was conducted. Groups were compared using the chi-squared test or rank-sum analysis. Conditional logistic regression was used to estimate odds ratios (ORs) for HIVICK. Incidences of overall ESRD and with/without combined antiretroviral therapy (cART) exposure were calculated. RESULTS: HIVICK patients were predominantly African American (92%). Compared with matched controls, patients with HIVICK were more likely to have HIV RNA >400 copies/ml (OR, 2.5; 95% confidence interval [95% CI], 1.2 to 5.2), diabetes (OR, 2.8; 95% CI, 1.1 to 6.8), and hypertension (OR, 2.3; 95% CI, 1.2 to 4.5). Compared with HIVAN, patients with HIVICK had more antiretroviral therapy exposure, lower HIV viral loads, and higher CD4 and estimated GFR. ESRD was less common in the HIVICK versus the HIVAN group (30% versus 82%; P<0.001), and the use of cART was not associated with ESRD in HIVICK patients (25% versus 26; P=0.39). CONCLUSIONS: HIVICK was predominantly observed in African-American patients and associated with advanced HIV disease. ESRD incidence is lower in HIVICK patients compared with those with HIVAN. Unlike HIVAN, cART use was not associated with the incidence of ESRD in HIVICK.

HIV-associated nephropathy patients with and without apolipoprotein L1 gene variants have similar clinical and pathological characteristics.

Recently, an association was found between nondiabetic kidney disease in African Americans and two independent sequence variants in the APOL1 gene, encoding apolipoprotein L1. In this study we determined the frequency of APOL1 risk variants in patients with biopsy-proven HIV-associated nephropathy (HIVAN) and distinctive pathological characteristics potentially driven by those risk variants. Among 76 patients with HIVAN, 60 were successfully genotyped for APOL1 G1 and G2 polymorphisms. In this cohort, 37 had two risk alleles, 18 were heterozygous, and 5 had neither risk variant. There were no differences in the pathological findings of HIVAN and the number of APOL1 risk alleles. Further, the progression to end-stage kidney disease or death did not differ by the number of risk alleles. Median renal survival was 9.3 months in patients with zero or one risk allele compared to 11.7 months in patients with two APOL1 risk alleles. Thus, our study suggests that although the majority of African-American patients with HIVAN have two APOL1 risk alleles other as yet unknown factors in the host, including genetic risk variants and environmental or viral factors, may influence the development of this disorder in those with zero or one APOL1 risk allele.

False-negative hepatitis B virus (HBV) surface antigen in a vaccinated dialysis patient with a high level of HBV DNA in the United States.

Screening with hepatitis B surface antigen (HBsAg) is highly recommended for at-risk individuals. Mutations in the HBsAg can result in an inability to detect the virus during routine screening. We describe a hemodialysis patient found to have high levels of hepatitis B virus (HBV) DNA and HBV antibody but negative HBsAg on two routine assays.