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1.  HIV Viremia and T-Cell Activation Differentially Affect the Performance of Glomerular Filtration Rate Equations Based on Creatinine and Cystatin C 
PLoS ONE  2013;8(12):e82028.
Background
Serum creatinine and cystatin C are used as markers of glomerular filtration rate (GFR). The performance of these GFR markers relative to exogenously measured GFR (mGFR) in HIV-positive individuals is not well established.
Methods
We assessed the performance of the chronic kidney disease epidemiology collaboration equations based on serum concentrations of creatinine (eGFRcr), cystatin C (eGFRcys) and both biomarkers combined (eGFRcr-cys) in 187 HIV-positive and 98 HIV-negative participants. Measured GFR was calculated by plasma iohexol clearance. Bias and accuracy were defined as the difference between eGFR and mGFR and the percentage of eGFR observations within 30% of mGFR, respectively. Activated CD4 and CD8 T-cells (CD38+ HLA-DR+) were measured by flow cytometry.
Results
The median mGFR was >100 ml/min/1.73 m2 in both groups. All equations tended to be less accurate in HIV-positive than in HIV-negative subjects, with eGFRcr-cys being the most accurate overall. In the HIV-positive group, eGFRcys was significantly less accurate and more biased than eGFRcr and eGFRcr_cys. Additionally eGFRcys bias and accuracy were strongly associated with use of antiretroviral therapy, HIV RNA suppression, and percentages of activated CD4 or CD8 T-cells. Hepatitis C seropositivity was associated with larger eGFRcys bias in both HIV-positive and HIV-negative groups. In contrast, eGFRcr accuracy and bias were not associated with HIV-related factors, T-cell activation, or hepatitis C.
Conclusions
The performance of eGFRcys relative to mGFR was strongly correlated with HIV treatment factors and markers of T-cell activation, which may limit its usefulness as a GFR marker in this population.
doi:10.1371/journal.pone.0082028
PMCID: PMC3871673  PMID: 24376511
2.  Lenalidomide-Induced Acute Interstitial Nephritis 
The Oncologist  2010;15(9):961-964.
The first case of biopsy-proven lenalidomide-induced acute interstitial nephritis is presented.
doi:10.1634/theoncologist.2010-0070
PMCID: PMC3228035  PMID: 20709889
Kidney failure; Acute; Lenalidomide; Multiple myeloma
3.  Blood Pressure Excursions Below the Cerebral Autoregulation Threshold During Cardiac Surgery Are Associated With Acute Kidney Injury 
Critical care medicine  2013;41(2):464-471.
Objectives
To determine whether mean arterial blood pressure (MAP) excursions below the lower limit of cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB) are associated with acute kidney injury (AKI) after surgery.
Setting
Tertiary care medical center.
Patients
Four hundred ten patients undergoing cardiac surgery with CPB.
Design
Prospective observational study.
Interventions
None.
Measurements and Main Results
Autoregulation was monitored during CPB by calculating a continuous, moving Pearson’s correlation coefficient between MAP and processed near-infrared spectroscopy signals to generate the variable cerebral oximetry index (COx). When MAP is below the lower limit of autoregulation, COx approaches 1, because CBF is pressure passive. An identifiable lower limit of autoregulation was ascertained in 348 patients. Based on the RIFLE criteria, AKI developed within 7 days of surgery in 121 (34.8%) of these patients. Although the average MAP during CPB did not differ, the MAP at the limit of autoregulation and the duration and degree to which MAP was below the autoregulation threshold (mmHg × min/hr of CPB) were both higher in patients with AKI than in those without AKI. Excursions of MAP below the lower limit of autoregulation (relative risk, 1.02, 95% confidence interval, 1.01 to 1.03, p<0.0001) and diabetes (relative risk, 1.78, 95% confidence interval, 1.27 to 2.50, p=0.001) were independently associated with for AKI.
Conclusions
Excursions of MAP below the limit of autoregulation and not absolute MAP are independently associated with for AKI. Monitoring COx may provide a novel method for precisely guiding MAP targets during CPB.
doi:10.1097/CCM.0b013e31826ab3a1
PMCID: PMC3769417  PMID: 23263580
Cerebral autoregulation; blood pressure; cardiac surgery; acute kidney injury
4.  Vitamin D Deficiency and Persistent Proteinuria among HIV-infected and –uninfected Injection Drug Users 
AIDS (London, England)  2012;26(3):295-302.
Objective
Proteinuria occurs commonly among HIV-infected and -uninfected injection drug users (IDUs) and is associated with increased mortality risk. Vitamin D deficiency, highly prevalent among IDUs and potentially modifiable, may contribute to proteinuria. To determine whether vitamin D is associated with proteinuria in this population, we conducted a cross-sectional study in the AIDS Linked to the IntraVenous Experience (ALIVE) Study.
Methods
25(OH)-vitamin D levels were measured in 268 HIV-infected and 614 HIV-uninfected participants. The association between vitamin D deficiency (<10 ng/mL) and urinary protein excretion was evaluated by linear regression. The odds of persistent proteinuria (urine protein-to-creatinine ratio >200 mg/g on two occasions) associated with vitamin D deficiency was examined using logistic regression.
Results
One-third of participants were vitamin D-deficient. Vitamin D deficiency was independently associated with higher urinary protein excretion (P<0.05) among HIV-infected and diabetic IDUs (P-interaction<0.05 for all). Persistent proteinuria occurred in 18% of participants. Vitamin D deficiency was associated with >6-fold odds of persistent proteinuria among diabetic IDUs (odds ratio [OR]=6.29, 95% confidence interval [CI]: 1.54, 25.69) independent of sociodemographic characteristics, co-morbid conditions, body mass index, and impaired kidney function (estimated GFR <60 mL/min|1.73 m2); no association, however, was observed among non-diabetic IDUs (OR=1.06, 95% CI: 0.64, 1.76) (P-interaction<0.05).
Conclusions
Vitamin D deficiency was associated with higher urinary protein excretion among those with HIV infection and diabetes. Vitamin D deficiency was independently associated with persistent proteinuria among diabetic IDUs, although not in non-diabetic persons. Whether vitamin D repletion ameliorates proteinuria in these patients requires further study.
doi:10.1097/QAD.0b013e32834f33a2
PMCID: PMC3766727  PMID: 22156964
Vitamin D deficiency; proteinuria; HIV; injection drug use; diabetes
5.  HIV-associated nephropathy patients with and without apolipoprotein L1 gene variants have similar clinical and pathologic characteristics 
Kidney international  2012;82(3):338-343.
Recently, an association was found between non-diabetic 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 none 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 none or one APOL1 risk allele.
doi:10.1038/ki.2012.111
PMCID: PMC3463138  PMID: 22495294
6.  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.
doi:10.1128/CVI.05696-11
PMCID: PMC3346338  PMID: 22441395
7.  Recent developments in HIV-related kidney disease 
HIV therapy  2010;4(5):589-603.
Although kidney disease has been a recognized complication of HIV infection since the beginning of the HIV epidemic, its epidemiology, underlying causes and treatment have evolved in developed countries where HAART has been widely available. HIV-associated nephropathy and HIV immune complex-mediated kidney disease were the prominent renal diagnoses in the earlier period of the HIV epidemic. While HIV immune complex-mediated kidney disease remains a common finding among HIV-infected individuals with kidney disease, the incidence of HIV-associated nephropathy has been diminishing in developed countries. The role of the metabolic effects of long-term HAART exposure and nephrotoxicity of certain antiretroviral medications on the development and progression of chronic kidney disease is now of increasing concern. The long-term clinical implications of acute kidney injury among HIV-infected persons are increasingly recognized. Kidney disease in HIV-infected persons continues to be a major risk factor for morbidity and mortality in this patient population; therefore, early recognition and treatment of kidney disease are imperative in lessening the impact of kidney disease on the health of HIV-infected individuals. This review focuses on recent developments and ongoing challenges in the understanding, diagnosis and management of HIV-related kidney disease.
doi:10.2217/hiv.10.42
PMCID: PMC3038636  PMID: 21331321
glomerular filtration rate; HIV; HIVAN; kidney disease; serum creatinine; tenofovir
8.  A prospective study of protein excretion using short-interval timed urine collections in patients with lupus nephritis 
Kidney international  2009;76(12):1284-1288.
The 24-h urine protein-to-creatinine ratio is the gold standard in evaluating proteinuria in lupus nephritis; however, the urine collection is inconvenient to the patient. Random spot urine protein-to-creatinine ratios, although convenient, have poor agreement with the 24-h ratios in these patients. Here, we sought to define a timed collection interval providing accurate and precise data and patient convenience. Urine from 41 patients, in 2 medical centers, with biopsy-proven lupus nephritis was collected at 6-h intervals for 24 h. The protein-to-creatinine ratio of each short collection was then compared with that of a 24-h collection made by combining the 6-h samples. A first morning void and spot urine samples were collected before and after the 24-h collection, respectively. There was significant diurnal variation with peak proteinuria at 6–12 h and nadir at 18–24 h. Each 6-h collection showed excellent correlation and concordance with the 24-h protein-to-creatinine ratio, but the 12–24-h interval had the best agreement. In contrast to the random spot urines, the first morning void also had excellent correlation and concordance, but underestimated the 24-h protein-to-creatinine ratio. Our study shows that a 12-h overnight urine collection is the best surrogate, with excellent agreement with the 24-h protein-to-creatinine ratio, and it is convenient for patients. There was little variability between centers, an important feature for clinical trials.
doi:10.1038/ki.2009.344
PMCID: PMC3093656  PMID: 19759526
glomerulonephritis; lupus nephritis; nephritis; proteinuria systemic lupus erythematosus
9.  Kidney Function and the Risk of Cardiovascular Events in HIV-1 Infected Patients 
AIDS (London, England)  2010;24(3):387-394.
Objective:
Cardiovascular events are a significant cause of mortality in HIV/AIDS patients. The objective is to determine the correlation between kidney function and the risk of cardiovascular events in the HIV-infected population.
Design:
Nested, matched, case-control study design was employed.
Methods:
We performed a single-center study of 315 HIV-infected patients (63 cases who had cardiovascular events and 252 controls). Estimated glomerular filtration rate (eGFR), calculated by the CKD-EPI and the MDRD equation, and proteinuria were the primary exposures of interest.
Results:
Mean eGFR was significantly lower in the cases compared to controls (68·4 vs. 103·2 ml/min/1·73m2, p<0·001 by CKD-Epi and 69·0 vs. 103·1 ml/min/1·73m2, p<0·001 by MDRD). In univariate analysis, an eGFR of <60 ml/min/1·73m2 was associated with a 15·9 fold increased odds of a cardiovascular event compared to an eGFR ≥ 60 ml/min/1·73m2 (p<0·001). In multivariate analysis, a 10 ml/min/1·73m2 decrease in eGFR was associated with a 20% increased odds of a cardiovascular event (odds ratio 1·2, 95% CI 1·1–1·4). The prevalence of proteinuria in the cases was approximately twice that of controls (51% vs. 25%, p<0·001). Proteinuria was associated with cardiovascular events both in univariate and multivariate analyses (OR of 3·6, 95% CI 1·9–7·0 and 2·2, 95% CI 1·1–4·8 respectively). Traditional cardiovascular risk factors like history of previous cardiovascular events, diabetes mellitus, and dyslipidemia along with low CD4 counts were also found as significant predictors of risk of cardiovascular events.
Conclusion:
Our study shows a significant independent association between decreased kidney function and increased risk of CVE in HIV-1-infected patients.
doi:10.1097/QAD.0b013e3283359253
PMCID: PMC2877370  PMID: 20019575
HIV-1 infections; Myocardial Infarction; Cerebrovascular accident (Stroke); Glomerular Filtration Rate; Proteinuria
10.  Screening for Chronic Kidney Disease in HIV-Infected Patients 
With improved survival afforded by highly-active antiretroviral therapy (HAART), CKD has emerged as one of the primary comorbid conditions affecting human immunodeficiency virus (HIV)-infected individuals. Although CKD in HIV-infected individuals is classically thought of as a consequence of advanced HIV infection such as in the case of HIV-associated nephropathy (HIVAN), several factors likely contribute to the development CKD in HIV infection. These factors include genetic predisposition, age-related decline in kidney function, HAART-related metabolic changes, exposure to multiple nephrotoxic medications, and concurrent conditions such as hepatitis C or illicit drug use. Similar to the general population, proteinuria and impaired kidney function are associated with faster progression to acquired immune deficiency syndrome (AIDS) and death. Given the prevalence and impact of kidney disease on the course of HIV infection and its management, current guidelines recommend screening all HIV-infected individuals for kidney disease. This review focuses on the current guidelines for kidney disease screening and discusses traditional as well as promising strategies for detecting CKD in this vulnerable population.
doi:10.1053/j.ackd.2009.07.014
PMCID: PMC2818858  PMID: 20005486
HIV infection; proteinuria; estimated GFR; MDRD equation; cystatin C
11.  Decreased Kidney Function in a Community-based Cohort of HIV-Infected and HIV-Negative Individuals in Rakai, Uganda 
Background
High prevalences of reduced glomerular filtration rate (GFR) have been reported from HIV-infected individuals in sub-Saharan Africa when initiating antiretroviral therapy. However little is known about natural history HIV-related kidney disease or about background rates of reduced GFR in HIV-negative individuals in this region.
Methods
We estimated GFR from first and last available stored serum samples from 1202 HIV-infected and 664 age-matched and sex-matched HIV-negative individuals in a community-based cohort of HIV-infected and HIV-negative individuals in Rakai, Uganda, between 1994 and 2003. We assessed the prevalence and incidence of mildly (60–89 ml·min−1·1.73 m−2) and moderately (<60 ml·min−1 · 1.73 m−2) reduced GFR using standard analytical methods.
Results
At baseline, 8.4% of HIV-infected and 4.7% of HIV-negative individuals had mildly or moderately reduced GFR (P = 0.002). During follow-up, the rates of decline to a lower GFR category were of 32.4 and 20.3 per 1000 person-years in HIV-infected and HIV-negative subjects, respectively (P = 0.019).
Conclusions
In an unselected community sample of HIV-infected individuals followed in Rakai, Uganda, before the availability of antiretroviral therapy, the prevalence of decreased GFR and the incidence of a decline in GFR category during follow-up were both significantly higher in HIV-infected subjects compared with HIV-negative subjects, although moderately reduced GFR was uncommon.
doi:10.1097/QAI.0b013e3181e8d5a8
PMCID: PMC2974780  PMID: 20613548
Africa; chronic kidney disease; cohort study; HIV infection; Uganda
12.  Chronic Kidney Disease Incidence, and Progression to End-Stage Renal Disease, in HIV-Infected Individuals: A Tale of Two Races 
The Journal of infectious diseases  2008;197(11):1548-1557.
Background
Little is known about the racial differences in the incidence and progression of HIV-related chronic kidney disease (CKD) that underlie African American–white disparities in HIV-related end-stage renal disease (ESRD).
Methods
In a cohort in Baltimore, Maryland, we measured CKD incidence, glomerular filtration rate (GFR) slope, and progression to ESRD in 3332 African American and 927 white HIV-infected subjects.
Results
A total of 284 subjects developed CKD, 100 (35%) of whom subsequently developed ESRD. African American subjects were at slightly increased risk for incident CKD, compared with white subjects (hazard ratio [HR], 1.9 [95% confidence interval {CI}, 1.2–2.8]). However, once CKD had commenced, the African American subjects developed ESRD markedly faster than did the white subjects (HR, 17.7 [95% CI, 2.5–127.0]), and, correspondingly, their GFR decline after diagnosis of CKD was 6-fold more rapid (P < .001). In the subset of African American subjects for whom kidney-biopsy data were available, progression to ESRD was significantly faster than that in white subjects with CKD, irrespective of the presence of HIV-associated nephropathy.
Conclusions
The results of this study suggest that African American–white disparities in HIV-related ESRD are explained predominantly by a more aggressive natural disease history in African Americans and less by racial differences in CKD incidence.
doi:10.1086/587994
PMCID: PMC2553209  PMID: 18422458

Results 1-12 (12)