Hepatitis: Szczech LA

Kalim S, Szczech LA, Wyatt CM. · Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. · Semin Nephrol. · Pubmed #19013326 No free full text.

Abstract: Acute kidney injury is common in human immunodeficiency virus (HIV)-infected patients, and has been associated with increased morbidity and mortality. Before the introduction of effective antiretroviral therapy, acute kidney injury in HIV-positive patients was most commonly the result of volume depletion, septicemia, or nephrotoxic medications. Acute kidney injury remains a significant problem in the antiretroviral era, and still commonly is attributed to infection or nephrotoxic medications. Less common causes such as direct infectious insults, immune restoration inflammatory syndrome, rhabdomyolysis, and obstruction should be considered when the underlying process is not obvious. In addition to advanced HIV disease, several other patient characteristics have emerged as potential risk factors for acute kidney injury in the antiretroviral era, including older age, diabetes, pre-existing chronic kidney disease, and hepatitis co-infection or liver disease.

Odden MC, Scherzer R, Bacchetti P, Szczech LA, Sidney S, Grunfeld C, Shlipak MG. · Department of Medicine, San FranciscoVeterans Affairs Medical Center 4150 Clement Street, San Francisco, CA 94121, USA. · Arch Intern Med. · Pubmed #17998494 links to  free full text

Abstract: BACKGROUND: Although studies have reported a high prevalence of end-stage renal disease in human immunodeficiency virus (HIV)-infected individuals, little is known about moderate impairments in kidney function. Cystatin C measurement may be more sensitive than creatinine for detecting impaired kidney function in persons with HIV. METHODS: We evaluated kidney function in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) cohort, a representative sample of 1008 HIV-infected persons and 290 controls from the Coronary Artery Risk Development in Young Adults (CARDIA) study in the United States. RESULTS: Cystatin C level was elevated in HIV-infected individuals; the mean +/- SD cystatin C level was 0.92 +/- 0.22 mg/L in those infected with HIV and 0.76 +/- 0.15 mg/L in controls (P < .001). In contrast, both mean creatinine levels and estimated glomerular filtration rates appeared similar in HIV-infected individuals and controls (0.87 +/- 0.21 vs 0.85 +/- 0.19 mg/dL [to convert to micromoles per liter, multiply by 88.4] [P = .35] and 110 +/- 26 vs 106 +/- 23 mL/min/1.73 m(2) [P = .06], respectively). Persons with HIV infection were more likely to have a cystatin C level greater than 1.0 mg/L (OR, 9.8; 95% confidence interval, 4.4-22.0 [P <.001]), a threshold demonstrated to be associated with increased risk for death and cardiovascular and kidney disease. Among participants with HIV, potentially modifiable risk factors for kidney disease, hypertension, and low high-density lipoprotein concentration were associated with a higher cystatin C level, as were lower CD4 lymphocyte count and coinfection with hepatitis C virus (all P < .001). CONCLUSIONS: Individuals infected with HIV had substantially worse kidney function when measured by cystatin C level compared with HIV-negative controls, whereas mean creatinine levels and estimated glomerular filtration rates were similar. Cystatin C measurement could be a useful clinical tool to identify HIV-infected persons at increased risk for kidney and cardiovascular disease.

Franceschini N, Napravnik S, Finn WF, Szczech LA, Eron JJ. · Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC 27514, USA. · J Acquir Immune Defic Syndr. · Pubmed #16639352 No free full text.

Abstract: BACKGROUND: Low CD4 cell counts predict HIV-related morbidity and mortality and may be associated with acute renal failure (ARF). OBJECTIVE: To estimate the effect of CD4 cell count on the incidence rate (IR) of ARF in ambulatory HIV-infected patients with access to highly active antiretroviral therapy. METHODS: Observational clinical cohort of HIV-infected patients recruited from a university-based infectious diseases clinic, between 2000 and 2002, and followed up until December 31, 2002. Poisson log-linear regression models were used to calculate ARF IRs, IR differences, and IR ratios. RESULTS: The mean age of the 705 study participants was 40 years, two thirds were male, and 61% were African American. Incidence rates of ARF were higher at lower CD4 cell counts and among patients who were coinfected with hepatitis C. Patients with hepatitis C coinfection who also had low CD4 cell counts had the highest adjusted IR of ARF. CONCLUSION: Immunosuppression and hepatitis C virus coinfection are associated with increased IRs of ARF in ambulatory HIV-1-infected patients.

Franceschini N, Napravnik S, Eron JJ, Szczech LA, Finn WF. · Division of Nephrology and Hypertension, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA. · Kidney Int. · Pubmed #15780107 No free full text.

Abstract: BACKGROUND: Acute renal failure (ARF) is a cause of renal dysfunction in human immunodeficiency virus (HIV)-infected patients. Its incidence and causes have not been studied since the introduction of highly active antiretroviral therapy (HAART) in HIV ambulatory patients. METHODS: This is a prospective cohort study of 754 HIV patients, 18 years or older, seen at a university-based infectious disease clinic between 2000 and 2002. ARF was identified using proportional increases in serum creatinine from baseline and by chart review. Clinical conditions were assessed at the time of the ARF event. ARF incidence rates (IR) were calculated by dividing the number of events by person time at risk. To compare patients with and without ARF, t test or chi-square test were used. RESULTS: Patient's mean age was 40 years; 68% were male and 61% were black. One hundred-eleven ARF events occurred in 71 subjects (IR 5.9 per 100 person-years; 95% CI 4.9, 7.1). ARF was more common in men, in those with CD4 cell count <200 cells/mm(3), and HIV RNA levels >10,000 copies/mL. These patients more often had acquired immunodeficiency syndrome (AIDS), hepatitis C infection (HCV), and have received HAART. ARF was mainly community-acquired, due to prerenal causes or acute tubular necrosis, and associated with opportunistic infections and drugs. Liver disease was a cause of ARF in HCV-infected patients. CONCLUSION: ARF is common in ambulatory HIV patients. Immunosuppression, infection, and HCV are important conditions associated with ARF in the post-HAART era.

Szczech LA, Gupta SK, Habash R, Guasch A, Kalayjian R, Appel R, Fields TA, Svetkey LP, Flanagan KH, Klotman PE, Winston JA. · Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. · Kidney Int. · Pubmed #15327410 No free full text.

Abstract: BACKGROUND: While an understanding of the epidemiology and clinical course of HIV-associated nephropathy (HIVAN) is growing, little is known about the risk factors and clinical course of the other renal diseases that may also occur as a complication of HIV infection. This study was undertaken to compare HIVAN to the spectrum of other kidney diseases seen among HIV-infected patients. METHODS: This retrospective cohort study included all HIV-infected patients who underwent renal biopsy during the course of their clinical care at six major medical centers. Demographic and clinical information were abstracted from each patient's clinical record. Time to initiation of renal replacement therapy was compared for patients with lesions other than HIVAN to patients with HIVAN using Cox proportional hazards regression. RESULTS: Eighty-nine patients (47 with lesions other than HIVAN and 42 with HIVAN) were available for inclusion. Patients with lesions other than HIVAN were less likely to be black (37/47 vs. 42/42, P= 0.02), more likely to have a positive hepatitis B surface antigen (10/37 vs. 4/42, P= 0.04), less likely to have the diagnosis of hypertension (24/46 vs. 31/42, P= 0.03), more likely to have a greater creatinine clearance at time of biopsy (60.6 vs. 39.0 cc/min, P= 0.008), and have a greater CD4 lymphocyte count at time of biopsy (287 vs. 187 cells/mL, P= 0.04) compared to patients with HIVAN. Lesions other than HIVAN were associated with a longer time to initiation of renal replacement therapy compared with HIVAN (HR 0.33, 95% CI 0.15-0.71, P= 0.005). Other factors associated with a longer time to renal replacement therapy included higher creatinine clearance at time of biopsy, greater CD4(+) lymphocyte count, the absence of hepatitis C antibody, and the use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The type of renal disease (HIVAN vs. other) interacted significantly with HIV-1 RNA level and the use of antiretroviral therapy (P= 0.0001 and 0.006, respectively). Among patients with lesions other than HIVAN, the presence of nondetectable HIV-1 RNA was not associated with a greater risk of progression of renal disease (HR 0.27, P= 0.24). Among patients with HIVAN, because all patients had detectable virus at the time of institution of renal replacement therapy, this highly significant association could not be quantified. Among patients with lesions other than HIVAN, the use of antiretroviral therapy was not associated with the progression to renal replacement therapy (HR 3.29, P= 0.06). Among patients with HIVAN, the use of antiretroviral therapy was associated with a slower progression to renal replacement therapy (HR 0.24, P= 0.03). CONCLUSION: Among HIV-infected patients with renal disease other than HIVAN, viral suppression and the use of antiretroviral therapy are not associated with a beneficial effect on renal function; thus, additional therapeutic strategies may need to be utilized. Because renal histology is associated with prognostic differences, these data provide outcomes information that will improve the clinical utility of renal biopsy among HIV-infected patients with renal disease.

Gardner LI, Klein RS, Szczech LA, Phelps RM, Tashima K, Rompalo AM, Schuman P, Sadek RF, Tong TC, Greenberg A, Holmberg SD, Anonymous00065. · Centers for Disease Control, Mailstop E-45, Division of HIV/AIDS, 1600 Clifton Road, NE, Atlanta, GA 30333, USA. · J Acquir Immune Defic Syndr. · Pubmed #14600579 No free full text.

Abstract: BACKGROUND: The rates and risk factors for overall and medical condition-specific hospitalizations in HIV-positive women have not been examined in detail or compared with rates in risk factor-matched HIV-negative women. OBJECTIVE: To determine the rates and risk factors for overall and condition-specific hospitalizations. METHODS: Prospective cohort study of 885 HIV-positive women and 425 HIV-negative women followed for semiannual research visits between 1993 and 2000 in 4 urban locations in the United States. Outcome measures were hospitalization diagnoses with diabetes mellitus, nonacute renal conditions, cardiovascular conditions, liver conditions, AIDS defining conditions, and overall hospitalizations. Clinical and laboratory risk factors were assessed at research visits every 6 months, and effects of risk factors on hospitalization rates were calculated using generalized estimating equations and Poisson regression. RESULTS: Renal laboratory abnormalities, hypertension, and clinical AIDS were each associated with 3 of the 5 condition-specific hospitalization rates. Over time, diabetes-, nonacute renal-, and cardiovascular-related rates were flat or slightly increased and liver-related rates were significantly increased in HIV-positive women. Hospitalization rates with an AIDS-defining condition declined sharply in the latter half of the study period. CONCLUSIONS: In this population of largely African-American, inner-city, HIV-infected women, renal abnormalities, hypertension, and hepatitis C virus infection were common. Rate ratios indicated that "non-AIDS" risk factors were important predictors of hospitalization. In the highly active antiretroviral therapy era, clinicians must pay attention to these risk factors for morbidity and should closely monitor renal abnormalities, hypertension, and hepatitis status.

Szczech LA, Kalayjian R, Rodriguez R, Gupta S, Coladonato J, Winston J, Anonymous00220. · Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. · Kidney Int. · Pubmed #12753321 No free full text.

Abstract: BACKGROUND: Human immunodeficiency virus (HIV)-related renal disease is the third leading cause of end-stage renal disease (ESRD) among African Americans aged 24 to 60 years. This study describes the clinical characteristics and antiretroviral dosing patterns of HIV-infected patients receiving dialysis to define the clinical needs of this growing population. METHODS: Demographic and clinical information was collected on all HIV-infected patients incident to dialysis after January 1, 1998 until January 1, 2001 at five medical centers. The cohort was described overall and by subgroups based on hepatitis status, CD4 lymphocyte count, and use of antiretroviral therapy. Continuous and categoric variables were compared using either the Wilcoxon rank sum or Student t test and Fisher's exact or chi-square tests, as appropriate. RESULTS: A total of 89 patients were included, 55 of whom were alive at the time of data collection. The mean age was 44.6 years (range, 22.7 to 66.9 years), 74.2% were male, and 83.2% patients were African Americans. While only 45.9% of patients undergoing renal biopsy were diagnosed with HIV-associated nephropathy (HIVAN), the majority of patients who had not undergone biopsy carried the clinical diagnosis of HIVAN (69.8%, P = 0.03). Of the cohort, 19.7% tested hepatitis B surface antigen positive, and 67.1% had reactive antibody tests for hepatitis C. Patients with hepatitis C were more likely to have experienced intravenous drug use as a risk behavior for HIV acquisition (OR 8.2; 95% CI 2.39, 27.9; P = 0.001] and to be older (OR 1.1 per year of age; 95% CI 1.02, 1.2; P = 0.01). A total of 60.7% of patients were receiving antiretroviral medication at last follow-up. Among patients alive and receiving antiretroviral medications at the time of data collection, absolute CD4+ count rose (268 vs. 339 cells/mL, P = 0.03), while among patients alive, but not receiving antiretroviral medications, absolute CD4+ count did not change (389 vs. 392 cells/mL, P = 0.11) during similar periods of follow-up. No difference was seen between initial and current HIV RNA levels for either group. Among patients receiving antiretroviral medications, there were significant variations in dosing regimens. The greatest variation was seen in the prescribing patterns of lamivudine with a 12-fold difference among patients. CONCLUSION: The projected growth of the HIV-infected ESRD population requires a better understanding of the clinical needs of this population. The high prevalence of coinfection with hepatitis C as well as the wide variations in dosing patterns for antiretroviral medications are areas that require further investigation to minimize morbidity and mortality among this group.

Szczech LA, Gange SJ, van der Horst C, Bartlett JA, Young M, Cohen MH, Anastos K, Klassen PS, Svetkey LP. · Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. · Kidney Int. · Pubmed #11786101 links to  free full text

Abstract: BACKGROUND: Glomerular disease with proteinuria and renal failure are complications of human immunodeficiency virus (HIV) infection. While studies suggest risk factors for both include black race and lower CD4 lymphocyte count, they have not been established in population-based cohorts. This study examines the risk factors for proteinuria and renal failure in a large cohort of HIV-infected women not selected for the presence of renal disease. METHODS: This prospective cohort includes 2059 women enrolled in the Women's Interagency HIV study (WIHS). WIHS is a longitudinal study of the clinical course of HIV infection in which subjects are followed biannually with a detailed exam including urine analysis, serum creatinine, CD4 lymphocyte count, and HIV RNA level. Proteinuria was defined as > or =+1 on urine dipstick exam on at least two consecutive urine analyses, and renal failure was defined as a doubling of serum creatinine. Multivariable logistic regression was used to estimate the associations between clinical variables and the presence of proteinuria on initial evaluation in a cross-sectional analysis. Cox proportional hazards regression was used to estimate the associations between clinical variables and time to renal failure among study participants with proteinuria in a prospective longitudinal analysis. RESULTS: Of 2057 HIV-positive women, 32% (N=671) had proteinuria on initial evaluation. Predictors of proteinuria include increasing (log) HIV RNA level [odds ratio (OR)=1.05], black race (OR=2.0), absolute CD4 lymphocyte count < or =200 cells/mm3 (OR=1.41), and the presence of hepatitis C antibody (OR=1.27; all P < 0.0001). Absolute CD4 lymphocyte count < or =200 cells/mm3 [hazard ratio (HR)=3.57, P=0.001], detectable HIV RNA level (HR=2.33, P=0.02), increasing systolic blood pressure (HR=1.02, P=0.002), and decreasing albumin (HR=3.33, P=0.0001) and increasing creatinine (1.67, P=0.0001) were all associated with the development of renal failure. CONCLUSIONS: This analysis establishes the associations between both increasing HIV RNA level and decreasing CD4 lymphocyte count with the presence of proteinuria and occurrence of renal failure. Additionally, it demonstrates an association between proteinuria and a positive hepatitis C antibody. To lessen the presence and progression of renal disease among HIV-infected patients, future research should focus on suppression of the HIV RNA level and improvement in CD4 lymphocyte count.