Biomedical subjects

Lynda Anne Szczech

Publications and source records attributed to Lynda Anne Szczech.

At least 19 recordsLinked to original sources

PubMed2006

The uncertain significance of anti-glomerular basement membrane antibody among HIV-infected persons with kidney disease.

Glomerular lesions that complicate patients with human immunodeficiency virus (HIV) infection include HIV-associated nephropathy, membranous glomerulopathy, and immune-complex glomerulonephritides. This case series presents 3 patients with clinically significant renal disease and positive test results for anti-glomerular basement membrane (anti-GBM) antigen. Characteristic histological findings that would suggest anti-GBM antibodies have a significant role in the pathological state of each patient's kidney disease were absent. In addition, each patient recovered without specific treatment for anti-GBM disease. This case series suggests that anti-GBM antibodies likely are related to the B-cell expansion previously described in patients with HIV infection. We propose that clinicians interpret results of anti-GBM antibody tests carefully for patients with HIV infection, considering biopsy before empiric therapy, particularly in a clinical presentation that is atypical for Goodpasture disease.

AIDS-Associated Nephropathy↗

PubMed2005

Intradialytic blood volume monitoring in ambulatory hemodialysis patients: a randomized trial.

Complications related to inadequate volume management are common during hemodialysis. This trial tested the hypothesis that availability of an intradialytic blood volume monitoring (IBVM) device improves fluid removal, reducing morbidity. A six-center, randomized trial with 6 mo of intervention comparing IBVM using Crit-Line versus conventional clinical monitoring was conducted. The average rate of non-access-related hospitalizations was compared across treatment groups using Poisson regression. Mortality analysis used the Kaplan Meier method. A total of 227 patients were randomized to Crit-Line, and 216 were randomized to conventional monitoring. Both groups had similar baseline characteristics. During the study, no differences in weight, BP, or number of dialysis-related complications were observed. There were 120 and 81 non-access-related hospitalizations in the Crit-Line and conventional monitoring groups. The adjusted risk ratio for non-access-related and access-related hospitalization was 1.61 (95% confidence interval 1.15 to 2.25; P = 0.01) and 1.52 (95% confidence interval 1.02 to 2.28; P = 0.04) for the Crit-Line monitoring group. Mortality was 8.7% in the Crit-Line monitoring group and 3.3% in the conventional group (P = 0.021). Standardized mortality ratios comparing the Crit-Line and conventional monitoring groups to the prevalent hemodialysis population were 0.77 (NS) and 0.26 (P < 0.001). Hospitalization rates were 1.51 and 1.03 events/yr in the Crit-Line and standard monitoring groups, compared with 2.01 for the prevalent hemodialysis population. IBVM was associated with higher nonvascular and vascular access-related hospitalizations and mortality compared with conventional monitoring. The atypically low hospitalization and mortality rates for the conventional monitoring group suggest that these findings should be generalized to the US hemodialysis population with caution.

Adult↗

PubMed2004

Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy.

BACKGROUND: The associations of proteinuria and an elevated creatinine level with progression to acquired immunodeficiency syndrome (AIDS) and death in the era of highly antiretroviral therapy (HAART) have not been fully described. METHODS: This analysis includes 2038 human immunodeficiency virus (HIV)-infected women from the Women's Interagency HIV Study. Time to the development of a new AIDS-defining illness (ADI) and death was modeled using proportional hazards regression before the widespread availability of HAART and after initiation of HAART. RESULTS: Of the 2038 subjects, the 14.1% of women with proteinuria had lower CD4 lymphocyte counts and higher viral loads (P<.0001 for all) at baseline and before initiation of HAART. Before the widespread availability of HAART, proteinuria was associated with an increased risk for development of ADI (hazard ratio [HR], 1.37; P=.005), and proteinuria and an elevated creatinine level were both associated with an increased risk of death (for proteinuria: HR, 1.35 [P=.04]; for creatinine: HR, 1.72 per decrease in the inverse unit [P=.02]). Among women initiating HAART, an elevated creatinine level remained associated with an increased risk of development of ADI (HR, 1.54 per decrease in the inverse unit; P=.03), and proteinuria and an elevated creatinine level were associated with an increased risk of death (for proteinuria: HR, 2.07 [P=.005]; for creatinine: HR, 1.96 per decrease in the inverse unit [P=.04]). CONCLUSIONS: Proteinuria and an elevated creatinine level were associated with an increased risk of death and development of ADI. These associations may reflect the direct role of the kidney in modulating HIV disease, or they may act as markers of greater comorbidity.

Adult↗

PubMed2004

The evaluation of underlying cardiovascular disease among patients with end-stage renal disease.

Although coronary artery disease (CAD) is highly prevalent among patients with chronic kidney disease (CKD), interventions proven to reduce cardiovascular disease (CVD) mortality are underutilized in this population of patients. Given the burden of CVD in this population, knowledge of specific diagnostic tests for detection and evaluation of CAD in patients with end-stage renal disease (ESRD) and their correlation with outcomes is imperative for the practicing nephrologist. Studies that examine the use of exercise electrocardiography testing, pharmacologic stress imaging, single-photon emission computed tomographic myocardial perfusion imaging, electron beam computed tomography, and dobutamine stress echocardiography among patients with ESRD are detailed with recommendations for the noninvasive evaluation of CAD in this population.

Algorithms↗

PubMed2004

The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection.

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.

AIDS-Associated Nephropathy↗

PubMed2004

Projecting the United States ESRD population: issues regarding treatment of patients with ESRD.

In 2001, there were 406,081 patients who received treatment for end-stage renal disease (ESRD), increasing by 4.2% since 2000. The number of patients with ESRD has grown consistently over the past decade, with the greatest rate of growth occurring among patients older than 75 years of age, and patients with comorbidities such as diabetes mellitus and hypertension. Current projections indicate that the population of patients with ESRD may reach more than 2 million by 2030. The overall mortality rate has fallen by 10% since 1988, with the greatest decline among patients incident to dialysis, and an increase among patients receiving dialysis for greater than five years. While the rate of hospitalization for ESRD patients has remained relatively constant, recent improvements in mortality are temporally associated with a greater proportion of patients achieving adequate benchmarks of care in dialytic processes, such as anemia correction and dose of dialysis. The ESRD program consumes 6.4% of the Medicare budget. On a per-patient per month basis, Medicare costs have risen between 1991 and 2001. While payments fell slightly during 1998 and 1999 because of changes in Medicare policies, more recent years have seen an upswing in total expenditures, presumably related to use of injectables not included in the composite rate. Continued growth in the number of new patients reaching ESRD, as well as improved mortality rates of ESRD patients, are both contributing to the current rise and projected epidemic of ESRD over the next 25 years. The current public health strategy of identification of patients with early kidney disease to slow their progression to ESRD, in addition to aggressive treatment strategies to minimize the morbidity and mortality of patients with ESRD, is essential toward affecting the growth and health of this population.

Adult↗

PubMed2004

The impact of calcimimetic agents on the use of different classes of phosphate binders: results of recent clinical trials.

Calcimimetic agents bind to and activate the calcium-sensing receptor in the parathyroid glands, lowering the threshold for its activation by extracellular calcium and diminishing parathyroid hormone release from parathyroid cells. In three large randomized, controlled trials, cinacalcet given at doses of 30 to 180 mg orally each day was associated with effective reduction in parathyroid hormone levels over 26 weeks compared with placebo, and was consistently associated with a decrement in serum calcium, phosphorus levels, as well as a decrement in calcium-phosphorus product. In one study, there was a 5% incidence of hypocalcemia (serum calcium levels < 7.5 mg/dL on at least two consecutive measurements) among patients receiving cinacalcet, and less than 1% of patients receiving standard therapy (P < 0.0001). While there were no demonstrated differences between groups with regard to use of phosphate binders and vitamin D sterols in these randomized controlled trials, arguably, the combination of the effects on serum calcium, phosphorus, and calcium-phosphorus product may bring increased focus on the increased mortality risk associated with hypocalcemia.

Calcium↗

PubMed2004

The impact of antiretroviral therapy on HIVAN.

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AIDS-Associated Nephropathy↗

PubMed2004

Definition of proteinuria among women with HIV infection.

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Female↗

PubMed2003

The clinical characteristics and antiretroviral dosing patterns of HIV-infected patients receiving dialysis.

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.

AIDS-Associated Nephropathy↗

PubMed2003

HIV-associated nephropathy: a review of the epidemiology and clinical course in the HAART era.

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AIDS-Associated Nephropathy↗

PubMed2003

Interactions between dialysis-related volume exposures, nutritional surrogates and mortality among ESRD patients.

BACKGROUND: Interdialytic weight gain is used as a surrogate for volume expansion in haemodialysis patients and as an indicator of non-compliance. Increased weight gain is associated with both a greater mortality risk and better nutrition indices. This analysis characterizes the association between dialysis-related volume expansion and mortality in the context of its interaction with nutritional surrogates. METHODS: All patients receiving haemodialysis through Fresenius Medical Care-North America during 1998 were included. The percentage reduction in weight or intradialytic weight loss (IDWL%) was defined as the difference between the average of pre- and post-dialysis weights from the last 3 months of 1997 expressed as a percentage of post-dialysis weight. Associations between IDWL% and clinical and demographic variables were estimated using linear regression. The association between mortality risk and IDWL% was estimated using Cox proportional hazards regression. RESULTS: Younger age, male gender, the presence of diabetes mellitus, decreasing cholesterol, post-dialysis weight and pre-dialysis blood pressure (systolic and pulse pressure) were associated with increased IDWL%. Increasing IDWL% was associated with increasing phosphorus, creatinine, albumin, potassium and urea reduction ratio. Increasing IDWL% was significantly associated with mortality at 1 year [hazard ratio (HR) = 1.07, P = 0.003]. Among patients with diabetes mellitus, increasing IDWL% was associated with a mortality HR of 1.03 (P = 0.02). Among patients without diabetes mellitus, increasing IDWL% was not associated with an increased mortality risk. Increasing IDWL% is associated with a greater mortality risk among patients with creatinine <7.26, which failed to remain significant for patients whose creatinine was >or=7.26 mg/dl. Increasing IDWL% is associated with a greater mortality risk among patients with greater post-dialysis weight, greater body mass index and lower serum sodium measurements. CONCLUSIONS: This study confirms and extends the findings of the deleterious association between increasing IDWL% and mortality among patients with diabetes mellitus and among subgroups based on serum creatinine and body weight. The putative deleterious effect of dialysis-related volume expansion on mortality must be interpreted in the context of the patient's diabetic and nutritional status.

Adolescent↗

PubMed2003

Chronic kidney disease, mortality, and treatment strategies among patients with clinically significant coronary artery disease.

Cardiovascular disease is an important cause of mortality among patients with chronic kidney disease (CKD). This study describes associations between CKD, cardiac revascularization strategies, and mortality among patients with CKD and cardiovascular disease. All patients undergoing cardiac catheterization at Duke University Medical Center (1995 to 2000) with documented stenosis > or =75% of at least one coronary artery and available creatinine data were included. CKD was staged using creatinine clearance (CrCl) derived from the Cockcroft-Gault formula (normal, > or = 90 ml/min; mild, 60 to 89 ml/min; moderate, 30 to 59 ml/min; severe, 15 to 29 ml/min). Cox proportional-hazard regression estimated the relationship between clinical variables, including CrCl and percutaneous coronary artery intervention (PCI), coronary artery bypass grafting (CABG), medical management, and patient survival. There were 4584 patients included, and 24% had CrCl <60 ml/min. Each 10-ml/min decrement in CrCl was associated with an increase in mortality (hazard ratio, 1.14; P < 0.0001). CABG was associated with a survival benefit among patients with both normal renal function and patients with CKD compared with medical management. In patients with normal renal function, CABG was not associated with survival benefit over PCI. However, in patients with CKD, CABG was associated with improved survival. PCI was associated with a survival benefit compared with medical management among patients with normal, mildly, and moderately impaired renal function. Among patients with severe CKD, PCI was not associated with improved survival. CABG is associated with greater mortality reduction than PCI in severe CKD.

Aged↗

PubMed2002

Predictors of proteinuria and renal failure among women with HIV infection.

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.

Adult↗

PubMedDate not supplied

An introduction to epidemiology and biostatistics and issues in interpretation of studies.

Biometry↗

PubMedDate not supplied

Study designs and their potential influence on conclusions.

Epidemiology is the basic medical science that focuses on the distribution and determinants of disease frequency in human populations. An understanding of the tools of epidemiology is helpful in defining the limitations of medical research and evaluating the conclusions of studies. This is the second in a series of three articles whose objective is to present the basic concepts of epidemiology and biostatistics, highlighted by examples of these concepts applied in the medical literature studying patients receiving dialysis. This article describes the study designs of case-control, cohort, and randomized trials and issues in the conduct and analysis of each. Several studies examining the association between hematocrit and survival of dialysis patients are discussed. Their differences in design and methods are discussed in the context of their effect on study conclusions. The goal of this article is to present the reader with the issues of study design and the limitations they impose on study conclusions. Through the examination of these methods, the reader will be able to rigorously examine study methods and understand how design affects study conclusions and their application to patient care.

Case-Control Studies↗

PubMedDate not supplied

Key concepts in biostatistics: using statistics to answer the question "is there a difference?".

Biostatistics seeks to answer the question "Is there a difference?" in the rate of a disease or characteristic among subgroups of patients. The goal of this article is to introduce and define measures used in epidemiology and discuss different types of analyses in clinical research with an emphasis on the concepts and implications of the analyses rather than the mathematics. The implications of the use of measures such as incidence and prevalence, as well as odds, risk, and hazards ratios may affect study conclusions. An understanding of the distinction between these summary measures is essential. The concepts of univariate and multivariate analyses, a discussion of what it means to control for potential confounders, and a description of statistical power and significance are also presented. These concepts are integral to the design and analysis of clinical studies. An understanding of their advantages and applications will enhance the reader's ability to understand and evaluate the literature.

Analysis of Variance↗

PubMedDate not supplied

Nondialytic management of hyperkalemia and pulmonary edema among end-stage renal disease patients: an evaluation of the evidence.

Congestive heart failure (CHF) and hyperkalemia are the two leading reasons for emergency dialysis among individuals with end-stage renal disease (ESRD). While hemodialysis provides definitive treatment of both hyperkalemia and volume overload among ESRD patients, for those who present outside of "regular dialysis hours," institution of dialysis may be delayed. Nondialytic management can be instituted immediately and should be the initial therapy in the management of hyperkalemia and CHF in these individuals. Current available evidence does not allow conclusions as to whether treatment with nondialytic strategies alone results in different outcomes than nondialytic strategies coupled with emergent hemodialysis. Therefore, whether or not nondialytic management alone is appropriate remains a matter of individual judgment that should be decided on a case-by-case basis.

Calcium↗