Mohamed G. Atta

Chronic Kidney Disease Incidence, and Progression to End-Stage Renal Disease, in HIV-Infected Individuals: A Tale of Two Races

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.

Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patients individual circumstances.

End-stage renal disease and chronic kidney disease in a cohort of African-American HIV-infected and at-risk HIV-seronegative participants followed between 1988 and 2004

Background:HIV-infected African-Americans are at increased risk of end-stage renal disease requiring renal replacement therapy (RRT). Objectives:To compare the incidence of RRT in HIV-infected and HIV-seronegative African-Americans and describe temporal trends in RRT and chronic kidney disease (CKD) in HIV infection. Design:Cohort study in Baltimore including 4509 HIV-infected and 1746 HIV-seronegative African-Americans. Methods:Incident RRT was defined by matching participant identifiers with the US Renal Data System; CKD was defined as an estimated glomerular filtration rate < 60 ml/min per 1.73m2 for ≥ 3 months. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated by indirect adjustment. Risk factors for RRT were assessed by person-time methods and Poisson regression. Results:RRT was initiated in 24 HIV-seronegative subjects over 13 415 person-years of follow-up (SIR, 2.3; 95% CI, 1.5–3.4), in 51 HIV-infected participants without AIDS over 10 780 person-years (SIR, 6.9; 95% CI, 5.1–9.0), and in 125 participants with AIDS over 9833 person-years. SIR, 16.1; 95% CI, 13.4–19.2). In HIV-infected African-Americans, RRT incidences were 5.8 and 9.7/1000 person-years in the pre-HAART and HAART eras, respectively (adjusted rate ratio 1.2; 95% CI, 0.8–1.9). In supplementary analyses, CKD incidence declined significantly in the HAART era compared with pre-HAART, but the CKD period prevalence increased. Conclusions:Nearly 1% of HIV-infected African-Americans initiated RRT annually, a rate that was similar in the HAART and pre-HAART eras. While new cases of CKD decreased, the prevalence of CKD increased in the HAART era, primarily because survival in those with HIV-associated CKD has improved.

Observations on a Cohort of HIV-Infected Patients Undergoing Native Renal Biopsy

Aims: This study aims to explore the spectrum of renal disease in HIV-infected patients, identify clinical predictors of HIV-associated nephropathy (HIVAN), and investigate the performance of renal biopsy in HIV-infected patients. Method: Of 263 HIV-infected patients with renal disease evaluated between 1995 and 2004, 152 had a renal biopsy, while 111 had not. A group comparison was performed. Results: The leading biopsy diagnoses were HIVAN (35%), noncollapsing focal segmental glomerulosclerosis (22%), and acute interstitial nephritis (7.9%), amongst over a dozen others. There was a trend of decreasing yearly incidence of HIVAN diagnoses, paralleling the use of antiretroviral therapy. By multivariate logistic regression, CD4 counts >200 cells/mm3 and higher estimated glomerular filtration rate were strong negative predictors of HIVAN. HIVAN patients were more likely to require dialysis (p < 0.0001) and had worse overall survival (p = 0.02). Younger age and lower estimated glomerular filtration rate were significant predictors of renal biopsy in multivariate regression analysis. More biopsied patients progressed to dialysis (51 vs. 25%, p = 0.001) and death (15 vs. 5.4%, p = 0.001), despite more frequent corticosteroid treatment (29 vs. 3.6%, p = 0.001). Conclusion: These findings may reflect more severe acute and/or chronic disease at the time of biopsy and suggests that earlier renal biopsy may be warranted in HIV-infected patients, especially in light of the changing spectrum of renal disease in this group.

Kidney Function and the Risk of Cardiovascular Events in HIV-1 Infected Patients

Objective:Cardiovascular events (CVEs) are a significant cause of mortality in HIV/AIDS patients. The objective is to determine the correlation between kidney function and the risk of CVEs 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 patients who had CVEs and 252 controls). Estimated glomerular filtration rate (eGFR), calculated by the Chronic Kidney Disease Epidemiology Collaboration formula and the Modification of Diet in Renal Disease equation, and proteinuria were the primary exposures of interest. Results:Mean eGFR was significantly lower in the patients compared with controls (68.4 vs. 103.2 ml/min per 1.73 m2, P < 0.001 by Chronic Kidney Disease Epidemiology Collaboration formula and 69.0 vs. 103.1 ml/min per 1.73 m2, P < 0.001 by Modification of Diet in Renal Disease equation). In univariate analysis, an eGFR of less than 60 ml/min per 1.73 m2 was associated with a 15.9-fold increased odds of a CVE compared with an eGFR of at least 60 ml/min per 1.73 m2 (P < 0.001). In multivariate analysis, a 10 ml/min per 1.73 m2 decrease in eGFR was associated with a 20% increased odds of a CVE (odds ratio 1.2, 95% confidence interval 1.1–1.4). The prevalence of proteinuria in the patients was approximately twice that of controls (51 vs. 25%, P < 0.001). Proteinuria was associated with CVEs both in univariate and multivariate analyses (odds ratio 3.6, 95% confidence interval 1.9–7.0 and odds ratio 2.2, 95% confidence interval 1.1–4.8, respectively). Traditional cardiovascular risk factors, such as history of previous CVEs, diabetes mellitus, and dyslipidemia, along with low CD4 cell counts were also found as significant predictors of risk of CVEs. Conclusion:Our study shows a significant independent association between decreased kidney function and increased risk of CVE in HIV-1-infected patients.

APOL1 Risk Variants Predict Histopathology and Progression to ESRD in HIV-Related Kidney Disease

With earlier institution of antiretroviral therapy, kidney diseases other than HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes for these diseases are typically worse among those infected with HIV, but the reasons for this are not clear. Here, we examined the role of APOL1 risk variants in predicting renal histopathology and progression to ESRD in 98 HIV-infected African Americans with non-HIVAN kidney disease on biopsy. We used survival analysis to determine time to ESRD associated with APOL1 genotype. Among the 29 patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1 risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly three-fold higher risk for ESRD compared with those with one or zero risk alleles (P=0.03). In summary, these data demonstrate an association between APOL1 variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible use for APOL1 genotyping to help guide the care of HIV-infected patients.

HIV Type 1 RNA Level as a Clinical Indicator of Renal Pathology in HIV-Infected Patients

To determine the value of human immunodeficiency virus type 1 (HIV-1) RNA level in distinguishing HIV-associated nephropathy from non-HIV-associated nephropathy renal pathological conditions, we retrospectively compared renal histopathological findings for 86 HIV-infected patients according to HIV-1 RNA levels. We found that HIV-associated nephropathy was unlikely among patients with HIV-1 RNA levels <400 copies/mL. Hypertensive vascular disease surpassed HIV-associated nephropathy as the most common renal pathological finding among the entire cohort. HIV-1 RNA level did not correlate with renal survival.

Renal disease in patients with HIV infection: epidemiology, pathogenesis and management.

With the introduction of highly active antiretroviral therapy, we have witnessed prolonged survival with the potential for normal life expectancy in HIV-infected individuals. With improved survival and increasing age, HIV-infected patients are increasingly likely to experience co-morbidities that affect the general population, including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C, cigarette smoking and injection drug use. Furthermore, they have exposures unique to this population, including antiretrovirais and other medications. Therefore, the differential diagnosis is vast.Early identification (through efficient screening) and definitive diagnosis (by kidney biopsy when indicated) of kidney disease in HIV-infected individuals are critical to optimal management. Earlier interventions with disease-specific therapy, often with the help of a nephrologist, are likely to lead to better outcomes. In those with chronic kidney disease, interventions, such as aggressive blood pressure control with the use of ACE inhibitors or angiotensin receptor antagonists where tolerated, tight blood glucose control in those with diabetes, and avoidance of potentially nephrotoxic medications, can slow progression and prevent end-stage renal disease. Only with greater awareness of kidney-disease manifestations and their implications in this particularly vulnerable population will we be able to achieve success in confronting this growing problem.

Kidney biopsy in HIV: beyond HIV-associated nephropathy.

A 57-year-old African-American woman with human unodeficiency virus (HIV) infection for 18 years epatitis C presents with an acute decrease in glome ltration rate (GFR) and nephrotic-range proteinuria sup mposed on chronic kidney disease (CKD). She was no ntiretroviral therapy because of nonadherence, and her v oad was 138,000 copies/mL, with a CD4 count of 365 L. he had a remote history of intravenous cocaine and h buse. Serum creatinine levels until 14 months earlier anged from 0.9 to 1.0 mg/dL (80 to 88.4 mol/L; estimated FR [eGFR] using the Modification of Diet in Renal ase Study equation 60 mL/min/1.73 m [ 1 mL/s/1.73 ]). One year before presentation, serum creatinine l as 1.2 mg/dL (106 mol/L; eGFR, 58 mL/min/1.73 m 2

Combined percutaneous mechanical and chemical thrombectomy for renal vein thrombosis in kidney transplant recipients.

Renal vein thrombosis occurring after the immediate post‐transplant period often leads to loss of the transplant organ. We report two cases of renal vein thrombosis in the setting of de novo membranous nephropathy occurring 5 and 26 months post‐transplantation. Both cases were treated with percutaneous mechanical thrombectomy and localized catheter‐directed thrombolysis with resolution of clot burden, and regained kidney function after thrombolysis without subsequent thromboses. Percutaneous mechanical thrombolysis can be safely done in renal transplant recipients and should be considered in patients with renal vein thrombosis beyond the immediate post‐operative period in order to minimize exposure to systemic thrombolysis.