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Kidney Disease & HIV
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Age-associated loss of kidney function has been recognized for decades. With aging, many subjects exhibit progressive decreases in glomerular filtration rate (GFR) and renal blood flow (RBF), with wide variability among individuals.
Individuals age >65 years old are the fastest expanding population demographic throughout the developed world. Consequently, more aged patients than before are receiving diagnoses of impaired renal function and nephrosclerosis—age-associated histologic changes in the kidneys. With age, there is a decline in total nephron size and number, tubulointerstitial changes, glomerular basement membrane thickening, and increased glomerulosclerosis.
Population GFR declines with age, with longitudinal studies differing in their reported rates of decline.13,14 Although the Modification of Diet in Renal Disease Study suggested renal function declined at a rate of 3.8 ml/min per year per 1.73 m2, rates as low as 0.4 ml/min per year per 1.73 m2 in The Netherlands have been described.15-18 A Japanese cohort study suggests that the rate of GFR decline increases with advancing age.19
Among 4217 adults, 3814 (90%) had at least one creatinine. The mean population GFR was 93.3 ml/min/1.73m2. An estimated 32,080 persons or 7.6% [95% confidence interval: 6.6%- 8.6%] of HIV-infected adults in care had CKD [5.7% had Stage 3 CKD (GFR 30-59 ml/min/1.73m2), 0.6% had Stage 4 CKD (GFR 15-29 ml/min/1.73m2), and 1.3% had Stage 5 CKD (GFR <15 ml/min/1.73m2)]. Among adults aged ≥60 years, 21% had CKD. https://www.natap.org/2013/CROI/croi_146.htm
Kidney Disease in Patients with HIV Infection and AIDS - (03/02/09)
"The aging of an HIV-infected population is another important pathway by which the incidence of CKD can be expected to continue to increase. GFR normally decreases with age. The prevalence of CKD in the elderly population now approaches 50% [21]. Other risk factors for CKD in HIV-infected patients are high viral load, low CD4+ lymphocyte count, and hepatitis C virus coinfection [17]. The importance of recognizing CKD is underscored by the strong correlation between CKD and both morbidity and mortality. In the HIV Epidemiology Research Study, proteinuria or an elevated serum creatinine level was associated with an increased risk of hospitalization and mortality [22, 23]. In the Women's Interagency HIV Study, elevated creatinine level and proteinuria were similarly predictive of an increased risk of an AIDS-defining illness and mortality [24].”
Diabetes mellitus and hypertension are the 2 most frequent causes of CKD in the general population. They increase the CKD risk 10-fold and account for 71% of all ESRD cases [3, 9]. Diabetes and hypertension are increasingly common among persons with HIV infection. The prevalence of diabetes was 14% in the Multicenter AIDS Cohort Study, 4-fold higher than in seronegative control persons [10], and was associated with cumulative exposure to nucleoside reverse-transcriptase inhibitors but not protease inhibitors (PIs) [11, 12]. Among those included in the Multicenter AIDS Cohort Study, the prevalence of hypertension is 3-fold higher than in age- and sex-matched control persons (34.2% vs. 11.9%; ), and hypertensive persons with HIV infection are more likely to have insulin resistance and metabolic syndrome (64..3% vs. 16.9%; ) [13].
Race is an important risk factor for CKD. Young, male blacks have an 11-fold increased risk of CKD, compared with their white counterparts [15]. Five new cases of ESRD develop for every 100 cases of CKD in black persons, whereas only 1 new ESRD case develops for every 100 cases of CKD in whites.
Glycemic control is critically important in delaying the progression of diabetic nephropathy. The American Diabetes Association recommends that adults with diabetes strive to maintain a glycated hemoglobin A1C level of <7.0%, preprandial plasma glucose level of 90-130 mg/dL (5.0-7.2 mmol/L), and peak postprandial plasma glucose level of <180 mg/dL (<10.0 mmol/L).
Kidney disease tends to be asymptomatic and is usually not the primary focus of a visit to an HIV clinic [28]. The presence of kidney disease should be anticipated, and screening and proper interpretation of the relationship between serum creatinine level and GFR are recommended.
As patients infected with human immunodeficiency virus (HIV) live longer while receiving antiretroviral therapy, kidney diseases have emerged as significant causes of morbidity and mortality. Black race, older age, hypertension, diabetes, low CD4+ cell count, and high viral load remain important risk factors for kidney disease in this population.
Chronic kidney disease should be diagnosed in its early stages through routine screening and careful attention to changes in glomerular filtration rate or creatinine clearance. Hypertension and diabetes must be aggressively treated. Antiretroviral regimens themselves have been implicated in acute or chronic kidney disease. The risk of kidney disease associated with the widely used agent tenofovir continues to be studied, although its incidence in reported clinical trials and observational studies remains quite low. Future studies about the relationship between black race and kidney disease, as well as strategies for early detection and intervention of kidney disease, hold promise for meaningful reductions in morbidity and mortality associated with kidney disease.
Kidney function should be assessed according to existing Infectious Diseases Society of America guidelines [28]. All patients should have a screening urinalysis and a calculated estimate of GFR. Those at high risk for kidney disease (i.e., those with black race, CD4+ count <200 cells/mm3, HIV RNA levels >4000 copies/mL, diabetes, hypertension, or coinfection) should be screened annually to detect subtle changes over time. The standard urinary dipstick is a sufficient screen for proteinuria, but diabetic patients must be tested for microalbuminuria, defined as urinary albumin excretion of 30-300 μg/mg creatinine, a range not detected using conventional dipsticks [56]. Microalbuminuria in diabetic patients predicts subsequent decreases in GFR, and treatment with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers is indicated [57]. Microalbuminuria in nondiabetic patients has been linked to future cardiovascular events [58], a risk that may be modified by angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers [59]. Several issues warrant further study when considering routine testing for microalbuminuria in nondiabetic patients with HIV infection: the reproducibility of the measurements, their proper timing (before or after initiation of ART), and proven benefits of long-term treatment with angiotensin-converting enzyme inhibitors or receptor blockers.
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