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Background: Highly active antiretroviral therapy (HAART), especially tenofovir DFcontaining regimens, has been implicated in albuminuria., Objective: We prospectively evaluated the effects of HAART on albumin-to-creatinine ratios (ACRs) in antiretroviral-naïve HIV-infected individuals., Methods: One hundred and two (102) newly diagnosed, antiretroviral-naïve, human immunodeficiency virus (HIV)-infected persons were treated with Tenofovir disoproxil fumarate/ Emtricitabine/Efavirenz (TDF/FTC/EFV), n=33; Zidovudine/Lamivudine/Nevirapine (ZDV/3TC/NVP), n=53; and Zidovudine/Lamivudine/Efavirenz (ZDV/3TC/EFV), n=16. Diabetes mellitus and hypertension were excluded. ACRs and glomerular filtration rates (eGFR) were estimated at baseline, and at 1, 3, 6 and 9 months post-therapy; the prevalence of albuminuria (ACR ≥ 300mg/g), and microalbuminuria (ACR 30-300mg/g) were similarly estimated. HAART effects on normal ACR (0-30mg/g) were also monitored., Results: At baseline, one patient (0.9%) had nephrotic-range albuminuria with ACR of 2450mg/g. Overall, 8 (7.8%) patients had albuminuria; 53 (51.9%) had microalbuminuria; while 41 (40.2%) had normal ACRs, 28 (27.5% of 102) of which had nonalbuminuric renal insufficiency. eGFR and ACRs improved concurrently on HAART (ACR, Wilks' lambda 0.439, power 0.763, p=0.032); albuminuria improved significantly on all the 3 regimens at 9 months (p=0.006, 0.012 and <0.001 respectively). Microalbuminuria resolved earlier (1 month) with ZDV/3TC/NVP than with TDF/FTC/EFV and ZDV/3TC/EFV (24.31mg/g versus 76.51mg/g and 63.59mg/g; p=0.028, 0.016 respectively). Microalbuminuria relapsed on TDF/FTC/EFV and ZDV/3TC/EFV at 6 months but resolved again at 9 months (66.7 versus 29 mg/g, p=0.006; and 51.2 versus 9.5mg/g, p=0.001 respectively); no relapse on ZDV/3TC/NVP. At 9 months, ZDV/3TC/EFV caused the greatest resolution of microalbuminuria (85.7% decline in ACR from baseline) compared with ZDV/3TC/NVP (72.5% decline) and TDF/FTC/EFV (63.9% decline). In multivariate analyses, predictors of ACR include older age (Odds ratio OR 2.8, p= 0.025); female gender (OR, 3.4, p =0.014); CD4+ (OR 0.99, p=0.002)., Conclusion: HIV induces renal impairment. Thus, albuminuria, microalbuminuria and nonalbuminuric renal insufficiency are highly prevalent in antiretroviral-naïve HIV-infected persons but nephrotic-range albuminuria is uncommon. Albuminuria and/microalbuminuria and eGFR improve concurrently on HAART (with/without tenofovir DF). Zidovudine-based HAART (ZDV/3TC/NVP) resolves microalbuminuria earlier, and without relapse, unlike Tenovofir-based regimen and zidovudine with efavirenz (ZDV/3TC/EFV)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hepatitis C virus (HCV) infection is common and can accelerate chronic kidney disease (CKD) progression. Direct-acting antiviral (DAA) therapies against hepatitis C have consistently shown rates of sustained viral remission. However, the effect on kidney function is unknown. In a retrospective observational cohort study of HCV-infected patients receiving DAA therapies from 2013 to 2017, the slopes of estimated glomerular filtration rate (eGFR) decline were compared in the three years before DAA therapy to the slope after therapy. Pre- and post-treatment albuminuria values were also compared. In all, 1,178 patients were included; mean age of 56, 64% male, 71% white, 21% were diabetic, and 42% with cirrhosis. In patients with eGFR less than 60ml/min per 1.73m 2 , the annual decline in eGFR in the three years prior to treatment was -5.98 ml/min per year (95% confidence interval -7.30 to -4.67) and improved to -1.32 ml/min per year (95% confidence interval -4.50 to 1.88) after DAA therapy. In patients with eGFR greater than 60ml/min per 1.73m 2 the annual decline in eGFR in the three years prior to treatment was -1.43 ml/min per year (95% confidence interval -1.78 to -1.08) and after DAA therapy was -2.32 ml/min per year (95% confidence interval -3.36 to -1.03). Albuminuria improved significantly in patients without diabetes, but not in those with diabetes. Predictors of eGFR improvement included having CKD at baseline and being non-diabetic. Events of acute kidney injury were rare, occurring in 29 patients, and unrelated to antiviral therapy in 76% of cases. Thus, DAA therapy for HCVs infection may slow CKD progression., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Puumala hantavirus (PUUV) infected patients typically suffer from acute kidney injury (AKI). Adipokines have inflammation modulating functions in acute diseases including AKI. We examined plasma levels of three adipokines (resistin, leptin, and adiponectin) in acute PUUV infection and their associations with disease severity., Methods: This study included 79 patients hospitalized due to acute PUUV infection. Plasma resistin, leptin, adiponectin, as well as IL-6 and CRP, were measured at the acute phase, recovery phase and one year after hospitalization., Results: Plasma resistin levels were significantly higher in the acute phase compared to the recovery phase and one year after (median resistin 28 pg/mL (11-107) vs. 17 pg/mL (7-36) vs. 14 pg/mL (7-31), p<0.001). Maximum resistin concentration correlated with maximum plasma creatinine levels (r = 0.63; p<0.001). The higher the amount of albuminuria in the urine dipstick test (0-1+, 2+ or 3+) at admission, the higher the median of maximum resistin (24.7 pg/mL, 25.4 pg/mL and 39.6 pg/mL, respectively, p = 0.002). High resistin was also an independent risk factor for severe AKI (creatinine ≥353.6μmol/L) (OR 1.08, 95% CI 1.02-1.14). Neither plasma leptin nor adiponectin level had any correlation with creatinine concentration or the amount of albuminuria., Conclusions: Plasma resistin independently associates with the severity of AKI in acute PUUV infection. The association of resistin with the amount of albuminuria suggests that the level of plasma resistin is not only influenced by renal clearance but could have some role in the pathogenesis of AKI during PUUV infection., Competing Interests: The authors have declared that no competing interests exist.

Background/aims: Antiviral monotherapy is recommended for hepatitis B virus-associated glomerulonephritis (HBV-GN) treatment. Although considered superior to interferon-α in several respects, nucleotide/nucleoside analog (NA) monotherapy has not been studied. This metaanalysis evaluates the efficacy and safety of NA monotherapy for treating HBV-GN., Methods: We searched for controlled clinical trials of NA monotherapy for HBVGN in the MEDLINE, Embase, Cochrane Library, Chinese BioMedical Literature on disc, Chinese National Knowledge Infrastructure, and Wanfang databases. Primary outcome measures were proteinuria remission, HBV-DNA negative conversion rate, and hepatitis B e-antigen (HBeAg) clearance. Secondary outcome measures were variations in proteinuria, serum albumin, alanine aminotransferase (ALT), and serum creatinine (Scr)., Results: Ten trials involving 325 patients were included: four randomized controlled trials, two cohort clinical trials, and four self-controlled studies. Based on the fixed-effects model, we found significant proteinuria remission rate improvement in the NA group (relative risk (RR): 3.60, 95% confidence interval (CI): 1.99 – 6.50), negative conversion rate of HBV-DNA (RR: 2.20, 95% CI: 1.55 – 3.13), and clearance of HBeAg (RR: 4.49, 95% CI: 1.29 – 15.67). Improvement in ALT (mean difference (MD): 56.60, 95% CI: 50.41 – 62.79) was found with the fixedeffects model, and a slight decrease in Scr (MD: 25.25, 95% CI: –17.11 – 67.61, p = 0.24) was shown., Conclusions: HBV-GN proteinuria remission with elevated serum albumin, decreased HBV replication, and improved HBeAg clearance could be achieved using NA monotherapy. Furthermore, NA monotherapy may protect renal function in HBV-GN patients by preventing Scr elevation.

Background: Antiretroviral therapy (ART) is associated with improved kidney function; however, the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney function and proteinuria., Methods: We examined changes in urine protein:creatinine (UPCR) and urine albumin:creatinine (UACR) ratios in 245 ART-naive participants in A5202 randomized in a substudy to blinded NRTI (abacavir/lamivudine, ABC/3TC, n = 124 or TDF/emtricitabine, TDF/FTC, n = 121) with open-label protease inhibitor (PI) atazanavir/ritonavir or nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz., Results: At baseline, 18% of participants had clinically significant proteinuria (UPCR ≥200 mg/g), and 11% had clinically significant albuminuria (UACR ≥30 mg/g). The prevalence of clinically significant proteinuria and albuminuria decreased from baseline to week 96 in all treatment groups. In intention-to-treat analyses, there was a significant effect of NRTI component on fold change in UPCR (P = 0.011) and UACR (P = 0.018) from baseline to week 96, with greater improvements in participants randomized to ABC/3TC. There was no significant effect of NNRTI/PI component on fold change in UPCR (P = 0.23) or UACR (P = 0.88), and no significant interactions between NRTI and NNRTI/PI components., Conclusions: In this prespecified secondary analysis, ART initiation was associated with improvements in proteinuria and albuminuria, with significantly greater improvements in participants randomized to ABC/3TC versus TDF/FTC. These are the first data from a randomized trial to suggest that initiation of TDF/FTC may not be associated with the same degree of improvement in proteinuria and albuminuria that have been reported with other regimens. Future studies should consider the long-term clinical significance of these findings.

Unlabelled: HCV is an important cause of renal disease. Taal and Brenner have identified risk factors for CKD and have suggested that these risk factors be incorporated into a renal risk score analogous to the Framingham cardiovascular score. Given the high HCV-renal disease comorbidity, we sought to assess risk factors for CKD in patients with HCV chronic hepatitis., Methods: One hundred-seventeen patients with HCV chronic hepatitis (mean age: 50.68 +/- 9.14 years; 86 female and 31 male) hospitalized in the Department of Hepatology during 2009 were enrolled into the study. All patients were assessed for the risk factors for CKD proposed by Taal and Brenner: albuminuria, diabetes mellitus, hypertension, obesity, anemia, hypercholesterolemia, hypertriglyceridemia, nephrotoxins, primary renal disease, associated urological disorder, cardiovascular disease and family history of CKD. Renal function (GFR-CKD-Epi) was also evaluated., Statistical Analysis: Pearson's correlation coefficient and Odds Ratio (OR) was performed using SPSS17 and Epi 3.2.2., Results: The prevalence of albuminuria was 21.36%, of hypertension was 20.51%, of obesity was 21.36%, and hypercholesterolemia was present in 41.02% of the cases. Renal function was as follows: 10.25% (12/117) of the patients had a GFR < 60 mL/min/1.73 sqm.; 64.95% (76/117) of the patients had a GFR between 60-89 mL/min/1.73 sqm.; and 24.78% (29/117) had a GFR > or = 90 mL/min/1.73 sqm., Conclusions: Our study shows that HCV chronic hepatitis is associated with renal function impairment in a high percentage of patients. Prominent risk factors for CKD are present in these patients, such as albuminuria, hypertension, obesity, and hypercholesterolemia, which need to be actively searched and addressed therapeutically.

Individuals with HIV infection and two apolipoprotein L1 gene (APOL1) risk variants frequently develop nephropathy. Here we tested whether non-HIV viral infections influence nephropathy risk via interactions with APOL1 by assessing APOL1 genotypes and presence of urine JC and BK polyoma virus and plasma HHV6 and CMV by quantitative polymerase chain reaction. We analyzed 300 samples from unrelated and related first-degree relatives of African Americans with nondiabetic nephropathy using linear and nonlinear mixed models to account for familial relationships. The four groups evaluated were APOL1 zero/one versus two risk alleles, with or without nephropathy. Urine JCV and BKV were detected in 90 and 29 patients, respectively, whereas HHV6 and CMV were rare. Adjusting for family age at nephropathy, gender, and ancestry, presence of JCV genomic DNA in urine and APOL1 risk alleles were significantly negatively associated with elevated serum cystatin C, albuminuria (albumin-to-creatinine ratio over 30 mg/g), and kidney disease defined as an eGFR under 60 ml/min per 1.73 m(2) and/or albuminuria in an additive (APOL1 plus JCV) model. BK viruria was not associated with kidney disease. Thus, African Americans at increased risk for APOL1-associated nephropathy (two APOL1 risk variants) with JC viruria had a lower prevalence of kidney disease, suggesting that JCV interaction with APOL1 genotype may influence kidney disease risk.

With the widespread use of combination antiretroviral agents, the incidence of HIV-associated nephropathy has decreased. Currently, HIV-infected patients live much longer and often suffer from comorbidities such as diabetes mellitus. Recent epidemiological studies suggest that concurrent HIV infection and diabetes mellitus may have a synergistic effect on the incidence of chronic kidney disease. To address this, we determined whether HIV-1 transgene expression accelerates diabetic kidney injury using a diabetic HIV-1 transgenic (Tg26) murine model. Diabetes was initially induced with low-dose streptozotocin in both Tg26 and wild-type mice on a C57BL/6 background, which is resistant to classic HIV-associated nephropathy. Although diabetic nephropathy is minimally observed on the C57BL/6 background, diabetic Tg26 mice exhibited a significant increase in glomerular injury compared with nondiabetic Tg26 mice and diabetic wild-type mice. Validation of microarray gene expression analysis from isolated glomeruli showed a significant upregulation of proinflammatory pathways in diabetic Tg26 mice. Thus, our study found that expression of HIV-1 genes aggravates diabetic kidney disease.

Background and Objectives: Clinically, hepatitis B virus (HBV) infection is observed to be associated with nephropathy. However, previous population-based studies failed to show an association between HBV infection and CKD. Therefore, this cross-sectional study was designed to further explore this association., Design, Setting, Participants, & Measurements: A representative sample of 6854 Chinese adults aged 30-75 years was tested for levels of serum hepatitis B surface antigen, alanine aminotransferase (ALT), creatinine, urinary albumin/creatinine ratio, and potential CKD risk factors., Results: Neither HBV infection nor elevated ALT (ALT+; ≥ sex-specific 90th percentile of ALT levels of noninfected persons) was significantly associated with reduced estimated GFR (eGFR < 60 ml/min per 1.73 m(2)). Compared with noninfected persons, HBV-infected persons with ALT+, but not those with ALT- (P=0.26), were more likely to have reduced eGFR (odds ratio, 4.07; 95% confidence interval, 1.18-14.0; P=0.03). Further analysis with a general linear model revealed a significant difference in eGFR (mean ± SEM) between HBV-infected and noninfected persons (87.8±0.8 versus 90.2±0.4 ml/min per 1.73 m(2); P=0.002). This difference was mainly derived from that between HBV-infected persons with ALT+ and noninfected persons, with an average difference in eGFR of -4.5 (95% confidence interval, -0.9 to -8.1; P=0.01). HBV infection and ALT+, alone or in combination, were not significantly associated with albuminuria or CKD., Conclusions: HBV infection with elevated ALT, rather than HBV infection alone, was associated with reduced renal function.

Background: There is increasing evidence of hypertension and microalbuminuria in HIV-infected patients, and these are two important risk factors for renal and cardiovascular disease. Anti-hypertensive drugs inhibiting the renin-angiotensin system exert an antiproteinuric effect. Telmisartan, an angiotensin II receptor blocker and partial peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist that is approved for the treatment of hypertension, appears to exert a nephroprotective effect independent of blood pressure reduction in the general population., Objective: The aim of this preliminary study was to evaluate possible nephroprotective effects of telmisartan in hypertensive HIV-positive patients with microalbuminuria., Patients and Methods: Caucasian male patients with HIV infection (n=13) receiving stable combined antiretroviral therapy (without therapeutic changes for > 12 months) and a recent diagnosis of grade 1 hypertension were treated with daily oral telmisartan 80 mg for 6 months. Patients had suppressed viremia and a CD4 cell count > 300 cells/mL for 6 months, and microalbuminuria > 5 mg/dL. Systolic and diastolic blood pressure (SBP, DBP), triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), microalbuminuria, Modification of Diet Renal Disease-Glomerular Filtration Rate (MDRD-GFR), vascular endothelial growth factor (VEGF) and endothelin-1 were measured at baseline and at one, three and six months. All statistical analyses were performed using SAS 9.2., Results: A significant reduction of microalbuminuria (p < 0.001) with stable MDRD-GFR was observed, although the main indices of renal function showed no substantial change. A significant reduction in mean SBP and DBP was observed at T1 and confirmed at T3 and T6 (SBP p < 0.001 and DBP p < 0.001), and there was BP normalization. Metabolic assessments showed an improvement in lipid parameters, and a significant decrease in insulin resistance assessed by the homeostasis model assessment index-insulin resistance (HOMA-IR) (p = 0.04). In addition, there was a statistically significant reduction in ESR (p = 0.02) and a non significant reduction in CRP. Other results included a significant reduction in serum VEGF and endothelin-1 levels (p < 0.001)., Conclusions: From these preliminary findings, telmisartan has demonstrated efficacy in the control of hypertension and microalbuminuria in HIV-infected patients. Decreased microalbuminuria with stable MDRD-GFR may be indicative of a nephroprotective effect of telmisartan; mechanisms causing microalbuminuria in patients with HIV could be related to infection, chronic inflammation, and endothelial dysfunction. The decreased endothelin-1 and VEGF levels in patients in this study may be related to an endothelial protective effect of telmisartan. This study reports the first observation of renal and endothelial protective effects of telmisartan in HIV-positive patients.

Background: This study examines the association between microalbuminuria and the development of proteinuria among HIV-infected persons., Methods: A total of 948 subjects provided urine samples for albumin, protein and creatinine measurements semiannually. Microalbuminuria was defined as an albumin-to-creatinine ratio of >30 mg/g. Proteinuria was defined as a protein-to-creatinine ratio of > or =0.350 mg/mg. The progression from microalbuminuria to proteinuria was described., Results: At baseline, 69.4% of the subjects had no detectable proteinuria, 20.2% had microalbuminuria, and 10.4% had proteinuria. Subjects with microalbuminuria and proteinuria were more likely to be black (P=0.02), have lower CD4 cell counts (P=0.02 comparing subjects without abnormal urine protein excretion to subjects with microalbuminuria; P=0.0001 comparing subjects with microalbuminuria to subjects with proteinuria), and have a higher HIV RNA level (P=0.08 and 0.04, respectively). Among 658 subjects with normal urine protein, 82.7% continued to have no abnormality, 14.3% developed microalbuminuria, and 3.0% developed proteinuria. Subjects without baseline proteinuria (i.e. either normal protein excretion or microalbuminuria) who developed proteinuria were more likely to have microalbuminuria (P=0.001), a lower CD4 cell count (P=0.06), and a higher plasma HIV RNA (P=0.03) than those who did not progress to proteinuria. In multivariate analysis, only microalbuminuria remained associated with the development of proteinuria (odds ratio 2.9; 95% confidence interval 1.5, 5.5; P=0.001)., Conclusion: Microalbuminuria predicts the development of proteinuria among HIV-infected persons. Because proteinuria has been linked to poorer outcomes, strategies to affect microalbuminuria should be tested.

Objective: Microalbuminuria is associated with increased risk of cardiovascular disease and mortality. The objective of the study was to evaluate if HIV infection was an independent risk factor for microalbuminuria., Design: Cross sectional., Methods: The relationship between HIV infection and microalbuminuria was assessed using subjects enrolled in the study of Fat Redistribution and Metabolic Change in HIV Infection, which consists of HIV-positive and control men and women. Participants with proteinuria (dipstick >or= 1+) were excluded., Results: Microalbuminuria (urinary albumin/creatinine ratio, ACR > 30 mg/g) was present in 11% of HIV infected, and 2% of control participants (P < 0.001); a fivefold odds after multivariate adjustment (odds ratio, 5.11; 95% confidence interval, 1.97-13.31; P=0.0008). Several cardiovascular risk factors were associated with higher ACR in HIV participants: insulin resistance (HOMA > 4; 32%, P < 0.0001), systolic blood pressure (21%, P = 0.01 for 120-140 versus < 120 mmHg, and 43%, P = 0.06 for > 140 versus < 120 mmHg), and family history of hypertension (17%, P = 0.03). Higher CD4 cell count was associated with lower albumin/creatinine ratio (-24%, P = 0.009 for 200-400 versus < 200 cells/ml and -26%, P = 0.005 for > 400 versus < 200 cells/ml)., Conclusion: HIV infection had a strong and independent association with microalbuminuria, the severity of which was predicted by markers of insulin resistance, hypertension, and advanced HIV infection. These associations warrant further investigation, as the increased prevalence of microalbuminuria in HIV infection may be a harbinger of future risk of cardiovascular and kidney diseases.