Novel biomarkers in patients with uncontrolled hypertension with and without kidney damage.

INTRODUCTION: Estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR) are insensitive biomarkers for early detection of hypertension-mediated organ damage (HMOD). In this nationwide cross-sectional study, we assessed potential biomarkers for early HMOD in healthy persons and patients with hypertension. We hypothesised that plasma levels of biomarkers: (1) are different between healthy controls and patients with hypertension, (2): can classify patients with hypertension according to the degree of hypertension severity. DESIGN AND METHODS: Patients with hypertension prescribed ≥2 antihypertensive agents were selected from a multicentre study. Healthy controls were selected from an ongoing study of living kidney donor candidates. Uncontrolled hypertension was defined as systolic daytime ambulatory blood pressure ≥135 mmHg. Kidney HMOD was defined by ACR > 3.0 mg/mmol or eGFR < 60 mL/min/1.73 m2. Patients with hypertension were categorised into three groups: (1) controlled hypertension; (2) uncontrolled hypertension without kidney HMOD; (3) uncontrolled hypertension with kidney HMOD. Fifteen biomarkers were analysed using a Luminex bead-based immunoassay, and nine fell within the specified analytical range. RESULTS: Plasma levels of Interleukin 1 receptor antagonist (IL-1RA), neutrophil gelatinase-associated lipocalin (NGAL) and uromodulin were significantly different between healthy controls (n = 39) and patients with hypertension (n = 176). In regression models, with controlled hypertension (n = 55) as the reference category, none of the biomarkers were associated with uncontrolled hypertension without (n = 59) and with (n = 62) kidney HMOD. In models adjusted for cardiovascular risk factors and eGFR, osteopontin (OPN) was associated with uncontrolled hypertension without kidney HMOD (odds ratio (OR) 1.77 (1.05-2.98), p = 0.03), and regulated upon activation normal T-cell expressed and secreted (RANTES) with uncontrolled hypertension with kidney HMOD (OR 0.57 (0.34-0.95), p = 0.03). CONCLUSIONS: None of the biomarkers could differentiate our hypertension groups when established risk factors were considered. Plasma OPN may identify patients with uncontrolled hypertension at risk for kidney HMOD.

What is the context? In order to tailor individualised hypertension treatment, a risk assessment for cardiovascular disease (CVD) must be performed. This includes evaluation of established hypertension-mediated organ damage (HMOD), such as the presence of kidney damage and associated risk factors. Today, kidney function is assessed by blood and urine samples. However, today's blood and urine samples are not sensitive enough to capture kidney damage due to hypertension at a stage when prevention may be most effective.What is new? In this study, we evaluated plasma levels of biomarkers related to endothelial and kidney cell pathology, inflammation and fibrosis in healthy patients and patients with hypertension. We hypothesised that plasma levels of biomarkers could differentiate between different degrees of hypertension severity.Healthy controls had lower Interleukin 1 receptor antagonist (IL-1RA) and neutrophil gelatinase-associated lipocalin (NGAL) levels, but higher uromodulin compared to patients with hypertension. Except for osteopontin (OPN), all biomarkers showed significant trends in median biomarker levels across study groups. However, as hypertension severity increased, the median plasma OPN levels also rose. None of the biomarker could consistently differentiate the hypertension severity groups after considering established risk factors. However, OPN may be an early biomarker for kidney damage in hypertension.What is the impact? Biomarkers for early detection of organ damage in hypertension may guide targeted treatment. Plasma OPN may have potential to identify those at risk for hypertensive kidney damage. However, the studied biomarkers lack consistent discrimination across hypertension severity levels.

Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management.

BACKGROUND: Following kidney transplantation (KT), cytomegalovirus (CMV) infection remains an important challenge. Both prophylactic and preemptive antiviral protocols are used for CMV high-risk kidney recipients (donor seropositive/recipient seronegative; D+/R-). We performed a nationwide comparison of the 2 strategies in de novo D+/R- KT recipients accessing long-term outcomes. METHODS: A nationwide retrospective study was conducted from 2007 to 2018, with follow-up until February 1, 2022. All adult D+/R- and R+ KT recipients were included. During the first 4 y, D+/R- recipients were managed preemptively, changing to 6 mo of valganciclovir prophylaxis from 2011. To adjust for the 2 time eras, de novo intermediate-risk (R+) recipients, who received preemptive CMV therapy throughout the study period, served as longitudinal controls for possible confounders. RESULTS: A total of 2198 KT recipients (D+/R-, n = 428; R+, n = 1770) were included with a median follow-up of 9.4 (range, 3.1-15.1) y. As expected, a greater proportion experienced a CMV infection in the preemptive era compared with the prophylactic era and with a shorter time from KT to CMV infection ( P < 0.001). However, there were no differences in long-term outcomes such as patient death (47/146 [32%] versus 57/282 [20%]; P = 0.3), graft loss (64/146 [44%] versus 71/282 [25%]; P = 0.5), or death censored graft loss (26/146 [18%] versus 26/282 [9%]; P = 0.9) in the preemptive versus prophylactic era. Long-term outcomes in R+ recipients showed no signs of sequential era-related bias. CONCLUSIONS: There were no significant differences in relevant long-term outcomes between preemptive and prophylactic CMV-preventive strategies in D+/R- kidney transplant recipients.

Kidney Transplant Recipient Behavior During the Early COVID-19 Pandemic: A National Survey Study in Norway.

RATIONALE & OBJECTIVE: Studies published from countries with a high prevalence of COVID-19 have found increased incidence and a more severe disease course of coronavirus disease 2019 (COVID-19) in kidney transplant recipients than in the general population. We investigated how the first wave of the COVID-19 pandemic affected the everyday life of kidney transplant recipients in a country with a low infection burden. STUDY DESIGN: Prospective case-control study. SETTING & PARTICIPANTS: All adult kidney transplant recipients in Norway with a functioning graft and listed in the public phone registry (n = 3,060) and a group of randomly recruited individuals >18 years from the general population (n = 20,000) were invited to participate in the study by an SMS text message. In parallel, all kidney transplant recipients in Norway were invited to measure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG from mid-June to October 2020. PREDICTORS: The participants were asked to fill out a questionnaire focused on everyday life, travel history, exposure to known COVID-19 cases, and demographics. ANALYTICAL APPROACH: Groups were compared with independent tests using 2-sided 0.05 significance levels. RESULTS: A total of 1,007 kidney transplant recipients and 4,409 controls answered the questionnaire. The kidney transplant recipients reported being more concerned about SARS-CoV-2 infection (27%) than the control group (7%; P value < 0.001); ie, they behaved more carefully in their everyday life (not going to the grocery store, 5.9% vs 0.9%, P < 0.001; keeping at least 1 meter distance, 16.6% vs 5.8%, P < 0.001). Of the kidney transplant responders, 81% had a SARS-CoV-2 IgG taken; all were negative. LIMITATIONS: Mortality data is not reliable because of the low number of SARS-CoV-2 infected kidney transplant recipients in Norway. The relatively low questionnaire response rate for kidney transplant recipients is not optimal. CONCLUSIONS: The questionnaire shows that kidney transplant recipients have behaved more carefully compared with the general population with less social interaction and a very high degree of adherence to governmental advice.