Disease Course, Management and Outcomes in Kidney Transplant Recipients with SARS-CoV-2 Infection during the Omicron-Variant Wave: A Single-Center Experience.

BACKGROUND: Since December 2019, kidney transplant recipients (KTRs) have experienced a great impact of the coronavirus disease 2019 (COVID-19) pandemic, with a higher risk of morbidity and mortality compared to the general population. Preliminary data in KTRs suggest that the Omicron variant, which has been dominant since December 2021, is more infectious than the previous ones but is associated with reduced risk of severity and low lethality rates. The purpose of our study was to assess the disease course and outcomes of the SARS-CoV-2 infection in KTRs during the Omicron-surge. METHODS: This retrospective study included 451 KTRs diagnosed with SARS-CoV-2 infection between 1 December 2021 and 30 September 2022. Demographic and clinical characteristics at the time of infection, vaccination data, treatment, clinical course, and outcomes were recorded and analyzed. RESULTS: Mean age was 51.8 ± 13.7 years with a male predominance (61.2%). The majority (76.1%) were vaccinated with at least three doses of the available mRNA vaccines, although serology revealed low anti-SARS-CoV-2 antibody titers before infection (33 [3.3-1205] AU/mL). Only 6% of the patients experienced moderate-severe disease. Accordingly, there was low prevalence of adverse outcomes, such as SARS-CoV-2-related hospitalization (11.3%) and death (0.9%). Multivariate analysis revealed that only age significantly increased the risk of SARS-CoV-2-related hospitalization. CONCLUSIONS: During the Omicron wave, the clinical course of the SARS-CoV-2 infection in KTRs has substantially changed, with lower rates of moderate and severe disease and a low prevalence of adverse outcomes. Prospective clinical trials are warranted to further elucidate the evolving pathogenesis, management, and long-term outcomes of COVID-19 in such high-risk populations.

Kidney transplantation and kidney donation do not affect short-term blood pressure variability.

PURPOSE: Blood pressure variability (BPV) is an independent cardiovascular risk factor in CKD. Kidney transplantation (KTx) is associated with improved BP levels for kidney transplant recipient (KTRs), without evoking significant changes in donors. The aim of this study was to assess the short- and mid-time effects of KTx and donation on short-term BPV in KTRs and their respective living kidney donors. MATERIALS AND METHODS: Forty KTRs and their respective donors were evaluated with 24-h ABPM (Mobil-O-Graph-NG) at baseline (1 month before), 3-months and 12-months after KTx. Standard-deviation (SD), weighted-SD (wSD), coefficient-of-variation (CV), average-real-variability (ARV) and variability independent of mean (VIM) for SBP/DBP were calculated with validated formulas. RESULTS: All 24-h systolic and diastolic BPV indexes studied did not change significantly from baseline to 3-month (SBP-wSD: 12.8 ± 3.0 vs 13.2 ± 3.4 mmHg, p = 0.608; SBP-ARV: 10.3 ± 2.4 vs 10.8 ± 2.6 mmHg, p = 0.463) and 12-month evaluation (SBP-wSD 12.8 ± 3.0 vs 12.1 ± 2.8; p = 0.424 and SBP-ARV: 10.3 ± 2.4 vs 10.2 ± 2.5; p = 0.615) after kidney transplantation in the KTRs.In kidney donors, all 24-h systolic BPV indices displayed a trend towards higher values at 3 months compared to baseline, but without reaching statistical significance (SBP-wSD: 12.2 ± 2.8 vs 13.6 ± 4.2 mmHg, p = 0.107 and SBP-ARV: 10.1 ± 2.1 vs 11.2 ± 3.1 mmHg, p = 0.099), the levels of 24-h systolic SBP indices at 12-months were almost identical to baseline values. 24-h diastolic BPV indices at 3-month and 12-month evaluation were similar to baseline. CONCLUSION: Short-term BPV did not change significantly 3 and 12 months after kidney transplantation/donation neither in KTRs nor in living kidney donors. Longitudinal studies examining associations of BPV with adverse outcomes in these individuals are needed.

What is the context? Previous studies have shown that both office and ambulatory BP levels are significantly reduced after kidney transplantation in KTRs.On the other hand, existing evidence suggests that kidney donors' BP levels do not change significantly after kidney donation.Existing studies on BPV in KTRs are limited. The available data for living kidney donors are even fewer.What is new? This is the first study assessing short-term BPV levels in ΚTRs undergoing living donor kidney transplantation, and their respective donors in short-term and mid-term follow-up. The main findings were:All 24-h, daytime and night-time BPV indexes did not change significantly from baseline to 3- and 12-month evaluation after kidney transplantation in the KTRs.No significant changes for the 24-h, daytime and night-time BPV were observed in their respective kidney donors at the same follow-up periods.What is the impact?High BPV, which seems to remain unaltered after kidney transplantation, may be one of the many factors involved in the high cardiovascular risk observed in KTRs.Unchanged BPV levels further supports the evidence suggesting no higher risks of arrhythmias, cardiovascular events or death after living kidney donation.

Sex-related short-term blood pressure variability differences in kidney transplant recipients.

OBJECTIVE: Kidney transplant recipients (KTRs) display higher cardiovascular morbidity and mortality than the general population. Increased short-term blood pressure variability (BPV) is associated with a higher risk of adverse cardiovascular outcomes in chronic kidney disease (CKD). The aim of this study is to investigate sex differences in short-term BPV in KTRs. METHODS: In total, 136 male and 69 female KTRs with valid 24 h ambulatory blood pressure monitoring were included in this analysis. Systolic and diastolic BPV indices [SD, weighted SD (wSD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM)] were calculated with validated formulas for the 24 h, daytime and nighttime periods. RESULTS: Age, time from transplantation surgery and history of major comorbidities did not differ between men and women. During the 24-h period, systolic BPV indices did not differ between men and women (SBP-ARV: 9.4 ± 2.2 vs. 9.9 ± 2.5; P = 0.212). During the daytime period, SBP-CV and SBP-VIM were significantly higher in females compared with male participants (SBP-CV: 9.9 ± 2.4 vs. 11 ± 3.1%; P = 0.022 and SBP-VIM: 12.6 ± 3.0 vs 14.2 ± 3.9; P = 0.008); daytime SBP-SD and SBP-ARV, and all studied indexes during nighttime did not differ between groups. No significant between-group differences in 24 h and daytime diastolic BPV indices were detected. Nighttime DBP-CV was marginally higher in men (12.0 ± 3.6 vs. 11.4 ± 4.0; P = 0.053); the rest nighttime diastolic BPV indices measured were also nonsignificantly higher in men. CONCLUSION: In conclusion, 24-h systolic and diastolic BPV parameters did not differ between male and female KTRs, but short-term BPV over the respective day- and nighttime periods showed different trends in men and women. Further studies are needed to examine possible differences in long-term BPV in KTRs.

Ambulatory blood pressure trajectories and blood pressure variability in kidney transplant recipients: a comparative study against chronic kidney disease patients.

BACKGROUND: Hypertension is a major cardiovascular risk factor in both kidney transplant recipients (KTRs) and patients with chronic kidney disease (CKD). Ambulatory blood pressure monitoring (ABPM) is considered the gold-standard method for hypertension management in these subjects. This is the first study evaluating the full ambulatory blood pressure (BP) profile and short-term BP variability (BPV) in KTRs versus CKD patients without kidney replacement therapy. METHODS: Ninety-three KTRs were matched with 93 CKD patients for age, sex, and estimated glomerular filtration rate. All participants underwent 24-hour ABPM. Mean ambulatory BP levels, BP trajectories, and BPV indices (standard deviation [SD], weighted SD, and average real variability) were compared between the two groups. RESULTS: There were no significant between-group differences in 24-hour systolic BP (SBP)/diastolic BP (DBP) (KTRs: 126.9 ± 13.1/79.1 ± 7.9 mmHg vs. CKD: 128.1 ± 11.2/77.9 ± 8.1 mmHg, p = 0.52/0.29), daytime SBP/DBP and nighttime SBP; nighttime DBP was slightly higher in KTRs (KTRs: 76.5 ± 8.8 mmHg vs. CKD: 73.8 ± 8.8 mmHg, p = 0.04). Repeated measurements analysis of variance showed a significant effect of time on both ambulatory SBP and DBP (SBP: F = [19, 3002] = 11.735, p < 0.001, partial η2 = 0.069) but not of KTR/CKD status (SBP: F = [1, 158] = 0.668, p = 0.42, partial η2 = 0.004). Ambulatory systolic/diastolic BPV indices were not different between KTRs and CKD patients, except for 24-hour DBP SD that was slightly higher in the latter group (KTRs: 10.2 ± 2.2 mmHg vs. CKD: 10.9 ± 2.6 mmHg, p = 0.04). No differences were noted in dipping pattern between the two groups. CONCLUSION: Mean ambulatory BP levels, BP trajectories, and short-term BPV indices are not significantly different between KTRs and CKD patients, suggesting that KTRs have a similar ambulatory BP profile compared to CKD patients without kidney replacement therapy.

Ambulatory blood pressure trajectories and blood pressure variability in kidney transplant recipients: a comparative study against haemodialysis patients.

Background: Hypertension is the most prevalent cardiovascular risk factor in kidney transplant recipients (KTRs). Preliminary data suggest similar ambulatory blood pressure (BP) levels in KTRs and haemodialysis (HD) patients. This is the first study comparing the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus HD patients. Methods: A total of 204 KTRs were matched (2:1 ratio) with 102 HD patients for age and gender. BP levels, BP trajectories and BPV indices over a 24-h ambulatory BP monitoring (ABPM) in KTRs were compared against both the first and second 24-h periods of a standard 48-h ABPM in HD patients. To evaluate the effect of renal replacement treatment and time on ambulatory BP levels, a two-way ANOVA for repeated measurements was performed. Results: KTRs had significantly lower systolic blood pressure (SBP) and pulse-pressure (PP) levels compared with HD patients during all periods studied (24-h SBP: KTR: 126.5 ± 12.1 mmHg; HD first 24 h: 132.0 ± 18.1 mmHg; P = 0.006; second 24 h: 134.3 ± 17.7 mmHg; P < 0.001); no significant differences were noted for diastolic blood pressure levels with the exception of the second nighttime. Repeated measurements ANOVA showed a significant effect of renal replacement therapy modality and time on ambulatory SBP levels during all periods studied, and a significant interaction between them; the greatest between-group difference in BP (KTRs-HD in mmHg) was observed at the end of the second 24 h [-13.9 mmHg (95% confidence interval -21.5 to -6.2); P < 0.001]. Ambulatory systolic and diastolic BPV indices were significantly lower in KTRs than in HD patients during all periods studied (24-h SBP average real variability: KTRs: 9.6 ± 2.3 mmHg; HD first 24 h: 10.3 ± 3.0 mmHg; P = 0.032; second 24 h: 11.5 ± 3.0 mmHg; P < 0.001). No differences were noted in dipping pattern between the two groups. Conclusions: SBP and PP levels and trajectories, and BPV were significantly lower in KTRs compared with age- and gender-matched HD patients during all periods studied. These findings suggest a more favourable ambulatory BP profile in KTRs, in contrast to previous observations.

Occurrence of Severe SARS-CoV-2 Infection in Fully Vaccinated Solid Organ Transplant Recipients.

The present study presents the clinical outcome of SARS-CoV-2 disease in relation to the humoral response in fully vaccinated solid organ transplant (SOT) recipients. Our patient cohort consists of 455 SOT recipients, vaccinated with one of the 2 approved mRNA vaccines. The antibody response was measured 1 month after the second dose, and previously infected patients have been excluded. Of the 449 remaining patients, 15 (3.34%) tested positive, using SARS-CoV-2 polymerase chain reaction. Their mean age was 43.7 ±14.4 years, and median time from transplantation was 7.8 years (1.2-30.2). Eleven patients (73.3%) had been vaccinated with BNT162b2 and 4 (26.7%) with the mRNA1273 vaccine. At the time of infection 9 (60%) patients had a negative (<50 AU/mL) antibody titer, and 6 (40%) had a positive one (>50 AU/mL). Median antibody titer, 27.4± 14.0 days after the second dose, measured at 13 AU/mL (0-7480 AU/mL). Renal function did not appear to be affected by the disease. Τhe mean estimated glomerular filtration rate at diagnosis was 48 ± 15 mL/min, and when in a 29-day (1-101) median follow-up was 53.9± 20.9 mL/min. Of the 15 patients, 7 had mild symptoms and were not hospitalized, and of the remaining 8 (53.3%) who needed hospitalization 7 had severe disease and 2 of them expired. The study confirms the variable and often severe course of coronavirus 2019 infection in SOT recipients, even after their full vaccination, highlighting the need to vaccinate their close relatives and to accelerate the implementation of the booster dose of vaccine.

Prevalence and factors associated with hyperkalaemia in stable kidney transplant recipients.

BACKGROUND: Hyperkalaemia is a frequent and potentially life-threatening condition in patients with chronic kidney disease (CKD). Even after successful kidney transplantation (KTx), KTx recipients have mild to severe CKD. Moreover, they share comorbid conditions and frequently use medications that predispose to hyperkalaemia. This study aimed to examine the prevalence and factors associated with hyperkalaemia in this population. METHODS: Over a pre-specified period of 6 months (1 September 2019 to 31 March 2020), we recorded in cross-sectional fashion information on serum potassium (K+) and relevant demographics, comorbidities, medications, laboratory and transplant-associated variables in clinically stable KTx recipients attending the Transplant Outpatient Clinic of our Department. Ηyperkalaemia was classified as follows: serum K+ level >5.0 mEq/L; and further as >5.0 mEq/L with concomitant use of sodium (Na+) polystyrene sulphonate; serum K+ ≥5.2 mEq/L; serum K+ ≥5.5 mEq/L. Univariate and multiple logistic regression analyses were used to identify factors associated with serum K+ >5.0 mEq/L. RESULTS: The study population consisted of 582 stable KTx recipients, 369 (63.4%) males, aged 52.4 ± 13.5 years, with estimated glomerular filtration rate (eGFR) of 55.8 ± 20.1 mL/min/1.73 m2 transplanted for >1 year. The prevalence of hyperkalaemia defined as K+ >5.0 mEq/L; >5.0 mEq/L and use of Na+ polystyrene sulphonate; K+ ≥5.2; or K+ ≥5.5 mEq/L, was: 22.7, 22.7, 14.4 and 4.1% (132, 132, 84 and 24 patients), respectively. In multivariate analysis, male gender [odds ratio (OR) = 2.020, 95% confidence interval (CI) 1.264-3.227] and use of renin-angiotensin-aldosterone system (RAAS) blockers (OR = 1.628, 95% CI 1.045-2.536) were independently associated with hyperkalaemia, while higher eGFR (OR = 0.967, 95% CI 0.955-0.979) and use of non-K+-sparing diuretics (OR = 0.140, 95% CI 0.046-0.430) were associated with lower odds of the disorder. CONCLUSIONS: The prevalence of mild hyperkalaemia in stable KTx recipients is relatively high but that of moderate or severe hyperkalaemia is low. Among a wide range of factors studied, only male gender and RAAS blockade were associated with increased odds of hyperkalaemia, while higher eGFR and diuretics were associated with decreased odds of hyperkalaemia.

A parallel evaluation of short- and mid-term changes of ambulatory blood pressure in kidney transplant recipients and kidney donors.

Introduction: Kidney transplantation (KTx) is associated with improved blood pressure (BP) levels for kidney transplant recipients (KTRs) without evoking significant changes in donors. However, there is a paucity of studies offering simultaneous detailed evaluation of BP profiles over time in transplant donor-recipient pairs. The aim of the present study was the parallel evaluation of ambulatory BP levels and trajectories in KTRs and their respective living kidney donors in the short and mid-term following KTx. Methods: The study enrolled 40 prospective adult KTRs and their 40 respective donors. All participants were evaluated with 24-h ambulatory BP monitoring (Mobil-O-Graph NG device) at three time points: baseline (1 month before KTx), 3 months and 12 months after KTx. Results: In KTRs, 3-month 24-h systolic BP (SBP) was marginally reduced and 12-month 24-h SBP significantly reduced compared with baseline [131.9 ± 13.3 versus 126.4 ± 11.9 mmHg (P = .075) and 123.9 ± 10.3 mmHg (P = .009),  respectively]. At both the 3- and 12-month time points, 24-h diastolic BP (DBP) was significantly reduced [86.7 ± 11.5 versus 82.2 ± 8.1 mmHg (P = .043) and 80.3 ± 8.5 mmHg (P = .009)]. Similar observations were made for day- and night time SBP and DBP. Repeated-measures analysis of variance (ANOVA) showed a significant gradual decrease over time in mean 24-h SBP [F(1.463, 39.505) = 3.616; P = .049, partial η 2 = 0.118] and DBP [F(1.374, 37.089) = 11.34; P = .055, partial η 2 = 0.116]. In contrast, in kidney donors, 24-h SBP [118.5 ± 11.6 versus 118.2 ± 12.8 mmHg (P = .626) and 119.2 ± 11.4 mmHg (P = .748)] and DBP did not change at 3 or 12 months compared with baseline; repeated measures ANOVA showed no differences in the mean 24-h SBP and DBP levels over time. The number of antihypertensive agents decreas in KTRs and remained stable in donors. Conclusions: KTx reduces ambulatory BP levels and trajectories in KTRs at 3 months and further so at 12 months post-surgery. Kidney donation does not affect the ambulatory BP levels and trajectories of donors at the same intervals.

Sex differences in ambulatory blood pressure levels, control, and phenotypes of hypertension in kidney transplant recipients.

OBJECTIVES: Ambulatory blood pressure (BP) control is worse in men compared with women with chronic kidney disease (CKD) and this may partially explain the faster CKD progression in men. This is the first study investigating possible sex differences in prevalence, control and phenotypes of hypertension in kidney transplant recipients (KTRs) with office-BP and 24-h ambulatory BP monitoring (ABPM). METHODS: This cross-sectional study included 136 male and 69 female stable KTRs who underwent office-BP measurements and 24-h ABPM. Hypertension thresholds for office and ambulatory BP were defined according to the 2017 ACC/AHA and 2021 KDIGO guidelines for KTRs. RESULTS: Age, time from transplantation, eGFR and history of major comorbidities did not differ between groups. Office SBP/DBP levels were insignificantly higher in men than women (130.3 ±â€Š16.3/77.3 ±â€Š9.4 vs. 126.4 ±â€Š17.8/74.9 ±â€Š11.5 mmHg; P = 0.118/0.104) but daytime SBP/DBP was significantly higher in men (128.5 ±â€Š12.1/83.0 ±â€Š8.2 vs. 124.6 ±â€Š11.9/80.3 ±â€Š9.3 mmHg; P = 0.032/P = 0.044). No significant between-group differences were detected for night-time BP. The prevalence of hypertension was similar by office-BP criteria (93.4 vs. 91.3%; P = 0.589), but higher in men than women with ABPM (100 vs. 95.7%; P = 0.014). The use of ACEIs/ARBs and CCBs was more common in men. Office-BP control was similar (43.3 vs. 44.4%, P = 0.882), but 24-h control was significantly lower in men than women (16.9 vs. 30.3%; P = 0.029). White-coat hypertension was similar (5.1 vs. 7.6%; P = 0.493), whereas masked hypertension was insignificantly more prevalent in men than women (35.3 vs. 24.2%; P = 0.113). CONCLUSION: BP levels, hypertension prevalence and control are similar by office criteria but significantly different by ABPM criteria between male and female KTRs. Worse ambulatory BP control in male compared with female KTRs may interfere with renal and cardiovascular outcomes.

Diagnostic Performance of Office versus Ambulatory Blood Pressure in Kidney Transplant Recipients.

INTRODUCTION: Hypertension is the most prominent risk factor in kidney transplant recipients (KTRs). No study so far assessed in parallel the prevalence, control, and phenotypes of blood pressure (BP) or the accuracy of currently recommended office BP diagnostic thresholds in diagnosing elevated ambulatory BP in KTRs. METHODS: 205 stable KTRs underwent office BP measurements and 24-h ambulatory BP monitoring (ABPM). Hypertension was defined as follows: (1) office BP ≥140/90 mm Hg or use of antihypertensive agents following the current European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines, (2) office BP ≥130/80 mm Hg or use of antihypertensive agents following the current American College of Cardiology/American Heart Association (ACC/AHA) guidelines, (3) ABPM ≥130/80 mm Hg or use of antihypertensive agents, and (4) ABPM ≥125/75 mm Hg or use of antihypertensive agents. RESULTS: Hypertension prevalence by office BP was 88.3% with ESC/ESH and 92.7% with ACC/AHA definitions compared to 94.1 and 98.5% at relevant ABPM thresholds. Control rates among hypertensive patients were 69.6 and 43.7% with office BP compared to 38.3 and 21.3% with ABPM, respectively. Both for prevalence (κ-statistics = 0.52, p < 0.001 and 0.32, and p < 0.001) and control rates (κ-statistics = 0.21, p < 0.001 and 0.22, and p < 0.001, respectively), there was moderate or fair agreement of the 2 techniques. White-coat and masked hypertension were diagnosed in 6.7 and 39.5% of patients at the 140/90 threshold and 5.9 and 31.7% of patients at the 130/80 threshold. An office BP ≥140/90 mm Hg had 35.3% sensitivity and 84.9% specificity for the diagnosis of 24-h BP ≥130/80 mm Hg. An office BP ≥130/80 mm Hg had 59.7% sensitivity and 73.9% specificity for the diagnosis of 24-h BP ≥125/75 mm Hg. Receiver operating curve analyses confirmed this poor diagnostic performance. CONCLUSIONS: At both corresponding thresholds studied, ABPM revealed particularly high hypertension prevalence and poor BP control in KTRs. Misclassification of KTRs by office BP is substantial, due to particularly high rates of masked hypertension. The diagnostic accuracy of office BP for identifying elevated ambulatory BP is poor. These findings call for a wider use of ABPM in KTRs.

A Systematic Review of COVID-19 Infection in Kidney Transplant Recipients: A Universal Effort to Preserve Patients' Lives and Allografts.

The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to physicians and healthcare systems worldwide. Evidence about kidney transplant (KTx) recipients is still limited. A systematic literature review was performed. We included 63 articles published from 1 January until 7 July 2020, reporting on 420 adult KTx recipients with confirmed COVID-19. The mean age of patients was 55 ± 15 years. There was a male predominance (67%). The majority (74%) were deceased donor recipients, and 23% were recently transplanted (<1 year). Most patients (88%) had at least one comorbidity, 29% had two, and 18% three. Ninety-three percent of cases were hospitalized. Among them, 30% were admitted to the intensive care unit, 45% developed acute respiratory distress syndrome, and 44% had acute kidney injury with 23% needing renal replacement therapy. From the hospitalized patients a total of 22% died, 59% were discharged, and 19% were still in hospital at the time of publication. Immunosuppression was reduced in 27%, discontinued in 31%, and remained unchanged in 5%. Hydroxychloroquine was administered to 78% of patients, antibiotics to 73%, and antivirals to 30% while 25% received corticosteroid boluses, 28% received anti-interleukin agents, and 8% were given immunoglobulin. The main finding of our analysis was that the incidence of COVID-19 among kidney transplant patients is not particularly high, but when they do get infected, this is related to significant morbidity and mortality.

Arterial Stiffness in Patients With Renal Transplantation; Associations With Co-morbid Conditions, Evolution, and Prognostic Importance for Cardiovascular and Renal Outcomes.

Patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD), are at increased risk of cardiovascular events and mortality. The spectrum of arterial remodeling in CKD and ESRD includes atheromatosis of middle-sized conduit arteries and, most importantly, the process of arteriosclerosis, characterized by increased arterial stiffness of aorta and the large arteries. Longitudinal studies showed that arterial stiffness and abnormal wave reflections are independent cardiovascular risk factors in several populations, including patients with CKD and ESRD. Kidney transplantation is the treatment of choice for patients with ESRD, associated with improved survival and better quality of life in relation to hemodialysis or peritoneal dialysis. However, cardiovascular mortality in transplanted patients remains much higher than that in general population, a finding that is at least partly attributed to adverse lesions in the vascular tree of these patients, generated during the progression of CKD, which do not fully reverse after renal transplantation. This article attempts to provide an overview of the field of arterial stiffness in renal transplantation, discussing in detail available studies on the degree and the associations of arterial stiffness with other co-morbidities in renal transplant recipients, the prognostic significance of arterial stiffness for cardiovascular events, renal events and mortality in these individuals, as well as studies examining the changes in arterial stiffness following renal transplantation.