Impact of Blood Pressure on Risk of Graft Failure or Death Among Patients After Kidney Transplantation in a 10-Year Observational Period: A Single-Center Retrospective Analysis.

BACKGROUND Hypertension is a risk factor for graft failure and mortality among kidney transplant recipients (KTRs). The aim of the study was to examine blood pressure (BP) as a factor that contributes to graft failure or death during a 10-year observation period. MATERIAL AND METHODS The study group comprised 70 KTRs who were treated according to their clinical state. Data were collected at 1 month and 1 year after transplantation and included office and ambulatory BP monitoring (ABPM) BP values, eGFR, proteinuria, and BMI. During the observation period, 6 patients died, and 10 lost the graft, but not during the first year. RESULTS Office and ABPM BP values were within normal ranges and did not differ from each other. eGRF and BMI were higher at 1 year compared to 1 month after transplantation, and proteinuria decreased. Among those who died, DBP was lower compared to those of survivors with graft failure. Proteinuria and donor age were positively correlated with BP. CONCLUSIONS Monitoring of BP and adequate treatment of hypertension resulting in BP values within normal values among KTRs contribute to longer survival of the graft and recipient. Older donor age and proteinuria could predict post-transplant hypertension. Low diastolic BP of the recipient could increase the risk of death among KTRs. Despite the fact that ABPM is the blood pressure measurement method of choice, appropriate standard office measurement could also be used for BP monitoring.

Unexpectedly High Efficacy of SARS-CoV-2 BNT162b2 Vaccine in Liver versus Kidney Transplant Recipients-Is It Related to Immunosuppression Only?

The BNT162b2 vaccine is reportedly effective in preventing severe disease in more than 90% of the general population, but its efficacy in transplant recipients remains controversial. We aimed to determine the immune response to the BNT162b2 vaccine in kidney (KTRs) and liver transplant recipients (LTRs). In this retrospective cohort study, we included randomly 65 KTRs and 65 LTRs, who received two 30 µg doses of BNT162b2 vaccine in 3-to6-week intervals. We analyzed the anti-SARS-CoV-2 spike protein IgG antibody (anti-S1 Ab) titer, biochemical liver and renal tests, immunosuppressive drug trough level, and clinical follow up 4-6 weeks after the first dose and 4-8 weeks after the second dose. The level of protective antibodies was 57.1% in KTRs and 88.9% in LTRs after the second dose. The anti-S1 Ab response was significantly associated with sex, age, and history of COVID-19. A tacrolimus dose at vaccination but not its trough level was significantly correlated with the increase in anti-S1 Ab titer after the second vaccine dose in LTRs. Rejection episodes did not occur after vaccination. Our results showed a higher than previously reported humoral response to the BNT162b2 vaccine in KTRs and LTRs, which was dependent upon age, type of transplanted organ, and immunosuppression.

Plasma microRNA-126-3p and neutrophil-to-lymphocyte ratio in patients with chronic kidney disease: relationships to ambulatory 24-h blood pressure.

Pro-inflammatory milieu of chronic kidney disease (CKD) results in endothelial damage and contributes to increased cardiovascular risk. The aim of the study was to evaluate association between neutrophil-to-lymphocyte ratio (NLR) and plasma relative expression of endothelially abundant miR-126-3p with circadian blood pressure (BP) pattern in CKD patients. This single-center observational study involved CKD stage 1-5 patients and healthy age- and sex-matched control subjects. All study participants had 24-h automatic blood pressure measurement (ABPM) performed. Plasma miRNA was quantified by qRT-PCR, in relation to endogenous U6 snRNA. In total, 90 CKD patients (60 ± 14 years, 52% males, 33 renal transplant recipients) and 25 healthy control subjects (55 ± 13 years, 48% males, p > 0.05) were enrolled in the study. We observed a positive correlation between miR-126-3p and average nighttime SBP (rho = 0.27, P = 0.02), average nighttime DBP (rho = 0.32, P = 0.003), night-day SBP ratio (ND-SBP), rho = 0.23, P = 0.03 and night-day DBP ratio (ND-DBP), rho = 0.26, P = 0.02. A positive association was found between NLR and average nighttime SBP (rho = 0.25, P = 0.01), ND-SBP (rho = 0.26, P = 0.006), and ND-DBP (rho = 0.28, P = 0.03). In the multiple regression model, NLR remained an independent predictor of average nighttime SBP (Beta per log change of NLR [95% CI]: 11.2 [1.8-10.6], P = 0.02), whereas miR-126-3p of nighttime DBP (1.88 [0.48; 3.28], p = 0.009), The results of our study point towards a link between both NLR and miR-126-3p and nighttime hypertension in CKD patients.

Simple platelet markers: Mean platelet volume and congestive heart failure coexistent with periodontal disease. Pilot studies.

BACKGROUND: Conducted pilot study concerning mean platelet volume (MPV) parameter among patients suffering from congestive heart failure and periodontal disease. METHODS: Examination of dynamic changes of platelet and periodontal markers in group of 50 patients before and an average of 6 months subsequent to professional periodontal treatment. RESULTS: Both platelet and periodontal parameters decreased after periodontal treatment, what is more, the decrease of MPV value due to periodontal disease/mm improvement was shown to be statistically significant (p = 0.05). CONCLUSIONS: Improvement of periodontal status may influence decrease of MPV value and increase of congestive heart failure treatment efficacy and effect patient comfort. It is a new, not frequently used pattern of chronic disease treatment optimalization.

CXCL12 in Patients with Chronic Kidney Disease and Healthy Controls: Relationships to Ambulatory 24-Hour Blood Pressure and Echocardiographic Measures.

BACKGROUND/AIMS: Chronic kidney disease is a pro-inflammatory condition where the interplay between different regulatory pathways and immune cells mediates an unfavorable remodeling of the vascular wall and myocardial hypertrophy. These mechanisms include the action of CXCL12. The aim of this study is to evaluate the association between serum CXCL12 with left ventricular hypertrophy (LVH) and blood pressure control in chronic kidney disease (CKD) patients. METHODS: This single-center observational study involved 90 stable CKD stage 1-5 patients (including 33 renal transplant recipients) and 25 healthy age- and sex-matched control subjects. CXCL12 was quantified by ELISA. 24-h ambulatory blood pressure monitoring was performed in 90 patients and 25 healthy controls. Left ventricular mass index (LVMI) was calculated based on the transthoracic echocardiography measurements in 27 patients out of the CKD population and in the whole control group. RESULTS: CXCL12 correlated significantly with LVMI by multivariate regression analysis (coefficient B = 0.33, p = 0.02) together with age (B = 0.30, p = 0.03) and gender (B = 0.41, p = 0.003). A positive correlation was observed between CXCL12 and average 24-h systolic blood pressure (SBP) (rho = 0.35, p = 0.001), daytime SBP (rho = 0.35, p = 0.001), and nocturnal SBP (rho = 0.30, p = 0.002). Nocturnal hypertension was frequent (46% of CKD patients). CONCLUSIONS: The results of our study point towards a link between CXCL12 and LVH as well as blood pressure control among patients with CKD, supporting the thesis that CXCL12 may be regarded as a new potential uremic toxin.

Circadian and short-term blood pressure abnormalities after liver transplantation.

Liver transplantation remains the only therapeutic method in end-stage liver disease. Cardiovascular system diseases, including arterial hypertension, are considered one of the main risk factors increasing mortality in this population. The aim of the study was the evaluation of circadian blood pressure patterns in liver transplant recipients. In a group of 107 liver transplant recipients, a 24-hour ambulatory blood pressure monitoring (ABPM) was performed. The ABPM revealed arterial hypertension in 88.79% and unsatisfactory blood pressure (BP) control in 71.03% of the study participants. The abnormal circadian BP pattern was observed in 90.65% of liver recipients. The subgroup of patients with preserved BP circadian rhythm was characterized by higher standard deviation (SD) and coefficient of variation (CV) values for 24-hour systolic, diastolic and mean arterial blood pressure (SBP, DBP, and MAP). There were no such differences for other short-term blood pressure variability (ST BPV) parameters: SD and CV of day-time and night-time SBP, DBP and MAP values. Arterial hypertension and circadian BP abnormalities are present in a majority of liver transplant recipients. BP circadian rhythm is not associated with ST BPV parameters assessed separately during awake and sleep period which suggests that both groups of parameters could reflect different cardiovascular phenomena after liver transplantation.

Plasma microRNA-155-5p is increased among patients with chronic kidney disease and nocturnal hypertension.

MicroRNAs play multiple roles in the regulation of blood pressure (BP). Nevertheless, to date, no study has assessed the association between microRNA plasma expression and BP control in chronic kidney disease (CKD) patients. Given this background, we evaluated the plasma expression of miR-155-5p, a translational inhibitor of angiotensin receptor type I, in CKD patients, to determine the association between miR-155-5p level and BP control. In this single-center cross-sectional study, we analyzed the miR-155-5p concentration by quantitative reverse transcriptase polymerase chain reaction using the U6 snRNA as a reference gene and 24-hour ambulatory blood pressure monitoring in CKD patients (stage ≥2) in relation to a control group of healthy age-matched and gender-matched individuals, with normal BP proven by the ambulatory blood pressure monitoring. We enrolled a total of 105 patients with CKD (stages 2-5, including 33 kidney renal transplant recipients), aged 59 ± 14 years; 47% males and 26 healthy volunteers (aged 55 ± 13, 50% male). Within the study group, a total of 36 patients (40%) presented with an average 24-hour systolic BP (SBP) ≥130 mm Hg and 41 patients (45%) presented nocturnal hypertension (NHT; SBP ≥120 mm Hg or diastolic BP ≥ 70 mm Hg). miRNA-155-5p was increased in plasma of CKD patients with median expression relative to control subjects equal to 2.92 (1.34-5.58). Interestingly, the plasma miRNA-155-5p expression was significantly higher in patients with NHT: 4.04 (2.92-10.8) versus 2.01 (1.21-3.07), P = .001 and its expression maintained an independent association with the average nocturnal SBP (coefficient B = 4.368, P = .047) by a multivariate regression analysis adjusted for confounders. The miR-155-5p was increased among CKD patients and further increased among subjects presenting with NHT. Further studies are warranted to determine the role of this non-coding RNA as a potential novel biomarker and therapeutic target in the non-dipping CKD individuals, characterized by increased cardiovascular risk.

Plasmatic NT-proBNP concentrations in patients with coexistent periodontal disease and congestive heart failure: pilot studies.

BACKGROUND: The presented pilot study was conducted in order to evaluate dynamic fluctuations of blood inflammation markers among patients with congestive heart failure (CHF) and coexistent periodontitis (PD). AIM: The study hypothesis stated that elimination of chronic inflammation caused by PD has a significant impact on inflammation markers and, secondarily, also on the course and prognosis of CHF. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and tumour necrosis factor alpha (TNF-α) markers were assessed due to their proven diagnostic significance. METHODS: Blood samples were collected at the time of CHF patients' admission to the clinical ward (I examination) and then after 3-9 months (average six months) after periodontal treatment completion (II examination). With antibiotic cover, basic periodontal parameters (such as CAL, PD, PI, BOP) were evaluated, scaling and root-planning were performed, and orthopantomogram X-rays were conducted. Patients received instructions about domestic oral hygiene procedures. Measurements were repeated during a second examination of blood samples. Obtained results were compared and statistically analysed. RESULTS: The initial outcome of the study confirmed the hypothesis that maintaining good and complex oral hygiene has an essential impact on blood concentration of NT-proBNP and TNF-α markers. CONCLUSIONS: Exploration of possibilities considering medical help and treatment optimisation seems to be evident also according to improvement of prognosis, therapy effectiveness, and patient comfort. Foregoing conclusions about biomarkers are, according to authors' best knowledge, the first such results reported in medical literature.

Blood pressure and intracranial aneurysms in autosomal dominant polycystic kidney disease.

BACKGROUND/AIMS: Autosomal dominant polycystic kidney disease (ADPKD) is correlated with an increased frequency of both intracranial aneurysms (ICANs), and arterial hypertension (AH). The aim of our study was to search for the association between blood pressure (BP) and ICANs in ADPKD patients. METHODS: Sixty-eight adult, pre-dialysis phase ADPKD patients underwent both screening for ICANs with magnetic resonance angiography of the brain, and ambulatory blood pressure monitoring (ABPM). RESULTS: ICANs were diagnosed in 10 patients (ICAN+ group), while in 58 were not (ICAN- group). The nighttime maximum diastolic blood pressure (DBP), maximum increase in DBP from measurement to measurement (positive delta of DBP) at night, and the standard deviation of the daytime mean arterial pressure were significantly higher in ICAN+ compared to ICAN- patients. Additionally, in a subgroup of patients after 45 years-of-age, ICAN+ patients had significantly higher maximum 24-hour and daytime systolic blood pressure, maximum 24-hour, daytime, nighttime DBP, maximum daytime and nighttime positive delta of DBP compared to ICAN- cases. CONCLUSIONS: Development of ICANs in hypertensive ADPKD patients is accompanied with higher values of some BP parameters measured by ABPM. Hypertensive ADPKD patients with substantial fluctuations in BP assessed by ABPM, especially those after 45 years-of-age, should become candidates for screening for ICANs.

Prevention of hepatitis B recurrence after liver transplantation using lamivudine and hepatitis B immune globulin.

BACKGROUND: Patients undergoing liver transplantation (ltx) for hepatitis B-related liver disease are prone to recurrence. Historically, ltx has been associated with aggressive reinfection and poor survival results. The mainstay of prophylaxis has been passive immunotherapy with hepatitis B immune globulin(HBIG). Antiviral prophylaxis with lamivudine appears to reduce hepatitis B virus (HBV)infection after liver transplantation. However, HBV recurrence remains common. This study retrospectively evaluated a single center's experience with cohort of patients who underwent ltx for HBV-related chronic and acute liver disease. We examined the effect of a combined of intravenous HBIG and lamivudine viral prophylactic therapy on HBV recurrence and the outcome of ltx. MATERIAL/METHODS: Eighteen patients underwent transplantation for HBV liver disease at our center. Before ltx all patients were HBsAg positive and 3 were HBV DNA positive. HBV recurrence was defined by HBsAg seropositivity after ltx. HBIG monotherapy was used in 2 (15%) patients, lamivudine monotherapy in 4 (31%), and lamivudine and HBIG combination in 7 (54%). Hepatocellular carcinoma was present in 1 patients. Maintenance immunosuppression regimens consisted of either a cyclosporine- or tacrolimus-based drug regimen. RESULTS: Overall 1-year and 3-years patient survival rates were 60% and 60%, respectively, and 1-year and 3-years graft survival was 60% and 60% respectively. Among 7 patients receiving receiving combination HBIG and lamivudine, one patient died. He was retransplanted 9 months after first transplantation secondary to biliary complication caused by late hepatic artery thrombosis. Of the 6 surviving patients, 4 patients currently have normal allograft function. Allograft dysfunction developed in two patients because of ischemic biliary strictures. Among seven patients, who received HBIG and lamivudine, one did not receive proper administration of the prophylactic regimen and graft became infected. Serologic HBV recurrence was diagnosed after 9 months after transplantation. CONCLUSIONS: Liver transplantation for HBV under combination viral prophylaxis results in good survival rates. A good outcome is possible after liver transplantation for HBV liver disease using HBIG dosed by pharmacokinetic parameters in combination with lamivudine. Viral prophylactic therapy has effectively reduced HBV recurrence and prolonged survival outcome.

[Treatment of diabetes mellitus in patients after renal transplantation]. / Problemy leczenia cukrzycy u chorych po zabiegu przeszczepienia nerki.

Diabetes mellitus (DM) is the most common metabolic disease, an independent risk factor of coronary disease, and shortens lifetime in all populations of patients, including kidney transplant recipients. Patients after kidney transplantation are exceptionally predisposed to develop or to exacerbate the preexisting DM. Age, DM in family, CMV infections, genetic factor (HLA A26 and B27), immunosuppressive treatment with steroids or calcineurin inhibitors belong to the major risk factors of diabetes. We analyzed 1300 renal transplant recipients in our center. Out of them 153 suffered from DM. DM de novo revealed 80 pts. Mean age in type I pts was 44.88 years and in type II pts was 57.27 years. De novo diabetics were 56.41 years old in average. CMV infection, potentially pathogenic in development of DM de novo, coexisted in 7.5% of these cases as frequently as in whole TPN population. Most frequently detected HLA antigens were: A2, B8 and DR5. Use of cyclosporine and tacrolimus promoted incidence of DM. We conclude, that low percentage of de novo DM in patients after renal transplantation may result from flexibility in administration of immunosuppressive regimens. Cyclosporine and tacrolimus treatment was switched to sirolimus or mycophenolate mofetil when the glucose intolerance was detected to prevent development of DM.

[Noninvasive monitoring of chronic glomerulonephritides progression]. / Nieinwazyjne monitorowanie progresji przewleklych klebuszkowych zapalen nerek.

Progression to end-stage renal failure is the final common pathway of many forms of glomerular diseases, independent of the type of initial insult. Tubulointerstitial fibrosis is tis near invariable finding and significant prognostic feature. We have reviewed immunological (cytokines, inflammatory cells) and nonimmunological factors (extracellular matrix proteins and proteolytic enzymes), being involved in mechanisms leading from glomerular disease to tubulointerstitial scarring, from the point of view of potential clinical usefulness of measuring its urine activities and levels to noninvasive diagnostic of kidney diseases.

[Expression of mRNA for growth factors and cytokines in the renal artery wall of chronically rejected renal allograft]. / Ekspresja mRNA czynników wzrostu i cytokin w scianie tetnicy nerkowej przeszczepionej nerki w okresie przewleklego odrzucania.

The vascular hallmark of chronic rejection (CR), as well as of atherosclerosis, is initial hyperplasia. It results from migration and proliferation of vascular smooth muscle cell and increased deposition of extracellular matrix proteins. A possible mechanism responsible for formation of neointima is the release of growth factors and cytokines, such as: transforming growth factor beta (TGF-beta), tumour necrosis factor alfa (TNF-alpha), interleukin 1 (IL-1) and interleukin 6 (IL-6). The expression of these factors in the renal artery wall of chronically rejected allografts was quantified. The renal artery samples were obtained from patients with chronic renal allograft rejection, undergoing graftectomy (n = 11) and patients with autosomal dominant polycystic kidney disease (ADPKD), undergoing nephrectomy (n = 4). Total RNA was isolated and the expression of mRNA for TGF-beta, TNF-alpha, IL-1 and IL-6 was measured using a real time PCR. In patients with CR the expression levels of TGF-beta, TNF-alpha and IL-1 mRNA were higher than in control group. No difference between groups was detected for IL-6. In both groups a correlation was detected between age and TGF-beta expression. The increased expression of TGF-beta, TNF-alpha and IL-1 may be a key factor in the neointimal formation and pathogenesis of CR. The increase in the TGF-b expression with age might be a protective mechanism in atherosclerosis.

[Effect of immunosuppressive treatment on diurnal profile of blood pressure]. / Wplyw leczenia immunosupresyjnego na dobowy profil cisnienia tetniczego krwi.

Prevalence of arterial hypertension suddenly rose in patients after renal transplantation since cyclosporine A was introduced. Arterial hypertension is now diagnosed in 67-90% of patients after renal transplantation. It has not only negative effect on cardiovascular system but also shortens survival of renal graft. Ambulatory blood pressure monitoring (ABPM) enables evaluation of diumal profile of BP and efficacy of treatment. This diagnostic tool is very useful in the management of these patients. Nocturnal hypertension was 2.5 times more frequent than daytime elevation of BP in the group of 58 consecutive renal transplant patients treated with calcineurin inhibitors who were assessed by ABPM at our department. Lack of nocturnal dip of BP was observed in most of the patients. Conversion from calcineurin inhibitors (cyclosporine A, tacrolimus) to sirolimus or mycophenolate mofetil may improve BP profile in this group of patients.