The role of non-HLA antibodies named antiendothelin A receptor antibodies is potentially significant but not established. The significance of the endothelin A receptor (ETAR) and its expression in ...renal biopsy has not been defined. We decided to evaluate the presence and relevance of ETARs in renal transplant biopsy for cause.
The aim of our study was to evaluate the immunoreactivity of the ETAR and its significance in patients who had a renal transplant biopsy due to deterioration of transplant function (biopsy for cause) with detailed characterization of staining in small and intermediate arteries of renal transplant biopsies.
Immunohistochemical expression of ETARs was analyzed in 162 renal transplant biopsies. Microscopic evaluation of ETAR expression (polyclonal antibody) was performed on paraffin sections. ETAR expression was analyzed in renal blood vessels (small and intermediate arteries) based on three-step scale.
We analyzed 154 patients who had renal allograft biopsy between 6 days and 24 years (median 597 days) after transplantation. Positive staining of ETAR in small and intermediate arteries was noticed in 9 patients. Among these patients, 4 had early biopsies (<3 months after transplantation), all developed acute tubular necrosis, and 1 developed additionally acute humoral rejection. Further, 4 patients had late biopsy (1-8 years after transplantation) and all developed characteristics of antibody mediated rejection. Lastly, 1 patient had no characteristic changes in the biopsy 4 months after transplantation. Graft loss 1 year after biopsy was higher in patients who were ETAR-positive but statistical significance was not achieved.
The expression of endothelin receptors in renal blood vessels (small and intermediate arteries) seems to be important in diagnosis of damage during acute tubular necrosis and antibody-mediated rejection.
Hypertension is prevalent in most patients after renal transplantation, and it is the main factor contributing to cardiovascular diseases that cause death of a significant number of these patients. ...Up to 95% of patients after transplantation have hypertension, and among them are patients with refractory hypertension. Elevated blood pressure is one of the causes of deterioration of transplant function and may accelerate transplant loss.
We present the first case in the world of a patient (who was 61 years old) in whom denervation of native renal arteries was performed after renal transplantation (2004). The patient was suffering from uncontrolled refractory hypertension. Antihypertensive therapy was used but the effect was not satisfactory. The patient received amlodipine, bisoprolol, clonidine, furosemide, and doxazosin in high doses. Clinical assessments with ambulatory blood pressure monitoring revealed a predominant blood pressure 149/96 with incidents of hypertensive crises. High blood pressure is a cardiovascular risk factor and it also has a significant influence on transplant failure, which was the reason for performing the denervation. The procedure was carried out through the femoral artery with the use of a 6F guiding catheter. During a 3-year observation, significant decreases in ambulatory blood pressure monitoring systolic and diastolic blood pressures were observed after the procedure (149/96 mm Hg vs 134/91 mm Hg before and after the denervation, respectively). There was a significant regression of left ventricle mass (577 g before denervation vs 470 g after 3 years). The functioning of the renal transplant became stable after 3 years of observation (38 mL/min before denervation and 38 mL/min after 3 years).
The first case in the world of a renal transplant patient who had denervation of native renal arteries has demonstrated a positive effect in controlling blood pressure over a 3-year observation. Three years after denervation, a reduction of heart hypertrophy and stabilization of renal function were noted. The presented case shows that denervation of native renal arteries denervation may be successful and safe in kidney transplant recipients.
•Refractory hypertension remains a big problem in patients after kidney transplantation.•Renal artery denervation is a method of treatment of a refractory hypertension.•Renal artery denervation is a new way to decrease heart hypertrophy.
ABSTRACT
Background
We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with ...advanced chronic kidney disease (CKD).
Methods
The EQUAL study is a European observational prospective cohort study with an incident eGFR <20 ml/min per 1.73 m2 and ≥65 years of age. The evolution of each clinical indicator was explored using generalized additive models during the 4 years preceding death.
Results
We included 661 decedents with a median time to death of 2.0 years (IQR 0.9–3.2). During the years preceding death, eGFR, Subjective Global Assessment score, and blood pressure declined, with accelerations seen at 6 months preceding death. Serum hemoglobin, hematocrit, cholesterol, calcium, albumin, and sodium values declined slowly during follow-up, with accelerations observed between 6 and 12 months preceding death. Physical and mental quality of life declined linearly throughout follow-up. The number of reported symptoms was stable up to 2 years prior to death, with an acceleration observed at 1 year prior to death. The rate of hospitalization was stable at around one hospitalization per person year, increasing exponentially at 6 months preceding death.
Conclusions
We identified clinically relevant physiological accelerations in patient trajectories that began ∼6 to 12 months prior to death, which are likely multifactorial in nature, but correlate with a surge in hospitalizations. Further research should focus on how to effectively use this knowledge to inform patient and family expectations, to benefit the planning of (end-of-life) care, and to establish clinical alert systems.
Graphical Abstract
Graphical Abstract
Background People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic kidney ...disease (CKD). The aim of this study was to prospectively study the association between cTnT and GFR over time in older advanced-stage CKD patients not on dialysis. Methods and Results The EQUAL (European Quality Study) study is an observational prospective cohort study in stage 4 to 5 CKD patients aged ≥65 years not on dialysis (incident estimated GFR, <20 mL/min/1.73 m²). The EQUAL cohort used for the purpose of this study includes 171 patients followed in Sweden between April 2012 and December 2018. We used linear mixed models, adjusted for important groups of confounders, to investigate the effect of both measured GFR and estimated GFR on high-sensitivity cTnT (hs-cTnT) trajectory over 4 years. Almost all patients had at least 1 hs-cTnT measurement elevated above the 99th percentile of the general reference population (≤14 ng/L). On average, hs-cTnT increased by 16%/year (95% CI, 13-19;
<0.0001). Each 15 mL/min/1.73 m
lower mean estimated GFR was associated with a 23% (95% CI, 14-31;
<0.0001) higher baseline hs-cTnT and 9% (95% CI, 5-13%;
<0.0001) steeper increase in hs-cTnT. The effect of estimated GFR on hs-cTnT trajectory was somewhat lower than a previous myocardial infarction (15%), but higher than presence of diabetes mellitus (4%) and male sex (5%). Conclusions In CKD patients, hs-cTnT increases over time as renal function decreases. Lower CKD stage (each 15 mL/min/1.73 m
lower) is independently associated with a steeper hs-cTnT increase over time in the same range as other established cardiovascular risk factors.
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