Magnetic resonance imaging 3t and total fibrotic volume in autosomal dominant polycystic kidney disease

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal hereditary disorder. Several authors have attempted to identify a kidney damage marker for predicting the prognosis and the effectiveness of therapy in ADPKD. The aim of this study was to identify and quantify in ADPKD, through a novel MR protocol with 3 Tesla (MRI 3Tesla), the presence of parenchymal fibrotic tissue at early stage of disease, able to correlate the glomerular filtrate and to predict the loss of the function renal. MATERIAL AND METHODS: 15 ADPKD patients undergone to renal MRI 3Tesla at T0 and revaluated after follow up (T1) of 5 years. We have evaluated renal function, plasma aldosterone concentration (PAC), insulin resistance and surrogate markers of atherosclerosis (carotid intima media thickness (IMT), ankle/brachial index (ABI) and left ventricular mass index (LVMI). RESULTS: Our study showed a significant negative correlation between total kidney volume and estimated glomerular filtration rate (eGFR) during observational observation (p<0.02). Moreover, we showed a negative correlation between eGFR with Total Fibrotic Volume (TFV) (p<0.04) and Total Perfusion Volume/Total kidney Volume(<0.02). Moreover TFV was correlated positively with PAC (p<0.05), insulin values (p<0.05), ABI (p <0.05) and LVMI(p<0.01). CONCLUSIONS: The MRI 3Tesla, despite the high costs, could be considered an useful and non-invasive method in the evaluation of fibrotic tissue and progression of the disease in ADPKD patients. Further clinical trials on larger group are due to confirm the results of this pilot study, suggesting that MRI 3Tesla can be useful to evaluate the effectiveness of new therapeutic strategies. This article is protected by copyright. All rights reserved

reduction in heart rate variability in autosomal dominant polycystic kidney disease

Introduction: Cardiovascular disease is one of the main causes of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Autonomic dysfunction is associated with an increased risk for all cardiovascular events in the general population and can be evaluated with heart rate variability (HRV). Objective: To evaluate HRV in ADPKD patients with mild hypertension versus hypertensive patients with organ damage and healthy controls (HC). Materials and Methods: We have enrolled 65 patients: 21 ADPKD patients (10 males), 20 patients with hypertension (14 males), and 24 HC (10 males). Biochemical analysis, clinical evaluation, anthropometric data, intima-media thickness, 24-h ECG Holter recording, and echocardiography were investigated at the time of enrollment. Results: No significant differences in HRV parameters were found between ADPKD with mild hypertension and hypertensive patients with organ damage. The median of HRV variables in time domain as SDNN (global autonomic activity) was significantly lower in ADPKD and hypertensive patients than HC (p < 0.05). In the frequency domain analysis, low frequency (LF), which mainly reflects the sympathetic component, showed higher values in ADPKD and hypertensive patients than HC during the night (p < 0.01). During the night, the sympathovagal balance, LF/high frequency (HF), showed higher values in ADPKD and hypertensive patients than HC (p < 0.0001). Conversely, LF day was lower in ADPKD and hypertensive patients than HC (p < 0.01). HF, which mainly reflects the parasympathetic component, was lower in ADPKD and hypertensive patients during the night than HC (p < 0.0001). Conclusions: HRV reduction is present in ADPKD patients with mild hypertension in the absence of organ damage. The evaluation of sympathovagal balance can provide novel information on the cardiovascular risk in ADPKD patients in addition to classical risk factors

Bioelectrical Impedance Vector Analysis and Brain Natriuretic Peptide in the Evaluation of Patients with Chronic Kidney Disease in Hemodialitic Treatment

Introduction: Setting dry weight (DW) in hemodialysis (HD) patients is still a hard issue. Several clinical, hematochemical, and instrumental parameters have been considered. In the last years, bioelectrical impedance vector analysis (BIVA) became the main method to evaluate body composition and water body percentage. However, it is still difficult to assess the nutritional status and identify a correct DW in HD patients. Aim: The aim of the study was to set DW and nutritional status, combining BIVA with phase angle (PhA) and serum brain natriuretic peptide (BNP) in HD patients. Methods: We evaluated PhA and BNP modifications before (T0), after HD section (T1), and after 60 days (T2), in all patients treated in our HD center. Results: A total of 50 patients (36 males) with a mean age of 70.1 ± 8.85 years were recruited. We did not report significant changes in BNP and PhA between T0 and T1, while they were significantly different between T0 and T2. We also reported a significant difference between T0 and T2 in ECW/TBW, while we did not show significant variations in ECM/BMC between T0, T1, and T2 indicating a stability of the nutritional status. PhA, BNP, and ECW/TBW returned to a normal value in patients in which we reached a DW, also considering clinical parameters such as blood pressure and antihypertensive therapy. The weight loss obtained with the evaluation of the BIVA and the BNP was 1.2–5.7 kg, greater than that calculated empirically which stood at around 0.9–4.3 kg. Conclusion: We suggest to carry out BIVA with PhA combined with BNP to assess an adequate DW and evaluate a correct nutritional status in HD patients

Parasympathetic activity and total fibrotic kidney in autosomal-dominant polycystic kidney disease patients: a pilot study

PurposeRenin-angiotensin system hyperactivation in autosomal-dominant polycystic kidney disease (ADPKD) patients leads to early hypertension. Cystic enlargement probably causes parenchymal hypoxia, renin secretion, and endothelial dysfunction. Sympathetic and parasympathetic balance is altered in this condition, especially during the night, also affecting blood pressure circadian rhythm. Aim of this study was to evaluate sympathetic/parasympathetic balance using heart rate variability (HRV) parameters and find a correlation between HRV and renal damage progression, as total kidney volume enlargement, in ADPKD patients.MethodsSixteen adult ADPKD patients were enrolled in the study. Eleven patients (68.8%) were male, and the median age was 42 years (IQR 36-47.5). HRV parameters were calculated using 24 h-ECG Holter. A kidney magnetic resonance imaging (MRI) scan 3 Tesla was performed to evaluate total kidney volume (TKV) and total fibrotic volume (TFV).ResultsA statistically significant positive linear correlation was observed between length of kidneys and frequency domain parameters as low frequency (LF) (r = 0.595, p &lt; 0.05) and LFday (r = 0.587, p &lt; 0.05). Moreover, a statistically significant positive linear correlation exists between high frequency (HF) and TFV (r = 0.804, p &lt; 0.01) or height-adjusted (ha) TFV (r = 0.801, p &lt; 0.01). Finally, we found a statistically significant positive linear correlation between HFnight and TKV (r = 0.608, p &lt; 0.05), ha-TKV (r = 0.685, p &lt; 0.01), TFV (r = 0.594, p &lt; 0.05), and ha-TFV (r = 0.615, p &lt; 0.05).ConclusionWe suppose that the increase in TKV and TFV could lead to a parasympathetic tone hyperactivation, probably in response to hypoxic stress and vasoconstriction due to cystic enlargement

Contrast-Induced Acute Kidney Injury and Endothelial Dysfunction: The Role of Vascular and Biochemical Parameters

Introduction: Contrast-induced acute kidney injury (CIAKI) is one of the main causes of acute renal failure in hospitalized patients, following the administration of iodinated contrast medium used for CT scans and angiographic procedures. CIAKI determines a high cardiovascular risk and appears to be one of the most feared complications of coronary angiography, causing a notable worsening of the prognosis with high morbidity and mortality. Aim: To evaluate a possible association between the renal resistive index (RRI) and the development of CIAKI, as well as an association with the main subclinical markers of atherosclerosis and the main cardiovascular risk factors. Materials and Methods: We enrolled 101 patients with an indication for coronary angiography. Patients underwent an assessment of renal function (serum nitrogen and basal creatinine, 48 and 72 h after administration of contrast medium), inflammation (C reactive protein (CRP), serum calcium and phosphorus, intact parathormone (iPTH), 25-hydroxyvitaminD (25-OH-VitD), serum uric acid (SUA), total cholesterol, serum triglycerides, serum glucose and insulin). All patients also carried out an evaluation of RRI, intima-media thickness (IMT), interventricular septum (IVS) and the ankle-brachial index (ABI). Results: 101 patients (68 male), with a mean age of 73.0 ± 15.0 years, were enrolled for the study; 35 are affected by type 2 diabetes mellitus. A total of 19 cases of CIAKI were reported (19%), while among diabetic patients we reported an incidence of 23% (8 patients). In our study, patients with CIAKI had significantly higher RRI (p &lt; 0.001) and IMT (p &lt; 0.001) with respect to the patients who did not develop CIAKI. Furthermore, patients with CIAKI had significantly higher CRP (p &lt; 0.001) and SUA (p &lt; 0.006). Conclusions: We showed a significant difference in RRI, IMT, SUA and CRP values between the population developing CIAKI and patients without CIAKI. This data appears relevant considering that RRI and IMT are low-cost, non-invasive and easily reproducible markers of endothelial dysfunction and atherosclerosis

Sonographic evaluation of hypertension: Role of atrophic index and renal resistive index

Abstract Hypertension can cause structural and functional renal damage. Intrarenal ultrasound parameters have been extensively investigated in hypertensive patients and among the parameters introduced, the renal resistive index (RI) is associated with the progression of chronic kidney disease and hypertension. Atrophic index (AI) is an indirect anatomical ultrasound index that reports the atrophic changes of the renal parenchyma and it is mainly studied in chronic glomerular diseases. The present study aimed to evaluate renal RI and AI in hypertensive patients with normal renal function. AI showed correlations with all parameters associated with renal function reduction (age, creatinine, and intrarenal arterial stiffness). AI, in combination with RI, can represent in hypertensive patients an additional marker for renal damage progression

Assessment of Cardiovascular Disease in Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited kidney disease which leads to progressive kidney failure. About 5–10% of patients requiring renal replacement therapy are affected by ADPKD. Cardiovascular diseases are the main causes of morbidity and mortality in these patients with ADPKD; arterial hypertension (AH) is the first symptom with a very early onset. Anyway, some other cardiovascular abnormalities have been reported in ADPKD regardless of the presence of AH. With this background, we conducted a systematic review, collecting all randomized controlled trials (RCTs) and quasi-RCTs found on the main databases; we evaluated the evidence about different imaging techniques to grade the cardiovascular risk in a very early stage of disease. This review aims to describe all cardiovascular assessments in ADPKD patients to improve clinicians’ ability to discover cardiovascular involvement early, allowing appropriate therapies promptly

Evaluation of partial pressure CO2 change in the dialyzer blood inlet during hemodialysis as a measure of vascular access recirculation

Introduction: Vascular access recirculation during hemodialysis is associated with reduced effectiveness and worse survival outcomes. To evaluate recirculation, an increase in pCO(2) in the blood of the arterial line during hemodialysis (threshold of 4.5 mmHg) was proposed. The blood returning from the dialyzer in the venous line has significantly higher pCO2, so in the presence of recirculation, pCO2 in the arterial blood line may increase (Delta pCO(2)) during hemodialysis sessions. The aim of our study was to evaluate Delta pCO(2) as a diagnostic tool for vascular access recirculation in chronic hemodialysis patients. Methods: We evaluated vascular access recirculation with Delta pCO(2) and compared it with the results of a urea recirculation test, which is the gold standard. Delta pCO(2) was obtained from the difference in pCO(2) in the arterial line at baseline (pCO(2)T1) and after 5 min of hemodialysis (pCO(2)T.2). Delta pCO(2) = pCO(2)T2-pCO(2)T1. Findings: In 70 hemodialysis patients (mean age: 70.52 +/- 13.97 years; hemodialysis vintage of 41.36 +/- 34.54, KT/V 1.4 +/- 0.3), Delta pCO(2) was 4 +/- 4 mmHg, and urea recirculation was 7% +/- 9%. Vascular access recirculation was identified using both methods in 17 of 70 patients, who showed a Delta pCO(2) of 10 +/- 5 mmHg and urea recirculation of 20% +/- 9%; time in months of hemodialysis was the only difference between vascular access recirculation and non-vascular access recirculation patients (22 +/- 19 vs. 46 +/- 36, p: 0.05). In the non-vascular access recirculation group, the average Delta pCO(2) was 1.9 +/- 2 (p: 0.001), and the urea recirculation % was 2.8 +/- 3 (p: 0.001). The Delta pCO(2) correlated with the urea recirculation % (R: 0.728; p &lt; 0.001). Discussion: Delta pCO(2) in the arterial blood line during hemodialysis is an effective and reliable diagnostic tool for identifying recirculation of the vascular access but not its magnitude. The Delta pCO(2) test application is simple and economical and does not require special equipment

mTORC1/rpS6 and p-FAK-Y407 signaling regulate spermatogenesis: Insights from studies of the adjudin pharmaceutical/toxicant model

In rodents and humans, the major cellular events at spermatogenesis include self-renewal of spermatogonial stem cells and undifferentiated spermatogonia via mitosis, commitment of spermatogonia to differentiation and transformation to spermatocytes, meiosis, spermiogenesis, and the release of spermatozoa at spermiation. While details of the morphological changes during these cellular events have been delineated, knowledge gap exists between the morphological changes in the seminiferous epithelium and the underlying molecular mechanism(s) that regulate these cellular events. Even though many of the regulatory proteins and biomolecules that modulate spermatogenesis are known based on studies using genetic models, the underlying regulatory mechanism(s), in particular signaling pathways/proteins, remain unexplored since much of the information regarding the signaling regulation is unknown. Studies in the past decade, however, have unequivocally demonstrated that the testis is using several signaling proteins and/or pathways to regulate multiple cellular events to modulate spermatogenesis. These include mTORC1/rpS6/Akt1/2 and p-FAK-Y407. While selective inhibitors and/or agonists and antagonists are available to examine some of these signaling proteins, their use have limitations due to their specificities and also potential systemic cytotoxicity. On the other hand, the use of genetic models has had profound implications for our understanding of the molecular regulation of spermatogenesis, and these knockout (null) models have also revealed the factors that are critical for spermatogenesis. Nonetheless, additional studies using in vitro and in vivo models are necessary to unravel the signaling pathways involved in regulating seminiferous epithelial cycle. Emerging data from studies, such as the use of the adjudin pharmaceutical/toxicant model, have illustrated that this non-hormonal male contraceptive drug is utilizing specific signaling pathways/proteins to induce specific defects in spermatogenesis, yielding mechanistic insights on the regulation of spermatogenesis. We sought to review these recent data in this article, highlighting an interesting approach that can be considered for future studies

Ischemic nephropaty: the role of the renal artery stenosis re-vascularization on renal stem cells

We report the case of a 65-year-old man with acute GFR decline to 37 mL/min and uncontrolled high blood pressure. He was suspected for renovascular hypertension and underwent a renal color Doppler ultrasound scan that detected a bilateral atherosclerotic renal artery stenosis. A digital selective angiography by percutaneous transluminal angioplasty and stenting (PTRAs) was successfully performed. Blood pressure rapidly normalized, GFR increased within a few days, and proteinuria disappeared thereafter. These clinical goals were accompanied by a significant increase of circulating renal stem cells (RSC) and a slight increase of resistive index (RI) in both kidneys. This single observation suggests the need for extensive studies aimed at evaluating the predictive power of RI and RSC in detecting post-ischemic renal repair mechanisms