Predictive models in chronic kidney disease: essential tools in clinical practice.

PURPOSE OF REVIEW: The integration of risk prediction in managing chronic kidney disease (CKD) is universally considered a key point of routine clinical practice to guide time-sensitive choices, such as dialysis access planning or counseling on kidney transplant options. Several prognostic models have been developed and validated to provide individualized evaluation of kidney failure risk in CKD patients. This review aims to analyze the current evidence on existing predictive models and evaluate the different advantages and disadvantages of these tools. RECENT FINDINGS: Since Tangri et al. introduced the Kidney Failure Risk Equation in 2011, the nephrological scientific community focused its interest in enhancing available algorithms and finding new prognostic equations. Although current models can predict kidney failure with high discrimination, different questions remain unsolved. Thus, this field is open to new possibilities and discoveries. SUMMARY: Accurately informing patients of their prognoses can result in tailored therapy with important clinical and psychological implications. Over the last 5 years, the number of disease-modifying therapeutic options has considerably increased, providing possibilities to not only prevent the kidney failure onset in patients with advanced CKD but also delay progression from early stages in at-risk individuals.

The vascular disease of diabetic kidney disease.

The incidence of cardiovascular disease (CVD) is increased in patients with diabetic kidney disease (DKD). Aortic stiffness is a well-accepted biomarker for cardiovascular (CV) events in all stages of CKD. The worldwide prevalence of diabetes continues to grow, as does the prevalence of DKD. Insulin resistance, hyperglycaemia, hypertension and the metabolic abnormalities of type-2 diabetes are all involved in the pathogenesis of CVD. The effect of these toxins on cardiac and vascular function is amplified by the worsening of renal function and the parallel rise of uraemic toxins. In this narrative review, we analysed why arterial stiffening can be considered a vascular mediator between diabetes and cardiac dysfunction, and we discussed the strong CV and nephroprotective effects of sodium-glucose cotransporter type 2 inhibitors (SGLT2i).

Scattering as a Quantum Metrology Problem: A Quantum Walk Approach.

We address the scattering of a quantum particle by a one-dimensional barrier potential over a set of discrete positions. We formalize the problem as a continuous-time quantum walk on a lattice with an impurity and use the quantum Fisher information as a means to quantify the maximal possible accuracy in the estimation of the height of the barrier. We introduce suitable initial states of the walker and derive the reflection and transmission probabilities of the scattered state. We show that while the quantum Fisher information is affected by the width and central momentum of the initial wave packet, this dependency is weaker for the quantum signal-to-noise ratio. We also show that a dichotomic position measurement provides a nearly optimal detection scheme.

COVID-19 and the Kidneys: An Update.

The new coronavirus disease 2019 (COVID-19) has become a world health emergency. The disease predominantly effects individuals between 30 and 79 years of age with 81% of cases being classified as mild. Despite the majority of the general population displaying symptoms similar to the common cold, COVID-19 has also induced alveolar damage resulting in progressive respiratory failure with fatalities noted in 6.4% of cases. Direct viral injury, uncontrolled inflammation, activation of coagulation, and complement cascades are thought to participate in disease pathogenesis. Patients with COVID-19 have displayed kidney damage through acute kidney injury, mild proteinuria, hematuria, or slight elevation in creatinine possibly as consequence of kidney tropism of the virus and multiorgan failure. The impact of COVID-19 on patients with pre-existing kidney impairment, including those with chronic kidney disease, kidney transplant recipients, and individuals on hemodialysis (HD) has not yet been clearly established. No specific treatments for COVID-19 have been found yet. Research has revealed several agents that may have potential efficacy against COVID-19, and many of these molecules have demonstrated preliminary efficacy against COVID-19 and are currently being tested in clinical trials.

Evidence of potent humoral immune activity in COVID-19-infected kidney transplant recipients.

Whether kidney transplant recipients are capable of mounting an effective anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adaptive immune response despite chronic immunosuppression is unknown and has important implications for therapy. Herein, we analyzed peripheral blood cell surface and intracellular cytokine phenotyping by flow cytometry along with serum antibody testing in 18 kidney transplant recipients with active coronavirus disease 2019 (COVID-19) infection and 36 matched, transplanted controls without COVID-19. We observed significantly fewer total lymphocytes and fewer circulating memory CD4+ and CD8+ T cells in the COVID-19 subjects. We also showed fewer anergic and senescent CD8+ T cells in COVID-19 individuals, but no differences in exhausted CD8+ T cells, nor in any of these CD4+ T cell subsets between groups. We also observed greater frequencies of activated B cells in the COVID-19 patients. Sixteen of 18 COVID-19 subjects tested for anti-SARS-CoV-2 serum antibodies showed positive immunoglobulin M or immunoglobulin G titers. Additional analyses showed no significant correlation among immune phenotypes and degrees of COVID-19 disease severity. Our findings indicate that immunosuppressed kidney transplant recipients admitted to the hospital with acute COVID-19 infection can mount SARS-CoV-2-reactive adaptive immune responses. The findings raise the possibility that empiric reductions in immunosuppressive therapy for all kidney transplant recipients with active COVID-19 may not be required.

Kidney allograft fibrosis: what we learned from latest translational research studies.

To add new molecular and pathogenetic insights into the biological machinery associated to kidney allograft fibrosis is a major research target in nephrology and organ transplant translational medicine. Interstitial fibrosis associated to tubular atrophy (IF/TA) is, in fact, an inevitable and progressive process that occurs in almost every type of chronic allograft injury (particularly in grafts from expanded criteria donors) characterized by profound remodeling and excessive production/deposition of fibrillar extracellular matrix (ECM) with a great clinical impact. IF/TA is detectable in more than 50% of kidney allografts at 2 years. However, although well studied, the complete cellular/biological network associated with IF/TA is only partially evaluated. In the last few years, then, thanks to the introduction of new biomolecular technologies, inflammation in scarred/fibrotic parenchyma areas (recently acknowledged by the BANFF classification) has been recognized as a pivotal element able to accelerate the onset and development of the allograft chronic damage. Therefore, in this review, we focused on some new pathogenetic elements involved in graft fibrosis (including epithelial/endothelial to mesenchymal transition, oxidative stress, activation of Wnt and Hedgehog signaling pathways, fatty acids oxidation and cellular senescence) that, in our opinion, could become in future good candidates as potential biomarkers and therapeutic targets.

Quantum Probes for Ohmic Environments at Thermal Equilibrium.

It is often the case that the environment of a quantum system may be described as a bath of oscillators with an ohmic density of states. In turn, the precise characterization of these classes of environments is a crucial tool to engineer decoherence or to tailor quantum information protocols. Recently, the use of quantum probes in characterizing ohmic environments at zero-temperature has been discussed, showing that a single qubit provides precise estimation of the cutoff frequency. On the other hand, thermal noise often spoil quantum probing schemes, and for this reason we here extend the analysis to a complex system at thermal equilibrium. In particular, we discuss the interplay between thermal fluctuations and time evolution in determining the precision attainable by quantum probes. Our results show that the presence of thermal fluctuations degrades the precision for low values of the cutoff frequency, i.e., values of the order ω c ≲ T (in natural units). For larger values of ω c , decoherence is mostly due to the structure of environment, rather than thermal fluctuations, such that quantum probing by a single qubit is still an effective estimation procedure.

Microscopic description for the emergence of collective dissipation in extended quantum systems.

Practical implementations of quantum technology are limited by unavoidable effects of decoherence and dissipation. With achieved experimental control for individual atoms and photons, more complex platforms composed by several units can be assembled enabling distinctive forms of dissipation and decoherence, in independent heat baths or collectively into a common bath, with dramatic consequences for the preservation of quantum coherence. The cross-over between these two regimes has been widely attributed in the literature to the system units being farther apart than the bath's correlation length. Starting from a microscopic model of a structured environment (a crystal) sensed by two bosonic probes, here we show the failure of such conceptual relation, and identify the exact physical mechanism underlying this cross-over, displaying a sharp contrast between dephasing and dissipative baths. Depending on the frequency of the system and, crucially, on its orientation with respect to the crystal axes, collective dissipation becomes possible for very large distances between probes, opening new avenues to deal with decoherence in phononic baths.

Treatment with angiotensin-converting enzyme inhibitors is associated with a reduction in short-term mortality in older patients with acute ischemic stroke.

BACKGROUND: Stroke is the third cause of death in older people living in Western countries. We tested the hypothesis that angiotensin-converting enzyme inhibitors (A-I) might affect short-term (30 day) mortality in older persons with severe acute ischemic stroke. METHODS: We analyzed data from a retrospective study including 475 consecutive older patients hospitalized for acute ischemic stroke. Mean age was 78.4 +/- 9.2 years; 58.2% were female. Stroke type was classified according to the Oxford Community Stroke Project (OCSP). RESULTS: Mortality rate was 28%. Thirty-two percent of patients were treated with A-I; mortality was 16.5% in patients treated compared with 33.3% in those not treated (chi(2) p =.001). The odds ratio for mortality in treated patients was: 0.47 (0.25-0.89) after full adjustment (age, sex, mean diastolic and systolic blood pressure, previous stroke and/or transient ischemic attack, congestive heart failure, atrial fibrillation, diabetes, hypertension, coronary heart disease, and previous treatment with A-I); 0.29 (0.09-0.89) in patients with altered level of consciousness after full adjustment; 0.60 (0.33-1.12) after adjustment for OCSP classification, age, and sex; and 0.30 (0.08-0.97) in total anterior circulation infarction stroke type after full adjustment. CONCLUSIONS: Our data suggest that treatment with A-I might reduce short-term mortality in older patients with acute ischemic stroke. Randomized clinical trials should confirm this possible specific effect of A-I.

Prescription of anti-oedema agents and short-term mortality in older patients with acute ischaemic stroke.

BACKGROUND AND OBJECTIVE: In Western countries, stroke is the third most common cause of death and one of the main causes of disability in individuals aged over 65 years. Mortality at 1 month after stroke is still high, at around 25-30%. Despite the widespread use of anti-oedema agents in clinical practice, there are only a few studies that have investigated the effect of these drugs on stroke outcome. In this study we evaluated the effect of intravenously administered glycerol or mannitol individually and in combination with corticosteroids, on short-term mortality (30 days). The sample included patients aged over 65 years who were admitted to hospital for acute ischaemic stroke. STUDY DESIGN: This was a retrospective cohort study. The odds ratio, estimated by means of multivariate logistic regression method, was used to compare short-term mortality risk across treatment groups after adjusting for possible confounders. METHODS: This study included 442 consecutive patients aged over 65 years with severe ischaemic stroke who were admitted to either the University School of Internal Medicine (Ferrara) or the Geriatric Department (Perugia), Italy, over a 4-year period (1996-2000). All patients underwent a computed tomography (CT) scan of the brain within 72 hours of admission. Stroke type was classified according to the system used by the Oxfordshire Community Stroke Project. The data recorded included: (i) clinical features of stroke; (ii) detailed medical history, including vascular risk factors (arterial hypertension, diabetes mellitus, atrial fibrillation, coronary heart disease, congestive heart failure, alcohol abuse, smoking, previous transient ischaemic attacks or stroke); (iii) 12-lead ECG; and (iv) routine blood analysis and urine tests. RESULTS: No reduction in short-term mortality risk was observed in patients treated with intravenous (IV) glycerol. However, an increase in short-term mortality risk was observed in the patients who were concurrently treated with IV corticosteroids. Similarly, treatment with mannitol did not reduce the risk of short-term mortality; however, concurrent treatment with IV corticosteroids did not show a significant rise in short-term mortality risk. When treatment with IV glycerol and mannitol was considered together, the treatment did not decrease short-term mortality risk, while concurrent therapy with corticosteroids was associated with an increase in short-term mortality risk. CONCLUSION: This study does not support the use of IV osmotic agents such as glycerol or mannitol in the prevention of short-term mortality in older patients with acute ischaemic stroke. Furthermore, our data suggest a possible harmful effect of IV corticosteroids on short-term mortality risk.

Validation of the five-item geriatric depression scale in elderly subjects in three different settings.

OBJECTIVES: To test the effectiveness of a five-item version of the Geriatric Depression Scale (GDS) for the screening of depression in community-dwelling older subjects, hospitalized older patients, and nursing home residents. DESIGN: A cross-sectional study. SETTING: A geriatric acute care ward, a geriatric outpatient clinic, and a nursing home. PARTICIPANTS: One hundred eighty-one cognitively intact older subjects. MEASUREMENT: All the participants had a comprehensive geriatric assessment including a neuropsychological evaluation by a geriatrician experienced in the management of depression. The five-item GDS was compared with the 15-item version of the GDS using the clinical diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria as the criterion standard. The sensitivity, the specificity, the overall accuracy, positive and negative predictive values, and positive and negative likelihood ratios were calculated. The agreement between each of two different versions of the GDS and the clinical diagnosis and the test-retest and the interrater reliability of the five-item scale were also evaluated. RESULTS: In the whole sample, 48.1% of the subjects were depressed. The five-item GDS had a sensitivity of 0.94 (0.91-0.98), a specificity of 0.81 (0.75-0.87), a positive predictive value of 0.81 (0.75-0.87), a negative predictive value of 0.94 (0.90-0.97), a positive likelihood ratio of 4.92 (4.39-5.5), and a negative likelihood ratio of 0.07 (0.06-0.08). The five-item GDS and the 15-item GDS showed a significant agreement with the clinical diagnosis of depression (kappa = 0.74 for both scales). The five-item GDS had good interrater reliability (kappa = 0.88) and test-retest reliability (kappa = 0.84). Similar values were obtained in each setting and in both sexes. CONCLUSION: The five-item GDS is as effective as the 15-item GDS for the screening of depression in cognitively intact older subjects.

Proton magnetic resonance spectroscopy reveals similar white matter biochemical changes in patients with chronic hypertension and early Alzheimer's disease.

OBJECTIVES: Hypertension is a risk factor for dementia and is associated with some of the brain changes that are found in Alzheimer's disease and other neurodegenerative diseases, such as atrophy and neurofibrillary tangles. We evaluated the cerebral white matter biochemical pattern in healthy older subjects, older patients with chronic hypertension, and patients with Alzheimer's disease (AD) using proton magnetic resonance spectroscopy (1H-MRS). DESIGN: Cross-sectional study. SETTING: University-affiliated outpatient clinic. PARTICIPANTS: Ten healthy older subjects, 10 cognitively intact older patients with chronic hypertension, and 10 older patients with early AD. MEASUREMENTS: All subjects underwent clinical examination, neuropsychological assessment, and 1H-MRS to measure N-acetylaspartate (NAA), myoinositol, choline, and creatine resonance signals in an 8-cm3 voxel located in the paratrigonal white matter region bilaterally. NAA/creatine, myoinositol/creatine, and choline/creatine ratios were measured, and the mean values were compared using one-way analysis of variance with Tukey test for post hoc analysis. RESULTS: A significantly higher mean myoinositol/creatine (ratio +/- standard deviation) was found in hypertensive patients (0.67 +/- 0.05) and in AD patients (0.68 +/- 0.08) than in controls (0.56 +/- 0.04) (P <.001). Conversely neither NAA/creatine ratio nor choline/creatine ratio differed among the three groups. CONCLUSIONS: In this study, cognitively intact chronic hypertensive older patients had a higher white matter myoinositol/creatine ratio compared with healthy older subjects, suggesting that myoinositol may be a sensitive marker of the effects of chronic hypertension on the brain. Moreover, the similar increase of myoinositol/creatine ratio in patients with hypertension and in those with early AD provides further evidence of common brain changes with these conditions.