A focus on CKD reporting and inappropriate prescribing among older patients discharged from geriatric and nephrology units throughout Italy: A nationwide multicenter retrospective cross-sectional study.

Older hospitalized patients with chronic kidney disease (CKD) are part of the geriatric population with a substantial risk of potentially inappropriate medication (PIM) use. The high rates of multimorbidity and polypharmacy, along with the progressive decline of eGFR, contribute to increasing the risk of drug-drug and drug-disease interactions, overdosing, and adverse drug reactions (ADRs). In this multicenter cross-sectional study, we aimed to evaluate the prevalence of CKD under-reporting and PIMs among older patients discharged from acute geriatric and nephrology units throughout Italy. Renal function was determined by estimated glomerular filtration rate (eGFR) through the Berlin Initiative Study (BIS) equation; the prevalence of PIMs was calculated by revising drug prescriptions at discharge according to STOPP criteria, Beers criteria, and summaries of product characteristics (smPCs). A descriptive analysis was performed to compare the clinical and pharmacological characteristics of patients in the two distinct settings; univariate and multivariate logistic regression models were performed to explore factors associated with CKD under-reporting in the discharge report forms and PIM prevalence. Overall, the study population consisted of 2,057 patients, aged 83 (77-89) years, more commonly women, with a median of seven (5-10) drugs prescribed at discharge. CKD under-reporting was present in 50.8% of the study population, with higher rates in geriatric vs. nephrology units (71.1% vs. 10.2%, p < 0.001). 18.5% of the study population was discharged with at least one renally inappropriate medication; factors associated with at least one contraindicated drug at discharge were the number of drugs (PR 1.09, 95% CI 1.14-1.19); atrial fibrillation (PR 1.35, 95% CI 1.01-1.81); diabetes (PR 1.61, 95% CI 1.21-2.13); being hospitalized in nephrology units (PR 1.62, 95% CI 1.14-2.31), CKD stage 3b (PR 2.35, 95% CI 1.34-4.13), and stage 4-5 (PR 14.01, 95% CI 7.36-26.72). Conversely, CKD under-reporting was not associated with the outcome. In summary, CKD under-reporting and inappropriate medication use were common in older patients discharged from hospital; the relatively high number of PIMs in both nephrology and geriatric settings underlines the need to improve appropriate prescribing during hospital stay and to decrease the risk of ADRs and side effects in this highly vulnerable population.

On the Mechanism of Cocrystal Mechanochemical Reaction via Low Melting Eutectic: A Time-Resolved In Situ Monitoring Investigation.

Mechanochemistry has become a sustainable and attractive cost-effective synthetic technique, largely used within the frame of crystal engineering. Cocrystals, namely, crystalline compounds made of different chemical entities within the same crystal structure, are typically synthesized in bulk via mechanochemistry; however, whereas the macroscopic aspects of grinding are becoming clear, the fundamental principles that underlie mechanochemical cocrystallization at the microscopic level remain poorly understood. Time-resolved in situ (TRIS) monitoring approaches have opened the door to exceptional detail regarding mechanochemical reactions. We here report a clear example of cocrystallization between two solid coformers that proceeds through the formation of a metastable low melting binary eutectic phase. The overall cocrystallization process has been monitored by time-resolved in situ (TRIS) synchrotron X-ray powder diffraction with a customized ball milling setup, currently available at µSpot beamline at BESSY-II, Helmholtz-Zentrum Berlin. The binary system and the low melting eutectic phase were further characterized via DSC, HSM, and VT-XRPD.

Ultrasonographic Assessment of Atherosclerotic Renal Artery Stenosis in Elderly Patients with Chronic Kidney Disease: An Italian Cohort Study.

Although atherosclerotic renal artery stenosis (ARAS) is strictly associated with high cardiovascular risk and mortality, it often may remain unrecognized being clinically silent and frequently masked by co-morbidities especially in elderly patients with coexisting chronic kidney disease (CKD). The present observational study was conducted in elderly CKD-patients with atherosclerosis on other arterial beds. The aims were assessment of (1) ARAS prevalence; (2) best predictor(s) of ARAS, using duplex ultrasound; and (3) cardiovascular and renal outcomes at one-year follow-up. The cohort was represented by 607 consecutive in-patients. Inclusion criteria were age ≥65 years; CKD stages 2−5 not on dialysis; single or multiple atherosclerotic plaque on epiaortic vessels, abdominal aorta, aortic arch, coronary arteries, peripheral arteries that had been previously ascertained by one or more procedures. Duplex ultrasound was used to detect ARAS. Multiple regression analysis and ROS curve were performed to identify the predictors of ARAS. ARAS was found in 53 (44%) out of 120 patients who met the inclusion criteria. In univariate analysis, GFR (b = −0.021; p = 0.02); hemoglobin (b = −0.233; p = 0.02); BMI (b = 0.134; p = 0.036) and atherosclerosis of abdominal aorta and/or peripheral vessels (b = 1.025; p < 0.001) were associated with ARAS. In multivariable analysis, abdominal aorta and/or peripheral atherosclerosis was a significant (p = 0.002) predictor of ARAS. The area under the ROC curve was 0.655 (C.I. = 0.532−0.777; p = 0.019). ARAS is common in older CKD patients with extra-renal atherosclerosis, with the highest prevalence in those with aortic and peripheral atherosclerosis. ARAS may pass by unnoticed in everyday clinical practice.

Low eGFR Is a Strong Predictor of Worse Outcome in Hospitalized COVID-19 Patients.

BACKGROUND: The clinical course of COVID-19 is more severe in elderly patients with cardio-metabolic co-morbidities. Chronic kidney disease is considered an independent cardiovascular risk factor. We aimed to evaluate the impact of reduced eGFR on the composite outcome of admission to ICU and death in a sample of consecutive COVID-19 hospitalized patients. METHODS: We retrospectively evaluated clinical records of a consecutive sample of hospitalized COVID-19 patients. A total of 231 patients were considered for statistical analysis. The whole sample was divided in two groups on the basis of eGFR value, e.g., ≥ or <60 mL/min/1.73 m2. Patients with low eGFR were further divided among those with a history of chronic kidney disease (CKD) and those without (AKI, acute kidney injury). The primary outcome was a composite of admission to ICU or death, whichever occurred first. The single components were secondary outcomes. RESULTS: Seventy-nine (34.2%) patients reached the composite outcome. A total of 64 patients (27.7%) died during hospitalization, and 41 (17.7%) were admitted to the ICU. A significantly higher number of events was present among patients with low eGFR (p < 0.0001). Age (p < 0.001), SpO2 (p < 0.001), previous anti-platelet treatment (p = 0.006), Charlson's Comorbidities Index (p < 0.001), serum creatinine (p < 0.001), eGFR (p = 0.003), low eGFR (p < 0.001), blood glucose levels (p < 0.001), and LDH (p = 0.003) were significantly associated with the main outcome in univariate analysis. Low eGFR (HR 1.64, 95% CI 1.02-2.63, p = 0.040) and age (HR per 5 years 1.22, 95% CI 1.10-1.36, p < 0.001) were significantly and independently associated with the main outcome in the multivariate model. Patients with AKI showed an increased hazard ratio to reach the combined outcome (p = 0.059), while those patients with both CKD had a significantly higher probability of developing the combined outcome (p < 0.001). CONCLUSIONS: Patients with reduced eGFR at admission should be considered at high risk for clinical deterioration and death, requiring the best supportive treatment in order to prevent the worst outcome.

Renal Resistive Index of the Main Renal Arteries and Transmitral Flow in Hypertensive Patients.

In hypertensive patients, diastolic dysfunction is related to increased resistive index (RI) of parenchymal renal arteries. To determine the existence of a link between RI of the main renal arteries (RRI) and diastolic dysfunction, a group of 127 hypertensive patients, with glomerular filtration rates >50 mL/min (mean estimated glomerular filtration rate: 88.6 ± 15.2 mL/min) and no comorbidities, was studied. RRI and transmitral flow were evaluated using the deceleration time (DT) and E/A ratio. A statistically significant correlation between RRI and DT (>240 ms) was noted (p < 0.001). The RRI cutoff that best discriminated patients with DT >240 ms was 0.675. For each unitary increment of 10 mm in DT, the log-transformed RRI significantly increased by a mean of 0.006 point (p < 0.001). This study revealed the importance of the link between RRI and transmitral DT in addition to the renowned significance of the increase in RI as a cardiovascular risk factor in hypertensive patients without comorbidities.

Ultrasonography of Quadriceps Femoris Muscle and Subcutaneous Fat Tissue and Body Composition by BIVA in Chronic Dialysis Patients.

Protein Energy Wasting (PEW) in hemodialysis (HD) patients is a multifactorial condition due to specific pathology-related pathogenetic mechanisms, leading to loss of skeletal muscle mass in HD patients. Computed Tomography and Magnetic Resonance Imaging still represent the gold standard techniques for body composition assessment. However, their widespread application in clinical practice is difficult and body composition evaluation in HD patients is mainly based on conventional anthropometric nutritional indexes and bioelectrical impedance vector analysis (BIVA). Little data is currently available on ultrasound (US)-based measurements of muscle mass and fat tissue in this clinical setting. The purpose of our study is to ascertain: (1) if there are differences between quadriceps rectus femoris muscle (QRFM) thickness and abdominal/thigh subcutaneous fat tissue (SFT) measured by US between HD patients and healthy subjects; (2) if there is any correlation between QRFM and abdominal/thigh SFT thickness by US, and BIVA/conventional nutritional indexes in HD patients. We enrolled 65 consecutive HD patients and 33 healthy subjects. Demographic and laboratory were collected. The malnutrition inflammation score (MIS) was calculated. Using B-mode US system, the QRFM and SFT thicknesses were measured at the level of three landmarks in both thighs (superior anterior iliac spine, upper pole of the patella, the midpoint of the tract included between the previous points). SFT was also measured at the level of the periumbilical point. The mono frequency (50 KHz) BIVA was conducted using bioelectrical measurements (Rz, resistance; Xc, reactance; adjusted for height, Rz/H and Xc/H; PA, phase angle). 58.5% were men and the mean age was 69 (SD 13.7) years. QRFM and thigh SFT thicknesses were reduced in HD patients as compared to healthy subjects (p < 0.01). Similarly, also BIVA parameters, expression of lean body mass, were lower (p < 0.001), except for Rz and Rz/H in HD patients. The average QRFM thickness of both thighs at top, mid, lower landmarks were positively correlated with PA and body cell mass (BCM) by BIVA, while negatively correlated with Rz/H (p < 0.05). Abdominal SFT was positively correlated with PA, BCM and basal metabolic rate (BMR) (p < 0.05). Our study shows that ultrasound QRFM and thigh SFT thicknesses were reduced in HD patients and that muscle ultrasound measurements were significantly correlated with BIVA parameters.

[Encrusted Pyelitis during a case of Thrombotic Thrombocytopenic Purpura].

Encrusted pyelitis is a chronic urinary tract infection associated with mucosal encrustation induced by urea splitting bacteria. More than 40 bacteria have been implicated but the most frequent is Corynebacterium group D2. Predisposing factors are debilitating chronic diseases and preexisting urological procedures. Immunosoppression is an important cofactor. For these reasons the disease is almost always nosocomially acquired and renal transplant recipients are at particular risk. The symptoms are not specific and long lasting: dysuria, flank pain and gross haematuria are the most frequent; fever is present in two-thirds. The demonstration of urine splitting bacteria in constantly alkaline urines and radiological evidence of extensive calcification of pelvicalyceal system, ureter and bladder at US or CT scan in a clinical context of predisposing factors are the mainstay of diagnosis. Treatment is based on adapted antibiotic therapy, acidification of urine and excision of plaques of calcified encrustation. The prognosis relies on timing of diagnosis; delay can be detrimental and result in patient's death and graft loss. We describe a unique case of 69-year-old man with two contemporary diseases: autoimmune thrombotic thrombocytopenic purpura and encrusted pyelitis with a fatal evolution.

[Between old and new targets: blood pressure control in hypertensive outpatients].

OBJECTIVE: In developed countries, blood pressure (BP) control has increased over the past few decades and is now approaching 70% of patients. Herewith we report the results of a cross-sectional study carried out on hypertensive outpatients. DESIGN AND METHODS: In a cohort of 1,412 consecutive hypertensive outpatients (790 females, 622 males; mean age: 60.3±12.2 years) evaluated from January 2015 to December 2016, the following parameters were assessed: age, gender, body mass index (BMI), waist circumference (WC), smoking habits, BP in the sitting position, estimated glomerular filtration rate (eGFR), serum glucose, lipid profile, antihypertensive drugs prescribed. In agreement with the European guidelines, hypertension was defined as sitting BP ≥140/90 mmHg or use of antihypertensive drugs. Patients whose BP was <140/90 mmHg were considered as having achieved BP control. Furthermore, in compliance with the redefinition of hypertension suggested by the American College of Cardiology/American Heart Association (ACC/AHA), a second level of BP control (BP <130/80 mmHg) was evaluated. RESULTS: Overall, 75.7% of hypertensive patients achieved BP levels <140/90 mmHg, while 50.5% achieved BP levels <130/80 mmHg. In both contexts, compared with patients whose BP was not controlled, those achieving the BP targets were mainly younger and females with a lower prevalence of obesity, diabetes and chronic kidney disease. Furthermore, they also had a lower WC and a higher eGFR. CONCLUSIONS: Nearly 76% of patients achieved the BP target of <140/90 mmHg, a result which is higher than the 70% achieved in Europe, and 50.6% achieved that of <130/80 mmHg, a result which is slightly higher than the 47% recently reported in USA.

[PRES (Posterior Reversible Encephalopathy Syndrome): potential complication of hypertensive crisis. Case report and literature review].

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological syndrome, usually reversible, characterized by vasogenic oedema in cerebral posterior regions in patients with autoimmune diseases, nephropathies, hypertensive crisis, eclampsia and exposure to cytotoxic drugs. The main symptoms are: headache, nausea, vomiting, seizures, visual disturbance and altered consciousness. Complications as cerebral hemorrhage and recurrences are rare. We describe a case of a 65 years old woman, affected by chronic kidney disease, recently exacerbated, diabetes and hypertension in treatment, who showed an heterogeneous clinical presentation with vomiting, headache, blurred vision and impaired consciousness during an episode of acute hypertension. After an adjustement of the antihypertensive treatment we observed a regression of symptoms in one week. FLAIR sequences on MRI showed cerebral bilateral vasogenic oedema in posterior regions, typical for PRES. This case was suggestive for PRES and a prompt adjustement of the antihypertensive treatment was critical for clinical recovery. Brain MRI was crucial for diagnosis. It is important for clinicians to recognize PRES as a possible complication of renal disease and hypertensive crisis.

Usefulness of US imaging in overhydrated nephropathic patients.

Achievement of a normal hydration status is one of the major targets of hemodialysis. It is based on the estimation of "dry weight", the term used to define normal body fluid content. The concept of dry weight in hemodialysis patients is clinically undisputed, but it is not always easy to achieve in this population. Assessment of hydration status by clinical evaluation is imprecise and often unreliable. Measurement of the inferior vena cava (IVC) diameter has been shown to reflect individual fluid status. The relationship between variation in IVC diameter before and after hemodialysis session and weight loss has been investigated. Ultrasound (US) measurement of the IVC diameter is considered a valid measure of the hydration status and is routinely used in hemodialysis patients. Moreover, a relationship between IVC diameter, respiratory activity and hydration status, evaluated by considering both plasma volume and central venous pressure, has been demonstrated. In conclusion, assessment of hydration status based on blood pressure and central venous pressure can be considered reliable only in patients without signs of heart failure.

[Uremic encephalopathy in regular dialysis treatment: uremic stroke?]. / Encefalopatia uremica in paziente in trattamento emodialitico cronico: stroke uremico? Descrizione di un caso clinico.

This case report a 59 years-old male in regular dialysis treatment with neurologic emergency characterized by neurologic signs as deep sopor the cause of which was uremic encephalopathy. At presentation, laboratory investigations revealed creatinine 12,75 mg/dl, BUN 174 mg/% and hyperkalemia 7,5 mq/L. The most common abnormal test results were EEG and ECG. CT brain showed no evidence of hemorrhagic areas or hematoma subdural. The patient was treated with hemodialysis and after the first hour of hemodialysis, laboratory control revealed hypokaliemia with metabolic acidosis due to arteiovenous fistula recirculation. After placement of jugular venous hemodialysis catheter and intensive treatment, the patient showed gradual improvement of uremic stroke due to arteriovenous fistula recirculation for high grade venous stenoses. Arteriovenous fistula dysfunction remains a major contributor to the morbidity and mortality of hemodialysis patients. The failure of a newly created AVF to mature and to develop stenosis in an estabilished AVF are two common clinical predicaments. The goal is to identify a dysfunctional AVF early enough to intervene in a timely manner, either to assist the maturation process or to prevent thrombosis. Most clinical features of neurologic complications in uremics are nonspecific and do not reliable, but it is important to identify specific causes such as vascular access recirculation for adequate treatment and regression of uremic stroke.

[Primary hyperaldosteronism: a diagnostic algorithm]. / L'iperaldosteronismo primitivo: algoritmo diagnostico.

Primary aldosteronism is the most frequent form of secondary hypertension. It is characterized by an autonomous, inappropriately high and unsuppressible production of aldosterone. The prevalence of aldosteronism in the general population is from 5-12% with bilateral adrenal hyperplasia and aldosterone-producing adenoma being the two main causes. Primary aldosteronism may either be sporadic or familial, the latter variant occurring in at least three forms: type I (or glucocorticoid-remediable aldosteronism), type II and type III. The diagnosis is based on the aldosterone/renin ratio as a screening test, subsequent confirmatory tests, and on CT/MR imaging studies. Adrenal vein sampling is the gold standard test for diagnosing the major subtypes and for identifying the surgically correctable forms. Genetic testing is used to exclude the familial forms.

Adsorption dialysis: from physical principles to clinical applications.

The uremic syndrome is characterized by the retention of various solutes that would normally be excreted by the kidneys. The substances that interact negatively with biologic functions are called uremic toxins. Over the past five decades, the membranes used for the treatment of chronic kidney disease have continuously evolved. The exposure of blood to any extracorporeal artificial surface results in the activation of several pathways within the body, including those involving coagulation and complement activation. One of the by-products of this generalized activation process is protein adsorption to the membrane surface, another phenomenon which can have a significant impact on solute removal. In fact, an array of studies showed that with increasing size of middle-sized proteins and other compounds, relatively more clearance is achieved by membrane adsorption compared with loss into the dialysate. A high adsorptive capacity, one of the main features of polymethylmethacrylate (PMMA) membranes, is very helpful and may both increase the total amount of solutes removed and remove different kinds of solutes. In this setting, a few studies have shown a variety of efficient clinical implications for adsorption hemodialysis, such as uremic pruritus, anemia, carpal tunnel syndrome and renal amyloidosis, immune dysfunction and improved response to vaccination. In addition, nutrition and survival were also improved using PMMA membranes.

[Ultrasonography in the hyperhydrated patient]. / La semeiotica ecografica nel paziente iperidratato.

The achievement of a normal hydration state is one of the major targets of hemodialysis. It is based on the estimation of ''dry weight'', which corresponds to the normal body fluid content. Even though the concept of dry weight in hemodialysis patients is clinically undisputed, it is not always easy to achieve in this population. Assessment of the hydration state by clinical examination is imprecise and often unreliable. Measurement of the inferior vena cava (IVC) diameter has been shown to reflect individual fluid status. The relationship between the variation of the IVC diameter before and after the hemodialysis session and weight loss has been investigated. Measurement of the IVC diameter by ultrasound is considered a valid measure of the hydration state and can be routinely used in hemodialysis patients. Moreover, a relationship between IVC diameter, respiratory activity and the hydration state, evaluated by considering both plasma volume and central venous pressure, has been demonstrated. In conclusion, assessment of the hydration state based on blood pressure and central venous pressure can be considered reliable only in patients without signs of heart failure.

[Parenchymal complications of the transplanted kidney: the role of color-Doppler imaging]. / Le complicanze parenchimali del rene trapiantato: il ruolo dell'eco-color-Doppler.

Kidney transplantation is the treatment of choice for end-stage renal disease, given the better quality of life of transplanted patients when compared to patients on maintenance dialysis. In spite of surgical improvements and new immunosuppressive regimens, part of the transplanted grafts still develop chronic dysfunction. Ultrasonography, both in B-mode and with Doppler ultrasound, is an important diagnostic tool in case of clinical conditions which might impair kidney function. Even though ultrasonography is considered fundamental in the diagnosis of vascular and surgical complications of the transplanted kidney, its role is not fully understood in case of parenchymal complications of the graft. The specificity of Doppler ultrasound is low both in case of acute complications such as acute tubular necrosis, drug toxicity and acute rejection, and in case of chronic conditions such as chronic allograft nephropathy. Single determinations of resistance indices present low diagnostic accuracy, which is higher in case of successive measurements performed during the follow-up of the graft. Modern techniques including tissue pulsatility index, maximal fractional area and contrast-enhanced ultrasound increase the diagnostic power of ultrasonography in case of parenchymal complications of the transplanted kidney.

[Prevalence and control of hypertension in chronic hemodialysis patients: results of a single-centre clinical audit]. / Prevalenza e controllo dell'ipertensione arteriosa nei pazienti in trattamento emodialitico cronico: risultati di un audit clinico monocentrico.

Hypertension (HTN) is very common in chronic hemodialysis patients, with a prevalence of 72%, a very poor control and an annual mortality of 23%. We report the results of a clinical audit on prevalence and control of HTN in our hemodialysis patients. The following parameters in a cohort of 89 patients were assessed in one-month observational study, conducted in October 2010: blood pressure (BP) before the beginning (preHD BP) and after the end of the treatment (postHD BP), age, sex, comorbidity, serum hemoglobin (Hb) levels, plasma and dialysate sodium levels, interdialytic weight gain (IWG), serum parathyroid hormone (PTH) levels, prescription of erythropoiesis stimulating agents (ESA) and of antihypertensive drugs. In agreeement to the current guidelines, patients with preHD BP ≤140/90 mmHg and postHD BP ≤130/80 mmHg were considered normortensive. Forty-nine patients (55%) were found to be hypertensive. The following comorbidities, graded as 1+ to 3+, were detected: ischemic/hypertrophic cardiopathy, dyslipidemia, peripheral arteriopathy, diabetes mellitus. Only 14.3% of patients achieved both preHD and postHD BP targets. Compared to patients whose BP was not controlled, those achieving BP targets were younger, had lower dialysate sodium levels and showed a greater IWG. No significant difference there was in serum Hb levels, plasma sodium levels, serum PTH levels, prescription of antihypertensive drugs and ESA. Our data confirm the high prevalence of HTN and the unsatisfactory BP control in hemodialysis patients. A low-salt diet, probing for dry-weight and the antihypertensive medication may help to achieve the BP control.