Pharmacotherapy considerations in patients who develop acute kidney injury during anti-cancer therapy.

INTRODUCTION: Acute kidney injury (AKI) frequently develops in patients receiving cancer therapy and requires a wide differential diagnosis due to possible role of unique cancer and drug-related factors, in addition to common pre- and post-renal causes. Rapid development of new molecular targeted anti-cancer drugs and immunotherapies has opened unprecedented possibilities of treatment at the price of an increased spectrum of renal side effects. AREAS COVERED: The present review aims at providing a state-of-the-art picture of AKI in cancer patient (PubMed and Embase libraries were searched from inception to January 2024), with a focus on differential diagnosis and management of diverse clinical settings. Reports of parenchymal AKI due to glomerular, microvascular, tubular and interstitial damage have been constantly increasing. Complex electrolyte and acid-base disorders can coexist. The role of renal biopsy and possible therapeutic approaches are also discussed. EXPERT OPINION: Onconephrology has become an important subspecialty of clinical nephrology, requiring constantly updated skills and a high degree of interdisciplinary integration to tackle diagnostic challenges and even therapeutic and ethical dilemmas. Integrated onconephrological guidelines and availability of biomarkers may provide new tools for management of this unique type of patients in the near future.

SA-ß-Gal in Kidney Tubules as a Predictor of Renal Outcome in Patients with Chronic Kidney Disease.

Cellular senescence has emerged as an important driver of aging and age-related disease in the kidney. The activity of ß-galactosidase at pH 6 (SA-ß-Gal) is a classic maker of senescence in cellular biology; however, the predictive role of kidney tissue SA-ß-Gal on eGFR loss in chronic kidney disease (CKD) is still not understood. We retrospectively studied the expression of SA-ß-Gal in kidney biopsies obtained in a cohort [n = 22] of incident patients who were followed up for 3 years as standard of care. SA-ß-Gal staining was approximately fourfold higher in the tubular compartment of patients with CKD vs. controls [26.0 ± 9 vs. 7.4 ± 6% positive tubuli in patients vs. controls; p < 0.025]. Tubular expressions of SA-ß-Gal, but not proteinuria, at the time of biopsy correlated with eGFR loss at the follow up; moreover, SA-ß-Gal expression in more than 30% of kidney tubules was associated with fast progressive kidney disease. In conclusion, our study shows that SA-ß-Gal is upregulated in the kidney tubular compartment of adult patients affected by CKD and suggests that tubular SA-ß-Gal is associated with accelerated loss of renal function.

Interdialytic weight gain is not associated with symptoms of depression or apathy in patients on chronic hemodialysis.

PURPOSE: Little is known about the relationships between apathy, depressive symptoms and interdialytic weight gain (IDWG) in patients on chronic hemodialysis. Aim of the present study is to investigate the association between IDWG and symptoms of depression and apathy in hemodialysis patients. METHODS: A total of 139 chronic patients of the HD units between January 2020 and December 2021 were included in the present cross-sectional study. IDWG was calculated as the difference between the pre-HD weight and the weight registered after the previous session; the average of the sessions in a month was registered. Apathy Evaluation Scale (AES) was adopted to evaluate apathy. Depression was assessed by Beck Depression Inventory (BDI). RESULTS: Ninety-three patients had IDWG% ≤ 4 and 46 had an IDWG% > 4. Correlation between IDWG% and BDI as well that between IDWG% and AES were not statistically significant. Median BDI and mean AES did not differ significantly between the groups. In addition, 104 patients had a BDI < 16 and 35 had a BDI ≥ 6. Seventy-five patients had an AES score ≤ 35 and 63 had a AES score > 35. The IDWG (kg) and the IDWG% did not differ significantly between the two groups. CONCLUSION: IDWG is not associated with symptoms of depression or apathy in hemodialysis patients. Thus, these results may question if the use of behavioral intervention aimed at improving motivation is warranted in the hemodialysis population to reduce the IDWG.

Post-dialysis fatigue: Comparison of bicarbonate hemodialysis and online hemodiafiltration.

INTRODUCTION: The present cross-sectional study aimed to compare the prevalence, the characteristics of post-dialysis fatigue and the length of recovery time after hemodialysis in prevalent end-stage renal disease patients (ESRD) receiving bicarbonate hemodialysis (HD) or hemodiafiltration (HDF). METHODS: Patients were suffering from post-dialysis fatigue if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Moreover, each patient was invited to rate the intensity, duration, and frequency of post-dialysis fatigue from 1 to 5. In order to assess RECOVERY TIME AFTER DIALYSIS, patients were invited to answer to the following single open-ended question: "How long does it take you to recover from a dialysis session?" FINDINGS: We included 335 patients: 252 received HD and 83 received HDF. Post-dialysis fatigue was present in 204 patients (60.9%). Prevalence of post-dialysis fatigue did not differ significantly between patients on HD (62.3%) and on HDF (56.6%; p = 0.430). Median recovery time after dialysis was 180 min [180-240] and did not differ significantly between the two subgroups (180 min [130-240] and 240 min [120-332] p = 0.671, respectively). Median post-dialysis fatigue intensity, duration, and frequency were 3 [1-5], 3 [1-5], and 4 [1-5] and did not differ significantly between patients on HD and on HDF. At the multivariate analysis, age, ADL and hemoglobin levels were the independent predictors of the HDF treatment. DISCUSSION: Prevalence and characteristics of post-dialysis fatigue do not differ significantly between patients receiving bicarbonate HD or HDF.

Fatigue and apathy in patients on chronic hemodialysis.

INTRODUCTION: This study explores the link between fatigue and apathy in patients on chronic hemodialysis (HD). METHODS: One hundred thirty-nine chronic HD patients underwent the assessment of fatigue, apathy, depression, and their functional status, with the fatigue severity scale (FSS), the Apathy Evaluation Scale (AES), the beck depression inventory (BDI), the activity of daily living (ADL), and instrumental activity of daily living (IADL). RESULTS: Patients with high FSS had a significantly lower ADL and IADL score, higher BDI, Charlson Comorbidity Index, and AES score, and lower serum levels of creatinine, compared to low FSS patients. FSS was highly correlated with the AES, as well as with the BDI and the AES correlates with the BDI. At multiple regression analyses, only apathy and IADL were independent predictor variables of fatigue in HD population. CONCLUSION: Future longitudinal studies could determine if apathy is a causative factor for fatigue manifestation and development in HD patients.

[Preliminary report on the Covid-19 outbreak in Valle d'Aosta dialysis centers].

Valle d'Aosta, Italy's smallest region, faced a Covid-19 epidemic trend of absolute relevance. In line with data concerning the local general population, the predominance of the illness among uremic patients has been high. The authors report here preliminary data on the spread of this disease within the region and on the clinical trend of the infected patients who needed to be hospitalised.

[Monocentric experience of left atrial appendage occlusion among patients with advanced chronic kidney disease and non-valvular atrial fibrillation].

Atrial fibrillation is the most common cardiac disorder among chronic nephropathic patients. Possible therapeutic approaches include the use of anticoagulants, which are able to reduce the risk of thromboembolism but lead to an increasing bleeding risk, especially in this cohort of patients. Also, novel oral anticoagulant agents (NAO), due to their mainly renal clearance, are a relative contraindication in advanced renal disease. As an alternative to the oral anticoagulant therapy, left atrial appendage occlusion seems a promising opportunity in high risk, difficult to manage patients. Since there is limited evidence of LAAO in advanced chronic renal disease or dialysis patients, we report here a monocenter experience on 12 patients (6 of which in regular dialytic treatment) with a median clinical follow-up of fourteen months (3-22 months).

Intensity, Duration, and Frequency of Post-Dialysis Fatigue in Patients on Chronic Haemodialysis.

BACKGROUND: Although frequent and debilitating, little is known about the characteristics of post-dialysis fatigue (PDF). OBJECTIVE: To characterise the intensity, duration and frequency of PDF and the associated variables in patients on chronic haemodialyses. DESIGN: Prospective, observational and multicenter study. PATIENTS: We studied 271 patients. MEASUREMENTS: Patients were considered to be suffering from PDF if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis? Then, each patient was invited to rate the intensity, duration and frequency of PDF from 1 to 5. RESULTS: One hundred sixty-four patients (60.5%) had PDF. The median [95% confidence interval (CI)] scores of PDF intensity, duration and frequency were 3 (3-4), 3 (3-4) and 4 (4-4), respectively. The median (95% CI) of the sum of the scores (Sum Score) of PDF intensity, duration and frequency was 11 (10-12). Seventy four patients had a Sum Score ≥ 12. Using multiple regression analysis, PDF intensity was associated with dialytic age and ultrafiltration rate (UFR), PDF duration with dialytic age, while PDF fatigue frequency was associated with height. The Sum Score was associated with dialytic age and recovery time and negatively associated with daily activity, height and UFR (ml/kg/h). CONCLUSION: The intensity, duration and frequency of PDF are high in a large percentage of patients, suggesting that PDF is an intense event in terms of quantity and quality. Understanding the relationship between the variables associated with PDF and its intensity, duration and frequency may help better understand the underlying mechanisms of this burdensome condition.

[Monoclonal gammopathy of renal significance and membranoproliferative glomerulonephritis: a complex relationship with promising therapeutic opportunities].

In the last few years, the increasing awareness of the complex interaction between monoclonal component and renal damage has determined not only a new classification of the associated disorders, called Monoclonal Gammopathy of Renal Significance (MGRS), but has also contributed to emphasize the importance of an early diagnosis of the renal involvement, which is often hard to detect but can evolve towards terminal uraemia; it has also pointed at the need to treat these disorders with aggressive regimens, even if they are not strictly neoplastic. The case described here presented urinary abnormalities and renal failure secondary to a membranoproliferative glomerulonephritis (MPGN), with intensively positive immunofluorescence (IF) for monoclonal k light chain and C3, and in the absence of a neoplastic lympho-proliferative disorder documented on bone marrow biopsy. After the final diagnosis of MGRS, the patient was treated with several cycles of a therapy including dexamethasone, cyclophosphamide and bortezomib, showing a good functional and clinical response.

Recovery Time after Hemodialysis Is Inversely Associated with the Ultrafiltration Rate.

INTRODUCTION: The present study aimed to determine the variables that are associated with a longer dialysis recovery time (DRT) and to define the relationship that exists between DRT and the ultrafiltration rate (UFR) in prevalent chronic hemodialysis (CHD) patients. METHODS: We studied 210 prevalent CHD of 5 hemodialysis units in Central Italy. Patients were invited to answer to the question: "How long does it take you to recover from a dialysis session?" Answers to this question were subsequently converted into minutes. Demographic, clinical and laboratory parameters were recorded for each patient as well as the UFR (mL/kg/h), the dialysate sodium concentration and temperature. RESULTS: Median DRT was 180 min (60-420). Ninety five (45%) patients had a DRT ≥ the median value. Mean UFR was 9.2 ± 3.0 mL/kg/h. Patients with a lower DRT had a less prevalent disability in the instrumental activities daily living, had a higher UFR, and a lower dialysate temperature, as compared with subjects with higher DRT. According to the logistic regression model, UFR was associated with a DRT below the median (i.e., 180) in the unadjusted model (OR 1.12; 95% CI 1.02-1.23; p = 0.019), after adjusting for age and sex (OR 1.11; 95% CI 1.01-1.22; p = 0.025), and in the fully adjusted model (OR 1.11; 95% CI 1.04-1.22; p = 0.040). UFR increase was associated with increasing probability of DRT below the median (p for trend = 0.035). The highest tertile of DRT was associated with UFR below the mean value (i.e., 9.2 mL/kg/h) in multinomial logistic regression having the lowest DRT tertile as reference. DRT was significantly lower in patients with UFR > 13 mL/kg/h than in patients with UFR 10-13 or < 10 mL/kg/h. CONCLUSION: DRT is inversely associated with UFR in CHD patients. Whether a high UFR should be recommended to reduce the DRT needs to be elucidated through an adequate prospective randomized study.

Prevalence and Severity of Postdialysis Fatigue Are Higher in Patients on Chronic Hemodialysis With Functional Disability.

The aim of the present study was to determine the intensity, duration, frequency and prevalence of postdialysis fatigue (PDF) in patients on chronic hemodialysis (PCD) with and without functional disability. Patients underwent assessment of functional ability by the Katz ADL (activity daily living) questionnaire and the Lawton and Brody scale for the instrumental activity daily living (IADL) fatigue using the SF-36 Vitality Subscale, comorbidity through the Charlson comorbidity score index (CDI), and time of recovery after hemodialysis (TIRD). We studied 271 PCD. ADL and IADL disabilities were present in 75 (27.6%) and 168 (62%) patients, respectively. Patients with ADL disability were significantly older and showed higher CDI scores, and lower levels of serum albumin and Kt/V. Prevalence of PDF was significantly higher in patients with ADL disability as well as its severity, intensity, duration and frequency. Patients with IADL disability were significantly older, had a higher CCI score, had lower levels of serum albumin and Kt/V, and had a higher severity, intensity, duration and frequency of PDF. At multivariate regression analysis, ADL disability was positively associated with age, prevalence and severity of PDF, and dialysate temperature and inversely associated with serum albumin levels. IADL disability was instead positively associated with age and dialysate temperature and inversely associated with serum albumin levels. In conclusion, prevalence and severity of PDF are significantly higher in PCD with ADL disability than in those without it. This knowledge may have important implications for the development of interventions to reduce PDF in PCD.

Effects of Low-Protein, and Supplemented Very Low-Protein Diets, on Muscle Protein Turnover in Patients With CKD.

INTRODUCTION: Early studies have shown that patients with chronic kidney disease (CKD) are able to maintain nitrogen balance despite significantly lower protein intake, but how and to what extent muscle protein metabolism adapts to a low-protein diet (LPD) or to a supplemented very LPD (sVLPD) is still unexplored. METHODS: We studied muscle protein turnover by the forearm perfusion method associated with the kinetics of 2H-phenylalanine in patients with CKD: (i) in a parallel study in subjects randomized to usual diet (1.1 g protein/kg, n = 5) or LPD (0.55 g protein/kg, n = 6) (Protocol 1); (ii) in a crossover, self-controlled study in subjects on a 0.55 g/kg LPD followed by a sVLPD (0.45 g/kg + amino/ketoacids 0.1 g/kg, n = 6) (Protocol 2). RESULTS: As compared with a 1.1 g/kg containing diet, a 0.55 g/kg LPD induced the following: (i) a 17% to 40% decrease in muscle protein degradation and net protein balance, respectively, (ii) no change in muscle protein synthesis, (iii) a slight (by approximately 7%, P < 0.06) decrease in whole-body protein degradation, and (iv) an increase in the efficiency of muscle protein turnover. As compared with an LPD, an sVLPD induced the following: (i) no change in muscle protein degradation, and (ii) an approximately 50% decrease in the negative net protein balance, and an increase in the efficiency of muscle protein turnover. CONCLUSION: The results of these studies indicate that in patients with CKD the adaptation of muscle protein metabolism to restrained protein intake can be obtained via combined responses of protein degradation and the efficiency of recycling of amino acids deriving from protein breakdown.

Prevalence and associated variables of post-dialysis fatigue: Results of a prospective multicentre study.

AIM: The study aims to determine prevalence and severity of PDF and to define its associated variables. METHODS: In five haemodialysis units of northern-centre Italy, patients were regarded to suffer from PDF if they spontaneously offered this complaint when asked the open-ended question: Do you feel better or worse after dialysis? If worse, please specify in which way. A complaint of fatigue would be probed further with questions directed at its duration, frequency and intensity, allowing creation of a fatigue index of severity (one third of the sum of these three parameters, each rated from 1 to 5). Patients were stratified into three groups according the severity of PDF: 1) score = 0; 2) score = 1-3; 3) score > 3. RESULTS: We studied 271 patients: 164 had PDF and 107 did not. PDF patients had significantly longer time of recovery after dialysis (TIRD). TIRD was significantly associated with PDF duration, intensity, and frequency. Patients with PDF were older and had a lower ADL score. At multivariate analysis, PDF was significantly associated with TIRD. In a multivariate model that did not include TIRD, PDF was independently associated with age and ADL. Sixty patients had moderate PDF and 104 had severe PDF. In patients with severe PDF, age and dialytic age were higher, ADL and IADL scores were lower, TIRD was longer and the ultrafiltration rate was lower. At multivariate analysis, PDF severity was independently associated with TIRD. In the model without TIRD, PDF severity was associated with ADL only. CONCLUSION: Post-dialysis fatigue is frequent and associated with age and ADL. Dialytic variables seem unrelated to PDF.

Structure⁻Properties Relations for Polyamide 6, Part 1: Influence of the Thermal History during Compression Moulding on Deformation and Failure Kinetics.

The deformation and failure kinetics of polyamide 6 samples prepared by several thermal histories were investigated by tests at different temperatures and relative humidities. PA6 samples were produced in quiescent condition and multiple cooling procedure. A characterization was performed to investigate the effect of the different thermal histories and the effect of hydration on both structures and glass transition temperature. The mechanical properties were investigated by tensile and creep tests at different temperatures and relative humidity. In order to describe the experimental results, the Ree⁻Eyring equation, modified with the "apparent temperature", was employed. In addition, the results of time-to-failure (creep tests) were described by the use of the "critical strain" concept. Eventually, a link between the Eyring theory and the structure evolution was made, i.e., a relation between the rate factors and the average lamellar thickness.

Structure-Properties Relations for Polyamide 6, Part 2: Influence of Processing Conditions during Injection Moulding on Deformation and Failure Kinetics.

The effect of processing conditions during injection on the structure formation and mechanical properties of injection molded polyamide 6 samples was investigated in detail. A large effect of the mold temperature on the crystallographic properties was observed. Also the the effect of pressure and shear flow was taken in to consideration and analysed. The yield and failure kinetics, including time-to-failure, were studied by performing tensile and creep tests at several test temperatures and relative humidities. As far as mechanical properties are concerned, a strong influence of temperature and relative humidity on the yield stress and time-to-failure was found. A semi-empirical model, able to describe yield and failure kinetics, was applied to the experimental results and related to the crystalline phase present in the sample. In agreement with findings in the literature it is observed that for high mold temperatures the sample morphology is more stable with respect to humidity and temperature than in case of low mold temperatures and this effects could be successfully captured by the model. The samples molded at low temperatures showed, during mechanical testing, a strong evolution of the crystallographic properties when exposed to high testing temperature and high relative humidity, i.e., an increase of crystallinity or a crystal phase transition. This makes a full description of the mechanical behavior rather complicated.

[Severe multifactorial hyponatremia]. / Severa iponatremia a genesi multifattoriale.

Hyponatremia is the most common electrolyte disorder observed in hospitalized patients. The most severe forms are neurological and potentially fatal emergencies; yet increased morbidity, length of hospital stay and costs associated with less severe forms are aspects of major concern. Nephrologists are frequently consulted regarding the therapeutic management and the key pathophysiological issues of hyponatremia, as this latter aspect represents a true challenge in an emergency setting. We report a case of a woman admitted to the emergency room for gait instability caused by a very severe multifactorial hyponatremia with a favourable clinical outcome.

Toll-like receptor 4 signalling mediates inflammation in skeletal muscle of patients with chronic kidney disease.

BACKGROUND: Inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia but why uremia up-regulates pro-inflammatory cytokines is unknown. Toll-like receptors (TLRs) regulate locally the innate immune responses, but it is unknown whether in chronic kidney disease (CKD) TLR4 muscle signalling is altered. The aim of the study is to investigate whether in CKD muscle, TLRs had abnormal function and may be involved in transcription of pro-inflammatory cytokine. METHODS: TLR4, phospho-p65, phospho-ikBα, tumour necrosis factor (TNF)-α, phospho p38, Murf 1, and atrogin were studied in skeletal muscle from nondiabetic CKD stage 5 patients (n = 29) and controls (n = 14) by immunohistochemistry, western blot, and RT-PCR. Muscle cell cultures (C2C12) exposed to uremic serum were employed to study TLR4 expression (western blot and RT-PCR) and TLR-driven signalling. TLR4 signalling was abrogated by a small molecule chemical inhibitor or TLR4 siRNA. Phospho AKT and phospho p38 were evaluated by western blot. RESULTS: CKD subjects had elevated TLR4 gene and protein expression. Also expression of NFkB, p38 MAPK and the NFkB-regulated gene TNF-α was increased. At multivariate analysis, TLR4 protein content was predicted by eGFR and Subjective Global Assessment, suggesting that the progressive decline in renal function and wasting mediate TLR4 activation. In C2C12, uremic serum increased TLR4 as well as TNF-α and down-regulated pAkt. These effects were prevented by blockade of TLR4. CONCLUSIONS: CKD promotes muscle inflammation through an up-regulation of TLR4, which may activate downward inflammatory signals such as TNF-α and NFkB-regulated genes.

Interorgan handling of fibroblast growth factor-23 in humans.

Fibroblast growth factor-23 (FGF-23) accumulates in blood of patients with chronic kidney disease (CKD) and is associated both with cardiovascular complications and disease progression. However, our knowledge of the sites and mechanisms that regulate plasma FGF-23 is still incomplete. We measured plasma intact FGF-23 across the kidney, splanchnic organs, and lung in 11 patients [estimated glomerular filtration rate (eGFR) 60 ± 6 ml/min] during elective diagnostic cardiac catheterizations. In these patients FGF-23 was removed by the kidney, with a fractional extraction (FE) of ∼22%. The FE of FGF-23 across the kidney was similar to that of creatinine (∼17%, P = NS). In addition, the FGF-23 FE by the kidney was significantly directly related to eGFR (r = 0.709 P = 0.018) and to kidney creatinine FE (r = 0.736 P = 0.013) but only as a trend to plasma phosphate levels (r = 0.55, P = 0.18). There was no difference in FGF-23 levels in blood perfusing splanchnic organs and cardiopulmonary bed. However, the arterial-venous difference of FGF-23 across the lung was directly related to FGF-23 pulmonary artery levels, suggesting that the lung, and possibly the heart, participate in the homeostasis of plasma FGF-23 when its systemic levels are increased. Our data show that the human kidney is the only site for FGF-23 removal from blood and suggest that FGF-23 is predominantly removed by glomerular filtration. The kidney ability to remove FGF-23 from the circulation likely accounts for the early increase in blood of FGF-23 in patients with CKD.

Peripheral artery disease and blood pressure profile abnormalities in hemodialysis patients.

BACKGROUND: Patients undergoing chronic hemodialysis (HD) are at increased risk for peripheral artery disease (PAD). Both ankle-brachial index (ABI) and ambulatory blood pressure monitoring (ABPM) in the interdialytic period have been shown to be strong predictors of all-cause mortality. METHODS: This cross-sectional study investigated the relationship between ABPM profile and ABI in 81 HD patients. ABPM was measured throughout a 44-h midweek interdialytic period. Pre-dialysis ABI was evaluated with a BOSO ABI device. An ABI value <0.9 or ≥1.3 was defined as abnormal. RESULTS: In the whole study group (72 % males, mean age 67 ± 14 years), there was an increase in BP (p < 0.05) and in systolic BP night/day ratio (n/dSR, p = 0.01) during the interdialytic period. Patients with abnormal ABI (n = 29) more frequently had a positive history for cerebrovascular accident and PAD and higher proBNP values than those with normal ABI (n = 52). No difference was detected among ABPM-derived components except for the n/dSR (p = 0.02). Patients with abnormal ABI showed a significantly increased n/dSR (p = 0.02) and ambulatory arterial stiffness index (AASI) (p = 0.006) on the second day compared to the first. Patients with n/dSR >1 during day 2 (n = 34) were older, showed significantly higher proBNP and AASI and were more likely to reveal abnormal ABI compared to those with a lower n/dSR (p = 0.006). CONCLUSIONS: Abnormal ABI in HD patients is associated to changes in interdialytic ABPM pattern, namely higher n/dSR on day 2. These data may indicate the pathophysiological mechanisms underlying the worse outcome observed in HD patients.