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Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages, it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay., (© 2024. The Author(s).)

In the past decade, scientific research in the area of Nephrology has focused on evaluating the clinical utility and performance of various biomarkers for diagnosis, risk stratification and prognosis. Before implementing a biomarker in everyday clinical practice for screening a specific disease context, specific statistic measures are necessary to evaluate the diagnostic accuracy and performance of this biomarker. Receiver Operating Characteristic (ROC) Curve analysis is an important statistical method used to estimate the discriminatory performance of a novel diagnostic test, identify the optimal cut-off value for a test that maximizes sensitivity and specificity, and evaluate the predictive value of a certain biomarker or risk, prediction score. Herein, through practical examples, we aim to present a simple methodological approach to explain in detail the principles and applications of ROC curve analysis in the field of nephrology pertaining diagnosis and prognosis., (© 2024. The Author(s).)

The assessment of risk and effect size of a specific endpoint associated to the presence/absence of a certain exposure is a hallmark in clinical and epidemiological research. In fact, before recommending any treatment, it is mandatory to investigate the magnitude of the benefits and harms between the exposure under investigation (e.g. a given treatment) and a specific disease or event. To do this, clinicians and statisticians use absolute (risk differences, number needed to treat, likelihood to be helped or harmed) and relative (risk ratio, incidence rate ratio, hazard ratio and odds ratio) measures of effect. Herein, using a series of clinical examples, we aim to present a step by step methodologic approach of measures of effect in the area of nephrology and urology., (© 2023. The Author(s).)

Oxidative stress (OS) has been recognized as a pathophysiologic mechanism underlying the development and progression of chronic kidney disease (CKD). OS, which results from the disturbance of balance among pro-oxidants and antioxidants favoring the pro-oxidants, is present even in early CKD and increases progressively along with deterioration of kidney function to end-stage kidney disease (ESKD). In ESKD, OS is further exacerbated mainly due to dialysis procedures per se and predisposes to increased cardiovascular morbidity and mortality. Therefore, since OS plays a pivotal role in the pathogenesis and progression of atherosclerosis in uremic patients, several strategies aiming to ameliorate OS in these patients have been proposed. Among those, N-acetylcysteine (NAC), a thiol-containing antioxidant agent, has attracted special attention due to its pleiotropic functions and beneficial effect in various OS-related entities including paracetamol overdose and prevention of contrast-induced nephropathy. In this review, we present the currently available literature on the antioxidant and anti-inflammatory properties of NAC in CKD, including hemodialysis and peritoneal dialysis., (© 2023. The Author(s).)

Background/aim: End-stage kidney disease (ESKD) is strongly associated with factors that aggravate the physical activity level and body composition status of hemodialysis patients (HD). Even though exercise in HD patients have shown remarkable benefits on hemodialysis adequacy, it is yet inconclusive if exercise can positively affect body composition parameters or if dialysis adequacy may affect body composition status. This study aimed to investigate the effect of a 6-month intradialytic exercise training program on dialysis adequacy indices and body composition parameters in HD patients., Study Design: A total of 24 HD patients were randomly assigned into two equally sized groups. The exercise group (EX group) participated in a 6-month intradialytic moderate-intensity aerobic exercise training program at the beginning of the HD sessions, three times a week for 60 min, and maintained a Borg's Rating of Perceived Exertion score between 13 and 14. The Control group (C group) remained untrained. At baseline, during, and at the end of the 6-month study, we assessed single-pool Kt/V, urea reduction ratio (URR), and body composition parameters, such as extracellular water (ECW)/ intracellular water (ICW) ratio, body mass index (BMI) and lean tissue mass (LTM). In all patients, the 6-min-walking test (6MWT) was performed as a marker of physical performance., Results: A significant increase of both Kt/V (increase by 19%, p = 0.01), and URR (increase by 7%, p = 0.03) values has been observed in the EX group after the 6-month training program. Similarly, a statistically significant increase in 6MWT distance (from 442 ± 67 m to 481 ± 68 m, p = 0.02) in the EX group has also been found, compared to the C group (from 393 ± 59 m to 427 ± 81 m, p = 0.06). Neither EX nor C group has shown significant changes in body composition parameters. After training, linear regression analysis revealed a strong positive correlation between Kt/V and 6MWT changes (r = 0.74, p = 0.04) in the EX group., Conclusions: Six months of intradialytic aerobic exercise might increase dialysis adequacy, by increasing Kt/V and URR, and physical performance, regardless of changes in body composition indices., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Observational studies have shown that among patients on hemodialysis, hyperkalemia is strongly associated with excess risk for cardiovascular-related hospitalizations and sudden cardiac death. However, the actual burden of hyperkalemia, the rates of its recurrence and seasonality in its variation still remain unclear., Methods: Between June 2020 and May 2021, 1786 mid-week pre-dialysis serum potassium (sK) measurements were retrospectively recorded from 149 patients receiving thrice-weekly hemodialysis in a single-center in Thessaloniki, Greece. The prevalence, recurrence and seasonal variation of hyperkalemia were assessed using three pre-specified sK thresholds (≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L)., Results: At baseline, 60.4%, 42.2% and 13.4% of patients had sK levels ≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L, respectively. At any time-point during follow-up, 85.2%, 69.8% and 38.9% of patients experienced at least one hyperkalemic event ≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L, respectively. Of the 104 patients experiencing an initial sK elevation ≥ 5.5 mmol/L, hyperkalemia at the same threshold reoccurred in 60.6% at month 1, in 47.1% at month 2 and in 46.1% at month 3 of follow-up. Seasonal variation was also observed, with the prevalence of hyperkalemia to be significantly higher in summer. Shorter delivered hemodialysis < 4 h/session (OR: 2.568; 95% CI 1.045-6.313) and the use of a high dialysate K concentration (OR: 14.646; 95% CI 2.727-78.647) were the 2 factors that were independently associated with hyperkalemia., Conclusion: The present study shows that among hemodialysis patients, the rates of hyperkalemia prevalence and recurrence are very high, reflecting the large unmet need to identify more effective potassium-lowering therapeutic interventions in this high-risk population., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Although coronavirus disease (COVID-19) is primarily a respiratory disease, the kidney may be among the target organs of infection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Independently of baseline kidney function, acute kidney injury (AKI) is a common complication of COVID-19, associated with increased mortality and morbidity. Most frequently, COVID-19 causes acute tubular necrosis; however, in some cases, collapsing focal segmental glomerulosclerosis and direct viral tropism of the kidneys have also been documented. AKI secondary to COVID-19 has a multi-factorial origin. Even mild impairment of renal function is an independent risk factor for COVID-19 infection, hospitalisation and mortality. Dialysis patients also carry an increased risk of other severe COVID-related complications, including arrhythmias, shock, acute respiratory distress syndrome and acute heart failure. In such patients, COVID-19 may even present with atypical clinical symptoms, including gastrointestinal disorders and deterioration of mental status. More research is needed on the exact effects of SARS-CoV-2 on the kidneys. Finally, it remains to be proven whether the outcome of patients with kidney disease may be improved with anticipated vaccination programmes., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: We aimed to assess whether high-density lipoprotein (HDL) cholesterol modifies the association between adiponectin and incident cardiovascular (CV) morbidity and mortality in Type 2 Diabetes Mellitus (T2DM) and vice versa., Methods: At baseline, 106 T2DM participants with various degrees of renal function were enrolled and followed up over a period of 7 years with fatal/nonfatal CV events as outcome., Results: During the follow-up, 49 participants experienced incident CV events (28 fatal, 21 nonfatal). On univariate Fine and Gray sub-hazard models, HDL cholesterol was a strong modifier of the association between adiponectin and CV outcomes both on crude (P = 0.011) and gender- and eGFR-adjusted models (P = 0.010). The protective effect for CV events portended by a fixed increase in adiponectin (1 μg/ml) was progressively higher across increasing values of HDL cholesterol. Moreover, plasma adiponectin also modified the protective effect of HDL on CV outcomes both in crude and multivariate analyses. We found a mutual effect modification between adiponectin and HDL as risk factors of CV events in participants with T2DM., Conclusion: Our results are coherent with the hypothesis that HDL cholesterol might play a pivotal role in the interpretation of the association between adiponectin and the risk of adverse CV outcomes in this population., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: We aimed to investigate the prevalence of thyroid hormone abnormalities and the relationship between free triiodothyronine (fT3), thyroid stimulating hormone (TSH) and free thyroxine (fT4) serum levels with kidney function and proteinuria in 4108 subsequent patients admitted to a Nephrology Clinic at a tertiary Medical Centre., Methods: All patients were categorized based on their estimated glomerular filtration rate (eGFR) as follows: normal-eGFR ≥ 60 ml/min, mild kidney impairment-30 ≤ eGFR < 60 ml/min, and severe kidney impairment-eGFR < 30 ml/min., Results: Subjects with normal eGFR presented a laboratory constellation of hypothyroidism in 3.38% and "low-T3 syndrome" in 8.28%, while subjects with severe kidney impairment were diagnosed with hypothyroidism in 2.82% and "low-T3 syndrome" in 22.9%. Multivariate regression analysis showed that eGFR was a strong independent predictor of serum fT3 levels in patients with eGFR < 60 ml/min. Impaired kidney function was associated with low fT4 and fT3 but not TSH. Our findings showed an inverse correlation of fT3 and fT4 levels and proteinuria range. FT4 inversely correlated with the extent of proteinuria in all subgroups of patients. In contrast, the inverse correlation of fT3 serum levels and proteinuria disappeared in patients with eGFR < 60 ml/min., Conclusion: In a large cohort of inpatients, the prevalence of low-T3 syndrome was 2.5 times higher in patients with advanced kidney disease, compared to those with normal kidney function. In advanced CKD, both eGFR and proteinuria were strongly correlated with thyroid hormones. Therefore, close screening of the "thyroid profile" in patients with any stage of CKD, especially to those with proteinuria, might be warranted., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

The use of Automated Peritoneal Dialysis (APD) in its various forms has increased over the past few years mainly in developed countries. This could be attributed to improved cycler design, apparent lifestyle benefits and the ability to achieve adequacy and ultrafiltration targets. However, the dilemma of choosing the superior modality between APD and Continuous Ambulatory Peritoneal Dialysis (CAPD) has not yet been resolved. When it comes to fast transporters and assisted PD, APD is certainly considered the most suitable Peritoneal Dialysis (PD) modality. Improved patients' compliance, lower intraperitoneal pressure and possibly lower incidence of peritonitis have been also associated with APD. However, concerns regarding increased cost, a more rapid decline in residual renal function, inadequate sodium removal and disturbed sleep are APD's setbacks. Besides APD superiority over CAPD in fast transporters, the other medical advantages of APD still remain controversial. In any case, APD should be readily available for all patients starting PD and the most important indication for its implementation remains patient's choice.

A preliminary step when planning a randomized clinical trial (RCT) is the sample size calculation. This is the determination of the optimal number of patients which ensures an adequate power to the study to detect as statistically significant a certain between-arms difference, if any, in the frequency/magnitude of a specific endpoint. The sample size calculation is performed by specific calculators requiring as input variables the expected effect size, the alpha error (α), the beta error (β) and the allocation ratio, this latter being the ratio between the number of participants allocated to the arms of a RCT. Herein, we provide a series of examples of sample size calculation in the context of superiority RCTs in elderly.

The hazard ratio is a measure of effect which is of paramount importance in etiological research, that is in studies aimed at assessing the strength of the causal relationship between a given treatment/exposure and a certain outcome. Despite the widespread use of the hazard ratio as a measure of effect in scientific reports and articles, the interpretation of this index is often accompanied by some misconceptions which can jeopardize the critical appraisal of randomized clinical trials (RCTs) and observational studies as well. Herein, using a series of examples derived from RCTs in the elderly subjects, we address major pitfalls regarding the interpretation of the hazard ratio in geriatric research.

Prognosis aims at estimating the future course of a given disease in probabilistic terms. As in diagnosis, where clinicians are interested in knowing the accuracy of a new test to identify patients affected by a given disease, in prognosis they wish to accurately identify patients at risk of a future event conditional to one or more prognostic factors. Thus, accurate risk predictions play a primary role in all fields of clinical medicine and in geriatrics as well because they can help clinicians to tailor the intensity of a treatment and to schedule clinical surveillance according to the risk of the concerned patient. Statistical methods able to evaluate the prognostic accuracy of a risk score demand the assessment of discrimination (the Harrell's C-index), calibration (Hosmer-May test) and risk reclassification abilities (IDI, an index of risk reclassification) of the same risk prediction rule whereas, in spite of the popular belief that traditional statistical techniques providing relative measures of effect (such as the hazard ratio derived by Cox regression analysis or the odds ratio obtained by logistic regression analysis) could be per se enough to assess the prognostic value of a biomarker or of a risk score. In this paper we provide a brief theoretical background of each statistical test and a practical approach to the issue. For didactic purposes, in the paper we also provide a dataset (n = 40) to allow the reader to train in the application of the proposed statistical methods.

In 2016, the International Society of Peritoneal Dialysis (ISPD) published guidelines that focus on the importance of both prevention and treatment of peritonitis. For once more, the need for annual reporting of peritonitis rates and recording of peritonitis and exit-site infections, isolated microorganism and antimicrobial susceptibilities as a central component of a quality improvement program is highlighted. Data on new antibiotic regimens, techniques for microorganism isolation and peritoneal dialysis solutions are included. Training of both peritoneal dialysis nurses and patients seems to be crucial, while the modifiable risk factors for peritonitis seem to be of great interest. In this article, we record the changes in the last ISPD (2016) guidelines compared to the previous ones published in 2010.

Purpose: Control of hydration status is an important constituent of adequate and efficient hemodialysis (HD) treatment. Nevertheless, there are no precise clinical indices for early recognition of small changes in fluid status of patients undergoing chronic hemodialysis therapy. This study aimed to evaluate and compare the widely used and reliable method of indexed inferior vena cava diameter (IVCDi) with established and more recently available techniques (bioelectrical impedance analysis [BIA], continuous blood volume monitoring [Crit-line], and the B-line score [BLS] with lung ultrasonography) for estimating the hydration status of patients on HD., Methods: Fifty-three patients undergoing chronic HD thrice weekly were included in the study. Evaluation of hydration status methods (IVCDi, BLS, BIA, and Crit-line) was performed thrice weekly before and after HD. Receiver operating characteristic curve analysis was performed to evaluate the discriminative power of (methods) the BLS, BIA, and Crit-line for predicting over- and underhydration of patients, as determined by the reference method, IVCDi., Results: BLS showed the most promising results in predicting overhydration, as determined by IVCDi, compared with BIA and Crit-line and presented a sensitivity of 77% and specificity of 74%. The accuracy of the BLS was higher than that of BIA (0.81 vs. 0.71, p = 0.032) and Crit-line (0.61, p = 0.001). BLS also showed more promising results in predicting underhydration, as determined by IVCDi, than BIA and Crit-line and presented a sensitivity of 78% and a specificity of 73%. The accuracy of the BLS was higher than that of BIA (0.83 vs. 0.76, p = 0.035) and Crit-line (0.50, p < 0.001)., Conclusions: The BLS is a useful and easily performed technique that has recently become available for accurate evaluation of dry weight and fluid status in patients with end-stage renal disease undergoing chronic HD. This method might help recognize asymptomatic lung congestion in these patients.