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Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care
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Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (16 June 2023) | Viewed by 22934

Special Issue Editor

Prof. Dr. Giacomo Garibotto

E-Mail Website
Guest Editor
1. Department of Internal Medicine, Division of Nephrology, Dialysis and Transplantation, University of Genoa, Viale Benedetto 15,6, I-16132 Genoa, Italy
2. IRCCS Ospedale Policlinico San Martino, Genoa, Italy
Interests: chronic kidney disease; nutrition; diabetic nephropathy; inflammation; oxidative stress; amino acid and protein metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The past decades have witnessed tremendous progress in our understanding of the mechanisms underlying progression of chronic kidney disease (CKD) a condition characterized by disabling complications and increased mortality and morbidity.

New theories have been recently developed for prevention or treatment of kidney fibrosis and cell loss.  In addition recent progress in our understanding of CKD pathophysiology together with  the development of novel therapeutic agents has led to a renewed attention on the treatment of CKD–associated metabolic complications. As we enter a new era of treatment for CKD, all these important issues are addressed in this volume.

Issues:

  • SGLT2 inhibitors for treatment of nondiabetic CKD and cardiorenal syndromes
  • Mineralocorticoid antagonism for treatment of diabetic and nondiabetic kidney disease
  • NRF2 activators and antioxidants
  • Senolytic drugs
  • Native Vitamin D
  • Correction of metabolic acidosis and CKD progression
  • HIF1 stabilizers
  • New paradigms on potassium restriction in CKD
  • Plantbased low protein diets for conservative tratment of CKD

Prof. Dr. Giacomo Garibotto
Guest Editor

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CKD
  • cell senescence
  • diabetic kidney disease
  • hyperkalaemia
  • oxidative stress
  • Nrf2
  • metabolic acidosis
  • mineralocorticoid antagonism
  • vitamin D
  • SGLT2

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Published Papers (10 papers)

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Editorial

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3 pages, 190 KiB  
Editorial
Treatment of Chronic Kidney Disease: Moving Forward
by Giacomo Garibotto, Daniela Picciotto and Pasquale Esposito
J. Clin. Med. 2022, 11(23), 6948; https://doi.org/10.3390/jcm11236948 - 25 Nov 2022
Cited by 2 | Viewed by 2345
Abstract
Chronic kidney disease (CKD) affects ~10% of the adult population [...] Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care)

Research

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13 pages, 3448 KiB  
Article
Circulating microRNA Profiles for Premature Cardiovascular Death in Patients with Kidney Failure with Replacement Therapy
by Canan Kuscu, Yamini Mallisetty, Surabhi Naik, Zhongji Han, Caleb J. Berta, Cem Kuscu, Csaba P. Kovesdy and Keiichi Sumida
J. Clin. Med. 2023, 12(15), 5010; https://doi.org/10.3390/jcm12155010 - 30 Jul 2023
Cited by 1 | Viewed by 1438
Abstract
Introduction: Patients with kidney failure with replacement therapy (KFRT) suffer from a disproportionately high cardiovascular disease burden. Circulating small non-coding RNAs (c-sncRNAs) have emerged as novel epigenetic regulators and are suggested as novel biomarkers and therapeutic targets for cardiovascular disease; however, little is [...] Read more.
Introduction: Patients with kidney failure with replacement therapy (KFRT) suffer from a disproportionately high cardiovascular disease burden. Circulating small non-coding RNAs (c-sncRNAs) have emerged as novel epigenetic regulators and are suggested as novel biomarkers and therapeutic targets for cardiovascular disease; however, little is known about the associations of c-sncRNAs with premature cardiovascular death in KFRT. Methods: In a pilot case-control study of 50 hemodialysis patients who died of cardiovascular events as cases, and 50 matched hemodialysis controls who remained alive during a median follow-up of 2.0 years, we performed c-sncRNAs profiles using next-generation sequencing to identify differentially expressed circulating microRNAs (c-miRNAs) between the plasma of cases and that of controls. mRNA target prediction and pathway enrichment analysis were performed to examine the functional relevance of differentially expressed c-miRNAs to cardiovascular pathophysiology. The association of differentially expressed c-miRNAs with cardiovascular mortality was examined using multivariable conditional logistic regression. Results: The patient characteristics were similar between cases and controls, with a mean age of 63 years, 48% male, and 54% African American in both groups. We detected a total of 613 miRNAs in the plasma, among which five miRNAs (i.e., miR-129-1-5p, miR-500b-3p, miR-125b-1-3p, miR-3648-2-5p, and miR-3150b-3p) were identified to be differentially expressed between cases and controls with cut-offs of p < 0.05 and log2 fold-change (log2FC) > 1. When using more stringent cut-offs of p-adjusted < 0.05 and log2FC > 1, only miR-129-1-5p remained significantly differentially expressed, with higher levels of miR-129-1-5p in the cases than in the controls. The pathway enrichment analysis using predicted miR-129-1-5p mRNA targets demonstrated enrichment in adrenergic signaling in cardiomyocytes, arrhythmogenic right ventricular cardiomyopathy, and oxytocin signaling pathways. In parallel, the circulating miR-129-1-5p levels were significantly associated with the risk of cardiovascular death (adjusted OR [95% CI], 1.68 [1.01–2.81] for one increase in log-transformed miR-129-1-5p counts), independent of potential confounders. Conclusions: Circulating miR-129-1-5p may serve as a novel biomarker for premature cardiovascular death in KFRT. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care)
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15 pages, 306 KiB  
Article
Final Stage of Chronic Kidney Disease with Conservative Kidney Management or Renal Replacement Therapy: A Primary-Care Population Study
by Daniel Bundó, Oriol Cunillera, Ariadna Arbiol-Roca, Sílvia Cobo-Guerrero, Jose Romano, Neus Gil-Terron, Xavier Fulladosa, Jordi Comas, Inés Rama, Josep M. Cruzado and Betlem Salvador-Gonzalez
J. Clin. Med. 2023, 12(14), 4602; https://doi.org/10.3390/jcm12144602 - 11 Jul 2023
Cited by 1 | Viewed by 1286
Abstract
Background: Studies focus on the incidence and risk factors (RFs) associated with reaching the final stage of chronic kidney disease (CKD-G5) and receiving kidney replacement therapy (KRT). Analysis of those related to reaching CKD-G5 while receiving conservative kidney management (CKM) has been neglected. [...] Read more.
Background: Studies focus on the incidence and risk factors (RFs) associated with reaching the final stage of chronic kidney disease (CKD-G5) and receiving kidney replacement therapy (KRT). Analysis of those related to reaching CKD-G5 while receiving conservative kidney management (CKM) has been neglected. Methods: Retrospective cohort study analysing electronic health records of individuals aged ≥ 50 with eGFR < 60 mL/min/m2. Cumulative incidence rates of CKD-G5, with and without KRT, were calculated. Multinomial regression models determined odds ratios (ORs) for CKD-G5 progression with KRT, CKM, or death. Results: Among 332,164 patients, the cumulative incidence of CKD-G5 was 2.79 cases per 100 person-years. The rates were 1.92 for CKD-G5 with KRT and 0.87 for CKD-G5 with CKM. Low eGFR and albuminuria were the primary RFs. Male gender and uncontrolled blood pressure had a greater impact on KRT (OR = 2.63 CI, 1.63) than on CKD-G5 with CKM (OR = 1.45 CI, 1.31). Increasing age and rurality reduced the probability of KRT but increased the probability of CKD-G5 with CKM. Higher incomes decreased the likelihood of developing CKD-G5 with and without KRT (OR = 0.49 CI). Conclusion: One-third of CKD-G5 cases receive CKM. Those are typically older, female, rural residents with lower incomes and with lesser proteinuria or cardiovascular RF. The likelihood of receiving KRT is influenced by location and socioeconomic disparities. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care)
11 pages, 1458 KiB  
Article
MCP1 Could Mediate FGF23 and Omega 6/Omega 3 Correlation Inversion in CKD
by Deborah Mattinzoli, Stefano Turolo, Carlo Maria Alfieri, Masami Ikehata, Lara Caldiroli, Silvia Armelloni, Giovanni Montini, Carlo Agostoni, Piergiorgio Messa, Simone Vettoretti and Giuseppe Castellano
J. Clin. Med. 2022, 11(23), 7099; https://doi.org/10.3390/jcm11237099 - 30 Nov 2022
Cited by 4 | Viewed by 2082
Abstract
Fibroblast growth factor 23 (FGF23) concentrations rise after the early stages of chronic kidney disease (CKD). FGF23 is involved in inflammatory reactions closely associated with an incremented risk of cardiovascular disease (CVD). There is growing evidence that omega-6 (n-6) and n-3 polyunsaturated fatty [...] Read more.
Fibroblast growth factor 23 (FGF23) concentrations rise after the early stages of chronic kidney disease (CKD). FGF23 is involved in inflammatory reactions closely associated with an incremented risk of cardiovascular disease (CVD). There is growing evidence that omega-6 (n-6) and n-3 polyunsaturated fatty acids (PUFA) can modulate inflammation through several mediators producing an opposite effect on cardiovascular (CV) risks. In this study, we explore whether there is any correlation between PUFA, FGF23, and inflammation in CKD patients. We evaluated, cross-sectionally, 56 patients at different stages of CKD. Monocyte chemoattractant protein 1 (MCP1), and intact and c-terminal FGF23 (iFGF23, cFGF23) were quantified by the ELISA, and the fatty acids (FA) profile was analyzed by gas chromatography. Concurrently with an eGFR decrease (p < 0.01) and an MCP1 increase (p = 0.031), we observed an inversion of the correlation between FGF23 and the n-6/n-3 ratio. This last correlation was inversed in CKD stage 3 (r2 (−) 0.502 p = 0.029) and direct in stage 5 (r2 0.657 p = 0.020). The increase in MCP1 seems to trigger events in the inversion of the correlation between FGF23 and the n-6/n-3 PUFA ratio. This result strongly encourages future studies on basal pathways, on possible pharmacological interventions, and on managing kidney transplant patients treated with immunosuppressive therapy. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care)
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12 pages, 283 KiB  
Article
Comorbid Depression and Diabetes Are Associated with Impaired Health-Related Quality of Life in Chronic Kidney Disease Patients
by Janine Wirkner, Matthias Scheuch, Thomas Dabers, Sabrina Freiin von Rheinbaben, Beate Fiene, Simone Aymanns, Karlhans Endlich, Nicole Endlich, Uwe Lendeckel, Rainer Rettig, Hans Jörgen Grabe and Sylvia Stracke
J. Clin. Med. 2022, 11(16), 4671; https://doi.org/10.3390/jcm11164671 - 10 Aug 2022
Cited by 5 | Viewed by 2121
Abstract
Given the increasing prevalence of chronic kidney disease (CKD) and its impact on health care, it is important to better understand the multiple factors influencing health-related quality of life (HRQOL), particularly since they have been shown to affect CKD outcomes. Determinants of HRQOL [...] Read more.
Given the increasing prevalence of chronic kidney disease (CKD) and its impact on health care, it is important to better understand the multiple factors influencing health-related quality of life (HRQOL), particularly since they have been shown to affect CKD outcomes. Determinants of HRQOL as measured by the validated Kidney Disease Quality of Life questionnaire (KDQOL) and the Patient Health Questionnaire depression screener (PHQ-9) were assessed in a routine CKD patient sample, the Greifswald Approach to Individualized Medicine (GANI_MED) renal cohort (N = 160), including a wide range of self-reported data, sociodemographic and laboratory measures. Compared to the general population, CKD patients had lower HRQOL indices. Dialysis was associated with (1) low levels of physical functioning, (2) increased impairments by symptoms and problems, and (3) more effects and burden of kidney disease. HRQOL is seriously affected in CKD patients. However, impairments were found irrespective of eGFR decline and albuminuria. Rather, the comorbid conditions of depression and diabetes predicted a lower HRQOL (physical component score). Further studies should address whether recognizing and treating depression may not only improve HRQOL but also promote survival and lower hospitalization rates of CKD patients. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care)

Review

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27 pages, 10531 KiB  
Review
The Role of Plant-Based Diets in Preventing and Mitigating Chronic Kidney Disease: More Light than Shadows
by Diana Zarantonello and Giuliano Brunori
J. Clin. Med. 2023, 12(19), 6137; https://doi.org/10.3390/jcm12196137 - 22 Sep 2023
Cited by 4 | Viewed by 3198
Abstract
Chronic kidney disease (CKD) is a non-communicable disease that affects >10% of the general population worldwide; the number of patients affected by CKD is increasing due in part to the rise in risk factors such as obesity, hypertension, and diabetes mellitus. As many [...] Read more.
Chronic kidney disease (CKD) is a non-communicable disease that affects >10% of the general population worldwide; the number of patients affected by CKD is increasing due in part to the rise in risk factors such as obesity, hypertension, and diabetes mellitus. As many studies show, diet can be an important tool for preventing and mitigating the onset of non-communicable diseases. Plant-based diets (PBDs) are those that emphasize the consumption of plant foods and may or may not include small or moderate amounts of animal foods. Recently, these diets have received increasing interest because they have been associated with favourable effects on health and also appear to protect against the development and progression of CKD. PBDs, which are associated with protein restrictions, seem to offer adjunctive advantages in patients with chronic kidney disease, as compared to conventional low-protein diets that include animal proteins. The principal aims of this review are to provide a comprehensive overview of the existing literature regarding the role of plant-based diets and low-protein, plant-based diets in the context of chronic kidney disease. Moreover, we try to clarify the definition of plant-based diets, and then we analyse possible concerns about the use of PBDs in patients with chronic kidney disease (nutritional deficiency and hyperkalaemia risk). Finally, we offer some strategies to increase the nutritional value of plant-based low-protein diets. In the Materials and Methods section, many studies about plant-based diets and low-protein plant-based diets (e.g., the very-low-protein diet and vegan low-protein diet, LPD) in chronic kidney disease were considered. In the Results and Conclusion section, current data, most from observational studies, agree upon the protective effect of plant-based diets on kidney function. Moreover, in patients with advanced CKD, low-protein plant-based options, especially a very-low-protein diet supplemented with heteroanalogues (VLPDs), compared to a conventional LPD appear to offer adjunctive advances in terms of delaying dialysis and mitigating metabolic disturbances. However, further studies are necessary to better investigate the possible metabolic and cardiovascular advantages of plant-based LPDs versus conventional LPDs. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care)
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15 pages, 785 KiB  
Review
Main Barriers to the Introduction of a Home Haemodialysis Programme in Poland: A Review of the Challenges for Implementation and Criteria for a Successful Programme
by Dana Kendzia, Federica Lima, Jacek Zawierucha, Ellen Busink, Christian Apel, Jacek Stanislaw Malyszko, Pawel Zebrowski and Jolanta Malyszko
J. Clin. Med. 2022, 11(14), 4166; https://doi.org/10.3390/jcm11144166 - 18 Jul 2022
Viewed by 2239
Abstract
Introduction: Home dialysis in Poland is restricted to the peritoneal dialysis (PD) modality, with the majority of dialysis patients treated using in-centre haemodialysis (ICHD). Home haemodialysis (HHD) is an additional home therapy to PD and provides an attractive alternative to ICHD that combines [...] Read more.
Introduction: Home dialysis in Poland is restricted to the peritoneal dialysis (PD) modality, with the majority of dialysis patients treated using in-centre haemodialysis (ICHD). Home haemodialysis (HHD) is an additional home therapy to PD and provides an attractive alternative to ICHD that combines dialysis with social distancing; eliminates transportation needs; and offers clinical, economic, and quality of life benefits. However, HHD is not currently provided in Poland. This review was performed to provide an overview of the main barriers to the introduction of a HHD programme in Poland. Main findings: The main high-level barrier to introducing HHD in Poland is the absence of specific health legislation required for clinician prescribing of HHD. Other barriers to overcome include clear definition of reimbursement, patient training and education (including infrastructure and experienced personnel), organisation of logistics, and management of complications. Partnering with a large care network for HHD represents an alternative option to payers for the provision of a new HHD service. This may reduce some of the barriers which need to be overcome when compared with the creation of a new HHD service and its supporting network due to the pre-existing infrastructure, processes, and staff of a large care network. Conclusions: Provision of HHD is not solely about the provision of home treatment, but also the organisation and definition of a range of support services that are required to deliver the service. HHD should be viewed as an additional, complementary option to existing dialysis modalities which enables choice of modality best suited to a patient’s needs. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care)
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Other

16 pages, 526 KiB  
Systematic Review
Medication Review with Follow-Up for End-Stage Renal Disease: Drug-Related Problems and Negative Outcomes Associated with Medication—A Systematic Review
by Alfonso Pereira-Céspedes, Alberto Jiménez-Morales, Magdalena Palomares-Bayo, Fernando Martínez-Martínez and Miguel Ángel Calleja-Hernández
J. Clin. Med. 2023, 12(15), 5080; https://doi.org/10.3390/jcm12155080 - 2 Aug 2023
Cited by 1 | Viewed by 1639
Abstract
Background: This article reviews the available scientific literature on drug-related problems and negative outcomes associated with medications identified by medication review with follow-up for end-stage renal disease and discussed with the physicians. Methods: A systematic review was conducted of the scientific literature retrieved [...] Read more.
Background: This article reviews the available scientific literature on drug-related problems and negative outcomes associated with medications identified by medication review with follow-up for end-stage renal disease and discussed with the physicians. Methods: A systematic review was conducted of the scientific literature retrieved from the following databases: MEDLINE (via PubMed), Web of Science, SCOPUS, Cochrane Library: The Cochrane Central Register and Control Trials (CENTRAL) and Literatura Latinoamericana y del Caribe (LILACS), Medicina en Español (MEDES), and the SciELO bibliographic database (a collection of scientific journals). The following terms were used as descriptors and searched in free text: “end-stage renal disease”, “medication review”, “drug-related problems”, and “negative outcomes associated with medication”. The following limits were applied: “humans” and “adults (more than 18 years)”. Results: A total of 59 references were recovered and, after applying inclusion/exclusion criteria, 16 articles were selected. Of these selected articles, 15 provided information on drug-related problems and only 1 on negative outcomes associated with medications. Conclusions: It can be concluded that drug-related problems and negative outcomes associated with medications affect patients with end-stage renal disease, mainly those receiving renal replacement therapy. More evidence is needed, especially on negative outcomes associated with medication. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care)
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27 pages, 2594 KiB  
Systematic Review
Prevalence and Severity of Lower Gastrointestinal Symptoms amongst Non-Dialysis Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis
by Jakub Ruszkowski, Katarzyna Majkutewicz, Zbigniew Heleniak, Jacek M. Witkowski and Alicja Dębska-Ślizień
J. Clin. Med. 2022, 11(21), 6363; https://doi.org/10.3390/jcm11216363 - 28 Oct 2022
Cited by 6 | Viewed by 3229
Abstract
Chronic kidney disease (CKD) patients experience a wide range of symptoms that deteriorate their health-related quality of life (HRQoL). We aimed to estimate the prevalence and severity of lower gastrointestinal (GI) symptoms in non-dialysis CKD adult outpatients, and to summarize the relationships between [...] Read more.
Chronic kidney disease (CKD) patients experience a wide range of symptoms that deteriorate their health-related quality of life (HRQoL). We aimed to estimate the prevalence and severity of lower gastrointestinal (GI) symptoms in non-dialysis CKD adult outpatients, and to summarize the relationships between these symptoms and HRQoL, laboratory test results, and clinical data. The protocol of the study was preregistered (PROSPERO CRD42021255122). We searched MEDLINE, Scopus, Web of Science, and grey literature sources from the databases’ inception up until 27 November 2021. Wide citation chasing was conducted. Single proportions (prevalence of functional constipation, self-reported constipation, diarrhea, abdominal bloating, fecal incontinence, and abdominal/rectal pain) were pooled using generalized linear mixed models. A total of 37 studies with 12,074 patients were included. We found that lower GI symptoms, especially self-reported abdominal bloating [CKD G1–2: 48.45% (95% CI: 43.5–53.4%; 2 studies); G3: 46.95% (95% CI: 45.0–48.9%; 2 studies), G4–5: 36.1% (95% CI: 25.4–48.5%; 8 studies)] and constipation [CKD G1–2: 31.8% (95% CI: 13.9–54.9%); G3: 29.8% (95% CI: 21.2–40.1%; 4 studies); G4–5: 38.8% (95% CI: 30.9–47.4%); 22 studies)], were common in non-dialysis CKD patients. The severity of the symptoms was limited. Self-reported constipation was most consistently associated with worse HRQoL, whereas hard stool consistency was associated with higher uremic toxins levels. To conclude, since lower GI symptoms are common in CKD, using symptom questionnaires that do not take them into account cannot provide full insight into the patient’s experience. Further studies are needed to cover identified knowledge gaps, including the exploration of the pathophysiology of GI symptoms in CKD with multi-omics data. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care)
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11 pages, 825 KiB  
Systematic Review
Randomized Controlled Trials on Renin Angiotensin Aldosterone System Inhibitors in Chronic Kidney Disease Stages 3–5: Are They Robust? A Fragility Index Analysis
by Ivana Capuano, Pasquale Buonanno, Eleonora Riccio, Antonio Bianco and Antonio Pisani
J. Clin. Med. 2022, 11(20), 6184; https://doi.org/10.3390/jcm11206184 - 20 Oct 2022
Cited by 2 | Viewed by 2333
Abstract
Inhibition of the renin-angiotensin-aldosterone system (RAAS) is broadly recommended in many nephrological guidelines to prevent chronic kidney disease (CKD) progression. This work aimed to analyze the robustness of randomized controlled trials (RCTs) investigating the renal and cardiovascular outcomes in CKD stages 3–5 patients [...] Read more.
Inhibition of the renin-angiotensin-aldosterone system (RAAS) is broadly recommended in many nephrological guidelines to prevent chronic kidney disease (CKD) progression. This work aimed to analyze the robustness of randomized controlled trials (RCTs) investigating the renal and cardiovascular outcomes in CKD stages 3–5 patients treated with RAAS inhibitors (RAASi). We searched for RCTs in MEDLINE (PubMed), EMBASE databases, and the Cochrane register. Fragility indexes (FIs) for every primary and secondary outcome were calculated according to Walsh et al., who first described this novel metric, suggesting 8 as the cut-off to consider a study robust. Spearman coefficient was calculated to correlate FI to p value and sample size of statistically significant primary and secondary outcomes. Twenty-two studies met the inclusion criteria, including 80,455 patients. Sample size considerably varied among the studies (median: 1693.5, range: 73–17,276). The median follow-up was 38 months (range 24–58). The overall median of both primary and secondary outcomes was 0 (range 0–117 and range 0–55, respectively). The median of FI for primary and secondary outcomes with a p value lower than 0.05 was 6 (range: 1–117) and 7.5 (range: 1–55), respectively. The medians of the FI for primary outcomes with a p value lower than 0.05 in CKD and no CKD patients were 5.5 (range 1–117) and 22 (range 1–80), respectively. Only a few RCTs have been shown to be robust. Our analysis underlined the need for further research with appropriate sample sizes and study design to explore the real potentialities of RAASi in the progression of CKD. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Triggering New Paradigms of Treatment and Care)
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