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A Changing Perspective for Treatment of Chronic Kidney Disease

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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 (31 March 2021) | Viewed by 50680

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Prof. Dr. Giacomo Garibotto

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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
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Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) has become an enormous worldwide health problem, both in developed and less developed countries. The incidence and prevalence of CKD is high, and is associated with increased mortality and morbidity. Of note, CKD is the 12th most common primary cause of death, accounting for about 1 million deaths per year worldwide. CKD and end-stage renal disease are characterized by the progressive development of a series of complications, such as anemia, hyperkalemia, hypervolemia, mineral and bone disorders (CKD-MBD), metabolic acidosis, hyperuricemia and wasting; all of these complications have been shown to be associated with adverse outcomes, and can contribute either individually or in association to the cardiovascular morbidity and mortality observed in CKD. While at this time CKD progression is not treated with high efficacy, new biomarkers of kidney fibrosis have become available in recent years and new treatments for kidney fibrosis and cell loss could become soon available. 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 which are now are amenable to therapeutic interventions. All these important issues are addressed in this volume.

Issues:

New options for anemia in CKD

New options for treatment of hyperkalemia

New targets for treatment of metabolic acidosis

Can we target oxidative stress in CKD?

Native vitamin D: is so important?

A CKD-MBD perspective in 2020

A new paradigm: treating hyperuricemia

Kidney fibrosis: new biomarkers and treatments

How should we evaluate CKD progression?

Prevention of acute kidney injury in an aging population

Prevention of cardiovascular mortality in CKD: a 2020 perspective

Nutrition in CKD: a 2020 perspective

Prof. Giacomo Garibotto
Guest Editor

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Keywords

chronic kidney disease
eGFR
kidney fibrosis
anemia
acidosis
hyperkalemia
cardiovascular disease
AKI
aging

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

5 pages, 209 KiB

Open AccessEditorial

A Changing Perspective for Treatment of Chronic Kidney Disease

by Giacomo Garibotto

J. Clin. Med. 2021, 10(17), 3840; https://doi.org/10.3390/jcm10173840 - 27 Aug 2021

Cited by 5 | Viewed by 2062

Abstract

Chronic kidney disease (CKD) is now an enormous worldwide health problem [...] Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

Research

Jump to: Editorial, Review

9 pages, 817 KiB

Open AccessArticle

Association between MANBA Gene Variants and Chronic Kidney Disease in a Korean Population

by Hye-Rim Kim, Hyun-Seok Jin and Yong-Bin Eom

J. Clin. Med. 2021, 10(11), 2255; https://doi.org/10.3390/jcm10112255 - 23 May 2021

Cited by 4 | Viewed by 2242

Abstract

Chronic kidney disease (CKD), a damaged condition of the kidneys, is a global public health problem that can be caused by diabetes, hypertension, and other disorders. Recently, the MANBA gene was identified in CKD by integrating CKD-related variants and kidney expression quantitative trait loci (eQTL) data. This study evaluated the effects of MANBA gene variants on CKD and kidney function-related traits using a Korean cohort. We also analyzed the association of MANBA gene variants with kidney-related traits such as the estimated glomerular filtration rate (eGFR), and blood urea nitrogen (BUN), creatinine, and uric acid levels using linear regression analysis. As a result, 14 single nucleotide polymorphisms (SNPs) were replicated in CKD (p < 0.05), consistent with previous studies. Among them, rs4496586, which was the most significant for CKD and kidney function-related traits, was associated with a decreased CKD risk in participants with the homozygous minor allele (CC), increased eGFR, and decreased creatinine and uric acid concentrations. Furthermore, the association analysis between the rs4496586 genotype and MANBA gene expression in human tubules and glomeruli showed high MANBA gene expression in the minor allele carriers. In conclusion, this study demonstrated that MANBA gene variants were associated with CKD and kidney function-related traits in a Korean cohort. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

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10 pages, 713 KiB

Open AccessArticle

Association between Multidimensional Prognostic Index and Hospitalization and Mortality among Older Adults with Chronic Kidney Disease on Conservative or on Replacement Therapy

by Silvia Lai, Maria Ida Amabile, Sandro Mazzaferro, Giovanni Imbimbo, Anna Paola Mitterhofer, Alessandro Galani, Filippo Aucella, Giuliano Brunori, Paolo Menè, Alessio Molfino and The Study Group on Geriatric Nephrology of the Italian Society of Nephrology (SIN)

J. Clin. Med. 2020, 9(12), 3965; https://doi.org/10.3390/jcm9123965 - 7 Dec 2020

Cited by 8 | Viewed by 2044

Abstract

The prevalence of renal disease is constantly increasing in older adults and a prognostic evaluation by a valid tool may play a key role in treatment management. We aimed to assess the association(s) between the multidimensional prognostic index (MPI) and both the hospitalization and mortality among older adults with renal disease. Patients with chronic kidney disease (CKD) (stage 3–5 KDOQI) and on dialysis were considered. Clinical parameters were registered at baseline and after 2 years. In all the patients, the MPI was calculated and divided into grade 0 (low risk), 1 (moderate risk), and 2 (severe risk). Hospitalizations and mortality were recorded during the follow-up and analyzed according to MPI grade. A total of 173 patients, with a median age of 76 years, on conservative (n = 105) and replacement therapy (32 patients on hemodialysis, 36 patients on peritoneal dialysis) were enrolled. Of them, 60 patients were in MPI grade 0, 102 in grade 1, and 11 in grade 2. The median duration of all the hospitalizations was 6 days and the number of deaths was 33. MPI significantly correlated with days of hospitalization (r = 0.801, p < 0.00001) and number of hospitalizations per year (r = 0.808, p < 0.00001), which was higher in MPI grade 2 compared to grade 1 (p < 0.001) and to grade 0 (p < 0.001). We found a significant association between MPI grades and mortality (p < 0.001). Our results indicate that MPI was associated with outcomes in patients with renal disease, suggesting that a multidimensional evaluation should be implemented in this clinical setting. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

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11 pages, 2004 KiB

Open AccessArticle

Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKD

by Nima Abbasian, Alison H. Goodall, James O. Burton, Debbie Bursnall, Alan Bevington and Nigel J. Brunskill

J. Clin. Med. 2020, 9(11), 3534; https://doi.org/10.3390/jcm9113534 - 1 Nov 2020

Cited by 10 | Viewed by 2724

Abstract

Hyperphosphatemia has been proposed as a cardiovascular risk factor, contributing to long-term vascular calcification in hyperphosphatemic Chronic Kidney Disease (CKD) patients. However, more recent studies have also demonstrated acute effects of inorganic phosphate (Pi) on endothelial cells in vitro, especially generation of pro-coagulant endothelial microvesicles (MV). Hitherto, such direct effects of hyperphosphatemia have not been reported in vivo. Thirty-six male Sprague-Dawley rats were randomly allocated to three experimental groups: (1) CKD induced by partial nephrectomy receiving high (1.2%) dietary phosphorus; (2) CKD receiving low (0.2%) dietary phosphorus; and (3) sham-operated controls receiving 1.2% phosphorus. After 14 days the animals were sacrificed and plasma MVs counted by nanoparticle tracking analysis. MVs isolated by centrifugation were assayed for pro-coagulant activity by calibrated automated thrombography, and relative content of endothelium-derived MVs was assessed by anti-CD144 immunoblotting. When compared with sham controls, high phosphorus CKD rats were shown to be hyperphosphatemic (4.11 ± 0.23 versus 2.41 ± 0.22 mM Pi, p < 0.0001) with elevated total plasma MVs (2.24 ± 0.37 versus 1.31 ± 0.24 × 10⁸ per ml, p < 0.01), showing increased CD144 expression (145 ± 25% of control value, p < 0.0001), and enhanced procoagulant activity (18.06 ± 1.75 versus 4.99 ± 1.77 nM peak thrombin, p < 0.0001). These effects were abolished in the low phosphorus CKD group. In this rat model, hyperphosphatemia (or a Pi-dependent hormonal response derived from it) is sufficient to induce a marked increase in circulating pro-coagulant MVs, demonstrating an important link between hyperphosphatemia and thrombotic risk in CKD. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

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10 pages, 621 KiB

Open AccessArticle

Relationship among Left Ventricular Hypertrophy, Cardiovascular Events, and Preferred Blood Pressure Measurement Timing in Hemodialysis Patients

by Hiroaki Io, Junichiro Nakata, Hiroyuki Inoshita, Masanori Ishizaka, Yasuhiko Tomino and Yusuke Suzuki

J. Clin. Med. 2020, 9(11), 3512; https://doi.org/10.3390/jcm9113512 - 30 Oct 2020

Cited by 8 | Viewed by 1924

Abstract

This study aimed to identify the ideal timing and setting for measuring blood pressure (BP) and determine whether the left ventricular mass index (LVMI) is an independent risk factor associated with increased cardiovascular events in hemodialysis (HD) patients. BP and LVMI were measured at baseline and at 6 and 12 months after HD initiation. BP was monitored and recorded at nine different time points, including before and after HD over a one-week period (HDBP). The mean BP measurement was calculated as the weekly averaged BP (WABP). LVMI was significantly correlated with home BP, in-office BP, HDBP, and WABP. Receiver operating characteristic analysis indicated that the cutoff LVMI value for cardiovascular events was 156 g/m². LVMI and diabetes mellitus were significant influencing factors for cardiovascular events (hazards ratio (95% confidence interval): diabetes mellitus, 2.84 (1.17,7.45); LVMI > 156 g/m², 2.86 (1.22,6.99)). Pre-HDBP, post-HDBP, and WABP were independently associated with higher LVMI in the follow-up periods. Hemoglobin and human atrial natriuretic peptide (hANP) levels were associated with LVMI beyond 12 months after HD initiation. Treatment of hypertension, overhydration based on hANP, and anemia may reduce the progression of LVMI and help identify HD patients at high risk for cardiovascular events. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

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11 pages, 238 KiB

Open AccessArticle

by Ilse J. M. Hagedoorn, Christina M. Gant, Sanne v. Huizen, Ronald G. H. J. Maatman, Gerjan Navis, Stephan J. L. Bakker and Gozewijn D. Laverman

J. Clin. Med. 2020, 9(8), 2432; https://doi.org/10.3390/jcm9082432 - 30 Jul 2020

Cited by 27 | Viewed by 2629

Abstract

Background: Environmental factors contributing to diabetic kidney disease are incompletely understood. We investigated whether blood cadmium and lead concentrations were associated with the prevalence of diabetic kidney disease, and to what extent lifestyle-related exposures (diet and smoking) contribute to blood cadmium and lead concentrations. Material and methods: In a cross-sectional analysis in 231 patients with type 2 diabetes included in the DIAbetes and LifEstyle Cohort Twente (DIALECT-1), blood cadmium and lead concentrations were determined using inductively coupled plasma mass spectrometry. The associations between diet (derived from food frequency questionnaire), smoking and cadmium and lead were determined using multivariate linear regression. The associations between cadmium and lead and diabetic kidney disease (albumin excretion >30 mg/24 h and/or creatinine clearance <60 mL/min/1.73 m²) were determined using multivariate logistic regression. Results: Median blood concentrations were 2.94 nmol/L (interquartile range (IQR): 1.78–4.98 nmol/L) for cadmium and 0.07 µmol/L (IQR: 0.04–0.09 µmol/L) for lead, i.e., below acute toxicity values. Every doubling of lead concentration was associated with a 1.75 (95% confidence interval (CI): 1.11–2.74) times higher risk for albuminuria. In addition, both cadmium (odds ratio (OR) 1.50 95% CI: 1.02–2.21) and lead (OR 1.83 95% CI: 1.07–3.15) were associated with an increased risk for reduced creatinine clearance. Both passive smoking and active smoking were positively associated with cadmium concentration. Alcohol intake was positively associated with lead concentration. No positive associations were found between dietary intake and cadmium or lead. Conclusions: The association between cadmium and lead and the prevalence of diabetic kidney disease suggests cadmium and lead might contribute to the development of diabetic kidney disease. Exposure to cadmium and lead could be a so far underappreciated nephrotoxic mechanism of smoking and alcohol consumption. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

14 pages, 2254 KiB

Open AccessArticle

Robust Association between Acute Kidney Injury after Radical Nephrectomy and Long-term Renal Function

by Won Ho Kim, Kyung Won Shin, Sang-Hwan Ji, Young-Eun Jang, Ji-Hyun Lee, Chang Wook Jeong, Cheol Kwak and Young-Jin Lim

J. Clin. Med. 2020, 9(3), 619; https://doi.org/10.3390/jcm9030619 - 25 Feb 2020

Cited by 11 | Viewed by 3028

Abstract

The association between acute kidney injury (AKI) and long-term renal function after radical nephrectomy has not been evaluated fully. We reviewed 558 cases of radical nephrectomy. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria. Values of estimated glomerular filtration rate (eGFR) were collected up to 36 months (median 35 months) after surgery. The primary outcome was new-onset chronic kidney disease (CKD) stage 3a or higher or all-cause mortality within three years after nephrectomy. The functional change ratio (FCR) of eGFR was defined as the ratio of the most recent GFR (24–36 months after surgery) to the new baseline during 3–12 months. A multivariable Cox proportional hazard regression analysis for new-onset CKD and a multivariable linear regression analysis for FCR were performed to evaluate the association between AKI and long-term renal outcomes. A correlation analysis was performed with the serum creatinine ratio and used to determine AKI and FCR. AKI occurred in 43.2% (n = 241/558) and our primary outcome developed in 40.5% (n = 226/558) of patients. The incidence of new-onset CKD was significantly higher in patients with AKI than those without at all follow-up time points after surgery. The Cox regression analysis showed a graded association between AKI and our primary outcome (AKI stage 1: Hazard ratio 1.71, 95% confidence interval 1.25–2.32; AKI stage 2 or 3: Hazard ratio 2.72, 95% confidence interval 1.78–4.10). The linear regression analysis for FCR showed that AKI was significantly associated with FCR (β = −0.168 ± 0.322, p = 0.011). There was a significant negative correlation between the serum creatinine ratio and FCR. In conclusion, our analysis demonstrated a robust and graded association between AKI after radical nephrectomy and long-term renal functional deterioration. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

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12 pages, 1528 KiB

Open AccessArticle

Clustering Heatmap for Visualizing and Exploring Complex and High-dimensional Data Related to Chronic Kidney Disease

by Cheng-Sheng Yu, Chang-Hsien Lin, Yu-Jiun Lin, Shiyng-Yu Lin, Sen-Te Wang, Jenny L Wu, Ming-Hui Tsai and Shy-Shin Chang

J. Clin. Med. 2020, 9(2), 403; https://doi.org/10.3390/jcm9020403 - 2 Feb 2020

Cited by 20 | Viewed by 6838

Abstract

Background: Preventive medicine and primary health care are essential for patients with chronic kidney disease (CKD) because the symptoms of CKD may not appear until the renal function is severely compromised. Early identification of the risk factors of CKD is critical for preventing kidney damage and adverse outcomes. Early recognition of rapid progression to advanced CKD in certain high-risk populations is vital. Methods: This is a retrospective cohort study, the population screened and the site where the study has been performed. Multivariate statistical analysis was used to assess the prediction of CKD as many potential risk factors are involved. The clustering heatmap and random forest provides an interactive visualization for the classification of patients with different CKD stages. Results: uric acid, blood urea nitrogen, waist circumference, serum glutamic oxaloacetic transaminase, and hemoglobin A1c (HbA1c) were significantly associated with CKD. CKD was highly associated with obesity, hyperglycemia, and liver function. Hypertension and HbA1c were in the same cluster with a similar pattern, whereas high-density lipoprotein cholesterol had an opposite pattern, which was also verified using heatmap. Early staged CKD patients who are grouped into the same cluster as advanced staged CKD patients could be at high risk for rapid decline of kidney function and should be closely monitored. Conclusions: The clustering heatmap provided a new predictive model of health care management for patients at high risk of rapid CKD progression. This model could help physicians make an accurate diagnosis of this progressive and complex disease. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

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Review

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8 pages, 1705 KiB

Open AccessReview

Treating Hyperuricemia: The Last Word Hasn’t Been Said Yet

by Elisa Russo, Daniela Verzola, Giovanna Leoncini, Francesca Cappadona, Pasquale Esposito, Roberto Pontremoli and Francesca Viazzi

J. Clin. Med. 2021, 10(4), 819; https://doi.org/10.3390/jcm10040819 - 17 Feb 2021

Cited by 13 | Viewed by 3235

Abstract

Gout as well as asymptomatic hyperuricemia have been associated with several traditional cardiovascular risk factors and chronic kidney disease. Both in vitro studies and animal models support a role for uric acid mediating both hemodynamic and tissue toxicity leading to glomerular and tubule-interstitial damage, respectively. Nevertheless, two recent well designed and carried out trials failed to show the benefit of allopurinol treatment on kidney outcomes, casting doubts on expectations of renal protection by the use of urate lowering treatment. With the aim of providing possible explanations for the lack of effect of urate lowering treatment on chronic kidney disease progression, we will critically review results from all available randomized controlled trials comparing a urate-lowering agent with placebo or no study medication for at least 12 months and report renal clinical outcomes. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

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17 pages, 317 KiB

Open AccessReview

New Treatment Options for Hyperkalemia in Patients with Chronic Kidney Disease

by Pasquale Esposito, Novella Evelina Conti, Valeria Falqui, Leda Cipriani, Daniela Picciotto, Francesca Costigliolo, Giacomo Garibotto, Michela Saio and Francesca Viazzi

J. Clin. Med. 2020, 9(8), 2337; https://doi.org/10.3390/jcm9082337 - 22 Jul 2020

Cited by 17 | Viewed by 6406

Abstract

Hyperkalemia may cause life-threatening cardiac and neuromuscular alterations, and it is associated with high mortality rates. Its treatment includes a multifaceted approach, guided by potassium levels and clinical presentation. In general, treatment of hyperkalemia may be directed towards stabilizing cell membrane potential, promoting transcellular potassium shift and lowering total K⁺ body content. The latter can be obtained by dialysis, or by increasing potassium elimination by urine or the gastrointestinal tract. Until recently, the only therapeutic option for increasing fecal K⁺ excretion was represented by the cation-exchanging resin sodium polystyrene sulfonate. However, despite its common use, the efficacy of this drug has been poorly studied in controlled studies, and concerns about its safety have been reported. Interestingly, new drugs, namely patiromer and sodium zirconium cyclosilicate, have been developed to treat hyperkalemia by increasing gastrointestinal potassium elimination. These medications have proved their efficacy and safety in large clinical trials, involving subjects at high risk of hyperkalemia, such as patients with heart failure and chronic kidney disease. In this review, we discuss the mechanisms of action and the updated data of patiromer and sodium zirconium cyclosilicate, considering that the availability of these new treatment options offers the possibility of improving the management of both acute and chronic hyperkalemia. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

16 pages, 1460 KiB

Open AccessReview

Calciprotein Particles and Serum Calcification Propensity: Hallmarks of Vascular Calcifications in Patients with Chronic Kidney Disease

by Ciprian N. Silaghi, Tamás Ilyés, Adriana J. Van Ballegooijen and Alexandra M. Crăciun

J. Clin. Med. 2020, 9(5), 1287; https://doi.org/10.3390/jcm9051287 - 29 Apr 2020

Cited by 25 | Viewed by 4265

Abstract

Cardiovascular complications are one of the leading causes of mortality worldwide and are strongly associated with atherosclerosis and vascular calcification (VC). Patients with chronic kidney disease (CKD) have a higher prevalence of VC as renal function declines, which will result in increased mortality. Serum calciprotein particles (CPPs) are colloidal nanoparticles that have a prominent role in the initiation and progression of VC. The T₅₀ test is a novel test that measures the conversion of primary to secondary calciprotein particles indicating the tendency of serum to calcify. Therefore, we accomplished a comprehensive review as the first integrated approach to clarify fundamental aspects that influence serum CPP levels and T₅₀, and to explore the effects of CPP and calcification propensity on various chronic disease outcomes. In addition, new topics were raised regarding possible clinical uses of T₅₀ in the assessment of VC, particularly in patients with CKD, including possible opportunities in VC management. The relationships between serum calcification propensity and cardiovascular and all-cause mortality were also addressed. The review is the outcome of a comprehensive search on available literature and could open new directions to control VC. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

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20 pages, 1269 KiB

Open AccessReview

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

by José Luis Górriz, María José Soler, Juan F. Navarro-González, Clara García-Carro, María Jesús Puchades, Luis D’Marco, Alberto Martínez Castelao, Beatriz Fernández-Fernández, Alberto Ortiz, Carmen Górriz-Zambrano, Jorge Navarro-Pérez and Juan José Gorgojo-Martinez

J. Clin. Med. 2020, 9(4), 947; https://doi.org/10.3390/jcm9040947 - 30 Mar 2020

Cited by 94 | Viewed by 12257

Abstract

Type 2 diabetes mellitus (T2DM) represents the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESKD), and diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes. Despite advances in the nephroprotective treatment of T2DM, DKD remains the most common complication, driving the need for renal replacement therapies (RRT) worldwide, and its incidence is increasing. Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin–angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of anti-hyperglycemic drugs shown to improve cardiovascular and renal events in DKD. In this regard, GLP-1RA offer the potential for adequate glycemic control in multiple stages of DKD without an increased risk of hypoglycemia, preventing the onset of macroalbuminuria and slowing the decline of glomerular filtration rate (GFR) in diabetic patients, also bringing additional benefit in weight reduction, cardiovascular and other kidney outcomes. Results from ongoing trials are pending to assess the impact of GLP-1RA treatments on primary kidney endpoints in DKD. Full article

(This article belongs to the Special Issue A Changing Perspective for Treatment of Chronic Kidney Disease)

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