Research Updates in Chronic Kidney Disease

A topical collection in Life (ISSN 2075-1729). This collection belongs to the section "Physiology and Pathology".

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Editors

Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), Università di Palermo, 129 - 90127 Palermo, Italy
Interests: cardiology; internal medicine; echocardiography; hypertension; cardiovascular risk; chronic kidney disease
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), Via del Vespro 129 - 90127 Palermo, Italy
Interests: hypertension; atherosclerosis; insulin resistance; echocardiography; diabetes; blood pressure; internal medicine; cardiovascular medicine; heart failure; myocardial infarction

Topical Collection Information

Dear Colleagues,

The global rise in the number of patients with chronic kidney disease (CKD) and consequent end-stage renal disease (ESRD) necessitating renal replacement therapy is threatening to reach epidemic proportions over the next decade, and only a small number of countries have robust economies able to meet the challenges posed. New epidemiologic evidence points to an even more alarming issue: the rising prevalence of mild-to-moderate renal dysfunction in the general population, especially among hypertensive, diabetic, and obese patients. This condition is about 100 times more common than ESRD, and even if it does not necessarily progress to ESRD, it contributes significantly to increasing cardiovascular risk.

In fact, while it is well known that cardiovascular complications represent the main cause of death in patients with ESRD, with a prevalence of 10 to 30 times higher for the age group between 25 and 75 years, it has been shown that the risk in developing these cardiovascular complications increases even in the presence of early renal abnormalities and tends to grow with the progress of kidney disease. This condition involves a large proportion of the population and therefore carries important social and financial implications that are likely to increase in the near future.

A change in the global approach to CKD, from the treatment of ESRD to much more aggressive primary and secondary prevention, is therefore imperative.

This Special Issue will therefore focus on several aspects of CKD, with a particular attention to the mechanisms of its development and progression, noninvasive tools that are useful in the detection of its early manifestations, and to multifactorial therapeutic strategies aimed at reducing CV and renal risk.

Dr. Emilio Nardi
Dr. Giuseppe Mule
Guest Editors

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Keywords

  • chronic kidney disease
  • dialysis
  • glomerular filtration rate
  • end-stage renal disease
  • proteinuria

Published Papers (16 papers)

2022

Jump to: 2021

18 pages, 969 KiB  
Review
Rethinking Chronic Kidney Disease in the Aging Population
by Gaetano Alfano, Rossella Perrone, Francesco Fontana, Giulia Ligabue, Silvia Giovanella, Annachiara Ferrari, Mariacristina Gregorini, Gianni Cappelli, Riccardo Magistroni and Gabriele Donati
Life 2022, 12(11), 1724; https://doi.org/10.3390/life12111724 - 28 Oct 2022
Cited by 8 | Viewed by 3583
Abstract
The process of aging population will inevitably increase age-related comorbidities including chronic kidney disease (CKD). In light of this demographic transition, the lack of an age-adjusted CKD classification may enormously increase the number of new diagnoses of CKD in old subjects with an [...] Read more.
The process of aging population will inevitably increase age-related comorbidities including chronic kidney disease (CKD). In light of this demographic transition, the lack of an age-adjusted CKD classification may enormously increase the number of new diagnoses of CKD in old subjects with an indolent decline in kidney function. Overdiagnosis of CKD will inevitably lead to important clinical consequences and pronounced negative effects on the health-related quality of life of these patients. Based on these data, an appropriate workup for the diagnosis of CKD is critical in reducing the burden of CKD worldwide. Optimal management of CKD should be based on prevention and reduction of risk factors associated with kidney injury. Once the diagnosis of CKD has been made, an appropriate staging of kidney disease and timely prescriptions of promising nephroprotective drugs (e.g., RAAS, SGLT-2 inhibitors, finerenone) appear crucial to slow down the progression toward end-stage kidney disease (ESKD). The management of elderly, comorbid and frail patients also opens new questions on the appropriate renal replacement therapy for this subset of the population. The non-dialytic management of CKD in old subjects with short life expectancy features as a valid option in patient-centered care programs. Considering the multiple implications of CKD for global public health, this review examines the prevalence, diagnosis and principles of treatment of kidney disease in the aging population. Full article
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2021

Jump to: 2022

17 pages, 1956 KiB  
Article
Cholemic Nephropathy as Cause of Acute and Chronic Kidney Disease. Update on an Under-Diagnosed Disease
by Francesca Tinti, Ilaria Umbro, Mariadomenica D’Alessandro, Silvia Lai, Manuela Merli, Annalisa Noce, Nicola Di Daniele, Sandro Mazzaferro and Anna Paola Mitterhofer
Life 2021, 11(11), 1200; https://doi.org/10.3390/life11111200 - 06 Nov 2021
Cited by 7 | Viewed by 2705
Abstract
Cholemic nephropathy (CN) is a recognized cause of acute kidney injury (AKI) in patients with severe hyperbilirubinemia (sHyb) and jaundice. Pathophysiological mechanisms of CN are not completely understood, but it seems caused both by direct toxicity of cholephiles and bile casts formation in [...] Read more.
Cholemic nephropathy (CN) is a recognized cause of acute kidney injury (AKI) in patients with severe hyperbilirubinemia (sHyb) and jaundice. Pathophysiological mechanisms of CN are not completely understood, but it seems caused both by direct toxicity of cholephiles and bile casts formation in nephrons enhanced by prolonged exposure to sHyb, particularly in the presence of promoting factors, as highlighted by a literature reviewed and by personal experience. The aim of our update is to retrace CN in its pathophysiology, risk factors, diagnosis and treatment, underlining the role of sHyb, promoting factors, and CN-AKI diagnostic criteria in the different clinical settings associated with this often-concealed disease. Our purpose is to focus on clinical manifestation of CN, exploring the possible transition to CKD. Cholemic nephropathy is an overlooked clinical entity that enters differential diagnosis with other causes of AKI. Early diagnosis and treatment are essential because renal injury could be fully reversible as rapidly as bilirubin levels are reduced. In conclusion, our proposal is to introduce an alert for considering CN in diagnostic and prognostic scores that include bilirubin and/or creatinine with acute renal involvement, with the aim of early diagnosis and treatment of sHyb to reduce the burden on renal outcome. Full article
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11 pages, 565 KiB  
Article
Metabolic Constellations, Clusters, and Renal Function: Findings from the 2013–2018 National Health and Nutrition Examination Surveys
by Kathleen E. Adair, Kelly R. Ylitalo, Jeffrey S. Forsse, LesLee K. Funderburk and Rodney G. Bowden
Life 2021, 11(9), 904; https://doi.org/10.3390/life11090904 - 30 Aug 2021
Cited by 2 | Viewed by 1690
Abstract
Metabolic syndrome (MetS) is associated with decreased renal function and chronic kidney disease (CKD). To date, no research regarding the sixteen possible constellations resulting in the diagnosis of MetS has been elucidated. The purpose of this study is to report renal function in [...] Read more.
Metabolic syndrome (MetS) is associated with decreased renal function and chronic kidney disease (CKD). To date, no research regarding the sixteen possible constellations resulting in the diagnosis of MetS has been elucidated. The purpose of this study is to report renal function in sixteen metabolic constellations grouped into four metabolic clusters. Individuals (n = 2767; representing 86,652,073 individuals) from the 2013–2018 National Health and Nutrition Examination Surveys who met the criteria for MetS were included. Sixteen possible constellations of three or more risk factors were analyzed for renal function. Four metabolic clusters representing MetS with hyperglycemia (Cluster I), MetS with hypertension (Cluster II), MetS with hyperglycemia and hypertension (Cluster III), or MetS with normoglycemia and normotension (Cluster IV) were assessed for renal function and CKD status. Cluster III had the highest odds of CKD (OR = 2.57, 95% CL = 1.79, 3.68). Clusters II and III had the lowest renal function and were not different from one another (87.82 and 87.28 mL/min/1.73 m2, p = 0.71). The constellation with the lowest renal function consisted of hypertension, high triglycerides, and a large waist circumference (82.86 mL/min/1.73 m2), whereas the constellation with the highest renal function consisted of hyperglycemia, low HDL, and a large waist circumference (107.46 mL/min/1.73 m2). The sixteen constellations of MetS do not have the same effects on renal function. More research is needed to understand the relationship between the various iterations of MetS and renal function. Full article
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14 pages, 574 KiB  
Article
Metabolic Health, Obesity, and Renal Function: 2013–2018 National Health and Nutrition Examination Surveys
by Kathleen E. Adair, Rodney G. Bowden, LesLee K. Funderburk, Jeffrey S. Forsse and Kelly R. Ylitalo
Life 2021, 11(9), 888; https://doi.org/10.3390/life11090888 - 28 Aug 2021
Cited by 8 | Viewed by 1896
Abstract
Rising rates of metabolic syndrome, obesity, and mortality from chronic kidney disease (CKD) have prompted further investigation into the association between metabolic phenotypes and CKD. Purpose: To report the frequency of strictly defined metabolic phenotypes, renal function within each phenotype, and individual risk [...] Read more.
Rising rates of metabolic syndrome, obesity, and mortality from chronic kidney disease (CKD) have prompted further investigation into the association between metabolic phenotypes and CKD. Purpose: To report the frequency of strictly defined metabolic phenotypes, renal function within each phenotype, and individual risk factors associated with reduced renal function. We utilized the 2013–2018 National Health and Nutrition Examination Surveys (NHANES) and complex survey sample weighting techniques to represent 220 million non-institutionalized U.S. civilians. Metabolic health was defined as having zero of the risk factors defined by the National Cholesterol Education Program with the exception of obesity, which was defined as BMI ≥ 30 kg/m2 in non-Asians and BMI ≥ 25 kg/m2 in Asians. The metabolically healthy normal (MUN) phenotype comprised the highest proportion of the population (38.40%), whereas the metabolically healthy obese (MHO) was the smallest (5.59%). Compared to the MHN reference group, renal function was lowest in the strictly defined MUN (B = −9.60, p < 0.001) and highest in the MHO (B = 2.50, p > 0.05), and this persisted when an increased number of risk factors were used to define metabolic syndrome. Systolic blood pressure had the strongest correlation with overall eGFR (r = −0.25, p < 0.001), and individuals with low HDL had higher renal function compared to the overall sample. The MUN phenotype had the greatest association with poor renal function. While the MHO had higher renal function, this may be due to a transient state caused by renal hyperfiltration. Further research should be done to investigate the association between dyslipidemia and CKD. Full article
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16 pages, 1458 KiB  
Review
Chronic Kidney Disease as a Systemic Inflammatory Syndrome: Update on Mechanisms Involved and Potential Treatment
by Francesca Tinti, Silvia Lai, Annalisa Noce, Silverio Rotondi, Giulia Marrone, Sandro Mazzaferro, Nicola Di Daniele and Anna Paola Mitterhofer
Life 2021, 11(5), 419; https://doi.org/10.3390/life11050419 - 05 May 2021
Cited by 45 | Viewed by 4959
Abstract
Chronic kidney disease (CKD) is characterized by manifestations and symptoms involving systemic organs and apparatus, associated with elevated cardiovascular morbidity and mortality, bone disease, and other tissue involvement. Arterial hypertension (AH), diabetes mellitus (DM), and dyslipidemia, with glomerular or congenital diseases, are the [...] Read more.
Chronic kidney disease (CKD) is characterized by manifestations and symptoms involving systemic organs and apparatus, associated with elevated cardiovascular morbidity and mortality, bone disease, and other tissue involvement. Arterial hypertension (AH), diabetes mellitus (DM), and dyslipidemia, with glomerular or congenital diseases, are the traditional risk factors recognized as the main causes of progressive kidney dysfunction evolving into uremia. Acute kidney injury (AKI) has recently been considered an additional risk factor for the worsening of CKD or the development of CKD de novo. Evidence underlies the role of systemic inflammation as a linking factor between AKI and CKD, recognizing the role of inflammation in AKI evolution to CKD. Moreover, abnormal increases in oxidative stress (OS) and inflammatory status in CKD seem to exert an important pathogenetic role, with significant involvement in the clinical management of this condition. With our revision, we want to focus on and update the inflammatory mechanisms responsible for the pathologic conditions associated with CKD, with particular attention on the development of AKI and AKI-CKD de novo, the alteration of calcium-phosphorus metabolism with bone disease and CKD-MBD syndrome, the status of malnutrition and malnutrition–inflammation complex syndrome (MICS) and protein-energy wasting (PEW), uremic sarcopenia, the status of OS, and the different inflammatory pathways, highlighting a new approach to CKD. The depth comprehension of the mechanisms underlying the development of inflammation in CKD may present new possible therapeutic approaches in CKD and hopefully improve the management of correlated morbidities and provide a reduction in associated mortality. Full article
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21 pages, 1586 KiB  
Review
Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside
by Sungjin Chung and Gheun-Ho Kim
Life 2021, 11(5), 389; https://doi.org/10.3390/life11050389 - 25 Apr 2021
Cited by 7 | Viewed by 4319
Abstract
New drugs were recently developed to treat hyperglycemia in patients with type 2 diabetes mellitus (T2D). However, metformin remains the first-line anti-diabetic agent because of its cost-effectiveness. It has pleiotropic action that produces cardiovascular benefits, and it can be useful in diabetic nephropathy, [...] Read more.
New drugs were recently developed to treat hyperglycemia in patients with type 2 diabetes mellitus (T2D). However, metformin remains the first-line anti-diabetic agent because of its cost-effectiveness. It has pleiotropic action that produces cardiovascular benefits, and it can be useful in diabetic nephropathy, although metformin-associated lactic acidosis is a hindrance to its use in patients with kidney failure. New anti-diabetic agents, including glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors, also produce cardiovascular or renal benefits in T2D patients. Their glucose-independent beneficial actions can lead to cardiorenal protection via hemodynamic stabilization and inflammatory modulation. Systemic hypertension is relieved by natriuresis and improved vascular dysfunction. Enhanced tubuloglomerular feedback can be restored by SGLT-2 inhibition, reducing glomerular hypertension. Patients with non-diabetic kidney disease might also benefit from those drugs because hypertension, proteinuria, oxidative stress, and inflammation are common factors in the progression of kidney disease, irrespective of the presence of diabetes. In various animal models of non-diabetic kidney disease, metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors were favorable to kidney morphology and function. They strikingly attenuated biomarkers of oxidative stress and inflammatory responses in diseased kidneys. However, whether those animal results translate to patients with non-diabetic kidney disease has yet to be evaluated. Considering the paucity of new agents to treat kidney disease and the minimal adverse effects of metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors, these anti-diabetic agents could be used in patients with non-diabetic kidney disease. This paper provides a rationale for clinical trials that apply metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors to non-diabetic kidney disease. Full article
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10 pages, 240 KiB  
Article
Is Preptin a New Bone Metabolism Parameter in Hemodialysis Patients?
by Małgorzata Kałużna, Krzysztof Pawlaczyk, Krzysztof Schwermer, Krzysztof Hoppe, Aisha Yusuf Ibrahim, Magdalena Czlapka-Matyasik, Elżbieta Wrotkowska, Katarzyna Ziemnicka, Andrzej Oko and Marek Ruchała
Life 2021, 11(4), 341; https://doi.org/10.3390/life11040341 - 12 Apr 2021
Cited by 3 | Viewed by 2068
Abstract
Background: Preptin is a bone-anabolic pancreatic peptide hormone. Its role in bone metabolism has been studied in rats and in patients with diabetes, but its levels and significance in bone metabolism in hemodialyzed (HD) patients is unknown. Methods: The relationships between preptin and [...] Read more.
Background: Preptin is a bone-anabolic pancreatic peptide hormone. Its role in bone metabolism has been studied in rats and in patients with diabetes, but its levels and significance in bone metabolism in hemodialyzed (HD) patients is unknown. Methods: The relationships between preptin and anthropometric and biochemical parameters related to bone metabolism were studied in 73 patients on chronic hemodialysis (48 males, 25 females; mean age of 57 years; HD vintage of 69.7 months). Of these subjects, 36 patients had diabetes or impaired glucose tolerance (DM/IGT), and 37 patients had normal glucose tolerance (NGT). Dual-energy X-ray absorptiometry of the femoral neck and lumbar spine were also performed. Results: No differences were observed in preptin levels between DM/IGT and NGT HD patients. Preptin was positively correlated with HD vintage (r = 0.312, p = 0.007). Negative correlations between preptin and bone mineral density (BMD), T-score, and Z-score in the lumbar spine (L2-L4) were observed (r = −0.319, p = 0.009; r = −0.341, p = 0.005; r = −0.375, p = 0.002). Preptin was positively correlated with parathormone (PTH) levels (r = 0.379, p < 0.001) and osteocalcin levels (r = 0.262, p = 0.027). Conclusions: The results indicate that preptin may reflect on bone and mineral metabolism disturbances seen in HD patients. The significant correlation of preptin with PTH and osteocalcin suggests that preptin may be important in indirect measurement of bone turnover in HD patients. Full article
14 pages, 794 KiB  
Review
Lipoprotein Abnormalities in Chronic Kidney Disease and Renal Transplantation
by Carlo Maria Barbagallo, Angelo Baldassare Cefalù, Antonina Giammanco, Davide Noto, Rosalia Caldarella, Marcello Ciaccio, Maurizio Rocco Averna and Emilio Nardi
Life 2021, 11(4), 315; https://doi.org/10.3390/life11040315 - 05 Apr 2021
Cited by 10 | Viewed by 3083
Abstract
Chronic kidney disease (CKD) is one of the most important risk factors for cardiovascular disease (CVD). Despite the kidney having no direct implications for lipoproteins metabolism, advanced CKD dyslipidemia is usually present in patients with CKD, and the frequent lipid and lipoprotein alterations [...] Read more.
Chronic kidney disease (CKD) is one of the most important risk factors for cardiovascular disease (CVD). Despite the kidney having no direct implications for lipoproteins metabolism, advanced CKD dyslipidemia is usually present in patients with CKD, and the frequent lipid and lipoprotein alterations occurring in these patients play a role of primary importance in the development of CVD. Although hypertriglyceridemia is the main disorder, a number of lipoprotein abnormalities occur in these patients. Different enzymes pathways and proteins involved in lipoprotein metabolism are impaired in CKD. In addition, treatment of uremia may modify the expression of lipoprotein pattern as well as determine acute changes. In renal transplantation recipients, the main lipid alteration is hypercholesterolemia, while hypertriglyceridemia is less pronounced. In this review we have analyzed lipid and lipoprotein disturbances in CKD and also their relationship with progression of renal disease. Hypolipidemic treatments may also change the natural history of CVD in CKD patients and may represent important strategies in the management of CKD patients. Full article
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26 pages, 439 KiB  
Review
Multifaceted Sexual Dysfunction in Dialyzing Men and Women: Pathophysiology, Diagnostics, and Therapeutics
by Jadzia Chou, Thomas Kiebalo, Piotr Jagiello and Krzysztof Pawlaczyk
Life 2021, 11(4), 311; https://doi.org/10.3390/life11040311 - 02 Apr 2021
Cited by 7 | Viewed by 3198
Abstract
Patient survival continues to increase with the growing quality of dialysis and management of chronic kidney disease (CKD). As such, chronic therapy must include considerations of quality of life (QOL), and this includes the disproportionate prevalence of sexual dysfunction (SD) in this patient [...] Read more.
Patient survival continues to increase with the growing quality of dialysis and management of chronic kidney disease (CKD). As such, chronic therapy must include considerations of quality of life (QOL), and this includes the disproportionate prevalence of sexual dysfunction (SD) in this patient population. This review aims to describe the pathophysiological and the psychosocial causes of SD with regard to renal replacement therapy, particularly hemo- and peritoneal dialysis. The differences in its manifestation in men and women are compared, including hormonal imbalances—and therefore fertility, libido, and sexual satisfaction—the experience of depression and anxiety, and QOL. The impact of comorbidities and the iatrogenic causes of SD are described. This review also presents validated scales for screening and diagnosis of SD in CKD patients and outlines novel therapies and strategies for the effective management of SD. Increased prevalence of CKD invariably increases the number of patients with SD, and it is crucial for health care professional teams to become familiar with the clinical tools used to manage this sensitive and under-quantified field. As a known predictor of QOL, sexual function should become a point of focus in the pursuit of patient-centered care, particularly as we seek to achieve as “normal” a life as possible for individuals who receive dialysis. Full article
8 pages, 431 KiB  
Communication
Tenofovir Alafenamide Rescues Renal Tubules in Patients with Chronic Hepatitis B
by Tomoya Sano, Takumi Kawaguchi, Tatsuya Ide, Keisuke Amano, Reiichiro Kuwahara, Teruko Arinaga-Hino and Takuji Torimura
Life 2021, 11(3), 263; https://doi.org/10.3390/life11030263 - 23 Mar 2021
Cited by 3 | Viewed by 2695
Abstract
Nucles(t)ide analogs (NAs) are effective for chronic hepatitis B (CHB). NAs suppress hepatic decompensation and hepatocarcinogenesis, leading to a dramatic improvement of the natural course of patients with CHB. However, renal dysfunction is becoming an important issue for the management of CHB. Renal [...] Read more.
Nucles(t)ide analogs (NAs) are effective for chronic hepatitis B (CHB). NAs suppress hepatic decompensation and hepatocarcinogenesis, leading to a dramatic improvement of the natural course of patients with CHB. However, renal dysfunction is becoming an important issue for the management of CHB. Renal dysfunction develops in patients with the long-term treatment of NAs including adefovir dipivoxil and tenofovir disoproxil fumarate. Recently, several studies have reported that the newly approved tenofovir alafenamide (TAF) has a safe profile for the kidney due to greater plasma stability. In this mini-review, we discuss the effectiveness of switching to TAF for NAs-related renal tubular dysfunction in patients with CHB. Full article
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11 pages, 4031 KiB  
Article
A Novel Dipeptidyl Peptidase-4 Inhibitor DA-1229 Ameliorates Tubulointerstitial Fibrosis in Cyclosporine Nephrotoxicity in Mice
by Hye Sook Min, Ji Eun Lee, Jung Yeon Ghee, Young Sun Kang, Jin Joo Cha, Jee Young Han, Sang Youb Han and Dae Ryong Cha
Life 2021, 11(3), 251; https://doi.org/10.3390/life11030251 - 18 Mar 2021
Cited by 3 | Viewed by 1997
Abstract
Cyclosporine A (CyA) is an immunosuppressive agent that induces nephrotoxicity with long-term treatment. The roles of DPP-4 and its inhibitors in cyclosporine nephrotoxicity are not fully understood. Therefore, we investigated the effects of a novel DPP-4 inhibitor, DA-1229, on the progression of renal [...] Read more.
Cyclosporine A (CyA) is an immunosuppressive agent that induces nephrotoxicity with long-term treatment. The roles of DPP-4 and its inhibitors in cyclosporine nephrotoxicity are not fully understood. Therefore, we investigated the effects of a novel DPP-4 inhibitor, DA-1229, on the progression of renal disease in an experimental cyclosporine nephrotoxicity model. Chronic cyclosporine nephrotoxicity was induced in six-week-old male ICR mice by subcutaneous injections of CyA at a dose of 30 mg/kg for four weeks. Animals were treated with DA-1229 at a dose of 300 mg/kg per day in food for four weeks. Although DPP-4 activity did not increase in the kidneys of mice with induced cyclosporine nephrotoxicity, DA-1229 treatment significantly suppressed DPP-4 activity in both plasma and renal tissues. DPP-4 inhibition by DA-1229 led to significantly decreased albuminuria and urinary excretion of 8-isoprosatane. DPP-4 inhibition also substantially suppressed pro-inflammatory effects, profibrotic molecules, and macrophage infiltration, and led to the improvement in renal structural changes. Our results suggest that DPP-4 inhibition by DA-1229 provides renoprotective effects in an animal model of cyclosporine nephrotoxicity via antioxidant, anti-inflammatory, and anti-fibrotic mechanisms. DPP-4 inhibition may be a useful new therapeutic approach for the management of progressive renal disease in cyclosporine nephrotoxicity. Full article
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12 pages, 834 KiB  
Review
Non-Albumin Proteinuria (NAP) as a Complementary Marker for Diabetic Kidney Disease (DKD)
by Jaehyun Bae, Young Jun Won and Byung-Wan Lee
Life 2021, 11(3), 224; https://doi.org/10.3390/life11030224 - 10 Mar 2021
Cited by 6 | Viewed by 3409
Abstract
Diabetic kidney disease (DKD) is one of the most common forms of chronic kidney disease. Its pathogenic mechanism is complex, and it can affect entire structures of the kidney. However, conventional approaches to early stage DKD have focused on changes to the glomerulus. [...] Read more.
Diabetic kidney disease (DKD) is one of the most common forms of chronic kidney disease. Its pathogenic mechanism is complex, and it can affect entire structures of the kidney. However, conventional approaches to early stage DKD have focused on changes to the glomerulus. Current standard screening tools for DKD, albuminuria, and estimated glomerular filtration rate are insufficient to reflect early tubular injury. Therefore, many tubular biomarkers have been suggested. Non-albumin proteinuria (NAP) contains a wide range of tubular biomarkers and is convenient to measure. We reviewed the clinical meanings of NAP and its significance as a marker for early stage DKD. Full article
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12 pages, 486 KiB  
Article
Circulating Renalase as Predictor of Renal and Cardiovascular Outcomes in Pre-Dialysis CKD Patients: A 5-Year Prospective Cohort Study
by Ana Cerqueira, Janete Quelhas-Santos, Inês Ferreira, Susana Sampaio, Miguel Relvas, Nídia Marques, Cláudia Camila Dias and Manuel Pestana
Life 2021, 11(3), 210; https://doi.org/10.3390/life11030210 - 08 Mar 2021
Cited by 3 | Viewed by 1630
Abstract
Chronic kidney disease (CKD) is an independent risk factor for adverse cardiovascular and cerebrovascular events (MACCEs), and mortality since the earlier stages. Therefore, it is critical to identify the link between CKD and cardiovascular risk (CVR) through early and reliable biomarkers. Acknowledging that [...] Read more.
Chronic kidney disease (CKD) is an independent risk factor for adverse cardiovascular and cerebrovascular events (MACCEs), and mortality since the earlier stages. Therefore, it is critical to identify the link between CKD and cardiovascular risk (CVR) through early and reliable biomarkers. Acknowledging that CKD and CKD progression are associated with increased sympathetic tone, which is implicated in CVR, and that renalase metabolizes catecholamines, we aimed to evaluate the relationship between renalase serum levels (RNLS) and cardiovascular and renal outcomes. The study included 40 pre-dialysis CKD patients (19F:21M) with median age of 61 (IQ 45–66) years. At baseline, we measured RNLS as well as routine biomarkers of renal and cardiovascular risk. A prospective analysis was performed to determine whether RNLS are associated with CKD progression, MACCEs, hospitalizations and all-cause mortality. At baseline, the median level of RNLS and median estimated glomerular filtration rate (eGFR) were 63.5 (IQ 48.4–82.7) µg/mL and 47 (IQ 13–119) mL/min/1.73 m2, respectively. In univariate analysis, RNLS were strongly associated with eGFR, age and Charlson Index. Over the course of a mean follow-up of 65 (47 to 70) months, 3 (7.5%) deaths, 2 (5%) fatal MACCEs, 17 (42.5%) hospital admissions occurred, and 16 (40%) patients experienced CKD progression. In univariate analysis, RNLS were associated with CKD progression (p = 0.001), hospitalizations (p = 0.001) and all-cause mortality (p = 0.022) but not with MACCEs (p = 0.094). In adjusted analysis, RNLS predicted CKD progression and hospitalizations regardless of age, Charlson comorbidity index, cardiovascular disease, hypertension, diabetes and dyslipidemia. Our results suggest that RNLS, closely related with renal function, might have a potential role as predictor of renal outcomes, hospitalizations, and mortality in pre-dialysis CKD patients. Full article
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9 pages, 263 KiB  
Article
Metabolic Phenotypes and Chronic Kidney Disease: A Cross-Sectional Assessment of Patients from a Large Federally Qualified Health Center
by Kathleen E. Adair, Nicholas von Waaden, Matthew Rafalski, Burritt W. Hess, Sally P. Weaver and Rodney G. Bowden
Life 2021, 11(2), 175; https://doi.org/10.3390/life11020175 - 23 Feb 2021
Cited by 7 | Viewed by 2367
Abstract
The purpose of this study is to determine if renal function varies by metabolic phenotype. A total of 9599 patients from a large Federally Qualified Health Center (FQHC) were included in the analysis. Metabolic health was classified as the absence of metabolic abnormalities [...] Read more.
The purpose of this study is to determine if renal function varies by metabolic phenotype. A total of 9599 patients from a large Federally Qualified Health Center (FQHC) were included in the analysis. Metabolic health was classified as the absence of metabolic abnormalities defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, excluding waist circumference. Obesity was defined as body mass index >30 kg/m2 and renal health as an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2. Linear and logistic regressions were used to analyze the data. The metabolically healthy overweight (MHO) phenotype had the highest eGFR (104.86 ± 28.76 mL/min/1.72 m2) and lowest unadjusted odds of chronic kidney disease (CKD) (OR = 0.46, 95%CI = 0.168, 1.267, p = 0.133), while the metabolically unhealthy normal weight (MUN) phenotype demonstrated the lowest eGFR (91.34 ± 33.28 mL/min/1.72 m2) and the highest unadjusted odds of CKD (OR = 3.63, p < 0.0001). After controlling for age, sex, and smoking status, the metabolically unhealthy obese (MUO) (OR = 1.80, 95%CI = 1.08, 3.00, p = 0.024) was the only phenotype with significantly higher odds of CKD as compared to the reference. We demonstrate that the metabolically unhealthy phenotypes have the highest odds of CKD compared to metabolically healthy individuals. Full article
10 pages, 234 KiB  
Article
Status of Nutrition in Hemodialysis Patients Survey (SNIPS): Nutrition Intake in Obese and Overweight vs. Healthy Weight Patients
by Mona Boaz, Vered Kaufman-Shriqui, Odile Azoulay and Talia Weinstein
Life 2021, 11(2), 166; https://doi.org/10.3390/life11020166 - 21 Feb 2021
Cited by 1 | Viewed by 2036
Abstract
Elevated body mass index (BMI) has been associated with improved survival and fewer hospitalizations in hemodialysis patients; however, it is not clear that dietary intake is associated with increased BMI in hemodialysis patients. The present analysis was designed to compare energy and macronutrient [...] Read more.
Elevated body mass index (BMI) has been associated with improved survival and fewer hospitalizations in hemodialysis patients; however, it is not clear that dietary intake is associated with increased BMI in hemodialysis patients. The present analysis was designed to compare energy and macronutrient intake and distribution, as well as compliance with the International Society of Renal Nutrition and Metabolism (ISRNM) dietary guidelines, by body weight status (overweight/obese vs. normal weight) in hemodialysis patients. The status of nutrition in hemodialysis patients survey (SNIPS) cohort is a cross-sectional study including a representative sample of individuals on hemodialysis treated in hospital dialysis centers throughout Israel. Of the 375 patients eligible for the current analysis, 60.1% had BMI ≥ 25 kg/m2 (overweight/obese). For each participant, the following measures were recorded: dietary intake, blood biochemistry, anthropometric and hemodynamic measures. These were compared by body weight status. Compared to their normal-weight counterparts, overweight/obese hemodialysis patients did not differ by energy and macronutrient intake, distribution of these nutrients in the diet. Regardless of body weight status, hemodialysis patients have poor compliance with ISRNM dietary guidelines. Full article
8 pages, 1279 KiB  
Communication
Dysfunction of Mitochondrial Dynamics in Drosophila Model of Diabetic Nephropathy
by Kiyoung Kim, Sun Joo Cha, Hyun-Jun Choi, Jeong Suk Kang and Eun Young Lee
Life 2021, 11(1), 67; https://doi.org/10.3390/life11010067 - 18 Jan 2021
Cited by 6 | Viewed by 2975
Abstract
Although mitochondrial dysfunction is associated with the development and progression of diabetic nephropathy (DN), its mechanisms are poorly understood, and it remains debatable whether mitochondrial morphological change is a cause of DN. In this study, a Drosophila DN model was established by treating [...] Read more.
Although mitochondrial dysfunction is associated with the development and progression of diabetic nephropathy (DN), its mechanisms are poorly understood, and it remains debatable whether mitochondrial morphological change is a cause of DN. In this study, a Drosophila DN model was established by treating a chronic high-sucrose diet that exhibits similar phenotypes in animals. Results showed that flies fed a chronic high-sucrose diet exhibited a reduction in lifespan, as well as increased lipid droplets in fat body tissue. Furthermore, the chronic high-sucrose diet effectively induced the morphological abnormalities of nephrocytes in Drosophila. High-sucrose diet induced mitochondria fusion in nephrocytes by increasing Opa1 and Marf expression. These findings establish Drosophila as a useful model for studying novel regulators and molecular mechanisms for imbalanced mitochondrial dynamics in the pathogenesis of DN. Furthermore, understanding the pathology of mitochondrial dysfunction regarding morphological changes in DN would facilitate the development of novel therapeutics. Full article
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