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Diabetic Kidney Disease: Epidemiology, Risk Factors for Disease Progression and Cardiovascular Complications, Novel Diagnostics and Treatments

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 (5 December 2023) | Viewed by 23212

Special Issue Editors


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Guest Editor
Department of Nephrology and Transplant Center, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
Interests: chronic kidney disease; diabetic kidney disease; kidney transplantation; posttransplant diabetes; chronic rejection

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Guest Editor
Department of Internal Medicine III, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany
Interests: chronic kidney disease; diabetic kidney disease; cardiovascular risk; kidney transplantation

Special Issue Information

Dear Colleagues,

Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide, with a significant increase in risk for cardiovascular events, dialysis dependence and premature mortality. Given the increasing prevalence of type 2 DM, the global burden of DKD is expected to further increase in future. Thus, there is a strong socioeconomic and health imperative to improve outcomes for people with DKD.

Predicting the evolution of DKD remains difficult as its progression is highly variable. To prevent kidney failure and reduce mortality, understanding of epidemiology as well as early identification of risk factors for disease progression and cardiovascular complications is important. There is also a clear clinical need for novel noninvasive diagnostics to enhance our understanding of DKD pathophysiology, progression and risk stratification, and to assess efficacy and modes of action of new therapeutic interventions.

Since the introduction of angiotensin converting enzyme (ACE) inhibitors in the 1990s and angiotensin II receptor blockers (ARBs) in the early 2000s for the treatment of DKD, the advents of sodium-glucose cotransporter 2 (SGLT2) inhibitors and new mineralocorticoid receptor antagonists have been evolutionary additions to the therapeutic repertoire of DKD.

The scope of this Special Issue is to provide critical insights into the current knowledge of epidemiology, risk factors for disease progression and cardiovascular complications as well as novel diagnostics and treatments for DKD.

We cordially invite you to submit relevant papers for consideration for peer review and expeditious publication in this Special Issue of the Journal of Clinical Medicine. All original investigations as well as comprehensive reviews are welcome.

Dr. Seema Baid-Agrawal
Dr. Martin Busch
Guest Editors

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Keywords

  • diabetic kidney disease
  • diagnostics
  • epidemiology
  • risk factors
  • progression
  • cardiovascular events
  • treatment

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Published Papers (8 papers)

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Research

Jump to: Review

14 pages, 4959 KiB  
Article
Adropin Predicts Chronic Kidney Disease in Type 2 Diabetes Mellitus Patients with Chronic Heart Failure
by Tetiana A. Berezina, Zeljko Obradovic, Elke Boxhammer, Alexander A. Berezin, Michael Lichtenauer and Alexander E. Berezin
J. Clin. Med. 2023, 12(6), 2231; https://doi.org/10.3390/jcm12062231 - 13 Mar 2023
Cited by 8 | Viewed by 2444
Abstract
Adropin is a multifunctional secreted protein, which is involved in the metabolic modulation of the heart-brain-kidney axis in heart failure (HF). The aim of the study was to detect the plausible predictive value of serum levels of adropin for chronic kidney disease (CKD) [...] Read more.
Adropin is a multifunctional secreted protein, which is involved in the metabolic modulation of the heart-brain-kidney axis in heart failure (HF). The aim of the study was to detect the plausible predictive value of serum levels of adropin for chronic kidney disease (CKD) grades 1–3 in type 2 diabetes mellitus (T2DM) patients with chronic HF. We enrolled 417 T2DM individuals with chronic HF and subdivided them into two groups depending on the presence of CKD. The control group was composed of 25 healthy individuals and 30 T2DM patients without HF and CKD. All eligible patients underwent an ultrasound examination. Adropin was detected by ELISA in blood samples at the study baseline. We found that adropin levels in T2DM patients without HF and CKD were significantly lower than in healthy volunteers, but they were higher than in T2DM patients with known HF. The optimal cut-off point for adropin levels was 2.3 ng/mL (area under the curve [AUC] = 0.86; 95% CI = 0.78–0.95; sensitivity = 81.3%, specificity = 77.4%). The multivariate logistic regression adjusted for albuminuria/proteinuria showed that serum levels of adropin <2.30 ng/mL (OR = 1.55; p = 0.001) independently predicted CKD. Conclusions: Low levels of adropin in T2DM patients with chronic CH seem to be an independent predictor of CKD at stages 1–3. Full article
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10 pages, 532 KiB  
Article
Heterogeneity in Kidney Histology and Its Clinical Indicators in Type 2 Diabetes Mellitus: A Retrospective Study
by Shivendra Singh, Prem Shankar Patel and Archana Archana
J. Clin. Med. 2023, 12(5), 1778; https://doi.org/10.3390/jcm12051778 - 23 Feb 2023
Cited by 4 | Viewed by 1715
Abstract
The heterogeneous spectrum of kidney disease in diabetes ranges from albuminuric or non-albuminuric diabetic kidney disease to non-diabetic kidney diseases. Presumptive clinical diagnosis of diabetic kidney disease may lead to an erroneous diagnosis. Material and Method: We analyzed the clinical profile and kidney [...] Read more.
The heterogeneous spectrum of kidney disease in diabetes ranges from albuminuric or non-albuminuric diabetic kidney disease to non-diabetic kidney diseases. Presumptive clinical diagnosis of diabetic kidney disease may lead to an erroneous diagnosis. Material and Method: We analyzed the clinical profile and kidney biopsy of a total of 66 type 2 diabetes patients. Based on kidney histology, they were divided into—Class I (Diabetic Nephropathy), Class II (Non-diabetic kidney disease), and Class III (Mixed lesion). Demographic data, clinical presentation, and laboratory values were collected and analyzed. This study tried to examine the heterogeneity in kidney disease, its clinical indicator, and the role of kidney biopsy in the diagnosis of kidney disease in diabetes. Results: Class I consisted of 36(54.5%), class II 17(25.8%), and class III 13(19.7%) patients. The commonest clinical presentation was nephrotic syndrome 33(50%) followed by chronic kidney disease 16(24.4%) and asymptomatic urinary abnormality 8(12.1%). Diabetic retinopathy (DR) was present in 27(41%) cases. DR was significantly higher in the class I patients (p < 0.05). Specificity and positive predictive values of DR for DN were 0.83 and 0.81, respectively (sensitivity 0.61; negative predictive values 0.64). The Association of the duration of diabetes and the level of proteinuria with DN was statistically not significant (p > 0.05). Idiopathic MN (6) and Amyloidosis (2) were the most common isolated NDKD; whereas diffuse proliferative glomerulonephritis (DPGN) (7) was the commonest NDKD in mixed disease. Another common form of NDKD in mixed disease was Thrombotic Microangiopathy (2) and IgA nephropathy (2). NDKD was observed in 5(18.5%) cases in presence of DR. We noted biopsy-proven DN even in 14(35.9%) cases without DR, in 4(50%) cases with microalbuminuria and 14(38.9%) cases with a short duration of diabetes. Conclusion: Almost half (45%) of cases with atypical presentation have non-diabetic kidney disease (NDKD), though even among these cases with atypical presentation diabetic nephropathy (either alone or in mixed form) is commonly seen in 74.2% of cases. DN has been seen in a subset of cases without DR, with microalbuminuria, and with a short duration of diabetes. Clinical indicators were insensitive in distinguishing DN Vs NDKD. Hence, a kidney biopsy may be a potential tool for the accurate diagnosis of kidney disease. Full article
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15 pages, 2199 KiB  
Article
Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus: A Changing Spectrum with Therapeutic Ascendancy
by Narayan Prasad, Vamsidhar Veeranki, Dharmendra Bhadauria, Ravi Kushwaha, Jeyakumar Meyyappan, Anupama Kaul, Manas Patel, Manas Behera, Monika Yachha, Vinita Agrawal and Manoj Jain
J. Clin. Med. 2023, 12(4), 1705; https://doi.org/10.3390/jcm12041705 - 20 Feb 2023
Cited by 4 | Viewed by 4350
Abstract
Background and objectives: Owing to changing epidemiology and therapeutic practices, a change in the spectrum of renal involvement in Type-2 diabetes mellitus (T2DM) has also been noted. The treatment of non-diabetic kidney disease (NDKD) differs from diabetic kidney disease (DKD) and the reversibility [...] Read more.
Background and objectives: Owing to changing epidemiology and therapeutic practices, a change in the spectrum of renal involvement in Type-2 diabetes mellitus (T2DM) has also been noted. The treatment of non-diabetic kidney disease (NDKD) differs from diabetic kidney disease (DKD) and the reversibility of NDKD in many cases to normal, prompts biopsy for rapid and accurate diagnosis. Data are scarce on kidney biopsy findings in T2DM. Study design & setting: In this observational study, we prospectively collected the data of kidney biopsies of patients aged 18 years with T2DM admitted between 1 August 2005 and 31 July 2022. The clinical, demographic and histopathological data were evaluated. The spectrum of kidney involvement in the form of DKD and/or NDKD was studied. The impact of these findings with the use of drugs retarding disease progression was also analyzed. Results: A total of 5485 biopsies were performed during the study period and of these 538 patients had T2DM. The mean age of the study population was 56.9 ± 11.5 years and 81% were males. The mean duration of DM was 6.4 ± 6.1 years. Diabetic retinopathy (DR) was noted in 29.7%. The most common indication for biopsy was an acute rise in creatinine (147, 27.3%). Amongst the 538 diabetic patients who underwent biopsy, histological features only of DKD were noted in 166 patients (33%), NDKD alone in 262 (49%) and NDKD with DKD lesions in 110 (20%). On multivariate analysis, duration of DM less than 5 years, absence of CAD, absence of DR, oliguria at presentation, an acute rise in creatinine and low C3 were associated with NDKD. Conclusions: The prevalence of NDKD among diabetics and ATIN in particular might be on an increasing trend in the current era of changing T2DM epidemiological patterns. The use of anti-pro-teinuric agents was associated with lesser degrees of histopathological chronicity in T2DM. Full article
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11 pages, 3890 KiB  
Article
Ultrasonography Measurement of Renal Dimension and Its Correlation with Age, Body Indices, and eGFR in Type 1 Diabetes Mellitus Patients: Real World Data in Taiwan
by Hsuan-An Su, Jung-Fu Chen, Chung-Ming Fu, Yueh-Ting Lee, Yi Wang, Chiang-Chi Huang, Jin-Bor Chen, Chien-Te Lee and Chien-Hsing Wu
J. Clin. Med. 2023, 12(3), 1109; https://doi.org/10.3390/jcm12031109 - 31 Jan 2023
Viewed by 1816
Abstract
Background: Assessment of renal size is clinically significant for the screening, diagnosis, and follow-up of renal diseases as the basis of clinical decisions. However, the relationship of renal dimension with age, body indices, and the estimated glomerular filtration rate (eGFR) has rarely been [...] Read more.
Background: Assessment of renal size is clinically significant for the screening, diagnosis, and follow-up of renal diseases as the basis of clinical decisions. However, the relationship of renal dimension with age, body indices, and the estimated glomerular filtration rate (eGFR) has rarely been reported in the Chinese type 1 diabetes mellitus (T1DM) population. Methods: A total of 220 T1DM patients were retrospectively analyzed from the Chang Gung Research Database in Taiwan. Demographic data, laboratory data, and ultrasonographic images from January 2001 to November 2018 were extracted. Results: Eighty-five participants (38.6%) were male. The mean age was 34.2 years. The median eGFR was 60.0 mL/min/1.73 m2. The mean ultrasonographic left and right renal lengths (LL and RL) with S.D. were 10.9 ± 1.5 cm and 11.0 ± 1.1 cm, respectively. Renal lengths were longer with increasing body height and body weight but shorter with increasing age in patients with T1DM. In trajectory analysis, a linear mixed model revealed no significant trend in the changes in eGFR during the follow-up period. Moreover, renal length did not play a significant role in predicting KDIGO CKD stage 5 in the cohort. Conclusions: Renal length and its comparison to the reference ranges demonstrated very limited advantages in predicting renal function decline in T1DM patients. Full article
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11 pages, 918 KiB  
Article
Diabetic Kidney Disease versus Primary Glomerular Disease: A Propensity Score-Matched Analysis of Association between Ambulatory Blood-Pressure Monitoring and Target-Organ Damage
by Tiantian Yu, Shicong Song, Xiaoqiu Chen, Tanqi Lou, Jun Zhang, Hui Peng, Man Li and Cheng Wang
J. Clin. Med. 2023, 12(1), 167; https://doi.org/10.3390/jcm12010167 - 25 Dec 2022
Cited by 1 | Viewed by 1597
Abstract
Diabetic kidney disease (DKD) and primary glomerular disease (PGD) are the main causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). This study was conducted to compare the characteristics of ambulatory blood-pressure monitoring (ABPM) and its relationship with target-organ damage (TOD) [...] Read more.
Diabetic kidney disease (DKD) and primary glomerular disease (PGD) are the main causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). This study was conducted to compare the characteristics of ambulatory blood-pressure monitoring (ABPM) and its relationship with target-organ damage (TOD) in patients with DKD and PGD matched by propensity score. The assessment of TOD included macroalbuminuria, left ventricular hypertrophy (LVH) and macrovascular disease. Propensity-score weighting (PSW) was used in stratified analysis. Results: Patients with DKD had a higher prevalence of abnormal blood-pressure patterns such as reversed dipper pattern, nocturnal hypertension, and sustained hypertension and had a higher prevalence of TOD than did patients with PGD. Logistic regression indicated that patients with DKD were more related to TOD than to PGD. The stratified analysis indicated that DKD patients with white-coat hypertension, masked hypertension and sustained hypertension had closer relationships with TOD compared with PGD patients. Conclusion: Patients with type 2 diabetic kidney disease had more abnormal blood-pressure patterns and were more closely related to target organ damage than were patients with primary glomerular disease. Full article
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Review

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28 pages, 1712 KiB  
Review
Magnetic Resonance Imaging in Clinical Trials of Diabetic Kidney Disease
by Iris Friedli, Seema Baid-Agrawal, Robert Unwin, Arvid Morell, Lars Johansson and Paul D. Hockings
J. Clin. Med. 2023, 12(14), 4625; https://doi.org/10.3390/jcm12144625 - 11 Jul 2023
Cited by 1 | Viewed by 2429
Abstract
Chronic kidney disease (CKD) associated with diabetes mellitus (DM) (known as diabetic kidney disease, DKD) is a serious and growing healthcare problem worldwide. In DM patients, DKD is generally diagnosed based on the presence of albuminuria and a reduced glomerular filtration rate. Diagnosis [...] Read more.
Chronic kidney disease (CKD) associated with diabetes mellitus (DM) (known as diabetic kidney disease, DKD) is a serious and growing healthcare problem worldwide. In DM patients, DKD is generally diagnosed based on the presence of albuminuria and a reduced glomerular filtration rate. Diagnosis rarely includes an invasive kidney biopsy, although DKD has some characteristic histological features, and kidney fibrosis and nephron loss cause disease progression that eventually ends in kidney failure. Alternative sensitive and reliable non-invasive biomarkers are needed for DKD (and CKD in general) to improve timely diagnosis and aid disease monitoring without the need for a kidney biopsy. Such biomarkers may also serve as endpoints in clinical trials of new treatments. Non-invasive magnetic resonance imaging (MRI), particularly multiparametric MRI, may achieve these goals. In this article, we review emerging data on MRI techniques and their scientific, clinical, and economic value in DKD/CKD for diagnosis, assessment of disease pathogenesis and progression, and as potential biomarkers for clinical trial use that may also increase our understanding of the efficacy and mode(s) of action of potential DKD therapeutic interventions. We also consider how multi-site MRI studies are conducted and the challenges that should be addressed to increase wider application of MRI in DKD. Full article
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16 pages, 489 KiB  
Review
Nephroprotective Properties of Antidiabetic Drugs
by Christian Gerdes, Nicolle Müller, Gunter Wolf and Martin Busch
J. Clin. Med. 2023, 12(10), 3377; https://doi.org/10.3390/jcm12103377 - 10 May 2023
Cited by 12 | Viewed by 5132
Abstract
Chronic kidney disease (CKD) is associated with increased morbidity and mortality, especially from cardiovascular (CV) causes, and especially in people with diabetes mellitus (DM). Already the presence of DM increases CV risk and potentiates the risk of CKD. Therefore, besides glycemic control, prevention [...] Read more.
Chronic kidney disease (CKD) is associated with increased morbidity and mortality, especially from cardiovascular (CV) causes, and especially in people with diabetes mellitus (DM). Already the presence of DM increases CV risk and potentiates the risk of CKD. Therefore, besides glycemic control, prevention and treatment of CKD to slow its progression are of clinical importance. A significant nephroprotective effect of novel antidiabetic drugs, namely sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and glucagon-like peptide 1 receptor agonists (GLP1-RA), has been shown on top of their glucose-lowering effects and was confirmed in cardiovascular outcome trials. GLP1-RA mainly reduced the risk of macroalbuminuria, whereas SGLT2-I were also associated with a lower risk of declining glomerular filtration rate (GFR) over time. The nephroprotective effects of SGLT2-I are also evident in people without DM. According to current guidelines, SGLT2-I and/or GLP1-RA are recommended for people with DM who have chronic kidney disease and/or increased cardiovascular risk. However, other antidiabetic drugs offer nephroprotective properties, which will also be discussed in this review. Full article
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15 pages, 1182 KiB  
Review
Sex-Related Aspects in Diabetic Kidney Disease—An Update
by Ivonne Loeffler and Nadja Ziller
J. Clin. Med. 2023, 12(8), 2834; https://doi.org/10.3390/jcm12082834 - 12 Apr 2023
Cited by 4 | Viewed by 2769
Abstract
Differences between the sexes exist in many diseases, and in most cases, being a specific sex is considered a risk factor in the development and/or progression. This is not quite so clear in diabetic kidney disease (DKD), the development and severity of which [...] Read more.
Differences between the sexes exist in many diseases, and in most cases, being a specific sex is considered a risk factor in the development and/or progression. This is not quite so clear in diabetic kidney disease (DKD), the development and severity of which depends on many general factors, such as the duration of diabetes mellitus, glycemic control, and biological risk factors. Similarly, sex-specific factors, such as puberty or andro-/menopause, also determine the microvascular complications in both the male and female sex. In particular, the fact that diabetes mellitus itself influences sex hormone levels, which in turn seem to be involved in renal pathophysiology, highlights the complexity of the question of sex differences in DKD. The major objective of this review is to summarize and simplify the current knowledge on biological sex-related aspects in the development/progression but also treatment strategies of human DKD. It also highlights findings from basic preclinical research that may provide explanations for these differences. Full article
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