Effect of Patient-Centered Self-Management Program on Blood Pressure, Renal Function Control, and the Quality of Life of Patients With Hypertensive Nephropathy: A Longitudinal Randomized Controlled Trial

This longitudinal study with a randomized controlled trial evaluated the long-term effectiveness of the patient-centered self-management intervention program on the control of blood pressure and renal function, as well as the quality of life of patients with hypertensive nephropathy. The control group ( n = 38) received usual care while the experimental group ( n = 38) participated in a patient-centered self-management program. After the pre-test, the intervention was performed with the experimental group once a week for a total of 4 weeks. Then, the post-test was performed 1, 3, and 6 months later. A questionnaire was used to collect the demographic data and disease characteristics, laboratory data, and quality of life scale. This study tracked three time points (i.e., 1, 3, and 6 months) after the intervention and found that the experimental group achieved significant results in controlling systolic blood pressure ( p < 0.001), diastolic blood pressure ( p = 0.007), and eGFR ( p = 0.013). Significant results were achieved in the overall quality of life ( p < 0.001) and the quality of life in the physical (PHC; p < 0.001) and mental health components (MHC; p < 0.001). Furthermore, the effects in the experimental group lasted for as long as 6 months and were better than those in the control group. Moreover, this program can provide nursing staff with a reference different from traditional health education methods.

Variable expression of eighteen common housekeeping genes in human non-cancerous kidney biopsies

Housekeeping, or reference genes (RGs) are, by definition, loci with stable expression profiles that are widely used as internal controls to normalize mRNA levels. However, due to specific events, such as pathological changes, or technical procedures, their expression might be altered, failing to fulfil critical normalization pre-requisites. To identify RG genes suitable as internal controls in human non-cancerous kidney tissue, we selected 18 RG candidates based on previous data and screen them in 30 expression datasets (>800 patients), including our own, publicly available or provided by independent groups. Datasets included specimens from patients with hypertensive and diabetic nephropathy, Fabry disease, focal segmental glomerulosclerosis, IgA nephropathy, membranous nephropathy, and minimal change disease. We examined both microdissected and whole section-based datasets. Expression variability of 4 candidate genes (YWHAZ, SLC4A1AP, RPS13 and ACTB) was further examined by qPCR in biopsies from patients with hypertensive nephropathy (n = 11) and healthy controls (n = 5). Only YWHAZ gene expression remained stable in all datasets whereas SLC4A1AP was stable in all but one Fabry dataset. All other RGs were differentially expressed in at least 2 datasets, and in 4.5 datasets on average. No differences in YWHAZ, SLC4A1AP, RPS13 and ACTB gene expression between hypertensive and control biopsies were detected by qPCR. Although RGs suitable to all techniques and tissues are unlikely to exist, our data suggest that in non-cancerous kidney biopsies expression of YWHAZ and SLC4AIAP genes is stable and suitable for normalization purposes.

Dual-Specificity Phosphatases and Kidney Diseases

<b><i>Background:</i></b> Dual-specificity phosphatases (DUSPs) belong to the family of protein tyrosine phosphatases, which can dephosphorylate both serine/threonine and tyrosine residues. During the past decades, DUSPs have been implicated in various physiological and pathological activities. Besides mitogen-activated protein kinases (MAPKs) as the main substrates, other protein and nonprotein substrates can also be dephosphorylated by DUSPs. Aberrant regulations of DUSPs have been found in various diseases such as cancer, neurological disorders, and kidney diseases, suggesting the involvement of DUSPs in the pathogenesis of diseases. <b><i>Summary:</i></b> In this review, we summarize the general characteristics of DUSPs and the research progress made in the field of kidney diseases, including diabetic nephropathy, hypertensive nephropathy, chronic kidney disease, acute kidney injury, and lupus nephritis. As the main biochemical function of DUSPs is to dephosphorylate MAPKs activity, decreased DUSPs are found in kidney disease models, whereas forced DUSPs expression reverses the disease presentation, which was proved by using transgenic or gene knockout model. <b><i>Key Messages:</i></b> Mounting evidence demonstrates that DUSPs have essential physiological and pathological functions in kidney disease. Fully understanding the functions and mechanisms of DUSPs in kidney disease contributes to their clinical application in translation medicine.

Molecular Mechanisms of Hypertensive Nephropathy: Renoprotective Effect of Losartan through Hsp70

Hypertensive nephrosclerosis is the second most common cause of end-stage renal disease after diabetes. For years, hypertensive kidney disease has been focused on the afferent arterioles and glomeruli damage and the involvement of the renin angiotensin system (RAS). Nonetheless, in recent years, novel evidence has demonstrated that persistent high blood pressure injures tubular cells, leading to epithelial–mesenchymal transition (EMT) and tubulointerstitial fibrosis. Injury primarily determined at the glomerular level by hypertension causes changes in post-glomerular peritubular capillaries that in turn induce endothelial damage and hypoxia. Microvasculature dysfunction, by inducing hypoxic environment, triggers inflammation, EMT with epithelial cells dedifferentiation and fibrosis. Hypertensive kidney disease also includes podocyte effacement and loss, leading to disruption of the filtration barrier. This review highlights the molecular mechanisms and histologic aspects involved in the pathophysiology of hypertensive kidney disease incorporating knowledge about EMT and tubulointerstitial fibrosis. The role of the Hsp70 chaperone on the angiotensin II–induced EMT after angiotensin II type 1 receptor (AT1R) blockage, as a possible molecular target for therapeutic strategy against hypertensive renal damage is discussed.

Kidney biopsy in very elderly patients: indications, therapeutic impact and complications

Background Few data is available on the risk/benefit balance of native kidney biopsy (KB) in very elderly patients. Methods Multicenter retrospective cohort study in the Aix-Marseille area: the results of KB and medical charts of all patients over 85 years biopsied between January 2010 and December 2018 were reviewed. Results 104 patients were included. Median age was 87 years. Indications for KB were: acute kidney injury (AKI) in 69.2% of patients, nephrotic syndrome (NS) with AKI in 13.5%, NS without AKI in 12.5%, and proteinuria in 4.8%. Median serum creatinine was 262 μmol/L, 21% of patients required dialysis at the time of KB. Significant bleeding occurred in 7 (6.7%) patients, requiring blood cell transfusion in 4 (3.8%), and radiological embolization in 1 (1%). The most frequent pathological diagnoses were: non-diabetic glomerular diseases (29.8%, including pauci-immune crescentic glomerulonephritis in 9.6%), hypertensive nephropathy (27.9%), acute interstitial nephritis (16.3%), renal involvement of hematological malignancy (8.7%), and acute tubular necrosis (6.7%). After KB, 51 (49%) patients received a specific treatment: corticosteroids (41.3%), cyclophosphamide (6.7%), rituximab (6.7%), bortezomib (3.8%), other chemotherapies (3.8%). Median overall survival was 31 months. Conclusions KB can reveal a diagnosis with therapeutic impact even in very elderly patients. Severe bleeding was not frequent in this cohort, but KB may have not been performed in more vulnerable patients.

The structure and features of the course of chronic kidney disease in patients with coronary heart disease and comorbid diseases

Aim. To investigate the prevalence, structure, and features of the course of chronic kidney disease (CKD) in patients with coronary heart disease (CHD) associated with comorbid diseases. Methods. The observation group consisted of 257 patients of the Interregional Clinical Diagnostic Center (Kazan) with coronary heart disease (20142018): 183 males and 74 females, aged from 38 to 95 years (mean age 61.80.6). Observation program: clinical examination; serum creatinine and lipid profiles, the albumin/creatinine ratio in a single portion of urine, morning urine osmolality, glomerular filtration rate estimated by the CKD-EPI; renal scintigraphy, ultrasonography of the kidneys, renal Doppler ultrasound and angiography. Chronic kidney disease was diagnosed if one of the criteria was met: the glomerular filtration rate 60 ml/min/1.73 m2 or the ratio of albumin to creatinine in urine (ACR) 30 mg/g. Statistical analysis was performed by using the methods of variational statistics: determination of the arithmetic mean (M), standard error of the mean (m) and difference significance according to the Student's test (t). Results. Examination of patients revealed the following comorbid diseases and syndromes: hypertension (90.7%), hyper- and dyslipidemia (96.5%), overweight/obesity (74.3%), diabetes mellitus (17.9%), chronic heart failure stages IIIa according to StrazheskoVasilenko classification (100%). 164 (63.8%) patients were first time diagnosed with chronic kidney disease: hypertensive nephropathy in 66.4%, ischemic renal disease in 21.9%, diabetic nephropathy in 2.4%, a combination of diabetic and hypertensive nephropathy in 9.3%. 51.2% of patients had stage 2 of chronic kidney disease, 42.1% stage 3, 6.7% stage 4 or 5. A feature of chronic kidney disease is its latent course (absence of complaints and clinical manifestations) and, as a consequence, unidentified diagnosis at the prehospital stage, which is generally characteristic of secondary nephropathies in cardiovascular diseases and these comorbid conditions. Conclusion. Chronic kidney disease was first diagnosed in 63.8% of patients with coronary heart disease with 1 to 5 comorbid diseases; a feature of chronic kidney disease is its secondary nature, the course of the disease is hidden by underlying and/or comorbid disease and, as a result, its late diagnosis.

Proteomics to Metabolomics: A New Insight Into the Pathogenesis of Hypertensive Nephropathy

Background Hypertensive nephropathy (HN) is a high burden disorder and a leading cause of end-stage renal disorder. In spite of huge investigations, the underlying mechanisms are yet largely unknown. Systems biology is a promising approach to provide a comprehensive insight towards this complex disorder. Methods Protein expression profiles of kidney tubule and cortex sub-compartments were retrieved from the PRIDE database and the quality of the datasets were assessed using principal component analysis (PCA) and hierarchical clustering. Differentially expressed proteins (DEPs) were detected and their attributed metabolites were enriched and their interactions were assessed in multi-layer networks. Moreover, considering the DEPs and the predicted metabolites, key biomedical phenomena with a leading role in HN pathogenesis were proposed. Results Amino acid and purine metabolisms are the most prominent alteration in kidney cortex whereas dysregulation of energy hemostasis is a key pathogenic mechanism in tubule. Besides, actin cytoskeleton disorganization is an enriched pathway in both anatomical areas. Conclusion The proteomics profiles of kidney sub-compartments were analyzed using a top-down approach to infer the main pathogenic processes. The constructed holistic map of HN can be exploited to propose novel therapeutic strategies.