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Endocrine Jun 2024Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in...
BACKGROUND
Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in proteinuria and the risk of diabetic microvascular complications.
METHODS
Study participants were 71,825 DM patients who received urine dipstick test for proteinuria both in 2003-2004 and 2006-2007. They were categorized into four groups according to changes in proteinuria over 3 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1+). Cox-proportional hazard model was used in assessing the adjusted hazard ratios (HR) and 95% confidence interval (CI) for incidence of retinopathy, and neuropathy (adjusted HR [95% CI]).
RESULT
In all of DM patients, risk for comprehensive incidence of retinopathy and neuropathy increased in all types of proteinuria changes. In type 1 DM, HR for retinopathy and neuropathy generally increased in order of negative (reference), resolved (2.175 [1.150-4.114] and 1.335 [0.909-1.961]), incident (2.088 [1.185-3.680] and 1.753 [1.275-2.409]), and persistent proteinuria (1.314 [0.418-4.134] and 2.098 [1.274-3.455]). This pattern of relationship was similarly observed in type 2 DM for retinopathy and neuropathy: negative (reference), resolved (1.490 [1.082-2.051] and 1.164 [0.988-1.371]), incident (1.570 [1.161-2.123] and 1.291 [1.112-1.500]), and persistent proteinuria (2.309 [1.407-3.788] and 1.272 [0.945-1.712]).
CONCLUSION
Risk for diabetic retinopathy and neuropathy generally increased in order of negative, resolved, incident, and persistent proteinuria. Once manifested proteinuria was associated with the increased risk of diabetic retinopathy and neuropathy even after remission of proteinuria.
PubMed: 38907116
DOI: 10.1007/s12020-024-03928-8 -
Nefrologia Jun 2024There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the...
BACKGROUND
There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the expression of C4d in FSGS subtypes in percutaneous native renal biopsies in a second-level hospital and its correlation with clinical, biochemical and histological variables.
MATERIAL AND METHODS
A retrospective study in paraffin blocks of patients with biopsy with FSGS aged 16-65 years, indistinct sex, not diabetic or obese. Immunohistochemistry was performed for C4d and their expression was analyzing in non-sclerosed glomerular capillaries (GC) and sclerosis areas (SA). Clinical and biochemical variables were recorded. The cases were divided into C4d positive and C4d negative groups and compared. The correlation between C4d staining scores in CG and SA with clinical and biochemical variables were analyzed.
RESULTS
Twenty samples were analyzed, 4 for each subtype. At the time of biopsy average age 38.8 ± 18.6 years, 65% male, 8.7% were hypertension. The percentage of positivity for C4d was 40% in GC, 30% SA and 35% in mesangium. The highest expression was for cellular and collapsing subtypes. C4d positivity cases had increased proteinuria (p = 0.035). A significant correlation was found between percentage of C4d expression in CG with SA (p = 0.012) and SA with tubular atrophy and interstitial fibrosis (p < 0.05).
CONCLUSIONS
C4d expression in FSGS predominated in the cellular and collapsing subtypes, which translates complement activation. C4d is a possible surrogate marker in GSFS.
PubMed: 38906767
DOI: 10.1016/j.nefroe.2023.04.007 -
International Urology and Nephrology Jun 2024Renal involvement in Crohn's Disease (CD) was rare in the population. Little was known between IgA nephropathy and CD. This study aimed to investigate the differences in...
BACKGROUND AND AIM
Renal involvement in Crohn's Disease (CD) was rare in the population. Little was known between IgA nephropathy and CD. This study aimed to investigate the differences in clinical and outcome features of CD-associated IgA nephropathy (CD-IgAN) and primary IgA nephropathy (PIgAN).
METHODS
Clinical data of patients diagnosed with IgAN by kidney biopsy were collected in the Sixth Affiliated Hospital of Sun Yat-sen University from January 1st, 2016 to June 1st, 2023. 17 patients with CD-IgAN and 87 patients with PIgAN were enrolled in this retrospective study.
RESULTS
Compared with PIgAN patients, CD-IgAN patients had lower levels of urinary protein excretion (1.57 g per 24 h vs. 0.33 g per 24 h, p < 0.01), but higher levels of estimated glomerular filtration rate (77.63 ± 40.11 ml per min per 1.73m vs. 104.53 ± 32.97 ml per min per 1.73m, p = 0.008). From the point of renal pathology of PIgAN, patients with CD-IgAN had a less incidence of tubular atrophy or interstitial fibrosis (p = 0.001). CD-IgAN patients had a higher incidence of complete remission of proteinuria (45.8% vs. 81.8%, p = 0.031) or hematuria (10.4% vs. 45.4%, p = 0.019) than PIgAN patients after twelve-month treatments.
CONCLUSIONS
CD-IgAN manifests a milder progression of renal function than those PIgAN. After the treatment, proteinuria or hematuria are more prone to remit in patients with CD-IgAN.
PubMed: 38904865
DOI: 10.1007/s11255-024-04106-5 -
Current Aging Science 2024Sarcopenia is one of the most common geriatric syndromes in the elderly. It is defined as a decrease in muscle mass and function, and it can lead to physical disability,... (Review)
Review
Sarcopenia is one of the most common geriatric syndromes in the elderly. It is defined as a decrease in muscle mass and function, and it can lead to physical disability, falls, poor quality of life, impaired immune system, and death. It is known that, the frequency of sarcopenia increases in the kidney patient population compared to healthy individuals. Although it is known that kidney disease can lead to sarcopenia; our knowledge of whether sarcopenia causes kidney disease is limited. Prior studies have suggested that protein energy wasting may be a risk of de novo CKD. Proteinuria is an important manifestation of kidney disease and there is a relationship between sarcopenia and proteinuria in diabetes, geriatric population, kidney transplant, and nephrotic syndrome. Does proteinuria cause sarcopenia or ? Are they both the results of common mechanisms? This issue is not clearly known. In this review, we examined the relationship between sarcopenia and proteinuria in the light of other studies.
Topics: Humans; Sarcopenia; Proteinuria; Aged; Aging; Risk Factors; Muscle, Skeletal; Age Factors
PubMed: 38904152
DOI: 10.2174/0118746098232969231106091204 -
Frontiers in Medicine 2024Fabry disease (FD) is an X-linked disorder resulting in a deficiency of α-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD...
Fabry disease (FD) is an X-linked disorder resulting in a deficiency of α-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD patients, characterized by a late-onset phenotype, almost normal to mild lyso-Gb3 elevation, and mild clinical symptoms, despite low GLA activity. This is due to the structural features of the R112H GLA protein. We herein report the case of a 42-year-old male patient with late-onset FD with a R112H mutation. The patient exhibited only renal involvement with no other organ damage and was successfully treated with galactosidase beta and subsequent migalastat for approximately 10 years. Especially, migalastat was clinically effective in normalizing plasma lyso-Gb3 levels and inhibiting the progression of renal damage associated with FD. Therefore, the use of migalastat in the FD patients with R112H mutation is highly recommended based on this case report.
PubMed: 38903807
DOI: 10.3389/fmed.2024.1383309 -
BMC Public Health Jun 2024Anaemia among preeclamptic (PE) women is a major undefined health issue in Bangladesh. This study explored the risk factors associated with anaemia and mapped the...
BACKGROUND
Anaemia among preeclamptic (PE) women is a major undefined health issue in Bangladesh. This study explored the risk factors associated with anaemia and mapped the regional influences to understand the geographical inequalities.
METHODS
Data from 180 respondents were prospectively collected from the Preeclampsia ward of Dhaka Medical College Hospital (DMCH), Bangladesh. Anaemia was defined as a blood haemoglobin level less than 11.0 g/dl. Preeclampsia was defined as systolic blood pressure (SBP) ≥ 140 mmHg and diastolic blood pressure (DBP) ≥ 90 mmHg with proteinuria. Factors associated with anaemia were explored using the chi-square test. Logistic regression (LR) was done to determine the level of association with the risk factors.
RESULTS
Among the participants, 28.9% were identified as having early onset and 71.1% reported late onset of PE. 38.9% of the subjects were non-anaemic, whereas mild, moderate, and severe anaemia was found among 38.3%, 17.8%, and 5% of patients respectively. The following factors were identified; including age range 25-34 (OR: 0.169, p < 0.05), a lower education level (OR: 3.106, p < 0.05), service-holder mothers (OR: 0.604, p < 0.05), pregnancy interval of less than 24 months (OR: 4.646, p < 0.05), and gestational diabetes mellitus (OR: 2.702, p < 0.05). Dhaka district (IR: 1.46), Narayanganj district (IR: 1.11), and Munshiganj district (IR: 0.96) had the highest incidence rates.
CONCLUSION
Determinants of anaemia must be considered with importance. In the future, periodic follow-ups of anaemia should be scheduled with a health care program and prevent maternal fatality and fetus morbidity in patients with PE.
Topics: Humans; Female; Bangladesh; Anemia; Pregnancy; Pre-Eclampsia; Adult; Cross-Sectional Studies; Risk Factors; Young Adult; Health Status Disparities; Socioeconomic Factors; Prospective Studies
PubMed: 38902634
DOI: 10.1186/s12889-024-18176-8 -
Nutrition & Diabetes Jun 2024Dietary-resistant starch is emerging as a potential therapeutic tool to limit the negative effects of diabetes on the kidneys. However, its metabolic and...
BACKGROUND
Dietary-resistant starch is emerging as a potential therapeutic tool to limit the negative effects of diabetes on the kidneys. However, its metabolic and immunomodulatory effects have not yet been fully elucidated.
METHODS
Six-week-old db/db mice were fed a diet containing 12.5% resistant starch or a control diet matched for equivalent regular starch for 10 weeks. db/m mice receiving the control diet were utilised as non-diabetic controls. Freshly collected kidneys were digested for flow cytometry analysis of immune cell populations. Kidney injury was determined by measuring albuminuria, histology, and immunohistochemistry. Portal vein plasma was collected for targeted analysis of microbially-derived metabolites. Intestinal histology and tight junction protein expression were assessed.
RESULTS
Resistant starch limited the development of albuminuria in db/db mice. Diabetic db/db mice displayed a decline in portal vein plasma levels of acetate, propionate, and butyrate, which was increased with resistant starch supplementation. Diabetic db/db mice receiving resistant starch had a microbially-derived metabolite profile similar to that of non-diabetic db/m mice. The intestinal permeability markers lipopolysaccharide and lipopolysaccharide binding protein were increased in db/db mice consuming the control diet, which was not seen in db/db mice receiving resistant starch supplementation. Diabetes was associated with an increase in the kidney neutrophil population, neutrophil activation, number of C5aR1+ neutrophils, and urinary complement C5a excretion, all of which were reduced with resistant starch. These pro-inflammatory changes appear independent of fibrotic changes in the kidney.
CONCLUSIONS
Resistant starch supplementation in diabetes promotes beneficial circulating microbially-derived metabolites and improves intestinal permeability, accompanied by a modulation in the inflammatory profile of the kidney including neutrophil infiltration, complement activation, and albuminuria. These findings indicate that resistant starch can regulate immune and inflammatory responses in the kidney and support the therapeutic potential of resistant starch supplementation in diabetes on kidney health.
Topics: Animals; Mice; Kidney; Albuminuria; Male; Neutrophil Infiltration; Diabetic Nephropathies; Resistant Starch; Gastrointestinal Microbiome; Starch; Diabetes Mellitus, Experimental; Mice, Inbred C57BL
PubMed: 38902253
DOI: 10.1038/s41387-024-00305-2 -
The British Journal of General Practice... Jun 2024In the UK, chronic kidney disease (CKD) is a prevalent, silent and strong predictor of cardiovascular disease. Identification of CKD is poor in primary care,...
BACKGROUND
In the UK, chronic kidney disease (CKD) is a prevalent, silent and strong predictor of cardiovascular disease. Identification of CKD is poor in primary care, particularly in minority ethnic and socio-economically deprived groups.
AIM
To investigate feasibility of remote ACR testing to improve the detection and management of CKD in underserved groups.
METHOD
13 591 tests were sent out across South East London. Individuals with diabetes and no ACR in the past year were offered a remote ACR test to complete at home with a smartphone using a validated app (Healthy.io). We extracted data on demographics, medical comorbidities and medication. Analyses (Stata) describe who completed the test.
RESULTS
Twenty-seven practices agreed to participate. Analyses of 6082 tests sent show the test completion rate was 46.8%. Adjusted odds ratios demonstrated that people were less likely to complete testing if over 70 years (OR 0.71, 95% CI 0.57 to 0.89) and over 80 (OR 0.43, CI 95% 0.33 to 0.56) compared to <40 years old; people from CORE20 groups (most deprived quintile) were also less likely to complete testing (OR 0.68, 95% CI 0.61 to 0.76) and those with missing data and those with no recorded healthcare interactions within the last 5 years were also less likely to complete testing.
DISCUSSION
Remote ACR testing presents an opportunity to diagnose early CKD but there is still inequity in who completes testing. Engagement with stakeholders is needed to explore innovative ways to implement remote ACR testing to achieve equitable CKD screening.
Topics: Humans; Renal Insufficiency, Chronic; Quality Improvement; Primary Health Care; Male; Female; Middle Aged; Aged; Adult; London; Feasibility Studies; Healthcare Disparities; Albuminuria; Aged, 80 and over
PubMed: 38902069
DOI: 10.3399/bjgp24X737997 -
Biomedical Journal Jun 2024The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides...
BACKGROUND
The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides derived from the medicinal fungus Hirsutella sinensis produced anti-inflammatory, anti-diabetic and anti-obesity effects by modulating the gut microbiota and increasing the abundance of the commensal Parabacteroides goldsteinii in mice fed with a high-fat diet.
METHODS
We examined the effects of the prebiotics, H. sinensis polysaccharides, and probiotic, P. goldsteinii, in a mouse model of imiquimod-induced systemic lupus erythematosus.
RESULTS
The fungal polysaccharides and P. goldsteinii reduced markers of lupus severity, including the increase of spleen weight, proteinuria, and serum levels of anti-DNA auto-antibodies and signal transducer and activator of transcription 4 (STAT4). Moreover, the polysaccharides and P. goldsteinii improved markers of kidney and liver functions such as creatinine, blood urea nitrogen, glomerulus damage and fibrosis, and serum liver enzymes. However, the prebiotics and probiotics did not influence gut microbiota composition, colonic histology, or expression of tight junction proteins in colon tissues.
CONCLUSIONS
Our results indicate that H. sinensis polysaccharides and the probiotic P. goldsteinii can reduce lupus markers in imiquimod-treated mice. These prebiotics and probiotics may therefore be added to other interventions conducive of a healthy lifestyle in order to counter autoimmune diseases.
PubMed: 38901796
DOI: 10.1016/j.bj.2024.100754 -
Kidney & Blood Pressure Research Jun 2024The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient...
INTRODUCTION
The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient outcomes. While SIRT2 is implicated in diabetes pathogenesis, its correlation with diabetic nephropathy remains unexplored. This study was designed to evaluate the association of circulating and urine SIRT2 levels with diabetic kidney injury, as well as potential underlying mechanisms.
METHODS
In T2DM patients, db/db mice, and high-glucose plus palmitic acid treated HK-2 cell models, ELISA, immunoturbidimetry, immunohistochemistry, western blot and RT-qPCR were used to detect SIRT2 levels and kidneys damage. According to urinary albumin/creatinine ratio (UACR), 163 T2DM patients were divided into three groups. Spearman correlation analysis was used to investigate the relationship between urinary sirtuin2/creatinine ratio (USCR) and biomarkers of kidney injury. The influencing factors of proteinuria in T2DM patients were analyzed by Logistic regression model.
RESULTS
In our findings, the Macro group exhibited the highest USCR levels as UACR increased. There was a positive association between USCR and UACR, α1-microglobulin/creatinine ratio (UαCR), β2-microglobulin/creatinine ratio (UβCR), and retinol-binding protein/creatinine ratio (URCR), with a negative correlation observed with eGFR. Logistic ordered multiclassification regression analysis, adjusting for confounding variables, confirmed that USCR remained a significant risk factor for the severity of proteinuria in T2DM patients. In the kidney tissue of db/db mice, increased KIM-1 levels were associated with increased SIRT2 levels. Increased SIRT2 protein levels were also observed in renal tubular epithelial cells treated with high-glucose plus palmitic acid. Moreover, SIRT2 promotes the expression of pro-inflammatory factors TNF-α and IL-6 by modulating the phosphorylation of p38 MAPK and pJNK in renal tubular cells induced by high glucose and palmitic acid.
CONCLUSION
Urinary SIRT2 is closely related to eGFR, renal tubule injury and urinary albumin excretion in T2DM patients, which is expected to be an important indicator to comprehensively reflect renal injury.
PubMed: 38901411
DOI: 10.1159/000539886