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Biochemia Medica Jun 2024Diabetic kidney disease (DKD) is one of the major microvascular complications of type 1 diabetes mellitus (T1DM). Some studies suggest that changes of renal tubular...
INTRODUCTION
Diabetic kidney disease (DKD) is one of the major microvascular complications of type 1 diabetes mellitus (T1DM). Some studies suggest that changes of renal tubular components emerge before the glomerular lesions thus introducing the concept of diabetic tubulopathy with urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a potential marker of DKD. This concept was not confirmed in all studies.
MATERIALS AND METHODS
In 198 T1DM patients with median age 15 years and diabetes duration over one year, an albumin/creatinine ratio (ACR) was determined and uNGAL measured in spot urine sample. Urine samples for ACR and uNGAL were also collected in the control group of 100 healthy children of similar age.
RESULTS
There was no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects (6.9 (2.8-20.1) ng/mL 7.9 (2.9-21.0) ng/mL, P = 0.969 and 6.8 (2.2-18.4) ng/mg 6.5 (1.9-13.4) ng/mg, P = 0.448, respectively) or between T1DM subjects with albuminuria A2 and albuminuria A1 (P = 0.573 and 0.595, respectively). Among T1DM patients 168 (85%) had normal uNGAL concentrations, while in 30 (15%) patients uNGAL was above the defined cut-off value of 30.9 ng/mL. There was no difference in BMI, HbA1c and diabetes duration between patients with elevated uNGAL compared to those with normal uNGAL.
CONCLUSIONS
We found no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects or between albuminuria A2 and albuminuria A1 T1DM subjects. Therefore, uNGAL should not be recommended as a single marker for detecting diabetic kidney disease in children and adolescents.
Topics: Humans; Diabetes Mellitus, Type 1; Adolescent; Female; Male; Lipocalin-2; Child; Diabetic Nephropathies; Biomarkers; Creatinine; Albuminuria; Case-Control Studies
PubMed: 38882580
DOI: 10.11613/BM.2024.020709 -
Experimental Biology and Medicine... 2024Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD)...
Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD) proteins to the actin cytoskeleton. Previous studies have shown that the expression of ZO-1 is decreased in chronic kidney disease (CKD). Thus, elucidation of the regulation mechanism of ZO-1 has considerable clinical importance. Triptolide (TP) has been reported to exert a strong antiproteinuric effect by inhibiting podocyte epithelial mesenchymal transition (EMT) and inflammatory response. However, the underlying mechanisms are still unclear. We found that TP upregulates ZO-1 expression and increases the fluorescence intensity of ZO-1 in a puromycin aminonucleoside (PAN)-induced podocyte injury model. Permeablity assay showed TP decreases podocyte permeability in PAN-treated podocyte. TP also upregulates the DNA demethylase TET2. Our results showed that treatment with the DNA methyltransferase inhibitors 5-azacytidine (5-AzaC) and RG108 significantly increased ZO-1 expression in PAN-treated podocytes. Methylated DNA immunoprecipitation (MeDIP) and hydroxymethylated DNA immunoprecipitation (hMeDIP) results showed that TP regulates the methylation status of the ZO-1 promoter. Knockdown of TET2 decreased ZO-1 expression and increased methylation of its promoter, resulting in the increase of podocyte permeability. Altogether, these results indicate that TP upregulates the expression of ZO-1 and decreases podocyte permeability through TET2-mediated 5 mC demethylation. These findings suggest that TP may alleviate podocyte permeability through TET2-mediated hydroxymethylation of ZO-1.
Topics: Podocytes; Zonula Occludens-1 Protein; Phenanthrenes; Diterpenes; Epoxy Compounds; Dioxygenases; Animals; DNA-Binding Proteins; Mice; Proto-Oncogene Proteins; Permeability; Humans; DNA Methylation
PubMed: 38881848
DOI: 10.3389/ebm.2024.10051 -
The Journal of the Association of... Jun 2024Metabolic syndrome (MetS) is one of the most important emerging pandemics of the 21st century and is associated with renal dysfunction in a significant number of... (Observational Study)
Observational Study
INTRODUCTION
Metabolic syndrome (MetS) is one of the most important emerging pandemics of the 21st century and is associated with renal dysfunction in a significant number of subjects, the association of which is shown to be of greater significance in the South Asian population.
AIMS AND OBJECTIVES
The prevalence of renal dysfunction in patients with MetS is the primary outcome. The secondary outcome is to assess the strength and significance of the association between the individual components of MetS and the presence of renal dysfunction.
MATERIALS AND METHODS
This is a hospital-based cross-sectional observational study conducted for 2 years in a tertiary care hospital in India. A total of 100 diagnosed subjects of MetS were taken as cases and underwent relevant blood tests. Data were collected and analyzed in a Statistical Package for the Social Sciences (SPSS) v29 sheet.
RESULTS
Over a period of 18 months, 100 subjects with MetS were documented, among which 66% had albuminuria, with microalbuminuria being 24% and the rest being macroalbuminuria. Among the same subjects, 30% had an estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73m. Waist circumference (WC) [measured by the National Institutes of Health (NIH) protocol] had the strongest association with increased albuminuria ( = 0.540; -value < 0.001) as well as reduced eGFR ( = 0.460; -value < 0.001).
CONCLUSION
All the components of MetS, for example, increased WC, hypertension, increased fasting glucose, raised triglyceride (TG), and low high-density lipoprotein (HDL), have statistically significant correlations with increased urine albumin-to-creatinine ratio (ACR) and decreased eGFR, signifying glomerular injury and renal dysfunction, respectively.
Topics: Humans; Metabolic Syndrome; Cross-Sectional Studies; Female; Prevalence; Male; Middle Aged; Glomerular Filtration Rate; India; Adult; Albuminuria; Waist Circumference
PubMed: 38881129
DOI: 10.59556/japi.72.0565 -
The Journal of the Association of... Jun 2024The modified Ponticelli regimen (mPR) is a first-line therapy in patients with idiopathic membranous nephropathy (IMN); however, it has a less favorable safety profile.... (Randomized Controlled Trial)
Randomized Controlled Trial
Mycophenolate Mofetil with Steroid, a Reasonable Alternative to Current First-line Therapy, for Idiopathic Membranous Nephropathy in Resource-constrained Settings: A Randomized, Open-label Study.
BACKGROUND
The modified Ponticelli regimen (mPR) is a first-line therapy in patients with idiopathic membranous nephropathy (IMN); however, it has a less favorable safety profile. Though mycophenolate mofetil (MMF) + steroid (S) is not recommended by Kidney Disease Improving Global Outcomes guidelines, it can be used as an alternative to mPR due to higher tolerability and steroid-sparing effect. Thus, we compared the safety and effectiveness of MMF + S and mPR regimens in patients with IMN.
METHODS
This randomized, open-label study enrolled patients with adult-onset nephrotic syndrome (NS) and biopsy-proven IMN. Forty-two patients were allocated to MMF + S group (MMF 1 gm twice daily + oral prednisolone 0.5 mg/kg/day; = 21) and mPR group [methylprednisolone (1 gm intravenous) for 3 days followed by alternating monthly cycles of oral prednisolone (0.5 mg/kg/day) for the next 27 days and cyclophosphamide (2 mg/kg/day) for 6 months; = 21]. The primary outcome measure was change in urinary protein creatinine ratio (UPCR).
RESULTS
At 6 months, both groups demonstrated a significant increase in serum albumin levels and estimated glomerular filtration rate (eGFR) (both -values <0.0001) as well as a decrease in 24-hour proteinuria (MMF + S group: -value = 0.003, and mPR group: -value <0.0001) and UPCR (both -values <0.0001). However, the groups did not differ in any of these parameters at any of the monthly follow-up visits. Moreover, the groups did not differ significantly in terms of the composite remission rates (61.91% for MMF + S group and 71.43% for mPR group).
CONCLUSION
MMF + S and mPR had comparable tolerability and effectiveness, with MMF-associated advantage of reduced steroid exposure.
Topics: Humans; Glomerulonephritis, Membranous; Mycophenolic Acid; Male; Female; Adult; Immunosuppressive Agents; Drug Therapy, Combination; Prednisolone; Middle Aged; Glucocorticoids; Cyclophosphamide; Methylprednisolone; Treatment Outcome
PubMed: 38881128
DOI: 10.59556/japi.72.0558 -
The Journal of the Association of... May 2024Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease, leading to chronic kidney disease. The disease is characterized by microscopic hematuria,...
Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease, leading to chronic kidney disease. The disease is characterized by microscopic hematuria, gross episodic hematuria, hypertension, and subnephrotic proteinuria with or without renal function impairment. It affects individuals of all age groups, commonly seen in 10-40 years of age. It is progressive in nature and leads to chronic kidney disease, necessitating renal replacement therapy. This case series of in a tertiary care hospital in Western India highlights the presentation of this disease in young adults, its aggressive course, its rapid progression, and its early recurrence in the posttransplant period. It also summarizes the treatment recommendations for IgA recurrence in kidney recipients. The disease is known to have a high chance of posttransplant recurrence. Optimizing renin-angiotensin-aldosterone system (RAAS) blockade, blood pressure control, and increasing immunosuppression in rapidly deteriorating cases are the strategies recommended to treat IgA recurrence in kidney transplant recipients.
Topics: Humans; Glomerulonephritis, IGA; Kidney Transplantation; Recurrence; Male; Adult; Renal Insufficiency, Chronic; Female; Young Adult
PubMed: 38881117
DOI: 10.59556/japi.72.0525 -
Clinical Journal of Gastroenterology Jun 2024Secondary amyloidosis (AA) is a disorder of protein conformation associated with inflammatory disorders. Detailed reports of patients diagnosed with AA and inflammatory...
Secondary amyloidosis (AA) is a disorder of protein conformation associated with inflammatory disorders. Detailed reports of patients diagnosed with AA and inflammatory bowel disease (IBD) are limited. This study reports the cases of eight patients, across three tertiary medical centers, diagnosed with both IBD and AA between 2000 and 2020. Seven patients had a diagnosis of Crohn disease (CD), while one had ulcerative colitis (UC). All patients were diagnosed with AA after being diagnosed with IBD (median: 15 years later). The small bowel (62.5%) and the colon (62.5%) were the most common IBD locations. 4 patients had undergone TNF-alpha inhibitor therapy and all CD patients required surgical treatment of their IBD. A history of fistula or abscess was identified in 5 patients. The most common initial site of AA was the kidney (75%). All 8 patients presented with some form of renal dysfunction and proteinuria (median: 1500 mg/24 h). Hypoalbuminemia was found in most patients. Six patients developed chronic kidney disease and 4 required dialysis. Anti TNF-alpha antibody therapy led to rapid improvement of renal function in one of four patients who received it. Three patients required a renal transplant. Four patients had died upon the latest follow-up (5-year survival: 75%). The presence of proteinuria, fistula, or abscess should serve as indicators for potentially increased AA risk in CD patients.
PubMed: 38880849
DOI: 10.1007/s12328-024-02003-z -
Methods in Cell Biology 2024Renal injury often occurs as a complication in autoimmune diseases such as systemic lupus erythematosus (SLE). It is estimated that a minimum of 20% SLE patients develop...
Renal injury often occurs as a complication in autoimmune diseases such as systemic lupus erythematosus (SLE). It is estimated that a minimum of 20% SLE patients develop lupus nephritis, a condition that can be fatal when the pathology progresses to end-stage renal disease. Studies in animal models showed that incidence of immune cell infiltrates in the kidney was linked to pathological injury and correlated with severe lupus nephritis. Thus, preventing immune cell infiltration into the kidney is a potential approach to impede the progression to an end-stage disease. A requirement to investigate the role of kidney-infiltrating leukocytes is the development of reproducible and efficient protocols for purification and characterization of immune cells in kidney samples. This chapter describes a detailed methodology that discriminates tissue-resident leukocytes from blood-circulating cells that are found in kidney. Our protocol was designed to maximize cell viability and to reduce variability among samples, with a combination of intravascular staining and magnetic bead separation for leukocyte enrichment. Experiments included as example were performed with FcγRIIb[KO] mice, a well-characterized murine model of SLE. We identified T cells and macrophages as the primary leukocyte subsets infiltrating into the kidney during severe nephritis, and we extensively characterized them phenotypically by flow cytometry.
Topics: Animals; Lupus Nephritis; Mice; Disease Models, Animal; Kidney; Leukocytes; Cell Separation; Mice, Knockout; Macrophages; Flow Cytometry; T-Lymphocytes; Receptors, IgG
PubMed: 38880521
DOI: 10.1016/bs.mcb.2024.03.007 -
Journal of Stroke and Cerebrovascular... Jun 2024Alport syndrome is a genetic disorder caused by mutations in the COL4A5 gene, which encodes type IV collagen α5 chain, leading to chronic nephritis, hearing loss, and...
BACKGROUND
Alport syndrome is a genetic disorder caused by mutations in the COL4A5 gene, which encodes type IV collagen α5 chain, leading to chronic nephritis, hearing loss, and ocular abnormalities. Recent reports suggest this genetic mutation may also increase the risk of cerebral aneurysms and fibromuscular dysplasia, indicating a potential association with vascular vulnerability.
CASE PRESENTATION
A 66-year-old woman was admitted with recurrent transient weakness of the left hand, which had gradually worsened in duration over three months. Her medical history included chronic nephritis since childhood. Her two sons had end-stage renal disease and hearing loss since their 20s, and her mother also had chronic kidney disease and hearing loss. One son had a history of traumatic subarachnoid hemorrhage, and the other had spinal epidural hematoma. On admission, she had reduced renal function with proteinuria, acute cerebral infarction in the subcortical white matter of the right fronto-parietal and parieto-occipital lobes, and multiple intracranial arterial stenoses (ICAS), including the right middle and right posterior cerebral artery. Vessel wall imaging of the right middle cerebral artery showed a concentric stenotic pattern. Genetic tests identified a pathogenic missense mutation in exon 24 of COL4A5 (exon 24:c.G1700 >C: p.(Gly567Arg)) that was heterozygous for the patient and hemizygous for her son. She was diagnosed with Alport syndrome.
CONCLUSION
It is important to consider Alport syndrome as a possible cause of ICAS in patients with a family history of renal failure or hearing loss and to conduct a genetic analysis of type IV collagen genes. (249/250 words).
PubMed: 38880363
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107816 -
Clinical and Experimental Nephrology Jun 2024Although vaccination has been reported to reduce the morbidity and severity of COVID-19 infection in patients with kidney disease, gross hematuria is frequently reported...
BACKGROUND
Although vaccination has been reported to reduce the morbidity and severity of COVID-19 infection in patients with kidney disease, gross hematuria is frequently reported following vaccination in patients with IgA nephropathy. We investigated the frequency of gross hematuria following COVID-19 vaccination and its effect on renal function in IgA nephropathy patients.
METHODS
Adverse reactions after two or more COVID-19 vaccine doses were investigated in 295 IgA nephropathy patients attending Osaka Cty general hospital from September 2021 to November 2022. We compared differences in background characteristics and other adverse reactions between groups with and without gross hematuria after vaccination, and examined changes in renal function and proteinuria.
RESULTS
Twenty-eight patients (9.5%) had gross hematuria. The median age of patients with and without gross hematuria was 44 (29-48) and 49 (42-61) years, respectively, indicating a significant difference. The percentage of patients with microscopic hematuria before vaccination differed significantly between those with (65.2%) and without (32%) gross hematuria. Adverse reactions, such as fever, chills, headache and arthralgia, were more frequent in patients with gross hematuria. There was no difference in renal functional decline after approximately 1 year between patients with and without gross hematuria. We also found no significant changes in estimated glomerular filtration rate or proteinuria before and after vaccination in the gross hematuria group. However, some patients clearly had worsening of renal function.
CONCLUSIONS
While COVID-19 vaccination is beneficial, care is required since it might adversely affect renal function in some patients.
PubMed: 38879735
DOI: 10.1007/s10157-024-02521-7 -
Clinical Immunology (Orlando, Fla.) Jun 2024Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to...
Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFβ and C5b-9, in nephrotoxic nephritis (NTN), an experimental model that mimics human lupus nephritis. Proteinuria, loss of renal function and kidney histopathology were attenuated in RGC-32 KO NTN mice. RGC-32 KO NTN mice displayed downregulation of the CCL20/CCR6 and CXCL9/CXCR3 ligand/receptor pairs resulting in decreased renal recruitment of IL-17 and IFNγ cells and subsequent decrease in the influx of innate immune cells. RGC-32 deficiency attenuated renal fibrosis as demonstrated by decreased deposition of collagen I, III and fibronectin. Thus, RGC-32 is a unique mediator shared by the Th17 and Th1 dependent proinflammatory and profibrotic pathways and a potential novel therapeutic target in the treatment of immune complex mediated glomerulonephritis such as lupus nephritis.
PubMed: 38878807
DOI: 10.1016/j.clim.2024.110279