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Frontiers in Pediatrics 2024To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA).
OBJECTIVES
To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA).
METHODS
A total of 40 pediatric patients, 20 (50%) with JIA and 20 (50%) healthy control subjects, were studied, and performed the renal function on 24-h collection and the 24-h ambulatory blood pressure monitoring (ABPM). Moreover, we compared renal function and blood pressure trends between the groups of JIA patients with different disease activities.
RESULTS
No statistically significant differences were observed between patients with JIA and healthy children in terms of glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tubular reabsorption of phosphate (TRP), and calcium-creatinine urine ratio (CaU/CrU). In contrast, we observed significantly higher values in JIA patients than in controls for the presence of hematuria ( < 0.0001) and proteinuria ( < 0.0001). Compared to the control group there were significantly higher values of hematuria and proteinuria/day in both groups of JIA patients with low disease activity (respectively, = 0.0001 and = 0.0002) and moderate disease activity (respectively = 0.0001 and = 0.0012). Systolic and diastolic dipping were significantly reduced in patients with JIA compared with healthy controls ( < 0.0001 and < 0.0001, respectively).
CONCLUSIONS
Our study showed that children with JIA, already in the early stages of the disease, have higher values of hematuria and proteinuria, which are early warning signs of nephropathy. Therefore, detailed screening of renal function and pressure monitoring in patients are necessary to monitor their evolution over time.
PubMed: 38895193
DOI: 10.3389/fped.2024.1395961 -
Nutrients May 2024Low protein diet (LPD) seems beneficial in ameliorating the complications of chronic kidney disease (CKD), in reducing proteinuria and the decline in kidney function,...
Low protein diet (LPD) seems beneficial in ameliorating the complications of chronic kidney disease (CKD), in reducing proteinuria and the decline in kidney function, thus postponing the need for kidney replacement therapy (KRT). However, this type of intervention was less investigated in diabetic kidney disease (DKD). This is a single-center, prospective, interventional study that aims to assess the efficacy of reducing proteinuria and the rate of decline in the estimated glomerular filtration rate (eGFR). Patients with advanced DKD (stable proteinuria > 3 g/g and eGFR < 30 mL/min) with a good nutritional status and accepting a LPD were evaluated for inclusion. Ninety-two of the 452 screened patients (66% males, median age 61 years, proteinuria 4.8 g/g creatininuria, eGFR 11.7 mL/min/1.73 m) completed the study. Intervention consisted of LPD supplemented with ketoanalogues of essential amino acids (KA) along with conventional nephroprotective therapy. Efficacy parameters were the variation in proteinuria and in eGFR from baseline to the end of the study. Proteinuria decreased 3-fold, and the rate of decline in eGFR decreased 5-fold in the intervention phase. No patient initiated KRT or died. LPD supplemented with KA seems effective in safely postponing KRT by reducing proteinuria and the decline in kidney function in advanced DKD.
Topics: Humans; Male; Proteinuria; Glomerular Filtration Rate; Middle Aged; Diet, Protein-Restricted; Diabetic Nephropathies; Female; Prospective Studies; Aged; Amino Acids, Essential; Treatment Outcome
PubMed: 38892620
DOI: 10.3390/nu16111687 -
International Journal of Molecular... May 2024Pathogenic variants in the gene lead to a systemic disease with karyomegalic interstitial nephritis (KIN) at the forefront clinically. The phenotypic-genotypic features...
Pathogenic variants in the gene lead to a systemic disease with karyomegalic interstitial nephritis (KIN) at the forefront clinically. The phenotypic-genotypic features of a mutation-related disease involving five members of a Hungarian Caucasian family are presented. Each had adult-onset chronic kidney disease of unknown cause treated with renal replacement therapy and elevated liver enzymes. Short stature, emaciation, latte-colored skin, freckles, and a hawk-like nose in four patients, a limited intellect in two patients, and chronic restrictive lung disease in one patient completed the phenotype. Severe infections occurred in four patients. All five patients had ceased. Four patients underwent autopsy. KIN and extrarenal karyomegaly were observed histologically; the livers showed no specific abnormality. The genotyping using formalin-fixed tissue samples detected a hitherto undescribed homozygous mutation (c.1673_1674insT/p.Met558lfs*4; exon 5) in three of these patients and a heterozygous mutation in one patient. The reason for the heterozygosity is discussed. In addition, 56 family members consented to the screening for mutation from which 17 individuals proved to be heterozygous carriers; a blood chemistry evaluation of their kidney and liver function did not find any abnormality. The clinical presentation of FAN1-related disease was multifaceted, and not yet described manifestations were observed besides kidney and liver disease. Mutation in this gene should be suspected in adults with small kidneys of unknown cause, elevated liver enzymes, and recurrent infections, even without a family history.
Topics: Humans; Male; Female; Hungary; Mutation; Adult; Phenotype; Pedigree; Middle Aged; Exodeoxyribonucleases; Multifunctional Enzymes; Endodeoxyribonucleases; Genotype; Renal Insufficiency, Chronic
PubMed: 38892095
DOI: 10.3390/ijms25115907 -
International Journal of Molecular... May 2024Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading...
Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.
Topics: MicroRNAs; Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 1; Male; Female; Adult; Middle Aged; Down-Regulation; Biomarkers; Albuminuria; Receptor, IGF Type 1; Glomerular Filtration Rate
PubMed: 38891851
DOI: 10.3390/ijms25115663 -
Advances in Rheumatology (London,... Jun 2024To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN).
OBJECTIVE
To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN).
METHODS
Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion.
RESULTS
All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy.
CONCLUSION
This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.
Topics: Lupus Nephritis; Humans; Immunosuppressive Agents; Brazil; Societies, Medical; Creatinine; Proteinuria; Mycophenolic Acid; Antibodies, Monoclonal, Humanized; Rheumatology; Rituximab; Biopsy; Cyclophosphamide; Leflunomide; Glucocorticoids; Hydroxychloroquine; Azathioprine; Remission Induction; Cyclosporine; Evidence-Based Medicine; Consensus; Disease Progression; Kidney Failure, Chronic; Randomized Controlled Trials as Topic
PubMed: 38890752
DOI: 10.1186/s42358-024-00386-8 -
Scientific Reports Jun 2024Proteinuria poses a substantial risk for the progression of chronic kidney disease (CKD) and its related complications. Kidneys excrete hundreds of individual proteins,...
Proteinuria poses a substantial risk for the progression of chronic kidney disease (CKD) and its related complications. Kidneys excrete hundreds of individual proteins, some with a potential impact on CKD progression or as a marker of the disease. However, the available data on specific urinary proteins and their relationship with CKD severity remain limited. Therefore, we aimed to investigate the urinary proteome and its association with kidney function in CKD patients and healthy controls. The proteomic analysis of urine samples showed CKD stage-specific differences in the number of detected proteins and the exponentially modified protein abundance index for total protein (p = 0.007). Notably, specific urinary proteins such as B2MG, FETUA, VTDB, and AMBP exhibited robust negative associations with kidney function in CKD patients compared to controls. Also, A1AG2, CD44, CD59, CERU, KNG1, LV39, OSTP, RNAS1, SH3L3, and UROM proteins showed positive associations with kidney function in the entire cohort, while LV39, A1BG, and CERU consistently displayed positive associations in patients compared to controls. This study suggests that specific urinary proteins, which were found to be negatively or positively associated with the kidney function of CKD patients, can serve as markers of dysfunctional or functional kidneys, respectively.
Topics: Humans; Renal Insufficiency, Chronic; Biomarkers; Male; Female; Proteomics; Middle Aged; Aged; Adult; Proteome; Proteinuria; Case-Control Studies
PubMed: 38890379
DOI: 10.1038/s41598-024-64833-8 -
Medicina Clinica Jun 2024Copper metabolism disorder disease is thought to contribute to renal symptoms in Wilson's disease (WD). Nonetheless, there remains limited knowledge regarding the...
OBJECTIVE
Copper metabolism disorder disease is thought to contribute to renal symptoms in Wilson's disease (WD). Nonetheless, there remains limited knowledge regarding the precise characteristics of renal damage in individuals with Wilson's disease, encompassing clinical presentations, biochemical indicators, imaging findings, and renal histopathological alterations.
METHODS
In this study, 20 patients diagnosed with Wilson's disease and renal involvement were enrolled in our hospital. These patients met the validated European criteria for Wilson's disease, and those with primary kidney disease or secondary renal damage caused by other underlying conditions were excluded. The baseline data of patients were collected. Various biochemical and hematological parameters were monitored. Biochemical examinations were measured using an automatic biochemistry analyzer, blood routines were tested by flow cytometry analysis, 24-h urine copper was tested by atomic absorption spectrophotometer. Besides, CER was measured by turbidimetric immunoassay with a Hitachi 7020 automatic biochemical analyzer (the intraplate and interplate coefficients of variation were 2.7% and 5.13% respectively). Copper oxidase was tested by colorimetric method using p-phenylenediamine hydrochloride (the intraplate and interplate coefficients of variation were both <10%). Diagnostic criteria for Wilson's disease and kidney damage were established based on the European Association for the Study of the Liver (EASL) and CKD Epidemiology Collaboration guidelines, respectively. Statistical analysis was carried out using t-tests and χ tests in SPSS 22.0 software. Significant differences were considered when P<0.05.
RESULTS
In those patients with Wilson's disease-related renal damage, edema, gross hematuria, oliguria, and lumbar pain were present in most patients. Microscopic haematuria and proteinuria were also observed in 19 patients. Compared to patients without renal involvement, those with renal complications exhibited a significant increase in white blood cell (WBC) and neutrophil counts (P<0.05). Additionally, patients with renal damage showed a noteworthy rise in both diastolic and systolic blood pressure, along with a significant reduction in hemoglobin levels (P<0.05). Color Doppler ultrasound results revealed diffuse lesions in both kidneys in 12 patients, renal cysts were identified in 5 patients, and 2 patients exhibited abnormal renal blood flow signals. Meanwhile, varying degrees of IgA, IgM, IgG-based immunoglobulins, complement C3 and C1q deposition in the glomerular mesangial area were detected by immunofluorescence. Furthermore, renal puncture biopsy results revealed a spectrum of findings, including minimal change nephrosis in 1 case, IgA nephropathy in 3 cases, atypical membranous proliferative nephropathy in 2 cases, and focal segmental glomerulosclerosis in 1 case.
CONCLUSION
This study comprehensively elucidates the distinct attributes of renal damage related to Wilson's disease, while also speculating that renal dysfunction in Wilson's disease could be linked to immune complex deposition. Depending on the underlying pathogenesis, kidney injury associated with Wilson's disease can be classified as primary or secondary. To slow down the progression of renal impairment, it is essential to undergo a renal biopsy pathological examination as early as possible to clarify the type of impairment and take the appropriate treatment.
PubMed: 38890098
DOI: 10.1016/j.medcli.2024.02.004 -
Veterinary and Comparative Oncology Jun 2024MAPK has been reported as a key oncogenic pathway for canine histiocytic sarcoma, which can be pharmacologically targeted with trametinib, a small inhibitor of MEK1/2....
MAPK has been reported as a key oncogenic pathway for canine histiocytic sarcoma, which can be pharmacologically targeted with trametinib, a small inhibitor of MEK1/2. Preliminary data showed promising antitumor activity in in vitro and in vivo models and represented a proof of concept to translate the findings from bench to bedside. In this phase I, dose escalating study using a 3 + 3 cohort design, trametinib was evaluated in 18 dogs with cancer. Adverse events were graded according to VCOG-CTCAE v2. Blood samples and tumour biopsies were collected for pharmacokinetic and pharmacodynamic assessment. Trametinib was well tolerated with a maximum tolerated dose of 0.5 mg/m/day, PO. Dose-limiting toxicities included systemic hypertension, proteinuria, lethargy and elevated ALP, and were all Grade 3. The drug exposures increased more than linearly with dose since the elimination of trametinib was saturable. At a dose of 500 μg Q24h (0.5 mg/m/day in a 30 kg dog), approximately 70% of dogs had an average steady-state concentration of 10 ng/mL, achieved after approximately 2 weeks. This threshold was associated with clinical efficacy in humans. Target engagement was not observed in biospecimens collected on Days 0 and 7. In conclusion, trametinib was considered safe in dogs with cancer, and the dose of 0.5 mg/m/day was the recommended dose for phase II studies.
PubMed: 38889903
DOI: 10.1111/vco.12989 -
BMC Pregnancy and Childbirth Jun 2024IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis, with complex pathogenic mechanisms involving abnormal B-cell activation. As a novel...
BACKGROUND
IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis, with complex pathogenic mechanisms involving abnormal B-cell activation. As a novel biologic agent, telitacicept inhibits both B-lymphocyte stimulating factor and a proliferation-inducing ligand. It also inhibits both B cells and plasma cells and the production of galactose-deficient IgA1 (Gd-IgA1) and its autoantibodies, thus exerting an immunosuppressive effect. Women with IgAN are at a higher risk of adverse pregnancy outcomes such as preeclampsia and miscarriage, especially those with uncontrolled massive proteinuria and advanced chronic kidney disease. Therefore, IgAN disease control before and during pregnancy is essential. Here, we report the case of a woman with IgAN who had a successful pregnancy with significant improvement and long-term remission after treatment with telitacicept. This is the first report of a pregnancy following exposure to telitacicept.
CONCLUSION
This report describes the efficacy of telitacicept in patients with IgAN and explores its value in women of childbearing age, suggesting effective and safe treatment options for women who wish to conceive.
Topics: Humans; Female; Glomerulonephritis, IGA; Pregnancy; Adult; Pregnancy Complications; Pregnancy Outcome
PubMed: 38886682
DOI: 10.1186/s12884-024-06632-7 -
Clinica Chimica Acta; International... Jun 2024Renin-angiotensin system inhibitors (RASi) treatment is the basic therapy for IgA nephropathy (IgAN) patients. However, there is few of biomarker that can predict the...
BACKGROUND
Renin-angiotensin system inhibitors (RASi) treatment is the basic therapy for IgA nephropathy (IgAN) patients. However, there is few of biomarker that can predict the efficacy of RASi. This study aimed to find urinary exosomal mRNAs related to the therapeutic effect of RASi in the treatment of proteinuria in IgAN patients.
METHODS
We divided IgAN patients in screening cohort into A1 (proteinuria increase at 3 months), B1 (proteinuria decrease less than 50 % at 3 months), C1 (proteinuria decrease more than 50 % at 3 months) groups according to changes of proteinuria after treatment. The urinary exosomes were collected before biopsy, RNAs were extracted and analyzed with the microarray assay. The candidate genes were screened by differentially expressed genes (DEGs) analysis and then validated by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort. A receiver operating characteristic (ROC) curve was used to evaluate gene performance in predicting therapeutic effect on RASi reducing proteinuria in IgAN patients.
RESULTS
ECE1 and PDE1A mRNAs were significantly different among the three groups, and were gradually decreased among A1, B1 and C1 groups. In the validation cohort, the level of urinary exosomal ECE1 and PDE1A mRNAs were also significantly lower in A2 group compared with C2 group(ECE1, P < 0.001;PDE1A, P < 0.01). Besides, the level of ECE1 mRNA was also lower in B2 group compared with C2 group (P < 0.01). The ROC curve verified that urinary exosomal ECE1 and PDE1A gene level predicted RASi efficacy in IgAN patients with area under curve (AUC) 0.68 and 0.63 respectively.
CONCLUSION
Urinary exosomal ECE1 and PDE1A mRNAs expression can serve as potential biomarkers for predicting the RASi efficacy to reduce proteinuria in IgAN patients.
PubMed: 38885756
DOI: 10.1016/j.cca.2024.119750