[Idiopathic membranous nephropathy with focal segmental sclerosis].

AIM: To evaluate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis (FSGS) in a group of Russian patients. MATERIALS AND METHODS: 101 patients with morphologically verified IMN were enrolled in our single-center cohort retrospective study. The patients were divided into IMN group and IMN+FSGS group. The primary and secondary outcomes were analyzed in 59 patients, which had follow-up data for period more than 6 months. RESULTS: At the time of renal biopsy the median age was 46.0 (33.0; 55.0) years and the median follow-up was 6.8 (4.0; 15.6) months. Secondary FSGS was revealed in 15 (14.9%) patients with IMN. The IMN and IMN+FSGS groups did not differ in gender, age of onset IMN and age of renal biopsy. In the IMN+FSGS group proteinuria was higher and estimated glomerular filtration rate was lower than that in the IMN group (p<0.05). The systolic arterial pressure and creatinine levels in the IMN+FSGS group were slightly higher than in the IMN group, but the difference was not significant. Anti-PLA2R positivity was similar in both groups. Chronic kidney disease (CKD) progression was observed in 10/52 (19.2%) and 5/7 (71.4%) patients in IMN and IMN+FSGS groups, respectively. In a multivariate Cox regression model, age of renal biopsy (odds ratio - OR 1.12, 95% confidence interval - CI 1.03-1.22; р=0.07), FSGS (OR 0.05, 95% CI 0.01-0.34; р=0.002) и response to initial course of immunosuppression (OR 0.33, 95% CI 0.12-0.95; р=0.039) were associated with the CKD progression. CONCLUSION: In patients with IMN secondary FSGS is associated with a greater severity of proteinuria and a decrease in estimated glomerular filtration rate, and is also an independent factor of the CKD progression.

[Clinical and morphological correlations in patients with lupus nephritis: a retrospective study].

AIM: To analyze associations between clinical and morphological features of kidney involvement in patients with systemic lupus erythematosus. MATERIALS AND METHODS: In the retrospective cohort study, we enrolled adult (≥18 years) patients with morphologically proven lupus nephritis (LN) stratified according to the ISN/RPS classification. Systemic lupus erythematosus was classified in accordance with ACR/EULAR classification criteria (2019). Antiphospholipid syndrome was diagnosed according to the 2006 classification criteria. Disease activity was assessed with SELENA-SLEDAI score. RESULTS: We enrolled 62 patients with LN, among them 84% were females. Median age of SLE onset was 23 (16,3; 30,8) years. In all cases kidney involvement was accompanied by extrarenal manifestations, among which joint (82%), skin (57%) and hematological involvement (68%) was the most common. LN class I was proven in one patient, class II - in three patients, class III - in 24, including III+V in seven, class IV - in 18, including IV+V in two, class V - in 13, class VI - in three patients. APS nephropathy was diagnosed in 4 (6.5%) of patients with LN. The most common clinical manifestation was proteinuria (85%), however its prevalence, level and the frequency of nephrotic syndrome showed no significant differences between the LN classes. LN III/IV±V was characterized by the highest levels of serum creatinine (and the lowest eGFR) at the time of biopsy. CONCLUSION: LN is characterized by the high heterogeneity of the clinical and morphological manifestations, which makes LN class prediction impossible without kidney biopsy.

Association of serum homocysteine with vitamin B12 and folate levels in women with pre-eclampsia in a tertiary health care center in Nepal.

BACKGROUND: Pre-eclampsia is a syndrome that chiefly includes the development of new-onset hypertension and proteinuria after 20 weeks of pregnancy. Pre-eclampsia is one of the major causes of mortality and morbidity in Nepal. Hyperhomocysteinemia may be a cause of the endothelial dysfunction provoked by oxidative stress in pre-eclampsia. This study was designed to evaluate the association of homocysteine with Vitamin B12 and folate in patients with pre-eclampsia. METHOD: An observational cross sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving seventy two subjects with pre-eclampsia. Blood pressure, urinary protein levels, serum homocysteine, Vitamin B12 and folate levels were compared in both mild and severe forms of pre-eclampsia. Concentration of Vitamin B12 and folate were measured using Vitros ECI and homocysteine was measured using CLIA. SPSS 23.0 was used to analyze the data. Tests were performed with Mann Whitney Test and Spearman's rank correlation test. A p-value < 0.05 was considered statistically significant. RESULTS: This study showed no significant difference in age and weeks of gestation in both mild and severe forms of pre-eclampsia. Mean concentration of homocysteine was higher (13.1 ± 6.4 micromol/L) in severe Pre-eclampsia as compared to mild cases (7.6 ± 2.8 micromol/L). Mean concentration of folate was lower in severe cases (35.4 ± 24.1 micromol/L) when compared with mild cases of pre-eclampsia (57 ± 23.4 micromol/L). CONCLUSION: Homocysteine levels were increased in severe Pre-eclampsia when compared with mild pre-eclampsia and this finding can be used to predict and prevent complications in patients with pre-eclampsia.

4-Phenylbutyric Acid Treatment Reduces Low-Molecular-Weight Proteinuria in a Clcn5 Knock-in Mouse Model for Dent Disease-1.

Dent disease-1 (DD-1) is a rare X-linked tubular disorder characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and nephrocalcinosis. This disease is caused by inactivating mutations in the CLCN5 gene which encodes the voltage-gated ClC-5 chloride/proton antiporter. Currently, the treatment of DD-1 is only supportive and focused on delaying the progression of the disease. Here, we generated and characterized a Clcn5 knock-in mouse model that carries a pathogenic CLCN5 variant, c. 1566_1568delTGT; p.Val523del, which has been previously detected in several DD-1 unrelated patients, and presents the main clinical manifestations of DD-1 such as high levels of urinary b2-microglobulin, phosphate and calcium. Mutation p.Val523del causes partial ClC-5 retention in the endoplasmic reticulum. Additionally, we assessed the ability of sodium 4-phenylbutyrate, a small chemical chaperone, to ameliorate DD-1 symptoms in this mouse model. The proposed model would be of significant value in the investigation of the fundamental pathological processes underlying DD-1 and in the development of effective therapeutic strategies for this rare condition.

[Renal leukocyte chemokine type 2 amyloidosis: a clinicopathological analysis of fifteen cases].

Objective: To investigate the clinicopathological features of renal leukocyte chemokine type 2 amyloidosis (ALECT2). Methods: The prevalence, clinical characteristics, renal histopathological features, and renal outcome of 15 patients with ALECT2 by kidney biopsy were collected in the Department of Kidney Pathology, Shanxi Medical University Second Hospital, Taiyuan, China from January 1993 to December 2023. Immunohistochemistry and mass spectrometry for amyloid proteins were carried out. Results: Fifteen patients with ALECT2 were included in the study, representing 12.93% (15/116) of the renal biopsy-proven amyloidosis cases. There were 5 males and 10 females. The median age at diagnosis was 61 years. All patients had various degrees of proteinuria; 7 patients had nephrotic syndrome; 3 patients had renal insufficiency; 7 patients had microscopic hematuria. Renal biopsy showed that strongly orangophilic amyloid proteins distributed mainly in the renal cortical interstitium, vascular walls, the glomerular mesangium and/or glomerular basement membrane. Eight cases were diagnosed with ALECT2 alone and 7 cases combined with other renal diseases, including 4 cases with membranous nephropathy, 2 cases with IgA nephropathy, and 1 case with subacute tubular interstitial nephropathy. ALECT2 patients with concurrent renal disease showed a higher proteinuria level than those without (3.48 g/24 h versus 4.58 g/24 h). All patients were corroborated by immunohistochemistry to exhibit the specific location of LECT2 in the amyloid fibrils. Mass spectrometry analysis revealed LECT2 polypeptide in 9 patients. Except two patients with worsening renal function, the others showed stable renal function during the mean follow-up period of 12.5 months. Conclusions: ALECT2 is the second common type of renal amyloidosis in our center. The majority of ALECT2 patients show concurrent renal diseases, with a high rate of membranous nephropathy. Amyloid deposits distribute mainly in the cortical interstitium of the kidney, the glomerular mesangium and vascular walls. Mass spectrometry is the most sensitive and specific method for detecting LECT2 amyloidosis.

Construction and validation of a risk model of proteinuria in patients with omicron COVID-19: retrospective cohort study.

BACKGROUND: To explore the risk factors of proteinuria in Omicron variant patients and to construct and verify the risk predictive model. METHODS: 1091 Omicron patients who were hospitalized from August 2022 to November 2022 at Tianjin First Central Hospital were defined as the derivation cohort. 306 Omicron patients who were hospitalized from January 2022 to March 2022 at the same hospital were defined as the validation cohort. The risk factors of proteinuria in derivation cohort were screened by univariate and multivariate logistic regression analysis, and proteinuria predicting scoring system was constructed and the receiver operating characteristic(ROC)curve was drawn to test the prediction ability. The proteinuria risk model was externally validated in validation cohort. RESULTS: 7 factors including comorbidities, blood urea nitrogen (BUN), serum sodium (Na), uric acid (UA), C reactive protein (CRP) and vaccine dosages were included to construct a risk predictive model. The score ranged from -5 to 16. The area under the ROC curve(AUC) of the model was 0.8326(95% CI 0.7816 to 0.8835, p < 0.0001). Similarly to that observed in derivation cohort, the AUC is 0.833(95% CI 0.7808 to 0.9002, p < 0.0001), which verified good prediction ability and diagnostic accuracy in validation cohort. CONCLUSIONS: The risk model of proteinuria after Omicron infection had better assessing efficiency which could provide reference for clinical prediction of the risk of proteinuria in Omicron patients.

Role of omega-3 fatty acids in reducing proteinuria: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Proteinuria, a hallmark of renal and systemic disorders, is associated with adverse outcomes, especially in chronic kidney disease and cardiovascular disease. Omega-3 fatty acids have garnered attention for their cardiovascular benefits and potential therapeutic effects on proteinuria. This systematic review and meta-analysis aimed to evaluate the impact of omega-3 fatty acid supplementation on proteinuria levels across various kidney-related conditions. METHODS AND STUDY DESIGN: Studies published from 1989 to 2023 were systematically identified, including randomized controlled trials, cohort, case-control, and cross-sectional studies. Nine studies involving a total of 347 participants were included in the analysis. RESULTS: The meta-analysis revealed a neutral overall effect size of omega-3 fatty acid supplementation on proteinuria levels, assessed under both common and random effect models. Despite the lack of statistically significant evidence supporting the efficacy of omega-3 fatty acids in reducing proteinuria, the variability in interventions and patient populations suggests potential individual responses. CONCLUSIONS: The find-ings highlight the heterogeneity in responses to omega-3 fatty acid supplementation and emphasize the need for cautious interpretation. While no definitive conclusion can be drawn, the results underscore the importance of targeted research focusing on specific subgroups or conditions that may benefit from omega-3 supplementation. These findings contribute to the evolving understanding of personalized kidney health strategies and pave the way for further exploration and optimization of omega-3 fatty acids' therapeutic applications.

[The 508th case: recurrent edema of bilateral lower extremities with proteinuria].

A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient's nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 µmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5➝147 µmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 µmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.

Overview of clinical status, treatment, and long-term outcomes of pediatric autosomal-dominant polycystic kidney disease: a nationwide survey in Taiwan.

This retrospective study investigated the incidence, medication use, and outcomes in pediatric autosomal-dominant polycystic kidney disease (ADPKD) using Taiwan's National Health Insurance Research Database (NHIRD). A 1:4 matched control group of individuals included in the NHIRD during the same period was used for comparative analyses. A total of 621 pediatric patients were identified from 2009 to 2019 (mean age, 9.51 ± 6.43 years), and ADPKD incidence ranged from 2.32 to 4.45 per 100,000 individuals (cumulative incidence, 1.26-1.57%). The incidence of newly developed hypertension, anti-hypertensive agent use, nephrolithiasis, and proteinuria were significantly higher in the ADPKD group than the non-ADPKD group (0.7 vs. 0.04, 2.26 vs. 0.30, 0.4 vs. 0.02, and 0.73 vs. 0.05 per 100 person-years, respectively). The adjusted hazard ratios for developing hypertension, proteinuria, nephrolithiasis and anti-hypertensive agent use in cases of newly-diagnosed pediatric ADPKD were 12.36 (95% CI 4.92-31.0), 13.49 (95% CI 5.23-34.79), 13.17 (95% CI 2.48-69.98), and 6.38 (95% CI 4.12-9.89), respectively. The incidence of congenital cardiac defects, hematuria, urinary tract infections, gastrointestinal diverticulosis, dyslipidemia, and hyperuricemia were also higher in the ADPKD group. Our study offers valuable insights into the epidemiology of pediatric ADPKD in Taiwan and could help in formulating guidelines for its appropriate management.

Intermittent pulses of methylprednisolone with low-dose prednisone attenuate lupus symptoms in B6.MRL-Faslpr/J mice with fewer glucocorticoid side effects.

Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressant medications and remain the cornerstone of systemic lupus erythematosus (SLE) therapy. However, ongoing exposure to GCs has the potential to elicit multiple adverse effects. Considering the irreplaceability of GCs in SLE therapy, it is important to explore the optimal regimen of GCs. Here, we compared the long-term efficacy and safety of pulsed and oral GC therapy in a lupus-prone mouse model. Mice were grouped using a randomized block design. We monitored survival rates, proteinuria, serum autoantibodies, and complement 3 (C3) levels up to 28 weeks of age, and assessed renal damage, bone quality, lipid deposition in the liver and marrow, glucose metabolic parameters, and levels of hormones of the hypothalamic-pituitary-adrenal (HPA) axis. Finally, we explored the mechanisms underlying the superior efficacy of the pulse regimen over oral prednisone regimen. We found that both GC regimens alleviated the poor survival rate, proteinuria, and glomerulonephritis, while also reducing serum autoantibodies and increasing the level of C3. The pulsed GC regimen showed less resistance to insulin, less suppression of the HPA axis, less bone loss, and less bone marrow fat deposition than the oral GC regimen. Additionally, GC-induced leucine zipper (GILZ) was significantly overexpressed in the GC pulse group. These results suggest that the GC pulse regimen ameliorated symptoms in lupus-prone mice, with fewer side effects, which may be related to GILZ overexpression. Our findings offer a potentially promising GC treatment option for SLE.

Low-Protein Diets Could Be Effective and Safe in Elderly Patients with Advanced Diabetic Kidney Disease.

Low-protein diets (LPDs) seem to improve metabolic complications of advanced CKD, thus postponing kidney replacement therapy (KRT) initiation. However, the nutritional safety of LPDs remains debatable in patients with diabetic kidney disease (DKD), especially in the elderly. This is a sub-analysis of a prospective unicentric interventional study which assessed the effects of LPD in patients with advanced DKD, focusing on the feasibility and safety of LPD in elderly patients. Ninety-two patients with DKD and stable CKD stage 4+, proteinuria >3 g/g creatininuria, good nutritional status, with confirmed compliance to protein restriction, were enrolled and received LPD (0.6 g mixed proteins/kg-day) supplemented with ketoanalogues of essential amino acids for 12 months. Of the total group, 42% were elderly with a median eGFR 12.6 mL/min and a median proteinuria 5.14 g/g creatininuria. In elderly patients, proteinuria decreased by 70% compared to baseline. The rate of kidney function decline was 0.1 versus 0.5 mL/min-month before enrolment. Vascular events occurred in 15% of cases, not related to nutritional intervention, but to the severity of CKD and higher MAP. LPDs seem to be safe and effective in postponing KRT in elderly patients with advanced DKD while preserving the nutritional status.

Cyclosporine A Protects Podocytes by Regulating Transgelin in Adriamycin-Induced Podocyte Injury.

INTRODUCTION: The calcineurin inhibitor cyclosporine A (CsA) has been shown to effectively reduce proteinuria. However, its precise mechanism is still not fully understood. Our previous study showed that CsA reduced proteinuria by directly stabilizing the foot process (FP) cytoskeletal structure via cofilin-1, suggesting that synaptopodin, a podocyte-specific actin protein, is not the sole target of CsA in podocytes. METHODS: In this study, we established an adriamycin (ADR)-induced nephropathy rat model and a cultured podocyte injury model. We employed Western blotting and immunofluorescence techniques to assess the expression and distribution of transgelin, Krüppel-like factor-4 (KLF-4), nephrin, and synaptopodin. RESULTS: We observed a significant increase in proteinuria levels accompanied by loss of normal FP structure in the ADR-induced nephropathy rat model. The levels of the actin cross-linking protein transgelin were increased significantly, while those of the podocyte-specific molecules nephrin and synaptopodin were decreased in vivo. Treatment with CsA effectively reduced proteinuria while restoring FP effacement stability in ADR-induced nephropathy models and restoring the expression of transgelin, nephrin, and synaptopodin both in vivo and in vitro. Furthermore, CsA treatment dose-dependently decreased transgelin levels while significantly increasing KLF-4 expression in injured podocytes. In addition, CsA failed to downregulate transgelin when KLF-4 was specifically knocked down. CONCLUSION: Our findings suggest that CsA protects against podocyte injury by downregulating abnormally high levels of transgelin via upregulation of KLF-4 expression.

A single-center, open label, randomized, controlled study of hydroxychloroquine sulfate in the treatment of low risk PLA2R-associated membranous nephropathy.

OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) in the treatment of low risk phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). METHODS: A total of 110 patients with low risk PLA2R-associated MN were included in the study. Patients who met the inclusion and exclusion criteria were assigned randomly to two groups: the HCQ treatment group and the control group. The control group received standard supportive treatment according to the guidelines, while the HCQ treatment group received HCQ in addition to the supportive treatment. The clinical data of the patients were analyzed, with comparisons made at baseline and during the six-month follow-up period. Any adverse reactions were recorded. RESULTS: The baseline data were comparable between the HCQ treatment group and the control group. At the end of the six-month follow-up period, the reductions in urine protein excretion and serum PLA2R antibody titer were more notable in the HCQ treatment group than those in the control group, with these differences being statistically significant (p < 0.05). Compared to the control group, the HCQ treatment group had fewer patients who were converted from low risk to moderate-to-high risk (p = 0.084). There were also no severe adverse reactions in the HCQ treatment group. CONCLUSION: In patients with low risk PLA2R-associated MN, adequate supportive therapy combined with HCQ is superior to supportive therapy alone in controlling proteinuria and reducing serum PLA2R antibody titers. Additionally, our study demonstrated that the incidence of adverse reactions did not increase. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration No.: ChiCTR1900021757, Date of registration: 2019-03-08).

A Patient With Proteinuria, Myalgias, and Decreased Pigmentation of Facial Skin.

A patient had bilateral leg edema, insomnia, myalgias, paresthesias in the fingertips, lighter pigmentation of the facial skin compared with other areas of the body, proteinuria, and an elevated creatinine level. What is the diagnosis and what would you do next?

Proteomic Changes Induced by the Immunosuppressant Everolimus in Human Podocytes.

mTOR inhibitors (mTOR-Is) may induce proteinuria in kidney transplant recipients through podocyte damage. However, the mechanism has only been partially defined. Total cell lysates and supernatants of immortalized human podocytes treated with different doses of everolimus (EVE) (10, 100, 200, and 500 nM) for 24 h were subjected to mass spectrometry-based proteomics. Support vector machine and partial least squares discriminant analysis were used for data analysis. The results were validated in urine samples from 28 kidney transplant recipients receiving EVE as part of their immunosuppressive therapy. We identified more than 7000 differentially expressed proteins involved in several pathways, including kinases, cell cycle regulation, epithelial-mesenchymal transition, and protein synthesis, according to gene ontology. Among these, after statistical analysis, 65 showed an expression level significantly and directly correlated with EVE dosage. Polo-Like Kinase 1 (PLK1) content was increased, whereas osteopontin (SPP1) content was reduced in podocytes and supernatants in a dose-dependent manner and significantly correlated with EVE dose (p < 0.0001, FDR < 5%). Similar results were obtained in the urine of kidney transplant patients. This study analyzed the impact of different doses of mTOR-Is on podocytes, helping to understand not only the biological basis of their therapeutic effects but also the possible mechanisms underlying proteinuria.

Immunotactoid Glomerulopathy.

Immunotactoid glomerulopathy (ITG) is a rare glomerular disease that typically presents with proteinuria, hematuria, and kidney dysfunction. A kidney biopsy is essential to establish the diagnosis of ITG. ITG is characterized by glomerular electron-dense immunoglobulin deposits with hollow-cored microtubules. ITG is classified as either monoclonal or polyclonal based on immunofluorescence staining of the immunoglobulin deposits. Monoclonal ITG is associated with an underlying hematologic disorder in two-thirds of the cases, lymphoma and plasma cell dyscrasias being the most common. Polyclonal ITG is associated with autoimmune diseases but can be seen with hematologic disorders and chronic infections. Due to the preponderance of hematologic disorders in both monoclonal and polyclonal ITG, a thorough hematologic workup must be performed in all cases of ITG. In monoclonal ITG with a detectable clone, clone-directed therapy is administered to achieve hematologic remission, as the renal response is highly dependent on the hematologic response. In clone-negative monoclonal ITG, anti-B cell therapy is often used as a first-line therapy. Management of polyclonal ITG without an underlying hematologic disorder is poorly defined. Compared to monoclonal ITG, patients with polyclonal ITG have a higher risk of progression to end-stage kidney disease. Recurrence of ITG following kidney transplantation is common and is often associated with hematologic relapse.

Longitudinal Analysis of Renal Function Changes in Elderly Populations: Health Status Evaluation and Risk Factor Assessment.

Background: This study aims to investigate GFR decline in elderly subjects with varying physical conditions and analyze key risk factors impacting renal function changes. Methods: We obtained data from patients between 2017 and 2019, and matched healthy elderly subjects based on gender and age. Data collected for all subjects included annual measurements of fast blood glucose (GLU), glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-c), blood albumin (ALB), blood uric acid (UA), urine protein (UP), and systolic blood pressure (SBP). Additionally, information on coexisting diseases was gathered. The Full Age Spectrum (FAS) equation was used to calculate eGFR. Results: A total of 162 patients with complete 3-year renal dynamic imaging were included, including 84 patients in the kidney disease group (K group) and 78 patients in the non-kidney disease group (NK group). Ninety individuals were selected as the healthy group (H group). The annual decline rate in the K group was the fastest, which exceeded 5mL/min/1.73m2 (P < 0.05). Group (K group: ß=-40.31, P<0.001; NK group: ß=-26.96, P<0.001), ALB (ß=-0.38, P=0.038) and HbA1c (ß=1.36, P=0.029) had a significant negative impact on the eGFR changes. For participants who had negative proteinuria: K group had the most significant annual eGFR decline. Conclusion: The presence of kidney disease, along with proteinuria nor not, can lead to a marked acceleration in kidney function decline in elderly. We categorize elderly individuals with an annual eGFR decline of more than 5 mL/min/1.73m2 as the "kidney accelerated aging" population.

Biochemical and Oxidative Biomarkers in Preeclampsia.

OBJECTIVE: To determine the biochemical and oxidative stress parameters as biomarkers in preeclampsia. STUDY DESIGN: Cross-sectional analytical study. Place and Duration of the Study: Departments of Obstetrics / Gynaecology and Biochemistry, Quaid-e-Azam Medical College, Bahawalpur, Pakistan, from September 2022 to February 2023. METHODOLOGY: Women with preeclampsia were selected based on blood pressure exceeding 140/90 mmHg and proteinuria levels exceeding 300 mg/24 hours or showing a +1 on a dipstick test. Normotensive pregnant women were selected as controls. Venous blood was taken and centrifuged, and routine biochemical methods were used to estimate serum lipid profile levels and minerals. The estimation of oxidative stress enzymes was carried out manually using special chemicals. Student's t-test and Pearson's correlation were applied to analyse the result. RESULTS: The study included 228 subjects: 114 preeclampsia patients and 114 normal pregnant women as controls. The mean systolic blood pressure was measured at 166.25 mmHg and the diastolic blood pressure was 92.80 mmHg (p <0.001). All lipid profile estimations showed notable abnormalities, but the mean level of triglycerides (TGs) (214.90 ± 15.59 mg/dl) in preeclamptic patients was significantly elevated (p <0.05). In terms of minerals, all were deranged but magnesium (1.37 ± 0.35 mg/dl) and calcium (7.55 ± 0.45 mg/dl) were significantly decreased (p <0.05). All oxidative enzyme levels were increased (p <0.05) but malondialdehyde (MDA) with a mean level of 2.58 ± 0.40 nmol/ml was significantly elevated. The Pearson's correlation of these parameters with blood pressure also showed a positive association. CONCLUSION:  Total cholesterol triglyceride in the lipid profile, calcium and magnesium in minerals, and MDA in oxidative parameters were markedly deranged and exhibited significant associations with the severity of the disease, so could be used as disease biomarkers of preeclampsia. KEY WORDS: Preeclampsia, Gestational hypertension, Proteinuria, Lipid profile, Minerals, Oxidative stress.

Controversy between biopsy and risk in children with proteinuria: is there a paradigm war?

BACKGROUND: Proteinuria is a prevalent symptom of pediatric nephrology, while kidney biopsy remains the gold standard for kidney tissue analysis, and it is currently controversial. We report the rare case that the mutation in the AMN gene was considered to cause chronically isolated proteinuria and also suggest that renal biopsy should be chosen with caution in children with chronic isolated non-nephrotic levels of proteinuria and that genetic testing may be feasible for the early precise diagnosis. CASE PRESENTATION: A 35-month-old boy presented with excessive urine foaming for more than half a month; his proteinuria was considered non-nephrotic range and urine protein electrophoresis was suggestive of mixed proteinuria; other than that, the investigations are non-specific. Given the child's chronic isolated proteinuria and good renal function, we chose to refine the genetic test rather than a renal biopsy; a compound heterozygous variant was found in the AMN gene of this child which was caused by a point mutation in the father, and a partial chromosomal deletion in the mother. CONCLUSIONS: Cubilin(encoded by CUBN), amnionless(encoded by AMN), and megalin form a multiligand receptor complex; CUBN or AMN gene variants have been implicated as a hereditary cause of megaloblastic anemia, proteinuria, and neurological impairment. In the past few decades, chronic isolated proteinuria caused by CUBN gene variants is benign, non-progressive, and has normal renal function. However, the child is the first reported case of isolated proteinuria of AMN gene mutation, indicating that the earlier diagnostic genetic sequencing in an otherwise well, not nephrotic proteinuria child may be a convenient, cost-effective, and harmless option, challenging the traditional paradigm.