The association between obstructive sleep apnea (OSA) and proteinuria is undetermined, with few studies on hypertension, a high-risk group for renal impairment. Therefore, we aimed to explore whether OSA is an independent risk factor for proteinuria in patients with hypertension. We investigated the cross-sectional association between OSA and proteinuria. Participants were divided into groups by apnea hypopnea index (AHI) category. Multivariable Logistic regression analysis was used to evaluate the association between OSA severity, objectively measured sleep dimensions, and proteinuria which is mainly defined by 24-h urine protein quantification > 300 mg/24 h. Sensitivity analyses were performed by excluding those with comorbidities (primary aldosteronism and homocysteine ≥ 15 μmol/L). Of the 2106 participants, the mean age was 47.57 ± 10.50 years, 67.2% were men, and 75.9% were OSA patients. In total participants, compared with those without OSA, patients with mild OSA, moderate OSA, and severe OSA showed 1.09 (95% CI 0.80-1.40), 1.24 (95% CI 0.89-1.74) and 1.47 (95% CI 1.04-2.08) fold risk for proteinuria with a trend test P trend < 0.05. Each 10-unit increase in the AHI, oxygen desaturation index (ODI), and time spent with oxygen saturation < 90% (T90) was found to be associated with 13%, 10%, and 2% higher likelihood of proteinuria in the crude model, significant in adjusted models. The more severe the OSA is, the higher the risk of proteinuria. AHI and T90 are independently associated with a higher risk of structural renal damage in the population with hypertension.

Integrating sodium-glucose co-transporter 2 inhibitors (SGLT2i) into the treatment for chronic kidney disease (CKD) has marked a significant therapeutic advance in nephrology. Clinical trials such as DAPA-CKD and EMPA-KIDNEY have demonstrated the beneficial effects of SGLT2i in slowing CKD progression and reducing proteinuria. However, the applicability of these results to patients with glomerulonephritis is still unresolved due to various limitations. This manuscript combines the evidence supporting the use of SGLT2i in glomerular diseases, highlights the limitations and strikes a conclusive balance on their role in clinical practice.

UNASSIGNED: Hydroxychloroquine (HCQ) effectively improves lipid levels in patients with autoimmune diseases. This study aimed to examine the effect of HCQ on lipid profiles in patients with immunoglobulin A (IgA) nephropathy (IgAN) and determine whether alterations in lipid profiles can predict the efficacy of HCQ.
UNASSIGNED: This study retrospectively analyzed 77 patients, and the total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) decline rate after 3 months of HCQ treatment was selected as a predictor based on receiver operating curve analysis. Patients were then divided into low and high TC/HDL-C decline rate groups based on the optimal cutoff value. The Cox proportional hazard model and Kaplan-Meier curve were used to evaluate the value of the TC/HDL-C decline rate in predicting the efficacy of HCQ in patients with IgAN.
UNASSIGNED: Patients in the high TC/HDL-C decline rate group with ≥50% decrease in proteinuria from baseline experienced a significant improvement during the follow-up. Kaplan-Meier analysis revealed that a high TC/HDL-C decline rate was strongly associated with a higher proteinuria reduction rate in patients with IgAN. Furthermore, multivariate Cox analysis indicated that a higher reduction in the TC/HDL-C ratio (hazard ratio: 2.314; 95% confidence interval: 1.234-4.340; p = 0.009) was an independent predictive indicator for achieving ≥50% reduction in proteinuria with HCQ therapy in IgAN.
UNASSIGNED: HCQ effectively improves lipid profiles in patients with IgAN, and an early decrease in the TC/HDL-C ratio serves as a predictor of better outcomes in patients treated with HCQ.

Immunoglobulin A nephropathy (IgAN) often has a poor outcome, with many patients reaching kidney failure within their lifetime. Therefore, the primary goal for the treatment of IgAN should be to reduce nephron loss from the moment of diagnosis. To achieve this, IgAN must be recognized and treated as both a chronic kidney disease and an immunological disease. Agents that have received US Food and Drug Administration and European Medicines Agency approval for the treatment of IgAN include modified-release/targeted-release formulation budesonide (Nefecon) and sparsentan, a selective dual endothelin-A and angiotensin II receptor type 1 antagonist. Other agents, including selective endothelin receptor antagonists, selective or combined APRIL and BAFF antagonists, and a vast array of complement inhibitors are being investigated for the treatment of IgAN. Furthermore, treatment combinations are also being studied, including sodium-glucose cotransporter-2 inhibitors with endothelin receptor antagonists. Due to the complexity of IgAN, combination treatment, rather than a single-agent approach, may provide maximum benefit. With the number of treatments for IgAN likely to increase, combinations allowing safe and effective treatment to halt progression to kidney failure seem within grasp. While trials evaluating combinations are ongoing, more are needed to pave the way for a comprehensive IgAN treatment strategy. Furthermore, an approach to IgAN treatment in which agents are combined early to achieve rapid induction of remission and prevent unnecessary and irreversible nephron loss is required. Following remission, treatments may be adjusted and stripped back as necessary in the maintenance phase with close monitoring. This review discusses the current status of IgAN treatment and explores future strategies to improve outcomes for patients with IgAN.

Hemorrhagic fever with renal syndrome (HFRS) induced by Eurasian pathogenic orthohantaviruses is characterized by acute kidney injury (AKI) with often massive proteinuria. The mechanisms of the organ-specific manifestation are not completely understood. To analyze the role of glomerular and tubular damage in kidney injury induced by HFRS, we measured specific markers in urine samples of patients with acute Puumala virus (PUUV) infection and determined their correlation with disease severity. Levels of α1-microglobulin (α1-MG) and kidney injury molecule 1 (KIM-1), which is expressed by injured tubular epithelial cells, were measured to detect tubular dysfunction and injury. Immunoglobulin G (IgG) and the podocyte specific protein nephrin served as markers for glomerular injury. All four markers were elevated on admission. Markers of glomerular injury, IgG and nephrin, correlated with markers of disease severity such as length of hospitalization, serum creatinine, and proteinuria. In contrast, tubular injury did not correlate with these severity markers. Our results demonstrate that hantavirus infection induces both glomerular and tubular injury early in the clinical course. However, the glomerular dysfunction and podocyte injury seem to contribute directly to disease severity and to play a more central role in HFRS pathogenicity than direct damage to tubular epithelial cells.

Background and objectives: Pre-eclampsia (PE) is a pregnancy-specific condition characterized by significant health risks for pregnant women worldwide due to its status as a multi-organ disorder. High blood pressure (hypertension) with or without proteinuria is usually considered an initial clinical sign of PE. The pathogenesis of pre-eclampsia is highly complex and likely involves multiple factors, including poorly developed uterine spiral arterioles, immunological issues, placental ischemia or infarction, and genetic abnormalities. Inflammatory cytokine production, regulated by cytokine gene polymorphisms, is one of the factors likely contributing to the development of PE. The present study aimed to assess IL-6, IL-1β, and Apo B-100 gene polymorphism and to evaluate the association of these polymorphisms with PE. Materials and Methods: This cross-sectional observational study involved 99 participants aged 16 to 45 years from Bahawal Victoria Hospital Bahawalpur, Punjab, Pakistan. The participants were divided into three groups: Group 1 (PE with severe hypertension), Group 2 (PE with hypertension), and Group 3 (control), each comprising 33 individuals. Maternal blood samples were collected, DNA was extracted, and molecular genetic analysis of the IL-6, IL-1β, and Apo B-100 genes was performed using the PCR-RFLP method. Allelic frequencies were compared, and statistical analysis was conducted using SPSS 25, applying the Hardy-Weinberg equation and chi-square test to evaluate the results. Results: There are differences in the distribution of allelic frequencies for IL-6 -174G/C (CC, GC, GG), IL-1β-511C/T (CC, CT, TT), and Apo B-100 2488 C/T (CC, CT, TT) between pre-eclamptic patients and the control group. The analysis using the Hardy-Weinberg equilibrium and chi-square test showed an association between the IL-6-174 G/C polymorphism and the severity of pre-eclampsia. Conclusions: The polymorphisms of the IL-6, IL-1β, and Apo B-100 genes revealed different alleles. The IL-6 gene alone was found to be in disequilibrium according to the Hardy-Weinberg equation, indicating a potential link to the severity of pre-eclampsia in the population studied.

Background/Objectives: Proteinuria is documented as a risk factor for atrial fibrillation (AF) and can manifest in either reversible or continued forms. Our objective was to examine the relationship between the change in status for proteinuria and the risk of AF in a longitudinal cohort study on the general population nationwide. Methods: We included participants (n = 1,708,103) who underwent repetitive health examinations. The presence of proteinuria was determined by dipstick urinalysis results. The outcome was the occurrence of AF (International Classification of Diseases-10 code: I48). Results: All included participants, 1,666,111 (97.5%), 17,659 (1.0%), 19,696 (1.2%), and 4637 (0.3%), were categorized into groups of proteinuria-free, improved, progressed, and persistent, respectively. During a median follow-up of 14.5 years, 41,190 (2.4%) cases of AF occurred. In the multivariable analysis, the risk of AF was increased as the initial severity was more severe in the proteinuria-improved and proteinuria-persistent groups (p for trend < 0.001). In a further pairwise comparison, the proteinuria-improved group had a relatively lower risk of AF compared to the proteinuria-persistent group (HR: 0.751, 95% CI: 0.652-0.865, p < 0.001). Conclusions: Our study showed that the risk of AF can change according to alterations in proteinuria status. Notably, recovering from proteinuria can also be considered a modifiable risk factor for AF.

The management strategy for IgA nephropathy (IgAN), has undergone constant improvements since the disease entity was first described 50 years ago. However, it is still unknown how these changes affected the long-term renal survival of IgAN patients. We systematically evaluate changes in IgAN renal survival by searching PubMed, Embase, and the Cochrane Library Database of Systematic Reviews from inception to 19 May 2024. We included a large sample of 103076 IgAN cases from 158 studies. Renal survival rates were 94.16% (95% CI: 94.02% to 94.31%), 88.68% (95% CI: 88.48% to 88.87%), and 78.13% (95% CI: 77.82% to 78.43%) at three, five, and ten-year, respectively. Over the past few decades, there haven\'t been any sound changes in the 3-year and 5-year renal survival rates. The kidney survival rate in developed countries is higher than in developing countries. Researchers consistently show that while proteinuria < 1.0 g/24 h, renal survival rates increase dramatically. In IgAN, long-term renal survival fluctuated rather than continuously improving over time. Our system review\'s findings indicate that supportive care-the most important recommendation for managing IgAN has shown promising results. The long-term outcomes of IgAN could be significantly improved by the latest developed treatment options.

To explore the effect of different levels of systolic blood pressure (SBP) control on new-onset chronic kidney disease in hypertension multimorbidity. The hypertensive patients with multimorbidity information were enrolled from the Kailuan Study. The isolated hypertension patients undergoing physical examination during the same period were selected in a 1:1 ratio as control. Finally, 12,897 participants were divided into six groups: Group SBP < 110 mmHg, Group 110 ≤ SBP < 120 mmHg, Group 120 ≤ SBP < 130 mmHg, Group 130 ≤ SBP < 140 mmHg, Group 140 ≤ SBP < 160 mmHg and Group SBP ≥ 160 mmHg. The outcomes were new-onset CKD, new onset proteinuria, decline in eGFR and high or very high risk of CKD. Cox proportional hazards regression was used to examine the hazard ratios (HRs) of the outcomes among SBP levels. When 110 ≤ SBP < 120 mmHg, the incidence density of new-onset CKD, new onset proteinuria and decline in eGFR were 59.54, 20.23 and 29.96 per 1000 person-years, respectively. Compared to this group, the HR (95% CI) values for the risk of new-onset CKD from Group SBP < 110 mmHg to Group SBP ≥ 160 mmHg were 1.03 (0.81-1.32), 1.04 (0.91-1.19), 1.09 (0.95-1.16), 1.16 (1.02-1.21) and 1.18 (1.04-1.24), respectively. For patients over 65 years old, the risks of outcomes were increased when SBP < 120 mmHg. The lowest HR of high or very high risk of CKD for participants with or without multimorbidity occurred when 120 ≤ SBP < 130 mmHg. The HR of new-onset CKD in hypertension multimorbidity was lowest at 110-120 mmHg. The optimal SBP level was between 120 and 130 mmHg for individuals with high or very high risk of CKD. For patients over 65 years old, the low limit of target BP is advised to be not lower than 120 mmHg.

IgA nephropathy (IgAN) is considered the most common primary glomerulonephritis worldwide with a predilection for Asian-Pacific populations and relative rarity in those of African descent. Perhaps 20%-50% of patients progress to kidney failure. The pathogenesis is incompletely understood. Mesangial deposition of immune complexes containing galactose-deficient IgA1 complexed with anti-glycan IgG or IgA antibodies results in mesangial cell activation and proliferation, inflammatory cell recruitment, complement activation, and podocyte damage. Diagnosis requires a biopsy interpreted by the Oxford criteria. Additional pathologic features include podocytopathy, thrombotic microangiopathy, and C4d staining. Biomarkers predicting adverse outcomes include proteinuria, reduced GFR, hypertension, and pathology. Acceptable surrogate endpoints for therapeutic trials include ongoing proteinuria and rate of eGFR decline. The significance of persisting hematuria remains uncertain. The mainstay of therapy is supportive, consisting of lifestyle modifications, renin-angiotensin inhibition (if hypertensive or proteinuric), sodium-glucose-transporter 2 inhibition (if GFR reduced or proteinuric), and endothelin-receptor antagonism (if proteinuric). Immunosuppression should be considered for those at high risk after maximal supportive care. Corticosteroids are controversial with the most positive results observed in Chinese. They carry a high risk of serious side effects. Similarly, mycophenolate may be most effective in Chinese. Other immunosuppressants are of uncertain benefit. Tonsillectomy appears efficacious in Japanese. Active areas of investigation include B-cell inhibition with agents targeting the survival factors BAFF and APRIL and complement inhibition with agents targeting the alternate pathway (Factors B and D), the lectin pathway (MASP-2), and the common pathway (C3 and C5). Hopefully soon, the who and the how of immunosuppression will be clarified, and kidney failure can be forestalled.