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Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.

BACKGROUND: Effects of the renin-angiotensin-aldosterone system (RAAS) inhibitors enalapril and telmisartan on circulating RAAS in dogs with proteinuric chronic kidney disease (pCKD) are undescribed. OBJECTIVES: To characterize the RAAS in untreated dogs with pCKD compared to healthy, life-stage- and sex-matched controls, and in dogs with pCKD after 30 days of treatment with enalapril or telmisartan. ANIMALS: Dogs with pCKD (n = 36) and healthy controls (n = 20). METHODS: Retrospective study of banked samples and previously collected data. Day 0 serum equilibrium concentrations of angiotensin I, II, III, IV, 1-5, and 1-7, and aldosterone, and urinary aldosterone-to-creatinine ratio (UACR) from pCKD dogs were compared to values on day 30 of treatment with enalapril (0.5 mg/kg PO q12) or telmisartan (1 mg/kg PO q24h) and to those of healthy dogs. Data were analyzed using linear mixed models. RESULTS: Compared with healthy dogs, pCKD dogs had significantly higher Ang I, III, 1-5, and 1-7 concentrations, and UACR. Relative to pretreatment values, day 30 Ang II concentrations were significantly increased and decreased in telmisartan- and enalapril-treated pCKD dogs, respectively (both P

Objective: We evaluated the interaction of urinary protein-to-creatinine ratio (UPCR) with diabetes on the risk of cardiovascular events in a cohort study. Methods: The study population consisted of 639 participants with chronic kidney disease (CKD) stages 2–5, enrolled between 2010 and 2011 in Japan. Cox proportional hazards models were used to evaluate the independent and combined effects of the UPCR and diabetes on cardiovascular events. Results: During a median follow-up of 3 years, 59 participants developed cardiovascular events during follow-up. A notably higher risk of cardiovascular events was found in participants with proteinuria [hazards ratio (HR): 2.16, 95% confidence interval (95% CI): 1.17–3.97] compared to those without proteinuria at UPCR levels. In addition, the participants with diabetes had a higher risk of cardiovascular events (HR: 2.53, 95% CI: 1.49–4.30) than those without diabetes. Moreover, an interaction was found between UPCR and diabetes on cardiovascular events (P for interaction = 0.04). Participants with both proteinuria (UPCR ≥ 0.5 g/gCr) and diabetes had a 4.09 times higher risk of cardiovascular events (HR: 4.09, 95% CI: 1.97–8.47) compared with those without proteinuria (UPCR < 0.5 g/gCr) and diabetes. Conclusions: In summary, among participants with CKD stages 2–5, proteinuria and diabetes were found to independently and jointly affect the risk of cardiovascular events. Participants with proteinuria and diabetes had the highest risk of cardiovascular events compared with other groups. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionPatients with lupus nephritis (LN), a severe renal manifestation of systemic lupus erythematosus, should be monitored for progression of chronic kidney disease to end-stage renal disease but data on renal function testing in LN patients are limited. This real-world analysis aimed to evaluate nephrologists’ use of renal function tests to support LN diagnosis and monitoring and to examine the impact of disease progression in LN patients in Europe.Data were drawn from the Adelphi Lupus Disease Specific Programme, a cross-sectional survey of nephrologists and their next five consulting patients with LN in France, Germany, Italy, Spain, and the United Kingdom in 2021. Nephrologists provided demographic and clinical information for each patient and the same patients completed a self-reported questionnaire. Using a checkbox, patients provided informed consent to take part in the survey.Nephrologists (n = 72) provided data on 376 patients with LN. Estimated glomerular filtration rate (eGFR) or proteinuria testing was not undertaken in around 10% and 50% of these patients, respectively. Regression analysis predicted reduction in renal function (disease progression) following LN diagnosis whilst bivariate analyses showed significantly worse outcomes for patients with progressed disease: worse pain, fatigue, treatment satisfaction, and patient-reported health state and activity impairment.Our study revealed lower-than-expected nephrologist-reported use of renal function testing to support diagnosis/monitoring of patients with LN in real-world clinical settings in Europe. Lower quality of life (QoL) was observed in patients with more progressed disease. Increased use of renal function testing is needed so that all LN patients are monitored closely to manage disease progression and avoid the associated QoL impact. [ABSTRACT FROM AUTHOR]

Chronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR. [ABSTRACT FROM AUTHOR]

To evaluate whether the presence of proteinuria, although no longer mandatory in the revised diagnostic criteria, results in worse maternal and fetal outcomes in preeclampsia (PE). A retrospective cohort study was conducted, analyzing data from pregnant patients diagnosed with PE between January 2015 and December 2019 at a tertiary care center in Brazil. Ethical approval was obtained, and the patient records were reviewed to assess maternal and perinatal outcomes based on the revised diagnostic criteria by the College of Obstetricians and Gynecologists, focusing on the presence or absence of proteinuria. The study included 816 pregnant patients with PE, of whom 685 (83.9%) were diagnosed based on proteinuria. The revised criteria, which include indicators of organ damage, identified an additional 131 cases (16.4%). Analysis showed no significant differences in maternal outcomes between proteinuria and non‐proteinuria groups, including intensive care unit (ICU) admission, acute pulmonary edema (APE), HELLP syndrome, eclampsia, or C‐section rates. However, babies born to mothers with proteinuria PE experienced worse outcomes, including fetal growth restriction, low birth weight, ICU admission, and higher rates of preterm birth. Relative risk analysis demonstrated a high risk of babies being born with low birth weight, ICU admission, and being born preterm and very preterm in cases where proteinuria was present in mothers with PE. The presence of proteinuria is associated with significantly worse outcomes in babies born to mothers with preeclampsia, while no significant differences were observed in maternal outcomes. [ABSTRACT FROM AUTHOR]

Background: Few studies have observed the direct effect of obesity on renal prognoses in immunoglobulin A nephropathy (IgAN) or separately evaluated its effects according to sex. We aimed to evaluate the direct and indirect effects of obesity on the renal outcomes of IgAN and observe these effects separately according to renal function and sex. Methods: We extracted patients with body mass index (BMI) descriptions from a multicenter retrospective cohort analysis in Japan, and excluded those with < 30 days of follow-up, diabetes mellitus, and steroid treatment. Patients were divided into normal (n = 720; 18.5 ≤ BMI < 25) and obese (n = 212; BMI ≥ 25) groups, which were then compared. The endpoints were a 1.5-fold increase in serum creatinine levels and the initiation of renal replacement therapy. Results: The obese group was older, included more males, and was more likely have hypertension, dyslipidemia, proteinuria, tubular atrophy, and lower renal function than the normal group. Patients with an eGFR < 60 mL/min/1.73 m2 had well-matched characteristics between the groups; however, hypertension, low high-density lipoprotein cholesterol, and hypertriglyceridemia were more common in the obese group. Obesity contributed to tubular atrophy, even when adjusted for renal function. In addition, it contributed to proteinuria only in females. However, obesity itself was not a significant prognostic factor. Conclusions: Although no independent effect on renal prognosis was observed during the study period, the obese group had more risk factors for IgAN progression and obesity contributed to tubular atrophy and female proteinuria. Our results suggest that separately analyzing the prognostic effect of obesity according to sex is important. [ABSTRACT FROM AUTHOR]

Background: Rituximab is widely used in patients with steroid-dependent nephrotic syndrome. However, information on the effect of long-term rituximab treatment is limited. This study examined the efficacy of rituximab during and after treatment in adult patients with steroid-dependent nephrotic syndrome. Methods: This retrospective cohort study included 30 patients with steroid-dependent nephrotic syndrome. Patients received regular single-dose rituximab (500 mg) intravenously every 6 months. Discontinuation of rituximab was considered after four to six doses if there was no recurrence of nephrotic syndrome. Glucocorticoid discontinuation with remission, first relapse after rituximab initiation, and relapse after regular rituximab treatment discontinuation were evaluated. Results: The median age was 38 (range 18–67) years. Of 30 patients, 13 and 17 were men and women, respectively. Prior to rituximab treatment, the median number of nephrotic syndrome relapses in the patients was 5 (range 2– > 20). The 1 year discontinuation rate of glucocorticoids with remission was 83%. All patients discontinued glucocorticoid treatment at least once until 3 years and 7 months. The 1 and 2 year relapse rates after initiation of rituximab treatment were 0% and 3%, respectively. 25 patients discontinued regular rituximab treatment after a median number of six (4–12) doses. Six patients relapsed after discontinuing rituximab, and the 1 and 2 year relapse rates after the last regular rituximab treatment were 9% and 25%, respectively. Conclusion: All patients with steroid-dependent nephrotic syndrome who received rituximab could discontinue glucocorticoid treatment with remission, and three-fourths of the patients remained in remission for > 2 years after discontinuing rituximab treatment. [ABSTRACT FROM AUTHOR]

Sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) have demonstrated a blood pressure (BP) reduction benefit despite other indications for use. We evaluated BP changes and antihypertensive medication use pre‐ and post‐SGLT2i initiation among 12 960 patients with treated hypertension and among subgroups with apparent treatment‐resistant hypertension (aTRH) and/or proteinuria. Post‐SGLT2i initiation, the mean (SD) systolic blood pressure (SBP) was reduced from 133.9 (16.4) to 128.6 (15.5) mmHg and the mean diastolic blood pressure (DBP) was reduced from 70.8 (11.8) to 68.3 (11.3) mmHg among all patients. The mean SBP/DBP reduction was 5.3/2.5, 6.2/2.8, and 6.1/2.9 mmHg among all patients, patients with aTRH, and patients with proteinuria, respectively. Achieved BP < 130/80 mmHg increased by 12.5%, 16.9%, and 11.1% for all patients, patients with aTRH, and patients with proteinuria, respectively. Discontinuation of ≥ 1 antihypertensive medication within 12 months of SGLT2i initiation occurred in 33.4% overall, 47.6% of patients with aTRH, and 38.7% of patients with proteinuria. [ABSTRACT FROM AUTHOR]

Objectives Reportedly, patients with LN and low-level proteinuria have favourable short-term renal outcomes. We aimed to clarify the long-term renal outcomes and overall survival of these patients, and the significance of renal biopsy in the early phase with low-level proteinuria. Methods We included 144 Japanese patients with biopsy-proven LN from 10 hospitals. Low-level proteinuria was defined by a urine protein:creatinine ratio (UPCR) of ≤1 g/gCr based on previous reports. The outcomes were end-stage renal disease (ESRD) and death. Results Compared with patients with high-level proteinuria (UPCR >1 g/gCr), those with low-level proteinuria [ n  = 67 (46.5%)] had significantly improved renal function at the time of renal biopsy, and low activity index and chronicity index while the frequency of class III/IV was similar (79.1% vs 84.4%, P  = 0.409). In patients with low-level proteinuria, CYC usage was less, and the incidences of ESRD (3.0% vs 13.0%, P  = 0.036) and death (3.0% vs 16.9%, P  = 0.006) during the total observation period (median, 72 months) were low. Kaplan–Meier analysis showed significant differences in the incidence of ESRD and death between the groups. Multivariate Cox regression analysis revealed that the significant risk factors for ESRD were high chronicity index and hypertension, whereas those for death were increased age and high-level proteinuria. Conclusion Patients with LN and low-level proteinuria had favourable long-term renal and life outcomes. As these patients have substantial active pathological lesions, renal biopsy in the early phase with low-level proteinuria could enable early diagnosis and treatment and thus improve prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Glomerular injury may occur during pregnancy as a consequence of systemic disease and pregnancy‐related medical complications. While urinary nephrin has been shown to provide early identification of preeclampsia (PE) in high‐risk pregnancies, the role of urinary nephrin in determining glomerular injury in pregnant women is yet to be explored. This study aimed to investigate the use of urinary nephrin as a predictor for early glomerular injury in a study conducted at the Townville University Hospital. Methods and Materials: A cross‐sectional study was conducted. All pregnant women with a full dataset (n = 273) were classified into three categories according to their urinary albumin‐to‐creatinine ratio (ACR): normoalbuminuria, microalbuminuria and macroalbuminuria. Continuous variables were compared between groups, and the cut‐off value for the urinary nephrin‐to‐creatinine ratio (NCR) was determined to predict albuminuria as an indirect indicator of early glomerular injury. The percentages of pregnant women who had elevated nephrinuria were calculated for each of the ACR categories. Results: Urinary NCR positively correlated with urinary ACR (r = 0.29, p < 0.0001). Urinary NCR increased comparably in women with normoalbuminuria, microalbuminuria and macroalbuminuria. Using a cut‐off value of 14 ng/mg, nephrinuria was detected in 65% of women with normoalbuminuria, 95% with microalbuminuria and 100% with macroalbuminuria. Of the normoalbuminuric women who had an elevated urinary NCR (> 14 ng/mg), 78% were diagnosed with a hypertensive disorder and 63% were diagnosed with diabetes in pregnancy. In women with PE, urinary NCR and ACR were significantly higher when compared to women who did not develop PE. The AUC of the ROC for urinary NCR was 0.74 (95% CI: 0.650–0.824), with a sensitivity of 97% and a specificity of 36% to predict glomerular injury and a sensitivity of 93% and specificity of 42% to predict glomerular injury of PE. Conclusion: The study found that urinary NCR were elevated not only in women with micro‐ and macroalbuminuria but also in pregnant women with normoalbuminuria. Increased urinary NCR without increased urinary albumin may be associated with early glomerular injury. Urinary NCR may be a more sensitive marker than microalbuminuria to detect early glomerular injury in women with systemic disease and adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objective: Autoantibodies are a hallmark of lupus nephritis (LN), but their association with LN classes and treatment response are not adequately known. In this study, we quantified circulating autoantibodies in the Accelerating Medicines Partnership LN longitudinal cohort to identify serological biomarkers of LN histologic classification and treatment response and how these biomarkers change over time based on treatment response. Methods: Peripheral blood samples were collected from 279 patients with systemic lupus erythematosus undergoing diagnostic kidney biopsy based on proteinuria. Of these, 268 were diagnosed with LN. Thirteen autoantibody specificities were measured by bead‐based assays (Bio‐Rad Bioplex 2200) and anti‐C1q by enzyme‐linked immunosorbent assay at the time of biopsy (baseline) and at 3, 6, and 12 months after biopsy. Clinical response was determined at 12 months. Results: Proliferative LN (International Society of Nephrology/Renal Pathology Society class III/IV±V, n = 160) was associated with higher concentrations of anti‐C1q, anti‐chromatin, anti–double‐stranded DNA (dsDNA), and anti–ribosomal P autoantibodies compared to nonproliferative LN (classes I/II/V/VI, n = 108). Anti‐C1q and‐dsDNA were independently associated with proliferative LN. In proliferative LN, higher baseline anti‐C1q levels predicted complete response (area under the curve [AUC] 0.72; P = 0.002) better than baseline proteinuria (AUC 0.59; P = 0.21). Furthermore, all autoantibody levels except for anti‐La/SSB decreased over 12 months in patients with proliferative, but not membranous, LN with a complete response. Conclusion: Baseline levels of anti‐C1q and anti‐dsDNA may serve as noninvasive biomarkers of proliferative LN, and anti‐C1q may predict complete response at the time of kidney biopsy. In addition, tracking autoantibodies over time may provide further insights into treatment response and pathogenic mechanisms in patients with proliferative LN. [ABSTRACT FROM AUTHOR]

Introduction: Current rheumatology and nephrology society guidelines in lupus nephritis do not recommend renal biopsy for proteinuria of less than 500 mg/24 h. This might lead to a significant delay in the early diagnosis of lupus nephritis. Aim: The main aim of this study is to determine the nature of renal lesions in patients with low-grade proteinuria and to analyze the predictors for clinically significant lupus nephritis. Methods: This was a single-center, retrospective study. All consecutive patients of lupus nephritis, with low-grade proteinuria (200 mg to 500 mg/24 h) undergoing renal biopsy were enrolled in this study. The renal biopsies were classified into significant lesions (Class III/IV/V) and non-significant lesions (Class I and II). Treatment naïve groups and treatment-modified groups were analyzed separately. Predictive factors for significant renal lesions were determined by univariate and multivariate analysis. Results: We identified 183 patients of lupus with proteinuria between 200 and 500 mg / 24 h. Mean (SD) age was 30.2 (11.39) years with 167 (91.2%) of them being females. The mean (SD) baseline proteinuria was 351.03 (98.1) mg/24 h 85 patients (46.5%) had proliferative lupus nephritis where whereas 17 patients (9.3%) had membranous nephropathy. Crescents and fibrinoid necrosis were seen in 10 (5.46%) and 24 (13.11 %) patients respectively. Isolated proteinuria without any other sediments was seen in 95 patients (51.9%) of which 29 patients had proliferative lupus nephritis. Elevated Anti-double stranded DNA (anti-dsDNA), low C3, low C4 and the presence of urinary sediments were significantly associated with significant renal lesions in biopsy. Conclusion: Significant renal lesions were seen in around half of the patients with low-grade proteinuria underscoring the importance of performing a renal biopsy in this set of patients. Low C3 and C4, urinary sediments, and elevated anti-dsDNA were predictors for significant renal lesions. [ABSTRACT FROM AUTHOR]

Purpose: Based on the comparison of ramucirumab monoclonal antibody with control treatments in randomized controlled trials, this study aims to elucidate the role of ramucirumab monoclonal antibody in cancer therapy and its potential side effects, providing scientific evidence for clinical treatment. Methods: PubMed, Embase, Cochrane, and Web of Science were searched systematically to obtain the trials on ramucirumab in the treatment of gastric or gastroesophageal junction (GEJ) adenocarcinoma up to April 13, 2023. We included randomized controlled trials (RCTs) evaluating the efficacy and safety of ramucirumab as monotherapy and in combination with other chemotherapy agents as interventions for treating gastric or gastroesophageal junction (GEJ) adenocarcinoma. Results: After screening 2200 studies, we finally included 8 eligible studies (involving a total of 3,283 participants). Meta-analysis results showed that compared to the control group, ramucirumab monotherapy significantly improved overall survival (OS) (hazard ratio [HR] = 0.77, 95% confidence interval [CI] [0.67, 0.89]) and progression-free survival (PFS) (HR = 0.48, 95% CI [0.40, 0.58]). Similar results were obtained for ramucirumab combined with paclitaxel. In the treatment combining ramucirumab with paclitaxel, compared to monotherapy, three severe adverse reactions (grade ≥ 3) were observed with significantly increased risks (OR > 2). These include proteinuria (OR = 5.37, 95% CI [1.22, 23.54]), hypertension (OR = 4.02, 95% CI [2.63, 6.14]), and gastrointestinal perforation (OR = 4.64, 95% CI [1.00, 21.60]). Subgroup analysis further indicated that ramucirumab is effective in both non-East Asian and East Asian populations, with East Asian patients more prone to developing proteinuria, while having a lower incidence of hypertension. Additionally, ramucirumab demonstrated comparable efficacy between first-line and second-line treatments, with a higher incidence of proteinuria observed in second-line therapy. Conclusion: Ramucirumab significantly improves the prognosis of patients with gastric or gastroesophageal junction adenocarcinoma. When used in combination with paclitaxel, close monitoring of adverse reactions such as proteinuria (especially in East Asian populations), hypertension (especially in non-East Asian populations), and gastrointestinal perforation is essential. [ABSTRACT FROM AUTHOR]

Background: To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children. Methods: A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed. Results: A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury. Conclusions: Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients. [ABSTRACT FROM AUTHOR]

Background: Alport syndrome is a genetically heterogenous disorder resulting from variants in genes coding for alpha-3/4/5 chains of Collagen IV, which results in defective basement membranes in the kidney, cochlea and eye. The syndrome has different inheritance patterns and historically, was thought of as a disease affecting solely males. Case: A 15-year-old female presented with pedal oedema, hypertension and proteinuria. She underwent a kidney biopsy which showed findings in keeping with focal segmental glomerulosclerosis. Her condition was refractory to steroids. Steroid-resistant nephrotic syndrome genetics were sent, revealing a rare pathogenic variant in the COL4A5 gene. Conclusion: Heterozygous females with X-linked Alport syndrome can develop chronic kidney disease and hearing loss. Clinicians should be mindful when reviewing kidney histology to include Alport syndrome as a differential for female patients. COL4A3-5 genes should be included in all steroid-resistant nephrotic syndrome genetic panels. [ABSTRACT FROM AUTHOR]

Overactivation of mineralocorticoid receptors occurs in cardiorenal diseases. Many patients with type 2 diabetes often progress to chronic kidney disease (CKD) and require dialysis. Finerenone is the first oral non-steroidal mineralocorticoid receptor antagonist used in patients with diabetic kidney disease and heart failure. Finerenone (Kerendia®) is more potent than spironolactone in reducing inflammation and fibrosis in CKD and exerts its effect equally on the heart and kidneys, improving cardiovascular outcomes. Research demonstrates that finerenone improves proteinuria and glomerular filtration rate if taken alone or in combination with sodium-glucose transporter 2 inhibitors. Finerenone has been found to decrease mortality in patients with diabetic renal disease and improve quality of life. Its side effects, unlike those of spironolactone, do not include gynecomastia. However, it can result in hyperkalemia, which needs to be monitored. In this review, we aim to investigate the mechanisms of action of finerenone and its implications in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus and one of the leading causes of nephrotic syndrome. The disease exhibits heterogeneous outcomes with approximately 30% of cases progressing to end-stage renal disease. Traditionally, the standard approach of diagnosing MN involves performing a kidney biopsy. Nevertheless, kidney biopsy is an invasive procedure that poses risks for the patient including bleeding and pain, and bears greater costs for the health system. The clinical management of MN has steadily advanced owing to the identification of autoantibodies to the phospholipase A2 receptor (PLA2R) in 2009 and thrombospondin domain-containing 7A (THSD7A) in 2014 on the podocyte surface. At present, serum anti-PLA2R antibody detection and glomerular PLA2R antigen staining have been used for clinical diagnosis and prognosis, but the related detection of THSD7A has not been widely used in clinical practice. Here, we summarized the emerging knowledge regarding the roles THSD7A plays in MN and its clinical implications as diagnostic, prognostic, and therapeutic response as well as Methods for detecting serum THSD7A antibodies. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors in nephrotic patients on immunosuppression are underexplored. We evaluated dapagliflozin's impact in non-diabetic primary nephrotic syndrome. Methods: Randomized controlled clinical trial was conducted on 60 non-diabetic primary nephrotic syndrome patients, equally assigned to dapagliflozin and control groups. All patients received the standard of care medication and the Dapagliflozin group received 10 mg dapagliflozin in addition. Demographic data, nephrotic syndrome etiology, proteinuria levels, eGFR, and immunosuppression doses, were well-matched. After 6 months of follow up primary outcomes included changes in and eGFR. Results: Both groups exhibited significant reductions in proteinuria after 6 months, with the dapagliflozin group achieving a mean UPCR reduction of – 94.7%, and the control group – 86.7% (p < 0.001). However, the comparative change in proteinuria between both groups did not reach statistical significance (p = 0.158). Dapagliflozin initially led to a transient eGFR decline. Dapagliflozin also resulted in a significant mean body weight reduction (p < 0.001) and notable improvements in triglyceride levels compared to the control group (p = 0.045). Conclusion: In primary nephrotic syndrome patients, adjunct dapagliflozin may enhance the standard of care. While notable, the reduction in proteinuria was comparable to that of the control group by the study's end. Furthermore, after 6 months, eGFR remained stable in both groups. However, significant weight loss and serum triglyceride reduction were particularly pronounced in the dapagliflozin group. Further long-term investigations are necessary to address potential immunosuppression-related confounding effects in patients with primary glomerular disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Hypothesis/Objective Animals Methods Results Conclusion and Clinical Importance Primary glomerular disease resulting in protein‐losing nephropathy (PLN) is an uncommon cause of chronic kidney disease in cats, yet is important to recognize because it warrants specific treatment that impacts outcome.Characterize clinicopathologic findings, prognostic indicators, and short‐ (≤30 days) and long‐term survival of cats with PLN.Thirty‐seven cats with naturally occurring PLN.Medical records of cats with PLN admitted to a veterinary teaching hospital were retrospectively reviewed.Median age was 3 years (range, 1.5‐11.5 years) and 17/37 (46%) were males. Short‐term survival was 57%. The estimated median survival time of all cats was 424 days (95% confidence interval [CI], 0‐1098 days). Common clinical signs included lethargy (57%), edema (46%) and weight loss (35%). Edema was more common in short‐term survivors compared with nonsurvivors (odds ratio [OR], 0.21; 95% CI, 0.05‐0.86‐20.4; P = .04). Serum creatinine concentration at presentation was negatively associated with long‐term survival (OR, 1.3; 95% CI, 1.03‐1.52; P = .01). Administration of immunosuppressive and antiproteinuric medications was more common among short‐term survivors compared with nonsurvivors (18/20 [90%] vs 9/16 [56%]; OR, 7.0; 95% CI, 1.2‐40.8; P = .05 and 17/20 [85%] vs 7/16 [44%]; OR, 7.3; 95% CI, 1.5‐35.2; P = .01, respectively). Partial or complete remission was documented in 11/31 (36%) cats and was associated with both short (OR, 3.3; 95% CI, 1.7‐6.5; P < .001) and long‐term survival (P = .003).Cats with PLN have a guarded prognosis, but achieving remission improves outcome. Cats presented with edema rather than azotemia are more likely to respond to treatment. [ABSTRACT FROM AUTHOR]

Background: Late-onset type II Bartter syndrome is an exceedingly rare condition, with only six documented cases presenting symptoms and signs beyond infancy. We report a unique case of late-onset type II Bartter syndrome with an atypical presentation and clinical course following chemotherapy treatment during childhood. Case presentation: A 10-year-old boy, diagnosed with hepatoblastoma at age 2 and treated with cisplatin and epirubicin, presented with polyuria, polydipsia, failure to thrive, and electrolyte imbalances. He exhibited hypokalemia, metabolic alkalosis, and elevated urinary excretion of sodium, chloride, calcium, and magnesium. Whole exome sequencing and Sanger sequencing identified compound heterozygous variants in the KCNJ1 gene, confirming the diagnosis of type II Bartter syndrome. The patient's clinical presentation was distinct from previously reported cases, with an absence of nephrocalcinosis, unusually small and hyperechoic kidneys, and a substantial decline in kidney function. Treatment included oral potassium supplementation, spironolactone, and angiotensin-converting enzyme inhibitors. Conclusions: This case highlights the importance of considering late-onset Bartter syndrome in patients with a history of chemotherapy presenting with persistent electrolyte imbalances and ongoing renal dysfunction. The atypical features and rapid progression of chronic kidney disease in this patient may be attributed to the deleterious nature of the identified variants and the potential impact of previous chemotherapy on kidney susceptibility to damage. Careful monitoring and management of electrolyte imbalances and renal function are crucial in such cases. [ABSTRACT FROM AUTHOR]

Background Hypothesis Animals Methods Results Conclusion and Clinical Importance Oxidative stress is a potential contributor to chronic kidney disease (CKD) progression but has not been evaluated in dogs and cats with CKD.Oxidative stress is higher in animals with CKD compared with healthy controls and decreases with the advancing CKD stage. The aim of this study was to determine the presence and intensity of oxidative stress in dogs and cats at different CKD stages.Sixty dogs and 30 cats with naturally acquired CKD; 10 dogs and 14 cats, healthy controls.Analytical cross‐sectional study. Oxidative stress was evaluated by measuring the urinary concentration of F2‐isoprostane (uF2‐IsoPs) normalized to urinary creatinine.Urinary F2‐isoprostanes normalized to urinary creatinine of healthy dogs and of dogs with CKD Stages 1 to 4 was 3.3 ng/mg, 4.7 ng/mg (range, 1.0‐73.4), 2.4 ng/mg (range, 0.4‐7.8), 0.52 ng/mg (range, 0.01‐2.9), and 0.37 ng/mg (range, 0.01‐0.6), respectively. Urinary F2‐isoprostanes differed among CKD stages (P < .001), but not compared with controls. uF2‐IsoPs of healthy cats and cats with CKD Stages 1 to 4 was 0.68 ng/mg (range, 0.2‐1.4), 0.97 ng/mg (range, 0.4‐1.8), 0.6 ng/mg (range, 0.002‐2.0), 0.94 ng/mg (range, 0.3‐2.3), and 0.2 ng/mg (range, 0.01‐0.4). Urinary F2‐isoprostanes differed among stages (P = .05) but not compared with healthy controls.Oxidative stress might be present in dogs and cats with CKD. Its magnitude declines as the disease progresses, therefore, it should be considered a potential therapeutic target mostly at the early stages of the disease. [ABSTRACT FROM AUTHOR]

Proteinuria is an important risk factor for cardiovascular disease (CVD) and acts as a surrogate marker of renal damage. This study aimed to determine the association between changes in proteinuria and the occurrence of CVD. In our study, 1,708,712 participants who consecutively underwent national health examinations from 2003−2004 (first period) to 2005−2006 (second period) were included. They were classified into four groups based on the presence of proteinuria at the two consecutive health examinations: (1) normal (0 → 0), (2) proteinuria-improved (participants who had improved proteinuria (+ 1 → 0, + 2 → ≤ +1 [0 or + 1], ≥ +3 → ≤ +2 [0, + 1 or + 2]), (3) proteinuria-progressed (0 → ≥ +1, + 1 → ≥ +2, + 2 → ≥ +3), and (4) proteinuria-persistent (+ 1 → +1, + 2 → +2, ≥ +3 → ≥ +3). We used a multivariate Cox proportional hazards model to assess the occurrence of CVD according to changes of presence and severity of proteinuria. During a median of 14.2 years of follow-up, 143,041 participants (event rate, 8.37%) with composite CVD were observed. Compared with the normal group, the risk of incident risk of CVD was increased according to the severity of proteinuria in each of the persistent, progressed, and improved groups (p for trend < 0.001). In a pairwise comparison, the risk of composite CVD in the improved (hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.27–1.37), progressed (HR: 1.49, 95% CI: 1.44–1.54), and persistent groups (HR: 1.78, 95% CI: 1.64–1.94) were higher than that of the normal group. Furthermore, the improved group had a relatively lower risk of composite CVD compared to the persistent group (HR: 0.75, 95% CI: 0.69–0.83, p < 0.001). The incidence risk of composite CVD was associated with changes of presence and severity of proteinuria. Persistent proteinuria may be associated with increased risk of CVD, even compared with improved or progressed proteinuria status. [ABSTRACT FROM AUTHOR]