Correlation analysis of cofilin-1 with renal prognosis in primary IgA nephropathy.

PURPOSE: The purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN). METHODS: Patients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR < 60 ml/min/1.73m2. Logistic and Cox regression model were used to analyze the correlation among cofilin-1 and renal prognosis. RESULTS: 133 IgAN patients were included, with a male-to-female ratio of 1.25:1 and an age of 37.67 ± 13.78 years, as well as an average of eGFR was 71.63 (40.42,109.33) ml/min/1.73m2. 56 patients (42.1%) had decreased renal function at baseline, with the average of eGFR was 34.07 (16.72, 49.21) ml/min/1.73 m2. 12 of which developed to renal adverse prognosis. The average of follow-up time was 22.035 ± 8.992 months. The multivariate regression analysis showed that increased urinary cofilin-1 was an independent risk factor associated with baseline renal function decline and renal adverse prognosis in IgAN patients (P < 0.05). ROC curves showed great efficacy of urinary cofilin-1 levels in diagnosing baseline renal function decline and predicting renal adverse prognosis (the area under the ROC curve was 0.708 and 0.803). CONCLUSION: Cofilin-1 as a novel biomarker of podocyte lesion is closely related to renal function decline in IgAN. Cofilin-1 has certain clinical value in predicting the risk of renal adverse prognosis. Podocyte fusion affects the renal prognosis of IgAN.

C4d Is an Independent Predictor of the Kidney Failure in Primary IgA Nephropathy.

Background: C4d deposits are present in a substantial proportion of patients with IgA nephropathy (IgAN), indicating the activation of the lectin pathway (LP) of the complement system. It seems that patients with activated LP have worse renal prognosis. The aim of this study was to investigate the prevalence and prognostic significance of C4d in our cohort of patients with primary IgA nephropathy (pIgAN). Methods: Patients with pIgAN were recruited from a hospital register of kidney biopsies of the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb. Additional immunohistochemistry staining for C4d was performed on paraffin-embedded kidney tissue, and patients were stratified into being C4d positive or C4d negative. The clinical and histologic features of patients were analyzed and compared regarding C4d positivity. The primary outcome was defined as kidney failure (KF), and predictor variables of KF and renal survival were analyzed. Results: Of a total of 95 patients with pIgAN included in the study, C4d was present in 43 (45.3%). C4d-positive patients had a higher value of systolic (p = 0.039) and diastolic (p = 0.006) blood pressure at diagnosis as well as higher 24 h proteinuria (p = 0.018), serum urate (p = 0.033), and lower eGFR (p < 0.001). C4d-positive patients had worse renal survival (p < 0.001), higher rates of disease progression to KF (p < 0.001), and higher proteinuria (p < 0.001) and lower eGFR (p < 0.001) at the last follow-up. Glomerular C4d was an independent predictor of disease progression to KF (HR = 5.87 [0.95 CI 1.06-32.44], p = 0.032). Conclusions: C4d is an independent predictor of disease progression in patients with pIgAN. C4d may be used as an additional marker of progressive disease course in IgAN. The therapeutic implications of C4d status in IgAN, particularly in terms of complement inhibitors application, are not yet known.

Plasma Zinc Levels in Patients with Diabetic Nephropathy: Is there a Relationship with NLRP3 Inflammasome Activation and Renal Prognosis?

Zinc is an essential trace element, and impaired zinc homeostasis may be associated with inflammation in patients with diabetic nephropathy (DN). We investigated the influence of zinc level on nod-like receptor nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome expression and renal prognosis in patients with DN. We recruited 90 patients definitively diagnosed with DN by renal biopsy and 40 healthy controls. Zinc, NLRP3, interleukin (IL)-1ß, and IL-18 levels were detected in blood samples, and the correlations between these parameters were assessed. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) evaluated the predictive value of zinc and the NLRP3 inflammasome for DN. Furthermore, patients with DN were divided into low- and normal-zinc groups to observe differences in clinical indicators and identify expression of inflammatory-related factors in renal tissue. Kaplan-Meier survival curves predicted the impact of zinc levels on renal prognosis. We found that the plasma zinc concentration in patients with DN was lower, while NLRP3, IL-1ß, and IL-18 levels were higher than were those in patients without DN (P < 0.05). Zinc level was negatively correlated with NLRP3, IL-1ß, and IL-18 levels (P < 0.01). Zinc and the NLRP3 inflammasome were predictive of DN, but their combination improved the diagnostic value. The DCA curve demonstrated a good positive net benefit in the combined model. Compared to patients with low zinc levels, patients with normal zinc levels had lower expression of NLRP3 inflammasome and a better prognosis. Zinc has a protective effect on DN and may affect NLRP3 inflammasome activation.

Association of hyperphosphatemia with renal prognosis in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Serum phosphate (P) levels are generally lower in autosomal dominant polycystic kidney disease (ADPKD) than in other kidney disorders, potentially masking the clinical significance of hyperphosphatemia. This study aimed to determine if serum P levels can predict renal outcomes in ADPKD patients. METHODS: We included 235 patients with ADPKD who were not taking drugs to treat hyperphosphatemia. Survival analysis was performed for the renal outcome of a 50% reduction in estimated glomerular filtration rate or initiation of renal replacement therapy. RESULTS: Multivariable Cox regression analyses revealed that serum P (1 mg/dL increase, HR = 2.03, P < 0.0001) was a significant risk factor for kidney disease progression. Similarly, hyperphosphatemia (P > 3.5 mg/dL, HR = 2.05; P > 4.0 mg/dL, HR = 1.90; P > 4.5 mg/dL, HR = 2.78; P > 5.0 mg/dL, HR = 27.22) was significantly associated with renal prognosis. Kaplan-Meier analysis showed significantly lower kidney survival rates in patients with P > 3.5 mg/dL than in those without hyperphosphatemia (log-rank test, P < 0.0001), and similar Kaplan-Meier analysis results were found for P > 4.0 mg/dL, P > 4.5 mg/dL, and P > 5.0 mg/dL. The 2 year kidney survival rate for ADPKD patients with P > 3.5 mg/dL was 66.7% overall and 41.4% in those with stage 4-5 CKD. For patients with P > 4.0 mg/dL, the survival rate dropped to 46.8% overall and 28.2% in those with stage 4-5 CKD, indicating a very poor prognosis. CONCLUSION: Hyperphosphatemia was associated with renal prognosis in patients with ADPKD. In these patients, attention should be paid to even mild serum P elevation of > 3.5 or > 4.0 mg/dL.

Clinical features and prognosis of patients with anti-GBM disease combined with mesangial IgA deposition.

Introduction: Anti-GBM diseases with IgA deposition in the mesangial region are rarely described.The factors influencing renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition are unknown. Methods: We searched the pathological reports of the First Affiliated Hospital of Zhengzhou University from 2015 to 2023 and found that a total of 72 patients with the anti-GBM disease and 25 patients combined with mesangial IgA deposition. We studied the clinical and pathological features, renal prognosis, and the factors affecting renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Results: Their median age was 44 years, and their age distribution was unimodal. The proportion of oliguria or anuria in patients with anti-GBM disease combined with mesangial IgA deposition was significantly lower than that in patients with classic anti-GBM disease (13.04 vs. 42.31%, p=0.030). Their 24-hour urinary protein excretion was significantly higher [median:3.25 vs. 1.12g/24h, Interquartile range(IQR):1.032~3.945 vs. 0.63~1.79g/24h, p=0.020], serum creatinine (SCr) level at the initial diagnosis was lower(median:456.0 vs. 825.5µmol/L, IQR:270.0~702.0 vs. 515.8~1231.2µmol/L, p=0.002), peak SCr level was lower (median: 601.0 vs. 907.2µmol/L, IQR: 376.5~937.0 vs. 607.0~1361.2µmol/L, p=0.007), and their serum complement 3(C3) level was higher(median: 1.275 vs. 1.015g/L, IQR:1.097~1.462 vs. 0.850~1.220g/L, p=0.027). They had better renal outcomes during follow-up (p<0.001). After adjustment for hypertension, oliguria or anuria, and crescents%, IgA deposition in the mesangial region was still an independent protective factor (p=0.003) for ESRD in anti-GBM patients. Hypertension (p=0.026) and SCr levels at initial diagnosis (p=0.004) were risk factors for renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Discussion: Patients with anti-GBM disease combined with mesangial IgA deposition have less severe renal impairment and better renal prognosis than patients with classic anti-GBM disease.

Fractional excretion of total protein predicts renal prognosis in Japanese patients with primary membranous nephropathy.

Background: Primary membranous nephropathy (pMN) is one of the most common types of glomerulonephritis, with a third of patients progressing to renal insufficiency. Various prognostic factors have been reported, of which urinary protein and renal function are the most critical parameters. Fractional excretion of total protein (FETP) indicates protein leakage that accounts for creatinine kinetics and serum protein levels. In this study, we investigated the association between FETP and renal prognosis in pMN. Methods: We retrospectively identified 150 patients with pMN. FETP was calculated as follows: (serum creatinine × urine protein)/(serum protein × urine creatinine) %. We divided the patients into three groups according to FETP values and compared the clinicopathological findings. The primary outcome was an estimated glomerular filtration rate (eGFR) decrease of ≥30% from the baseline level. Results: FETP was associated with urinary protein and renal function, Ehrenreich and Churg stage, and global glomerulosclerosis. The primary outcome was observed in 38 patients (25.3%), and the frequency of the primary outcome was higher in the high FETP group (P = .001). FETP is higher than protein-creatinine ratio (PCR) in the area under the curve. In the multivariate analysis adjusted for age, eGFR, PCR and treatment, FETP was significantly associated with primary outcome (adjusted hazard ratio, 8.19; P = .019). Conclusions: FETP is a valuable indicator that can reflect the pathophysiology and is more useful than PCR as a predictor of renal prognosis in patients with Japanese pMN.

The predictive value of free thyroxine combined with tubular atrophy/interstitial fibrosis for poor prognosis in patients with IgA nephropathy.

Background: IgA nephropathy (IgAN), the most common type of glomerulonephritis, has great individual differences in prognosis. Many studies showed the relationship between thyroid hormones and chronic kidney disease. However, the relationship between free thyroxine (FT4), as a thyroid hormone, and IgAN is still unclear. This study aimed to evaluate the impact of FT4 on IgAN prognosis. Methods: This retrospective study involved 223 patients with biopsy-proven IgAN. The renal composite outcomes were defined as: (1) ESRD, defined as eGFR < 15 ml/(min·1.73 m2) or initiation of renal replacement therapy (hemodialysis, peritoneal dialysis, renal transplantation); (2) serum creatinine doubled from baseline; (3) eGFR decreased by more than 50% from baseline. The predictive value was determined by the area under the curve (AUC). Kaplan-Meier and Cox proportional hazards analyses assessed renal progression and prognosis. Results: After 38 (26-54) months of follow-up, 23 patients (10.3%) experienced renal composite outcomes. Kaplan-Meier survival curve analysis showed that the renal survival rate of the IgAN patients with FT4<15.18pmol/L was lower than that with FT4≥15.18pmol/L (P < 0. 001). Multivariate Cox regression model analysis showed that FT4 was a protective factor for poor prognosis of IgAN patients, whether as a continuous variable or a categorical variable (HR 0.68, 95%CI 0.51-0.90, P =0.007; HR 0.04, 95%CI 0.01-0.20, P <0.001). ROC curve analysis showed that FT4 combined with t score had a high predictive value for poor prognosis of IgAN patients (AUC=0.881, P<0.001). Conclusion: FT4 was a protective factor for IgAN. In addition, FT4 combined with tubular atrophy/interstitial fibrosis had a high predictive value for poor prognosis of IgAN.

Reproducibility and prognostic ability of chronicity parameters in kidney biopsy - Comprehensive evaluation comparing microscopy and artificial intelligence in digital pathology.

INTRODUCTION: Semi-quantitative scoring of various parameters in renal biopsy is accepted as an important tool to assess disease activity and prognostication. There are concerns on the impact of interobserver variability in its prognostic utility, generating a need for computerized quantification. METHODS: We studied 94 patients with renal biopsies, 45 with native diseases and 49 transplant patients with index biopsies for Polyomavirus nephropathy. Chronicity scores were evaluated using two methods. A standard definition diagram was agreed after international consultation and four renal pathologists scored each parameter in a double-blinded manner. Interstitial fibrosis (IF) score was assessed with five different computerized and AI-based algorithms on trichrome and PAS stains. RESULTS: There was strong prognostic correlation with renal function and graft outcome at a median follow-up ranging from 24 to 42 months respectively, independent of moderate concordance for pathologists scores. IF scores with two of the computerized algorithms showed significant correlation with estimated glomerular filtration rate (eGFR) at biopsy but not at the end of follow-up. There was poor concordance for AI based platforms. CONCLUSION: Chronicity scores are robust prognostic tools despite interobserver reproducibility. AI-algorithms have absolute precision but are limited by significant variation when different hardware and software algorithms are used for quantification.

Renal outcome of living kidney donors aged more than 70 years.

BACKGROUND: The number of marginal living kidney donors has increased. Medically complex donors who have hypertension, older age, or low estimated glomerular filtration rate (eGFR) have been more likely to be used. METHODS: We conducted a retrospective cohort study of living kidney donors at a single center. We analyzed 309 living donors and divided them into three groups: group with older donors (aged ≥70 years) (n = 41), middle-aged (aged 46-69 years) (n = 239), and young donors (aged <46 years) (N = 29). Donor factors associated with chronic kidney disease (CKD) stage 3b or worse within 5 years post-donation were investigated. RESULTS: Of the 309 live donors, 86 (27.8%) developed CKD stage3b or worse within 5 years post-donation. The incidence of CKD stage3b or worse within 5 years post-donation was significantly higher in older donor (p < 0.01). Cox regression models revealed that older donor ages and lower eGFR were significantly related to the development of CKD stage3b or worse, independent of comorbidities such as obesity and hypertension [hazard ratio (95% CI); 4.59 (1.02-20.6), p = 047, 0.95 (0.94-0.96), p ≤ 0.01, respectively]. However, recovery of eGFR 4-5 years after donation was noted in the middle-aged and older donor groups, whereas the level of eGFR remained unchanged in the young group. CONCLUSIONS: Older donors tend to develop CKD stage3b within 5 years post-donation but with the potential of recovery. Healthy older people (aged ≥70 years) could be candidates for living donors under careful monitoring of kidney function after donation.

Combined Effects of the Serum IgA/C3 Ratio and Glomerular C3 Staining on the Renal Outcome in Adult Immunoglobulin A Nephropathy.

INTRODUCTION: The aim of this study was to evaluate the predictive value of the serum IgA/C3 ratio and glomerular C3 deposits in kidney biopsy in adult IgA nephropathy. METHODS: The study included 718 adult IgAN patients diagnosed based on kidney biopsy. Patients without corticosteroids or immunosuppressive drugs >1 month were regularly followed up for at least 1 year or until the study endpoint. The optimum serum IgA/C3 ratio was calculated by the AUROC-based cutoff ratio. Proteinuria, creatinine, eGFR, serum IgA, and serum C3 were evaluated at baseline. Kidney biopsy was categorized using the Oxford classification, with a calculation of the MEST-C score. The degree of glomerular C3 staining was semiquantitatively determined (grade 0, no or trace; grade 1, mild; grade 2, moderate; grade 3, marked) by immunofluorescence microscopy. The patients were divided into four groups by the serum IgA/C3 ratio and glomerular C3 staining. RESULTS: The baseline data suggested that when the serum IgA/C3 ratio was at the same level, patients with a high glomerular C3 staining score (≥2) always had mesangial proliferation, segmental glomerulosclerosis, and tubular atrophy/interstitial fibrosis (group 1 vs. group 2; group 3 vs. group 4). When glomerular C3 staining was at the same level, proteinuria was significantly higher in patients with serum IgA/C3<2.806 (group 1 vs. group 3; group 2 vs. group 4), which was contrary to previous studies that have suggested that the serum level of IgA/C3 was associated with disease severity. Hence, this study set out to investigate the combined effects of the serum IgA/C3 ratio and glomerular C3 staining on the renal outcome in adult IgA nephropathy. Renal survival analysis indicated that serum IgA/C3 ≥2.806 and glomerular C3 staining ≥2 (group 1) may be correlated with a poorer prognosis, especially in different clinicopathological characteristics of IgAN patients based on the subgroup analysis. Multivariate Cox analysis demonstrated that hypertension, serum creatinine, CKD stage, T1/2 and C3 staining were independent predictive factors of renal survival. CONCLUSIONS: The combination of serum IgA/C3 and C3 staining may contribute to improved optimization of the prognostic model in IgAN patients, especially patients with different sexes and degrees of disease. However, further study is required for validation in the future.

Thickened Perirenal Fat Predicts Poor Renal Outcome in Patients with Immunoglobulin A Nephropathy: A Population-Based Retrospective Cohort Study.

Introduction: Perirenal fat is a pad that fills the retroperitoneal space outside the kidney, which affects kidney function in various ways. However, the association between perirenal fat and IgA nephropathy (IgAN) has not yet been elucidated. This study aimed to investigate the role of perirenal fat in predicting IgAN progression. Methods: A total of 473 patients with biopsy-proven IgAN and follow-up information were recruited, and perirenal fat thickness (PFT) was measured using color Doppler ultrasonography at renal biopsy. Patients were divided into two groups according to the median PFT: the low-PFT group (PFT ≤1.34 cm, n = 239) and the high PFT group (PFT >1.35 cm, n = 234). A total of 473 healthy participants were included in the control group. Basic clinical characteristics were assessed at the time of renal biopsy, and the relationship between PFT and combined endpoints was analyzed. The renal composite endpoints were defined as a two-fold increase in blood creatinine level, end-stage renal disease (dialysis over 3 months). Kaplan-Meier survival analysis was used to explore the role of PFT in the progression of IgAN. Three clinicopathological models of multivariate Cox regression analysis were established to evaluate the association between PFT and renal prognosis in patients with IgAN. Results: Compared to healthy subjects, patients with IgAN showed significantly higher PFT. After a median follow-up of 50 months, 75 of 473 patients (15.9%) with IgAN reached renal composite endpoints. Among those, 13 of 239 patients (5.4%) were in the low PFT group, and 62 of 234 patients (26.5%) were in the high PFT group (p < 0.001). The results of three Cox regression models (including demographics, pathological and clinical indicators, and PFT) demonstrated that a higher PFT was significantly associated with a higher risk of reaching renal composite endpoints in patients with IgAN. Conclusion: This study indicated a positive relationship between PFT at renal biopsy and renal progression in patients with IgAN, suggesting that perirenal fat might act as a marker of poor prognosis in patients with IgAN.

Clinical significance of amphiregulin in patients with chronic kidney disease.

BACKGROUND: Amphiregulin (AREG) is a ligand of epidermal growth factor receptor (EGFR), which plays an important role in injury-induced kidney fibrosis. However, the clinical significance of serum soluble AREG in chronic kidney disease (CKD) is unclear. In this study, we elucidated the clinical significance of serum soluble AREG in CKD by analyzing the association of serum soluble AREG levels with renal function and other clinical parameters in patients with CKD. METHODS: In total, 418 Japanese patients with CKD were enrolled, and serum samples were collected for the determination of soluble AREG and creatinine (Cr) levels, and other clinical parameters. Additionally, these parameters were evaluated after 2 and 3 years. Moreover, immunohistochemical assay was performed ate AREG expression in the kidney tissues of patients with CKD. RESULTS: Soluble AREG levels were positively correlated with serum Cr (p < 0.0001). Notably, initial AREG levels were positively correlated with changes in renal function (ΔCr) after 2 (p < 0.0001) and 3 years (P = 0.048). Additionally, soluble AREG levels were significantly higher (p < 0.05) in patients with diabetic nephropathy or primary hypertension. Moreover, AREG was highly expressed in renal tubular cells in patients with advanced CKD, but only weakly expressed in patients with preserved renal function. CONCLUSION: Serum soluble AREG levels were significantly correlated with renal function, and changes in renal function after 2 and 3 years, indicating that serum soluble AREG levels might serve as a biomarker of renal function and renal prognosis in CKD.

The association of normal-range serum phosphorus with immunoglobulin A nephropathy progression: a retrospective cohort study.

PURPOSE: The relationship between serum phosphorus and immunoglobulin A (IgA) nephropathy progression remains uncertain, especially normal-range serum phosphorus. Therefore, we herein examined the relationship between the normal-range serum phosphorus and the progression of IgA nephropathy. METHODS: One hundred sixty-two patients with primary IgA nephropathy were divided into three groups according to tertiles of baseline serum phosphorus (first tertile: 0.73-1.04 mmol/L; second tertile: 1.04-1.21 mmol/L; third tertile: 1.21-1.60 mmol/L). Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration. The composite outcome was defined as a decrease of at least 50% in eGFR from baseline or end-stage kidney disease (ESKD). The association of serum phosphorus with IgA nephropathy progression was estimated using Cox proportional hazards models, adjusting for potential confounders. RESULTS: During a median 16 month follow-up period, 15 patients reached a composite outcome. In the crude Cox proportional hazard model, baseline serum phosphorus as a continuous variable was associated with increased risk for adverse renal outcomes [hazard ratio (HR) = 63.510, 95% confidence interval (CI) = 3.953-1020.284, P = 0.003], and the high tertile of serum phosphorus group had an increased risk of the composite outcome by using the low tertile group as the reference (HR = 11.895, 95% CI = 1.522-92.993, P = 0.018). After adjustment for traditional risk factors, the high tertile of serum phosphorus group was significantly related to IgA nephropathy progression compared with the low tertile group (HR = 9.424, 95% CI = 1.019-87.165, P = 0.048). CONCLUSIONS: Relatively higher serum phosphorus levels within the normal range were significantly associated with the progression of IgA nephropathy.

Using Renal Elastography to Predict the Therapeutic Response of Nephrological Patients.

BACKGROUND: The standard method for assessing chronic renal damage is renal biopsy, which has limitations due to its invasiveness. Ultrasound elastography is a non-invasive technique that quantifies tissue elasticity and can be used to determine Young's modulus (YM). Although this breakthrough technology has been successfully employed to evaluate liver stiffness and the extent of fibrosis, its application in kidney-related conditions still needs improvement. METHODS: Our study aimed to verify the correlation between renal elastography and the chronic histological score determined via renal biopsy, evaluate the correlation between elastography and response to treatment in the short-term follow-up (6 months), and compare elastography data between renal disease patients (AKD-P) and healthy controls (HP). RESULTS: The analyzed population consisted of 82 patients (41 HP and 41 AKD-P). The AKD-P were divided into responders (R) or non-responders (NR) based on the criteria established by the guidelines. No association was found between renal stiffness and chronic histological score. Elastography data revealed median YM values of 6.15 kPa for AKD-P and 12.2 kPa for HP, with a statistically significant difference. The median YM values of the R and NR groups were 7.4 KPa and 5.6 KPa, respectively (p = 0.037). CONCLUSIONS: Patient responsiveness was associated with YM, with lower values observed in the NR group. We also found that the healthy controls exhibited significantly higher YM values than the renal disease population.

Immediate drop of urine osmolality upon tolvaptan initiation predicts impact on renal prognosis in patients with ADPKD.

BACKGROUND AND HYPOTHESIS: Tolvaptan, a vasopressin V2 receptor antagonist, is used for treating autosomal dominant polycystic kidney disease (ADPKD). We focused on changes in urinary osmolality (U-Osm) after tolvaptan initiation to determine whether they were associated with the therapeutic response to tolvaptan. METHODS: This was a single-centre, prospective, observational cohort study. Seventy-two patients with ADPKD who received tolvaptan were recruited. We analysed the relationship between changes in U-Osm and annual estimated glomerular filtration rate (eGFR) in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The mean value of U-Osm immediately before tolvaptan initiation was 351.8 ± 142.2 mosm/kg H2O, which decreased to 97.6 ± 23.8 mosm/kg H2O in the evening. The decrease in U-Osm was maintained in the outpatient clinic 1 month later. However, the values of U-Osm showed higher variability (160.2 ± 83.8 mosm/kg H2O) than did those in the first evening of tolvaptan administration. Multivariate analysis revealed that the baseline eGFR, baseline urinary protein, and U-Osm change in the evening of the day of admission (initial U-Osm drop) were significantly correlated with the subsequent annual change in eGFR. CONCLUSIONS: U-Osm can be measured easily and rapidly, and U-Osm change within a short time after tolvaptan initiation may be a useful index for the renal prognosis in actual clinical practice.

Risk of end-stage renal disease in patients with early-onset lupus nephritis: A population-based cohort study.

OBJECTIVE: To compare the risk of end-stage renal disease (ESRD) between patients with early-onset lupus nephritis (EOLN) and those with delayed-onset LN (DOLN). METHODS: This retrospective study of incident cases of systemic lupus erythematosus (SLE) used nationwide Korean claims databases and data from 2008 through 2018. We divided LN patients into two groups: the EOLN group (with LN onset within 12 months of SLE diagnoses) and the DOLN group (with LN onset later than 12 months after SLE diagnoses). Patients were observed from the date of LN diagnosis to the development of ESRD, death, or the last follow-up. Cox proportional hazards modeling was used to predict hazard ratios (HRs) for progression to ESRD with death as a competing risk. RESULTS: We identified 3779 incident SLE patients who developed LN during follow-up: 60 % (n = 2281) had EOLN, and 40 % (n = 1489) had DOLN. Sixty-nine patients with EOLN (3.0 %) and 29 patients with DOLN (1.9 %) progressed to ESRD. After adjusting for confounders, the ESRD risk associated with EOLN was comparable to the risk associated with DOLN (HR 1.10, 95 % confidence interval [CI] 0.57 to 2.11). In the subgroup of patients on aggressive immunosuppressive therapy (670 with EOLN and 179 with DOLN), the ESRD risk was higher in the DOLN group (HR 2.6, 95 % CI 1.11 to 6.10). CONCLUSION: The risk of ESRD was comparable between patients with EOLN and DOLN. However, among patients on aggressive immunosuppressive therapy, compared with EOLN, DOLN was associated with a higher risk of progression to ESRD.

Diagnostic value of α1-MG and URBP in early diabetic renal impairment.

Aims/Introduction: Diabetic kidney disease (DKD) is defined as diabetes with impaired renal function, elevated urinary albumin excretion, or both. DKD is one of the most common microvascular complications of diabetes and plays an important role in the cause of end-stage renal disease (ESRD). About 5% of people with type 2 diabetes (T2DM) already have kidney damage at the time they are diagnosed, but other triggers of renal insufficiency, such as obesity, hyperlipidemia, glomerular atherosclerosis are often present, making it difficult to define "diabetic kidney disease" or "diabetic nephropathy" precisely in epidemiology or clinical practice. Therefore, the aim of this study is to identify diabetic patients with CKD at an early stage, and evaluate the value of tubular injury markers including α1-microglobulin (α1-MG), ß2-microglobulin (ß2-MG), N-acetyl-beta-D-glucosaminidase (NAG) and Urinary retinol binding protein (URBP) in the development of diabetes to DKD. Materials and methods: We recruited a total of 182 hospitalized patients with T2DM in the First Affiliated Hospital of Zhengzhou University from February 2018 to April 2023. We collected basic clinical characteristics and laboratory biochemical parameters of the patients. Based on their levels of urinary albumin creatinine ratio (UACR) and glomerular filtration rate (GFR), patients were divided into DM group (UACR≤30 mg/g and eGFR≥90 mL/min/1.73 m2, n = 63) and DKD group (UACR>30 mg/g or eGFR<90 mL/min/1.73 m2, n = 119) excluding other causes of chronic kidney disease. We further developed diagnostic models to improve the ability to predict the risk of developing DKD by screening potential risk factors using univariate and multivariate logistic regression analysis. Calibration plots and curve analysis were used to validate the model and clinical usefulness. Next, we screened patients with relatively normal estimated glomerular filtration rate (eGFR) (≥90 mL/min/1.73 m2) to investigate whether tubular injury markers could accurately predict the risk of DKD in patients with normal renal function. We defined the rate of GFR decline as a prognostic indicator of renal function in patients and collected the information of the re-hospitalized DKD patients to determine whether the relevant indicators had an impact on the renal prognosis. Results: The patients with DKD had higher levels of tubular injury markers than patients with DM. URBP, α1-MG, eGFR were statistically different in both univariate and multivariate logistic regression analyses and displayed great predictive power after modeling with an area under curve of 0.987. The calibration curve showed medium agreement. Decision curve showed it would add more net benefits for clinical decision. After adjusting eGFR and serum creatinine (Scr), URBP was demonstrated to be associated with early renal function impairment. Conclusion: Tubular injury markers play an important role in early diabetic renal function impairment.

PKD1 Mutation Is a Biomarker for Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) occurs in 1 in 500-4000 people worldwide. Genetic mutation is a biomarker for predicting renal dysfunction in patients with ADPKD. In this study, we performed a genetic analysis of Japanese patients with ADPKD to investigate the prognostic utility of genetic mutations in predicting renal function outcomes. METHODS: Patients clinically diagnosed with ADPKD underwent a panel genetic test for germline mutations in PKD1 and PKD2. This study was conducted with the approval of the Ethics Committee of Juntendo University (no. 2019107). RESULTS: Of 436 patients, 366 (83.9%) had genetic mutations. Notably, patients with PKD1 mutation had a significantly decreased ΔeGFR/year compared to patients with PKD2 mutation, indicating a progression of renal dysfunction (-3.50 vs. -2.04 mL/min/1.73 m2/year, p = 0.066). Furthermore, PKD1 truncated mutations had a significantly decreased ΔeGFR/year compared to PKD1 non-truncated mutations in the population aged over 65 years (-6.56 vs. -2.16 mL/min/1.73 m2/year, p = 0.049). Multivariate analysis showed that PKD1 mutation was a more significant risk factor than PKD2 mutation (odds ratio, 1.81; 95% confidence interval, 1.11-3.16; p = 0.020). CONCLUSIONS: The analysis of germline mutations can predict renal prognosis in Japanese patients with ADPKD, and PKD1 mutation is a biomarker of ADPKD.

Combination of anti-C1qA08 and anti-mCRP a.a.35-47 antibodies is associated with renal prognosis of patients with lupus nephritis.

Objective: The aim of this study is to explore the prevalence and clinicopathological associations between anti-C1qA08 antibodies and anti-monomeric CRP (mCRP) a.a.35-47 antibodies and to explore the interaction between C1q and mCRP. Methods: Ninety patients with biopsy-proven lupus nephritis were included from a Chinese cohort. Plasma samples collected on the day of renal biopsy were tested for anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies. The associations between these two autoantibodies and clinicopathologic features and long-term prognosis were analyzed. The interaction between C1q and mCRP was further investigated by ELISA, and the key linear epitopes of the combination of cholesterol binding sequence (CBS; a.a.35-47) and C1qA08 were tested by competitive inhibition assays. The surface plasmon resonance (SPR) was used to further verify the results. Results: The prevalence of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were 50/90 (61.1%) and 45/90 (50.0%), respectively. Levels of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were negatively correlated with serum C3 concentrations ((0.5(0.22-1.19) g/L vs. 0.39(0.15-1.38) g/L, P=0.002) and (0.48(0.44-0.88) g/L vs. 0.41(0.15-1.38) g/L, P=0.028), respectively. Levels of anti-C1qA08 antibodies were correlated with the score of fibrous crescents and tubular atrophy (r=-0.256, P=0.014 and r=-0.25, P=0.016, respectively). The patients with double positive antibodies showed worse renal prognosis than that of the double negative group (HR 0.899 (95% CI: 0.739-1.059), P=0.0336). The binding of mCRP to C1q was confirmed by ELISA. The key linear epitopes of the combination were a.a.35-47 and C1qA08, which were confirmed by competitive inhibition experiments and SPR. Conclusion: The combination of anti-C1qA08 and anti-mCRP a.a.35-47 autoantibodies could predict a poor renal outcome. The key linear epitopes of the combination of C1q and mCRP were C1qA08 and a.a.35-47. A08 was an important epitope for the classical pathway complement activation and a.a.35-47 could inhibit this process.

Evaluation of three scoring systems for predicting renal prognosis in antineutrophil cytoplasmic antibody-associated glomerulonephritis.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) is characterized by rapidly progressive glomerulonephritis, and timely initiation of treatment and evaluation is critical to prevent the progression of renal disease to end-stage renal disease (ESRD). The aim of this study was to evaluate predictive value of the renal risk score (RRS), Birmingham vasculitis activity score (BVAS), and renal vascular lesions (RVLs) score for renal prognosis in AAGN. METHODS: A retrospective analysis of ninety-four patients diagnosed with AAGN after renal biopsy was performed. The RRS, BVAS, and RVLs score were evaluated in relation to clinicopathologic features and renal prognosis. A receiver operating characteristic curve (ROC) was used to evaluate their renal prognostic value. RESULTS: The median follow-up time was 36 months. Thirty-eight patients progressed to ESRD. Survival analysis showed that renal prognosis worsened in the RRS group in order of low, medium, and high RRS (P < 0.05). Within the RVLs group, the renal prognosis of the groups with severe and moderate RVLs was worse than that of the group without RVLs (P = 0.012, P < 0.001), and the group with mild RVLs was close to that of the group without RVLs. ROC analysis showed that the AUC of RRS, BVAS, RVLs score, RVLs score combined with RRS (RVLs score & RRS, RR), RVLs score, and RRS combined with BVAS (RVLs score & RRS & BVAS, RRB) were 0.865, 0.624, 0.763, 0.910, and 0.942, respectively. The predictive power of RRB and RR was comparable and significantly better than the RRS, BVAS, and RVLs score. Based on simplicity and validity, RR was selected as the best predictor, and the relationship between RRS, RVLs score, and RR was calculated using a linear fit, resulting in the linear equation RR = -0.4766 + 0.1231 × RVLs score + 0.395 × RRS (P < 0.001). CONCLUSIONS: In AAGN, the predictive power of RR for renal prognosis was superior to that of RRS, BVAS, and RVLs score. RR may serve as a new predictor of renal prognosis in AAGN.