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.

Combination of the gut microbiota and clinical indicators as a potential index for differentiating idiopathic membranous nephropathy and minimal change disease.

Objectives: Membranous nephropathy (MN) and minimal change disease (MCD) are two common types of nephrotic syndrome that have similar clinical presentations but require different treatment strategies. Currently, the definitive diagnosis for these conditions relies on invasive renal biopsy, which can be limited in clinical practice.Methods: In this study, we aimed to differentiate idiopathic MN (IMN) from MCD using clinical data and gut microbiota. We collected clinical data and stool samples from 115 healthy individuals, 115 IMN, and 45 MCD at the onset of disease and performed 16S rRNA sequencing. Through machine learning methods including random forest, logistic regression, and support vector machine, a classifier to differentiate IMN from MCD was constructed.Results: Baseline clinical data comparing the IMN and MCD groups showed that the MCD had higher levels of hemoglobin, uric acid, cystatin C, ß2-microglobulin, α1-microglobulin, total cholesterol, and low-density lipoprotein and lower levels of albumin and CD4+ T-cell counts. The gut microbiota of the two groups differed at all levels of the phylum and genus. Differential gut microbiota may disturb the integrity of the intestinal wall and lead to the passage of inflammatory mediators through the intestinal barrier, causing kidney injury. We constructed a noninvasive classifier with a discrimination efficacy of 0.939 that combined the clinical data and gut microbiota information to identify IMN and MCD.Conclusions: The classifier of the gut microbiota combined with clinical indicators has achieved good performance in identifying IMN and MCD, which provides a new approach for the noninvasive discrimination of different pathological types of kidney disease.

Renal insufficiency predicts worse prognosis in newly diagnosed IgD multiple myeloma patients.

Objective: IgD multiple myeloma (MM) is a rare type of MM, accounting for about 1%-2% of all MMs. IgD MM always causes kidney damage and even leads to renal failure, which is the most common complication. This study aimed to explore the risk factors of renal damage and prognosis of IgD MM patients. Design: From March 2018 to November 2021, 85 patients with IgD MM diagnosed for the first time at the First Affiliated Hospital of Zhengzhou University were included in this study. We collected information on clinical features and laboratory examinations. Patients were divided into the renal impairment (RI) (47/85) and non-renal impairment (no-RI) (38/85) groups. Binary logistic regression was used to explore risk factors of renal damage. The Chi-square test was used to analyze the difference in chemotherapy effect between the two groups. We also analyzed whether early dialysis was beneficial to acute renal failure (RF) in IgD MM patients. Finally, Kaplan-Meier was used to compare the survival of the two groups. Results: In IgD MM, 55.3% of patients had renal damage as a complication, of which up to 59.6% presented with acute renal failure as the first manifestation. Serum ß2-microglobulin (ß2-MG) was an independent risk factor for renal damage in IgD MM (p = 0.002), but cytogenetic analysis suggested that it had no effect on patients' renal damage. There was also no significant difference in the effect of chemotherapy between the two groups (p = 0.255). In patients with acute renal failure, there was no significant difference between dialysis and no dialysis groups in the proportion of patients with improved renal function after treatment. The median overall survival (OS) of the RI group was significantly shorter than that of the no-RI group (p = 0.042). In the RI group, the median OS was 29 months, and in the no-RI group, the median OS was > 40 months. Conclusion: Elevated serum ß2-MG is an independent risk factor for renal damage. Compared with the no-RI group, patients in the RI group had poorer prognosis and shorter median OS. For patients with acute renal failure as the first manifestation, the treatment of primary disease is more meaningful than dialysis.