Adequate dialysis is essential for improving dialysis therapies and reducing all-cause mortality in end-stage renal disease (ESRD) patients. Efficient removal of the uremic toxins in the blood remains the fundamental role of dialysis therapies. Therefore, urea clearance as assessed by urea kinetic modeling (Kt/Vurea) is a surrogate marker for dialysis adequacy in ESRD patients undergoing dialysis, and the NKF-DOQI recommends a Kt/Vurea of no less than 1.2. The current status of dialysis adequacy in Korea has not been fully investigated. Our Clinical Research Center for End Stage Renal Disease revealed that the mean Kt/Vurea in maintenance hemodialysis patients was 1.49±0.28, and 91.5% of patients satisfied the target level of Kt/Vurea. In addition to Kt/Vurea, clinical parameters such as the volume status, residual renal function, blood pressure, acid-base disorders, anemia, nutrition, inflammation, mineral metabolism, and middle molecule clearance are important for determining adequate dialysis treatment. Further evaluation of clinical parameters is needed to improve dialysis adequacy.
Abstract Background and Aims Presently, the clinical outcomes associated with IgA nephropathy exhibiting heavy proteinuria and the potential correlation between decreasing serum albumin levels and adverse prognosis have not been conclusively established. The present study was designed to elucidate the clinical and pathological characteristics of IgA nephropathy patients who present with nephrotic-range proteinuria, particularly in relation to serum albumin levels. Method This retrospective cohort study was conducted using data from biopsy-confirmed IgA nephropathy patients presenting with nephrotic-range proteinuria between 2017 and 2022 from eight university-affiliated hospitals in South Korea. Patients were stratified into two groups based on a serum albumin level of 3.0 g/dl. The study involved a comparative assessment of clinical and pathological characteristics across these two groups, as well as an evaluation of clinical prognosis with respect to the end-stage kidney disease (ESKD). Results The analysis included a total of 127 patients. Of these, 86 patients had a serum albumin level above 3.0 g/dl (designated as the preserved albumin group, or PA group), while 41 patients had levels below 3.0 g/dl (designated as the reduced albumin group, or RA group). The baseline characteristics of the two groups were found to be statistically similar. The mean age of the patients was 46.46 years, and 46.46% were male. In the laboratory findings, the RA group had significantly elevated erythrocyte sedimentation rate compared to the PA group. Additionally, total cholesterol and low-density lipoprotein-cholesterol levels were significantly higher in the RA group compared to the PA group. Proteinuria was observed to be significantly higher in the RA group. Pathological examinations demonstrated that in electron microscopy (EM) findings, the RA group exhibited a more pronounced diffuse foot process effacement. Over the course of one year, the trend in creatinine changes exhibited differences between the two groups over time (time x group interaction P = 0.002). Furthermore, it appeared that the reduction in the quantity of proteinuria was more substantial within the RA group (time x group interaction P = 0.001). During a median follow-up period of 25.22 months (ranging from 11.98 to 49.23 months), 14 patients (11.02%) in the PA group progressed to ESKD, compared with 10 patient (24.39 %) in the RA group. However, there was no statistically significant difference between the two groups in terms of progression to ESKD (P = 0.330). Conclusion In patients diagnosed with IgA nephropathy presenting with nephrotic-range proteinuria, a decline in serum albumin levels was associated with diffuse foot process effacement, and the decrease in serum albumin was not found to be associated with adverse prognosis.
The increasing interest in healthcare and health screening events is revealing additional cases of asymptomatic isolated microscopic hematuria (IMH). However, a consensus of the evaluation and explanation of the IMH prognosis is controversial among physicians. Here, we present the natural course of IMH together with the pathological diagnosis and features to provide supportive data when approaching patients with IMH. We retrospectively evaluated 350 patients with IMH who underwent a renal biopsy between 2002 and 2011, and the pathological diagnosis and chronic histopathological features (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) were reviewed. Deterioration of renal function was examined during follow up. The patients with IMH were evaluated for a mean of 86 months. IgA nephropathy was the most common diagnosis in 164 patients (46.9%). Chronic histopathological changes were observed in 166 (47.4%) but was not correlated with proteinuria or a decline in renal function. Ten patients developed proteinuria, and all of them had IgA nephropathy. Three patients progressed to chronic kidney disease with an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) but none progressed to end stage renal disease. In conclusion, IMH had a generally benign course during 7-years of observation, although IgA nephropathy should be monitored if it progresses to proteinuria. Future prospective randomized studies may help conclude the long-term prognosis and lead to a consensus for managing IMH.
Kidney organoids derived from human pluripotent stem cells (hPSCs) contain multilineage nephrogenic progenitor cells and can recapitulate the development of the kidney. Kidney organoids derived from hPSCs have the potential to be applied in regenerative medicine as well as renal disease modeling, drug screening, and nephrotoxicity testing. Despite biotechnological advances, individual differences in morphological and growth characteristics among kidney organoids need to be addressed before clinical and commercial application. In this study, we hypothesized that an automated noninvasive method based on deep learning of bright-field images of kidney organoids can predict their differentiation status.Bright-field images of kidney organoids were collected on day 18 after differentiation. To train convolutional neural networks (CNNs), we utilized a transfer learning approach. CNNs were trained to predict the differentiation of kidney organoids on bright-field images based on the messenger RNA expression of renal tubular epithelial cells as well as podocytes.The best prediction model was DenseNet121 with a total Pearson correlation coefficient score of 0.783 on a test dataset. W classified the kidney organoids into two categories: organoids with above-average gene expression (Positive) and those with below-average gene expression (Negative). Comparing the best-performing CNN with human-based classifiers, the CNN algorithm had a receiver operating characteristic-area under the curve (AUC) score of 0.85, while the experts had an AUC score of 0.48.These results confirmed our original hypothesis and demonstrated that our artificial intelligence algorithm can successfully recognize the differentiation status of kidney organoids.
Autophagy is a cellular process of degradation of damaged cytoplasmic components and regulates cell death or proliferation. Unilateral ureteral obstruction (UUO) is a model of progressive renal fibrosis in the obstructed kidney. And UUO is followed by compensatory cellular proliferation in the contralateral kidney. We investigate the role of autophagy in the obstructed kidney and contralateral kidney after UUO.To obtain the evidence and the patterns of autophagy during UUO, the rats were sacrificed 3, 7 and 14 days after UUO. To examine the efficacy of the autophagy inhibitors, 3-methyladenine (3-MA), the rats were treated daily with intraperitoneal injection of 3-MA (30 mg/kg per day) for 7 days.After UUO, autophagy was induced in the obstructed kidney in a time-dependent manner. Inhibition of autophagy by 3-MA enhanced tubular cell apoptosis and tubulointerstitial fibrosis in the obstructed kidney after UUO. In the contralateral kidney, autophagy was also induced and prolonged during UUO. Inhibition of autophagy by 3-MA increased the protein expression of proliferating cell nuclear antigen significantly in the contralateral kidney after UUO. The Akt-mammalian target of rapamycin (mTOR) signalling pathway was involved in the induction of autophagy after UUO in both kidneys.Our present results support that autophagy induced by UUO has a renoprotective role in the obstructed kidney and regulatory role of compensatory cellular proliferation in the contralateral kidney through Akt-mTOR signalling pathway.
β2-Microglobulin (β2-M) is a surrogate marker of middle-molecule uremic toxins and is associated with mortality in chronic hemodialysis patients. However, the impact of serum β2-M levels on mortality in peritoneal dialysis (PD) patients is uncertain. The purpose of this study was to examine the association of serum β2-M levels with all-cause mortality in PD patients.A total of 771 PD patients were selected from the Clinical Research Center registry for end-stage renal disease cohort in Korea. Patients were categorized into 3 groups by tertiles of serum β2-M levels. The primary outcome was all-cause mortality.The median value of serum β2-M was 23.6 mg/l (interquartile range 14.8-33.4 mg/l), and the median follow-up period was 39 months. The Kaplan-Meier analysis showed that the all-cause mortality rate was significantly different according to tertiles of serum β2-M in PD patients (p=0.03, log-rank). Multivariate Cox proportional analysis showed that the hazards ratio for all-cause mortality was 1.02 (95% CI 1.01-1.04, p=0.006) per 1 mg/l increase in β2-M after adjustment for multiple confounding factors that relate to malnutrition and inflammation marker. However, serum β2-M was not associated with all-cause mortality after adjustment for residual renal clearance.These results are supportive of the potential role of the serum β2-M level as a predictor of mortality in PD patients.