To summarize the clinicopathological features and prognosis of kidney injury after hematopoietic stem cell transplantation (HSCT), to provide basis for preventing its occurrence and development. By using a retrospective cohort study method, we collected the clinical and renal biopsy pathological data of all the patients who hospitalized in the Department of Nephrology of Peking University First Hospital from June 2011 to June 2021 with renal injury after HSCT and underwent renal biopsy, and prognosis was followed up by telephone. The clinical laboratory characteristics, renal pathology and prognosis, and their association were analyzed. The results showed that the most common clinical phenotype was chronic kidney disease (CKD,69.2%, 18/26), in this term 13/18 patients received stem cells from haploidentical donors, and 11/18 patients experienced with extrarenal graft-versus-host disease (GVHD). The most common pathologic phenotype was thrombotic microangiopathy (TMA, 61.5%, 16/26). Renal function returned to baseline level in 6 patients, and the kidney survival at 2 years and 5 years were 95.7% (22/23) and 87.5% (14/16), respectively. In conclusion, the clinical phenotype of renal injury after HSCT were mainly CKD, and the most common pathologic phenotype was TMA, the long-term prognosis was favourable.
Humans ; Retrospective Studies ; Kidney/pathology* ; Hematopoietic Stem Cell Transplantation/methods* ; Thrombotic Microangiopathies/pathology* ; Renal Insufficiency, Chronic/pathology*

This study aims to explore the effect of icariin(ICA) on mitochondrial dynamics in a rat model of chronic renal failure(CRF) and to investigate the molecular mechanism of ICA against renal interstitial fibrosis(RIF). CRF was induced in male Sprague-Dawley(SD) rats with 5/6(ablation and infarction, A/I) surgery(right kidney ablation and 2/3 infarction of the left kidney). Four weeks after surgery, the model rats were randomized into the following groups: 5/6(A/I) group, 5/6(A/I)+low-dose ICA group, and 5/6(A/I)+high-dose ICA group. Another 12 rats that received sham operation were randomly classified into 2 groups: sham group and sham+ICAH group. Eight weeks after treatment, the expression of collagen-Ⅰ(Col-Ⅰ), collagen-Ⅲ(Col-Ⅲ), mitochondrial dynamics-related proteins(p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2), and mitochondrial function-related proteins(TFAM, ATP6) in the remnant kidney tissues was detected by Western blot. The expression of α-smooth muscle actin(α-SMA) was examined by immunohistochemical(IHC) staining. The NRK-52 E cells, a rat proximal renal tubular epithelial cell line, were cultured in vitro and treated with ICA of different concentration. Cell viability was detected by CCK-8 assay. In NRK-52 E cells stimulated with 20 ng·mL~(-1) TGF-β1 for 24 h, the effect of ICA on fibronectin(Fn), connective tissue growth factor(CTGF), p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 was detected by Western blot, and the ATP content and the mitochondrial morphology were determined. The 20 ng·mL~(-1) TGF-β1-stimulated NRK-52 E cells were treated with or without 5 μmol·L~(-1) ICA+10 μmol·L~(-1) mitochondrial fusion promoter M1(MFP-M1) for 24 h and the expression of fibrosis markers Fn and CTGF was detected by Western blot. Western blot result showed that the levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were increased and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were decreased in 5/6(A/I) group compared with those in the sham group. The levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were significantly lower and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were significantly higher in ICA groups than that in 5/6(A/I) group. IHC staining demonstrated that for the expression of α-SMA in the renal interstitium was higher in the 5/6(A/I) group than in the sham group and that the expression in the ICA groups was significantly lower than that in the 5/6(A/I) group. Furthermore, the improvement in the fibrosis, mitochondrial dynamics, and mitochondrial function were particularly prominent in rats receiving the high dose of ICA. The in vitro experiment revealed that ICA dose-dependently inhibited the increase of Fn, CTGF, and p-Drp1 S616, increased p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6, elevated ATP content, and improved mitochondrial morphology of NRK-52 E cells stimulated by TGF-β1. ICA combined with MFP-M1 further down-regulated the expression of Fn and CTGF in NRK-52 E cells stimulated by TGF-β1 compared with ICA alone. In conclusion, ICA attenuated RIF of CRF by improving mitochondrial dynamics.
Adenosine Triphosphate/pharmacology* ; Animals ; Female ; Fibrosis ; Flavonoids ; Humans ; Infarction/pathology* ; Kidney ; Kidney Failure, Chronic ; Male ; Mitochondrial Dynamics ; Rats ; Rats, Sprague-Dawley ; Renal Insufficiency, Chronic ; Transforming Growth Factor beta1/metabolism*

Vascular calcification is the crucial factor of high cardiovascular disease morbidity and mortality in patients with chronic kidney disease (CKD), which causes a huge medical and economic burden. It is urgent to explore its pathogenesis and intervention methods. CKD-associated vascular calcification is an ectopic osteogenesis process actively regulated by multiple cells. Vascular smooth muscle cells (VSMCs) undergo osteogenic differentiation in a pro-calcification environment, and secrete matrix vesicles to form calcium and phosphorus crystal deposition sites, which are key events in the development of CKD-associated vascular calcification. This article reviews the new mechanism and technology of CKD-associated vascular calcification and discusses the role of the myokine Irisin in CKD-associated vascular calcification.
Humans ; Osteogenesis ; Renal Insufficiency, Chronic ; Vascular Calcification/pathology* ; Proteins ; Cardiovascular Diseases/complications* ; Disease Progression ; Myocytes, Smooth Muscle

Female ; Glomerulonephritis, IGA ; metabolism ; pathology ; Glomerulonephritis, Membranous ; metabolism ; pathology ; Glomerulosclerosis, Focal Segmental ; metabolism ; pathology ; Humans ; Kidney ; metabolism ; pathology ; Male ; Renal Insufficiency, Chronic ; metabolism ; pathology

Animals ; Big Data ; Humans ; Kidney ; metabolism ; pathology ; Kidney Failure, Chronic ; metabolism ; pathology ; Natural Language Processing ; Renal Insufficiency, Chronic ; metabolism ; pathology

BACKGROUND: High fluoride levels in drinking water in relation to the prevalence of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka were investigated using rats as an experimental model. METHOD: The effects of fluoride after oral administration of Sodium fluoride (NaF) at levels of 0, 0.5, 5 and 20 ppm F were evaluated in adult male Wistar rats. Thirty-six rats were randomly divided into 4 groups (n = 9), namely, control, test I, II, and III. Control group was given daily 1 ml/rat of distilled water and test groups I, II, and III were treated 1 ml/rat of NaF doses of 0.5, 5, and 20 ppm, respectively, by using a stomach tube. Three rats from the control group and each experimental group were sacrificed after 15, 30, and 60 days following treatment. Serological and histopathological investigations were carried out using blood, kidney, and liver. RESULTS: No significant differences were observed in body weight gain and relative organ weights of the liver and kidney in fluoride-treated groups compared to control group. After 60 days of fluoride administration, group I showed a mild portal inflammation with lytic necrosis while multiple areas of focal necrosis and various degrees of portal inflammation were observed in groups II and III. This was further confirmed by increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. As compared with control and other treated groups, group III showed a significantly higher serum AST activity (p < 0.05) and ALT activity (p < 0.05) after 60 days and ALP activity with a significant difference (p < 0.05) after 15, 30, and 60 days. The renal histological analysis showed normal histological features in all groups with the elevated serum creatinine levels in group III compared to those in the groups I and II (p < 0.05) after 60 days. Significantly elevated serum fluoride levels were observed in group II of 30 and 60 days and group III after 15, 30, and 60 days with respective to control groups (p < 0.05). CONCLUSION Taken together, these findings indicate that there can be some alterations in liver enzyme activities at early stages of fluoride intoxication followed by renal damage.
Animals ; Dose-Response Relationship, Drug ; Fluorides ; adverse effects ; Humans ; Kidney ; drug effects ; enzymology ; pathology ; Liver ; drug effects ; enzymology ; pathology ; Male ; Organ Size ; drug effects ; Random Allocation ; Rats ; Rats, Wistar ; Renal Insufficiency, Chronic ; etiology

BACKGROUNDChronic kidney disease (CKD) has become a public health problem. New interventions to slow or prevent disease progression are urgently needed. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of embryonic stem cells (ESCs) on the progression of CKD.

METHODSAdult male Sprague-Dawley rats were subjected to 5/6 nephrectomy. We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogels (GMs) on the 5/6 nephrectomized kidney. The viability of ESCs within the GMs was detected using in vitro two-photon fluorescence confocal imaging. Rats were sacrificed after 12 weeks. Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results. Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining.

RESULTSIn vitro, ESCs could be automatically loaded into the GMs. Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro. After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs.

CONCLUSIONSIn a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury.

Animals ; Cell Proliferation ; Cryogels ; Disease Progression ; Embryonic Stem Cells ; transplantation ; Gelatin ; administration & dosage ; Kidney ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley ; Renal Insufficiency, Chronic ; pathology ; therapy

We report 2 cases of chronic estimated glomerular filtration rate (eGFR) decline after unilateral adrenalectomy due to primary aldosteronism. The patients were diagnosed with unilateral adrenal cortical adenoma releasing aldosterone. Two patients were examined for hypertension and hypokalemia. Unilateral laparoscopic adrenalectomy was performed in both cases, and pathology confirmed adrenal cortical adenoma. After adrenalectomy, hypertension and hypokalemia improved to within normal range. However, the eGFR decreased postoperatively, and abdominal computed tomography scan showed decreased kidney size compared to previous images. Kidney biopsy was performed to delineate the exact cause of renal function deterioration and revealed hypertensive changes with chronic interstitial changes, indicating that glomerular hyperfiltration with aldosterone excess masked renal function damage. Physicians have to consider the probability of postadrenalectomy eGFR decline related to chronic hypertensive change.
Adrenalectomy* ; Adrenocortical Adenoma ; Aldosterone ; Biopsy ; Glomerular Filtration Rate ; Humans ; Hyperaldosteronism* ; Hypertension ; Hypokalemia ; Kidney ; Masks ; Pathology ; Reference Values ; Renal Insufficiency, Chronic

To investigate the changes of aortic stiffness and its influencing factors in patients with chronic kidney diseases (CKD).Eightyfour patients with CKD from Department of Nephrology, Zhejiang Provincial People's Hospital were divided into the dialysis group (CKD stage 5,=48) and non-dialysis group (CKD stage 3-5,=36). Clinical data, biochemical parameters and echocardiography findings were collected. SphygmoCor pulse wave analysis system was used to obtain pulse wave analysis (PWA) parameters including central aortic systolic blood pressure (CSP), central pulse pressure (CPP), augmented pressure (AP), augmentation index (AIX), and heart rate 75-adjusted augmentation index (HR75AIX). The influencing factors of aortic stiffness were analyzed by spearman correlation analysis and multiple regression analysis.CSP, CPP, AP, AIX and HR75AIX in dialysis patients had no significant differences compared with those in non-dialysis group (all>0.05). Spearman correlation analysis showed that CSP was positively correlated with systolic blood pressure, diastolic blood pressure, cholesterol, low-density lipoprotein cholesterol, left atrial diameter (LA),left ventricular systolic diameter (LVDs), left ventricular diastolic diameter (LVDd), and negatively correlated with calcium and hemoglobin levels. CPP was positively correlated with systolic blood pressure, age, LA, LVDd, and negatively correlated with diastolic blood pressure and hemoglobin levels. AP was positively correlated with systolic blood pressure, age, LA, LVDd, and negatively correlated with hemoglobin levels. AIX was positively correlated with systolic blood pressure, age, sodium, and negatively correlated with phosphorus levels. HR75AIX was positively correlated with systolic blood pressure, sodium, cholesterol, and negatively correlated with hemoglobin and albumin levels. Multiple regression analysis showed that higher systolic blood pressure was the independent risk factor for CSP (β=0.944,<0.01); lower diastolic blood pressure (β=0.939,<0.01) and higher systolic blood pressure (β=-1.010,<0.01) were the independent risk factors for CPP; older age (β=0.237,<0.01) and higher systolic blood pressure (β=0.200,<0.01) were the independent risk factors for AP; higher systolic blood pressure (β=0.163 and 0.115,<0.05 and<0.01) and higher sodium (β=0.646 and 0.625, all<0.05) were independent risk factors for both AIX and HR75AIX.No significant correlation is observed between aortic stiffness and CKD of different stages. Control blood pressure and restrict sodium intake may be effective means of delaying arterial stiffness in patients with CKD.
Age Factors ; Aorta ; pathology ; Blood Pressure ; physiology ; Cholesterol ; Dialysis ; Female ; Heart Atria ; Humans ; Male ; Middle Aged ; Regression Analysis ; Renal Insufficiency, Chronic ; complications ; Risk Factors ; Sodium, Dietary ; adverse effects ; Vascular Stiffness ; physiology

BACKGROUND/AIMS: While surgical resection remains the standard of care in the treatment of upper urinary tract malignancies, nephrectomy is a risk factor for the development of chronic kidney disease (CKD). The aim of this study was to determine whether histologic evaluation of non-neoplastic kidney could enable early identification of unrecognized kidney disease and could be of prognostic value in predicting postoperative renal outcomes. METHODS: We retrospectively analyzed 51 patients with upper urinary tract malignancies who received uninephrectomy or uninephroureterectomy. A thorough pathologic evaluation of non-neoplastic kidney including special stains, immunofluorescence, and electron microscopic studies was performed. The degree of parenchymal changes was graded from 0 to 15. RESULTS: Of 51 patients, only 13 showed normal kidney pathology. Fifteen patients showed glomerular abnormalities, 14 showed diabetic nephropathy, and 11 showed vascular nephropathy. There was one case each of reflux nephropathy and chronic pyelonephritis. The median histologic score was 5 points. Only 25.4% of patients had ≤ 3 points. Score more than 5 was observed in 47.1% of patients. Postoperative estimated glomerular filtration rate (eGFR) at 3 to 36 months were obtained from 90.2% of patients, and of those, 34.8% had de novo CKD. Since no one had CKD in partial nephrectomized patients, we determined risk factors for CKD in radical nephrectomized patients. Cox regression analysis revealed that postoperative AKI, preoperative eGFR, and histologic score of non-neoplastic kidney were the independent predictors for CKD. CONCLUSIONS: We conclude that routine pathologic evaluation of non-neoplastic kidney provides valuable diagnostic and prognostic information.
Coloring Agents ; Diabetic Nephropathies ; Fluorescent Antibody Technique ; Glomerular Filtration Rate ; Humans ; Kidney Diseases ; Kidney Neoplasms ; Kidney* ; Nephrectomy ; Pathology ; Pyelonephritis ; Renal Insufficiency, Chronic ; Retrospective Studies ; Risk Factors ; Standard of Care ; Urinary Tract*