Comparative analysis of roxadustat efficacy between maintenance hemodialysis and peritoneal dialysis patients.

BACKGROUND: This study evaluated the comparative efficacy of roxadustat for renal anemia between patients on maintenance hemodialysis (HD) and peritoneal dialysis (PD). MATERIALS AND METHODS: 93 maintenance dialysis patients who regularly followed up from August 2015 to June 2021 were enrolled. Despite receiving a therapeutic dose ≥ 12,000 U/week of erythropoiesis-stimulating agents (E+SA) in the past 12 weeks, this had not worked very well. Subjects were assigned to the HD group (n = 60) or the PD group (n = 33) based on their dialysis treatment modality. All patients received oral roxadustat and were followed up for 24 weeks, after which their hemoglobin, serum iron, transferrin saturation, and ferritin were tested. RESULTS: We observed that the hemoglobin level of PD patients was significantly increased from 76.1 ± 15.7 g/L to 106 ± 23.8 g/L (p < 0 .001), while it significantly increased from 73.8 ± 12.9 g/L to 100.7 ± 20.2 g/L (p < 0.001) in the HD patients. After 1 and 3 months of roxadustat treatment, the hemoglobin level and its change in the PD group was significantly higher compared to that in the HD group despite the higher dose of roxadustat in the latter group. In addition, roxadustat was noted to reduce cholesterol levels and stabilize serum iron levels in parallel with improving hemoglobin levels. CONCLUSION: Roxadustat can effectively increase the hemoglobin level of maintenance dialysis patients, even in those with low erythropoietin response or erythropoietin resistance, and, more importantly, its efficacy in PD patients was more significant.

Tolerance of peritoneal and residual renal function to intraperitoneal gadolinium-based agents: An animal experimental study of magnetic resonance peritoneography.

BACKGROUND: MR (Magnetic resonance) peritoneography is sensible for continuous ambulatory peritoneal dialysis (CAPD)-related complications, which could offer excellent soft-tissue contrast and allows a multiplanar imaging evaluation of complications. However, there is no study about the optimal concentration of the gadolinium-based agents nor the side effects of gadolinium-based agents on peritoneum and residual renal function. METHOD: Five different groups of uremic rats and two groups of normal rats were injected with a 40-ml mixture of peritoneal dialysate and gadolinium-based agents at varying concentrations prior to MR peritoneography. Thereafter, MR image obtained was evaluated by two experienced radiologists blinded to the concentrations. Peritoneal morphology and thickness of the uremic rats were also assessed using hematoxylin and eosin and Masson staining. Residual renal function was evaluated using serum creatinine levels and hematoxylin and eosin (HE) staining of pathological kidney sections. RESULTS AND CONCLUSION: The gadolinium-based agents used in this experiment have no significant effect on residual renal function. There is no obvious difference in the image quality at the different gadolinium-based agents concentration. Due to the adverse effects of gadolinium-based agents in the previous studies, we suggest reducing the dose of gadolinium-based agents during MR peritoneography to the lowest limits.

Renal pathology in patients with occupational exposure to carbon disulphide: A case series.

AIM: Carbon disulphide (CS2 ) is widely used as an organic solvent. However, there is little information available regarding the clinical manifestations and the pathological features of kidney injury caused by CS2 . The current study aimed to describe the renal manifestations of a group of patients with long-term occupational exposure to CS2 . METHODS: Ten patients with long-term exposure to CS2 and visiting a single centre were enrolled, with their clinical features recorded. Renal biopsies were taken from all patients, and their pathological findings were documented. RESULTS: All patients came from the same chemical fibre factory. Their mean age at enrollment was 36.9 ± 2.4 years, and each patient had a CS2 exposure duration exceeding 10 years. Eight patients (80%) presented with proteinuria and none had hematuria. Two patients (20%) had underlying hypertension and five (50%) had increased serum creatinine levels. Light microscopic examination of their renal biopsy specimens revealed diffuse mesangial cell proliferation and mesangial hyperplasia in all patients. Moreover, three patients (30%) had nodular hyperplasia, resembling the lesions of diabetic nephropathy. Variable degrees of tubular atrophy and interstitial infiltrations of lymphocytes and monocytes were observed in all patients. Similarly, lectron microscopic examination showed glomerular mesangial cell proliferation and mesangial hyperplasia. Immunopathological staining for IgA and IgG, complements or hepatitis B markers (hepatitis B surface antigen and e antigen-antibody) are negative in all patients. CONCLUSION: Long-term occupational exposure to CS2 may be associated with renal injury, although the renal pathological features are often non-specific.

Genistein improves mitochondrial function and inflammatory in rats with diabetic nephropathy via inhibiting MAPK/NF-κB pathway.

PURPOSE: To investigate the effect of genistein on inflammation and mitochondrial function of diabetic nephropathy. METHODS: Diabetic nephropathy model was established in Sprague-Dawley rats. Automatic biochemical analyzer was employed to detect the kidney function index, serum creatinine, serum urea nitrogen, and 24 h-urine protein and blood glucose. Hematoxylin and eosin staining and periodic acid Schiff staining were used to observe renal morphology. Mitochondrial changes and podocyte integrity were monitored by transmission electron microscope. The expression levels of mfn2, NOX4, P53, MAPK, and NF-κB were detected by Western blotting. The changes of mitochondrial membrane potential were measured by JC-1. The level of mfn2 was assessed by immunofluorescence assay. RESULTS: Genistein ameliorated the kidney function with reduced Scr and blood glucose. The expressions of NOX4, MAPK, p65 and p53 were downregulated, while the expression of mnf2 was the opposite in genistein-treated kidneys. Further investigations revealed that genistein reduced expansion of mesangial matrix and oxidative stress, protected podocyte integrity and increased mitochondrial membrane potential. CONCLUSIONS: Genistein could alleviate diabetic nephropathy through inhibiting MAPK/NF-κB pathway, improving mitochondrial function and anti-inflammatory.

Autosomal dominant tubulointerstitial kidney disease with a novel heterozygous missense mutation in the uromodulin gene: A case report.

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a progressive chronic disease that is inherited in an autosomal dominant fashion. Symptoms include hyperuricemia, gout, interstitial nephritis, renal cysts, and progressive renal damage that can lead to end-stage renal disease. Mutations in the uromodulin gene (UMOD) characterize the ADTKD-UMOD clinical subtype of this disease. To date, > 100 UMOD mutations have been identified. Early diagnosis of ADTKD-UMOD is important to treat the disease, slow down disease progression, and facilitate the identification of potentially affected family members. CASE SUMMARY: We report a 40-year-old man harboring a novel heterozygous missense mutation in UMOD (c.554G>T; p. Arg185Leu). The patient had hyperuricemia, gout, and chronic kidney disease. The same mutation was detected in his daughter, aunt and cousin. CONCLUSION: A single nucleotide substitution in exon 3 of UMOD was responsible for the heterozygous missense mutation (c.554G>T, p.Arg185Leu).

Abdominal hemorrhage after peritoneal dialysis catheter insertion: A rare cause of luteal rupture: A case report.

BACKGROUND: Abdominal hemorrhage is a complication of peritoneal dialysis catheter (PDC) insertion that cannot be neglected, and its causes are mainly related to surgical injury. This article reports a case of massive abdominal hemorrhage that was caused by a rare rupture of corpus luteum shortly after PDC during the initiation of peritoneal dialysis (PD) insertion. CASE SUMMARY: A 37-year-old woman was surgically placed a Tenckhoff catheter because of end-stage renal disease. On the third postoperative day, the color of the abdominal drainage fluid was pink, and deepened gradually. It turned pale after initiating conservative treatment. On the tenth postoperative day, the color of the abdominal drainage fluid suddenly turned dark red, and the color progressively deepened. The patient's hemoglobin dropped from 88 g/L to 57 g/L. Abdominal computed tomography (CT) indicated abdominal effusion and a high-density shadow in the abdominal cavity. The surgeon performed a laparotomy and found that the corpus luteum had ruptured on the right side and a left ovarian blood body had formed. The gynecologist repaired the ovary and performed a bilateral oophoroplasty. After the operation, the patient stopped bleeding and hemodialysis was temporarily stopped. PD was resumed after half a month. The patient's condition improved, and she was discharged 14 d after the laparotomy. CONCLUSION: If abdominal hemorrhage occurs in women of childbearing age after PDC insertion, luteal rupture should be considered as the cause.

Obstructive jaundice in a patient with polycystic liver disease complicated with polycystic kidney and polycystic lung: A case report.

RATIONALE: Polycystic liver disease (PLD) is an autosomal-dominant disorder that is commonly associated with autosomal-dominant polycystic kidney disease (PKD) but rarely complicated with polycystic lung. Here, we report the first case of severe obstructive jaundice caused by multiple liver cysts in a patient with PLD complicated by PKD and polycystic lung. PATIENT CONCERNS: A 72-year-old man with a history of PLD complicated with polycystic kidney presented with progressive jaundice, hematuria, poor appetite, nausea, and weight loss since 3 months. DIAGNOSIS: PLD complicated with PKD and polycystic lung was identified using computed tomography, and obstructive jaundice was identified using magnetic resonance imaging and magnetic resonance cholangiopancreatography. INTERVENTIONS: The patient could not undergo surgery, and was therefore treated with combined bilirubin adsorption and continuous veno-venous hemofiltration. OUTCOMES: The patient's symptoms and laboratory findings improved after bilirubin adsorption and continuous veno-venous hemofiltration. Unfortunately, the patient was unable to continue the treatment due to financial reasons, and died of shock most likely due to cyst rupture. LESSONS: Imaging examination of the lungs is necessary for patients with PLD. Although infrequent, jaundice can occur in these patients and cause severe hyperbilirubinemia. When surgery is contraindicated, blood purification may serve as an alternative treatment for patients with PLD-related obstructive jaundice.

[Analysis on clinical features and risk factors of death in 210 patients with acute mushroom poisoning].

OBJECTIVE: To analyze the clinical features and risk factors of death in patients with acute mushroom poisonings. METHODS: The clinical data of 210 patients with acute mushroom poisoning admitted to the Affiliated Hospital of Southwest Medical University from July 2013 to December 2016 and received follow-up for at least 6 months were retrospectively analyzed. The data included gender, age, hospitalization time, toadstool features, incubation period, clinical performance, laboratory indicators, and prognosis. According to the prognosis, the patients were divided into survival group and non-survival group, the clinical characteristics and organ or system involvement of the two groups were analyzed, and the risk factors of death in patients with acute mushroom poisoning were explored by univariate and Logistic regression analysis. RESULTS: All 210 patients were enrolled in the final analysis, with 172 patients (81.9%) in survival group, and 38 (18.1%) in non-survival group. Patients with an incubation period of 6-24 hours had the highest mortality [15.2% (32/210)]. Most toadstools were in white, red or yellow, with an intake of 20-500 g. More than 85% of patients had gastrointestinal reactions, and liver damage was the most common [58.1% (122/210)] in all patients. The patients with heart and nervous system damage had higher mortality [61.4% (27/44) and 61.3% (19/31)], and the more organs or systems involved, the higher the mortality was. Univariate analysis showed that incubation period ≥ 6 hours, white blood cell (WBC) ≥12×109/L, alanine aminotransferase (ALT)≥200 U/L, aspartate aminotransferase (AST) ≥ 200 U/L, lactate dehydrogenase (LDH) ≥ 500 U/L, prothrombin time (PT) ≥ 20 s, activated partial thrombin time (APTT) ≥ 40 s, prothrombin activity (PTA) ≤ 60%, Na+ ≤ 135 mmol/L, MB isoenzyme of creatine kinase (CK-MB) ≥ 5 µg/L and myoglobin (Mb) ≥ 100 µg/L were the risk factors of death in patients with acute mushroom poisoning. Multiple factors Logistic regression analysis showed that APTT ≥ 40 s had the greatest lethal risk and could increase the risk of death by 5.35 times [odds ratio (OR) = 6.35, 95% confidence interval (95%CI) = 1.24-32.44], indicating that APTT was an independent risk factor of death in patients with acute mushroom poisoning. CONCLUSIONS: The mortality of acute mushroom poisoning was high, and liver was the mainly involved organ. The incubation period, WBC, ALT, AST, LDH, PT, APTT, PTA, Na+, CK-MB and Mb could be early indicators to evaluate the prognosis in patients with acute mushroom poisoning, and patients with APTT ≥ 40 s had the greatest lethal risk.

Bone Morphogenetic Proteins 2/4 Are Upregulated during the Early Development of Vascular Calcification in Chronic Kidney Disease.

Vascular calcification is a main cause of increased cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. This study aimed to investigate the role of the bone morphogenetic protein (BMP) signaling pathway in the early development of vascular calcification in CKD. A CKD vascular calcification rat model was established by providing rats with a 1.8% high-phosphorus diet and an intragastric administration of 2.5% adenine suspension. The kidney and aortic pathologies were analyzed. Blood biochemical indicators, serum BMP-2 and BMP-4 levels, and aortic calcium content were determined. The expression levels of BMP-2, BMP-4, bone morphogenetic protein receptor-IA (BMPR-IA), and matrix Gla protein (MGP) in aorta were examined by quantitative real-time polymerase chain reaction and immunohistochemistry. Compared with the normal control (Nor) rats, the CKD rats exhibited a significantly decreased body weight and an increased kidney weight as well as abnormal renal function and calcium-phosphorus metabolism. Aortic von Kossa and Alizarin red staining showed massive granular deposition and formation of calcified nodules in aorta at 8 weeks. The aortic calcium content was significantly increased, which was positively correlated with the serum BMP-2 (r = 0.929; P < 0.01) and serum BMP-4 (r = 0.702; P < 0.01) levels in CKD rats. The rat aortic BMP-2 mRNA level in the CKD rats was persistently increased, and the BMP-4 mRNA level was prominently increased at the 4th week, declining thereafter. Strong staining of BMP-2, BMP-4, BMPR-IA, and MGP proteins was observed in the tunica media of the aorta from the 4th week after model induction. In conclusion, activation of the BMP signaling pathway is involved in the early development of vascular calcification in CKD. Therefore, elevated serum BMP-2 and BMP-4 levels may serve as serum markers for CKD vascular calcification.

[Aliskiren inhibits angiotensin II/angiotensin 1-7(Ang II/Ang1-7) signal pathway in rats with diabetic nephropathy].

Objective To investigate the role of aliskiren (AL) in the angiotensinII/ angiotensin 1-7 (AngII/Ang1-7) signal pathway in renal tissue of diabetic nephropathy (DN) rats. Methods 40 male SD rats were randomly divided into 4 groups including normal group, diabetes group, AL group and valsartan (Val) group. Animal models of diabetes were induced by high fat diet combined with small dose of streptozotocin injection. Rats in AL group were administered 50 mg/(kg.d) AL by gavage, and rats in Val group were administered 30 mg/(kg.d)Val by gavage. 24-hour urine protein (24 h-UP) were observed by Coomassie blue colorimetry at 2, 4 and 6 weeks after modeling, serum creatinine was detected by automatic biochemical analyser, kidney index [kidneys mass(g)/body mass (kg)] was measured. HE and PAS staining were used to observe renal pathological changes. Immunohistochemistry was used to detect the expression of ACE2, MAS receptor, AT1R and AT2R in the kidney. Results After 6 weeks of modeling, there was no significant difference in creatinine level among groups. The levels of glucose, 24 h-UP and kidney index in diabetes group, AL group and Val group significantly increased. Compared with diabetes group, the levels of 24 h-UP and kidney index were lower in AL group and Val group. Immunohistochemistry showed that the expression of AT2R and ACE2 was lower and the expression of MAS receptor was higher in AL group than diabetes group and Val group. Compared to normal group and Val group, AT1R expression was significantly up-regulated in AL group, without significant difference between diabetes group and AL group. Conclusion AL down-regulates the expression of AT2R and ACE2, thus inhibits the AngII/ Ang1-7 signal axis and improves/alleviates the symptoms in diabetic rats.

The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy Rats.

BACKGROUND: This study explored the changes in expression of vascular smooth muscle cell (VSMC) markers and osteogenic markers, as well as the involvement of Notch1-RBP-Jk/Msx2 pathway in a rat model of diabetic nephropathy (DN) with vascular calcification. METHODS: A rat model of DN with concomitant vascular calcification was created by intraperitoneal injection of streptozotocin followed by administration of vitamin D3 and nicotine. Biochemical analysis and histological examination of aortic tissue were performed. VSMC markers and osteogenic markers as well as target molecules in Notch1-RBP-Jk/Msx2 were determined by quantitative real-time polymerase chain reaction and immunohistochemical analysis. RESULTS: Serum calcium and phosphorus levels were significantly increased in model rats as compared to that in normal controls. Diabetic rats with vascular calcification exhibited mineral deposits in aortic intima-media accompanied by decreased expression of VSMC markers and increased expression of osteogenic markers. Notch1, RBP-Jk, Msx2, Jagged1, and N1-ICD were barely expressed in the aortic wall of normal rats. In contrast, these were significantly increased in the model group at all time points (8, 12, and 16 weeks), as compared to that in the normal rats. CONCLUSION: Activation of the Notch1-RBP-Jk/Msx2 signaling pathway may be involved in the development and progression of vascular calcification in DN.