The impact of acute kidney injury with or without recovery on long-term kidney outcome in patients undergoing living liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is associated with an increased incidence of poor liver graft and renal outcomes in patients who have undergone liver transplantation (LT). To date, no comprehensive study has compared patients with and without post-LT AKI and analyzed patients who recovered from AKI versus those who did not. METHODS: Patients who received living LT between January 2003 and January 2019 were enrolled. We diagnosed and classified AKI patients based on AKI-KDIGO guidelines by increment of creatinine after surgery when compared with serum creatinine on the day of surgery. The recovered AKI subgroup included recipients whose estimated glomerular filtration rate (eGFR) recovered more than 90% of baseline eGFR within 90 days after surgery. The risk of chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m2) was investigated. RESULTS: A total of 392 patients, 77.3% men and mean ± standard deviation age 54.1 ± 8.4 years, met the eligible criteria and were divided into two groups (AKI vs non-AKI) and 243 (62%) patients developed AKI within 7 days after surgery. Compared with the non-AKI group, the AKI group was associated with an adjusted hazard ratio of 1.55 (95% CI 1.12-2.14) for the risk of incident CKD. Among AKI patients, 160 (65.8%) patients recovered renal function and 83 (34.2%) patients did not. Compared with the non-AKI group, the AKI non-recovery group was associated with an adjusted hazard ratio of 2.87 (95% CI 1.95-4.21) for the risk of incident CKD, while the AKI recovery group had no significant difference in the adjusted risk of incident CKD. CONCLUSIONS: Post-LT AKI is associated with subsequent risk of CKD development. Taking into account recovery status, AKI was no longer associated with a higher risk of CKD if renal function recovered within 90 days after surgery. Identification and implementation of targeted and individualized therapies for patients at risk for AKI, particularly non-recovery AKI, is of paramount importance to reduce incident CKD during follow-up.

Association of Hematuria with Renal Progression and Survival in Patients Who Underwent Living Donor Liver Transplant.

BACKGROUND: This study aimed to determine the association between episodic or persistent hematuria after liver transplantation and long-term renal outcomes. METHODS: Patients who underwent living donor liver transplantation between July 2005 and June 2019 were recruited and divided into two groups based on the finding of microscopic or gross hematuria after transplantation. All patients were followed up from the index date until the end date in May 2020. The risks of chronic kidney disease, death, and 30% and 50% declines in estimated glomerular filtration rate (eGFR) were compared between groups. RESULTS: A total of 295 patients underwent urinalysis for various reasons after undergoing transplantation. Hematuria was detected in 100 patients (group A) but was not present in 195 patients (group B). Compared with group B, group A had a higher risk of renal progression, including eGFR decline >50% [aHR = 3.447 (95%CI: 2.24~5.30), p < 0.001] and worse survival. In addition, patients who took non-steroidal anti-inflammatory drugs (NSAIDs) continuously for over seven days within six months before transplant surgery had high risks of rapid renal progression, including a >30% decline in eGFR [aHR = 1.572 (95%CI: 1.12~2.21), p = 0.009)]. CONCLUSION: Development of hematuria after surgery in patients who underwent living donor liver transplant and were exposed to NSAIDs before surgery were associated with worse long-term renal dysfunction and survival.

Superiority of albumin-globulin ratio over albumin to predict mortality in patients undergoing peritoneal dialysis.

There is increasing evidence showing that albumin-globulin ratio (AGR) can predict the survival of patients in many types of malignancies. However, no study was done to explore the value of AGR in peritoneal dialysis (PD) patients. A total of 554 incident patients undergoing PD from January 2001 through July 2016 were enrolled for this retrospective observational study. The outcomes of interest were all-cause mortality and cardiovascular disease (CVD) mortality. Baseline patient's socio-demographic data, pharmacotherapy, comorbidities, laboratory and PD-related parameters were collected and used in the multivariate Cox models. The predictive value of AGR on mortality risk was compared with other markers using area under the receiver operating characteristic curve (AUC) analysis. Among the study participants, there were 265 (47.83%) men and the mean follow-up time was 3.87 ± 3.15 years. Univariate Cox analysis showed that low AGR was significantly associated with worse outcomes in terms of all-cause and CVD mortality and it remained an independent predictor in the multivariate models. The fully adjusted hazard ratios for the low AGR group versus high AGR group were 2.12 (95% CI 1.34-3.35, p = 0.001) and 2.58 (95% CI 1.42-4.7, p = 0.002) for all-cause and CVD mortality, respectively. The predictive ability of AGR for mortality risk was superior to that of other biomarkers based on AUC calculations. In conclusion, low AGR was independently associated with higher all-cause and CVD mortality risks in patients undergoing PD.

Synergistic Anticancer Effects of Gemcitabine with Pitavastatin on Pancreatic Cancer Cell Line MIA PaCa-2 in vitro and in vivo.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with an overall 5-year survival rate of 9.3%, and this malignancy is expected to become the second leading cause of cancer-related death by 2030. Gemcitabine resistance develops within weeks of PDAC patient's chemotherapeutic initiation. Statins, including pitavastatin, have been indicated to have anticancer effects in numerous human cancer cell lines. Thus, in this study, we hypothesized that a combination of gemcitabine and pitavastatin may have a greater anticancer effect than gemcitabine alone on the human pancreatic carcinoma cell line MIA PaCa-2. METHODS: The anticancer effects of gemcitabine with pitavastatin were evaluated using human MIA PaCa-2 cell line in vitro and in vivo Balb/c murine xenograft tumor model. Cell viability was assessed with CCK-8, and cell migration was stained by crystal violet. Cell cycle distribution, apoptosis and mitochondrial membrane potential were examined by flow cytometry. Activation of drug transporters (hENTs, hCNTs), intracellular drug activating (dCK) and inhibition of inactivating enzymes (RRMs) pathways were assessed by Western blotting analysis. Molecular mechanisms and signaling pathways of apoptosis, necrosis and autophagy also were assessed by Western blotting. RESULTS: We observed that gemcitabine and pitavastatin synergistically suppressed the proliferation of MIA PaCa-2 cells through causing sub-G1 and S phase cell cycle arrest. Activation of apoptosis/necrosis was confirmed by annexin V/propidium iodide double staining, which showed increasing levels of active caspase 3, cleaved poly(ADP-ribose) polymerase and the RIP1-RIP3-MLKL complex. Moreover, gemcitabine-pitavastatin-mediated S phase arrest downregulated cyclin A2/CDK2 and upregulated p21/p27 in MIA PaCa-2 cells. Furthermore, this combination improved drug cellular metabolism pathway, mitochondria function and activated autophagy as part of the cell death mechanism. In vivo, gemcitabine-pitavastatin effectively inhibited tumor growth in a nude mouse mode of Mia PaCa-2 xenografts without observed adverse effect. CONCLUSION: Combined gemcitabine-pitavastatin may be an effective novel treatment option for pancreatic cancer.

Silencing of hepcidin enforces the apoptosis in iron-induced human cardiomyocytes.

BACKGROUND: Iron is essential not only for erythropoisis but also for several bioenergetics' processes in myocardium. Hepcidin is a well-known regulator of iron homeostasis. Recently, researchers identified low hepcidin was independently associated with increased 3-year mortality among systolic heart failure patients. In addition, our previous in vivo study revealed that the left ventricular mass index increased in chronic kidney disease patients with lower serum hepcidin. We hypothesize that hepcidin interacts with the apoptotic pathway of cardiomyocytes during oxidative stress conditions. METHODS: To test this hypothesis, human cardiomyocytes were cultured and treated with ferrous iron. The possible underlying signaling pathways of cardiotoxicity were examined following knockdown studies using siRNAs of hepcidin (siRNA1 was used as a negative control and siRNA2 was used to silence hepcidin). RESULTS: We found that ferrous iron induces apoptosis in human cardiomyocytes in a dose-dependent manner. This iron-induced apoptosis was linked to enhanced caspase 8, reduced Bcl-2, Bcl-xL, phosphorylated Akt and GATA-4. Hepcidin levels increased in human cardiomyocytes pretreated with ferrous iron and returned to non-iron treated levels following siRNA2 transfection. In iron pretreated cardiomyocytes, the siRNA2 transfection further increased caspase 8 expression and decreased the expression of GATA-4, Bcl-2, Bcl-xL and phosphorylated Akt than iron pretreatment alone, but caspase 9 levels remained unchanged. CONCLUSIONS: Our findings suggest that hepcidin can rescue human cardiomyocytes from iron-induced apoptosis through the regulation of GATA-4/Bcl-2 and the extrinsic apoptotic pathway.

Anti-glomerular basement membrane glomerulonephritis with subsequent pulmonary hemorrhage in the course of pulmonary tuberculosis.

A 66-year-old man with uremia and on hemodialysis was referred to our hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure accompanied by hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). Circulating IgG anti-GBM antibody was not detected. Because the findings of renal biopsy suggested anti-GBM disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture submitted on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immunosuppressive agents were discontinued and antituberculous agents were administrated. No relapse of pulmonary hemorrhage occurred during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.

Comparison of typical endocapillary and atypical mesangial proliferation in postinfectious glomerulonephritis.

BACKGROUND: There is a broad spectrum of glomerular histological findings in postinfectious glomerulonephritis (PIGN). We conducted this retrospective study to compare the clinicopathological features between two distinct morphology of PIGN. METHODS: Thirteen patients with typical endocapillary proliferation and eight patients with atypical mesangial proliferation were enrolled in this study. The patients' records were reviewed with respect to clinical presentation, microbiology, serology, morphology of renal biopsy, and clinical course. RESULTS: In comparison of histological parameters, glomerular neutrophil infiltration was more commonly present in typical endocapillary proliferation group (p = 0.018). Glomerular IgA dominant or co-dominant deposition was more frequently seen in atypical mesangial proliferation group (p = 0.032). In a comparison of clinical parameters, atypical mesangial proliferation group had lesser degrees of proteinuria, higher serum levels of complement, and higher rates of staphylococcal infection, although none of the differences was statistically significant. Glomerular morphology did not seem to affect the renal outcome. Moreover, our data suggested that the percentage of patients with atypical mesangial proliferation significantly increased over time (p < 0.001). CONCLUSIONS: Atypical mesangial proliferation may represent a resolution stage of PIGN. The nature of subclinical infection with a more protracted course may contribute to the increasing recognition of this resolving PIGN at the time of renal biopsy. Another possible explanation is that the atypical morphology may be a peculiar pattern of post-staphylococcal glomerulonephritis, which was increasingly identified in PIGN over the past 10 years.