No abstract

To identify the factors mediating the progression of diabetic nephropathy (DN), we performed RNA sequencing of kidney biopsy samples from patients with early DN, advanced DN, and normal kidney tissue from nephrectomy samples. A set of genes that were upregulated at early but downregulated in late DN were shown to be largely renoprotective, which included genes in the retinoic acid pathway and glucagon-like peptide 1 receptor. Another group of genes that were downregulated at early but highly upregulated in advanced DN consisted mostly of genes associated with kidney disease pathogenesis, such as those related to immune response and fibrosis. Correlation with estimated glomerular filtration rate (eGFR) identified genes in the pathways of iron transport and cell differentiation to be positively associated with eGFR, while those in the immune response and fibrosis pathways were negatively associated. Correlation with various histopathological features also identified the association with the distinct gene ontological pathways. Deconvolution analysis of the RNA sequencing data set indicated a significant increase in monocytes, fibroblasts, and myofibroblasts in advanced DN kidneys. Our study thus provides potential molecular mechanisms for DN progression and association of differential gene expression with the functional and structural changes observed in patients with early and advanced DN.

Patients with both hypertension and hyperhomocysteinemia, termed H‐type hypertension, have a high risk for cardiocerebrovascular diseases. However, little is known about the prevalence of H‐type hypertension or its role in target organ damage in patients with chronic kidney disease (CKD). The authors recruited 1042 patients with CKD who were admitted to their hospital division. Multiple linear regression analyses were used to evaluate the association between H‐type hypertension and renal/cardiovascular parameters. A total of 460 (44.14%) CKD patients had H‐type hypertension. Multivariate logistic regression analysis showed that H‐type hypertension is associated with serum albumin, uric acid, estimated glomerular filtration rate (eGFR), and 24‐hour systolic blood pressure. Patients with H‐type hypertension had the worst renal function and left ventricular hypertrophy among all patients, while the levels of carotid intima‐media thickness (cIMT) in patients with H‐type hypertension were only slightly higher than in patients with normotension and normohomocysteinemia (P<.05). H‐type hypertension was associated with eGFR, left ventricular mass index, and cIMT according to multiple linear regression analyses. The prevalence of H‐type hypertension was high and H‐type hypertension was associated with target organ damage in patients with CKD.

Background: The prevalence of acute kidney injury (AKI) in COVID-19 patients is high, with poor prognosis. Early identification of COVID-19 patients who are at risk for AKI and may develop critical illness and death is of great importance. Objective: The aim of this study was to develop and validate a prognostic model of AKI and in-hospital death in patients with COVID-19, incorporating the new tubular injury biomarker urinary neutrophil gelatinase-associated lipocalin (u-NGAL) and artificial intelligence (AI)-based chest computed tomography (CT) analysis. Methods: A single-center cohort of patients with COVID-19from Wuhan Leishenshan Hospital were included in this study. Demographic characteristics, laboratory findings, and AI-assisted chest CT imaging variables identified on hospital admission were screened using least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a model for predicting the AKI risk. The accuracy of the AKI prediction model was measured using the concordance index (C-index), and the internal validity of the model was assessed by bootstrap resampling. A multivariate Cox regression model and Kaplan-Meier curves were analyzed for survival analysis in COVID-19 patients. Results: One hundred seventy-four patients were included. The median (±SD) age of the patients was 63.59 ± 13.79 years, and 83 (47.7%) were men.u-NGAL, serum creatinine, serum uric acid, and CT ground-glass opacity (GGO) volume were independent predictors of AKI, and all were selected in the nomogram. The prediction model was validated by internal bootstrapping resampling, showing results similar to those obtained from the original samples (i.e., 0.958; 95% CI 0.9097–0.9864). The C-index for predicting AKI was 0.955 (95% CI 0.916–0.995). Multivariate Cox proportional hazards regression confirmed that a high u-NGAL level, an increased GGO volume, and lymphopenia are strong predictors of a poor prognosis and a high risk of in-hospital death. Conclusions: This model provides a useful individualized risk estimate of AKI in patients with COVID-19. Measurement of u-NGAL and AI-based chest CT quantification are worthy of application and may help clinicians to identify patients with a poor prognosis in COVID-19 at an early stage.

BackgroundIsolated nocturnal hypertension (INH) has been studied among the general population and hypertensive patients. However, little insight is available on the prognostic effect of INH in patients with chronic kidney disease (CKD). This study investigated the prognostic effect of INH in a cohort of Chinese patients with nondialysis CKD.Methods and ResultsA total of 588 Chinese CKD patients who were admitted to the Third Affiliated Hospital of Sun Yat‐Sen University were enrolled in this study. We monitored blood pressure (BP) throughout the day and followed health outcomes in the 588 CKD patients admitted to our hospital division. We recorded time to total mortality, cardiovascular mortality, renal events, and cardiovascular events. A total of 370 (62.92%) individuals had nocturnal hypertension, which included 136 (23.13%) patients with INH. Multivariable Cox regression analyses showed that nocturnal BP was a significant risk factor for renal events and cardiovascular events in CKD patients, even when adjusted for clinic BP, 24‐hour BP, or daytime BP. Patients with nocturnal hypertension showed a worse prognosis compared with patients with nocturnal normotension (P<0.05), and nocturnal hypertension (versus nocturnal normotension) was associated with an increased risk for renal events (hazard ratio [HR], 3.81; 95% CI, 1.74–8.36) and cardiovascular events (HR, 8.34; 95% CI, 1.98–35.07). In addition, patients with INH had a worse prognosis than patients with normotension (P<0.017), whereas INH (versus normotension) was associated with a higher risk of renal events (HR, 2.78; 95% CI, 1.16–6.65) and cardiovascular events (HR, 6.82; 95% CI, 1.52–30.63).Conclusions INH was associated with a poor prognosis in Chinese nondialysis CKD patients.

The “reverse dipping” blood pressure (BP) pattern has been studied among the general population and in individuals suffering from hypertension. However, the prognosis of this pattern in chronic kidney disease (CKD) patients is not known. We monitored BP throughout the day and followed health outcomes in 588 CKD patients admitted to our hospital. Time to all-cause mortality, cardiovascular mortality, renal events and cardiovascular events was recorded. Multivariate-adjusted Cox regression analyses were carried out to detect the prognostic value of a reverse dipping BP pattern. Prevalence of a “dipper”, “non-dipper” and “reverse dippers” was 34.69%, 43.54% and 18.03%, respectively. Patients with a reverse dipping pattern had a higher prevalence of total mortality, cardiovascular mortality, renal events and cardiovascular events than patients with a dipping pattern (P < 0.025). Multivariate-adjusted Cox regression analyses showed that reverse dippers (versus dippers) were associated with a higher risk of total mortality (hazard ratio [HR], 5.08; 95% confidence interval [CI], 1.79~14.47), cardiovascular mortality (4.17; 1.25~13.88), renal events (3.00; 1.59~5.65) and cardiovascular events (4.12; 1.78~9.51) even after adjustment by 24-h systolic BP. These data suggest that a reverse dipping BP pattern, independent of 24-h levels of systolic BP, has prognostic value in CKD patients not undergoing dialysis.

Hyperhomocysteinemia (HHcy) is recognized as a risk factor for cardiovascular disease. However, the prevalence of HHcy and its role in association with target organ damage in patients with chronickidney disease (CKD) are not well understood. This cross-sectional study included 1042 CKD patients who were admitted to our hospital. Patients were divided into two groups: hyperhomocysteinemia and normohomocysteinemia. Multivariable linear regression analyses were used to evaluate the association between plasma homocysteine and renal/cardiovascular parameters. The prevalence of HHcy in patients with CKD was 52.78%, and the prevalence in CKD stage 1, stage 2, stage 3, stage 4 and stage 5 patients was 10.73%, 29.22%, 58.71%, 75.23% and 83.75%, respectively. Patients with HHcy had higher incidences of renal damage, left ventricular hypertrophy, left ventricular diastolic dysfunction and abnormal carotid intima-media thickness compared with patients with normohomocysteinemia (p < 0.05), while multivariable linear regression analyses showed plasma homocysteine was only associated with the estimated glomerular filtration rate (eGFR). eGFR, uric acid, albumin, gender, hemoglobin and calcium×phosphate were associated with levels of plasma homocysteine in these CKD patients. The prevalence of HHcy in Chinese patients with CKD was high, and serum homocysteine levels were associated with impaired renal function in these patients.

Mitochondrial abnormalities play critical roles in diabetic tubular injury progression. Dipeptidyl peptidase‐4 (DPP4) inhibitors are widely used antihyperglycemic agents that exert renal protective and positive effects against mitochondrial dysfunction in diabetic kidney disease (DKD). However, their underlying mechanism remains unclear. In this study, DPP4 upregulation, mitochondrial fragmentation, and altered mitochondrial dynamics‐associated protein expression were observed in the tubules of DBA2/J (D2) diabetic mice with unilateral nephrectomy and in albumin‐stimulated tubular cells. The inhibition of DPP4 by sitagliptin (Sita) ameliorated these mitochondrial perturbations both in vivo and in vitro, whereas DPP4 overexpression aggravated mitochondrial fusion‐fission disorder and tubular cell injury in albumin‐treated HK‐2 cells. Downstream of DPP4, the SDF‐1α/CXCR4 pathway was significantly suppressed in diabetic tubules. After Sita treatment, this signaling pathway was restored, and the mitochondrial dynamics was improved. Furthermore, a direct interaction between STAT3 and OPA1 was found in the mitochondria of tubular cells, and this effect was weakened by overloading albumin and by CXCR4 siRNA treatment, suggesting a possible link between DPP4‐mediated SDF‐1α/CXCR4/STAT3 signaling and mitochondrial dysfunction in diabetic tubular cells. The results suggest that a novel mechanism links the DPP4 enzyme to impaired mitochondrial dynamics homeostasis during tubular injury in DKD and highlight that the SDF‐1α/CXCR4/STAT3 signaling pathway could become a potential target for managing DKD.