Glomerular Hyperfiltration Predicts Kidney Function Decline and Mortality in Type 1 and Type 2 Diabetes: A 21-Year Longitudinal Study

Objective: To evaluate the prognostic value of glomerular hyperfiltration on long-term kidney-related outcomes and mortality in patients with diabetes. Research design and methods: We retrospectively analyzed 21-year longitudinal data from 314 patients with long-standing type 1 or type 2 diabetes. Glomerular hyperfiltration was identified based on the age- and sex-specific distribution of measured glomerular filtration rate (mGFR) by 99mTc-DTPA dynamic renal scintigraphy. The primary outcome was a composite of doubling of serum creatinine, end-stage kidney disease (ESKD), or cardiorenal death. The kidney-specific outcome was a composite of doubling of serum creatinine, ESKD, or renal death. Results: Over a median of 21.0 years, the primary composite outcome occurred in 25 (39.7%), 24 (38.1%), and 46 (24.5%) participants with high mGFR (H-mGFR) (n = 63), low mGFR (L-mGFR) (n = 63), or normal mGFR (N-mGFR) (n = 188), respectively. Compared with N-mGFR, the hazard ratio (HR) for the primary composite outcome was 2.09 (95% CI 1.25-3.49) in H-mGFR and 1.81 (1.05-3.16) in L-mGFR. The HR for the kidney-specific composite outcome was 4.95 (2.21-11.09) in H-mGFR and 3.81 (1.70-8.56) in L-mGFR. The HRs for doubling of serum creatinine and cardiorenal death were 4.86 (2.18-10.90) and 2.18 (1.24-3.83) in H-mGFR and 4.04 (1.77-9.20) and 2.26 (1.27-4.01) in L-mGFR, respectively. Conclusions: Glomerular hyperfiltration, similar to hypofiltration, increases the combined risk of worsening kidney function and mortality from cardiovascular or renal causes in patients with diabetes. These findings encourage the active screening of these patients to optimize risk stratification and treatment of subclinical kidney disease

Synergistic effect of chronic kidney disease, neuropathy, and retinopathy on all-cause mortality in type 1 and type 2 diabetes: a 21-year longitudinal study

BACKGROUND: The prognostic value of common and frequently associated diabetic microvascular complications (MVC), namely chronic kidney disease (CKD), cardiac autonomic neuropathy (CAN), peripheral neuropathy (DPN), and retinopathy (DR), is well established. However, the impact of their different combinations on long-term mortality has not been adequately assessed. METHODS: We retrospectively analyzed 21-year longitudinal data from 303 patients with long-standing type 1 (T1D) or type 2 diabetes (T2D), who were thoroughly characterized at baseline for the presence of MVC using (99m)Tc-DTPA dynamic renal scintigraphy, overnight urine collection, cardiovascular autonomic tests, monofilament testing, and dilated fundus oculi examination. RESULTS: After a 5,244 person-years follow-up, a total of 133 (43.9%) deaths occurred. The presence of CKD and CAN, regardless of other MVC, increased the adjusted all-cause mortality risk by 117% (HR 2.17 [1.45–3.26]) and 54% (HR 1.54 [1.01–2.36]), respectively. Concomitant CKD&CAN at baseline were associated with the highest mortality risk (HR 5.08 [2.52–10.26]), followed by CKD&DR (HR 2.95 [1.63–5.32]), and CAN&DR (HR 2.07 [1.11–3.85]). Compared with patients free from MVC, the mortality risk was only numerically higher in those with any isolated MVC (HR 1.52 [0.87–2.67]), while increased by 203% (HR 3.03 [1.62–5.68]) and 692% (HR 7.92 [2.93–21.37]) in patients with two and three concomitant MVC, respectively. CONCLUSIONS: Our study demonstrates the long-term, synergistic, negative effects of single and concomitant diabetic MVC on all-cause mortality, which should encourage comprehensive screenings for MCV in both T1D and T2D to improve risk stratification and treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01675-6

Prognostic value of 24-hour ambulatory blood pressure patterns in diabetes: A 21-year longitudinal study

Aims To establish the long-term prognostic value of abnormal circadian blood pressure (BP) patterns in diabetes. Materials and Methods We retrospectively examined a cohort of 349 outpatients with diabetes who were screened for microvascular complications and followed up for 21 years. Dipping, nondipping and reverse-dipping status were defined based on 24-hour ambulatory BP monitoring (ABPM) as >= 10% reduction, <10% reduction, and any increase in average nighttime versus daytime systolic BP (SBP), respectively. Results After 6251 person-years of follow-up (median [range] follow-up 21.0 [1.1-22.0] years, 52% women, age 57.1 +/- 11.9 years, 81.4% type 2 diabetes and 18.6% type 1 diabetes), a total of 136 deaths (39%) occurred. Compared with dippers, the nondippers and reverse dippers showed progressively higher prevalence of chronic kidney disease (CKD), cardiac autonomic neuropathy (CAN) and postural hypotension. Reverse dippers showed a 13.4% (2.5-year) reduction in mean overall survival and a twofold increased risk of all-cause mortality after adjustment for traditional risk factors (hazard ratio 2.2 [95% confidence interval 1.3-3.8]). Each 1% decrease in nighttime versus daytime SBP ratio was independently associated with a 4% reduction in 20-year mortality risk. Conclusions In patients with diabetes, reverse dipping is associated with a higher prevalence of CKD and CAN and more than doubled the adjusted risk of all-cause mortality over a 21-year observation

Additional file 1 of Synergistic effect of chronic kidney disease, neuropathy, and retinopathy on all-cause mortality in type 1 and type 2 diabetes: a 21-year longitudinal study

Additional file 1: Table S1. Baseline characteristics of the subgroup of study participants fully characterized for the presence of CKD, CAN, and DR. Table S2. Baseline characteristics of the study participants fully characterized for the presence of CKD, CAN, and DR stratified by the number of MVC

The relationship between cardiac injury, inflammation and coagulation in predicting COVID-19 outcome

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals

Hyperglycemia at hospital admission is associated with severity of the prognosis in patients hospitalized for COVID-19: The pisa COVID-19 study

OBJECTIVE To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS Hospitalized COVID-19 patients (N 5 271) were subdivided based on at-admission glycemic status: 1) glucose levels <7.78 mmol/L (NG) (N 5 149 [55.0%]; median glucose5.99mmol/L[range5.38–6.72]),2)known diabetesmellitus (DM)(N5 56[20.7%]; 9.18 mmol/L [7.67–12.71]), and 3) no diabetes and glucose levels ≥7.78 mmol/L (HG) (N 5 66 [24.3%]; 8.57 mmol/L [8.18–10.47]). RESULTS Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients.DMandHG patients hadhigherD-dimer andworseinflammatoryprofile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI1.27–3.81,P50.005)thaninNG(16.8%)andmarginallysoinDM(28.6%;1.73,0.92– 3.25, P 5 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03–3.15, P 5 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46–8.76, P 5 0.005) and marginally in Q5 (29.6%) (2.32, 0.91–5.96, P 5 0.079) vs. Q1. CONCLUSIONS Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19

Predictors of hospital-acquired bacterial and fungal superinfections in COVID-19: a prospective observational study

Background: Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. Objectives: To identify predictors of superinfections in COVID-19. Methods: Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred 48 h after hospital admission. Amultivariate analysis was performed to identify factors independently associated with superinfections. Results: Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11–29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5–39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4–13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2–11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7–7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1–7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445). Conclusions: The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced