Maria Elena Liberti

Sodium/Glucose Cotransporter 2 Inhibitors and Prevention of Diabetic Nephropathy: Targeting the Renal Tubule in Diabetes

Optimal prevention and treatment of chronic kidney disease in diabetes requires implementing therapies that specifically interfere with the pathogenesis of diabetic nephropathy. In this regard, significant attention has been given to alterations of the proximal tubule and resulting changes in glomerular filtration rate. At the onset of diabetes mellitus, hyperglycemia causes increases in proximal tubular reabsorption secondary to induction of tubular growth with associated increases in sodium/glucose cotransport. The increase in proximal reabsorption leads to a decrease in solute load to the macula densa, deactivation of the tubuloglomerular feedback, and increases in glomerular filtration rate. Because glomerular hyperfiltration currently is recognized as a risk factor for progression of kidney disease in diabetic patients, limiting proximal tubular reabsorption constitutes a potential target to reduce hyperfiltration. The recent introduction of sodium/glucose cotransporter 2 (SGLT2) inhibitors opens new therapeutic perspectives for this high-risk patient population. Experimental studies have shown that these new agents attenuate the progressive nature of diabetic nephropathy by blood glucose-dependent and -independent mechanisms. SGLT2 inhibition may prevent glomerular hyperfiltration independent of the effect of lowering blood glucose levels while limiting kidney growth, inflammation, and albuminuria through reductions in blood glucose levels. Clinical data for the potential role of the proximal tubule in the pathophysiology of diabetic nephropathy and the nephroprotective effects of SGLT2 inhibitors currently are limited compared to the more extensive experimental literature. We review the evidence supporting this working hypothesis by integrating the experimental findings with the available clinical data.

Independent Role of Underlying Kidney Disease on Renal Prognosis of Patients with Chronic Kidney Disease under Nephrology Care

Primary kidney disease is suggested to affect renal prognosis of CKD patients; however, whether nephrology care modifies this association is unknown. We studied patients with CKD stage I-IV treated in a renal clinic and with established diagnosis of CKD cause to evaluate whether the risk of renal event (composite of end-stage renal disease and eGFR decline ≥40%) linked to the specific diagnosis is modified by the achievement or maintenance in the first year of nephrology care of therapeutic goals for hypertension (BP ≤130/80 mmHg in patients with proteinuria ≥150 mg/24h and/or diabetes and ≤140/90 in those with proteinuria <150 mg/24h and without diabetes) anemia (hemoglobin, Hb ≥11 g/dL), and proteinuria (≤0.5 g/24h). Survival analysis started after first year of nephrology care. We studied 729 patients (age 64±15 y; males 59.1%; diabetes 34.7%; cardiovascular disease (CVD) 44.9%; hypertensive nephropathy, HTN 53.8%; glomerulonephritis, GN 17.3%; diabetic nephropathy, DN 15.9%; tubule-interstitial nephropathy, TIN 9.5%; polycystic kidney disease, PKD 3.6%). During first year of Nephrology care, therapy was overall intensified in most patients and prevalence of main therapeutic goals generally improved. During subsequent follow up (median 3.3 years, IQR 1.9-5.1), 163 renal events occurred. Cox analysis disclosed a higher risk for PKD (Hazard Ratio 5.46, 95% Confidence Intervals 2.28–10.6) and DN (1.28,2.99–3.05), versus HTN (reference), independently of age, gender, CVD, BMI, eGFR or CKD stage, use of RAS inhibitors and achievement or maintenance in the first year of nephrology care of each of the three main therapeutic goals. No interaction was found on the risk of CKD progression between diagnostic categories and month-12 eGFR (P=0.737), as with control of BP (P=0.374), Hb (P=0.248) or proteinuria (P=0.590). Therefore, in CKD patients under nephrology care, diagnosis of kidney disease should be considered in conjunction with the main risk factors to refine renal risk stratification.

Indoor Telemedicine in Hospital: a PDA-based Flexible Solution for Wireless Monitoring and Database Integration.

An integrated information flexible system is proposed in this paper for indoor medical applications. The system is intended to provide clinicians with a portable device enabling to discover and recognize patients and easily access their electronic record in a fast and secure way for consultation or updating. Moreover the developed solution allows communication with medical equipments for wireless monitoring of patients biosignals. Requirements for such a system are therefore high flexibility and mobility, as well as fast and secure wireless communication. These features were achieved combining the use of Bluetooth technology with a personal digital assistant, which was provided with a multilayer software architecture to allow easy access to hospital database and to communicate with external medical devices. A prototype was also realized and the testing phase has indicated good performances on both patient discovery and wireless monitoring

Reassessment of Ambulatory Blood Pressure Improves Renal Risk Stratification in Nondialysis Chronic Kidney Disease: Long-Term Cohort Study

In nondialysis chronic kidney disease, ambulatory blood pressure (ABP) performs better than clinic BP in predicting outcome, but whether repeated assessment of ABP further refines prognosis remains ill-defined. We recruited 182 consecutive hypertensive patients with nondialysis chronic kidney disease who underwent 2 ABPs 12 months apart to evaluate the enhancement in risk stratification provided by a second ABP obtained 1 year after baseline on the risk (hazard ratio and 95% confidence interval) of composite renal end point (death, chronic dialysis, and estimated glomerular filtration rate decline ≥40%). The difference in daytime and nighttime systolic BP between the 2 ABPs (daytime and nighttime bias) was added to a survival model including baseline ABP. Net reclassification improvement was also calculated. Age was 65.6±13.4 years; 36% had diabetes mellitus and 36% had previous cardiovascular event; estimated glomerular filtration rate was 42.2±19.6 mL/min per 1.73 m2, and clinic BP was 145±18/80±11 mm Hg. Baseline ABP (daytime, 131±16/75±10 and nighttime, 122±18/66±10 mm Hg) and daytime/nighttime BP goals (58.2% and 43.4%) did not change at month 12. Besides baseline ABP values, bias for daytime and nighttime systolic BP linearly associated with renal outcome (1.12, 1.04–1.21 and 1.18, 1.08–1.29 for every 5-mm Hg increase, respectively). Classification of patients at risk improved when considering nighttime systolic level at second ABP (net reclassification improvement, 0.224; 95% confidence interval, 0.005–0.435). Patients with first and second ABPs above target showed greater renal risk (2.15, 1.29–3.59 and 1.71, 1.07–2.72, for daytime and nighttime, respectively). In nondialysis chronic kidney disease, reassessment of ABP at 1 year further refines renal prognosis; such reassessment should specifically be considered in patients with uncontrolled BP at baseline.

Reassessment of Ambulatory Blood Pressure Improves Renal Risk Stratification in Nondialysis Chronic Kidney Disease

In nondialysis chronic kidney disease, ambulatory blood pressure (ABP) performs better than clinic BP in predicting outcome, but whether repeated assessment of ABP further refines prognosis remains ill-defined. We recruited 182 consecutive hypertensive patients with nondialysis chronic kidney disease who underwent 2 ABPs 12 months apart to evaluate the enhancement in risk stratification provided by a second ABP obtained 1 year after baseline on the risk (hazard ratio and 95% confidence interval) of composite renal end point (death, chronic dialysis, and estimated glomerular filtration rate decline ≥40%). The difference in daytime and nighttime systolic BP between the 2 ABPs (daytime and nighttime bias) was added to a survival model including baseline ABP. Net reclassification improvement was also calculated. Age was 65.6±13.4 years; 36% had diabetes mellitus and 36% had previous cardiovascular event; estimated glomerular filtration rate was 42.2±19.6 mL/min per 1.73 m2, and clinic BP was 145±18/80±11 mm Hg. Baseline ABP (daytime, 131±16/75±10 and nighttime, 122±18/66±10 mm Hg) and daytime/nighttime BP goals (58.2% and 43.4%) did not change at month 12. Besides baseline ABP values, bias for daytime and nighttime systolic BP linearly associated with renal outcome (1.12, 1.04–1.21 and 1.18, 1.08–1.29 for every 5-mm Hg increase, respectively). Classification of patients at risk improved when considering nighttime systolic level at second ABP (net reclassification improvement, 0.224; 95% confidence interval, 0.005–0.435). Patients with first and second ABPs above target showed greater renal risk (2.15, 1.29–3.59 and 1.71, 1.07–2.72, for daytime and nighttime, respectively). In nondialysis chronic kidney disease, reassessment of ABP at 1 year further refines renal prognosis; such reassessment should specifically be considered in patients with uncontrolled BP at baseline.

Reassessment of Ambulatory Blood Pressure Improves Renal Risk Stratification in Nondialysis Chronic Kidney DiseaseNovelty and Significance

In nondialysis chronic kidney disease, ambulatory blood pressure (ABP) performs better than clinic BP in predicting outcome, but whether repeated assessment of ABP further refines prognosis remains ill-defined. We recruited 182 consecutive hypertensive patients with nondialysis chronic kidney disease who underwent 2 ABPs 12 months apart to evaluate the enhancement in risk stratification provided by a second ABP obtained 1 year after baseline on the risk (hazard ratio and 95% confidence interval) of composite renal end point (death, chronic dialysis, and estimated glomerular filtration rate decline ≥40%). The difference in daytime and nighttime systolic BP between the 2 ABPs (daytime and nighttime bias) was added to a survival model including baseline ABP. Net reclassification improvement was also calculated. Age was 65.6±13.4 years; 36% had diabetes mellitus and 36% had previous cardiovascular event; estimated glomerular filtration rate was 42.2±19.6 mL/min per 1.73 m2, and clinic BP was 145±18/80±11 mm Hg. Baseline ABP (daytime, 131±16/75±10 and nighttime, 122±18/66±10 mm Hg) and daytime/nighttime BP goals (58.2% and 43.4%) did not change at month 12. Besides baseline ABP values, bias for daytime and nighttime systolic BP linearly associated with renal outcome (1.12, 1.04–1.21 and 1.18, 1.08–1.29 for every 5-mm Hg increase, respectively). Classification of patients at risk improved when considering nighttime systolic level at second ABP (net reclassification improvement, 0.224; 95% confidence interval, 0.005–0.435). Patients with first and second ABPs above target showed greater renal risk (2.15, 1.29–3.59 and 1.71, 1.07–2.72, for daytime and nighttime, respectively). In nondialysis chronic kidney disease, reassessment of ABP at 1 year further refines renal prognosis; such reassessment should specifically be considered in patients with uncontrolled BP at baseline.

Reassessment of Ambulatory Blood Pressure Improves Renal Risk Stratification in Nondialysis Chronic Kidney DiseaseNovelty and Significance: Long-Term Cohort Study

In nondialysis chronic kidney disease, ambulatory blood pressure (ABP) performs better than clinic BP in predicting outcome, but whether repeated assessment of ABP further refines prognosis remains ill-defined. We recruited 182 consecutive hypertensive patients with nondialysis chronic kidney disease who underwent 2 ABPs 12 months apart to evaluate the enhancement in risk stratification provided by a second ABP obtained 1 year after baseline on the risk (hazard ratio and 95% confidence interval) of composite renal end point (death, chronic dialysis, and estimated glomerular filtration rate decline ≥40%). The difference in daytime and nighttime systolic BP between the 2 ABPs (daytime and nighttime bias) was added to a survival model including baseline ABP. Net reclassification improvement was also calculated. Age was 65.6±13.4 years; 36% had diabetes mellitus and 36% had previous cardiovascular event; estimated glomerular filtration rate was 42.2±19.6 mL/min per 1.73 m2, and clinic BP was 145±18/80±11 mm Hg. Baseline ABP (daytime, 131±16/75±10 and nighttime, 122±18/66±10 mm Hg) and daytime/nighttime BP goals (58.2% and 43.4%) did not change at month 12. Besides baseline ABP values, bias for daytime and nighttime systolic BP linearly associated with renal outcome (1.12, 1.04–1.21 and 1.18, 1.08–1.29 for every 5-mm Hg increase, respectively). Classification of patients at risk improved when considering nighttime systolic level at second ABP (net reclassification improvement, 0.224; 95% confidence interval, 0.005–0.435). Patients with first and second ABPs above target showed greater renal risk (2.15, 1.29–3.59 and 1.71, 1.07–2.72, for daytime and nighttime, respectively). In nondialysis chronic kidney disease, reassessment of ABP at 1 year further refines renal prognosis; such reassessment should specifically be considered in patients with uncontrolled BP at baseline.