Background: To quantify the association between effects of interventions on carotid intimamedia thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were utilized. The primary outcome was a combined CVD endpoint defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the two using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized controlled trials involving 100,667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12,038 patients developed the combined CVD endpoint. Across all interventions, each 10 μm/year reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% credible interval 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/year would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74). Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary vs. secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

SummaryThe efficacy of tolvaptan for treating heart failure has already been shown. Adequate data relating to the effect of tolvaptan on the correlation of water balance in renal disease are not available. A retrospective study was conducted on the efficacy and adverse reactions of tolvaptan for treating nephrotic syndrome.The subjects were 26 patients with chronic kidney failure due to diabetic nephropathy with heart failure who were administered tolvaptan and seen between December 2011 and October 2013. The endpoints were urinary output, physical findings, and blood analyses. The expression of aquaporin-2 in the collecting duct, which is related to the action of tolvaptan, was investigated by immunohistochemistry using the kidney tissue obtained for the diagnosis.Responses were seen in 19 of the patients. In the histopathological investigation there was severe glomerulosclerosis in patients with diabetic nephropathy, but the responders were noticeable in that they only had mild tubulointerstitial damage. Non-responders exhibited profound tubulointerstitial damage. The expression of aquaporin-2 was determined in 8 patients, of which 7 were responders who tested positive for aquaporin-2. The remaining case was a non-responder who showed no expression of aquaporin-2.Tolvaptan is considered effective for some cases of nephrotic syndrome. There are no clear parameters for predicting an effect, but the present study showed that aquaporin-2 was expressed in the epithelial cells of the collecting ducts of tolvaptan responders. (Int Heart J 2014; 55: 533-538)

AST-120 has been used widely in Japan to slow the deterioration of renal function in patients with chronic kidney disease (CKD) by decreasing uremic toxins. The heart and the kidney are closely related, with cardiorenal interaction being very important. This retrospective study examined whether AST-120 influences the prevalence of dialysis induction, mortality, and cardiac and stroke events in CKD patients. The study included 278 patients diagnosed with chronic renal failure (CKD stage: III-V) in 2006. Of these patients, 128 received AST-120 (6 g/day), while the remaining 150 patients did not. A log-rank test was performed to compare dialysis induction, mortality, and cardiac and stroke events in the two groups. Univariate and multivariate Cox proportional hazard regression analyses were used to identify the potential factors that contributed to dialysis induction, mortality, and cardiac and stroke events over the next 5 years. Patient profiles before the study were almost the same other than age, primary disease (DM or non-DM) and urine volume. The prevalence of dialysis induction, mortality, and cardiac and stroke events in patients treated with AST-120 was significantly lower after 3 and 5 years (p < 0.0001) compared with the prevalence observed in the untreated patients. The absence of AST-120 treatment was associated independently with a high risk of dialysis induction (hazard ratio 4.979, 95 % CI 3.502-7.079, p < 0.0001), mortality (4.536, 2.666-7.720, p < 0.0001), cardiac event (3.590, 2.572-5.011, p < 0.001) and stroke (1.949, 1.342-2.829, p = 0.0005). The results of this retrospective analysis suggest that long-term treatment with AST-120 may improve the prognosis of CKD patients in the pre-dialysis stage. Long-term (i.e., >5 years) prospective randomized studies are needed to confirm the findings of the current study.

Introduction: Tubular injury is more important than glomerulopathy for renal prognosis in chronic kidney disease (CKD) patients. Numerous studies have demonstrated the active participation of the renin-angiotensin system (RAS) in CKD. However, whether addition of aliskiren, a direct renin inhibitor, to olmesartan improves renal tubular injury in CKD patients is unknown. Methods: This study compared the effects of aliskiren (300 mg daily), olmesartan (40 mg daily), and its combination therapy on urinary L-fatty acid binding protein (L-FABP), a marker of tubular injury in stage I or II CKD patients. It also examined which clinical variables were independently correlated with tubular damage. Results: Olmesartan or aliskiren monotherapy for 6 months comparably decreased blood pressure (BP) and proteinuria. BP and proteinuria levels were reduced more by combination therapy than by either monotherapy. Olmesartan or aliskiren decreased urinary L-FABP level, and combination therapy produced more incremental reduction in L-FABP level relative to each monotherapy. Multiple stepwise regression analysis revealed that BMI, low-density lipoprotein (LDL)-cholesterol and proteinuria were independently related to urinary L-FABP level. Conclusions:The present study demonstrated that addition of aliskiren to olmesartan decreased urinary L-FABP level partly via reduction of proteinuria in stage I or II CKD patients.

These results suggest the possibilities which LDL-apheresis is considered to contribute to survival extension and renal function maintenance of severe diabetic nephropathy patients.