Effect of high-salt diet on blood pressure and body fluid composition in patients with type 1 diabetes: randomized controlled intervention trial

INTRODUCTION: Patients with type 1 diabetes are susceptible to hypertension, possibly resulting from increased salt sensitivity and accompanied changes in body fluid composition. We examined the effect of a high-salt diet (HSD) in type 1 diabetes on hemodynamics, including blood pressure (BP) and body fluid composition. RESEARCH DESIGN AND METHODS: We studied eight male patients with type 1 diabetes and 12 matched healthy controls with normal BP, body mass index, and renal function. All subjects adhered to a low-salt diet and HSD for eight days in randomized order. On day 8 of each diet, extracellular fluid volume (ECFV) and plasma volume were calculated with the use of iohexol and 125I-albumin distribution. Hemodynamic measurements included BP, cardiac output (CO), and systemic vascular resistance. RESULTS: After HSD, patients with type 1 diabetes showed a BP increase (mean arterial pressure: 85 (5) mm Hg vs 80 (3) mm Hg; p<0.05), while BP in controls did not rise (78 (5) mm Hg vs 78 (5) mm Hg). Plasma volume increased after HSD in patients with type 1 diabetes (p<0.05) and not in controls (p=0.23). There was no significant difference in ECFV between diets, while HSD significantly increased CO, heart rate (HR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in type 1 diabetes but not in controls. There were no significant differences in systemic vascular resistance, although there was a trend towards an HSD-induced decrease in controls (p=0.09). CONCLUSIONS: In the present study, patients with type 1 diabetes show a salt-sensitive BP rise to HSD, which is accompanied by significant increases in plasma volume, CO, HR, and NT-proBNP. Underlying mechanisms for these responses need further research in order to unravel the increased susceptibility to hypertension and cardiovascular disease in diabetes. TRIAL REGISTRATION NUMBERS: NTR4095 and NTR4788

Sodium-induced changes of the endothelial surface layer and microcirculation

Reduction of sodium intake has been recognized as a target for improvement of global health and lowering of medical costs. However, this target has not been met in any country and the optimum of maximum daily sodium intake remains controversial. Furthermore, it is also not fully understood how sodium loading leads to increased blood pressure and increased risk of cardiovascular events, and why the blood pressure response following sodium loading is so heterogeneous among individuals. We propose that sodium-associated microcirculatory changes might explain the - not yet clarified - link between sodium and high blood pressure. This thesis illustrates that our knowledge regarding sodium in (cardiovascular) health and disease continues to be challenged. We have challenged the classical two compartment view on sodium and volume homeostasis (chapter 2) and we have demonstrated that healthy volunteers are able to osmotically inactivate sodium following saline infusion (chapter 3). Furthermore, we have shown that both a dietary sodium load and an acute intravenous sodium load have damaging effects on the endothelial surface layer and microcirculation, independent of blood pressure (chapter 4 and chapter 5). We propose that sulodexide, a mixture of constituents of the endothelial surface layer, might be a new interesting drug to lower blood pressure (chapter 6). Our studies provide new insights into the relation between sodium, endothelial surface layer and microcirculation and are relevant for patients with hypertension, volume overload (e.g. patients with kidney disease, heart failure, dialysis patients) and dysnatriemia

BK Virus Disease following Allogeneic Stem Cell Transplantation: a Cohort Analysis

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is an increasingly used modality for the treatment of hematological disorders that causes a state of immunosuppression. Infection is a major cause of morbidity and mortality in HSCT recipients. Reactivation of BK virus (BKV), a human polyomavirus, following allogeneic HSCT affects the genitourinary (GU) tract with manifestations ranging from asymptomatic viruria to severe hemorrhagic cystitis. Knowledge about epidemiology, morbidity and clinical spectrum of BKV disease is limited in this population. Aim of this study was to assess and quantify incidence, severity, risk factors and outcome of BKV disease following allogeneic HSCT. Patients and Methods: Patients that underwent a first allogeneic HSCT between January 1, 2010 and December 31, 2011 at BWH/DFCI were included in this study. Medical records were reviewed for patient and HSCT characteristics. BKV disease was defined as detection of BKV by PCR testing in association with GU symptoms. BKV disease was considered severe when patients had at least 1 of the following characteristics: hematuria with clot formation, imaging compatible with BKV disease, need for invasive GU interventions, or hospitalization for BKV disease management. Time at risk was censored at time of death, second HSCT or on July 1, 2012. Fisher's exact or Wilcoxon test were used to compare variables between patients with BKV disease and patients without BKV disease. Cox modeling was used to analyze potential risk factors for BKV disease. Results: BKV disease occurred in 88 (17.9%) of 491 patients who underwent HSCT during the study period for an overall incidence rate of 0.54/1000 patient days (95% CI, 0.43 – 0.67). Severe BKV disease occurred in 31 patients for an overall incidence rate of 0.17 per 1000 patient days (95% CI, 0.12 – 0.25). Dysuria, hematuria and frequency were the most frequent experienced symptoms among patients with BKV disease during their first BKV disease episode. Symptoms lasted a median of 31 days (range, 2 – 385; IQR 9-67 days). Cohort characteristics associated with increased BKV disease risk included myeloablative conditioning (p=0.01), cyclophosphamide conditioning (p=0.0008), cord blood HSCT (p=0.03), GVHD prophylaxis with mycophenolate (MMF, p=0.0006) and acute GVHD (aGVHD) grades II-IV (p< 0.0001). On multivariate Cox modeling, time-dependent aGVHD (adjusted HR [aHR] 3.60, 95% CI 2.20 – 5.89), MMF use (aHR 3.15, 95% CI 1.79 – 5.56), and cyclophosphamide use (aHR 1.96, 95% CI 1.26 – 3.06) remained significant predictors of BKV disease. Time-dependent aGVHD grade III-IV (aHR 8.74, 95% CI 3.93 – 19.40) and cord blood HSCT (aHR 4.47, 95% CI 1.65 – 12.14) were independent risk factors for severe BKV disease. Conclusion: BKV disease is a common complication of HSCT, associated with significant and prolonged morbidity, especially in the setting of aGVHD, cyclophosphamide and MMF use. Prospective studies are needed to better define the morbidity of BKV disease and to properly inform the impact of future prophylaxis and treatment trials.