Association of urinary sodium/potassium ratio with blood pressure: sex and racial differences.

BACKGROUND AND OBJECTIVES: Previous studies reporting an association between high BP and high sodium and low potassium intake or urinary sodium/potassium ratio (U[Na(+)]/[K(+)]) primarily included white men and did not control for cardiovascular risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This cross-sectional study investigated the association of U[Na(+)]/[K(+)] with BP in 3303 participants using robust linear regression. RESULTS: Mean age was 43±10 years, 56% of participants were women, and 52% were African American. BP was higher in African Americans than in non-African Americans, 131/81±20/11 versus 120/76±16/9 mmHg (P<0.001). Mean U[Na(+)]/[K(+)] was 4.4±3.0 in African Americans and 4.1±2.5 in non-African Americans (P=0.002), with medians (interquartile ranges) of 3.7 (3.2) and 3.6 (2.8). Systolic BP increased by 1.6 mmHg (95% confidence interval, 1.0, 2.2) and diastolic BP by 1.0 mmHg (95% confidence interval, 0.6, 1.4) for each 3-unit increase in U[Na(+)]/[K(+)] (P<0.001 for both). This association remained significant after adjusting for diabetes mellitus, smoking, body mass index, total cholesterol, GFR, and urine albumin/creatinine ratio. There was no interaction between African-American race and U[Na(+)]/[K(+)], but for any given value of U[Na(+)]/[K(+)], both systolic BP and diastolic BP were higher in African Americans than in non-African Americans. The diastolic BP increase was higher in men than in women per 3-unit increase in U[Na(+)]/[K(+)] (1.6 versus 0.9 mmHg, interaction P=0.03). CONCLUSIONS: Dietary Na(+) excess and K(+) deficiency may play an important role in the pathogenesis of hypertension independent of cardiovascular risk factors. This association may be more pronounced in men than in women.

A case of rare, fungal peritonitis caused by Histoplasma capsulatum in a patient on CAPD.

BACKGROUND: A 62-year-old man with a history of end-stage renal disease secondary to hypertension who was on continuous ambulatory peritoneal dialysis (CAPD), presented to a peritoneal dialysis clinic with subacute onset of abdominal pain, mainly in the epigastric region. INVESTIGATIONS: Full medical history, physical examination, laboratory tests, cultures of peritoneal dialysis fluid, radiography, ultrasonography and CT scanning of the abdomen and pelvis. DIAGNOSIS: Isolated fungal peritonitis caused by infection with Histoplasma capsulatum. MANAGEMENT: Removal of the peritoneal dialysis catheter, treatment with itraconazole for 6 months.

Inhibition of C-jun N-terminal kinase improves insulin sensitivity but worsens albuminuria in experimental diabetes.

C-jun N-terminal kinase (JNK) regulates both the development of insulin resistance and inflammation. Podocytes of the widely used db/db mouse model of diabetic nephropathy lose their ability to respond to insulin as albuminuria develops, in comparison to control db/+ mice. Here we tested whether JNK inhibition or its gene deletion would prevent albuminuria in experimental diabetes. Phosphorylated/total JNK was significantly increased in vivo in glomeruli of db/db compared to db/+ mice. Treatment of podocytes isolated from these two strains of mice with tumor necrosis factor-alpha caused greater phosphorylation of JNK in those obtained from diabetic animals. When db/db mice were treated with a cell-permeable TAT-JNK inhibitor peptide, their insulin sensitivity and glycemia significantly improved compared to controls. We induced diabetes in JNK1 knockout mice with streptozotocin and found that they had significantly better insulin sensitivity compared to diabetic wild-type or JNK2 knockout mice. Albuminuria was, however, worse in all mice treated with the JNK inhibitor and in diabetic JNK2 knockout mice compared to controls. Nephrin expression was also reduced in JNK inhibitor-treated mice compared to controls. A similar degree of mesangial expansion was found in all diabetic mice. Our study shows that targeting JNK to improve systemic insulin sensitivity does not necessarily prevent diabetic nephropathy.

Role of inflammation in diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD). Although the pathogenesis of DN is multifactorial, local inflammatory stress may result from both the metabolic and hemodynamic derangements observed in DN. Inflammatory markers such as Interleukin-18 and Tumor Necrosis Factor (TNF)-alpha are increased in the serum of patients with diabetes and DN. This occurs at a very early stage of disease, and correlates with the degree of albuminuria. Recent data suggest that standard pharmacologic interventions for DN, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists, may have anti-inflammatory properties that are independent of their hemodynamic effect. Although inflammation is traditionally thought of as a process resulting in macrophage infiltration, current scientific progress has lead to the novel idea that even cells distant from the blood stream, such as podocytes, can produce cytokines and can express molecules that are part of the co-stimulatory pathway. A strong translational research effort is currently aimed at defining the role of such molecules in cells other than lymphocytes and macrophages. Experimental animal models have recently provided evidence that some acute phase markers of inflammation such as intracellular cell adhesion molecule-1 (ICAM-1), TNF-alpha and Monocytes Chemoattractant Protein-1 (MCP-1) may have a causative role in the development of DN. Here, we review the current evidence supporting the role of inflammation in the early phases of clinical and experimental DN. A complete understanding of inflammatory pathways activated in DN may lead to the discovery of earlier and more reliable markers of DN than albuminuria and the identification of novel therapeutic targets.