Objective To compare the effects on proteinuria and blood pressure of addition of dietary sodium restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose.Design Multicentre crossover randomised controlled trial. Setting Outpatient clinics in the Netherlands.Participants 52 patients with non-diabetic nephropathy.Interventions All patients were treated during four 6 week periods, in random order, with angiotensin receptor blockade (valsartan 320 mg/day) or placebo, each combined with, consecutively, a low sodium diet (target 50 mmol Na + /day) and a regular sodium diet (target 200 mmol Na + /day), with a background of ACE inhibition (lisinopril 40 mg/day) during the entire study. The drug interventions were double blind; the dietary interventions were open label. Main outcome measuresThe primary outcome measure was proteinuria; the secondary outcome measure was blood pressure.Results Mean urinary sodium excretion, a measure of dietary sodium intake, was 106 (SE 5) mmol Na + /day during a low sodium diet and 184 (6) mmol Na + /day during a regular sodium diet (P<0.001). Geometric mean residual proteinuria was 1.68 (95% confidence interval 1.31 to 2.14) g/day during ACE inhibition plus a regular sodium diet. Addition of angiotensin receptor blockade to ACE inhibition reduced proteinuria to 1.44 (1.07 to 1.93) g/day (P=0.003), addition of a low sodium diet reduced it to 0.85 (0.66 to 1.10) g/day (P<0.001), and addition of angiotensin receptor blockade plus a low sodium diet reduced it to 0.67 (0.50 to 0.91) g/day (P<0.001). The reduction of proteinuria by the addition of a low sodium diet to ACE inhibition (51%, 95% confidence interval 43% to 58%) was significantly larger (P<0.001) than the reduction of proteinuria by the addition of angiotensin receptor blockade to ACE inhibition (21%, (8% to 32%) and was comparable (P=0.009, not significant after Bonferroni correction) to the reduction of proteinuria by the addition of both angiotensin receptor blockade and a low sodium diet to ACE inhibition (62%, 53% to 70%). Mean systolic blood pressure was 134 (3) mm Hg during ACE inhibition plus a regular sodium diet. Mean systolic blood pressure was not significantly altered by the addition of angiotensin receptor blockade (131 (3) mm Hg; P=0.12) but was reduced by the addition of a low sodium diet (123 (2) mm Hg; P<0.001) and angiotensin receptor blockade plus a low sodium diet (121 (3) mm Hg; P<0.001) to ACE inhibition. The reduction of systolic blood pressure by the addition of a low sodium diet (7% (SE 1%)) was significantly larger (P=0.003) than the reduction of systolic blood pressure by the addition of angiotensin receptor blockade (2% (1)) and was similar (P=0.14) to the reduction of systolic blood pressure by the addition of both angiotensin receptor blockade and low sodium diet (9% (1)), to ACE inhibition.Conclusions Dietary sodium restriction...
Vitamin K is essential for the activity of γ-carboxyglutamate (Gla)-proteins including matrix Gla28 protein and osteocalcin; an inhibitor of vascular calcification and a bone matrix protein, respectively. Insufficient vitamin K intake leads to the production of non-carboxylated, inactive proteins and this could contribute to the high risk of vascular calcification in hemodialysis patients. To help resolve this, we measured vitamin K(1) and K(2) intake (4-day food record), and the vitamin K status in 40 hemodialysis patients. The intake was low in these patients (median 140 μg/day), especially on days of dialysis and the weekend as compared to intakes reported in a reference population of healthy adults (mean K(1) and K(2) intake 200 μg/day and 31 μg/day, respectively). Non-carboxylated bone and coagulation proteins were found to be elevated in 33 hemodialysis patients, indicating subclinical hepatic vitamin K deficiency. Additionally, very high non-carboxylated matrix Gla28 protein levels, endemic to all patients, suggest vascular vitamin K deficiency. Thus, compared to healthy individuals, hemodialysis patients have a poor overall vitamin K status due to low intake. A randomized controlled trial is needed to test whether vitamin K supplementation reduces the risk of arterial calcification and mortality in hemodialysis patients.
The mechanisms by which SGLT‐2 inhibitors lower albuminuria are incompletely understood. We assessed in a post‐hoc analysis of a cross‐over trial the effects of the SGLT2 inhibitor dapagliflozin on glomerular markers (IgG to IgG4 and IgG to albumin), tubular markers (urinary KIM‐1, NGAL and LFABP) and inflammatory markers (urinary MCP‐1 and IL‐6) to provide more insight into kidney protective effects. Dapagliflozin decreased albuminuria by 43.9% (95% CI, 30.3%‐54.8%) and eGFR by 5.1 (2.0‐8.1) mL/min/1.73m2 compared to placebo. Dapagliflozin did not change glomerular charge or size selectivity index compared to placebo. Dapagliflozin decreased urinary KIM‐1 excretion by 22.6% (0.3%‐39.8%; P = .05) and IL‐6 excretion by 23.5% (1.4%‐40.6%; P = .04) compared to placebo, whereas no changes in NGAL, LFABP and MCP‐1 were observed. During dapagliflozin treatment, changes in albuminuria correlated with changes in eGFR (r = 0.36; P = .05) and KIM‐1 (r = 0.39; P = .05). In conclusion, the albuminuria‐lowering effect of 6 weeks of dapagliflozin therapy may be the result of decreased intraglomerular pressure or reduced tubular cell injury.
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