ABSTRACT
Observational studies have demonstrated that low blood pressure is related to poor clinical outcomes in patients with chronic kidney disease (CKD). Subgroup analyses from the SPRINT trial showed that targeting systolic blood pressure under 120 mmHg is less beneficial for patients with CKD. Although malnutrition and inflammation are common in patients with advanced CKD, such patients are usually excluded from clinical trials. Therefore, we hypothesized that malnutrition-inflammation-cachexia syndrome could explain this J-shaped relationship. To test this, we studied 2441 patients with CKD stages 3-5 who received anti-hypertensive treatment for at least one year. Averaged blood pressures of the first year were used in the analyses. Fine-Gray competing risks regression showed a J-shaped relationship between continuous systolic blood pressure and end-stage kidney disease (ESKD) with a nadir risk at a systolic blood pressure of 120 mmHg. Adjusted sub-distribution hazard ratios of categorical systolic blood pressure 100-109 and 110-119 mmHg were 2.17 (95% confidence interval: 1.21-3.89) and 1.37 (0.94-1.99) for ESKD, respectively, compared with systolic blood pressures of 120-129 mmHg. Cox regression also showed J-shaped relationships between continuous systolic or diastolic blood pressures, and the composite outcomes of cardiovascular events and all-cause mortality. Logistic regression demonstrated the odds ratios of blood pressure components for Malnutrition-Inflammation Scores over 4 were J-shaped. Sub-distribution hazard ratios of systolic blood pressure 100-119 mmHg for ESKD was higher in those with a Malnutrition-Inflammation Score over 4, compared to 0.93 (0.53-1.63) in those with a score of 4 or under with significant interaction. Thus, malnutrition-inflammation-cachexia syndrome is associated with low blood pressure and modifies the J-shaped relationship in patients with advanced CKD.
Subject(s)
Hypertension , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Antihypertensive Agents/therapeutic use , Blood Pressure , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Kidney Failure, Chronic/drug therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/drug therapy , SystoleABSTRACT
Sodium glucose cotransporter 2 inhibitors have shown a potential for renoprotection beyond blood glucose lowering. Glycosuria in nondiabetic patients with chronic kidney disease (CKD) is sometimes noted. Whether glycosuria in CKD implies a channelopathy or proximal tubulopathy is not known. The consequence of glycosuria in CKD is also not studied. We performed a cross-sectional study for the association between glycosuria and urine electrolyte excretion in 208 nondiabetic patients. Fractional excretion (FE) of glucose >4% was 3.4%, 6.3% and 62.5% in CKD stage 3, 4 and 5, respectively. These patients with glycosuria had higher FE sodium, FE potassium, FE uric acid, UPCR, and urine NGAL-creatinine ratio. We conducted a longitudinal study for the consequence of glycosuria, defined by dipstick, in 769 nondiabetic patients with stage 4-5 CKD. Glycosuria was associated with a decreased risk for end-stage renal disease (adjusted hazard ratio: 0.77; CI = 0.62-0.97; p = 0.024) and for rapid renal function decline (adjusted odds ratio: 0.63; CI = 0.43-0.95; p = 0.032); but glycosuria was not associated with all-cause mortality or cardiovascular events. The results were consistent in the propensity-score matched cohort. Glycosuria is associated with increased fractional excretion of electrolytes and is related to favorable renal outcomes in nondiabetic patients with stage 5 CKD.
Subject(s)
Glycosuria/urine , Kidney/physiopathology , Renal Insufficiency, Chronic/urine , Creatinine/urine , Cross-Sectional Studies , Electrolytes/urine , Female , Glomerular Filtration Rate/physiology , Humans , Kidney Failure, Chronic/urine , Longitudinal Studies , Male , Middle Aged , Proportional Hazards Models , Sodium-Glucose Transporter 2 Inhibitors , Uric Acid/urineABSTRACT
BACKGROUND: Systolic blood pressure (SBP) goal for chronic kidney disease (CKD) patients is ≤140mm Hg. However, the SBP target provides no suggested lower limit, and some studies indicate that a lower SBP target may be harmful. We aimed to investigate the J-shaped relationship between SBP and clinical outcomes in CKD patients and the factors that modify this relationship. METHODS: This prospective observational study enrolled 2,144 CKD stage 3-4 patients between November 2002 and May 2009 and followed them until July 2010 or death. Patients included were also enrolled within the Integrated CKD Care Program for Delaying Dialysis in a medical center and its branch hospital. Demographic, clinical, laboratory, and disease variables at baseline and end of observation were measured. RESULTS: In diabetic CKD patients, the hazard ratio (HR) at SBP 96-110mm Hg vs. 111-120mm Hg was 2.52 (95% confidence interval (CI) = 1.13-5.58) for cardiovascular outcomes and was 3.14 (95% CI = 1.16-8.49) for renal outcomes. In nondiabetic CKD patients, this J-shaped relationship was not seen. Heavy proteinuria was further found to modify the J-shaped relationship in diabetic CKD patients. The HR for renal outcomes at SBP 96-110mm Hg vs. 111-120mm Hg was 4.07 (95% CI = 1.18-13.99) in diabetic CKD patients with heavy proteinuria vs. 1.72 (95% CI = 0.13-22.5) in those without heavy proteinuria. CONCLUSIONS: Diabetic CKD patients have a J-shaped relationship between SBP and cardiovascular or renal outcomes, but nondiabetic CKD patients do not. The optimal SBP range might be narrower in the diabetic CKD patients.
