Sex, Age, and the Association of Serum Phosphorus With All-Cause Mortality in Adults With Normal Kidney Function.

BACKGROUND: High serum phosphorus levels are associated with cardiovascular morbidity and mortality in kidney disease. Although serum phosphorus levels possibly influence on mortality in individuals without kidney disease, this is uncertain because of the variable sex- and age-based distribution of serum phosphorus levels. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Clinical and biochemical data were collected from 138,735 adults undergoing routine health checkups in 3 tertiary hospitals. Individuals with estimated glomerular filtration rates < 60 mL/min/1.73 m2 and urine dipstick albumin ≥ 1+ were excluded. PREDICTOR: Sex-specific quartiles of serum phosphorus and sex. OUTCOMES: All-cause mortality. RESULTS: The study included 92,756 individuals. Generally, women showed higher serum phosphorus levels than men. In women, serum phosphorus levels increased with age until 60 years old, then decreased with age. Men with higher serum phosphorus levels were younger and less likely to have hypertension, whereas women with higher serum phosphorus levels were older and more likely to have diabetes and hypertension. During a median follow-up of 75 months, 1,646 participants died. In the overall population, higher serum phosphorus levels were an independent predictor for all-cause mortality after adjustment (adjusted HR for the highest vs. lowest quartile, 1.34; 95% CI, 1.15-1.56; P<0.001). We observed that this increased risk was present in men but not in women (adjusted HR of 1.43 [95% CI, 1.22-1.68] vs. 1.01 [95% CI, 0.76-1.33]), but interaction by sex was not significant (P=0.8). LIMITATIONS: A single phosphorus measurement and low power to test for interactions by sex and age. CONCLUSIONS: We demonstrated that higher serum phosphorus levels influenced all-cause mortality in individuals with normal kidney function. Our findings suggest that the association may differ by sex, but future studies with adequate power to test for effect modification are needed to confirm our findings.

Effects of sodium citrate on salt sensitivity and kidney injury in chronic renal failure.

Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.

Potassium intake and the prevalence of metabolic syndrome: the Korean National Health and Nutrition Examination Survey 2008-2010.

Lower potassium intake is considered to be correlated with diabetes incidence. However, few studies have investigated the effect of potassium intake on metabolic syndrome (MetS). Data was taken from the Korean National Health and Nutritional Examination Survey (2008-2010) using weighted adjustment. MetS was defined as per the revised National Cholesterol Education Program criteria. Homeostasis model assessment indices were calculated to diagnosis insulin resistance (IR). A total of 16,637 participants (44 ± 0.25 years) were included. Women ingested lower amounts of potassium (2.71 ± 0.02 g/day) than men (3.45 ± 0.03 g/day). A curvilinear association between potassium intake and MetS prevalence was found among women. Women with less than the Adequate Intake (4.7 g/day) of potassium had an 11% risk reduction for MetS (adjusted odds ratio [OR], 0.89; 95% confidence interval [CI], 0.82-0.96; P = 0.004) and a 10% risk reduction for IR (OR, 0.90; 95% CI, 0.82-0.99; P = 0.026) for every 1 g/day potassium increase. Compared with the reference group (3.5-4.5 g/day), potassium intake was inversely associated with an increased risk of MetS (1.5-2.5 g/day; OR, 1.29; 95% CI, 1.02-1.63; P = 0.035; <1.5 g/day; OR, 1.40; 95% CI, 1.06-1.85; P = 0.017) and IR (<1.5 g/day; OR, 1.36; 95% CI, 1.05-1.76; P = 0.021). This relationship was more prominent in postmenopausal women, but not observed among men. Higher potassium intake is significantly associated with a lower MetS prevalence in women, and IR is believed to be connected.

Serum phosphorus as a predictor of low-grade albuminuria in a general population without evidence of chronic kidney disease.

BACKGROUND: High levels of serum phosphorus, even within the normal range, have been associated with cardiovascular (CV) morbidity. Low-grade albuminuria (LGA) was demonstrated to be related to increased CV events in various study populations. The present study aimed to investigate the association between serum phosphorus levels and LGA in the general population. METHODS: We examined the individuals who had undergone health inspections. We evaluated the correlation between serum phosphorus and LGA in 8953 participants (mean age, 47.4 years) with estimated glomerular filtration rates (eGFRs)≥60 mL/min/1.73 m2 and urinary albumin-to-creatinine ratios (UACRs)<30 mg/g. Participants who underwent a colonoscopy were excluded. RESULTS: The mean UACR was significantly higher in the uppermost quartile group of serum phosphorus concentrations than in other quartile groups. In the multivariate regression analysis, serum phosphorus remained an independent predictor of increased UACR (B=0.610, P<0.001). Subgroup analyses showed that this association was maintained irrespective of age, gender, presence of hypertension or diabetes, body mass index and eGFR. CONCLUSIONS: In our population-based study, higher serum phosphorus was independently related to LGA in individuals without evidence of renal dysfunction. Further investigations are warranted to clarify the precise mechanism of the association between serum phosphorus and LGA.

High dose vitamin D3 attenuates the hypocalciuric effect of thiazide in hypercalciuric rats.

Thiazide is known to decrease urinary calcium excretion. We hypothesized that thiazide shows different hypocalciuric effects depending on the stimuli causing hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D(28K), and several sodium transporters were assessed in hypercalciuric rats induced by high calcium diet and vitamin D(3). Urine calcium excretion and the expression of transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ, high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2 decreased in the hypercalciuric rats, and only SGLT1 protein abundance was increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is attenuated in high calcium and vitamin D-induced hypercalciuric rats. This attenuation seems to have resulted from the lack of HCTZ's effect on protein abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and vitamin D.