Protein intake and kidney function in the middle-age population: contrast between cross-sectional and longitudinal data.

BACKGROUND: Protein intake is considered a determinant of glomerular filtration rate (GFR). Urinary urea is an objective marker of protein intake. The population-based study investigated, cross-sectionally and longitudinally, the association of protein intake with GFR, indexed by estimated GFR (eGFR). METHODS: Data were collected on overnight urinary urea, serum creatinine (S-cr), eGFR and other variables in 1522 men and women aged 45-64 years who participated in the Gubbio study (baseline). S-Cr, eGFR and other variables were re-assessed in 1144 of the 1425 survivors after 12-year follow-up. RESULTS: At baseline, mean ± SD was 84.0 ± 11.4 mL/min × 1.73 m(2) for eGFR calculated by CKD-Epi equation and 1.34 ± 0.57 g/day per kg of ideal weight for protein intake assessed by measurements of overnight urine excretion of urea nitrogen. Cross-sectional analyses of baseline data indicated a positive correlation of protein intake with eGFR (R = 0.180, P < 0.001). In multi-variable regression, 1 g/day higher protein intake related to 4.7 mL/min × 1.73 m(2) higher eGFR [95% confidence interval (CI) = 3.7/5.7]. At follow-up, mean ± SD of 12-year eGFR change was -11.6 ± 9.0 mL/min × 1.73 m(2). Baseline protein intake correlated with more negative eGFR change (R = -0.251, P < 0.001). In multi-variable regression, 1 g/day higher protein intake related to -4.1 mL/min × 1.73 m(2) more negative eGFR change (95% CI = -5.1/-3.1) and to 1.78 risk for incidence of eGFR < 60 mL/min × 1.73 m(2) (95% CI = 1.15/2.78). CONCLUSIONS: In middle-aged adults, high protein intake is associated cross-sectionally with higher GFR but longitudinally with greater GFR decline over time.

Glomerular filtration rate and serum phosphate: an inverse relationship diluted by age.

BACKGROUND: Available data indicate that serum phosphate increases only when glomerular filtration rate (GFR) falls into the low range (<60 mL/min x 1.73 m(2)). GFR and serum phosphate decrease with ageing. This population-based study investigated by age-controlled analyses the relationship of GFR with serum phosphate in adults with GFR above the low range. METHODS: Data were collected on age, sex, menstrual status, anthropometry, overnight urinary creatinine, dietary protein (overnight urinary urea), reported intake of milk/yogurt, serum creatinine, phosphate, calcium and total protein in 4034 adults (age 18-91 years) with GFR >or=60 mL/min x 1.73 m(2) as assessed by estimated GFR (eGFR, simplified MDRD equation) and creatinine clearance (overnight urinary creatinine/serum creatinine). RESULTS: The relationship of eGFR with serum phosphate was positive in men and null in women in univariate analyses (P = 0.001 and 0.148), negative in both sexes with age adjustment (P < 0.001). Age-adjusted results did not depend on colinearity between age and eGFR because the relationship was inverse also replacing eGFR with creatinine clearance (P < 0.001 in both sexes). In univariate regression analysis done separately by gender and six age-strata (18-24, 25-34, 35-44, 45-54, 55-64 and >or=65), the line of serum phosphate over eGFR was constantly inverse (range of P = 0.010/0.089) with the progressively lower y-axis intercept from young to older ages. The inverse relationship of eGFR or creatinine clearance with serum phosphate was significantly inverse also controlling for other variables (P < 0.01). CONCLUSIONS: GFR differences in the range >or=60 mL/min x 1.73 m(2) are inversely and independently related to serum phosphate. The relationship is undetectable without age-controlled procedures because, for serum phosphate, the effect of GFR differences above >or=60 mL/min x 1.73 m(2) is much smaller than the effect of age.

Early identification of kidney disease by eGFR: what is the prevalence of eGFR in the population?

The paper deals with the use of estimated glomerular filtration rate (eGFR) as marker of low kidney function in the population. Data were collected on serum creatinine, other laboratory indices, blood pressure, and medical history in a population sample of 2083 men and 2491 women aged between 18-95 years. Estimated GFR was calculated by the equation of Modification Diet in Renal Disease study. Disorders included in the analysis were hypertension, cardiovascular disease, high serum uric acid, high serum phosphorus/low serum calcium, anemia, and high serum potassium. Prevalence of low eGFR (eGFR <60 mL/min per 1.73 m2) increased with age: from <1% for ages 18-24 to >30% for ages > or =75, P<0.001. On the basis of these data, prevalence of low eGFR in the adult Italian population was 5.7% for men (n=1.3 million, 95%CI = 1.1/1.5) and 6.2% for women (n=1.5 million, 95%CI = 1.3/1.8). Disorders associated with kidney dysfunction were two or more in the majority of persons with low eGFR and were more frequent with lower eGFR (p<0.001). Previous diagnosis of kidney disease was reported by less than 5% in people with low eGFR and was progressively higher with higher serum creatinine or with number of associated disorders (p<0.03). Hypertension tended to be more frequently treated but not more frequently controlled in people with low eGFR. Data support the use of eGFR to identify people with or at risk of low kidney function. Awareness of kidney disease is low in people with low eGFR unless serum creatinine is very high or they have many associated disorders.

Urinary albumin and cardiovascular profile in the middle-aged population.

The moderate increase in urinary albumin excretion defined as microalbuminuria is not rare and is associated with cardiovascular risk factors. Microalbuminuria prevalence is low in the absence of cardiovascular risk factors and progressively increases with the number cardiovascular risk factors. The main correlate of microalbuminuria is blood pressure, either systolic or diastolic pressure. The relation between blood pressure and microalbuminuria is continuous and graded because the microalbuminuria prevalence increases with the severity of hypertension. Among hypertensive patients on drug treatment, blood pressure control is associated with a low prevalence of microalbuminuria. Thus, blood pressure appears as a determinant of microalbuminuria rather than a mere correlate. For hypercholesterolemia, smoking, and diabetes, data are less strong but point to an independent positive association with microalbuminuria. Altogether, data indicate that microalbuminuria in the population reflects the presence of cardiovascular risk factors. Data on microalbuminuria and coronary heart disease support this idea. There is a continuous and graded relation between urinary albumin excretion and coronary heart disease prevalence. High urinary albumin excretion is likely a sign of vascular damage existing both at the renal and cardiac levels and induced by 1 or more uncontrolled cardiovascular risk factors.

Unusual cases of chronic intoxication by vitamin D.

A 62-year-old man was hospitalized for recent renal colic and neurologic disorders. Routine biochemistry indicated the presence of hypercalcemia (serum total calcium = 15.3 mg/100 mL) and renal failure (serum creatinine = 3.72 mg/100 mL). The patient reported that he had been on treatment with a slow-release multivitamin preparation containing vitamin D and vitamin A, administered by i.m. injection. Plasma 25-OH vitamin D was > 150 ng/mL (normal range 16-74 ng/mL), plasma 1,25-(OH)2 vitamin D was 32.5 pg/mL (normal range 14-60 pg/mL), plasma parathyroid hormone 1.3 pg/mL (normal range 10-65 pg/mL). There were calcifications of left and right iliac artery at abdomen x-ray. Ultrasound and computed tomography of the glutei showed alterations of skeletal muscle and calcifications. Immediate treatment with infusion of isotonic saline, furosemide and prednisone induced rapid control of hypercalcemia and renal failure. Chronic treatment per os was discontinued after six months. The patient reported that the treatment with vitamin D had been prescribed by a physician also to his wife (55-year-old). For the woman, routine biochemistry indicated the presence of hypercalcemia (serum total calcium = 11.3 mg/100 mL) and renal failure (serum creatinine = 1.8 mg/ mL). Plasma 25-OH vitamin D was > 150 ng/mL, plasma 1,25-(OH)2 vitamin D 47.9 pg/mL, plasma parathyroid hormone was 2.5 pg/mL. Hypercalcemia was acutely treated by oral hydration, furosemide, and prednisone. Chronic treatment per os was discontinued after five months.