[Show abstract][Hide abstract] ABSTRACT: Chronic kidney disease is a widely recognized cardiovascular risk factor. Its detection within large populations depends upon the method used to estimate glomerular filtration. The Cockcroft and MDRD equations are widely used, although their accuracy is limited in certain cases.
The present study analyzes glomerular filtration values in 674 young, healthy subjects using five methods: Cockcroft, Cockcroft corrected for body surface, MDRD-4 Lund-Malmö and Sawyer formulas. Glomerular filtration values obtained with the first three methods were compared using ANOVA. The Spearman coefficient was calculated to estimate the correlation between MDRD-4 and Cockcroft values, and between Cockcroft values and body mass index.
There was a slight glomerular filtration rate decrease (< 90 ml/min) seen in 394 subjects using the Cockcroft equation, and in 344 subjects using the MDRD-4 formula. The prevalence of chronic kidney disease (glomerular filtration < 60 ml/min) was seen in 3 subjects using the MDRD-4 equation and 161 subjects using the Cockcroft formula. There was significant discordance, by method, between values obtained, with 40% of the population being classified into different stages (> 90 or < 90 ml/min) depending on the formula used. In 8% of the population there was even greater discordance, because they had strictly normal renal function according to MDRD-4 (> 90 ml/min) but fell into chronic kidney disease Stage 3 (< 60 ml/min) according to the Cockcroft formula. There was poor correlation between glomerular filtration rates obtained using the Cockcroft and MDRD-4 equations, suggesting that the subjects with a glomerular filtration rate decrease detected by the two methods were not the same ones. There was correlation between body mass index and glomerular filtration rates obtained with Cockcroft, Cockcroft corrected for body surface and Sawyer formulas and not with MDRD and Lund-Malmö equations.
There are important discrepancies between the methods used to assess renal function in healthy populations. These limitations must be taken into account when deciding on strategies for diagnosis and control of occult chronic kidney disease in the general population.
[Show abstract][Hide abstract] ABSTRACT: The role of mineral metabolism in cardiovascular pathologies has been studied almost exclusively in chronic kidney disease patients. There are no studies that relate mineral metabolism to pulse pressure in healthy populations.
692 subjects were initially selected. After applying clinical exclusion criteria, 659 subjects were recruited. Creatinine clearance was then calculated to detect subjects with occult chronic kidney disease. Statistical analysis was applied to the remaining population after excluding subjects with occult chronic kidney disease (n = 466). Pulse pressure, creatinine clearance, calcium, phosphorus, intact parathormone, 25-hydroxivitamin D3 and Bsm I genotype of the vitamin D receptor were determined. Means and frequencies were compared by ANOVA and Chi-square, respectively. Multivariate analysis was applied to the whole population and then to Caucasians, Sub-Saharans, Caucasian men and Caucasian women separately. Pulse pressure (PP) was the dependent variable, and adjustments were made for clinical and laboratory data.
The prevalence of occult chronic kidney disease was 32%. In subjects without kidney disease, phosphorus and vitamin D were independent predictors of elevated PP in Caucasian males whereas Bsm I genotype of the vitamin D was an independent predictor of elevated PP in the Caucasian population in both genders. No covariable showed relationship with PP in Sub-Saharan subjects.
Mineral metabolism influences pulse pressure in Caucasian men.
[Show abstract][Hide abstract] ABSTRACT: The K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease was published in October 2003. The objective of this study was to analyse the effect of the application of those guidelines on clinical practices and on the achievement of bone disease targets and quality standards.
We included in the study 342 patients dialysed in our three HD units during 2003 and 2004. Starting October 2003, the K-DOQI recommendations were introduced into practice. Parathyroid hormone (PTH) was measured every 3 months and the serum Ca and P levels, monthly. In patients whose medications were modified, PTH was measured monthly and Ca and P levels, weekly or biweekly.
The following are the main findings for 2004 (post-K/DOQI): an increased use of dialysates with a Ca concentration of 2.5 mEq/l (27.2-50.9%, P<0.001) and a reduced use of a dialysate calcium of 3.0 mEq/l (44.6-39.6%, P: NS) and 3.5 mEq/l (28-9.4%, P<0.001); a reduced use of calcium-based phosphate binders (891.9-565.5 mg Ca/day, P<0.001) and increased use of sevelamer hydrochloride (800 mg) (from 4.86 to 7.51 mg, tablets/day, P<0.001) lower serum Ca levels (9.7-9.4 mg/dl, P<0.01), and higher intact PTH levels (201.4-311.8 pg/ml, P<0.001), without changes in serum P levels; an increased proportion of patients with serum Ca levels within the K/DOQI target range (38.7-46.6%, P<0.01), resulting mainly from the reduced percentage of patients with hypercalcaemia (55-44.4%, P<0.01); a decreased proportion of patients with PTH<150 pg/ml (53.8-31.4%, P<0.001) but an increased proportion of patients with PTH>300 pg/ml, with no change in the proportion of patients with PTHs within the K/DOQI target range. Phosphorus levels and targets did not show significant differences between 2003 and 2004 (56.9-56.2%, P: NS).
The only way to ensure that K/DOQI guidelines actually improve medical outcomes is to emphasize implementation strategies and also the scientific evaluation of their effectiveness in clinical settings. In spite of the application of the K-DOQI recommendations, a large proportion of our patients stayed outside the proposed targets, which points to the need for more effective therapeutic options.
[Show abstract][Hide abstract] ABSTRACT: Hypokalemia is generally associated to neuromuscular symtoms, acid-base disorders and even to rhabdomyolysis. However, chronic hypokalemia can induce chronic renal failure through a characteristic tubulointerstitial damage consisting on vacuolization of epithelial tubular cells and interstitial fibrosis. This entity is called hypokalemic nephropathy, quite unusual and probably little know in our speciality. We present a clinical report of a patient admitted to our hospital with a severe hypokalemia secondary to an aldosterone producing adrenal adenoma that was diagnosed during admission. Besides hypokalemia the patient presented renal failure. Renal biopsy proved characteristic tubulointerstitial damage as described in hypokaliemic nephropathy. In summary, we report a Conn syndrome presenting as a hypokalemic nephropathy.
Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2006; 26(2):274-7. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Calcitriol has traditionally been the most widely used treatment for secondary hyperparathyroidism (SHPT) in uremic patients. There are currently no crossover equivalence studies of alphacalcidol versus calcitriol establishing which of the two derivatives is more active and better tolerated. The objective of this study was to compare the long term effect on control of PTH of similar doses of alphacalcidol versus calcitriol in the treatment of SHPT in these patients. METHODS: We conducted a retrospective study on 21 hemodialysis patients with stable SHPT of varying severity treated with intravenous calcitriol. In July 2002, the pharmacy of the reference hospital decided to substitute calcitriol for alphacalcidol based on the similarity of the two drugs. The conversion was made substituting a similar amount of drug. Mean absolute serum levels and percentage change in PTH, calcium and phosphorus were compared between the two periods and at 0, 3, 6, 9, 12 and 15 months after starting treatment with alphacalcidol. Student's t-test for paired means was used to compare the values between the two periods. RESULTS: In the calcitriol period, mean PTH levels were 275.2 +/- 111.7 pg/ml. The mean dose of drug used was 1.7 +/- 0.8 mcg postdialysis, and serum calcium and phosphorus levels were 10.1 +/- 0,5 mg/dl and 5,2 +/- 0,9 mg/dl, respectively (p < 0.01). Mean dialysate calcium content was 2,9 +/- 0,3 mEq/l. In the alphacalcidol period, PTH increased (441.6 +/- 178.3 pg/ml) (p < 0.001) and the percentage of patients with PTH < 300 pg/ml decreased (24% at the end of the period), in spite of significantly increasing the mean drug dose (2,3 +/- 0,9 mcg postdialysis) (p < 0.05). Serum calcium levels did not show significant differences (10.2 +/- 0.7 mg/dl) (p = NS), but phosphorus control was improved (4,7 +/- 0,5 mg/dl) (p < 0.01). The percentage of patients with PTH < 300 pg/ml decreased progressively from the start of treatment with alphacalcidol from 75% to 24% at the end of follow-up. Our results seem to suggest that the dose of alphacalcidol and calcitriol are not equivalent and we need to increase the dose of alphacalcidol to obtain a similar result to calcitriol on suppression of PTH in uremic patients with SPTH.
Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2006; 26(2):226-33. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several authors have documented beneficial effects of interferon (IFN) in chronic hepatitis C virus (HCV) infection among the dialysis population. Reports about mineral metabolism disturbances during IFN treatment are scarce, especially in dialysis patients. We report the case of a 49-year-old woman on hemodialysis with chronic HCV infection who developed significant decrease in serum calcium (Ca) and phosphorus (P) levels accompanied by relative hypoparathyroidism while being under treatment with alpha-IFN. These changes were closely related to IFN treatment, because they disappeared after INF was discontinued, reaching Ca and P levels which were similar to those of the pre-IFN period. Because IFN may induce immune disorders, several autoimmune markers were analyzed. All of them were negative or within the normal range. To further explore these mineral metabolism disturbances, a number ofparathyroid hormone (PTH) secretion-inhibiting factors, such as aluminum, magnesium, 25-hydroxyvitamin D, and calcitriol were excluded as a cause for these changes. We suggest that mineral metabolism should be carefully observed during interferon treatment in dialysis patients.
[Show abstract][Hide abstract] ABSTRACT: There are no studies that relate BsmI polymorphism of the vitamin D receptor (VDR) gene and with vitamin D to blood pressure (BP).
To analyze if this polymorphism and 25-hydroxyvitamin D levels (25OHD3) influence BP in a population of healthy subjects.
Transversal study on healthy population. Stepwise multiple regression analysis was performed to assess the association of BP with several clinical and biochemical data.
Industrial employees, blood donors, and army cadets from Lleida, Spain were recruited in October 2001. INDIVIDUALS: A total of 590 apparently healthy subjects (260 males and 330 females).
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were determined as the mean of three measurements. We also included age, gender, body mass index (BMI), serum levels of creatinine, calcium, phosphorus, intact parathyroid hormone (by two-site chemiluminometric assay), 25-hydroxyvitamin D (by radioimmunoassay) and BsmI genotype.
Since gender was strongly associated with both SBP and DBP, a separate analysis was performed for men and women. In males, SBP was associated with BMI, 25OHD3 (beta: 0.37, P < 0.000) and genotype (beta: -4.1, P < 0.001); and DBP with 25OHD3 (beta: 0.19, P < 0.008) and age. SBP was higher in men with bb genotype than in the other genotypes (P < 0.006). Moreover, there was a statistically significant positive correlation between 25OHD3 and both SBP (r: 0.53, P < 0.002) and DBP (r: 0.48, P < 0.005) in men with genotype BB. In women, neither 25OHD3 nor genotype were associated with BP levels.
BsmI polymorphism of the VDR gene influences BP in healthy men. A positive relationship between serum 25-hydroxyvitamin D levels and BP is present only in men with the BB genotype.
Journal of Hypertension 11/2003; 21(11):2069-75. DOI:10.1097/01.hjh.0000098139.70956.21 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atherosclerosis is the principal cause of myocardial infarction, stroke, and peripheral vascular disease, accounting for nearly half of all mortality in developed countries. The excessive growth of vascular smooth muscle cells is an important component in the development of atherosclerotic lesion. The direct effect of calcitriol and vitamin D analogs on the VSMCs proliferation is not clear. In this study we have analysed if calcitriol, Paricalcitol (19-nor-1,25-dihydroxy-vitamin D2) and EB1089 (experimental analog used as anticancerous) modify proliferation and the expression of vitamin D receptor (VDR) gene that is regulated at the transcriptional level by itself in the VSMCs. VSMCs proliferation was analysed by BrdU incorporation and VDR gene expression using RT-PCR. VSMCs proliferation was stimulated when calcitriol was added to the culture. VSMCs proliferation was significantly lower with analogs at the same dose. With regard to the functional study, the expression of VDR gene was upregulated by calcitriol at a concentration of 100 nM. There were no changes in this expression with the analogs. In conclusion, calcitriol, do not modify VSMCs proliferation. Therefore, Paricalcitol could have a minor proliferating effect on the wall of vessels that vitamin D.
Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2003; 23 Suppl 2:117-21. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of vitamin D in the regulation of blood pressure is unclear. There are no studies that relate Bsm I polymorphism with blood pressure.
To analyze if Bsm I polymorphism and 25-hydroxyvitamin D (25OHD3) influence blood pressure in healthy individuals with normal blood pressure.
Systolic (SBP) and diastolic (DBP) blood pressure, Body Mass Index (BMI), plasma creatinine, serum calcium, serum phosphorus, serum iPTH, serum 25OHD3 and Bsm I genotype were determined in 590 healthy individuals (260 men and 330 women). Data were analysed using a multiple linear regression model. SBP and DBP were defined as dependent variables and the rest of variables as independent.
Gender was strongly associated with both SBP (beta: -12.01, p: 0.000) and DBP (beta: -4.78, p: 0.000). Therefore, a separate analysis was performed according to gender. In males, SBP was associated with BMI (beta: 0.83, p: 0.001), 25OHD3, (beta: 0.36, p: 0.000) and genotype (beta: -3.90, p: 0.002); and DBP with 25OHD 3 (beta: 0.16, p: 0.018) and age (beta: 0.28, p: 0.000). Differences of blood pressure among the three genotypes were explored by analysis of variance. SBP was higher in men with bb genotype than in the other genotypes (p: 0.007). In females, 25OHD3 and genotype were not associated with blood pressure.
Healthy men with higher levels of vitamin D have higher levels of SBP and DBP. Moreover, men with bb genotype have the highest levels of SBP. Blood pressure levels in women are not influenced by vitamin D nor by Bsml genotype. Our data suggest a possible pathophysiological interaction between vitamin D and sex hormones in blood pressure control.
Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2003; 23 Suppl 2:32-6. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bsml vitamin D receptor (VDR) gene polymorphism has been reported to influence the progression of secondary hyperparathyroidism but it is not known how much the genetic background contributes to the need for parathyroidectomy (PTx). We investigated the influence of VDR gene polymorphism on PTx in patients with different dialysis vintage.
We studied 121 parathyroidectomized HD patients ("PTx " group). Patients who had required early parathyroidectomy ("early PTx" group) or late parathyroidectomy ("late PTx" group) were analyzed separately. The cut-off point between these two groups was 89 months (mean time on hemodialysis (HD) before parathyroidectomy). Serum intact parathyroid hormone, calcium, phosphorus and alkaline phosphatase were measured. Bsml genotypes were analyzed by polymerase chain reaction. Statistical analysis was done with univariant analysis of variance (ANOVA) to compare the genotype groups and general factorial ANOVA, entering time on HD as the dependent variable, with genotype, sex, age and chronic renal failure (CRF) etiology as factors. As a control group for the association studies we determined genotypic frequencies in 162 HD patients ("total HD" group), and in a healthy control population of 120 individuals ("healthy" group), tested by contingency table analysis and the chi-square test.
No significant differences were found between the genotypes except for the time on HD. General factorial ANOVA showed that the adjusted means of the time on HD were significantly different for the various genotypes (p = 0.015). The BB genotype was significantly less frequent in the "early PTx " group than in the "total HD" and "late PTx" groups.
Individuals with the BB genotype can remain longer on HD before they need parathyroidectomy.
Journal of nephrology 01/2003; 16(1):116-20. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Porphyria cutanea tarda is treated with phlebotomies in the absence of renal failure. However, in patients on maintenance hemodialysis, this will lead to the need for high doses of erythropoietin. We describe the case of a 63-year-old hemodialysis patient who had chronic hepatitis C virus and developed porphyria cutanea tarda after iron overload due to repeated transfusions. She was treated with erythropoietin and phlebotomies reaching clinical remission 4 months after beginning treatment.
Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2002; 22(6):570-3. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Percutaneous transluminal renal angioplasty (PTRA) has a beneficial effect on renal function in some, but not all, patients with atheromatous renal artery stenosis. Our aim is to identify factors influencing clinical success after PTRA in this group of patients. Seventy-three patients undergoing PTRA were studied; 14 patients were excluded from final analysis because of restenosis. All patients had chronic renal failure secondary to vascular nephropathy and renal artery stenosis. The diagnosis of renal artery stenosis was based on carbon dioxide digital angiography showing greater than 60% luminal narrowing. The rate of renal failure progression was assessed by the slope of the regression line of serum creatinine versus time. At least three consecutive creatinine measurements before and after angioplasty were required for study entry. Response to PTRA was made by comparison of the slope before and after PTRA. The association of age, serum creatinine level, proteinuria, renal size, pre-PTRA slope value, diabetes, ischemic heart disease, peripheral vascular disease, and cerebrovascular disease with response to PTRA was assessed by multiple regression analysis, with changes in slope values as the dependent variable. Renal function improved in 34 of 59 patients (57.6%). Mean follow-up was 627 +/- 284 (SD) days. The slope of the reciprocal serum creatinine plot before PTRA was significantly associated with a favorable change in progression rate after PTRA (beta = -0.012; P = 0.004). A scatter plot showed a statistically significant inverse correlation between pre-PTRA slope values and post-PTRA slope changes (r = -0.46; P = 0.000). Rapidly progressive renal failure is associated with a favorable response on renal failure progression after PTRA in patients with vascular nephropathy and renal artery stenosis.
American Journal of Kidney Diseases 02/2002; 39(1):60-6. DOI:10.1053/ajkd.2002.29881 · 5.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Calcitriol has traditionally been the most widely used treatment for secondary hyperparathyroidism (SHPT) in uremic patients. There are currently no crossover equivalence studies of alphacalcidol versus calcitriol establishing which of the two derivatives is more active and better tolerated. The objective of this study was to compare the long term effect on control of PTH of similar doses of alphacalcidol versus calcitriol in the treatment of SHPT in these patients. Methods: We conducted a retrospective study on 21 hemodialysis patients with stable SHPT of varying severity treated with intravenous calcitriol. In july 2002, the pharmacy of the reference hospital decided to substitute calcitriol for alpha-calcidol based on the similarity of the two drugs. The conversion was made subs-tituting a similar amount of drug. Mean absolute serum levels and percentage chan-ge in PTH, calcium and phosphorus were compared between the two periods and at 0, 3, 6, 9, 12 and 15 months after starting treatment with alphacalcidol. Stu-dent's t-test for paired means was used to compare the values between the two periods. Results: In the calcitriol period, mean PTH levels were 275.2 ± 111.7 pg/ml. The mean dose of drug used was 1.7 ± 0.8 mcg postdialysis, and serum calcium and phosphorus levels were 10.1 ± 0,5 mg/dl and 5,2 ± 0,9 mg/dl, respectively (p < 0.01). Mean dialysate calcium content was 2,9 ± 0,3 mEq/l. In the alphacalcidol period, PTH increased (441.6 ± 178.3 pg/ml) (p < 0.001) and the percentage of patients with PTH < 300 pg/ml decreased (24% at the end of the period), in spite of significantly increasing the mean drug dose (2,3 ± 0,9 mcg postdialysis) (p < 0.05). Serum calcium levels did not show significant differences (10.2 ± 0.7 mg/dl) (p = NS), but phosphorus control was improved (4,7 ± 0,5 mg/dl) (p < 0.01). The percentage of patients with PTH < 300 pg/ml decreased progressively from the start of treatment with alphacalcidol from 75% to 24% at the end of follow-up. Our results seem to suggest that the dose of alphacalcidol and calcitriol are not equivalent and we need to increase the dose of alphacalcidol to obtain a similar result to calcitriol on suppression of PTH in uremic patients with SPTH.