Occult chronic kidney disease: discordance among different methods used to estimate glomerular filtration rate in a healthy population.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Influence of mineral metabolism parameters on pulse pressure in healthy subjects.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Mineral metabolism influences pulse pressure in Caucasian men.

[A long-term comparative study of calcitriol versus alphacalcidol in patients with secondary hyperparathyroidism on hemodialysis]. / Estudio comparativo a largo plazo entre calcitriol y alfacalcidol en pacientes con hiperparatiroidismo secundario en hemodiálisis.

UNLABELLED: 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.

[Hypokaliemic nephropathy as a form of presentation of Conn syndrome]. / Nefropatía hipokaliémica como presentación de un síndrome de Conn.

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.

Relative hypoparathyroidism induced by interferon treatment in a hemodialysis patient.

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.

[Influence of the vitamin D receptor gene polymorphism and 25-hydroxyvitamin D on arterial pressure in health individuals]. / Influencia del polimorfismo del gen receptor de la vitamina D y de la 25-hidroxivitamina D en la tensión arterial de individuos sanos.

UNLABELLED: 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. OBJECTIVE: To analyze if Bsm I polymorphism and 25-hydroxyvitamin D (25OHD3) influence blood pressure in healthy individuals with normal blood pressure. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Differential effect of vitamin D analogues on the proliferation of vascular smooth muscle cells]. / Efecto diferencial de los análogos de la vitamina D en la proliferación de células de músculo liso vascular.

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.

[Porphyria cutanea tarda, hemodialysis and HCV hepatopathy]. / Porfiria cutánea tarda, hemodiálisis y hepatopatía VHC.

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.