[Clinical research based nephrology (bases for the constitution of an Evidence Based Nephrology Group in the Spanish Society of Nephrology)].
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Biomedical subjects
Publications and source records attributed to R Saracho.
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Secondary hyperparathyrodism (SH) is an early manifestation of chronic renal failure (CRF), which has serious complications. Moreover, treating SH is not a risk-free process. Once in its advanced state, it is extremely difficult to reverse and therefore it is critical an early intervention and prevention. An excess of phosphorus and a deficit of calcium and calcitriol are key factors in the evolution of SH. Despite the fact that plasma phosphorus levels remain normal until an extremely advanced stage of CRF, and even apparent hyperphosphatemia in mild CRF, it has been shown that restricting dietary levels of protein and phosphorus impedes the progression of SH. A decrease of protein in the diet also decreases the amount of calcium, thus the calcium levels must be supplemented in order to prevent their deficit. In addition to that slightly diminished levels of calcitriol can be observed in the early stages of CRF, thus it is logical to provide this hormone. However, administering calcitriol may induce hypercalcemia and hyperphosphatemia, which in turn risks the onset of cardiovascular calcifications and complications. Therefore, the calcitriol dosage should be small and then adjusted according to the degree of SH. Neither the PTH levels nor alterations in the phospho-calcium metabolism follow a linear increase appropriate to the decrease in renal function, therefore we propose a treatment strategy which adapts to the different degrees of renal failure.
INTRODUCTION: Valuation of doxazosin, system formulation modified, in the hypertension in the hemodialysis population. METHOD: Arterial Hypertension (AHT) has been studied in 77 patients (p) subjected to hemodialysis (HD). Mean age (mag) was 61 years (y), range 84y-25y; 66% were males. The underlying etiology was glomerular in 19%, tubulo-interstitial in 18%, congenital in 18%, vascular in 19% and diabetic in 26%. RESULTS: Doxazosin (system formulation modified, single daily dose (4 mg), treatment follow-up was completed in 16 patients subjected to HD for 24 weeks (wk). CONCLUSION: It is concluded that AHT is of great importance in HD, and can be adequately controlled with the new antihypertensive drugs. In this context, doxazosin affords excellent therapeutic control, efficiency and good pharmacological tolerance.
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BACKGROUND: BsmI vitamin D receptor (VDR) gene polymorphism has been associated with the severity of hyperparathyroidism in patients on hemodialysis. The aim of this study was to analyze the influence of this polymorphism on parathyroid function and serum calcitriol levels in patients with different degrees of chronic renal failure (CRF) before dialysis. METHODS: A total of 248 CRF patients, divided into three groups according to creatinine clearance (CCr; mild CRF group> 60 to </=85 ml/min, N = 54; moderate CRF group> 35 to </=60 ml/min, N = 113; severe CRF group> 10 to </=35 ml/min, N = 81), had their serum intact parathyroid hormone (iPTH) and calcitriol levels measured and BsmI genotype frequencies estimated by polymerase chain reaction (PCR) analysis. Diabetics, those on treatment with steroids, vitamin D or derivatives, and phosphorus binding agents were excluded. All those with serum calcium levels of <2.25 mmol/liter or> 2.5 mmol/liter and serum phosphorus levels of> 1.6 mmol/liter or who needed phosphorus binding agents were excluded. The statistical analysis was done with the general factorial analysis of variance entering first PTH and then calcitriol as the dependent variable; the genotype (BB, Bb and bb), sex and CCr group were defined as factors; and covariables included serum calcium, serum phosphorus, 1/creatinine versus time slope, PTH when calcitriol was the dependent variable, and calcitriol when PTH was the dependent variable. RESULTS: When serum PTH levels were entered as the dependent variable, serum calcium, CCr group, and the interaction of genotype with the CCr group were found to be significant factors (P = 0.025, P <0.001 and P = 0.039, respectively). When serum calcitriol levels were entered as the dependent variable, genotype, the interaction of genotype with CCr, the CCr group, and the 1/creatine versus time slope were found to be significant (P = 0.027, P = 0.028, P <0.001 and P = 0.044, respectively). The marginal means of PTH, adjusted with the general factorial analysis of variance across the three groups were: (a) mild CRF group, BB 5.3 pmol/liter (CI 0 to 13.8), Bb 5.5 pmol/liter (CI 2 to 9), bb 5.4 pmol/liter (CI 0.6 to 10.2); (b) moderate CRF group, BB 6.2 pmol/liter (CI 1.5 to 10.9), Bb 7.8 pmol/liter (CI 5.3 to 10.3), bb 7.5 pmol/liter (CI 4.8 to 10.1); (c) severe CRF group, BB 9.3 pmol/liter (CI 4.2 to 14.3), Bb 17.1 pmol/liter (CI 13.9 to 20.2), bb 21.9 pmol/liter (CI 18.7 to 25.2). The marginal means of calcitriol adjusted with the general factorial analysis of variance across the three groups were: (a) mild CRF group, BB 47 pg/ml (CI 37 to 57), Bb 40.9 pg/ml (CI 37 to 44.8), bb 32.6 pg/ml (CI 26.8 to 38. 4); (b) moderate CRF group, BB 24.1 pg/ml (CI 18.3 to 29.8), Bb 26.6 pg/ml (CI 23.5 to 29.7), bb 25.3 pg/ml (CI 22 to 28.6); (c) severe CRF group, BB 27.4 pg/ml (CI 21.3 to 33.5), Bb 19.4 pg/ml (CI 15.5 to 23.2), bb 20.4 pg/ml (CI 16.1 to 24.7). CONCLUSION: The progression of hyperparathyroidism is slower in predialysis patients with BB genotypes than in the other genotypes. Also, calcitriol levels are less reduced in the BB genotype, which may act to lessen the severity of secondary hyperparathyroidism.
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Angiotensin converting enzyme inhibitors (ACEIs) have been shown to be effective in the treatment of dialysis patients with high blood pressure, however, they also have been associated with anaphylactoid reactions at the start of dialysis, when they have been used concomitantly with AN69 membranes. A multicenter, open six-month study was designed to test the tolerability and efficacy of losartan as antihypertensive in patients under hemodialysis (HD), with particular emphasis on the appearance of anaphylactoid reactions. HD patients with systolic blood pressure (SBP) levels > or = 140 and/or diastolic blood pressure (DBP) > or = 90 mm Hg, previously nontreated, treated but uncontrolled, or treated with a poor tolerability, were included. The study performed three controls: baseline, at month 3, and at study completion. DBP and SBP levels were measured on the six HD sessions previous to the three visits in addition to biochemical and hematology measurements. Four hundred and six patients were included. The mean age was 55 years, 42% were women, and 23.6% of the patients were dialyzed with AN69 membranes. There was a significant reduction in pre- and postdialysis SBP and DBP at three and six months. Fifteen patients discontinued the study due to adverse reactions related to losartan, and in seven of them the adverse reaction was hypotension. Only two patients have reported a possible anaphylactoid reaction on treatment with AN69, in one of them the HD session had to be stopped and losartan was discontinued. On the contrary, nine patients with a history of previous anaphylactoid reaction, with ACEIs and AN69, have not shown this complication with losartan and AN69. We conclude that losartan is a well tolerated antihypertensive by HD patients, with a very low incidence of adverse reactions, and a lower prevalence of anaphylactoid reactions than those detected with ACEIs and AN69.
Diabetic patients on dialysis have lower levels of parathyroid hormone (PTH); however, there is no data regarding PTH levels with different degrees of chronic renal failure (CRF). We compared 58 diabetic patients with different degrees of CRF with 268 non-diabetic patients with CRF (serum creatinine >1.2 mg/dl). In both groups, we investigated the main biochemical parameters together with plasma calcium, phosphorus, magnesium, PTH and calcitriol. Diabetic patients showed lower levels of PTH than non-diabetics (P=0.003). The differences were observed in patients with creatinine clearance <70ml/min. We also observed differences in phosphorus, magnesium and tubular resorption of phosphate. In the group of diabetic patients, serum glucose correlated inversely with PTH. Our study suggests that poor control of diabetes (hyperglycaemia) may play a role in the pathogenesis of the hypoparathyroidism observed in patients with diabetes and CRF.
The aim of this study was to find out the relationship between body iron stores and serum aluminum levels among 82 stable CAPD patients. The influence of other factors such as time on CAPD and residual renal function was also considered. Thirty-three patients received aluminum hydroxide as a phosphate binder, and they had significantly higher aluminum levels (36.45 microg/l) than the patients who were not taking aluminum preparations (17.2 microg/l, p = 0.001). A statistically-significant correlation between serum aluminum levels and residual renal function and time on CAPD was also observed (p <0.05). However, there was no relationship between serum aluminum levels and serum iron, ferritin and transferrin saturation, neither between body iron stores and total excretion of aluminum (p >0.05). In previous reports, low serum iron levels were associated with high serum aluminum concentration among hemodialysis patients. However, this effect was not observed in the CAPD population under study. The highest risk of hyperaluminemia was found in the patients who were taking aluminum hydroxide, had worse residual renal function and had been longer on CAPD.
Secondary hyperparathyroidism (HPT) was evaluated in 157 patients with chronic renal failure (CRF). It was noted that HPT developed early in CRF at a time when plasma calcium and phosphorous were within normal limits. As creatinine clearance decreased below 80 mL/m, there was a significant decrease in plasma calcitriol and a slow and progressive significant increment in plasma parathyroid hormone (PTH). The effect of dietary intake of calcium and phosphorous was evaluated in these patients with early renal failure (ERF). They were divided into two groups. Group A was placed on a protein- and phosphorous-restricted diet (10 days) followed by a daily phosphorous-load diet (10 days). Group B had similar sequential diets plus a calcium supplement throughout the study. Dietary protein and phosphorous restriction resulted in an amelioration of the HPT only in the group of patients receiving calcium supplementation. The phosphate-load diet resulted in worsening of HPT in both groups. In summary, a deficit of calcitriol occurs early in CRF, which in turn leads to a significant increase in PTH. Phosphorous restriction, together with calcium supplementation, ameliorated the HPT of patients with ERF.
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The i-PTH response to changes in the peritoneal calcium balance was studied prospectively in a group of 13 stable CAPD patients, who presumably had adynamic bone disease, with low or normal i-PTH values and low aluminum in plasma. Five days after the reduction of dialysate calcium concentration from 1.75 mmol/l to 1 mmol/l, there was a significant elevation in the serum i-PTH. These increased PTH levels returned to baseline values when patients were changed to the 1.75 mmol/l Ca solution (p = 0.004). The changes in i-PTH mirrored the changes in peritoneal calcium balances. These results support the notion that the low or normal levels of i-PTH frequently seen in peritoneal dialysis patients are due to the hypercalcemic effects of the standard peritoneal dialysis solutions; in these patients, the parathyroid hormone production is normal since negative peritoneal balances of calcium are associated with an increase in serum i-PTH.
Renal function impairment and electrolyte disorders in hypothyroidism are frequently subtle and rarely observed in clinical practice. To assess the extent of these defects, serum concentration of electrolytes and glomerular filtration rate were estimated before and after thyroid replacement therapy in 41 patients with primary hypothyroidism. All patients had decreased glomerular filtration rates and 22 patients had increased serum creatinine levels. Although a relationship between creatinine clearance and serum thyrothropin-stimulating hormone was not found, a weak correlation between age and serum creatinine concentration was observed. Hyponatremia was documented in 45% of 22 patients with elevated serum creatinine but in only 21% of 19 patients with normal creatinine. All these defects were corrected by treatment with thyroid hormone. We conclude that creatinine clearance was slightly decreased in all patients with hypothyroidism, this decrease being more noticeable in elderly patients. The greater the impairment in renal function, the more common was the occurrence of hyponatremia.
Secondary hyperparathyroidism (HPT) develops early in chronic renal failure (CRF) at a time when plasma calcitriol levels are normal. At this time, PTH are higher than normal controls and serum phosphorous levels are lower. A decrement in total serum Ca is noted, after an oral phosphate load, only in patients with ERF. These data suggest that factors, other than a decrease in calcitriol synthesis, may be involved in the pathogenesis of HPT. A hypothesis is forwarded suggesting that an alteration in the newly cloned calcium sensor receptor may be the earliest abnormality in the HPT, preceding a decrease in plasma calcitriol levels.