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Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24 months. Patients were classified according to their Kidney Disease: Improving Global Outcomes PTH status at baseline and at 12 months, and mortality evaluated at 12 to 24 months using adjusted Cox analysis. Factors potentially involved in PTH status variability between baseline and 12 months were analyzed. A decrease in serum PTH from normal or high to low values between baseline and 12 months was associated with significantly increased cardiovascular mortality at 12 to 24 months (hazard ratio, 2.03; 95% confidence interval, 1.22-3.36). For patients with high or normal baseline PTH levels, the main independent factor at 6 months for a decrease to low PTH levels at 12 months was high dialysate calcium (1.75 mmol/L), whereas prescription of non-calcium-based phosphate binders was associated with a lower risk of PTH decrease. In the high cardiovascular (CV) mortality risk subgroup of patients who acquired a low PTH status at 12 months, the main independent factor at 12 months associated with significant 12- to 24-month CV mortality was high dialysate calcium (odds ratio, 5.44; 95% CI, 2.52-11.75). Thus, patients with a serum PTH decrease to low values after 1 year of hemodialysis treatment are at high risk of short-term CV death. High dialysate calcium was an important contributor to PTH oversuppression, and continued use was associated with increased CV mortality., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Disturbances in mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and are an important cause of morbidity, decreased quality of life, and extraskeletal calcification that have been associated with increased cardiovascular mortality. These disturbances have traditionally been termed renal osteodystrophy and classified based on bone biopsy. Kidney Disease: Improving Global Outcomes (KDIGO) sponsored a Controversies Conference on Renal Osteodystrophy to (1) develop a clear, clinically relevant, and internationally acceptable definition and classification system, (2) develop a consensus for bone biopsy evaluation and classification, and (3) evaluate laboratory and imaging markers for the clinical assessment of patients with CKD. It is recommended that (1) the term renal osteodystrophy be used exclusively to define alterations in bone morphology associated with CKD, which can be further assessed by histomorphometry, and the results reported based on a unified classification system that includes parameters of turnover, mineralization, and volume, and (2) the term CKD-Mineral and Bone Disorder (CKD-MBD) be used to describe a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD, which is manifested by abnormalities in bone and mineral metabolism and/or extra-skeletal calcification. The international adoption of these recommendations will greatly enhance communication, facilitate clinical decision-making, and promote the evolution of evidence-based clinical practice guidelines worldwide.

Unlabelled: AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: A potential target forN-acetylcysteine treatment in dialysis patients., Background: Oxidative stress largely contributes to hemodialysis-associated lethal complications, thus explaining the urgent need of antioxidant-based therapeutic strategies in hemodialysis patients. We previously identified advanced oxidation protein products (AOPP) in the uremic plasma as exquisite markers of oxidative stress and potent mediators of monocyte activation. The present study was aimed at searching whether (1) AOPP can also trigger activation of polymorphonuclear neutrophils (PMN), and (2) whether AOPP-induced activation could be inhibited by N-acetylcysteine (NAC), a widely used compound which has been shown to prevent oxidative injury to kidney., Methods: Both human serum albumin (HAS) AOPP (i.e., HOCl-modified HSA in vitro preparations and AOPP extracted from plasma of hemodialysis patients) were tested for their capacity to trigger phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase (MPO)-dependent activities as measured by lucigenin- and luminol-amplified chemiluminescence (CL), respectively, as compared to receptor-dependent [opsonized zymosan or receptor-independent phorbol myristate acetate (PMA)]. The effect of PMN priming by platelet-activating factor (PAF), and the effect of NAC on normal monocyte and on normal or hemodialysis patient's (N = 16) PMN oxidative responses were compared., Results: HSA-AOPP triggered in a HOCl dose-dependent manner both NADPH-oxidase- and MPO-dependent CL of PMN. This latter was further enhanced by PAF priming. Plasma-derived AOPP obtained from hemodialysis patients also triggered PMN respiratory burst. NAC significantly reduced HSA-AOPP-mediated responses of normal monocyte and of normal and uremic PMN but had no significant effect on opsonized zymosan- or PMA-induced CL responses., Conclusion: This dual potential of NAC to inhibit phagocyte oxidative responses induced by HSA-AOPP without affecting those mediated by compounds mimicking pathogens supports the proposal of a therapeutic trial with NAC aimed at reducing oxidative stress-related inflammation in hemodialysis patients.

Aim: Recently, it has been hypothesized that salt intake may be related to the risk of osteoporosis. The aim of this review was to summarize the evidence for such relationship and to discuss possible mechanisms., Data Synthesis: We performed a review of the scientific literature on osteoporosis, particularly its etiology, and then focussed on studies addressing the relation between salt intake on the one hand, and calcium balance, bone resorption, bone mineral density and fractures on the other. Although a relation between high salt intake and increased bone loss is biologically plausible, the most pertinent studies relating salt intake to bone mineral density are only suggestive of high salt consumption as a risk factor for osteoporosis. Unfortunately, studies on fracture risk and salt intake are lacking., Conclusion: The relationship between salt intake and osteoporosis is still controversial. A possible relation between salt intake and fracture risk should be addressed in future studies.

Unlabelled: Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy., Background: Folic acid supplementation is only partially efficacious in correcting moderate elevation of plasma total homocysteine (tHcy) concentrations observed in hemodialysis (HD) patients. Experimental and clinical data have suggested that this partial efficacy may be due to impairment of folic acid metabolism to 5-methyltetrahydrofolate (MTHF) and of MTHF transmembrane transport as well. To bypass these difficulties, we assessed the efficacy of intravenous (i.v.) folinic acid, a ready precursor of MTHF, on reducing plasma tHcy concentrations in HD patients., Methods: In a cohort of 37 patients on intermittent HD treatment, plasma tHcy concentrations were determined before and during i.v. supplementation of folinic acid (50 mg once per week), together with i.v. pyridoxine (250 mg 3 times per week), to prevent vitamin deficiency, particularly in those treated by recombinant erythropoietin., Results: Folinic acid and pyridoxine i.v. supplementation was given for 11.2 +/- 2.45 months (range 7.5 to 17 months). The mean plasma tHcy levels decreased significantly from 37. 3 +/- 5.8 microM at baseline to 12.3 +/- 5.4 microM on folinic acid treatment (P < 0.001). Moreover, 29 of the 37 patients (78%) had normal plasma tHcy levels at the end of follow-up (that is, <14.1 microM, mean 9.8 microM, range 6.2 to 13 microM). No adverse effects attributable to folinic acid treatment were observed during this time., Conclusions: Intravenous folinic acid therapy (50 mg) once per week associated with pyridoxine supplementation appears to be an effective and safe strategy to normalize plasma tHcy levels in the majority of chronic HD patients.

Oxidized low-density lipoproteins (oxLDL) play a crucial role in atherogenesis mainly via their capacity to bind and to activate macrophages. However, the role of the protein LDL moiety in this process is not yet established. In this study, human LDL were exposed to hypochlorous acid (HOCl), a selective protein oxidant, or copper sulfate (CuSO(4)), a major lipid oxidant, and tested for their capacity to activate the NADPH-oxidase of human THP-1- and U937-derived macrophages as measured by lucigenin chemiluminescence (CL). Compared to native LDL which had no effect, HOCl-oxLDL triggered potent CL responses in both U937 and THP-1 cells but only when these were fully differentiated into macrophages by phorbol myristate acetate. In contrast, Cu-oxLDL only triggered a moderate CL response of U937 cells and had little effect on THP-1 cells. While delipidation did not affect HOCl-oxLDL-induced CL response it abolished that induced by Cu-oxLDL. Interestingly, U937 cells showed higher CL responses to both types of oxLDL than THP-1 cells, a finding which could be related to their higher expression of the scavenger receptor CD36. Taken together these results strongly support the role of the protein moiety in oxLDL-induced macrophage activation., (Copyright 1999 Academic Press.)

Hypocalcemia, hyperphosphatemia, and resistance to the action of PTH are well characterized features in the setting of advanced chronic renal failure (CRF). Although the underlying mechanisms are ill-understood, clinical and experimental evidence points to both PTH receptor down-regulation and post-receptor abnormalities in their pathogenesis. In the present study we have examined the effect of advanced CRF in rats on the renal expression of PTH/PTHrP receptor (PTH-R). CRF was created by a standard two-step operation (5/6 nephrectomy). Four weeks thereafter, 19 uremic rats were compared with 23 sham-operated rats. Uremic rats had higher mean (+/- SD) plasma creatinine levels than control rats, 164 +/- 107 microM versus 43 +/- 5 microM, respectively. They also had higher plasma phosphorus and iPTH levels, 4.70 +/- 1.71 mM versus 2.59 +/- 0.37 mM and 561 +/- 336 versus 27 +/- 18 pg/ml, respectively. Mean plasma total calcium and blood ionized calcium were significantly lower in uremic than in control rats, 2.13 +/- 0.06 mM versus 2.61 +/- 0.10 mM and 1.07 +/- 0.11 versus 1.31 +/- 0.06 mM, respectively. Mean plasma calcitriol concentration was also significantly lower in uremic than in control rats, 39.8 +/- 14.6 and 80.4 +/- 15.2 pg/ml, respectively. Nine out of the 19 rats were examined for renal PTH-R gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Uronic-acid-rich protein (UAP) is a new urinary macromolecule which strongly inhibits calcium oxalate crystal formation. It is a glycoprotein with a molecular weight of about 35,000 Da, and its carbohydrate content is 8.5%. This inhibitor is composed of two polypeptidic chains crosslinked by chondroitin sulfate. It exhibits partial structural homology with alpha 1-microglobulin. The inhibitory activity seems to be supported by peptidic chains as determined by enzymatic assay.

Epidemiologic findings continue to add to the body of evidence supporting a relationship between calcium intake and blood pressure. These findings also indicate that there is a threshold of the potential protective effect of adequate calcium intake, below which the risk of hypertension increases at a greater rate. The set point of this threshold, estimated at 700-800 mg/d, may be modified by a variety of factors including dietary patterns and components, lifestyle, and genetics. This may explain, at least in part, the heterogeneous response observed in dietary-intervention studies. In animal models of hypertension it was shown that greater amounts of calcium must be given to cause a blood pressure change comparable with that in normal animals, suggesting that in high-risk human populations in which calcium metabolism may be disordered, calcium intake may have to be increased to amounts greater than 700-800 mg/d to demonstrate the blood-pressure-lowering effect. Calcium intake at or above the currently recommended daily allowance of 800 mg could be of potential benefit to certain racial groups, individuals ingesting excessive alcohol, and pregnant women, all of whom generally consume low amounts of calcium and who are at higher risk of developing hypertension.

Arterial hypertension in the spontaneously hypertensive rat (SHR) is associated with an abnormal Ca2+ homeostasis, compared with its normotensive control, the Wistar Kyoto rat (WKY). In particular, epithelial Ca2+ transport is perturbed, with intestinal absorption and renal tubular reabsorption being decreased in the adolescent and adult SHR. In the present study we examined Ca2+ uptake into isolated duodenal brush-border membrane vesicles (BBMV) in 12-14 week-old male rats. This uptake can be separated in a nonsaturable and a saturable component. The latter follows Michaelis-Menten kinetics. Vmax of this component was found to be significantly higher (p less than 0.05) in SHR than in WKY (0.58 +/- 0.19 versus 0.35 +/- 0.06 nmol/mg protein x 10 sec, mean +/- SD) whereas Km did not differ. Thus, the defect in the intestinal Ca2+ absorption previously identified in the SHR of this age is not due to a decrease in Ca uptake at the level of the duodenal brush-border membrane, but is most likely located in the baso-lateral membrane.

Intestinal calcium transport, renal tubular calcium reabsorption, and plasma 1.25 (OH)2 vitamin D3 (calcitriol) levels have all been reported to be diminished in the spontaneously hypertensive rat (SHR) compared with its genetic control the Wistar Kyoto rat (WKY). In the present study, absorptive duodenal and renal tubular epithelia of 12- to 14-week-old male SHR and WKY were examined by electron microscopy to determine whether such disturbances could be related to structural abnormalities. Patchy loss of microvilli in both duodenal and proximal tubular epithelia was observed in the SHR, whereas brush border membrane was entirely normal in the WKY. Irregular spaces were observed between the basal aspects of SHR intestinal epithelial cells and their basement membrane. In addition, the average height of duodenal and renal microvilli was reduced in the SHR. Two specific markers of the brush border membrane, alkaline phosphatase and villin, as well as the cytoplasmic vitamin-D dependent calcium-binding proteins, CaBP9K and CaBP28K were determined. Duodenal alkaline phosphatase activity was reduced in the SHR, compared with the WKY: 0.145 +/- 0.002 vs. 0.186 +/- 0.002 IE/min.microns 3 x 10(3) brush border, mean +/- SEM, N = 10 pairs, P less than 0.001. However, duodenal villin expression was not different from that of the WKY. Duodenal CaBP9K and renal CaBP28K content was diminished in the SHR: 21.0 +/- 0.80 vs. 29.9 +/- 2.19 micrograms/mg protein, N = 6 pairs, P less than 0.01 for duodenum, and 4.47 +/- 0.39 vs. 7.67 +/- 0.54 micrograms/mg protein, N = 6 pairs, P less than 0.001 for kidney. These data showing structural and functional abnormalities of intestinal and kidney cells in the SHR appear to reflect a disorder of transporting epithelia which may be either intrinsic or related to reduced circulating calcitriol.

The value of radionuclide bone scanning in the diagnosis of renal osteodystrophy is still debated. In order to re-examine this issue, 25 uremic patients treated by intermittent hemodialysis underwent 99m-Technetium Methylene Diphosphonate (99mTc-MDP) bone scan. They were subdivided into three groups according to quantitative bone histology. Group 1 (N = 8) had pure dialysis osteomalacia, group 2 (N = 7) mixed lesions, and group 3 (N = 10) pure osteitis fibrosa. The scintigraphic studies were interpreted by means of a five point semi-quantitative scale. Using this quantification, all but one group 1 patients had decreased bone tracer uptake, and all patients of group 3 had an increased uptake (chi square test of Yates, P less than 0.001). Among patients of group 2, bone uptake was decreased in the three patients with clearly reduced mineralization front and moderate osteitis fibrosa, but it was increased in all patients with severe osteitis fibrosa and subnormal mineralization front. A quantitative analysis of regional tracer uptake into bone was performed in two patients: one of group 2 and one of group 3. The results obtained clearly corroborated the semi-quantitative findings. Thus, in hemodialysis patients with symptomatic bone disease, the 99mTc-MDP bone scan provides useful information for the differential diagnosis between dialysis-related osteomalacia and secondary hyperparathyroidism. In patients with mixed lesions, the importance of bone tracer uptake appears to depend on the extent of the mineralization front and on the intensity of osteitis fibrosa.

Severe aluminium-induced osteomalacia is refractory to treatment with 1,25(OH)2D3 which frequently causes hypercalcemia. To further explore the mechanisms involved, we have utilized a model of short-term aluminium intoxication in the rat (total: 11 mg elemental aluminium in 3 weeks) to study (a) 1,25(OH)2D3 receptor status in a variety of classical and non-classical target organs for 1,25(OH)2D3; (b) circulating 1,25(OH)2D3 levels; (c) baseline duodenal calcium transport, utilising the Ussing chamber, to investigate the functional significance of receptor status in a classical target organ; and (d) duodenal calcium transport response to exogenously administered 1,25(OH)2D3. Both in the three week model and in the 16 week model (total: 41 mg elemental calcium) increased maximal specific binding capacity for 1,25(OH)2D3 (Nmax), that is, number of unoccupied receptors, was observed in nuclear fractions of all tissues studied. Receptor affinity, the apparent dissociation constant KD, was unchanged. Total binding capacity, measured after displacement of endogenous ligand by Mersalyl, that is, the sum of occupied plus non-occupied receptors, was also increased. Both circulating 1,25(OH)2D3, mucosa-to-serosa calcium flux (Jms) and net calcium flux (Jnet) were reduced under baseline conditions, suggesting the lack of a direct relationship between receptor expression and endorgan response. Following exogenous 1,25(OH)2D3 administration, calcium Jms and Jnet were significantly lower in the aluminium intoxicated animals, with the increment induced in Jnet in aluminium intoxicated animals being 63% of that induced in controls. Our data suggest that resistance to the action of 1,25(OH)2D3 in aluminium intoxication is postreceptor in nature.

Parathyroidectomy (PTx) is indicated in hemodialysis (HD) patients who have severe osteitis fibrosa unresponsive to vitamin D therapy or in whom the latter treatment is contraindicated. Immediately after PTx, plasma immunoreactive parathyroid hormone, calcium and phosphorus concentrations decline abruptly. However, little is known in such patients about the short-term effects of PTx on plasma alkaline phosphatase (AP) activity and plasma aluminum (Al) levels. The present, preliminary study was performed to determine such parameters in 37 HD patients, and to correlate them with data of bone histology. Mean plasma AP activity started to increase after PTx from day 4 onwards. Thus, AP values significantly higher than pre-PTx values were observed at day 7 and 14 (415 +/- 54 vs. 619 +/- 77 and 749 +/- 83 IU/liter, means +/- SEM; N = 37; P less than 0.05 and 0.001, respectively). This increase, in the absence of changes in liver function, was mainly due to the bone-specific iso-AP. Moreover, the degree of increase in plasma AP activity was higher in the subgroup with negative (group I, 21 patients) than in that with positive bone Al staining (group II, 16 patients). However, plasma osteocalcin (BGP) did not change after PTx (N = 8). Basal plasma Al levels were significantly higher in group II both before and two weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of parathyroidectomy on left-ventricular function was evaluated in chronic-haemodialysis patients with advanced hyperparathyroidism. Radionuclide angiocardiography (22 patients) and ultrasound echography (8 patients) revealed a significant increase in left-ventricular ejection fraction 1--2 weeks after parathyroidectomy. This improvement was associated with an augmented cardiac index (radionuclide method) and with an increase in mean velocity of circumferential myocardial fibre shortening (echocardiography). Circulating blood volume and erythrocyte space, as well as arterial blood-pressure, had changed little after parathyroidectomy, whereas plasma calcium, phosphate, and immunoreactive parathyroid hormone were significantly lower after surgery. Thus, correction of severe hyperparathyroidism led to a significant improvement in cardiac performance.

Using a discriminating gradient separation technique combined with careful analysis of lipid and apolipoprotein (apo) composition, serum lipoproteins of 20 chronically uremic patients have been compared with those of 19 normal controls matched for age and sex. In uremic subjects, serum VLDL concentration was markedly increased. These particles were enriched in protein and cholesterol and relatively poor in triglycerides (TG). They contained more frequently apo B-48, and a decreased proportion of apo E. Expressed in percent, total apo C was normal but the ratio of apo C-III2/apo C-III1 was elevated. Uremic IDL, whose serum concentration was markedly increased, were characterized by an increased proportion of protein. Total uremic LDL whose serum concentration was normal, contained less esterified cholesterol (EC) and more TG than normal LDL, their EC/TG ratio being very low. Moreover, the concentration of the mature subfraction of LDL having a mean density of 1.043 g/ml, was markedly decreased in uremic subjects. Taken together, these anomalies indicate a delayed transformation of VLDL into LDL in chronic renal failure. The decreased concentration of total HDL in uremic subjects was more marked in HDL2 (-46%) than HDL3 (-24%). Both uremic HDL2 and HDL3 were relatively enriched in TG, and uremic HDL3 were poorer in EC than normal HDL3.(ABSTRACT TRUNCATED AT 250 WORDS)

51 chronic haemodialysis patients with hypertriglyceridaemia were given a daily oral dose of 2.4 g D,L-carnitine for 30 days to investigate a possible hypolipaemic effect. After 30 days' D,L-carnitine treatment the mean (+/- SEM) serum triglyceride concentration had decreased significantly from 3.50 +/- 0.39 to 2.87 +/- 0.27 mmol/l. Serum total cholesterol did not change. However, HDL cholesterol increased significantly from 0.89 +/- 0.05 to 1.35 +/- 0.07 mmol/l. This decrease in serum triglycerides and return of HDL cholesterol to normal levels in haemodialysis patients may be the result of correction of carnitine deficiency. Such treatment could reduce the risk factors for atherosclerosis and coronary-artery disease in uraemic patients.

The influence of a dialysate calcium concentration of 8.0 mg/100 ml (treatment period 2) vs. 7.0 mg/100 ml (treatment period 1) on plasma calcium, phosphorus, serum immunoreactive parathyroid hormone (iPTH), bone histology, intestinal calcium absorption, and calcium transfer across the dialysis membrane was investigated in six patients with renal osteodystrophy undergoing intermittent hemodialysis. During the periods 1 and 2, the plasma calcium changes before and after dialysis were not significantly different. A significant increase in mean postdialysis plasma calcium level was observed during both periods when compared to mean predialysis level. A significant, inverse relation was found between predialysis plasma calcium and the increase in plasma calcium during hemodialysis runs. Calcium transfer across the dialysis membrane and fractional intestinal absorption of calcium in the postdialysis state were determined in four out of the six patients. During period 2, calcium transfer was higher in all four patients but intestinal calcium absorption was moderately higher only in one and strikingly lower in the remaining three patients when compared to period 1. Although brought up to 8.0 mg/100 ml, this higher dialysate calcium significantly decreased the level of serum iPTH only in one out of the six patients; in this patient, osteoclast count, active resorption surface, and periosteocytic osteolysis decreased. In a second patient, although the level of serum iPTH seemed to decrease markedly osteoclastic and osteocytic resorption did not change. In the remaining four patients, the level of serum iPTH was unchanged and bone resorption parameters were found unchanged or aggravated. It is concluded that providing additional calcium (using a dialysate calcium concentration of 8.0 mg/100 ml), the goal of which was to decrease secondary hyperparathyroidism, proved to be successful only in one patient and failed to do so in the five others. Secondary hyperparathyroidism was even found aggravated in three of them. Thus, the use of a dialysate calcium concentration of 8.0 mg/100 ml did not result in any advantage over that of 7.0 mg/100 ml in five out of six patients studied.

It has been suggested that in uremic bone, aluminum interferes with normal mineralization. Aluminum content and aluminum localization were studied in iliac crest biopsies of two groups of patients on regular hemodialysis; one group had histologic osteomalacia, and little or no bone resorption (group 1); the other, osteitis fibrosa and no mineralization defect (group 2). Group 1 patients had significantly higher plasma aluminum concentrations than those of group 2. No difference was found in bone aluminum content, which was above normal in both groups. In the bone samples of the osteomalacic subjects, aluminum was mainly localized at the limit between osteoid and calcified tissue, the site where the bone mineral is normally first deposited. Osteomalacia could not be related to hypocalcemia or to phosphate depletion. Active vitamin D derivatives (25-hydroxycholecalciferol and 1alpha-hydroxycholecalciferol) failed to prevent or to improve the bone disease. In the bone samples of group 2 subjects, aluminum could not be localized by the methods used, except in the two cases with greatly elevated bone aluminum, where it was mainly localized on cement lines. In group 2 subjects, immunoreactive parathyroid hormone plasma concentration, osteoclast surface, and marrow fibrosis were significantly higher than they were in group 1 subjects. It is concluded that in bone from uremic patients on regular dialysis, aluminum can induce a particular form of osteomalacia, resistant to the vitamin D active derivatives. The bone disease is only observed in the absence of severe secondary hyperparathyroidism. This suggests that parathyroid hormone may be involved in the development of the aluminum-induced mineralization defect.

In this study, we have investigated plasma pyridoxal 5'-phosphate (PLP) concentrations in undialyzed and dialyzed uremic patients and in kidney transplant subjects, using an enzymatic technique with thermal deproteinization to liberate PLP from plasma proteins. The specificity of the reaction indicates no interference with pyridoxal and only 3% interference with pyridoxamine phosphate. In 17 hemodialyzed patients, a deficiency of about 50% of plasma PLP concentration is found as compared to 25 healthy subjects (22.2 +/- 2.47 vs. 48.8 +/- 3.00 nmol . l-1), as mean +/- SEM). In seven undialyzed uremic patients with end-stage renal failure, the plasma PLP concentration is also decreased (29.3 +/- 1.74 nmol . l-1). The absence of PLP in plasma ultrafiltrates demonstrates that no loss of PLP occurs due to hemodialysis. The daily oral supplementation with 250-750 mg pyridoxal induces a supraphysiological increase in plasma PLP concentration in hemodialyzed as well as in undialyzed patients. In 116 non-uremic kidney transplant subjects, the mean plasma PLP concentration was 33.8 +/- 3.50 nmol . l-1). In 65% of these patients, a marked deficit (below 20 nmol . l-1) was observed. In conclusion, uremic patients have a deficient vitamin B6 state. Its correction with pyridoxal to restore physiological plasma PLP concentration necessitates oral supplementation with lower doses that those widely used at present. In kidney transplant patients a similar plasma PLP deficiency is observed in the absence of chronic renal failure.