The spectrum of bone disease in predialysis and dialysis patients has changed during the last decade. The incidence of aplastic bone disease has increased and this can not be attributed to bone aluminum deposition; moreover, low bone cellular activity is present despite a moderate elevation in PTH levels. This study compares PTH levels and types of bone disease in both predialysis and dialysis patients from the same geographical area. We prospectively studied 119 unselected end-stage renal disease patients: 38 were immediately predialysis (PreD), 49 on hemodialysis (HD), and 32 on CAPD. A bone biopsy was performed in all patients. Aplastic bone disease with < 5% bone surface aluminum was a common finding (48%, 32%, and 48%, in PreD, HD, and CAPD, respectively). In all groups, an intact PTH level below 120 pg/ml was highly predictive of low bone turnover. Conversely, a PTH level above 450 pg/ml was always associated with histologic features of hyperparathyroid bone disease. Among the bone histomorphometric parameters, osteoblast surface showed the best correlation with intact PTH in each group, and the slope of the regression line for this correlation was significantly steeper in HD and CAPD than PreD patients. Thus, the range of PTH (95% confidence limit bands) needed to obtain a normal osteoblast surface of 1.5% was greater in preD than in HD and CAPD patients (300 to 500 vs. 75 to 260 pg/ml, respectively). In all groups some degree of marrow fibrosis was observed when PTH levels were greater than 250 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Lack of resolution of hyperparathyroidism after long-term renal transplantation is common. The relative roles of the graft function attained and the degree of pre-transplant hyperparathyroidism have not been established. Intact parathyroid hormone (iPTH) and several clinical parameters were studied before and 68.6+/-26.8 months (range: 30-124) after renal transplantation in 62 patients (20 females/42 males) with good renal function (creatinine <2 mg/dl). iPTH decreased from 214+/-229 pre-transplantation to 116+/-70 pg/ml post-transplantation (P<0.01). However, only 22.6% of patients had PTH concentrations in the normal range, and values greater than twice the upper normal limit were not uncommon (27.4%). Of the many variables analysed, creatinine (r=0.43; P=0.001) and pre-transplant PTH (r=0.31; P=0.02) significantly correlated with post-transplant PTH. After selecting patients with serum creatinine <1.5 mg/dl (n=46), pre-transplant PTH emerged as the more important predictor of post-transplant PTH (r=0.58; P<0.0001). After controlling for creatinine, the partial correlation was r=0.53, P<0.0001. We concluded that spontaneous resolution of hyperparathyroidism after renal transplantation is uncommon. In addition, the magnitude of pre-transplant hyperparathyroidism and the renal function determine the long-term post-transplant parathyroid function.
Dietary intervention, phosphate (P) removal during dialysis and, especially, phosphate binders are current methods for the management of hyperphosphataemia. Ideally, the amount of P absorbed from the diet should equal the amount of P removed during dialysis, and this must occur in the context of an adequate protein intake. We evaluated the relationship between P intake and protein intake in 60 stable chronic uraemic patients (mean age 55+/-15 years, 25% diabetics, 68% males) on standard 4 h haemodialysis. The dietary counselling was relatively free for protein and calories. Nutrient intake was recorded during a 5 day period, and average daily ingestion of P and proteins was calculated using a computerized diet analysis system. A highly significant correlation was observed between protein and P intake. The mean daily ingestion of P and proteins was 998+/-316 mg and 64+/-19 g (1+/-0.4 g/kg/day), respectively. For an optimal protein diet of 1-1.2 g/kg/day, the P intake was 778-1444 mg. The amount of P removed by haemodialysis, extrapolated to an average week, is 250-300 mg/day. Since approximately 40% of P ingested is absorbed from the gut by uraemic patients treated with intestinal P binders, 750 mg of P intake should be the critical value above which a positive balance of P may occur. This value corresponds to a protein intake of 45-50 g per day (>0.8 g/kg body weight/day for a 60 kg patient). In patients undergoing standard chronic haemodialysis, a neutral P balance is difficult to achieve, despite phosphate binder therapy, when protein intake is >50 g. Additional protein restriction, in order to obtain a neutral balance, may impose the risk of protein malnutrition.
Aplastic bone disease (ABD) is a common form of renal osteodystrophy and is characterized by a defect in bone matrix formation and mineralization without an increase in osteoid thickness. The prevalence and pathogenesis of ABD in predialysis patients is largely unknown. We prospectively studied 92 unselected predialysis patients with a creatinine clearance < 10 ml/min/1.73 m2 and a mean age of 45 +/- 2 years (61 M, 31 F). None of the study patients had received any form of vitamin D therapy, and CaCO3 was the primary phosphate binder. Aplastic bone disease was observed in 30 (32%) patients. Stainable bone aluminium surface was < 3% in all ABD patients. Patients with ABD were older (52 +/- 3 versus 42 +/- 2 years; P < 0.01) and had reduced serum intact PTH compared to non-ABD patients (199 +/- 25 versus 561 +/- 87 pg/ml; P < 0.001). Patients with diabetes mellitus showed lower PTH values (179 +/- 31 versus 432 +/- 62 pg/ml; P < 0.001) and a lower incidence of advanced hyperparathyroidism bone lesions (16% versus 46%; P < 0.05) than non-diabetic patients. However, diabetes was not clearly associated with low bone turnover disease (56% in diabetics versus 41% in non-diabetics; P = 0.1). A second bone biopsy was obtained in eleven ABD patients after a period of 16.6 +/- 2.2 months on maintenance dialysis with a dialysate calcium of 7 mg/dl. Bone histology was unchanged in 10 patients, and one evolved to mild hyperparathyroidism. Trabecular bone volume did not change (22.7 +/- 1.7 versus 20.7 +/- 1.7%), and the stainable bone aluminium surface remained < 3%.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal transplant patients immunosuppressed with cyclosporine A (CsA) exhibit both a significant bone loss and an increased rate of bone fractures. An association between common allelic variants of the the vitamin D receptor (VDR) gene and bone mineral density and turnover has been reported in adults. However, the genetic influence on the rate of bone loss after renal transplantation has not been explored. We prospectively determined the changes in spinal mineral density in 34 consecutive nondiabetic adults who received a cadaveric renal allograft. Serum biochemical markers of bone metabolism and the vertebral mineral density (VMD) assessed by quantitative computed tomography were determined at the time of transplantation and three and twelve months later. In fifteen patients the histomorphometric features of iliac bone were analyzed at baseline and twelve months after transplantation. VDR alleles were typed by a PCR assay based on a polymorphic BsmI restriction site. Patients with the so-called "favorable" bb genotype (N = 12) were compared with those with the Bb or BB genotype (N = 22). Baseline VMD was similar in patients with or without the favorable bb genotype. Three months after transplantation the mean (+/- SD) VMD decreased 14 +/- 13.3 percent in all patients (16.5 +/- 13.1% in patients homozygous for the b allele and 13.77 +/- 13.9% in those with Bb or BB genotypes). The rate of VMD loss at this time inversely correlated with pretransplant PTH levels (r = -0.40; P < 0.05). Between 3 and 12 months after transplantation, patients with the favorable bb genotype recovered more VMD than those with Bb or BB types and showed a significantly higher Z score at the end of the follow-up (-0.37 +/- 1.16 vs. -1.10 +/- 1.20, respectively; P < 0.05). The beneficial effect of bb genotype was independent of the prevailing PTH levels and was also observed in those patients with a baseline PTH level < 250 pg/ml (final Z score: bb, -0.42 +/- 1.3, N = 11; Bb/BB, -1.35 +/- 0.8, N = 11, P < 0.05). At the end of follow-up, the histomorphometric studies showed a higher bone formation rate adjusted for PTH levels in patients with the Bb or BB genotype than in those with the favorable bb genotype (0.29 +/- 0.06 vs. 0.21 +/- 0.08 micron3/micron2/day respectively; P < 0.05). In conclusion, high pretransplant PTH levels enhance the early trabecular bone loss after renal transplantation, and functionally different alleles of the vitamin D receptor gene may condition the bone turnover and the degree of recovery of the bone mass.
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