Renal Volume in ADPKD Patient Evaluation.

The clinical manifestations of ADPKD are related to the growth of renal cysts. Renal volume has been recognised as the biomarker that is able to identify those patients at risk of complications (hypertension and haematuria) and at risk of progression to End Stage Renal Disease (ESRD). Recently, several scores have been introduced to predict the evolution of ADPKD. The Mayo Clinic Group developed a classification based on renal volume as measured by CT or MRI and corrected for age and height (Ht-TKV); this allowed predicting the evolution of the disease, but it has not been fully validated so far. In addition, it is used to identify patients labelled as "fast progressors" and eligible for Tolvaptan therapy according to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) recommendations. We studied 80 patients who underwent MRI and had been classified as ADPKD typical form (class 1A-1E). A significant correlation between renal volume, hypertension, and low GFR was found (p < 0.005). A progressive increase in disease severity has been found across the different Mayo classes; 41.2% were eligible for Tolvaptan therapy. The results demonstrate that the Mayo method is easy to perform and provides valid information in order to identify with rapidly progressing disease.

Changes in bone turnover after parathyroidectomy in dialysis patients: role of calcitriol administration.

BACKGROUND: Available data on changes in serum levels of bone markers after parathyroidectomy (PTx) in dialysis patients are not uniform. Changes are thought to be due to either a reduction in PTH activity per se or to a direct effect of vitamin D therapy on bone cells. We aimed to verify whether treatment with vitamin D modifies serum levels of markers of bone synthesis (alkaline phosphatase (AP), osteocalcin (BGP), procollagen type I C-terminal peptide (PICP)) and resorption (collagen type I C-terminal peptide (ICTP)) within a period of 15 days in haemodialysis patients with severe secondary hyperparathyroidism following PTx. METHODS: We randomized two groups (A, treatment and B, placebo, 10 patients each) with comparable basal PTH values and measured bone markers 3, 7 and 15 days after surgery. All patients were treated with calcium supplements (i.v. and p.o.), and group A also received calcitriol (2.4+/-1.0 microg/day, p.o.). RESULTS: In both groups, PTx induced significant changes in all the markers evaluated, except for BGP in group B. Compared to basal values, ICTP decreased from 481+/-152 ng/ml in group A and 277+/-126 ng/ml in group B to 267+/-94 and 185+/-71 ng/ml (M+/-SD) respectively, and PICP increased from 307+/-139 ng/ml in group A and 309+/-200 ng/ml in group B to 1129+/-725 and 1231+/-1267 ng/ml (M+/-SD) respectively, within 3 days of surgery. AP values increased after 15 days from 1115+/-734 mU/ml in group A and 1419+/-1225 mU/ml in group B to 1917+/-1225 and 1867+/-1295 mU/ml (M+/-SD) respectively. On the contrary, mean values of BGP were never different from basal levels after PTx in either group. In the two groups, the pattern of changes of all the bone markers after PTx was almost identical. Group A patients predictably required lower doses of oral calcium supplements to correct hypocalcaemia (16. 9+/-5.7 vs 22.1+/-5.0 g/10 days; M+/-SD, P<0.04). CONCLUSIONS: The opposite behaviour of serum PICP and ICTP after PTx, in both the treated and untreated groups suggests that quantitative uncoupling between bone synthesis and resorption is responsible for hypocalcaemia. This phenomenon, as reflected by the evaluated bone markers, is unaffected by calcitriol. Based on our data we conclude that immediately after parathyroid surgery, vitamin D therapy does not influence bone cell activity, but improves hypocalcaemia mainly through its known effect on intestinal calcium absorption.

Renal bone disease in 76 patients with varying degrees of predialysis chronic renal failure: a cross-sectional study.

BACKGROUND: Renal osteodystrophy has been studied less extensively in predialysis than in dialysis patients. Different types or histological patterns in their natural evolution from moderate to advanced severity of renal insufficiency are only partially known, with special regard to adynamic bone disease and its relationship with osteomalacia. METHODS: We conducted a cross-sectional retrospective study on 76 unselected patients with chronic renal failure undergoing conservative treatment, with a wide range of severity of renal insufficiency. All the patients were subjected to bone biopsy for histological and histomorphometric evaluation. The patients, 44 males and 32 females ranging in age from 18 to 72 years and with serum creatinine 1.2-11.4 mg/dl, had not been exposed to aluminium-containing drugs and had never been treated with vitamin D or calcitriol. RESULTS: Ten patients had normal bone, nine were diagnosed with adynamic bone disease, 26 with mild mixed osteodystrophy, seven with predominant osteomalacia, 22 with advance mixed osteodystrophy, and two with predominant hyperparathyroidism. Patients with adynamic bone disease had less severe chronic renal failure than the other pathological subgroups, intact PTH above the upper limit of normal, normocalcaemia, and reduced serum osteocalcin in line with a significantly lower ObS/BS. Osteomalacia was found in a more advanced stage of chronic renal failure with relative hypocalcaemia and more severe metabolic acidosis. A creatinine clearance of 20 ml/min served as a clear demarcation between this histological group and adynamic bone disease. CONCLUSIONS: It is postulated that adynamic bone disease is a form of renal osteodystrophy, separate from osteomalacia, appearing when bone resistance to PTH develops, probably a transient stage to more hyperparathyroid histological classes with increasing severity of chronic renal failure.

Diagnostic value of serum peptides of collagen synthesis and degradation in dialysis renal osteodystrophy.

The assay of serum peptides of bone collagen formation and degradation could potentially provide an indirect estimate of the rate of bone turnover. In our study we have measured serum levels of the carboxy-terminal propeptide of type I procollagen (PICP) as a marker of bone formation and serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption in 53 patients (47.7 +/- 10 years, M +/- SD) on haemodialysis (for 9.5 +/- 3.8 years) and affected by renal osteodystrophy. Besides PICP and ICTP, patients were also sampled for serum intact and C-terminal PTH, osteocalcin (BGP) and alkaline phosphatase (AP). A transiliac bone biopsy for histomorphometry was also performed in all. As expected both PTH assays, BGP and AP, were correlated reciprocally and to histomorphometric parameters. As for serum levels of PICP, they were on average increased (268.5 +/- 104.9 ng/ml, M +/- SD) compared to normals (range 66-176), but not correlated to classical humoral markers of hyperparathyroidism (PTH and AP), with the exception of BGP (with a rather low r value: 0.365, P < 0.01), nor to histomorphometric indices of bone resorption and formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic acidosis and osteodystrophic bone disease in predialysis chronic renal failure: effect of calcitriol treatment.

The role of metabolic acidosis on osteodystrophic bone lesions of chronic renal failure has been studied retrospectively in 24 patients, divided into two equal groups of 12, one with normal acid-base equilibrium (group A) and one with metabolic acidosis (group B). The two groups were found to differ significantly in serum levels of BGP (23.7 +/- 18 vs. 42.3 +/- 24 ng/ml, p < 0.02) and in several bone histomorphometric parameters such as osteoid volume (4.5 +/- 3.4 vs. 10.2 +/- 6.6%, p < 0.01), osteoid surface (27.7 +/- 18 vs. 48.4 +/- 19%, p < 0.01), single-labelled surface (7.94 +/- 2.9 vs. 15.8 +/- 9.9%, p < 0.02), mineralizing surface (60.69 +/- 26 vs. 30.89 +/- 15.8%, p < 0.003) and mineralization lag time (56.5 +/- 54 vs. 170.5 +/- 189 days, p < 0.05), with the acidotic group showing excess osteoid and a defect in mineralization. Osteomalacia was found only in the acidotic group, while the only 2 cases of adynamic bone disease (ABD) were in the nonacidotic group. Calcitriol administration, 0.25 micrograms daily for a period of 1 year, in 5 cases in group A and 6 cases in group B induced significant improvement of bone lesions mainly in group A. Two of these patients following treatment acquired the characteristics of ABD. In group B, the response to treatment was very limited, with 5 patients still showing persistence of the histological mixed type of bone disease. In conclusion, metabolic acidosis is accompanied by osteomalacia, pure or mixed variety, and shows a relative resistance to calcitriol administration. Normal acid-base equilibrium is more frequently associated with mild hyperparathyroidism and ABD, spontaneously or as a consequence of calcitriol administration.

Procollagen type 1 C-terminal extension peptide serum levels following parathyroidectomy in hyperparathyroid patients.

Procollagen type 1 is mainly synthesized by osteoblasts and, after cleavage of the N- and C-terminal extension peptides, is utilized for collagen fibril deposition in the osteoid tissue. Serum levels of C-terminal extension peptide (Pcoll-1-C) of the procollagen molecule has been considered a useful marker for the evaluation of the rate of osteoblastic procollagen synthesis. To appraise whether in vivo parathyroid hormone (PTH) plays a suppressive role in the synthesis of procollagen type 1, a study has been carried out in 16 patients, 10 with severe secondary hyperparathyroidism of chronic renal failure and 6 with primary hyperparathyroidism. Following parathyroidectomy (PTX), in chronic renal failure patients a 94% fall in serum intact iPTH and a decline of serum calcium to hypocalcemic levels requiring calcitriol administration were observed. Serum Pcoll-1-C increased markedly with a peak after 7 days and a subsequent decline. Similar changes were observed for alkaline phosphatase and osteocalcin. In primary hyperparathyroidism, PTX was followed by an 88% drop in iPTH and mild hypocalcemia not requiring calcitriol administration. Also in this group serum Pcoll-1-C increased significantly with the same time course, unaccompanied by changes in alkaline phosphatase and osteocalcin. In 4 unsuccessfully neck-operated control patients no change in serum Pcoll-1-C levels was recorded during a period of 2 weeks postoperatively. In conclusion, acute withholding of parathyroid hypersecretion is accompanied by an abrupt and transitory increase of serum Pcoll-1-C, not dependent on calcitriol administration. Hypocalcemia following PTX may in part be due to uncoupling of bone formation and resorption.