Search

Mitral annulus calcification, a common lesion of the elderly (over age 60 years), has been detected with increased frequency and at younger ages in patients with uraemia. To date a pathogenic role for dialysis and secondary hyperparathyroidism has been suggested only on the basis of older dialytic age and increased serum iPTH observed in the affected individuals. Because this is a potentially dangerous lesion we deemed it useful to evaluate more completely the respective roles of possible pathogenetic factors in uraemic individuals. Evaluation included echocardiography, ECG, limb radiography, and serum assays. A total of 225 dialysis (HD) patients, 67 chronic renal failure (CRF) patients on conservative treatment and 67 normal subjects were studied. Mitral annulus calcification was detected in 87 of 225 (38.6%) HD patients, 11 of 67 (16.4%) CRF and six of 67 (8.9%) normals. In HD, patients with calcification were older and on longer-term renal replacement therapy compared to those without calcification. They also had greater values of iPTH, BGP, AP, and Rx score of secondary hyperparathyroidism. Mitral annulus calcification was associated more frequently (x2= 14.8; P< 0.0001) with rhythm and cardiac conduction defects, but not with ectopic calcifications. Multiple stepwise regression analysis, with mitral annulus calcification score as dependent variable, selected dialysis duration, age, and iPTH (r= 0.368) as the most predictive parameters, with the first two carrying most of the information. The stratification of patients according with these two parameters showed a progressive increase in the frequency of calcification both with HD duration and age. Moreover, compared to those without, patients with calcification in the third, fourth, and fifth decades invariably showed significantly greater dialytic ages, while in the first year of HD they were significantly older. Finally, in all subjects a progressive increase (= 34.4; P< 0.000001) of prevalence of mitral annulus calcification in normals (0%), CRF (8.5%), and HD (36.7%) was observed only in those aged less than 60 years, but not over age 60 (normals=30%; CRF = 35%; HD= 42.3%; = NS). Over age 60, ageing and dialysis do not have additive effects. In conclusion, our data show that dialysis duration plays a major role in the development of mitral annulus calcification mainly in younger patients (under age 60) with the possibility of an increased mortality rate of affected patients. The pathogenetic mechanism seems to differ from that of other ectopic calcification, while secondary hyperparathyroidism seems to play an ancillary role. [ABSTRACT FROM PUBLISHER]

We describe two patients that had a history of recurrent renal stones and chronic renal insufficiency. The first case was a 51-year-old man with an adenine phophoribosyltransferase (APRT) deficiency who was diagnosed only after he had been referred for severe renal failure requiring hemodialysis. This led to a screening of the entire family, which identified six carriers and an additional affected relative (a 41-year-old man and the second case reported herein). Genetic analysis of the APRT gene revealed an atypical mutation previously described only once in a compound heterozygote.

Objective: To determine the type of mutation in a patient with clinical diagnosis of suspected APRT deficiency., Design and Methods: A 51-year-old male patient, with a clinical history of two prior episodes of renal colic with urinary stone excretion (reported as uric acid stones in the first episode and as calcium oxalate stones in the second), was admitted to the hospital with severe non-oliguric renal failure (1.06 mmol/L serum creatinine), severe hyponatremia (114 mmol/L Na(+)), metabolic acidosis (14 mmol/L HCO(3)(-)) and uricemia in the normal range. Abnormalities at renal scan and persistency of severe renal failure required to start haemodialysis. Results of renal biopsy prompted us to undertake a biochemical and molecular biological evaluation of the patient for suspected adenine phosphoribosyltransferase (APRT) deficiency., Results: HPLC analysis of serum and urine, for determining purine derivative profile, showed the pathological presence of adenine in both biological fluids (3.57 micromol/L and 7.11 micromol/mmol creatinine in serum and urine, respectively; not detectable in both fluids in healthy controls). APRT assay in a sample of patient hemolysate showed no detectable activity of the enzyme (25.56+/-9.55 U/L red blood cells in control healthy subjects). Molecular biological analysis of the amplified APRT gene revealed that the patient harboured in exon 3 a homozygous 254 bp deletion-8 bp insertion, previously described only once in a compound heterozygote. Analysis of the patient family showed that heterozygotes for this APRT gene mutation, in spite of a 69% lower APRT enzymatic activity than that of healthy subjects, had no detectable adenine concentrations in both serum and urine., Conclusions: Results of the first patient harbouring the homozygous 254 bp deletion-8 bp insertion of the APRT gene strongly indicated that definitive diagnosis of APRT deficiency (often under or misdiagnosed) would require a combined clinical, biochemical and molecular biological evaluation.

Background: Different parathyroid hormone (PTH) behavior during hemodialysis with different types of dialysis membranes has been reported. The behavior of intact parathyroid hormone (iPTH) adsorption using different dialysis membranes was assessed in 12 dialysis patients with secondary hyperparathyroidism., Methods: The study was performed according to a longitudinal scheme comprising three treatment modalities, each lasting 2 weeks, for 6 weeks altogether. The first treatment consisted of standard bicarbonate dialysis with low-flux polysulfone, followed by acetate-free biofiltration with high-flux-polysulfone or with polyacrylonitrile-AN69. In the first week of each period, dialysis was delivered by using a 1.3 m(2) surface area and subsequently, a 1.8 m(2) surface area. Intact parathyroid hormone was assayed on the blood and dialysate samples to calculate iPTH adsorption., Results: The results showed that polyacrylonitrile-AN69 and high-flux polysulfone induce a significantly larger drop in PTH serum levels as compared with low-flux-polysulfone, particularly in the first half of the dialysis session, while the ionized calcium increase is comparable in all different hemodialysis treatments. The measurement of iPTH in the dialysate showed lower values than those disappearing on the blood side, thus suggesting the presence of an adsorptive mechanism in the different dialysis membranes., Conclusion: High-flux polysulfone is endowed with a comparable adsorptive capacity per surface unit compared to polyacrylonitrile-AN69, although it seems to show a different behavior, as polyacrylonitrile-AN69 saturates early in the first hour of dialysis corresponding to its maximum adsorption power, while high-flux-polysulfone displays a more lasting adsorptive capacity. Thus, iPTH changes during hemodialysis also depend on dialyzer characteristics and the dialysis membrane adsorption.

Treatment with rhGH has been proven to be useful in children with chronic renal insufficiency and stunted growth. The aim of this study was to assess the usefulness of endocrinological provocative testing in predicting results to rhGH treatment. Endocrinological investigations performed in 14 children on renal replacement therapy did not correlate with increment of height velocity in the first year of rhGH therapy. It is concluded that no endocrinological testing is useful before starting rhGH treatment; other predictors of the response to rhGH administration are needed.

Insulin-like growth factor-1 (IGF-1), produced by osteoblasts following parathormone (PTH) stimulation, is a local hormone with autocrine and paracrine functions on bone formation. To evaluate whether circulating IGF-1 is also important in stimulating bone formation, a study was carried out on 28 patients with slowly progressing nondialytic chronic renal failure. 9 patients were treated with 1,25(OH)2D3, while 19 did not receive vitamin D metabolites. In all patients a transiliac bone biopsy for histomorphometric studies was obtained, and the following determinations were made: immunoreactive PTH (iPTH), osteocalcin, alkaline phosphatase, IGF-1, serum calcium, phosphate and creatinine. Serum IGF-1 levels were similar in the two groups of patients, and higher than normal. iPTH and osteocalcin were positively correlated with serum creatinine, osteoblast surface and the eroded surface, but did not correlate with IGF-1. A negative (n.s.) relationship was found between dynamic bone parameters and circulating IGF-1, with the mineral apposition rate reaching a significant level (p less than 0.05). In conclusion, the circulating levels of IGF-1 are not correlated with bone formation parameters, thus apparently showing no role in bone turnover or dependency on bone production of the growth factor. The results may favor the hypothesis of a negative feedback control of circulating IGF-1 by suppressive signals originating from active bone metabolic units.