Correlations between bone histopathology and serum biochemistry in uremic patients on chronic hemodialysis.

To define which noninvasive investigations are of value in predicting bone histology, we analyzed transiliac bone specimens (66 biopsies, 14 autopsies) from 80 uremic patients on chronic dialysis. Results were compared with values of different measurements of parathyroid hormone (PTH), alkaline phosphatase (APH), osteocalcin, calcitonin, baseline and post-deferroxamine (DFO) aluminium (Al),--beta 2 microglobulin, ferritin and bone mineral density. Among histomorphometric parameters, woven osteoid, active osteoblastic surface and resorption surface showed the best correlations with dynamic and biochemical marks of active bone metabolism. Among biochemical parameters, intact PTH and APH were better related to histomorphometric and dynamic bone parameters than other PTH measurements as well as osteocalcin, while calcitonin was related to no parameters. Stainable Al alone, and not total bone Al content was related to bone histology. Baseline Al was related to lamellar osteoid, while post-DFO Al was related to stainable Al. beta 2 microglobulin was positively related to active osteoid surface and ferritin was inversely related to the mineral apposition rate, while bone mineral density was related only to total bone volume. We conclude that, though definite diagnosis requires the use of histological methods, few simple biochemical parameters may offer insight to the bone metabolic status, useful to the physician in day to day clinical practice.

Recurrent secondary hyperparathyroidism due to parathyroid carcinoma: usefulness of Ki-67 immunostaining in the diagnosis of a malignant parathyroid tumor.

Parathyroid carcinoma is a very rare disease occurring in less than 2-3% of all the cases showing clinical features of primary hyperparathyroidism. Several histological markers have been used for distinguishing between benign and malignant tumors of the parathyroid glands. However, most of these markers are not easily applicable and clinical prognosis cannot be predicted by histopathological criteria alone. A recent study has drawn attention to the role of the cell cycle associated antigen Ki-67 detected by MIB-1 monoclonal immunocytochemistry in parathyroid tumors: in fact, Ki-67 seems to be a valuable marker of malignancy in such tumors since it permits an easy detection of proliferating and dividing cells. Here we report in detail a case of severe recurrent hyperparathyroidism in a 51-year-old female patient undergoing regular hemodialysis treatment. In the surgical specimens of the parathyroid glands, the tumor proliferative fraction of 56, expressed as the number of Ki-67-positive nuclei per thousand cells, and the mean mitosis count of 0.5, expressed as the percentage of the total amount of Ki-67 positive nuclei, support the diagnosis of parathyroid carcinoma despite the scanty amount of microscopical signs considered characteristic of malignancy, i.e. extensive thick fibrous bands or prominent nucleoli. To our knowledge this paper is the first clinical report that supports the diagnostic role of the cell cycle associated antigen Ki-67 in parathyroid carcinoma in a case of secondary hyperparathyroidism in a patient undergoing hemodialysis.

Bony content of oxalate in patients with primary hyperoxaluria or oxalosis-unrelated renal failure.

Oxalate retention occurs in end-stage renal failure. Regular dialysis treatment does not prevent progressive accumulation of oxalate in cases of ESRF due to primary hyperoxaluria (PH), whereas such accumulation seldom seems to occur in oxalosis-unrelated ESRF. To elucidate this issue we have measured the bony content of oxalate on biopsies of the iliac crest taken from 32 uremic patients, 7 of them with ESRF associated with PH1 (6 cases) or PH2 (1 case). Ten subjects with normal renal function and no evidence of metabolic bone disease were taken as controls. Only trace amounts levels of oxalate were detected in normal subjects and oxalate to phosphate ratio was below 3:10,000. Non-PH dialyzed patients exhibited fivefold increases in oxalate levels, which rose to 5.1 +/- 3.6 mumol/g bony tissue. Calcium oxalate was estimated to represent 0.18% of the hydroxyapatite content of bone. Oxalate amounts were neither related to pre-dialysis plasma levels of oxalate, nor with duration of dialysis treatment, suggesting that accumulation was not progressive disorder. Oxalate levels were slightly higher in patients with a low turnover osteodystrophy compared to those with a high turnover pattern. Dialyzed patients with PH had remarkable increases in oxalate levels, which ranged between 14.8 and 907 mumol/g bony tissue. Oxalate deposition appeared to be progressive in that oxalate levels were significantly related to time on dialysis. In three patients calcium oxalate was a significant fraction of the mineralized bone. The occurrence of calcium oxalate crystals affected the histomorphometric patterns, that were featured by an increase in resorptive areas and a decrease in bone formation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of primary hyperoxaluria type 2 (L-glyceric aciduria) in patients with maintained renal function or end-stage renal failure.

Primary hyperoxaluria (PH) type 1 and type 2 are autosomal recessive defects of oxalate metabolism resulting from glyoxylate accumulation which occurs by two distinct pathways. PH1 is associated to glycolic aciduria; PH2 to L-glyceric aciduria. Because hyperoxaluria leads to nephrolithiasis or nephrocalcinosis in both, they can be differentiated only through detection of the associated acidurias. However, glycolate and L-glycerate assays are not widely available and, in the setting of ESRF, diagnosis is hampered by a number of misleading events. At any stage of the disease diagnosis is crucial because there are differences between the two forms in clinical behaviour, long-term prognosis, and treatment. In this paper we outline diagnostic criteria for identification of PH2 in two patients, one with maintained renal function and one with ESRF on CPD, based on the use of a novel HPLC assay of L-glycerate in different body fluids. With the routine application of this procedure PH2 has been identified in two of 23 patients fulfilling criteria for diagnosis of PH. This suggests that the type 2 variant of PH may occur more frequently than so far suspected, and should be tested for even in the setting of ESRF.

Clinical, histological, and chemical characterization of ectopic calcification in dialyzed and non-dialyzed patients.

In a review of 11 cases of ectopic calcification (5 of which in dialyzed patients and one in a paraplegic), the authors attempt to characterize this disorder in all its various forms using histological, clinical, and chemical methods. In dialyzed patients, two contributing factors were identified: hyperphosphatemia (plus hypercalcemia) and secondary hyperparathyroidism. In hyperphosphatemic patients the calcifications are multiple, paraarticular, labile, and have a fluid-viscous consistency. In secondary hyperparathyroidism, in addition to the above metastatic calcification there is dystrophic calcification typically localized in the anterior muscles of the hip and thigh. The ectopic calcification of the non-dialyzed patients is true ossification. The precise moment of the onset of the lesion is not always discernable, but its evolution points to primary or secondary local irritation as the trigger. Ossification is the predominant phenomenon in the paraplegic as well, while the triggering mechanism is still unknown.

Mineralometry of the lumbar spine and histomorphometry of the iliac crest: preliminary results of a comparison of several parameters in the same individual.

Twelve patients affected with various bone pathologies (osteoporosis, renal osteodystrophy, osteogenesis imperfecta, hyperparathyroidism) were submitted to mineralometry of the lumbar spine with double photonic ray and transiliac biopsy for histomorphometry. A comparison of the values obtained for the mineralometric and histomorphometric parameters--despite the small number of cases--revealed a correlation between bone mineral content of the lumbar spine and trabecular and cortical bone volume of the iliac crest. The correlation is even more significant for the sum of these last two parameters. It may be concluded that: 1) both the methods have predictive values for an evaluation of osteopenia; 2) the measurement of cortical and subcortical bone volume increases the significance of the histomorphometric finding (which is usually limited to the trabecular bone volume); 3) there is a correlation between histomorphometry (iliac crest bone volume) and mineralometry (lumbar spine with double photonic ray) in the same individual.

Primary oxalosis mimicking hyperparathyroidism diagnosed after long-term hemodialysis.

Primary oxalosis is a rare inborn error of oxalate metabolism. Most cases are discovered in children, but occasionally symptoms begin later in life. Since early deaths in the past were from renal failure, prolonged survival obtained with chronic dialysis allows oxalosis to develop. This paper presents a 38-year-old man with an atypical history of type-I primary hyperoxaluria, not diagnosed until after 5 years of dialysis. Bone biopsy was performed because the biochemical and radiologic features did not seem consistent with a putative diagnosis of secondary hyperparathyroidism. This case emphasizes the clinical heterogeneity of this disorder, and the need for its considerations in the spectrum of dialysis-related bone diseases. It also stresses that bone oxalosis may mimic hyperparathyroidism, especially radiologically. Differential diagnosis is therefore mandatory.

Histomorphometric study of the dynamics of mineralization in a case of osteomalacia caused by anticonvulsants treated with 25(OH)d3.

The authors describe the experimental method used to make histomorphometric determinations in a case of osteomalacia caused by anticonvulsant drugs treated with 25(OH)D3. This comprised double fluorescent markings repeated at set time intervals after taking biopsy samples from the patient. This combined method of study enabled the effect of the treatment to be monitored throughout its course.