Plasma oxalate concentration and secondary oxalosis in patients with chronic renal failure.

To examine the association between hyperoxalaemia and secondary oxalosis, measurement of plasma oxalate concentration was combined with a search for tissue deposition of calcium oxalate crystals in patients with chronic renal disease. Two groups of patients were studied. In the first, samples of the inferior epigastric artery were taken from 35 patients at the time of renal transplantation. In the second, sections taken at necropsy from 23 patients with chronic renal failure in whom plasma oxalate had been measured before death were examined. Though plasma oxalate concentrations ranged between 6 and 116 mumol/l (four to 78 times greater than the upper limit of the reference range), no extrarenal deposits of oxalate were found in either study. Renal deposition of oxalate was associated with a plasma oxalate concentration of greater than 20 mumol/l. This study gives no support to the suggestion that hyperoxalaemia of the degree seen in patients with the type of chronic renal failure that is not due to primary hyperoxaluria confers an appreciable risk of extrarenal oxalosis.     

Atherosclerotic oxalosis in coronary arteries.

BACKGROUND: Systemic oxalosis may be hereditary or acquired. In these cases, calcium oxalate deposits have been reported in numerous tissues, including the media of arteries. In any category, calcium oxalate deposition has not been described within atherosclerotic plaques in any arteries. METHODS: As part of a retrospective clinicopathologic study, 80 hearts were obtained from the National Neurological AIDS Bank in an effort to study coronary atherosclerosis in patients infected with HIV. The population consisted of 66 HIV-positive and 14 HIV-negative patients with an average age of 47 years; 79% were males. Proximal coronary arteries were serially sectioned and processed routinely. Sections were studied by hematoxylin and eosin staining and, in selected cases, von Kossa stain and alizarin red S under different conditions, including polarized light, to allow distinction of calcium phosphate from calcium oxalate. Medical histories, autopsy reports, and general autopsy slides were reviewed. RESULTS: In four patients (three with AIDS), calcium oxalate crystals were observed within atherosclerotic plaques in the coronary arteries. Similar deposits were seen in the thyroid gland and other organs but not in the kidneys. None of the patients had chronic renal failure. CONCLUSION: The calcium oxalate crystal deposits observed in the atherosclerotic plaques in the coronary arteries of these four patients are unique in two ways: (a) these deposits have not previously been described in atherosclerotic plaques; (b) the patients did not demonstrate any of the recognized patterns of oxalosis. We suggest the phrase "atherosclerotic oxalosis" to describe this finding.     

Oxalosis in hemodialysis patients: a pathologic study of 80 cases

The incidence and distribution of deposition of oxalate crystals were studied in various organs of 80 patients with chronic renal failure maintained on hemodialysis for periods ranging from three weeks to seven years. The most frequently involved organs were the kidneys, thyroid, and myocardium. Less prominent deposit was found in the spleen and the lungs. Moderate to severe renal oxalosis was encountered more frequently in patients maintained for longer periods on hemodialysis. The therapeutic implication of distinguishing secondary from primary oxalosis is stressed. The identification and the mechanism of deposition of oxalate in tissues are discussed.     

Secondary oxalosis and sperm granuloma of the epididymis.

A 30 year old man with a 20 year history of chronic renal failure who presented with a testicular lesion is described. The lesional pathology, secondary oxalosis, and associated sperm granuloma of the epididymis was clinically considered to be an intrascrotal tumour. The oxalate crystal deposition was present within the rete testis, the ductuli efferents, and the epididymis along with sperm granulomata. This seems to be a rare complication of secondary oxalosis associated with chronic renal failure and having both clinical and pathological implications.     

Crystals in brain and meninges in primary hyperoxaluria and oxalosis.

A case of primary hyperoxaluria and oxalosis with chronic renal failure, crystalline myocarditis, and disseminated calcium oxalate crystal deposition in various tissues including the brain and meninges is described. Deposition of crystals in brain and meninges is exceptionally rare in primary oxalosis.     

Secondary hyperparathyroidism in chronic renal failure

The metabolic bone disease associated with chronic renal failure has been described collectively by the terms "renal osteodystrophy" or "renal-glomerular-osteodystrophy" and consists of osteomalacia, osteitis fibrosa, and osteosclerosis. The skeletal abnormalities may occur either alone or in combination with one another. An increased concentration of circulating immunoreactive-parathyroid hormone (i-PTH) is a recognized feature of patients with chronic renal failure, and the values are usually much higher than those found in patients with primary hyperparathyroidism associated with a parathyroid adenoma. It must, however, be recognized that the high circulatory concentrations of parathyroid hormone found in patients with chronic renal failure are of immunoassayable material which may or may not be of biological significance in respect of activity. A disturbance in the homeostatic control mechanism governing parathyroid hormone, the secretion rate, its metabolism, and target organ resistance to its action are of major importance in the pathogenesis of some aspects of the metabolic bone disease in patients with chronic renal failure. The pathogenesis of the secondary hyperparathyroidism of chronic renal failure, however, also involves disturbances in cholecalciferol metabolism, phosphate retention, and the uremic state per se.     

Glomerulopathy with renal tubular oxalosis in Japanese rock ptarmigan (Lagopus mutus).

Seven adult Japanese rock ptarmigan (Lagopus mutus) that died on a rearing farm and appeared to have suffered from glomerulopathy with renal tubular oxalosis were examined pathologically. Macroscopically, the kidneys showed enlargement of varying degrees. Histologically, the precipitation of a fibril-like substance in the mesangial area of the renal glomeruli was the most important and common lesion seen in the kidney. Calcification of glomeruli was observed in severe cases. In addition, oxalate precipitation in the lumen of the renal tubules was associated with glomerular lesions. The primary renal lesion may have been glomerulonephropathy, which was subsequently associated with tubular oxalosis as the secondary renal lesion.     

Excessive myocardial calcinosis in a chronic hemodialyzed patient

Summary Secondary oxalosis in chronic hemodialyzed patients is caused by impaired renal excretion and inadequate removal of oxalic acid during hemodialysis. Ascorbic acid is a precursor of oxalic acid. We report a parathyroidectomized patient with chronic renal failure, on hemodialysis, who received over a period of several months a total dose of 91.0 g ascorbic acid i.v. The plasma oxalic acid level in this patient was 14-fold higher than in healthy persons. Increased oxalic acid synthesis from its precursor ascorbic acid may be responsible for hyperoxalemia, high content of oxalic acid in myocardium, aorta and lung, and calcium oxalate deposition in soft tissues. Application of high doses of ascorbic acid should be avoided in hemodialysed patients with chronic renal failure.Abbreviations PTH parathyroid-hormone - RDT regular dialysis treatment     

Ultrasonography methods in the diagnosis of renal osteodystrophy

Bone disease, i.e. renal osteodystrophy, is commonly seen in patients with chronic renal failure. It encompasses all the disorders of mineral and bone metabolism associated with chronic renal insufficiency, i.e. secondary hyperparathyroidism, retention and accumulation of beta 2 microglobulin and aluminum. The most frequent cause of renal osteodystrophy is secondary hyperthyroidism, with a consequence of high turnover bone disease. Secondary hyperparathyroidism, i.e. increased parathyroid hormone (PTH) secretion and parathyroid gland hyperplasia, develops early in the course of chronic renal insufficiency. Hypocalcemia, phosphate retention and deficiency of calcitriol stimulate PTH synthesis and secretion and parathyroid cell proliferation, i.e. hyperplasia. Parathyroid cell proliferation is initially polyclonal (diffuse hyperplasia), and later it is monoclonal or multiclonal (nodular hyperplasia). Calcitriol receptors as well as calcium-sensing receptors are significantly reduced in parathyroid glands in nodular hyperplasia. Patients with such parathyroid gland hyperplasia are often resistant to vitamin D therapy. A specific form of bone disease is beta 2 amyloidosis. Destructive arthropathy, cystic changes and carpal tunnel syndrome are clinical manifestations of dialysis-related amyloidosis, which is one of the major complications in patients on longterm hemodialysis. Aluminum intoxication leads to the low turnover bone disease and consequential osteomalacia or aplastic bone lesions, the cause of which has not yet been fully clarified. Ultrasound can be a useful, economical and noninvasive method in the evaluation of renal osteodystrophy. Ultrasound waves are very important for noninvasive imaging of soft tissue, especially parathyroid glands, pathologic changes of the joints, and for detection of metastatic calcifications. They are also useful in the evaluation of skeletal status in dialysis patients. Ultrasound waves of a frequency above the limit of human hearing are used in the morphological diagnosis of parathyroid gland. Today, because of its simplicity and non-invasiveness, it is a generally accepted method for the detection of enlarged parathyroid gland in patients with secondary hyperparathyroidism, for the monitoring of pathologic changes, and for making decisions on the method of treatment based on the size and number of parathyroid glands. Ultrasound can distinguish nodal from diffuse parathyroid hyperplasia. Under ultrasound guidance it is possible to perform fine needle aspiration biopsy, to confirm ultrasound findings, and percutaneous inactivation of parathyroid gland (PEI) with alcohol. Ultrasound is useful in the diagnosis of pathologic changes of the musculoskeletal system in patients with beta 2 amyloidosis, to assess the process of its spread, especially in the shoulder joint where the changes are most pronounced (rotator cuff thickness, amyloid deposits as hyperechogenic pads, and detection of fluid in the joint), but it can also be used to examine other joints as well as soft tissue in which metastatic calcifications may occur. Standard ultrasound equipment (pulse-echo) and linear probe of 5-13 MHz are used, also serving for ultrasound examination of the neck, joints and soft tissue. Quantitative bone ultrasonometry is based on different physical characteristics of the ultrasound including: transmission, Speed Of Sound (SOS) in meters/sec and Broad Band Attenuation (BUA) in dB/MHz, and different concepts of the apparatus. These parameters depend on the strength and architecture of the bones and describe better the changes in bone structure in dialysis patients by calculation of the Stiffness Index (QUI), better than the standard bone densitometry by dual-energy x-ray absorptiometry, which only measures bone density. Combined ultrasound measurement of the bone in several locations may be successful in monitoring dialysis patients.     

Renal osteodystrophy in predialysis patients without stainable bone aluminum. A cross-sectional bone-histomorphometric study

Histomorphometry was performed on transiliac bone biopsies, double-labeled with tetracycline, from 60 consecutively admitted patients (20 women) at various stages of chronic renal failure (CRF). Eleven patients (1 woman) had normal bone resorption and formation indices. Bone resorption and osteoid formation increased with progression of renal failure, but abnormal values were seen even at slightly elevated creatinine levels. Mineralization lag time increased with CRF duration; prolonged values were only seen in patients with polycystic kidney disease or chronic pyelonephritis with advanced CRF. All patients with impaired mineralization also had increased bone resorption. Diabetes mellitus did not protect against skeletal lesions. The biochemical tests were too insensitive to predict type or severity of bone disease, and hand X-rays had no diagnostic value in early stages of renal osteodystrophy.     

Small intestinal infarction: a fatal complication of systemic oxalosis

Primary hyperoxaluria is a rare genetic disorder characterised by calcium oxalate nephrolithiasis and nephrocalcinosis leading to renal failure, often with extra-renal oxalate deposition (systemic oxalosis). Although ischaemic complications of crystal deposition in vessel walls are well recognised clinically, these usually take the form of peripheral limb or cutaneous ischaemia. This paper documents the first reported case of fatal intestinal infarction in a 49 year old woman with systemic oxalosis and advocates its consideration in the differential diagnosis of an acute abdomen in such patients.     

SECONDARY RENAL OXALOSIS

Various clinical and pathologic items were examined regarding renal oxalosis in 501 autopsy cases. The rubeanic acid method (Yasue) was applied to 501 kidney sections to demonstrate the presence of calcium oxalate crystals. The extent of renal oxalosis was determined by counting the black-stained crystals per 10 low-power field (1.3 cm²). Thus, severe oxalosis (more than 50 crystals) was observed in 38 cases; moderate oxalosis (between 10 and 50 crystals) in 19 cases; mild (fewer than 10 crystals) in 36 cases, and no deposition in 408 cases. Acute or chronic renal failure and xylitol infusion were found to be highly correlated to renal oxalosis. Cases with diabetes mellitus, with hepatocellular degeneration, or with glucose infusion, as well as neoplasms or some other alleged causes, were found to be primarily unrelated to renal oxalosis, even though the overlapping renal insufficiency, or xylitol infusion caused some of these items to appear related. In cases with xylitol infusion, the extent of renal oxalosis was shown to be dose-dependent: No severe or moderate oxalosis was observed in cases where the total dose of infusion was less than 100 g, while in cases over 500 g, 10/24, or 44 percent, showed severe oxalosis.     

Deranged Ca, Al and Mg content in the tissues of patients with chronic renal failure, as measured by non-destructive neutron activation analysis

Ca, Al and Mg content in the bone, aorta, skin and hair of 55 persons was measured by non-destructive neutron activation analysis. The Ca content in the bone of nondialyzed and dialyzed patients was found to decrease. Al and Mg were relatively higher than Ca in the patients compared to the controls. The present study suggests that fluctuation in the content of Al and Mg may have some relation to renal osteodystrophy such as osteomalacia as well as similar and related disorders. Al and Mg content in the aorta, and that of Ca in the hair of uremic patients, were higher than the controls. The mean Ca content in the skin of the patients was 25% higher than the controls. These findings indicate 1) that Al and Mg are possibly related to the advance of osteodystrophy, and 2) that Ca, Al and Mg deposits in the organs of uremic patients are a reflection of metabolic disorders in chronic renal failure.     

Oxalose Typ I im Kindesalter — Beobachtungen im Rahmen der terminalen Niereninsuffizienz beim Kind

Summary The difficulties of biochemical diagnosis in children and in chronic renal failure are discussed in detail, as well as the development of diagnostic and therapeutic possibilities in recent years, exemplified by 4 cases.Excretion of oxalate (and glycolate) may be incorrectly assumed to be normal with: a) uncritical application of the method of measurement, b) disregard of the clearly lower oxalate excretion in children (values should be referred to m² of body surface), c) disregard of a decreased glomerular filtration rate (values should be referred to the creatinine clearance). With compromised renal function the excretion of oxalate and glycolate in primary oxalosis drops to normal whereas plasma values increase considerably. In this case the biochemical diagnosis is possible only by measurement of plasma values of glycolate and oxalate. Consequently, extensive extrarenal deposition of calcium oxalate crystals will, as a rule, become clinically manifest only after chronic renal failure has turned irreversible.In recent years, several therapeutic procedures, have been developed. They are of therapeutic significance for the early stages of the disease as well. Observing especially conditions renal transplantation or combined hepatorenal transplantation can be managed with a successful outcome.As the perioxisomal enzyme is activated only in the liver cells, an early liver transplantation as a definitive treatment by enzyme replacement may be the successful therapy in the future.

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Abkürzungen NI Niereninsuffizienz - KOF Körperoberfläche - NTP Nierentransplantation - AGT Alanin-Glyoxalat-Aminotransferase     

Azotaemic renal osteodystrophy: a quantitative study on iliac bone

The histopathology of bone is described in 60 patients with chronic renal failure due to a variety of renal diseases. Changes of azotaemic renal osteodystrophy included osteitis fibrosa, osteomalacia, and osteosclerosis. Quantitative histology using a point-counting technique revealed a significant increase in total bone, mineralized bone, and osteoid in comparison with a control group of 68 individuals. Osteitis fibrosa due to secondary hyperparathyroidism occurred in 93%, osteomalacia in 40%, and osteosclerosis in 30% of patients. Woven bone formation was a characteristic feature and was related to the severity of osteitis fibrosa. There were significant correlations between the weights of parathyroid glands and the number of osteoclasts, amounts of woven bone, and marrow fibrosis in the ilium. Hyperparathyroidism caused degradation of mineralized bone but the loss was balanced or exceeded by the aggradation of woven mineralized bone. Woven bone formation together with excess osteoid gave rise to osteosclerosis. The histological findings indicate that hyperparathyroidism and osteitis fibrosa usually occur early in chronic renal failure and that osteomalacia develops subsequently.     

Early skeletal changes of the hand phalanges in patients with chronic renal failure

Appearance time and the severity of skeletal changes in patients with chronic renal failure are still not well defined. In 61 patients with incipient to advanced renal insufficiency (glomerular filtration rate 70 to 5 ml/min X 1.73 m2), bone alterations (acro-osteolysis, subeperiosteal and intracortical resorption) were mammographically studied in hand phalanges. A high correlation (p less than 0.001) was found between the radiological score and the severity of the renal insufficiency. The earliest changes of renal osteodystrophy occurred in the tufts. Biopsy specimens were taken from the iliac crest in 22 patients. Qualitative bone histology correlated significantly (p less than 0.001) with the total radiological score. Mammography offers an effective and non-invasive means of studying early skeletal changes in patients with chronic renal failure.     

Bone biopsy as a diagnostic tool in the assessment of renal osteodystrophy

When renal disease develops, mineral and vitamin D homeostasis is disrupted, resulting in diverse modifications in bone cells, bone structure and the rate of bone turnover. In end stage renal failure (ESRF) when patients require chronic maintenance dialysis, nearly all of them have abnormal bone histology known as renal osteodystrophy (ROD). Moreover, survival rates of patients on dialysis have increased because of therapeutic improvement and the resultant increase in duration of dialysis has led to a further rise in renal osteodystrophy. Because metabolic bone disease can produce fractures, bone pain, and deformities late in the course of the disease, prevention and early treatment are essential. Serum PTH and various bone markers are commonly used to assess bone changes in ESRF patients, but the diagnosis of underlying bone disease is still rather uncertain. To date, bone biopsy is the most powerful and informative diagnostic tool to provide precise information on the type and severity of renal osteodystrophy, and on the presence and amount of aluminum and strontium deposited in the bone. Bone biopsy is not only useful in clinical settings but also in research to assess the effects of therapies on bone. Although considered an invasive procedure, bone biopsy has been proven to be safe and free from major complications, but the operator's experience and skill is important in further minimizing morbidity. Alternatives to bone biopsy continue to be sought, but the non-invasive bone markers have not been proven to be sufficient in diagnostic performance related to bone turnover, mineralization process and bone cell abnormality. Hence, transiliac bone biopsy remains the gold standard for the diagnosis of renal osteodystrophy.     

Metabolic bone disease in chronic renal failure. II. Renal transplant patients.

Trabecular vertebral bone of renal transplant patients was quantitatively compared with bone from normal individuals and dialyzed and nondialyzed patienets with chronic renal failure reported in detail in an earlier study. Long- and short-term transplant patients have increased bone resorption and mineralization defects similar to renal osteodystrophy in dialyzed and nondialyzed patients. However, in transplant patients the magnitude of resorption is greater, and bone volume tends to decrease rather than increase. Resorptive activity in transplant patients is maximal during the first year after transplantation. Bone volume decreases continuously for at least 96 months after transplantation. Only decreased bone volume correlated with success or failure of the renal transplant. Morphologic findings in this study correlate with other clinical and morphologic data to suggest that reduction in bone volume in transplant patients results from a combination of persistent hyperparathyroidism and suppression of bone formation by steroid therapy.     

Osteocalcin in chronic hemodialysis patients as an additional parameter in the diagnosis of advanced secondary hyperparathyroidism

Osteocalcin (OC), also called Bone Gla Protein (BGP), is a bone matrix protein of 5800 MW synthesized by osteoblasts. Since OC is mainly metabolized in the kidney, its blood concentration is altered in renal failure. The relationship between OC and the calcium-phosphorus regulating hormones (parathyroid hormone, calcitonin) and the biochemical parameters of bone metabolism (serum calcium, serum phosphorus and serum alkaline phosphatase) was studied in 30 patients on chronic hemodialysis (mean age: 51 years; mean duration of dialysis treatment: 39 months). OC levels were significantly elevated in all patients on chronic hemodialysis (34.7 +/- 31.5 ng/ml) when compared to healthy subjects (6.25 +/- 1.39 ng/ml, p less than 0.001). In 2 patients the OC levels were excessively high (127.54 ng/ml; 148.02 ng/ml), which was associated with severe renal osteodystrophy due to secondary hyperparathyroidism. When divided into 2 groups in the patients with secondary hyperparathyroidism the mean OC value was markedly elevated (50.5 +/- 12.7 ng/ml) compared to the patients without secondary hyperparathyroidism (24.1 +/- 2.8 ng/ml) (p less than 0.05). 70 per cent of the patients on chronic hemodialysis with OC levels greater than 30 ng/ml showed moderate to severe scintigraphic findings of bone disease. In neither of the 2 groups could a correlation between OC and serum alkaline phosphatase be demonstrated. The results indicate, that OC levels could be useful additional parameter in hemodialyzed patients with secondary hyperparathyroidism and OC levels could reflect bone formation in these patients.     

血清BUN、Scr、PTH和核素骨扫描在肾性骨营养不良中的应用

目的 评价血清BUN、Scr、PTH和^99Tcm-MDP核素骨扫描在肾性骨营养不良中的临床应用价值.方法 75例慢性肾功能衰竭的患者在一周内接受血清BUN、Scr、PTH检测和^99Tcm标记的亚甲基二磷酸盐（^99Tcm-MDP）核素骨扫描,对核素骨扫描图像上可能出现的代谢性骨病显像特征的数量进行评价,并采用三级评分法对各代谢性骨病的图像特征进行半定量分析.结果 75例受检者血清BUN平均为20.31 ±7.95 mmol/L;血清Scr平均为730.2±275.4μmol/L;69例受检者的血清PTH平均为1477.4±781.9 pg/mL（13.7 ～ 3306 pg/mL）.核素骨扫描图像上,30例患者具备5个图像特征,具备4个、3个和2个图像特征的受检者数量分别为32例、11例和2例;半定量分析结果显示75例患者的合计评分范围为4 ～10分.结论 血清BUN,Scr、PTH结合99Tcm-MDP核素骨扫描有助于为肾性骨营养不良患者的诊断、鉴别诊断和疗效评价等方面提供有价值的信息.