Johanna Zingraff

Hemodialysis-associated amyloidosis and beta-2 microglobulin: Clinical and immunohistochemical study

The beta-2 microglobulin type of amyloidosis was identified in articular and para-articular tissues of 14 patients with non-amyloid nephropathies undergoing long-term hemodialysis. Ten patients had carpal tunnel syndrome, 13 had juxta-articular radiolucent cysts (complicated by spontaneous fractures of the femoral neck in three), and six had destructive arthropathies of the large joints of the limbs. Massive amyloid deposits were found in the synovium, capsule, ligaments, articular cartilage, and/or bone. They were characterized by Congo red-induced green birefringence that was sensitive to potassium permanganate treatment. They reacted with anti-beta-2 microglobulin antiserum, whereas they did not react with antibodies directed against AA protein, prealbumin, or immunoglobulins. These data suggest that the potentially disabling arthropathy of hemodialysis is due to amyloid lesions. The persistently elevated plasma beta-2 microglobulin levels may play a role in the pathogenesis of this recently recognized complication, and if so, this complication should be preventable.

Can the Nephrologist Prevent Dialysis-Related Amyloidosis?

The pathogenesis of dialysis-related amyloidosis is still poorly understood. Therefore, preventive measures can be proposed at present only on the basis of retrospective studies and hypothetical considerations. Two main solutions may be recommended, namely an effective dialytic removal of beta 2-microglobulin (beta 2-M), which is the protein precursor of dialysis amyloid, and the avoidance of bioincompatibility-associated phenomena such as those induced by dialysis membranes and endotoxins. Promising new imaging techniques such as computed tomography (CT) scan, nuclear magnetic resonance (NMR), and scintigraphy with specific tracers for amyloid may be helpful to evaluate the long-term results of different treatment schedules, including various strategies of renal replacement therapy.

Congestive cardiomyopathy in uraemic patients on long term haemodialysis.

Five uraemic patients who developed progressive cardiac failure with clinical evidence of congestive cardiomyopathy at the start or during haemodialysis treatment were studied. The diagnosis of cardiomyopathy, for which there was no apparent cause, was confirmed by angiocardiographic and haemodynamic studies. These showed a significant increase in left ventricular end-diastolic volume over normal values obtained in 12 patients without uraemia. The mean velocity of myocardial fibre shortening was significantly decreased, as was the index of normalised rigidity. Three of the five patients presented the complete picture of the disease. The other two also had considerable ventricular dilatation and a decreased index of normalised rigidity but normal ejection fraction and only moderately decreased myocardial contractility indices. This suggests that there may be primary involvement of normalised heart muscle rigidity followed by secondary changes in myocardial contractility in uraemic patients with congestive cardiomyopathy.

Porphyria cutanea tarda-like Syndrome in Hemodialyzed Patients

Among 500 patients on maintenance hemodialysis, 6 patients (5 young women and a 49-year-old man) developed bullous dermatosis, 2-54 months after initiating dialysis treatment. The skin lesions occurred mainly in sunlight-exposed areas, and 4 out of the 6 patients showed increased cutaneous fragility in response to trauma. Skin biopsy revealed subepidermal blisters for all of them, and skin immunofluorescence studies were negative for 2 patients. No increase in fecal or red cell coproporhyrin and protoporphyrin levels was found in any of the 6 patients. The syndrome was clinically and histologically indistinguishable from porphyria cutanea tarda.

Left Ventricular Function in Hemodialyzed Patients with Cardiomegaly

Left ventricular function was investigated in 21 chronic hemodialysis patients with cardiomegaly not due to major pericardial effusion. Angiographic and hemodynamic studies were performed in all, and

Radionuclide Exploration of Dialysis Amyloidosis: Preliminary Experience

The noninvasive diagnosis of amyloid arthropathy in dialysis patients is still uncertain. Therefore, we investigated the potential diagnostic value of the 99mTc-methylene diphosphonate scan in seven long-term hemodialysis patients suffering from chronic joint pain who had biopsy-proven osteoarticular amyloidosis of the recently discovered beta 2-microglobulin (beta 2-M) type. In six, but in none of five control patients on short-term hemodialysis, increased tracer uptake was found at the site of one or several articular and/or periarticular regions. Increased uptake at a given joint was often, but not always, associated with joint pain. It appeared to precede radiologically visible changes. In conclusion, the 99mTc-methylene diphosphonate scan may be of help in the early diagnosis of dialysis amyloidosis.

Effect of Calcitriol in the Control of Plasma Calcium after Parathyroidectomy

Severe, prolonged hypocalcemia in observed in some, but not all, hemodialysis patients after parathyroidectomy performed because of uncontrolled hyperparathyroidism. The aim of the present study was to investigate whether calcitriol and calcium supplementation in the immediate period after parathyroidectomy (days 1-14) was of more help in the control of plasma calcium than calcium supplementation alone. Fourteen hemodialysis patients were enrolled in a prospective, randomized, double-blind and placebo-controlled study. From the day after parathyroidectomy, 7 patients received calcitriol and the remaining 7 a placebo using incremental doses adjusted to the degree of hypocalcemia (up to 4 micrograms/day for calcitriol). Plasma calcium, phosphorus, alkaline phosphatase and immunoreactive parathyroid hormone levels before parathyroidectomy were comparable in both patients groups, as was the lowest plasma calcium achieved after parathyroidectomy. The decrease in plasma calcium after parathyroidectomy was related to plasma alkaline phosphatase and to the number of osteoclasts and osteoblasts on bone biopsy surface before parathyroidectomy. The mean decrement of plasma calcium (days 3-9) as compared to that before parathyroidectomy was less pronounced in calcitriol-treated than in placebo-treated patients (0.25 +/- 0.06 versus 0.45 +/- 0.05 mM, mean +/- SEM, p less than 0.025). Treatment with placebo was interrupted before day 14 because of persistent severe hypocalcemia in 4 of 7 patients, whereas calcitriol treatment was continued in all 7 patients up to 14 days. Patients on calcitriol treatment required less mean calcium supplements (days 1-9) than patients receiving placebo (37.4 +/- 3.2 versus 49.4 +/- 3.7 g, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Dialysis-Associated Amyloidosis

Dialysis-related arthropathy represents a major complication of uremic patients treated by hemodialysis or other renal replacement therapies. Nearly 10 years ago, this syndrome was shown to be associated with a new type of amyloid, mainly composed of beta-2 microglobulin (beta 2-M). Retention of the beta 2-M protein due to chronic renal failure, although unquestionably a prerequisite for the occurrence of beta 2-M amyloidosis, appears not to be the unique pathogenetic factor involved in this complication. A role has also been attributed to an enhanced local or systemic generation of inflammatory mediators, an increased production of beta 2-M, and an altered metabolism of the molecule including partial proteolysis and glycation. It is possible that factors related to renal replacement therapy such as dialysis membrane biocompatibility also play a role. However, the clarification of the precise underlying mechanism(s) awaits further study. Because dialysis technology has progressed considerably during the last decade, a significant beta 2-M removal can be achieved at present using high-flux dialyzers. Moreover, a marked reduction in bioincompatibility during the dialysis procedure as manifested by activation of complement and stimulation of mononuclear blood cells can now be attained. Future studies will tell whether technical progress in dialysis technique results in a decrease in the incidence of symptomatic dialysis-associated amyloidosis.

Polynévrite au cours de l’urémie chronique

La polynevrite de 10 malades atteints d’uremie chronique terminale a ete etudiee avant et apres transplantation renale. L’evolution des signes d’atteinte du neurone peripherique apres restauration de

Ascorbate-Cyanide Test on Red Blood Cells in Uremia: Effect of Guanidinopropionic Acid

Red blood cells (RBC) of uremic or control subjects have been exposed to an oxidative stress by ascorbate and cyanide. The spectrophotometric determination of the sulfhemoglobin production has been used as a reliable method for the measurement of the hexose monophosphate shunt. The sulfhemoglobin production by RBC was significantly higher in uremic than in control subjects. Uremic plasma increased this production in uremic as well as in control RBC while control plasma was ineffective under the same conditions. In vitro the guanidinopropionic acid had the same toxic effect on normal RBC. These results suggest that the abnormal sulfhemoglobin production by uremic RBC might be due to an increased plasma concentration of guanidinopropionic acid in uremia.