Disorders of hemostasis in chronic renal failure and renal transplantation

The presence of end-stage renal disease (ESRD) has been associated with profound clinical effects on hemostasis ranging from thrombosis to bleeding complications. The pathogenesis of uremic bleeding is multifactorial. It has been attributed to platelet dysfunction, the most important feature, particularly platelet-platelet and platelet-vessel wall interactions. Renal replacement therapy has helped reduce bleeding episodes, but the risk of morbidity and mortality due to hemorrhage persists. Abnormalities of blood coagulation and fibrinolysis predispose uremic patients to hypercoagulable state carrying the risk of atherosclerotic cardiovascular disease and thrombotic complications such as thrombosis of the vascular access wall. There are differences in the measurement of various hemostatic parameters in patients with ESRD concerning treatment with either hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Hemostatic disturbances are overlapped by changes in the coagulation/fibrinolytic system after renal transplantation (RT). Despite the etiology, renal transplant patients are at an increased risk of thromboembolic events as a consequence of prothrombotic clotting and fibrinolytic abnormalities. This hypercoagulable state is to a large extent associated with immunosuppressive drugs. This review will give a summary of views on hemostasis in patients with ESRD and after RT.     

Monocytes and human renal glomerular disease: a quantitative evaluation

Human renal biopsies (n = 177) were quantitatively evaluated by histochemical means (alpha-naphthyl acetate for nonspecific esterase) for the presence of monocytes within glomerular tufts (excluding crescents). The number of monocytes per glomerulus was counted to obtain the nonspecific esterase index. Histologic, electron microscopic, and direct immunofluorescent features were analyzed. Cases were grouped according to whether intraglomerular electron-dense deposits were present and, if so, their predominant position. Five groups were obtained: group I, subendothelial (39 biopsies); group II, mesangial (24 biopsies); group III, subepithelial (22 biopsies); group IV, intramembranous (2 biopsies); and group V, no detectable deposits (90 biopsies). For each group, the mean nonspecific esterase index was determined: I = 2.0, II = 0.28, III = 0.26, IV = 0.08, and V = 0.13. Group I was subdivided on the basis of whether extensive mesangiocapillary change was present or not. The mean nonspecific esterase index for the group I biopsies without mesangiocapillary change was 2.5, which was significantly higher than the scores for biopsies with mesangiocapillary change (0.2) and those from the other groups (p < 0.01). The results indicate an association between relatively high levels of intraglomerular monocytic infiltration and diseases characterized by having electron-dense immune deposits predominantly in the subendothelial position without extensive mesangiocapillary change. Diseases with predominantly subepithelial, mesangial, intramembranous, or no detectable deposits generally showed low numbers of intraglomerular monocytes.     

Relations between platelet and plasma-coagulative components of hemostasis in health and disease

The adhesive-aggregative activity of the platelets and the rate of blood clotting were compared in 125 healthy subjects during an emergency adaptation reaction (emotional stress, ACTH loading) and in 157 patients with heart and circulatory diseases during the period of crisis, and also during acute drug therapy. Changes in the platelets and plasma-coagulative components of hemostasis were found to be opposite in direction, and on this basis new ideas were put forward to explain the hemostatic function of the platelets.Department of Internal Medicine, Kuban Red Army Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Fedorov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 669–672, December, 1979.     

A comparison of the unlabeled enzyme method with immunofluorescence for the evaluation of human immunologic renal disease.

The application of the unlabeled enzyme method to immunostaining of human renal biopsy material is described. The specificity and sensitivity of this technic were compared with those of standard immunofluorescent staining procedures. The unlabeled enzyme method, although a lengthier procedure, has proven to be as specific and at least as sensitive as conventional fluorescent staining. The advantages of the procedure are its permanence, its compatibility with conventional staining procedures, and the avoidance of fluorescent microscopy for evaluation.     

A pedigree study of perinatally lethal renal disease.

A family study of perinatally lethal renal disease (PLRD) was undertaken in the State of Victoria, Australia, for the years 1961 to 1980. A total of 221 cases was ascertained through hospital and necropsy records and confirmed by necropsy findings. There were 134 cases of bilateral renal agenesis (BRA), 34 cases of unilateral agenesis with dysplasia of the other kidney (URA/RD), 42 cases of bilateral renal dysplasia (BRD), and 11 cases of renal aplasia. Parents of 131 babies were interviewed and 153 parents from 82 families had a renal ultrasound examination. In the period of best ascertainment (1975 to 1980) the frequency of PLRD was 0.27 per 1000 and of BRA 0.16 per 1000. There were 10 cases of sirenomelia, a frequency of 0.008 per 1000. For all families of PLRD, 15 of 423 (3.6%) sibs and three of 1579 (0.2%) first cousins were affected. One family had three sibs with BRA and four had two sibs with BRA. One pair of sibs and two first cousins had BRA in one and URA/RD in the other affected. One baby had BRD with an affected first cousin. The nature of the renal lesion was not established. When the index case had BRA, 14 in 283 (5.6%) sibs had PLRD. Where the index case had BRA and urogenital defects, but no birth defects in other organs, 12 of 148 sibs (8%) were affected. None of the sibs had BRA when the index case had BRA as part of a multiple malformation complex. In the multiple malformation group, however, five of 40 (12.5%) sibs had similar patterns of malformations. Renal ultrasound abnormalities were no more frequent in parents of two affected babies (one of 18) than in the other parents (nine of 135). Our findings confirm that BRA and URA are genetically related. There are a number of conclusions which are important for genetic counselling. There is a high likelihood of recurrence (8%) in sibs when the index case has BRA and urogenital abnormalities alone. When BRA is part of a multiple malformation complex, the risk of recurrence of multiple malformations is significant (12.5%), but risk recurrence of BRA is low. The finding of renal ultrasound abnormalities in the parents was not informative.     

A quantitative evaluation of blood-lymphocyte subpopulation in herpetic ocular disease

Data on changing contents of blood-lymphocytes' subpopulations in patients with ophthalmoherpes are reported. A higher number of blood cells expressing the surface activation antigens of HLA-DR+, CD71+ and CD95+, a lower number of T-helpers and a reduced value of the immune-regulating index were found to be typical of such changes. A more significant increase in the quantity of CD95+ lymphocytes, as observed in cases of severe ophthalmoherpes versus its moderate clinical course, could be a prognostication criterion. The essential shifts occurring in the T-cells' population denote the status of tension in the immune response provoked by an intensified reproduction of herpes simplex virus (HSV); at the same time, they are indicative of a certain deficit in the immune-protection mechanisms.     

Cell-mediated immunity in renal disease

It has been shown in experimental models that cell-mediated immunologic mechanisms can lead to glomerular as well as tubulointerstitial renal injury, with or without concomitant antibody-mediated effects. The glomerular lesions are characterized by varying combinations of monocyte and, to a lesser extent, lymphocyte influx, necrosis, and proliferation of intrinsic glomerular cells. The tubulointerstitial lesions have generally been characterized by interstitial infiltrates containing numerous T lymphocytes and, often, numerous macrophages, sometimes with invasion of tubules and tubular cell damage. Although similar renal abnormalities are seen in several human renal diseases, further evidence is obviously required to establish a pathogenetic role for cellular immunity. Analyses of infiltrating mononuclear cells by immunohistochemical methods, with monoclonal antibodies that identify subsets of T cells, have indirectly supported a role for delayed hypersensitivity reactions in tubulointerstitial nephritis resulting from drugs or associated with anti-TBM antibodies, as well as a role for both delayed hypersensitivity and cytolytic lymphocyte effects in renal allografts. However, only with the development of methods that permit the identification of subsets of lymphocytes with unique functions, as well as the identification of the antigen specificity of the cells, will it be possible to understand fully the renal lesions that are now suspected of being cell-mediated.     

Spontaneous renal disease in dogs

Renal disease is common in dogs. The incidence of significant renal disease increases with age. Many disease processes are subtle and subacute, and so many are not detected until they result in chronic renal failure. The causes of many renal diseases are not known but one must suspect immune-mediated damage in some.