Urine In Nephritis Research Articles

Monocytes Promote Crescent Formation in Anti-Myeloperoxidase Antibody–Induced Glomerulonephritis

Neutrophils and monocytes express anti-neutrophil cytoplasmic antibody (ANCA) antigens, and activation of these cells by ANCA is central to ANCA-associated vasculitis and necrotizing crescentic glomerulonephritis (NCGN). The importance of neutrophils is established; however, any role of monocytes is less clear. We tested the hypothesis that depletion of CCR2+ inflammatory monocytes and their derivatives would abrogate anti-myeloperoxidase (MPO) antibody-induced NCGN in a mouse model. We used passive anti-MPO antibody transfer for NCGN induction in wild-type mice or mice expressing the CCR2 promoter-controlled diphtheria toxin receptor. Both mouse strains showed similar circulating Ly6Chi and Ly6Clo monocytes and neutrophils at baseline. Diphtheria toxin robustly depleted circulating monocytes only in CCR2 promoter-controlled diphtheria toxin receptor mice, whereas neutrophil numbers were similar. Anti-MPO antibody transfer resulted in nephritic urine by dipstick and albuminuria by enzyme-linked immunosorbent assay, and monocyte depletion had no effect. However, monocyte depletion significantly reduced glomerular necrosis and crescent formation and abrogated monocyte, macrophage, and dendritic cell increase in the affected kidneys, whereas renal neutrophil numbers were not affected. Soluble CD163 increased in serum, but not in urine, with anti-MPO antibody treatment and was completely abolished with monocyte depletion. Our findings establish an important role of monocytes/macrophages for glomerular necrosis and crescent formation in a renal ANCA-associated vasculitis model.

Hydralazine Associated Pauci-Immune Glomerulonephritis

Hydralazine is a medication that has been used to manage hypertension and heart failure. In this case series, we report 4 patients who presented to a large, Midwestern academic medical center on chronic hydralazine therapy with acute kidney injury, nephritic urine sediment on urine microscopy, and the simultaneous presence of autoantibodies suggesting both drug-induced lupus and drug-induced vasculitis. All of them had evidence of pauci-immune glomerulonephritis on kidney biopsy. All the patients reported in our series are white women older than 60 years who were receiving hydralazine for more than 12 months at a dose of 150 mg or more. On initial presentation, all had evidence of acute kidney injury with nephritic sediment. These patients also had high titers of serum anti-neutrophil cytoplasmic antibodies of the antimyeloperoxidase subtype and simultaneous presence of multiple autoantibodies. All of them subsequently underwent a kidney biopsy, which revealed pauci-immune glomerulonephritis. This case series draws rheumatologists' attention to the possibility of pauci-immune glomerulonephritis in patients taking hydralazine, highlights the presence of multiple antibodies in these cases, and questions the long-term use of hydralazine especially in an elderly female population.

Cryoglobulinemia and Glomerular Rhomboid Inclusions in a Child With Acute Kidney Injury

Cryoglobulinemia is rarely reported in children, and kidney failure secondary to cryoglobulinemia is even more uncommon. We report the case of a 7-year-old boy with cryoglobulins and a systemic illness, including persistent fever, arthralgias, rash, hypocomplementemia, and acute kidney injury associated with nephritic urine sediment. An extensive workup showed no infectious, neoplastic, or rheumatological cause of his kidney injury. The kidney biopsy specimen showed membranoproliferative glomerulonephritis type 1 with electron microscopic evidence of rhomboid crystalloid inclusions. These inclusions have rarely been reported in adult patients with cryoglobulinemia. The patient underwent spontaneous remission, including full recovery of kidney function, and required no immune suppression. The patient's course is consistent with cryoglobulinemia-associated kidney injury, which supports the inclusion of essential cryoglobulinemia in the differential diagnosis of pediatric patients with hypocomplementemic glomerulonephritis.

Limited cutaneous systemic sclerosis associated with MPO-ANCA positive renal small vessel vasculitis of the microscopic polyangiitis type

Renal disease in systemic sclerosis may present in various patterns. A 66-year-old woman with a history of longstanding limited cutaneous systemic sclerosis of the CREST syndrome variant presented with a sudden left foot drop and rapidly progressive renal insufficiency associated with mild proteinuria, a nephritic urine sediment, and a urinary output of 900 mL/d. There was no history of intake of d -penicillamine, and there were no signs of malignant arterial hypertension or microangiopathic hemolytic anemia. Renal histology showed a small vessel vasculitis of the microscopic polyangiitis type. Serologic tests showed a marked increase of antineutrophil cytoplasmic antibodies with a perinuclear pattern and an elevated titer of antimyeloperoxidase antibodies. No clinical or laboratory signs of Sjögren’s syndrome were present. This clinical report adds new information to the spectrum of renal disease in systemic sclerosis. It discusses the association between systemic sclerosis and small vessel vasculitis of the microscopic polyangiitis type as well as the possible meaning of serologic markers.

Isoenzymes of N-acetyl-beta-D-glucosaminidase in kidney cortex and urine of normal and nephritic rats.

Induction of acute Heyman nephritis in rats gave a significant increase in the urinary excretion of protein (p less than 0.001) and N-acetyl-beta-D-glucosaminidase (NAG; p less than 0.01) 14 days after injection of antibody. The isoelectric points (IP) of NAG were studied by chromatofocusing of the urine, serum and various lysosomal populations purified from kidney cortex homogenates of normal and nephritic rats. The chromatofocusing profiles for serum NAG (IP = 5.8) were totally different from the patterns found in normal and nephritic urines. The acidic IPs of NAG in normal urine (IP = 5.0) were changed into slightly more basic values in nephritic urine (IP = 5.15). Similar changes were also demonstrated in normal urine after acidification and prolonged incubation. The chromatofocusing profile obtained for NAG in the large, dense lysosomes was almost identical to the pattern observed in nephritic urine and demonstrated IPs for NAG in a slightly more basic pH area than observed for small and medium-sized lysosomes. The difference in IP in normal and nephritic urines may therefore be due to an increased autolytic degradation of NAG or excretion of the enzyme from different populations of lysosomes.

Characterization of basement membrane antigens present in the urine of normal and nephritic rabbits.

Experimental glomerulonephritis was induced in rabbits with anti-rabbit glomerular basement membrane (RGBM) antisera raised in goats. The structural damage of the glomerular basement membrane (GBM) was characterized by excretion of basement membrane (BM) fragments into the urine which share determinants with enzyme-solubilized RGBM. Four BM antigens distinguished by molecular size, surface charge and antigenic structure were detected in the urine of nephritic animals. Quantitative determination showed an increased excretion of BM fragments into the urine of nephritic rabbits, corresponding to the development of renal injury. Fractionation studies of normal urine indicated the presence of trace amounts of two distinct BM antigens, immunologically identical or cross-reactive with two out of four BM antigens of acute nephritic urine. A severe glomerulonephritis developed in goats after injection with purified RGBM and is, in this sense, comparable to the effectiveness of heterologous BM in inducing kidney injury in sheep. Eluted antibodies from glomerulonephritic goat kidneys reacted with antigenic structures of the GBM obviously susceptible to collagenase treatment. On the other hand, urinary BM antigens failed to react with antibodies to tendon collagen suggesting that collagen is not an integral part of these antigens. The experimental evidence implicated the possibility of a nonspecific reaction between concentrated urine, or its chromatographic fractions, and goat sera, which may be confused with specific precipitates formed between urinary BM antigens and anti-RGBM antiserum.

The nature of urinary protein in eclampsia

The ratio of albumin to globulin in the urine of patients suffering from nephritis appears to bear a somewhat constant relationship to the type and severity of the renal disease present. Thus, Hiller, McIntosh and Van Slyke1 have found that it is usually above 10 in nephrosis, between 5 and 10 in acute nephritis, while in the advanced stages of chronic glomerular nephritis with urea retention and impaired kidney function, it falls below 5. They note, moreover, that cases of acute nephritis show a low ratio during the early stage followed by a higher one during recovery. In view of such facts, these authors attach a certain prognostic significance to the albumin:globulin ratio of the urine in nephritis and agree with the earlier students2, 3 of the subject that in general the prognosis is grave in patients showing relatively high urinary globulin.The nature of the urinary protein excreted in the various toxemias of pregnancy has apparently received little attention. The only approach that has been made to the problem, indeed, seems to be the study of Wallis4 reported in 1921, although Dr. Williams tells me that Emerson and Slemons many years ago made some observations in this service, which were not published. Wallis applied certain refractometric and nephelometric tests to the urinary proteins in various conditions and reached the conclusion that in “toxic albuminuria,” including eclampsia, the ratio of albumin to globulin was 2 to 1, while in nephritis it was 6 to 1. As the result of this study, he regards the urinary albumin:globulin ratio as a valuable means of differentiating preeclampsia from nephritis.The present paper reports a quantitative study of the urinary albumin and globulin in 21 cases of toxemia of pregnancy. The group comprises 9 cases of eclampsia, 4 of preeclampsia, 6 of chronic nephritis, and 2 of nephrosis complicating pregnancy. In several instances the corresponding figures for the serum proteins were also determined.

ALBUMINURIA IN THE MECHANISM OF DETOXIFICATION

It is our purpose in this paper to present data indicating that the presence of serum proteins in the urine in nephritis is due to their combination with other nitrogenous fractions of tissue origin, some of which are highly toxic. It is our belief that this combination acts as a detoxicating mechanism and that the elimination of this protein by the kidneys is due to alteration of normal serum proteins by their combination with other split protein products which render them foreign to the circulation. It has been apparent for some time that the renal element in nephritis is relatively unimportant and that theories of nephritis based solely on renal damage must be abandoned. The Aldrich and McClure1intradermal salt test as well as the series of experimental dehydrations reported by one of us2gives ample evidence that Martin Fischer was right in ascribing edema to a greater colloid affinity

SOME ASPECTS OF BLOOD CHEMISTRY IN PREGNANCY

The acceptance of the view that protein metabolism involves primarily the transformations of amino-acids —the degradation products of the proteins—in the organism has placed diverse aspects of bodily function in a new light. It has become easier also to realize why the proteins that are found in the urine under a variety of pathologic conditions are different from the albuminous compounds that are ingested. Wells 1 has pointed out that numerous attempts have been made by both chemical and immunologic methods to determine whether the proteins in the urine in nephritis come from the food, the blood, or from the renal cells themselves. In alimentary albuminuria, the urinary proteins seem not to be those of the food, but human proteins. In nephritis, differentiation between serum proteins and kidney proteins has not yet been satisfactorily accomplished. If urinary proteins do not represent the undestroyed residues of food proteins, it becomes a

PARENCHYMATOUS NEPHRITIS

Two important problems in the pathogenesis of "parenchymatous nephritis" are (1) the cause of the albuminuria and (2) the cause of the edema. The latter problem at least is concerned with an alteration in the equilibrium between the cells and body fluids; the most promising methods of handling such a problem are physicochemical. The present paper deals with the results obtained by applying one such method, namely, the determination of surface tension. Substances lowering surface tension have already been found in nephritic urine. It is known that substances which lower the surface tension at a phase boundary accumulate in greater concentration at such a boundary; and it is reasonable to suppose that at the interface, changes in permeability would result. In the present paper it will be shown that a marked lowering of the surface tension of the blood serum occurs in parenchymatous nephritis; in another paper, it will be

Bacteriology of urine in nephritis and experimental bacterial nephritis

The reports of careful bacteriologic investigation of the urine in cases of nephritis are not numerous, and have dealt chiefly with acute rather than chronic conditions. In many instances there is an obvious infection preceding or accompanying an acute nephritis, while prolonged search in chronic cases may fail to reveal any hidden or obscure infectious element. Nevertheless, the impression prevails with many good clinicians that chronic nephritis is infectious in origin. With this in mind a careful search was made for evidence of infection in the urine

"Burnam's Test" for Formaldehyd: a Question of Priority

To the Editor: —Hugh Cabot and O. R. T. L'Esperance in an article entitled The Excretion of Formaldehyd by the Kidneys of Patients Taking Hexamethylenamin, a Study of ( Boston Med. and Surg. Jour. , Oct. 24, 1912, p. 577), and later B. F. Jeness in an article entitled Burnam's Test for Formaldehyd in the Urine (The Journal, March 1, 1913, p. 662) described in detail a method for determining small quantities of formaldehyd in the urine, calling this method, both in the title and in the text, Burnam's test. This consists in the use of dilute solutions of phenylhydrazin hydrochlorid, sodium nitroprussid and sodium hydroxid. It is a delicate color reaction, for all practical purposes specific for formaldehyd and very sensitive, revealing the presence of minute quantities of formaldehyd, even in albuminous fluids, such as milk, nephritic urine, etc. This so-called Burnam's test was discovered by Rimini ( Ann.