CHRONIC NEPHRITIS WITH AND WITHOUT EDEMA: A STUDY OF CHOLESTEROL IN THESE CONDITIONS Francis D. Murphy J Clin Invest. 1927;5(1):63-99. https://doi.org/10.1172/JCI100149. Research Article Find the latest version: https://jci.me/100149/pdf CHRONIC NEPHRITIS WITH AND WITHOUT EDEMA: A STUDY OF CHOLESTEROL IN THESE CONDITIONS BY FRANCIS D. -MURPHY (From the Medical Clinic of Milwaukee County Hospital) (Received for publication August 5, 1927) Many attempts have been made to correlate the clinical symptoms and pathological changes in the kidney of chronic nephritis, but so far, no general agreement prevails concerning the importance of numerous factors held partially accountable for some of the chief symptoms. This is well illustrated in the case of edema, where many theories have been advanced to explain its presence, and have not been generally accepted, as shown by the extensive review of Loeb (1). Recently, considerable attention has been given to changes in the protein and lipoid content of the blood plasma in renal diseases es- pecially in cases of pure lipoid nephrosis. Numerous studies have appeared dealing with protein changes and their relation to symptoms of nephritis, while comparatively few have dealt with cholesterol and its association with nephritis. This article takes up observations made on a series of cases of chronic nephritis with and without edema and includes a few cases of hypertensive cardiovascular disease with edema from heart failure. The changes in the blood cholesterol, the presence of cholesterol esters in the urine and in the tubular epithelium in those conditions are especially dealt with. To avoid confusion, it should be understood that no cases of pure lipoid nephrosis are included here. The latter condition was studied and reported upon elsewhere (2). Of the thirty-one cases reported here, twenty-five had chronic nephritis and six were cases of hypertensive cardiovascular disease with edema from heart failure. Of the twenty-five patients with chronic nephritis, fourteen were edematous; in eleven no edema ap- peared; seventeen died, and fourteen of these were examined post mortem. Three of the six patients with hypertensive cardiovascular disease died and were examined post mortem. 63 64 CHOLESTEROL IN CHRONIC NEPHRITIS All of the patients classed as nephritis showed extensive glomerular involvement and the tubules were diseased in varying degree, from cloudy swelling to complete obliteration. Clinically, all the cases of nephritis under consideration fulfilled the requirements for a diag- nosis of chronic diffuse glomerular nephritis. Under older classifica- tions, those cases showing the edema, a heavy albuminuria, with slight retention of nitrogenous products would be classed as chronic paren- chymatous, while those with no edema, an excessive retention of nitrogenous products in the blood, and a great elevation of the blood pressure, would be placed with the chronic interstitial type. Under the classification of Christian (3) many of these cases would corre- spond to his combined type; chronic nephritis with edema and hyper- tension; the others would conform to his group: chronic nephritis with hypertension. Large and small white kidneys, mottled kidneys, and granular kidneys were found in this series. It seems significant that the edema appeared to be independent of either glomerular in- volvement or of simple tubular degeneration. The size, shape or color of the kidney bore no relation to the dropsy. Histologically, all cases exhibited tubular changes but those of the group showing edema were characterized by a special type of disease, namely, a lipoid deposit in the tubular epithelium, while those having no edema, had no lipoid deposit in the tubular epithelium. The chief object of this paper is to show that there exists an asso- ciation between chronic glomerular nephritis with edema on the one hand, and on the other, the following group of conditions: an elevation of the blood cholesterol, deposits of lipoid material in the tubular epithelium and the presence of doubly refracting lipoid bodies in the urine. As to the character of the association of the edema and the conditions mentioned-whether it points to a relationship as of cause and effect-even in the face of grave suspicion arising from a study of the cases, prudence suggests that judgment be suspended. For while these findings are present too constantly to be considered as mere coincidence, the significance of them in connection with the presence or absence of edema is obscure and may be related to other factors whose importance in this connection is still unknown. FRANCIS D. MURPHY 65 COMMENT ON CASE HISTORIES AND AUTOPSY FINDINGS (For detailed data see tables 1, 2 and 3, and appended protocols.) The cases presented may be divided into three groups: Group I, patients with chronic nephritis with edema (table 1); Group II, pa- tients with chronic nephritis with no edema (table 2); and Group III, patients with hypertensive cardiovascular disease with edema from heart failure (table 3). Besides the routine examinations, the blood cholesterol was determined and the urine examined for doubly re- fracting lipoids in each case, and where autopsies were performed the tissue was examined for doubly refracting lipoids. Cases in Group I (table 1) There were fourteen cases in this group; nine of them died of uremia and five are living. A post mortem examination was made in six. The chief clinical findings were edema, hypertension, hematuria and a reduced renal function progressing to a serious degree of renal insufficiency and terminating in uremia. Usually there was an elevation of blood cholesterol, although in case 12 it was subnormal and in case 2 it was only slightly elevated. The edema was usually not persistent, but came and went at irregular intervals and was not influenced to a great extent by any treatment instituted. Hyper- tension of varying degrees was present in all cases. There was some elevation of blood urea nitrogen in all cases, although in case 10, the increase was not great. Doubly refracting lipoids were found almost constantly in the urinary sediment of all cases except in case 12 where none was found on repeated examination. These lipoids were found regularly in all the cases during edema free period. It can be said that the magnitude of the edema was not matched by the number of doubly refracting lipoids present in the urine. It may also be stated that the degree of hypercholesterolemia did not parallel the amount of edema at all times. There was an extensive edema in case 6 at a time when the blood cholesterol was less than usual. Of the kidneys of this group examined post mortem, all had doubly refracting lipoids in the renal tubular epithelium, including case 12, in which none was found in the urine during ante-mortem observation. 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