Postgrad Med J: first published as 10.1136/pgmj.39.449.121 on 1 March 1963. Downloaded from POSTGRAD. MED. J. (I963), 39, 12I FUNCTIONAL ASPECTS OF THE DIFFERENTIAL DIAGNOSIS OF RENAL DISEASE JAN BROD, MI.D., D.Sc. Director, Institute for Cardiovascular Researc3t, Prague 4, Czechoslovakia IF we read through both the basic papers which process, which might be present only in other William Bright wrote some 136 and 127 years ago, portions of the organ. In chronic pyelonephritis, and which laid the foundations of clinical nephro- for example, we can find quite normal areas of logy, we can recognize in the detailed clinical kidney in close approximation to areas severely description the nephrotic syndrome, the effects altered by the chronic process. of severe hypertension and the signs of chronic However, morphological criteria are but one renal or cardiac insufficiency. These are the end- consequence of the disease-process-the other stages which follow almost all types of chronic consequence consisting of the renal functional renal disease, and these late phenomena cannot be changes, which are no less specific than the used to differentiate between the various morpho- details of micro-morphology. Our own work, logical entities which the pathologists later con- and that of others, has led us to the conclusion structed from the original tissue of ' Bright's that a study of renal function can give us a great disease '. Such a differentiation was, of course, to deal of information not only concerning the degree no purpose at the period when therapeutic of the disease process-hitherto its main applica-by copyright. medicine knew little else than venesection, tion-but also as to the nature of the disease calomel, diaphoretics, suction-cups and a few process, with a high degree of reliability. I hope other drugs which Bright prescribed with both that the material I shall present you, summarising enthusiasm and conviction for his patients. Even some 25 years of observations on 3,685 patients, in the century following Bright we had little else in will transmit this conviction to you as well. our therapeutic armamentarium than a low- protein, low-salt diet and fluid restriction, so that, Methods again, the differential diagnosis of renal disease The methods used by us in these studies are by no was to little avail. means highly specialized ones--they are within the http://pmj.bmj.com/ The situation in therapy today is quite different, reach of any local hospital, and in Czechoslovakia they and attempts at differential diagnosis have thereby have been introduced into the routine investigational procedure of most medical wards. In addition to history taken on considerable practical importance. Since and physical findings, they include: (i) qualitative and morphology of the kidney itself has been the clas- quantitative analysis of urine in terms of the content of sical criterion of diagnosis, kidney biopsy can be of protein and formed elements in the Addis sediment; great assistance, particularly when combined with (2) an approximation to glomerular filtration rate by means of the endogenous creatinine clearance in one histochemistry and electron microscopy of the 24-hour urine sample or in several 3- to 4-hour speci- on September 28, 2021 by guest. Protected biopsy material. These latter techniques have mens over the course of a single day; (3) measurement taught us a great deal of the early stages of kidney of the concentrating ability, which is a very sensitive disease, since such cases do not come to the post- indicator of tubular function; (4) in selected cases investigation of diluting ability; (5) in cases where mortem table. It must be stressed, however, that asymmetry of the disease-process is suspected, investiga- biopsy is not without risk, that it requires the tion of creatinine concentration or clearance measure- services of a pathologist experienced in inter- ments with urine obtained from each ureter separately preting such material, that even in the best of by catheterization; (6) where indicated, urography, pyelography, aortography or tomography with retro- hands about one-quarter of all biopsies ends up peritoneal air insufflation; (7) if bacterial infection is with no kidney tissue in the needle, that the biopsy suspected, the urine is cultured, and if the culture is piece may contain so few glomeruli that any positive then quantitative estimation of bacterial' interpretation at all is risky, and that one has no contamination of the urine is carried out. If there are more than io,ooo organisms per ml. of urine, bacterial guarantee at all that the region of kidney punc- infection is highly suspect, and if this count is greater tured by the needle actually contains the disease than ioo,ooo infection is certain. of Diseases Lecture given at the London Hospital on June 20, Functional Classification Renal I962, and at Bristol University on July 3, I962. The simplest method of functional classification Postgrad Med J: first published as 10.1136/pgmj.39.449.121 on 1 March 1963. Downloaded from I122 POSTGRADUATE MEDICAL JOURNAL March I963 of renal disease is according to the degree to which kidneys, and skin. Renal vasoconstriction may glomerular and tubular function is altered viz: result in a decrease in glomerular filtration. Such (i) There are disease-states which primarily in- a decrease of glomerular filtration in an otherwise volve glomerular filtration, leaving tubular intact nephron, regardless of how it comes about, function intact. has, among others, two consequences of interest: (2) There are others in which glomerular and (i) The decreased filtered load of osmotic material tubular function are altered in a more or less to the individual nephron has the opposite effect parallel fashion. on final osmolarity of the urine to that of the (3) There are further states in which tubular raised osmotic load in osmotic diuresis. Here, malfunction is the only demonstrable defect as we know, urine osmolarity decreases asympto- for long in the course of the disease, glomerular tically in the direction of plasma osmolarity. With alteration being a late development (Table I). a decrease in filtered osmotic load urine osmolarity is increased to high values, even in the absence of TABLE I ADH (Shannon, 1942; de Wardener and del FUNCTIONAL CLASSIFICATION OF CHRONIC Greco, I956). (2) When glomerular filtrate is low RENAL DISEASE and the plasma coursing through the glomerulus is I. GLOMERULAR FUNCTION RESTRICTED MORE THAN TUBULAR FUNCTION in contact with this structure for a longer-than- A. On Heemodynamic Basis: normal period, there is a greater-than-normal i. Orthostatic proteinuria diffusion of protein into the glomerular filtrate 2. Emotional proteinuria (Goverts and Lambert, 1953). At least in some 3. Exertional proteinuria nephrons this diffusion may lead to amounts 4. Heart failure 5. Essential hypertension (early) of protein in the lumen which cannot be re- B. On Organic Basis: absorbed in entirety by the tubular cells. The (a) Without grave changes of basal unreabsorbed remnant appears then in the urine membrane: along with occasional hyaline casts which are the Vascular nephrosclerosis of this but also with occasionalby copyright. (b) With grave changes of basal membrane: gel-form protein, I. Diabetic glomerulosclerosis tubular cells and granular casts due to saturation 2. Amyloidosis of these cells with protein transport and subse- 3. Nephropathia gravidarum quent disintegration (Addis, 1942). II. PARALLEL REDUCTION OF GLOMERULAR AND TUBULAR FUNCTION: This is the mechanism of proteinuria which Glomerulonephritis occurs with severe muscular exercise, and during III. TUBULAR FUNCTION RESTRICTED MORE THAN orthostasis in some individuals with circulatory GLOMERULAR FUNCTION: dysregulation in the erect posture (orthostatic i. Chronic pyelonephritis proteinuria), with so-called ' negative emotional 2. Polycystic kidney disease states' such as fear, anxiety, anticipation-thesehttp://pmj.bmj.com/ latter situations being haemodynamically com- In individual sub-groups it is of assistance to parable to preparation for muscular activity determine the quality of the glomerular ab- (Brod, Fencl, Hejl and Jirka, 1959), and in normality, the presence of the nephrotic syndrome, congestive failure. In the first three states hypertension, infection, etc. mentioned above, there is no protein in the morn- Disease-states with Primary Involvement of ing urine, which immediately suggests that there is the Glomerular Apparatus no organic disease in the kidneys themselves. on September 28, 2021 by guest. Protected Glomerular filtration can be decr¢ased by lesions Greater confusion can be caused by the proteinuria which restrict the filtration area with infiltration or of congestive failure, which lasts as long as failure scar formation, despite a lack of tubular involve- is present: if there is nocturia, the diurnal curve of ment, but also by any state causing vasoconstric- glomerular filtration shows a rise to normal at tion in the kidney. In the first group we find night, which is of diagnostic significance (Fig. i) diabetic glomerulosclerosis, renal amyloidosis, (Brod and Fejfar, 1950). In severe cases, where toxaemia of pregnancy and primary nephro- glomerular filtration is depressed over the entire sclerosis arising on the basis of hypertension of 24 hours and the protein and cellular content of 'long duration. In the second group we find states the urine is somewhat higher, high urine specific in which there is a generalized hlmodynamic gravity, which shows a normal nephron popula- reaction to an imbalance between the tissue re- tion even with a glomerular filtration rate as low as quirement of oxygen and the ability of the 50 to 30 ml./min., can exclude organic renal circulatory apparatus to deliver it to the tissues, disease. In these cases, blockage of the adre- resulting in vasodilation in muscles and adrenergic nergic mechanism by means of dibenamine will be vasoconstriction in the splanchnic bed, the followed by a rise in renal plasma flow and Postgrad Med J: first published as 10.1136/pgmj.39.449.121 on 1 March 1963.