TESTS OF RENAL FUNCTION

179 test of tubule function. Studies of the urinary sediment showed that in general the number of casts increased with increasing kidney damage. But hyaline casts are TESTS OF RENAL FUNCTION probably a reflection of proteinuria, and cellular and KIDNEY function may be impaired in three principal granular casts of tubule desquamation ; so if no distinction is made between them no specific relationships can ways : the renal plasma-flow may be reduced, the be expected, and none are reported. function or tubule be may glomerulus may be damaged, The urea-clearance has been generally accepted as a include each of these renal diseases Most deranged. test of glomerular filtration-rate, and the phenolIn essential different but to disorders, hyperdegrees. tension the chief fault is reduction in renal plasma-flow, sulphthalein excretion as a measure of renal tubule although tubule function is also early disturbed ; but the excretory function, but Kark et al. show that two substances is related to glomerular filtration-rate is well maintained. In acute impaired excretion of these rather than to individual derangeoverall main effect and its the is kidney damage sequelae glomerulonephritis reduction in glomerular filtration-rate, whereas renal ments. The blood-creatinine, blood-urea-nitrogen, and plasma-flow and tubule function are disturbed only later. blood-protein-nitrogen were measured in most of the In the nephrotic syndrome the basic fault is probably patients studied, and usually all were raised when increased glomerular permeability,l sometimes with extensive renal damage was apparent histologically. increased glomerular filtration-rate 23 and possibly dis- But distinct cellular changes could be observed without turbed tubule function 4 but with well-preserved renal nitrogen retention, which must be relegated to a lowly plasma-flow ; whereas in pyelonephritis tubule function position as an index of advanced and widespread disease. In these cases of systemic lupus erythematosus renal is early affected, followed closely by renal plasma-flow, with glomerular filtration-rate continuing almost nor- biopsy provided earlier and more exact and useful mally.5 Of course, in the later stages all three elements information on diagnosis and progress, and indicated treatment more precisely, than any of the indirect tests are disturbed in all renal diseases and it is often impossible to establish, even after death, the underlying disease of renal function. This work casts some doubt on the specificity of the urea-clearance and phenolsulphthalein process. For this reason tests of individual kidney excretion as tests of principally glomerular disease and functions have been harshly judged in some quarters, tubular disease respectively when the kidney is widely whereas in others obloquy has been no less pronounced, diseased. It is tempting to extend the results to other but on different grounds-namely, that they are cumberforms of renal disease, but this would probably be some, inexact, and difficult to interpret. Certainly they provide no short cut to anatomical or aetiological diag- unjustifiable. The recent clear demonstration 13 of the fundamental glomerular lesion of acute glomerulonoses ; and certainly they must be conducted under standard conditions of exercise, diet, and hydration.6 nephritis and its sequelae indicates that this disease may offer a better model for comparison of structural and But used and interpreted intelligently they aid diagnosis functional changes than one in which both elements are and decisions on treatment.7 Kark et a1.89 have studied the diffuse renal disease of concurrently disturbed early. It is to be hoped that systemic lupus erythematosus by percutaneous renal Kark and his associates will soon report their data on biopsy, and related the histological changes in the kidneys pyelonephritis and glomerulonephritis in similar fashion. with a series of simple tests of function, conducted conSEROLOGICAL DIAGNOSIS OF GLANDULAR FEVER currently. These were specific gravity, proteinuria, urine sediment, nitrogenous blood constituents, urea-clearance, onTHE serological diagnosis of glandular fever depends identifying specific heterogenetic antibodies, which and phenolsulphthalein excretion—all tests in daily use be agglutinating or haemolytic. may the the in U.S.A. and (except phenolsulphthalein test, An agglutinin, active against sheep cells, was described by at the moment unwarrantedly unfashionable) in this Paul and 14; this agglutinin is also active against horse country. Their first, and least surprising, conclusion is cells.15 ABunnell second type of agglutinin is active against human that tests of renal function are generally insensitive. group-0 erythrocytes sensitised by bacteriophage lysates of Because of the large reserve of renal tissue, considerable certain staphylococci and hæmolytic streptococci 16; such structural change can take place before measurable lysates contain a common hapten which is adsorbed to the functional damage becomes apparent. This might be red cell. A third type is active against human erythrocytes interpreted as an argument for the more frequent use of sensitised by exposure to egg cultures of Newcastle-disease renal biopsy. Their second conclusion-that proteinuria virus 1’ ; this is thought to be a hapten adsorption phenomenon, is a measure of damage in the glomerular basement but its relationship to the bacterial type of hapten is obscure. Haemolytic antibodies, active against sheep cells, but more membrane-might also have been predicted, but it is active ox cells, were first described by Bailey and good to have this point confirmed. The further observa- Raffel.18against tion that proteinuria is related to histological changes in The classical serological method of diagnosing glandular the tubule should be interpreted cautiously ; there are fever is the original Paul-Bunnell sheep-cell agglutination good grounds for believing that these changes may sometimes be secondary to the proteinuria itself. Specific test. But Messer 19 has lately advocated a rapid one-stage which agglutination of sheep cells, and neutralisagravity was found to relate equally well with glomerular, test in with ox-cell and guineapig extracts, are done simultion tubular, and overall kidney damage ; but if abnormal it was a good index of kidney disease. In view of this and taneously ; the result can be read after only an hour. other data 10-12 it should not be taken as an unequivocal The identification of ox-cell haemolyains was advocated by Mason 20 and Leyton,21 who found that ox-cell lysin could 1. Chinard, F. P., Lauson, H. D., Eder, H. A., Greif, R. L., Miller, exist in significant titre sometimes before, and sometimes A. J. clin. Invest. 1954, 33, 621. the development of sheep-cell agglutinin. The without, 2. Farr, L. E. Ibid, 1936, 15, 703. 3. Galan, E. Amer. J. Dis. Child. 1949, 77, 328. is not removed by sheep cells, and is presum, h2emolysin 4. See Lancet, 1957, i, 1288. ably a distinct entity. Because complement is used and 5. Smith, H. The Kidney. New York, 1951 ; p. 876. cell suspensions are variable, this is a more complex 6. Sargent, F., Johnson, R. E. Amer. J. clin. Nutr. 1956, 4, 446.

Annotations

7. Ham, H. T.

Diagnosis.

Syllabus of Laboratory Examinations Cambridge, Mass., 1952.

in Clinical

8. Kark, R. M., Pollack, V. E., Soothill, J. F., Pirani, C. L., Meuhrcke, R. C. Arch. intern. Med. 1957, 99, 176. 9. Meuhrcke, R. C., Kark, R. M., Pirani, C. L., Pollack, V. E.

Medicine, 1957, 36,

1.

10. Bradford, J. R. J. Physiol. 1899, 23, 415. 11. Hayman, J. M., Shumway, N. P., Dumke, P., Miller, M. J. clin.

Invest. 1939, 18, 195. 12. Platt, R.

Brit. med. J. 1952, i, 1313.

13. Mellors, R. C., Ortega, L. G. Amer. J. Path. 1956, 32, 455. 14. Paul, J. R., Bunnell, W. W. Amer. J. med. Sci. 1932, 183, 90. 15. Barrett, A. M., J. Hyg., Camb. 1941, 41, 330. 16. Fraser, K. B. J. Path. Bact. 1954, 67, 301. 17. Burnet, F. M., Anderson, S. G. Brit. J. exp. Path. 1946, 27, 236. 18. Bailey, G. H., Raffel, S. J. clin. Invest. 1935, 14, 228. 19. Messer, A. I. J. clin. Path. 1957, 10, 23. 20. Mason, J. K. J. Hyg., Camb. 1951, 49, 471. 21. Leyton, G. B. J. clin. Path. 1952, 5, 324.