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advantage of cognitive/behaviour therapy over drugtreatment must cast doubt over claims that cognitivedysfunction is primary in neurosis.9 Somebiochemical abnormality appears equally probable onthe basis of recent studies suggesting inheritance ofpanic disorder10 and abnormality of noradrenergicfunction in anxious patients.ll The failure to finddifferential effects between treatments for differentneurotic conditions must also weaken the view thatsuch diagnoses have a sound aetiological base.

Unfortunately, these negative fmdings leave groundsfor appeal since it is very difficult to study sample sizeslarge enough to reduce adequately the appreciable riskof type II error YBoth the Nottingham and Northwick Park

investigators seem prepared to advance the notion thata spectrum of psychotic disorder or neurotic disorderis more likely to be valid than a differentiated

diagnostic schema with discrete boundaries betweenconditions. However, there are two issues. The first iswhether the symptoms of mental illness and our

ability to describe and measure them will ever beadequate to identify a true underlying continuum or aset of bounded illnesses; this remains most uncertain.The second is whether a biological continuum can beidentified as a substrate for psychiatric symptoms andsyndromes. Disorders of dopaminergic transmissioncould perhaps provide an example of a biologicalcontinuum in psychosis. The actions of

pharmacologically specific compounds, either as

treatments or as challenge drugs, can be the basis foran assay of neurotransmitter function. Such

pharmacological investigation remains one of the fewcoherent approaches to the study of psychiatric illnessthat are available and the results will continue to be of

major importance to our understanding as well as ourpractice.

Progression of Chronic RenalFailure

Is there a degree of renal failure which inevitablyleads to progressive loss of remaining renal functioneven if the underlying disease process abates or isremoved? If so, what is the cause of this progressionand can it be modified? A series of challengingexperiments carried out in Brenner’s laboratory inBoston has led to the formulation of a simplehypothesis with major clinical implications.1 His team

9. Beck AT, Laude R, Bohnert M. Ideational components of anxiety neurosis. Arch GenPsychiatry 1974; 31: 319-25.

10. Noyes RJ, Crowe RR, Harris EL, Hamra BJ, McChesney CM, Chaudhry DR.Relationship between panic disorder and agoraphobia Arch Gen Psychiatry 1986;43: 227-32.

11. Charney DS, Heninger GR. Abnormal regulation of noradrenergic function in panicdisorders. Arch Gen Psychiatry 1986, 43: 1042-54

12. Young MJ, Bresnitz EA, Strom BL. Sample size nomograms for interpreting negativeclinical studies. Ann Intern Med 1983; 99: 248-51.

1. Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressivenature of kidney disease. N Engl J Med 1982, 307: 652-59

have used micropuncture techniques to reveal theintraglomerular events following extensive renalablation in Munich Wistar rats which have superficialglomeruli suitable for this type of study. The

remaining glomeruli hypertrophy and their bloodflow and filtration rate increase. Later, proteinuria andglomerular sclerosis develop progressively and renalfunction declines. These changes appear to be a directconsequence of a rise in the pressure of the glomerularcapillaries (PGc).2 They can be accelerated by ahigh-protein diet, particularly of animal origin,3 andameliorated by a low-protein diet* and angiotensinconverting enzyme (ACE) inhibitors5 (both of whichreduce PGc) and by heparin6 and even by exercise.’Thus, Brenner and colleagues proposed that

progressive renal failure resulted from hyperfiltrationassociated with a raised PGc in the glomeruli whichsurvived the original disease.1

Other factors that may contribute to progressiverenal failure include interstitial deposits of calciumphosphate associated with progressive interstitialfibrosis,8 hyperlipidaemia,9 and mesangial overloadleading to sclerosis.1O It is difficult, even in laboratoryanimals, to determine which factors are primary andwhich secondary. Moreover, there are differencesbetween strains of rats in their susceptibility to

progressive renal failure following extensive

nephrectomyll to which dogs appear to be immune.12The lessons derived from the surface glomeruli ofMunich Wistar rats may therefore not be generallyapplicable in clinical practice.

Observations of patients with chronic renal diseasesuggest that most progress to terminal renal failureand at a predictable rate. Two studies in the mid 1970sshowed that the reciprocal of the serum creatininedeclined linearly with time and was sufficientlyreliable to predict when dialysis would becomenecessary. 13,14 A new study from Liverpool of 108

2. Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BMHyperfiltration in remnant nephrons: a potentially adverse response to renalablation. Am J Physiol 1981, 241: F85-91.

3. Williams AJ, Walls J. Metabolic consequences of differing protein diets in

experimental renal disease Eur J Clin Invest 1987; 17: 117-22.4. Naith KA, Kren SM, Hostetter TH. Dietary protein restriction in established renal

injury in the rat J Clin Invest 1986; 78: 1199-205.5. Anderson S, Meyer TW, Rennke HG, Brenner BM. Control of glomerular

hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest1985, 76: 612-19.

6. Olson JL. Role of heparin as a protective agent following reduction of renal mass KidInt 1984; 25: 376-82.

7. Heifets M, David TA, Tegtmeyer E, Klahr S. Exercise training ameliorates

progressive renal disease in rats with subtotal nephrectomy. Kid Int 1987; 32:815-20.

8. Ibels LS, Alfrey AC, Haut L, Huffer WE. Preservation of function in experimentalrenal disease by dietary restriction of phosphate. N Engl J Med 1978; 298: 122-26.

9 Moorhead JF, Chan MK, El-Nahas M, Varghese Z. Lipid nephrotoxicity in chronicprogressive glomerular and tubulo-interstitial disease. Lancet 1982; ii: 1309-11

10. Grond J, Beukers JYB, Schilthuis MS, Weening JJ, Elema JD. Analysis of renalstructural and functional features in two rat strains with different susceptibility toglomerular sclerosis. Lab Invest 1986; 54: 77-83.

11. Weening JJ, Beukers JJB, Grond J, Elema JD. Genetic factors in focal segmentalglomerulosclerosis. Kid Int 1986; 29: 789-98.

12. Robertson JL, Goldsmidt M, Kronfeld DS, Tomaszewski JE, Hill GS, Bovee KC.Long term renal responses to high dietary protein in dogs with 75% nephrectomyKid Int 1986; 29: 511-19.

13. Mitch WE, Walser M, Buffington GA, Lemann J. A simple method of estimatingprogression of chronic renal failure Lancet 1976; ii: 1326-28.

14. Rutherford WE, Blondin J, Miller JP, Greenwalt AS, Vavra JD. Chronic progressiverenal disease: Rate of change of serum creatinine concentration. Kid Int 1977; 11:62-70

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patients with mild to moderate renal failure found thatlinear progression occurred in 70 and was morecommon in patients with glomerulonephritis,diabetes, chronic pyelonephritis, and polycystickidneys than in those with hypertension, analgesicnephropathy, obstructive uropathy, and, not

surprisingly, following acute renal failure.1s Thatdifferent causes of renal failure are associated withdifferent patterns of progression goes against thegeneral applicability of the hyperfiltration hypothesis.A linear progression does not identify the cause of thedeterioration and, since the mean rate of loss offunction of the various diagnostic subgroups differedwidely, it is likely that more than one process wasinvolved, including continued activity of the

underlying disease.If hyperfiltration were a major contributor to

progression, then patients with a higher proteinintake, higher blood pressure, and more proteinuriawould be expected to have a worse prognosis. TheLiverpool group analysed rate of progression against

- these factors and found that only proteinuriacorrelated significantly in the group as a whole.Proteinuria may not only be an indirect marker of PGcbut also cause it to rise in nephrotic patients withwell-preserved renal function. The charge of thepolyanion of the glomerular capillary wall is lost ormasked in patients with heavy proteinuria.16 As aconsequence, negatively charged large molecules mayclog up the capillary surface 17 and so reduce

glomerular filtration, as happens in minimal changenephropathy,18 with a compensatory rise in PGc. Thissequence of events could account for the adverse effectof heavy proteinuria on the prognosis of manydifferent forms of glomerular disease.There was no correlation between protein intake,

which ranged from 0-4 to 1 6 g/kg body-weight/day,and rate of progression of renal failure. Perhapsmeasures taken to control blood pressure concealed aneffect of diet, but the findings are another reminder ofthe dearth of good controlled data showing thatlow-protein diets slow progression-there have beennumerous reports to this effect but only one properlycontrolled triap9 Large, multicentre, prospectivecontrolled studies have been designed but haveproved remarkably difficult to execute. The Liverpoolworkers found a weak correlation between the calcium

phosphate product and linear decline in renal functionamong patients with mild renal failure. Since most

15 Williams PS, Fass G, Bone JM. Renal pathology and proteinuria determineprogression in untreated mild moderate chronic renal failure Quart J Med 1988;67: 343-54.

16 Cotran RS, Rennke HG. Anionic sites and the mechanism of proteinuria. N Engl JMed 1983; 309: 1050-52.

17. Kanwar YS, Rosenzweig LJ. Clogging of the glomerular basement membrane. J CellBiol 1982; 93: 489-94

18. Robson AM, Gianogiacomo J, Kienstra RA, Nagui ST, Inglefinger JR Normalglomerular permeability and its modification by minimal change nephroticsyndrome. J Clin Invest 1974; 54: 1190-99

19 Rosman JB, ter Wee PM, Meijer S, Piers-Becht TPhM, Sluiter WJ, Donker AJM.Prospective randomised trial of early dietary protein restriction in chronic renalfailure. Lancet 1984; ii: 1291-96.

phosphates in the diet are in food rich in protein, thereis some doubt whether a high protein diet is harmfulbecause of the protein itself or because of the

phosphates it contains. The Liverpool results arecompatible with the latter hypothesis.Management of patients with chronic renal failure

has not yet been radically changed by the intellectualferment caused by the hyperfiltration hypothesis. Theoriginal cause of the disease should be identified and, ifpossible, treated. Good blood pressure control is

essential 20 but it remains to be seen whether ACEinhibitors5 and calcium channel blocking agents21have any advantage over older hypotensive agents.Low-protein diets relieve many of the symptoms ofuraemia and may slow progression but it is not clearwhether this approach is effective in all patients orwhether it is additive to the effect of blood pressurecontrol. Serum phosphate should be controlled toprevent the development of hyperparathyroidism andperhaps to slow progression of renal failure. And thepatient should be prepared for dialysis.

PROGNOSIS OF PSORIATIC ARTHRITIS

As a result of Dennis Potter’s much televised SingingDetective, public awareness of psoriatic arthritis has neverbeen higher. The diagnosis may now conjure images of anappallingly disabling condition rendering its victim unableto hold a pencil, chew a sweet, or turn his head. How likely isa patient with psoriasis and inflammatory arthritis to get thismutilating form of joint disease? Wright described fivesubsets of psoriatic arthritis, of which arthritis mutilanscomprised only 5%.1 The remaining subsets were distaljoint arthritis, asymmetrical oligoarthritis, symmetricalpolyarthritis indistinguishable from rheumatoid arthritis,and ankylosing spondylitis. All were said to have a betterprognosis than rheumatoid arthritis. More recently, ananalysis of 220 patients with psoriatic arthritis has

challenged this concept.2 In this study, 40% of patients hada deforming erosive arthropathy, 17% had five or moredeformed joints, and 11 % were substantially disabled (ARAfunctional grade III or IV). This more gloomy viewsupports the findings of Stem that of patients aged 20 to 60,those diagnosed as having psoriatic arthritis were twice aslikely to be unemployed as those with psoriasis alone or withpsoriasis and other joint complaints. 3The long-term prognosis of the spondylitis of psoriasis

has received little attention. 5 % of patients with psoriaticarthritis have a condition very similar to ankylosingspondylitis and may represent the chance association of thetwo disorders. Another type of spinal or sacroiliac disease

20. Bergstrom J, Alverstrand A, Bucht H, Gutierrez A. Progression of chronic renalfailure in man is retarded with more frequent clinical follow-ups and better bloodpressure control. Clin Nephrol 1986; 25: 1-6.

21. Harris DCH, Hammond WS, Burke TJ, Schner RW Verapamil protects againstprogression of experimental chronic renal failure. Kid Int 1987; 31: 41-46.

I. Moll JMH, Wright V Psoriatic arthritis. Semin Arthritis Rheum 1973; 3: 55-78.2. Gladman DD, Shuckett R, Russell ML, Thorne JC, Schachter RK. Psoriatic arthritis

(PSA)—an analysis of 220 patients. Quart J Med 1987; 62: 127-413. Stern RS. The epidemiology of joint complaints in patients with psoriasis. J Rheumatol

1985; 12: 315-20.