M.R.C.Path. causes to the raised plasma urea in patients admitted

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1 Pstgradcuate Medical Jurnal (January 1979) 55, 1-14 The cause f the raised plasma urea f acute heart failure R D THOMAS MRCP D B MORGAN MRCPath ALISON NWILL AIMLS Departments f Cardilgy and Chemical Pathlgy, Leeds General Infirmary Summary The cncentratins f urea, urate, phsphate and creatinine were measured in the plasma f 3 cnsecutive patients admitted acutely with heart failure On admissin, 2 had a raised plasma urea, 21 had a raised plasma urate, but nly 6 had a raised plasma phsphate and nly 6 had a raised plasma creatinine A further 9 f the patients develped a raised plasma urea after admissin The increase in plasma urea present n admissin was greater than expected fr the fall in GFR (as indicated by the increase in plasma creatinine) The results fr plasma and urine taken tgether suggest that a majr cause f the raised plasma urea was an increased urea prductin rather than a reduced glmerular filtratin rate There was n bvius relatinship between plasma urea and clinical features, r diuretic therapy causes t the raised plasma urea in patients admitted acutely t hspital with heart failure In additin they have examined the relatinships between plasma urea and plasma urate, phsphate and creatinine in these patients n admissin, and made bservatins n the changes in plasma urea while the patients were in hspital Patients and methds Thirty-tw cnsecutive patients wh were admitted acutely t hspital because f heart failure were studied The diagnsis was based n a typical histry and clinical signs tgether with radilgical evidence f pulmnary venus hypertensin Tw patients were subsequently shwn t have chrnic renal failure and were excluded There were 19 men and 11 wmen aged years (mean 69 years) The majr cause f the heart failure was ischaemic Intrductin heart disease in 13 patients, cr pulmnale in 6, A raised plasma urea is cmmn in heart valvular failure disease in 5, cardimypathy in 1 and (Dmenet and vans, 1969; Thayer, 196) and the chrnic heart blck in 1 patient Fur elderly higher it is, the lwer the chances f survival patients had n bvius single cause fr the heart (Dmenet and vans, 1969; Mrgan, Carver and failure Twenty-eight f the 3 patients were being Payne, 1977) This rise is usually attributed t treated fr heart failure befre admissin The diminished renal functin (Thayer, 196), r t clinical signs and the radilgical features were treatment with diuretics (Greenblatt et al, 1977) graded n a simple scale f severity A sample f Hwever, in a recent survey, mst bld and an untimed hspital patients sample f urine were taken with a raised plasma urea and heart failure, had a within a day f admissin Further measurements nrmal plasma creatinine were made and, therefre, presumably during the admissin n bld samples had nrmal renal functin (Mrgan et taken fr clinical al, 1977) management The results were Apart frm diminished renal functin the ther tw cmpared with thse in 36 patients with chrnic pssible causes f a raised plasma urea are an increased prductin f urea and increased tubular repatients r wh had been admitted fr catheteriza- heart disease (grup ) wh were attending utabsrptin f urea Increased urea prductin has tin (Davidsn et al, 1976) been demnstrated in heart failure (Dmenet and Plasma urea, phsphate, and creatinine were vans, 1969; Ujjwal, Bhatnagar and measured with a Vickers M3 Multichannel Brdia, 1974) but its relative cntributin t the raised plasma Analyser Plasma urate was measured by the urea has nt been assessed The authrs have attempted t define the cntributin f these three standard AutAnalyser technique (N13A) Urine urea and creatinine were measured with a Vickers D3 Dualchannel Analyser The rati f urea t creatinine in the urine Crrespndence t: Prfessr D B Mrgan, Department (U/Cr) was taken as a measure f Chemical Pathlgy, The Martin Wing, The General f urea excretin rate and thus f urea prductin Infirmary, Leeds LS1 3X rate The percentage tubular resrptin f urea /79/1-1 $2 ( 1979 The Fellwship f Pstgraduate Medicine Pstgrad Med J: first published as 11136/pgmj n 1 January 1979 Dwnladed frm n 12 January 219 by guest Prtected by cpyright

2 'n 2 ~~~~~~ 3 2 li1 ~~~~~~ Raised plasma urea in acute heart failure 12,8 ' J -w * '8 z -4 2 *3 D w e 2 n ~ *- I a O- FIG 1 The plasma urea, urate phsphate and creatinine in the patients admitted acutely with heart failure () and the patients with chrnic heart disease () The hatched areas indicate the reference ranges f the Leeds General Hspital labratry (%R) was calculated frm the cncentratins f urea and creatinine in urine and plasma; %R= [1 Uu Crp] x 1 U, Cru], where Up, Uu and Crp and Cru are the cncentratins (mml/l) f urea and creatinine in plasma and urine respectively Results Figure 1 shws the distributins f plasma urea, urate, phsphate and creatinine in the 3 patients with heart failure () and in the 36 patients with chrnic heart disease () The plasma urea was abve the upper limit f nrmal (7-1 mml/l) in 2 (67%) f the patients in grup and in 14 (39Y/) f the patients in grup and, whereas 6 (2%) f grup had a plasma urea greater than 15 mml/l, there were n such values in grup The plasma urate was abve the upper limit f nrmal (-45 mml/l) in 2 (67%) f the patients with and 14 (38%) f the patients with and the frequency f raised values f plasma phsphate (>13 mml/l) was 2% in grup but zer in grup The plasma creatinine was abve the upper limit f nrmal (15 tml/l) in nly 6 (2%) f the patients in grup and nly 3 (8%) f patients in grup Furteen f the patients with a raised plasma urea had a plasma creatinine within the nrmal range The initial plasma urea in patients in grup was nt related t the age f the patient, the cause f the heart failure r the degree f cardimegaly r pulmnary venus hypertensin f the chest X-ray Althugh 2 patients with a systlic bld pressure less than 1 mmhg had the highest values f 11 Pstgrad Med J: first published as 11136/pgmj n 1 January 1979 Dwnladed frm n 12 January 219 by guest Prtected by cpyright

3 12 a a- a3 F a) CL R D Thmas, Alisn Newill and D B Mrgan %e eg* WJ r: 66 * P <1 z * Il I I Plasma urea (mml/l) 3- F 2 1 [I r= 68 P <-1 // vs a- a 1 5 L 12 F 8 '4 Ie I I Li r = 49 P < Plasma creatinine (/iml/l) * L ~ i±ljr r = ,/ P <-1 FIG 2 The relatin between plasma urate and urea, phsphate and urea, urea and creatinine and urate and creatinine in the patients with The values in the patients with were all within the bx and are nt shwn individually The lines indicate the relatin between the mean values which wuld be expected n the basis f a fall in GFR alne plasma urea, there was n ther relatinship with its severity f the clinical signs f heart failure Figure 2 shws that in grup there were significant crrelatins between plasma urea and each f plasma urate, phsphate and creatinine and between plasma urate and plasma creatinine Hwever, the increase in plasma urea and plasma urate was greater than wuld be expected frm a fall in GFR alne (as indicated by the rise in plasma creatinine), which wuld be a dubling f the plasma urea (and urate) fr a halving f GFR (dubling f the plasma creatinine) The 2 determinants f plasma urea, ther than GFR, are the rate f prductin f urea (which have been assessed by the urine U/Cr) and the tubular resrptin f urea Twenty-seven patients had urine cllectins and Fig 3 shws that ne-third f the patients with had a urine U/Cr abve the highest value in grup In cntrast, the tubular r 151 r resrptin f urea was the same in the 2 grups The rise in plasma urea in the patients with cmpared with thse with was abut equally due t an increase in urea excretin and a fall in GFR, the plasma urea was increased by a factr f 19 n the average, and the prprtinal increases due t increase in urea excretin and a fall in GFR were 1-5 and 14 respectively There was n crrelatin between the cntributin frm the 2 causes Further measurements were made in 28 patients Of the 11 patients whse plasma urea was nrmal n admissin, 9 develped a rise abve nrmal during the stay in hspital Plasma creatinine als increased in these patients but it did nt exceed the upper limit f nrmal There was a general trend fr the plasma urea t rise and then fall during admissin This subsequent fall was nt related t a reductin in the dse f diuretic therapy S Pstgrad Med J: first published as 11136/pgmj n 1 January 1979 Dwnladed frm n 12 January 219 by guest Prtected by cpyright

4 L Cs r c Raised plasma urea in acute heart failure IUU t% r s '- * ts FIG 3 The urine urea: creatinine rati and the percentage tubular resrptin f urea in the grups and Discussin In patients with chrnic heart disease the frequency f a raised plasma urea was 39%, and this is similar t 2 ther series (Thayer, 196; Ujjwal et al, 1974) In the present series, 67% f the patients with acute heart failure had a raised plasma urea n admissin t hspital and the frequency increased t 94%/ fr the whle admissin The frequency f a raised urate was als high (69/%) while that fr phsphate and creatine was lwer (2%) The plasma urea, urate and phsphate were directly related t the plasma creatinine in these patients Since raised values f these measurements are well recgnized features f renal failure this might suggest that the rise in plasma urea is due t impaired renal functin (Thayer, 196; Fishberg, 1947) Hwever, Dmenet and vans (1969), in a large clinical survey, suggested that the increase in plasma urea was largely due t an increased prductin f urea A third pssible explanatin is that there is an increased tubular resrptin f urea, and this has nt been previusly cnsidered The present authrs fund that the plasma urea was higher than wuld be expected fr an uncmplicated fall in GFR and, in 14 patients with a raised urea, the creatinine was nrmal This extra rise was caused by an increased prductin f urea and nt t an increased tubular resrptin f urea In the grup as a whle, the cntributin frm a fall in GFR was equal t that frm an increase in urea prductin, but these factrs were nt cr ,* 1 related It was nt pssible t define the exact cntributin in any individual patient, frm these factrs because f the wide range f nrmal values The assciatin between the administratin f diuretics and the rise in plasma urea in heart failure is ften assumed t be causal and due t vlume depletin (Greenblatt et al, 1977) Hwever, in mst f the patients in the present series in whm the plasma urea returned twards nrmal in hspital the dse f diuretics was either maintained r even increased and in nly 2 patients did it appear that vlume depletin had a significant rle It seems likely that the cntributin f diuretic therapy t the raised plasma urea f heart failure has been exaggerated This study suggests that a raised plasma urea, which is a very cmmn event in acute heart failure, shuld nt be assumed t be due t impaired renal functin r t treatment with diuretics Althugh a fall in GFR undubtedly cntributes, an equally imprtant factr fr the increase in the plasma urea is increased urea prductin, prbably frm increased prtein breakdwn This prtein breakdwn culd be regarded as part f the metablic respnse t acute stress r trauma rather than a cnsequence f circulatry failure, and in the lng term culd explain the muscle wasting f heart failure Acknwledgments We wish t thank the many physicians wh allwed us t study their patients, and the many staff wh helped us Dr C Davidsn kindly gave us permissin t include unpublished data frm a previus study 13 Pstgrad Med J: first published as 11136/pgmj n 1 January 1979 Dwnladed frm n 12 January 219 by guest Prtected by cpyright

5 14 R D Thmas, Alisn Newill and D B Mrgan References DAVIDSON, C, BURKINSHAW, L, MCLACHLAN, MSF & MORGAN, DB (1976) ffect f lng-term diuretic treatment n bdy-ptassium in heart disease Lancet, ii, 144 DOMNT, JG & VANS, DW (1969) Uraemia in cngestive heart failure Quarterly Jurnal f Medicine, 149, 117 FISHBRG, AM (1947) Hypertensin and Nephritis Lea & Febiger, Philadelphia GRNBLATT, DJ, DUHM, DW, ALLN, MD & KOCH- WSR, J (1977) Clinical txicity f fursemide in hspitalized patients A reprt frm the Bstn Cllabrative Drug Surveillance Prgram American Heart Jurnal, 94,6 MORGAN, DB, CARVR, M, & PAYN, RB (1977) Plasma creatinine and urea: creatinine rati in patients with raised plasma urea British Medical Jurnal, 2, 929 THAYR, JM (196) Renal abnrmalities in cngestive heart failure Stanfrd Medical Bulletin, 18, 129 UJJWAL, JS, BHATNAGAR, HNS & BORDIA, A (1974) Uraemia in cngestive heart failure Jurnal f Assciatin f Physicians f India, 22, 589 Pstgrad Med J: first published as 11136/pgmj n 1 January 1979 Dwnladed frm cpyright n 12 January 219 by guest Prtected by

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