Acta Nedica Scandinavicn. Vol. CXXXIX, fiisc. YI, 1951.

Prom the Medical and Surgical Departments of Drammen Hospital, Norway. Chiefs: Senior Physician Olaf Rnincke, M. D. and Senior Surgeon Knud Nicolaysen, M. 2).

Arterial Hypertension in Unilateral, Relid Disease with Inhibition of Growth, Treated with Nephrcctomy.

BY

HAAKON STORM MATHISEN.'

(Submitted for publication September 27, 1950.)

The concept of unilateral, renal disease as a cause of severe liyperteiisioii was based on clinical observations (Ask-l'pmark 1929) which antedate the production of satisfactory esperimcntal, renal liypertetisioti (Goldhlatt e t al. 1934).

In 1937 Butler started to operatc on patients suffering from hypertension a d unilateral, chronic pyellonephi itis.

More recently a considerablr nuiriber of patients have been operated on, no t a11 with success.

From Scandinavian countries sevrrnl cases have been reported (Dedichrn, H. G., Effersm, P., Hammarstriiin, S., Hilden, K., Holten, C., Kirstein, L., Lange, J., JIovin et al., Raaschou, F., h e r , .J. and Storiii Jlathiseii. H.) in sonic of which only a transient tlrcrease of I)lood pressure has bren obtained.

Iatlications.

Once the diagnosis of unilatrral renal disease has been estahlished and is con- zitlered a probable cause of hypertension, the problcni arises whether or not to advise operation.

Age and duration of the hypertension are important factors in the selection of patients for nephrectoniy.

Age enters into the picture for two reasons. Firstly hypertension after the age of 45 is niuch more probably ))essential)) than renal (Platt - 1948). Secondly sclerosis and arterial disease sreiii to proceed more rapidly in old vessels, probably in the contralateral kitliicy.

Municipal Hospital of Oslo, Dept. TI[, Ullevkl, Oslo, Nornay.

422 HAAKON STORM MATHIBEN.

The following iiidicatioiis for nephrectomy have been established b y Schroeder, H. A. and Fish, G. W. (1940): 1) The onset of arterial hypertension should he known to hare occurred recently. We

2) The renal lesion should he confined to one kidney a i d should be of such a nature

3) Renal function, as measured by the ability of both kidneys to coiiccntrate urine

4) Retinopathy should be absent and changes in the caliber of the retinal vexscls iiiiiii-

5) Arterial pressure should he persistently elevated.

place the time arbitrarilj~ a t 2 years.

that diminution of function has occurred in that kidney.

and by the nrea clearance test, should be within iiormal limits.

mal.

These criteria are rigid, some perhaps too rigid (Raaschou 1943) a--d only few of t h e cases operated on have fulfilled these requirements. Coiisequeiitly cure has not been obtained in more t h a n 10 t o 20 per cent (Homer Smi th 1943).

In 1949 Gasul e t al. found only 31 cases in t h e world literature, of which 9 were children, who after follow-up for 2 years had a coinplete iiormal blood pressure following nephrectomy. The following case fulfils t h e criteria for nephrectoiny laid down by Schroeder and Fish.

Case Repor t

On May 21., 1948, a 13 10/lz-year-old schoolgirl, born on July 19., 1934, was atlinitted to the Med. Dept. (Case no. 8911/48). The parents of the patient and a sister, 2 years older. were healthy. The father’s father and his brother suffered from hypertension. No known endocrine diseases had occurred in the family.

The patient had had mumps, measles and whooping cough. Otherwise she was healthy and had developed almost normally until the age of 11. In February 1946 her illness started with paroxysmal headache, lasting a couple o€ days, once a week, and with such heavy pains that she had to stay in bed. The headache, being unilateral and alternating between the right and left side, was accompanied by vomiting. Gynergen (ergotamine tartrate) had quite a good effect and might stop the attack. Gradually her headache grew more permanent, she did not keep pace in shoo1 and was able neither to learn her lessons nor to play. Back home (from school) she went to rest a t once and had to stay in bed several days a week.

The examination of schoolchildren, checking height a i d weight in spring and autumn, showed that since she started in school, she had been slightly smaller in stature than the average. During the two years 1946-1948 she had practically not grown a t all. I n April 1948, as an out-patient, her hloocl pressure mas found to be 2301130 mm Hg and her pulse 120. A neurological examination disclosed no disease of the central nervous system.

The patient was admitted for observation with a question of endocrine dysfunction. On admission she was 13 years and 10 months old, but her body weight and general development corresponded to that of a Norwegian girl aged 10 to 11, with height 137.5 cm and weight 34.i kg. All secofidary sex characteristics were absent, and her blood pressure was 200/130 mm Hg on the upper limbs and 230/170 on the lower limbs. ilfter an intravenous adniinistratioii of 5 ml of tetraethylammonium bromide a good vasodila- tation followed. but with insignificant change in the blood pressure. The diastolic pres- sure remained unchanged a t about 140 to 145 min Hg during the test. An Smycal (dniytal) test with 0.10 g of ainycal, given three times with an interval of 1 hour, resulted in a decrease in blood pressure of 20 niin Hg both in the systolic pressure, falling from 170 to 150, and in the diastolic. falling from 125 to 105. Ophthalmoscopy disclosed somewhat

ARTERIAL HYPERTENSION IN UNILATERAL, RENAL DISEASE. 423

Fig. 1. I<ocntgenogram of the intravenous pyelography. Tho right renal shaclo\\ i\ smallor than the left.

i i a row- arteries ant1 a few arteriovenous compressions. The electrocardiogram was iioriual and the h a d metabolic rate 108 7; (+ 8 yo). 8leinickcs reaction nepativc. Thcv was no proteinuria and the concentration test, by Addis-Pherky's method, showed a specific gravity of 1,024 in bladder urine; the urea clearance (mas.) was 61 96 of tlit norinal and blood urea 32 mg per 100 ml. The sediment count in a 12-hour urine speciincii resulted in 17,500,000 white cells, 1,300,000 red cells and no granulated casts, i. P. a i idd pyuria.

On cystoscopv (Fretheim) the ureteral orifices were found to he situated furthcr back than usual, ant1 both had a semilunar shape with the conrcsity upwarils. Fiiiir from the ureters sliowrl:

Riyht side LPft sine

Spccific U:L\ ity: 1,002 1.012 Urea: Microscop. exam.: d few white cclls. Some red cells.

354 mg per 100 nil 1.110 nig per 100 nil

I . e. urine from the right side was clear as water 11 itli a lower urea coiitcnt anti inirro-

Intravcnons pyelorraphy (Natvig): Pig. 1. The right renal shadow nieasures 10 x 3 cm and tlie left 11 x 6 rni. S o sliatlou. s of

calculi are risible. After intravenous injection of 10 nil ))Urotrasta a good esrrrtioii appears on the left sidr, where conditions are normal. The escretioii is also good on the right side, but the calices and pelvis are large compared to the small kidney. No obstruction in the ureters and usual shape of the bladder. Roentgen diagnosis: Small right kidney with a good function.

The retrograde pyelography gave no further information. Roentgenogrmi of the liead showed a small skull, with the sella turcica measuring S x 6 mm. The hands were alzo small, but all bone nuclei were present anti all epiphyseal lines open as normally

scopical pyiiria. The function of the right kidney was probably decreawi.

424 HAAKON STORM MATIIISEN.

for her age. Roentgenogram of heart and lungs was normal; von Pirquet test ricg;ttivc; blood sedimentation rate 11 inm and H b 107 94.

The patient was transferred to the Surg. Dept. and ori June 6., 1948, in ether anesthesia, n riglit nephrectomy was performed by Nicolaysen, described as follow: Usual oblique incision for renal approach. The small kidney, situated on a very high level, was quite easily removed with 10 cm of the ureter.

The kidney hat1 a peculiar shape and seemed to consist of a (wide) upper pole with a sniall, plumstone-sized lobe medially i n front of tho renal pelvis. On incision this lobe also proved to contain a small pelvis. While the ordinary kidney had a couple of normal calices and papillae, the pelvis of the small medial lobe had no papillae and a border of renal substance n-it.h a pathological appearance. Both pelves opened out to the same ureter.

After fixation the whole preparation was sent for histological exaniination. Result of the examination in the Pathological Department, State Hopsital, Oslo: A piece

of renal tissue weighing 25 g and measuring 4.7 x 4.2 x 2 . 5 cm, and fixed in formalin has heen received. The capsule, partly pulled off, is easily separated further, and is not visibly increased in thickness. The kidney consists of 2 part,s: 1) A part, well over plum-size with ii regular surface, except for a penny-sized, flat, somewhat retracted area corresponding to the one pole. 2 ) .4 part, well over the size of a Spanish nut, separated from the other part by a shallow sulcus and having a finely granulated surface with a few stellate re- tractions. The previous renal incision was extended and revealed in the plum-sized part of the kidney a normal or slightly thickened cortex with somewhat irregular demarcation from the medulla, which showed only one distinct papilla. In the parenchyma neither necroses nor hemorrhages are seen. A tubule (calyx?) as thick as a string and 1.5 cm long leads from the papilla. The nut-sized part of the kidney hat1 a very atrophic paren- chyma with no tlistJiiict boundary hetween t,he cortex and niedulla and a transversr section of 3 nini. The pelvis proper seenis to be in this arra, where at' least 4 atrophic calices, opening out to :L pelvis barely a s big as a11 almond kernel, are found. A tube as thick as a string and 1.5 cm long. 1t.ilding from here, unites with the previously described pelvis to a common ureter just outside the hilus area. Section shows a good passage and ;I wrinkled niucosa with no obvious pathological changes. The following sections werc taken: I ) The flat area including the accompanying I els. TI) the transition area between the flat and the normal one, 111) thc nut-sized area containing the pelvis, IY) th r distal cntl of the ureter.

-1 piece of TI) is cut in frozen section and stained with Sudan. Corresponiling to thc. atrophic area in I) thcre is on microscopical examination a border of renal tissue, in which all glomeruli are hyalinizetl, except ono single glomerulus and the corresponding proximal and distal convoluted t u l d e s . A few other and sninller areas with well preserved tubules are seen: otherwise, however, these are completely degeneratJetl, apart from sonie smaller collecting tubules. The stroma is increasetl considerably and heavily infiltra- t,ed mostly with lymphocytes with a few scattered eosinophilic granulocytes. Tn some places a considcrahle nuniber of comparatively large, rounded or oval cells are seen, (:it,her solitary or in groups: they h ive a light basophilic cytoplasm, often with it colour- less perinuclear zone and round or oval nuclei, some of them poor in chromat,in and sonie with a medium chromatin content, (Recher cells). Tlie arteries in this area show a comparatively moderate proliferation of the intima and the arterioles :I less proniinent diffuse, hyprrplastic scleroses.

Jn the area of more normal appearance most of thr glonicruli are well preservetl, with no ubvious proliferation of the intima or of the capsular epithelium. The capsular spaces are somewhat dilated. The proximal tubules are slightly autolyzed, but on the whole not dilated. The distal convoluted tuliules and especially some of the collecting tubules and terminal ducts, however are ohriously partly dilated. The arteries hrre show a very slight thickening of the intima. Some arterioles in the hilar glomeruli show a marked diffuse, hyperplastic sclerosis. I n this area the stroma has not incre:tsetl a n d is not in-

ARTISI<IAI, HYPPRTEXSION IN UKILATERAL, RENAL DISEAPE. 425

filtr,rttStl with lynipliocytes, and 110 tlefinito I h ~ h e r cells arc seen. A section from tlic ; t h v r nit~ntioiirci vessels rcvc;tls two mrrlinni-sizrd muscular artcries with a strongly plirat,rcl intt.rii;il elastic mmil)raTie, hit otherwise with no promincnt pathological changes. I I ) she\\-> the same transition Iwtwcrn pronounced atrophic and more normal prenchyni:i. Thr Iiytlronephrotic componrnt is soniewhat more olirious in t h o last-named area, 21s also some of the proximal tubules are a little dilated. 111) shows once again a consid- c m , l ) l t . atrophy of the parenchyma similar to that dcscritictl for the. opposite rcrial polc, b u t t i t w :I few clilattd tul)ulrs, filled with hyalinr masses. are also srcn. Yrar tlir 1)ountl:iry

\ Mephrecfom y

towards 11) patchrs of c:ilcific:ition, surrounding sonir trrniinal tlucts, are srcn. ' l ' h t - renal pelvis shows partly normal. partly a thickcncd stratified, transitional epithelium. with a niarkrtl liyperr~tiii~~ antl Iyniphocytic infiltration antl a few eosinophilic granulo- cytes in t.he suhjaccnt conrioctivc tissue. IV) is a section from thr ureter and shows a somewhat thickenctl and pirtly artificially desquamatetl epithelium with a nioderatc lymphocytic infiltration of th r mucosa and otherwise nothing abnormal. No cvitlenec, of a specific inf1anini:ition in any of the sections.

Pathologird d i n g ~ o s i s : Probably pyelonephritic contracted kidney. Moderate hytlro- nephrosis. Patches of nrt~criosclt~osis. Divided renal pelvis. June, 15th 1948.

Olav Torgersenjsign.

The patient stood the operation wcll, b u t a postoperative hemorrhage in the nephrec- tomy wound indicateti 2 blood trimsfusions of 500 ml, on the 6th and 9th postoperative days. The blood prrssurc fell from 160-170 mni Hg systolic and 130 inm Hg diastolic to 105/80 miti Hg on the (lay after the operation, antl has remainrd consistently low. (Pig. 2.) After 18 clays the patirnt was discharged in good health, and readmitted (to the Med. Dept,.) 2 months later, in August 1948. for her first re-survey. She was feeling q u i t e well and fit in cvrry respect)), had had no headache and had played, read e t r . with no difficulty. On :~htlominal examination a tumor as big as half an orangr was

42 6 ZIAAKON STORM NATIIISEN.

palpated just above the nephrectomy x a r and interpreted as an orgziiized hematoma. Later she has bcen controlled several times, both as an out-patient and as an iii-patient. The blood pressure has remained normal, a i d the 24-hour blood pressure ciii\-e 2 years after the operation is on a quite different level, the systolic pressure now I~eiiig continually below the diastolic pressure before the operation. Fig. 3. The last re-sir\ ey 111 Nay arid June 1950 (2 years after the nephrectomy) showed the following:

Blood pressure 100--115j'70--85 (see fig. 3 for 24-hour curve); Urine \\as clear, light- coloured with spec. grav. 1.025 (ilddis conceritration test, 50 nil urine froiii 7 to 9 o'clock), no protein, blood or sugar and no pathological findings on microscopy: urea clearance

_.'a. .I ... N A Y -50 -_._... _..... - . ,...

<.. .. ,.*. , ....I. 2.. ,. .... * . . , . .._

B. c 170

160

I S 0

I V o

I 3 0

120

/ l o

loo

90

Po

70

60

I I 13 16 I f ( 9 I ! 1 3 I 3 5 7 9 I I

Fig. 3. The 24-liour systolic and diastolic blood pressure curve before and about 2 y e i ~ r s after the operation. Thc systolic pressures after the nephrrctomy are all on a lover level tliaii the diastolic

oiics before the operation.

(max.) 87 yo of the nornial; blood urea 23 mgO/,; cholesterol 151 mgy0,; roentgenogram of heart and lungs negative; electrocardiogram normal. Ophthalmological examination (Wiborg): The fundus is probably a litte more hyperemic than usual. The reins, especially some branches, are somewhat tortuous, but otherwise no retinal changes: no hemorrhages or atrophic plaques. Visual acuity 7/7.

I n April 1950 her appendix was removed. She had suffered from SOIHC backache, and both before and after the nephrectomy a low intervertebral disc between the 6. and 7. thoracic vertebrae has been demonstrated roentgenologically. According to an orthopedic specialist (Nissen-Lie) who has examined her, this is snpposeetl to be due to a growth disturbance. Since the operation she has had no headache and is a t present working in a textile niill.

During the last 2 years she has increased in height l5.n cni and in weight 13.3 kg Fig. 4. Breasts have developed and the facial expression and somatir type are more mature. Fig. 5 a and b. During the last year pubes and axillary hair h a ~ t appeared faintly, but the menarche has not yet occurred.

Epicrisis.

A 13 lo/l,-year-old girl, sufferiiig from headache for 2 years, was found t o have a blood pressure of 230jl30 t o 200/130 niin Hg, a small right kidney with reduced

ARL'ERIAL IITPERTENSION IN U S I L A T E R A L . RENAL DISEASE. 4 2 i

Fig. 4. \Ycight and height measiirrtl onrc to twicr n y a r from tlir pntient's 7th to hrr 16th p i r . For comptirihcin tlir arrragr height and \wigtit of the girls in Oslo 1)rirn:u.y tinil srrotidiiry rc~ho~i l s ,

194.5, are gircn.

function, inild retinal changes and a growth inhibition evidenced by the fact that she had allnost not grown or developed a t all during these 2 years. Her height, weight and soiliatic development corresponded to that of a Korweginn girl aged 10 to 11.

After nephrectomy with removal of a kidney with signs pointing to a pyelo- nephritic contracted kidney, the blood pressure fell, and at all subsequent controls during 2 years it has remained a t 100-116 systolic and 70-85 mm Hg diastolic (24 hour curve).

The hradachc has disappeared completely, and in the course of 2 years after the

428 IIAAICON STORM MATHISEX

operation licr \\-eight, has increased froni 34.7 t o 48 kg (13 .3 kg) and her height from 137.5 to 1% cni (15.5 cm). Breasts have developed, and the countenance and body type are inore inatiire.

ARTERIAL I1TPEKTE:IiSION I N UNILATERAL, HESAL DISEASE. 429

Conimen t s.

‘rile reported cast seetns to be one of the few cases of unilateral renal diheaso with arterial hypertension in which nephrectomy has been performd in time to affect the 1)lood pressure before irreversible changes have occurred in the other kidney. -1ccording to -1sk-Uptnark this disease o(’curs most frequently in girls mid is supposed to lje due to a congenital anomaly of the right kidney.

This patient has attained a completely norrnal blood pressure which is still normal 2 years aftcr the nephrectomy. The retinal changes demonstrated have tlisappetired.

This case is of chpccial iiitercst as exact and periodic measurements of the h(,ight ant1 weight (once or twicc. a yrar) froin the age of 7 are at hand.

Thest nieasiireiiitiits show that the patient virtually did not increase in height :iiitl weight during the 2 years previous to the operation, and it \\-as during this tinit thiLt she also was complaining of headache, dizziiitm t tc .

-\fter the nephrectomy she increased in height from 137.5 to 153 cni (15.;) cm) and in weight from 34.7 to 48 kg ( 1 3 . 3 kg), which corresponds to a normid increase a t her age.

I h e n before hcr illness the patient was under the average size, and pro1)iibly she will hereafter hardly attain the height and weight of those of her own ape. Some similarity to a renal growth inhibition or renal infantilism (Hunt - 1927) was present in this case, but no rachitic-like bony derformities were recognized. d n improved general condition may have been of importance for hcr growth.

Summary.

-I case of considerable hypertension (B. P. 230/130) in a 13 1‘),’12 year-old girl is reported in detail. For 2 years the patient suffered from headache, vomiting, dizziness and virtually did not increase in height and weight during this time.

.ifter the removal of a small, atrophic right kidney, with signs pointing to pyelo- nephritic contracted kidney:

1) The blood pressure fell, and on controls i t has remained a t normal values (13. 1’. 100/70) for 2 years after the operation.

2) Simultaneously all her complaints disappeared. 3) -4 rapid increase in height and weight occurred and the somatic type became

‘rhis case has some similarity to the so-called renal growth inhi1)ition or renal inore mature.

infantilism.

Literature.

Atldis, T. anti Shevky, M. C.: Arch. Int. Med. 30: 659: 3932. - -isk-Uipmark, E.: -4cts Path. ct Microbiol. Scand. 6: 383: 1929. - Butler: A. M.: Journ. Cliii. In\ est. 16: 889: 1937. - Dedichen, H. G.: Tidsskr. f. d. norskc, LePgrfor. 65: 411: 194.1,. - Effer- hoe, P.: Acta 3letl. Scand. 131: 10: 1948. - Gasul, B. M., Glasser, J. M. and Grossnia~i,

430 IIAAKON STORM MATIIISEN.

Ba.: J . A. M. A. 139: 305: 1949. - Goldblatt, H., Lynch, J., Hanzal, R. F. and Summer- rille, W. W.: Journ. Exper. Ned. 59: 347: 1934. - Hamniarstrom, S.: Nord. Metl. 23: 1663: 1944. - Hilden, K.: Ugeskr. f. Leger 104: 639: 1942. - Holten, C.: Ugeskr. f. Lager 104: 644: 1942. - Hunt. F. C.: Am. J. of Diseas. of Childr. 34: 234: 1927. - Kirstein, L.: Nord. ?fed. 29: 193: 1946. - Lange, J.: Nord. Med. 30: 1259: 1946. - Movin, R., Sneborg Olsen, 9. and MiIholt Pedersen, A.: Ugeskr. f. L q e r 106: 643: 1944. - Platt, R.: Quart. Journ. Ned. 17: 836: 1948. - Raaschou, F.: Nord. Med. 17: 207: 1943. - Schroeder, H. ,4. and Fish, G. W.: Am. J. Med. Sc. 199: 601: 1940. - Smith, H. W.: Bull. N. XT. Acad. Mecl. 19: 449: 1943. - Storm Mathisen, H.: Tidsskr. f . d. norskr I m p f o r . 65: 410: 1945. - Oster, J.: Acta Med. Scand. 128: 42: 1947.